H'afiffli Wmm JH ■ I ■ H if Hi ■■■Hflffl ^ ■ 'Pi ■ H MB HP Ik Qass. Book COPYRIGHT DEPOSIT SURGICAL PATHOLOGY AND THERAPEUTICS BY JOHN COLLINS WARREN, M. D., LL.D., PROFESSOR OF SURGERY IN HARVARD UNIVERSITY ; SURGEON TO THE MASSACHUSETTS GENERAL HOSPITAL. ILLUSTRATED SECOND EDITION APPENDIX CONTAINING AN ENUMERATION OF THE SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS, TOGETHER WITH A SERIES OF SECTIONS ON REGIONAL BACTERIOLOGY PHILADELPHIA W. B. SAUNDERS 925 WALNUT STREET 1900 TWO COPIES RECEIVED, Ubr*ry of CongrM% Office of the ff" ? 9 1900 ftegltttr of Copyrights <^t fi\t 54282 Copyright, 1900, by W. B. SAUNDERS SfcCOND GOP*- WESTCOTT &. THOMSON, PRESS OF ELECTROTYPEHS, PHILADA. W. B. SAUNDERS, PHILADA. Felix qvi potvit rervm cognoscere cavsas Atqve metvs omnes et inexorabile fatvm svbiecit pedibvs strepitvmqve acherontis avari. Virgil, Georg. II. 490. PREFACE TO THE SECOND EDITION. In the second edition of this book the attempt has been made to embody all the important changes in a new Appendix which replaces the old one and the chapter on Antiseptic Surgery. In this new chapter the author has aimed to present in as prac- tical a manner as possible the resources of surgical pathology. In addition to an enumeration of the scientific aids to surgical diag- nosis, there is presented a series of sections on what may be termed regional bacteriology, in which are given a description of not only the flora of the affected part, but also the general principles of treating the affections which they produce, based upon the latest views of the best authorities. It is hoped in this way to make the book of value to specialists in many of the departments of medicine. The author begs to acknowledge his indebtedness to Drs. A. K. Stone, R. B. Greenough, J. L- Goodale, H. A. Lothrop, Farrar Cobb, Mark Richardson, F. B. Lund, and Mr. Walter Dodd in the preparation of this edition. 58 Beacon Street, Boston, January, 1 900. PREFACE The scientific portion of a surgical education was formerly re- garded as something apart and ornamental, but it has now become an eminently practical feature of the student's curriculum. No young practitioner can be regarded as thoroughly equipped for surgical work who is not both a good pathologist and an expert bacteriologist. The confidence born of a knowledge of Pathology and Bacteriology enables him to assume grave responsibilities and to grapple successfully with the most complicated problems. It is from men thus equipped that we have a right to hope that the future masters of surgery are to be evolved. An attempt is therefore made in this book to associate pathologi- cal conditions as closely as possible with the symptoms and treatment of surgical diseases, and to impress upon the student the value of these lines of study as a firm foundation for good clinical work. It is the Author's hope that the following pages will present to a large number of practising physicians, in a readable form, many subjects that received but little attention when they graduated. The illustrations by Mr. William J. Kaula are, with one or two exceptions, original. The drawings of microscopical sections are taken from specimens prepared for the purpose, and are intended to illustrate as closely as possible the results of modern micro- scopical technique. The Author takes this opportunity to acknowledge his indebted- ness to Dr. Arthur K. Stone for valuable assistance, and to express his appreciation of the courtesy extended to him by many of his colleagues during his labors. CONTENTS. • ?AGE I. Bacteriology 17 II. Surgical Bacteria 43 III. Hyperemia 79 IV. Simple Inflammation 92 1. The Process 92 V. Simple Inflammation {continued} no 2. Symptoms and Causes of Inflammation no 3. Varieties and Treatment of Inflammation 125 VI. Infective Inflammation 135 1. Etiology 135 VII. Infective Inflammation {continued) 155 2. Suppuration 155 3; Abscess 161 4. Ulcer 182 5. Fistulae 190 VIII. Infective Inflammation {continued) 193 6. Acute Osteomyelitis , 193 IX. The Process of Repair 218 X. Gangrene 256 XI. Shock 2^^ XII. Fever 301 XIII. Surgical Fevers 316 XIV. Septicemia 334 XV. Pyemia 356 XVI. Erysipelas 381 XVII. Hospital Gangrene 409 XVIII. Tetanus . . . 435 XIX. Hydrophobia ....:* 1 ....... . 453 7 8 CONTENTS. PAGE XX. Actinomycosis 469 XXI. Anthrax . 477 XXII. Glanders 485 XXIII. Snake-bite 495 XXIV. Tuberculosis 504 XXV. Surgical Tuberculosis oe Joints . 529 XXVI. Tuberculosis oe the Soft Parts 558 1. Tuberculosis of the Skin 558 2. Tuberculosis of the Mucous Membranes 565 3. Tubercular Peritonitis 569 4. Tuberculosis of the Genito-urinary Organs 573 5. Tuberculosis of the Mamma 583 6. Tuberculosis of the Lymphatic Glands . 585 7. Tuberculosis of the Tendon-sheaths 589 8. Scrofula 593 XXVII. Diseases of Bone 597 1. Osteomalacia .... 597 2. Rickets . . 603 3. Osteoporosis 609 4. Hyperplasia of Bone 612 5. Phosphorus-necrosis 617 6. Arthritis Deformans 620 7. Spinal Arthropathy 624 8. Ankylosis 625 9. Periostitis < 628 XXVIII. Tumors 633 XXIX. Carcinoma 638 1. Carcinoma of the Skin 648 2. Carcinoma of the Breast 662 3. Carcinoma of the Uterus 672 4. Carcinoma of the Tongue 677 5. Carcinoma of the CEsophagus 684 6. Carcinoma of the Larynx . . 686 7. Carcinoma of the Stomach 688 8. Carcinoma of the Intestines 689 9. Carcinoma of the Rectum 690 10. Carcinoma of the Bladder 694 11. Carcinoma of the Kidney 696 12. Carcinoma of the Testicle 698 CONTENTS. 9 PAGE XXX. Sarcoma 702 1. Sarcoma of Skin 709 2. Sarcoma of Bone 712 3. Sarcoma of Kidney 718 4. Sarcoma of Bladder 719 5 . Sarcoma of Uterus 720 6. Sarcoma of Testis 721 7. Sarcoma of Breast 723 8. Sarcoma of the Air-passages . , 725 9. Sarcoma of the Digestive Tract 729 10. Sarcoma of Brain , « 729 11. Lymphosarcoma 730 XXXI. Benign Tumors 737 1. Adenoma 7^7 2. Goitre 743 3. Cystoma 748 4. Papilloma 751 5. Fibroma 753 6. Myxoma 758 7. Lipoma 760 8. Glioma 763 9. Chondroma 765 10. Osteoma 769 11. Neuroma 771 12. Myoma 774 13. Angioma . . . . 777 14. Lymphangioma 781 APPENDIX. I. Scientific Aids to Surgical Diagnosis 785 Blood Examination 786 Bacteriological Examinations ■ 788 Urinary Conditions 790 Spinal Puncture 794 Feces 795 Microscopical Examination of Pieces of Tissue suspected of being of Malignant Growth 795 Rontgen Rays in Surgery 796 io APPENDIX. PAGE II. Surgical Bacteriology of the Skin 800 Avoidance of Wound-infection 801 Treatment of Wounds 807 III. Bacteriology of the Mouth and Pharynx, Eye, Ear, and Nose 812 The Mouth and Pharynx 812 Surgical Preparation of the Mouth for Operation . . . .813 Pathogenic Bacteria of the Mouth . 814 The Antiseptics of Tooth-filling . . 815 Diagnosis of Acute Infectious Inflammations of the Mouth 816 The Eye 816 The Ear 819 The Nose 820 IV. Bacteriology of the Genito-Urinary System 822 Predisposing Conditions ; Role Played by Bacteria in the Causation of Cystitis 823 Bacterial Invasion 824 Reaction of the Urine 824 Bacteria in the Vicinity of the Meatus Urinarius and in the Male Urethra 825 Bacteria of Cystitis 826 Routes of Invasion of the Genito-Urinary System by Micro- organisms 828 External Genitals and Urethra 828 Bladder 828 Kidney 829 Vulva and Vagina 831 Rectum and Anal Canal 831 Local Applications 832 V. Bacteriology of Peritonitis 834 VI. Bacteriology of the Gall-Bladder 842 VII. Sero-therapy in Tetanus, Tuberculosis, and Syphilis . . . 846 Tetanus 846 The Antistreptococcus Serum 848 Surgical Tuberculosis 849 Syphilis 850 LIST OF ILLUSTRATIONS. FIG. PAGE i. Arnold Sterilizer » 32 2. Potato Culture 33 3. Method of Filling Test-tubes with Nutrient Material 35 4. Petri Dish with Colonies 36 5. Bacteriological Syringe (H. C. Ernst) 40 6. Staphylococcus P3'ogenes Aureus (Colored) 43 7. Staphylococcus Pyogenes Albus (Colored) 43 8. Streptococcus Pyogenes {Colored) 45 9. Streptococcus Pyogenes (culture) (Colored) 46 10. Bacillus P}-ocyaneus (Colored) 47 11. Bacillus Coli Communis (Colored) 49 12. Gonococci (Colored) 51 13. Bacillus Tetani (Colored) 54 14. Hydrogen Jar for Anaerobic Cultures 55 15. Tuberculous Sputum (Colored) . 58 16. Tuberculous Urine (Colored) 58 17. Bacillus of Tuberculosis on Glycerin- Agar (Colored) 60 18. Bacillus Mallei (Colored) 62 19. Bacillus of Malignant CEdema ( Colored) 68 20. Bacillus Anthracis (Colored) 71 21. Section of Kidney from an Animal dead of Anthrax (Colored) ... jt, 22. Section of Tumor of a Calf, showing Actinomyces (Colored) ... yy 23. Blood-vessel, showing Diapedesis of Leucocytes 93 24. Leucaemic Blood, showing various forms of Leucocytes (Colored) . 99 25. Amceboid Movements of a Leucocyte 101 26. Karyokinesis in the Cells of a Sarcoma (Colored) 105 27. Metastatic Abscess of Kidney (Colored) 156 28. Portion of Wall of Lung Abscess, natural injection (Colored) . . 157 29. Pus-cells with Staphylococci 159 30. Pus-cells treated with Acetic Acid, and Crenated Red Blood-cor- puscles 159 31. Sterilized Test-tube and Swab for Collecting Pus and Fluids for Bacteriological Examination 160 32. Diagram of Tendon-sheaths of the Hand (Tillaux) 169 33. Columna Adiposa 176 11 12 LIST OF ILLUSTRATIONS. FIG. PAGE 34. Infiltration of Columna Adiposa and Subcutaneous Tissue with Pus in Carbuncle 178 35. Diagram of a Carbuncle 178 36. Ulcer of Leg [Colored) 183 ZJ. Point of Origin of Suppuration in Osteorrryelitis 197 38. Extension of Suppuration in Osteomyelitis 199 39. Necrosis of the Shaft and Periosteal Formation of Bone 199 40. Separation of Sequestrum and Formation of Involucrum 201 41. Unhealed Abscess-cavity, with Eburnation of Bony Tissue .... 201 42. Necrosis of Femur, the result of Acute Osteomyelitis (Colored) . . 207 43. Healing of Blood-clot, and Senn's Bone-chips 216 44. Healing hy Second Intention (Colored) 226 45. Vascular Spaces with Tissue filled with Leucocytes 227 46. Detail Study from a Deep Layer of Granulation Tissue, showing a vessel with epithelioid cells and spindle-cell growth 228 47. Development of Blood-vessel in Mesentery of an Embrj-o 230 48. Development of Blood-vessel in Mesentery of an Embryo : forma- tion of vascular loops = 231 49. Granulations compressing Blood-clot; injected specimen (Colored) . 232 50. Healing of Tendon : callus formation with absorption of blood-clot 233 51. Detail Stud}* of the End of the Divided Tendon (Colored) .... 234 52. Repair of Muscular Fibre (Colored) . . 237 53. Changes seen in the Repair of a Nerve after Division (Colored) . -. . 239 54. Experimental Fracture (Dog) at the end of the first week, showing blood-clot and detached fragment of bone (Colored) 244 55. Experimental Fracture (Dog) after forty-six days : ossification of callus (Colored) 245 56. Ossification of Osteoid Substance in Callus of a Dog (Colored) . . 247 57. Experimental Callus of a Dog (Colored) 248 58. Detail Study of Three-weeks' Callus, showing osteoblasts forming new bone (Colored) , . 248 59. Carotid Artery of Horse two weeks after ligature (Colored) .... 251 60. Carotid Artery of Horse two months after ligature (Colored) . . . 252 61. Femoral Artery of Man three months after ligature (Colored) . . . 253 62. Tibial Artery from a case of Senile Gangrene of the Foot (Colored) . 258 63. Gangrene of the Toes from Frost-bite (Colored) 269 64. Ganglion-cells from the Cord of a Cat ; stimulated and resting-cells 286 65. Traumatic Fever (chart) 318 66. Aseptic Fever due to the absorption of blood-clot (chart) 320 67. Infiltration of Muscular Tissue with Streptococci in a case of Septi- caemia of Man (Colored) 340 LIST OF ILLUSTRATIONS. 13 FIG. PAGE 68. Sapraemia (chart) 345 69. Septicaemia (chart) 346 70. Capillary Embolus of Streptococci in a Sarcoma {Colored) .... 350 71. Infiltration of Vessel-wall in Sarcoma {Colored) 351 72. Thrombus of Femoral Vein {Colored') 362 jt,. Pyaemia (chart) 368 74. Traumatic Fever followed by Erysipelas in a case of Lithotomy (chart) 391 75. Extravasation or " Miliary Abscess " in the cervical cord in a case of hydrophobia [Colored) 463 76. Submiliary Tubercle, showing giant - and epithelioid cells 506 jj. Tubercular Nodule of the Head of the Tibia {Colored) 516 78. Tubercular Abscess-cavity, being the point of origin of disease of the hip-joint {Colored) 517 79. Deformity from Absorption of Phalanx due to tubercular disease [Colored) 522 80. Angular Deformity from Pott's Disease {Colored) 524 81. Tuberculosis of the End of the Humerus, showing caries of the articular surface and osteophytes due to inflammation of the peri- osteum [Colored) 533 82. Tuberculosis of Tendon-sheaths or Palmar Bursal Tumor {Colored) 592 83. Trabecula of Bone in a case of Osteomalacia — on the left osteoclasts, and on the right osteoblasts {Colored) 597 84. Section of Femur in a case of Osteomalacia : below is the medulla rich in cells, and above, the periosteum [Colored) 599 85. Extreme Deformity of Skeleton due to Rickets 606 86. Calvarium of a case of Ostitis Deformans [Colored) 614 87. Arthritis Deformans, with Eburnation of Bone due to absorption of cartilage [Colored) 621 88. Ankylosis of the Hip-joint [Colored) 626 89. Cell-inclusions in Cancer of the Breast [Colored) 642 90. Cell-nests in Cancer of the Lip [Colored) 649 91. Tubular Epithelioma, from a case of Rodent Ulcer {Colored) ... 651 92. Noli-me-Tangere [Colored) 654 93. Medullary Carcinoma of the Breast 664 94. Scirrhous Cancer of Breast {Colored) 665 95. Brawny Infiltration of Breast in Cancer [Colored) 667 96. (Edema of Arm in late stages of Cancer of Breast {Colored) . . . . 668 97. Cancer of the Uterus 674 98. Cancer of the Rectum 691 99. Cancer of the Rectum, showing cylinder-cells 691 14 LIST OF ILLUSTRATIONS. FIG. PAGE ioo. Alveolar Sarcoma 705 101. Spindle-cell Sarcoma 706 102. Giant-cell Sarcoma {Colored) 706 103. Periosteal Sarcoma : amputation at the hip-joint {Colored) .... 714 104. Retroperitoneal Lymphosarcoma, showing cells and stroma ... 731 105. Lymphosarcoma {Colored) 7^2 106. Fibro-adenoma of Breast (Colored) 739 107. Diffuse Hypertrophy of the Breast {Colored) 741 108. Adenoma of Thyroid Gland ( Colored ) 744 109. Cystic Goitre {Colored) 744 no. Accessory Thyroid Gland at the Base of the Tongue 745 in. Section of Accessory Thyroid Tumor 745 112. Thyreoglossal Tract 746 113. Dermoid Cyst of Ovary {Colored) 750 114. Fibroma (Colored) 754 115. True Keloid {Colored) 756 116. Naso-pharyngeal Fibroma {Colored) 757 117. Myxoma {Colored) 759 118. Lipoma of Thigh {Colored) 761 119. Diffuse Lipoma of the Neck and Abdomen (Colored ) 762 120. Enchondroma of the Tibia {Colored) 766 121. Hyaline Enchondroma {Colored) 766 122. Enchondroma of the Thumb (Colored) . . 767 123. Mixed Cartilaginous Tumor of the Parotid Gland (Colored) . . . 767 124. Hyaline Enchondroma of the Scapula ( Colored ) 768 125. Ivory Exostosis of the Orbit {Colored) ...... 769 126. Osteoma of the Lower Jaw ( Colored ) 770 127. Neuroma from an Amputation-stump {Colored) 77^ 128. Myoma of the Uterus {Colored) 774 129. Angioma of the Lip and the Neck {Colored) 778 130. Cavernous Angioma {Colored) 779 131. Angioma of the Scalp (Colored) 780 132. Lymphangioma (Colored) 782 133. Fracture of the Neck of the Femur (skiagraph) 797 134. Dislocated Patella (skiagraph) 798 135. Renal Calculus (skiagraph) 799 PAGE Plate I. Shaft of Femur, showing the results of osteomyelitis . . 209 Plate II. Healing by first intention of an abdominal wound .... 223 Plate III. Diabetic Gangrene 264 Plate IV. Gangrene of Leg, following ligature of femoral artery . . . 265 SURGICAL Pathology and Therapeutics. Surgical Pathology and Therapeutics. I. BACTERIOLOGY. If one were to search literature for the earliest accounts of the germ-theory of disease, it might be necessary to consult the oldest writings of which we have any knowledge, for even among the ancients there were those who thought that disease was due to the invasion of the system by minute organisms. But it remained for Leeuwenhoek, in 1675, actually to demonstrate with his rude micro- scope the presence of infusoria in the saliva. The theory of a con- tagiitm vivum was taken up from time to time after that date, and Robert Boyle, a prominent writer of the same century, maintained that he who obtained a proper comprehension of fermentation would be able to interpret satisfactorily the various phenomena of disease, particularly of fevers. Spallanzani, in the eighteenth century, and after him Gay-Lussac, in 1810, experimented with fermentation. Cagniard-Latour and Schwann, in 1837, recognized that alcoholic fermentation was due to the presence of a living organism, the yeast plant ; but this view was opposed with all the weight which the authority of Liebig could bring to bear upon it, who believed that fermentation was of a purely chemical origin. In 1840, Dr. Farr applied the term "zymotic" (Cuficoatz, a fer- ment) to certain diseases supposed to be due to a fermentative pro- cess. Ten years later Davaine demonstrated the bacillus anthracis in the bodies of animals which had died of splenic fever. It was at that time thought, however, that disease might arise de novo, and that, although organisms might be present, it was possible that they might have been formed by "spontaneous generation." It was not, however, until Pasteur, in 1858, unveiled the mysteries of fermentation, and later disproved the theory of spontaneous generation, that the relation of micro-organisms to disease began to be understood. Pasteur's law of fermentation has been likened in its importance to Newton's law of gravitation. It is undoubt- 1 8 SURGICAL PATHOLOGY AND THERAPEUTICS. edly to him that credit should be given for furnishing the first reliable data from which the modern science of bacteriology has been evolved. Davaine, stimulated by Pasteur's researches, re- newed his studies of the bacillus of anthrax, and fully identified the organism as the cause of the disease. This bacillus may there- fore be placed, chronologically, at the head of the list of patho- genic bacteria. Pasteur showed also that putrescence is a form of fermentation due to the presence of micro-organisms, and he demonstrated that the changes taking place in the secretions of a wound were of a similar character. It was at about this time (1865) that Lister began to appreciate the bearing of this scientific work upon surgery, and commenced his studies upon the antiseptic treatment of wounds. This gave a powerful impetus to the study of the relation of micro- organisms to disease. No great advances were made at first, and much of the work done by Pasteur and his pupils at that period in the study of the diseases of man suffered for the want of suitable methods of investigation. Bacteria were cultivated almost exclu- sively in liquids, the bouillon of Pasteur. The cut surface of potatoes was found to give an idea of the coarse appearance of the growths, which the bouillon failed to show. When, finally, solid media were substituted as soil for the growths of the organisms — an improvement for which we are indebted to Koch, the great German observer — the separation of bacteria, and consequently their identification, for the first time became possible. Bacteria belong to the lowest order of the vegetable kingdom, and, with a few apparent exceptions, they may be said to form one group of the fungi, the schizomycetes or fission-fungi, in distinction from saccharomycetes or yeast-fungi, which produce alcoholic fer- mentation, and the mucorini or mould-fungi. The fungi are chiefly distinguished by the absence of chlorophyll, and therefore by their lack of power to assimilate inorganic substances, being thus depend- ent for their food upon living or upon dead organic matter ob- tained from other plants or from animals. Bacteria derive their name from fiaxrrjpiov, a rod, which many of them resemble in shape. The developed organisjn is in form a cell with a membrane and contents, but no nucleus. The contents consist of a more or less homogeneous protoplasm. This protoplasm possesses, in common with the nuclei of the cells of the tissues of the body, the property of being strongly stained by the aniline dyes. It is surrounded by a delicate membrane, which, according to Thoinot, appears like a BACTERIOLOGY. 19 condensation of the peripheral layers of the protoplasm, from which it is with difficulty separated. According to De Bary, this membrane is a condensation of the innermost and most compact layers of a gelatinous envelope, and consists of a substance closely allied to cellulose. When stained with aniline dyes the difference between protoplasm and envelope is not visible, but by special methods of treatment the contents may shrink, and the envelope then becomes more apparent; or, when treated with water, the outer lavers swell up and their gelatinous nature becomes evident. The cells thus appear to be enclosed in a capsule. During the process of division this material holds the organisms together, and forms at times a zooglcea, or glue-like mass, in which they are im- bedded. It is this material which may give the cultures their form and consistency when growing on solid or in fluid media. In water it collects at times in large masses after the enclosed bacteria have attained their growth and have died, and becomes an efficient aid in the sand filtration of water-supplies. Many of the bacterial growths are in the presence of oxygen highly colored, being red, yellow, green, or blue. According to some this coloring matter is in the protoplasm, but according to others it lies outside the cells, as in the case of the bacillus prodigiosus, a beautiful red growth, where the pigment is in granules which have been exuded. A considerable number of the bacteria possess no movement whatever. Among these are the entire family of micrococci and some bacilli, as the anthrax and tubercle bacilli. The great major- ity of bacteria are, however, according to the conditions under, which they live, able to change from the motile state to the non- motile, or vice versa. When examined in fluid they may be seen moving about in serpentine-like curves, or they may have a sort of oscillating movement around a central axis. These movements of the bacilli are supposed by some to be effected by cilia projecting from different portions of their bodies, but these prolongations have been shown to be continuous, not with the protoplasm, but with the cell-membrane, and therefore, according to some authorities, are not organs of locomotion. Moreover, many bacilli which have active movements are found to possess no cilia whatever, being propelled by the vibratory movements of the flexible cells. The oscillations of the micrococci, so familiar to all observers, are not true movements of the cells, but are due to molecular agitation, the so-called u Browmian movement." The principal forms of bacteria are the small globular forms, or micrococci (x6xxo~ } a berry), the bacilli or staff-shaped bacteria, 20 SURGICAL PATHOLOGY AND THERAPEUTICS. and the spirilla or spiral forms. The shape of the micrococci — or u cocci," as they are often called — is usually round, although some have a more or less oval contour. There are certain prefixes to the noun coccus that indicate the different groupings which this variety of bacteria take in their growth. Thus if the cocci tend to form in pairs, or two cocci are seen still connected together, they are termed 1 ' diplococci ; ' ' those arranged in single rows of ' ' chains ' ' are called ' ' streptococci ; ' ' and those grouped together in grape-like bunches are called ' ' staphylococci. ' ' ' The long, staff-shaped bacteria are known as "bacilli" {bacillus, a rod). When unusually long they have a slightly undulating shape, and are then known as ' ' lepto- thrix ' ' (leptothrix buccalis). Under the head of ' ' spirilla ' ' are in- cluded those bacteria which take the form of an arc of a circle or of a spiral. The " comma bacilli " of cholera are included in this cat- egory. There are in bacteriological nomenclature a great variety of terms which are hardly worth studying, as some of them have been discarded altogether, and about others little will be heard in labora- tory-work. The two principal forms seen in the different varieties of surgical bacteria are the micrococci and the bacilli. Nageli attached little importance to form : he believed that bacteria might not only change their shape from time to time, but in the course of years and under varying conditions also change in their pathogenic qualities. The same species, he believed, might at one time be concerned in the different forms of fermentation, at another in the decomposition of albuminous substances, or in typhus, cholera, or intermittent fever. The present opinion is that bacteria are divided into a limited number of varieties according to their action and form, but these varieties are never changed into other forms. The possibility of such a change from a harmless variety to a most malignant type, as Buchner supposed in the case of the hay and anthrax bacilli, is now understood to have been due to impurities of culture. Slight changes in form and appearance may be brought about by methods of preparation, staining, or cul- ture. The organism may vary also in appearance with age and activity, but there is nevertheless a form which it always preserves as the type of its normal development. Bacteria multiply either by division of the cells into two equal halves — that is, by "fission" — or by spore-formation. When a coccus divides, it becomes elongated or oval in shape, the middle portion becomes slightly contracted, and a delicate line appears between the two portions thus indicated. This line of division subsequently swells, and develops into a new membrane for each BACTERIOLOGY. 21 of the daughter-cells thus formed. If the mother-cell is origin- ally separated from other cells, this division forms the so-called "diplococcus." If, on the contrary, a number of cocci are attached to one another and remain so during division in a linear direction, we have the "streptococcus" formation. If the fission takes place in two directions perpendicular to one another, we have as a result an arraneement of the cells such as is seen in the micrococcus tetragenus. If, however, segmentation takes place in different directions in the different cells, then we obtain the grouping of cells characteristic of the "staphylococcus." Each form of micro- coccus develops according to one of these methods alone, and never varies in its mode of growth. The bacilli elongate slowly before fission, but the division of this form is not so easily recognized as that of the cocci. A number of bacilli and a few spirilla, after going through dif- ferent stages of development, ultimately undergo sporulation before the cell is finally destroyed. When sporulation takes place, the protoplasm seems to shrink together at certain points into denser masses, that may grow in a few hours to an oval, a round, or even a staff-like, structure, which refracts the light more strongly than the surrounding protoplasm. The spore thus formed possesses an extremely dense enveloping membrane, which, like the covering of vegetable seed, protects it from external influences until it can find conditions favorable for future growth. The cell is some- what distended by the spore, which may occur either in the middle or at the pole. While the spore is growing the protoplasm disap- pears, and a clear, refractive material takes its place. When it has reached its full development, the cell-membrane undergoes a gelat- inous softening, the cell breaks up, and the spore becomes free. There is usually only one spore to each cell ; as to. the nature of its contents nothing is really known. The vitality of the spore is shown by the fact that it will resist a temperature more than double that which suffices to destroy the bacillus. When, however, the spore begins to develop into a bacillus, it loses its tough envelope, elongates, and assumes the appearance of the mother-cell from which it escapes. At this period it is much more easily destroyed even than the bacillus, which when full grown has of course a much stronger membrane than the newly-formed organism. The conditions most favorable to spore-formation are those under which the nutriment for the bacilli has been exhausted and they are about to die. The cells may then leave behind them the seed for a future growth. 22 SURGICAL PATHOLOGY AND THERAPEUTICS. Bacteria, like all vegetable cells which do not contain chlo- rophyll, being unable to obtain for themselves sustenance from inorganic materials in the air or in the soil, grow only where organic material is present for their nourishment. They are to be found where organized life exists, except in the interior of the healthy organs of the body — in the air, in soil, in water, in cloth- ing, on the surface of our bodies, and in the intestinal canal. They grow best in alkaline or neutral media, and multiply, under favor- able conditions, with the most astounding rapidity : according to Cohn, a bacterium divides into two in the space of an hour, then into four at the end of a second hour, and into eight at the end of three hours. In twenty-four hours the number will amount to more than 16,500,000. "At the end of two days this bacterium will have multiplied to the incredible number of 281,500,000,000. .... The bacteria issuing from a single germ would fill the ocean in five days." Fortunately, the special conditions under which they can grow do not permit of any such rapid development. It is chiefly in dead organic substances that they find this favorable soil. It is now well understood that the process of decomposition is not only accompanied by them, but that through them alone it is also begun and carried on. To quote Cohn again : "Without the activity of bacteria all created things would retain their form and structure after death as well as the Egyptian mummies, or the wrecks sunk in the Dismal Swamp, or the bodies of the mammoth and rhino- ceros frozen for untold thousands of years in Siberian ice with uninjured hair and hide." Those bacteria which are concerned in the decomposition of dead substances of organic origin are called "saprophytic" or "saprogenic" (from oo~ip6z, putrid). A small number, however, grow in the living bodies of higher organisms. These develop at the expense of the tissues, and are, therefore, genuine parasitic organisms, whence they derive their name. Inasmuch as their presence in the body causes a morbid condition, they are generally called "pathogenic bacteria." Most of the parasitic organisms are, however, capable of growing in decomposing matter, and therefore may be saprophytic. In general it may be said that bacteria develop best at temper- atures varying from 30 to 40 C. There is little growth below 20 C. or above 40 C. The saphrophytic forms prefer a tempera- ture of about 24 C. ; the pathogenic organisms grow best at or near the temperature of the body. In studying the fermentations Pasteur discovered that certain BA CTERIOL OGY. 23 organisms could live without oxygen, and these he called anaerobic, while others were able to multiply only in the presence of air. The latter he called aerobic. The greater portion of the bacteria are aerobic, a slight dimi- nution in the amount of oxygen being sufficient to prevent their development. Others, however, can grow well in media rich in oxygen, but are able also to grow where there is no oxygen. The latter are sometimes called the ' l facultative-aerobic bacteria. ' ' Most of the pathogenic bacteria belong to this variety. The oxygen in the body, with the exception of the lungs, is not present in large quantities, and what little is found there is soon consumed. As illus- trating the action of the two kinds of bacteria, it may be well to give the following summary of Pasteur's theory of fermentation in decomposition: The process begins some twenty-four hours before outward manifestations are perceptible. During this time the bacteria (or the microbes, as Pasteur prefers to call them) fall upon the fluid, and the aerobic forms multiply with great rapidit}-, absorbing all the oxygen in the fluid. Owing to their great numbers, the fluid becomes cloudy. If the fluid is so shut off that oxygen cannot get at it, the aerobic forms die and are deposited at the bottom of the vessel. When all the oxygen is used up, the anaerobic begin to develop, and the process of decomposition advances in a corresponding ratio. If air is admitted, the aerobic organisms form a scum (mycoderma) on the surface, and gradually shut off all access of oxygen, so that the other variety may be able to develop. Mould-fungi may be found in this layer. Two chemical processes are going on in the mean time, owing to the action of the two varieties. The anaerobic cause a fermentation in the deeper parts by chang- ing the nitrogenous compounds into simpler but still complex combinations, while the aerobic, living at the expense of free oxygen, decompose these combinations still further until they are reduced to the simplest binary com- binations, water, carbonic acid, and ammonia. Although true fermentation is due to an organism that does not feed on oxygen, yet the process will go on better when free access of air is given, as this provides for the aerobic form, which is essential for the beginning and end of the process. If the decomposition is fully completed, the organisms die, and their remains will be destroyed by other bacteria; and this process will go on until the organic material is completely separated into the constituents of the atmospheric and mineral kingdoms. Light has also an influence upon the growth of bacteria; that is, the presence of sunlight is distinctly unfavorable to their develop- ment. Very important factors in the etiology of surgical diseases are the chemical products of the micro-organism, whether developed inside or outside the body. The saprophytic bacteria, although they are non-pathogenic, may produce powerful poisons by setting 24 SURGICAL PATHOLOGY AND THERAPEUTICS. up decomposition in necrosed fragments of tissue. As decompo- sition is not a specific process, but a general expression for a multitude of different chemical combinations, it is not surprising that there should be formed a large number of chemical sub- stances the nature of which is still quite imperfectly understood. Most prominent among those who have studied the substances are Selmi and Brieger, who have given the name ptomaines (nrwfia, a dead body) to substances developed during these processes. Ab- sorbed into the body, the ptomaines give rise to that class of infec- tion known as "putrid intoxication," or saprsemia. Among the ptomaines is the sulphate of sepsin, described by Bergmann. Selmi has described a series of alkaloids obtained from decompos- ing substances, which alkaloids resemble atropine, morphine, and curare in their physiological action; and Nencki has obtained a substance, the so-called u collidin," which produces a similar effect. Brieger has added to these substances cadaverin, putrescin, and several others. Some of Brieger' s ptomaines produced the most profound toxic disturbance, and others are more or less harmless. To the former class probably belong the "toxines." The term ptomaine, however, is now largely used to indicate all products of bacterial growth. Some of these substances have a deleterious in- fluence upon the micro-organisms themselves. During the process of certain fermentations acids are sometimes developed that check further bacterial growth, and the process of fermentation comes to a standstill. More will be said upon this subject, however, when studying the process of infection. Leucomaines are animal alkaloids which result from tissue-metabolism in the body independently of bacteria. Their role in pathology is not yet well denned. In addition to the chemical products of fermentation, putrefac- tion, and infection there may be pigment-formation. The organ- isms which produce these substances are known as u chromogenic bacteria," having been classified by themselves by some writers. They probably do not directly form this pigment, but a basic sub- stance, wmich subsequently, by contact with oxygen or chemical substances in the media in which the bacteria are growing, pro- duces the characteristic color. Other bacteria produce phosphores- cences, but with both of these varieties surgeons have little to do. The anaerobic bacteria have a decided tendency to produce gas-formation, the nature of which is not yet understood. The cholera bacteria when cultivated have a peculiar odor, and those of decomposition may be present even in pure cultures of many forms of bacteria. BACTERIOLOGY. 25 We come now to the study of these organisms, but all that will be attempted here will be to give a general idea of the best methods now in use in bacteriological laboratories. For details of this part of the subject the reader is referred to the text-books of Frankel and Baumgarten in the German language, Cornil and Babes in the French language, and Sternberg's Manual of Bacteriology. Before the methods now in use were adopted it was extremely difficult to see the very minute organisms under the microscope. In the process of staining and preparing a thin section every- thing was done to bring out as clearly as possible the anatomical elements of the tissues. The magnifying power used was suf- ficiently high for examining cells and fibres; higher powers cut off the light and made the picture obscure. There was obtained by the methods then employed a good view of what is called the "structure picture;" that is, the anatomical structure of the spe- cimen was satisfactorily observed. Now, in order to see bacteria properly, the specimen must be so arranged as to see as little as possible of the structure picture. These details are seen because their refractory power is different from the fluid in which the sec- tion lies. If the refracting powers were the same, these objects would not be seen. The elimination of the structure picture is accomplished by the Abbe condenser, which is placed beneath the object and between it and the mirror. In this way many more rays are collected and focused on the object than those thrown by the mirror alone. The field of vision is flooded with light even when very high powers are used, and the structure picture now disap- pears. If at any time it is desired to make the tissues more apparent, all that is necessary to do is to cut off some of the rays with the diaphragm, and a return can then be made to the conditions which existed when no condenser was used. The bacteria must be colored very deeply or they will also be obscured. The staining fluids in use in 1870 were principally carmine and haematoxylin. These fluids stained nuclei well, but they also stained the other elements of the tissue, and had but little if any power to stain bacteria. When the aniline dyes were tried a few years later, it was found possible to color the nuclei of the cells and the bacteria with great perfection. The picture thus obtained is called the " color picture. " If now it is desired to obtain the color picture alone, the condenser must be used without any diaphragm, but if it is desired to examine the structure of an uncolored section, if the condenser is used there must be employed the narrowest diaphragm in order to bring out the details. 26 SURGICAL PATHOLOGY AND THERAPEUTICS. But it is not always necessary to stain bacteria in order to see them, and they can be examined in liquids also. Supposing it is desired to examine a flask containing bouillon in which bacteria are growing. A platinum loop, previously passed through the flame of a Bunsen burner and allowed to cool, is dipped into the solution, and a minute drop is carried on its point to a carefully- cleaned cover-glass. The fluid must be spread out over the cover- glass so as to form a thin and even film. The glass is then turned over and laid upon the object-glass very carefully, so that no air- bubbles or dry places are allowed to remain. The thinnest possible capillary layer of fluid should lie between the two glasses. If the organisms to be examined are growing on a solid culture- soil, a drop of distilled water is first placed on a cover-glass, and a small fragment of the culture is removed on the point of the platinum needle and rubbed up in the water. The glasses are arranged as before : a high power and immersion must be used with a medium diaphragm. The bacteria will be seen moving about in the liquid. This method is used chiefly for the purpose of determining whether a specimen contains micro-organisms or not. The liquid cannot be preserved for any length of time, for it soon dries up. The "hanging-drop " method obviates this dif- ficulty. A drop of the fluid is obtained by a loop with due pre- cautions, and is placed upon the centre of the cover-glass. A little vaseline is painted around the outer border of the cover-glass, which is then turned over and placed upon a hollowed-out object- glass. The vaseline seals up the chamber thus formed. Dry cul- tures can be examined in this way as well as fluid cultures. The fewer organisms there are in the drop the better. The border of the drop is the best part to study, as many bacteria will become attached to the edge of the drop, and will not, therefore, be so active in their movements. The form and size of the bacterial cell can well be studied in this way, and the preparations can be preserved for some time, cultures being taken from them later. The principal object of this method is to study the motility of the bacteria. The commonest way of examining bacteria is by some one of the usual staining methods. It is well to remark here that most varieties of organisms have not any special staining reaction pecu- liar to themselves, but can be stained by the ordinary cover-glass and aniline-dye method. The aniline dyes are derived from coal-tar products. Those most frequently used are the basic dyes, such as geutian-violet r BACTERIOLOGY. 27 methyl-violet, methyl-blue, fuchsin, and Bismarck-brown. The element in them that holds the coloring matter is of a basic cha- racter. The acid dyes, as eosin and acid fuchsin, are used to obtain a diffused contrast stain in the tissues. With the basic dyes an excellent i ' color picture can be obtained. ' ' The acid dyes bring out not only the nuclei of the cells of the tis- sues, but their protoplasm also, and therefore produce more of a 4 'structure picture," while the bacteria are hardly stained at all. The dyes seem to color the bacteria by virtue of a chemical action. They are usually dissolved in concentrated alcohol by shaking up an excess of the powder in alcohol and allowing it to stand and settle, and the fluid is then filtered immediately before use. These solu- tions are kept on hand and are diluted for use. A flask should be filled two-thirds with distilled water, and the alcoholic solution is then added drop by drop, as long as the fluid in the flask remains transparent. Gentian-violet is a strong and very desirable coloring agent, but it can easily overstain. Methyl-violet is less powerful, but also less durable. Fuchsin is one of the finest coloring agents : it does not over- color and is very durable. Bismarck-brown, which colors slowly, is usually employed as a diffuse stain, and it would probably not be used at all except that it is very suitable for photography. Many of the dyes can be reinforced and finer details can be brought out when desired by the addition of mordant substances, such as alum and carbolic acid. Ziehl's solution, used for this purpose, consists of the following ingredients : Fuchsin, Alcohol, Carbolic acid, 5 per cent, solution, Heating the solution during the staining process also makes the coloring more intense and durable. A high degree of heat is, how- ever, not suitable for sections, but rather for dried specimens on the cover-glass, as will presently be seen. If the preparation has been too deeply or generally stained, the excess can be removed by washing out in water or in alcohol. A weak solution of acetic acid may be employed for this purpose. One of the best ways of demonstrating the presence of bacteria in tissues is that known as "Gram's method." The preparation gl n. 1. c c. 10. c. c. 90. 28 SURGICAL PATHOLOGY AND THERAPEUTICS. is first placed for one or two minutes in a solution of gentian- or methyl-violet in aniline-water. It is then placed for one minute in the following solution : iodine, i part ; iodide of potash, 2 parts ; distilled water, 300 parts. This solution forms with the dye a deposit confined entirely to the bacteria. The preparation is now placed in absolute alcohol until it appears colorless to the naked eye. The alcohol is removed with blotting-paper, and the speci- men is finally mounted in Canada balsam. This is considered one of the best methods of staining for those bacteria which it does not decolorize. If desirable there can now be obtained a staining of the tissues with carmine or eosine, and thus "a double staining" be accomplished, the bacteria being of a deep-blue color, while the tissues have the contrasts which the different shades of red afford. This method, though difficult in execution and inapplica- ble to many forms of bacteria, gives excellent results in those cases to which it is adapted, and the inability of a bacterium to take this stain is often of diagnostic value. Supposing, now, it is desired to examine the blood, or the juices of internal organs, or sputa for bacteria, or a culture, and to employ the staining process — for uncolored preparations are of little or no use to the bacteriologist — the first step is to spread out a minute portion of the substance, as has already been shown, upon the cover-glass with a sterilized platinum needle. To make the layer as thin and even as possible a second cover-glass is placed over the first and the two glasses rubbed gently together. When separated by carefully sliding apart the glasses afford two prepara- tions. They must now be laid down with the specimen uppermost, and be protected by a bell-glass while drying. One of the great difficulties in staining such a dried specimen is that, as soon as the dye is allowed to come in contact with it, the albuminous portions, if such are present, swell up and become fluid again, and precipi- tate particles of colored matter which ruin the preparation. This is overcome, however, by heating the cover-glass by passing it through a flame of a Bunsen burner three times quickly, the prep- aration being uppermost. This heating does not seem to interfere at all with the form or with the staining power of the bacteria, and it fixes the specimen upon the cover-glass. The coloring fluid selected is next dropped upon the specimen, which is afterward washed in distilled water, and the specimen is now ready for mounting. The preparation may be made upon the slide instead of upon the cover-glass, and be examined without the intervention of any cover-glass. This gives greater facility of manipulation, BACTERIOLOGY. 29 and the slide can readily be cleansed if a permanent specimen is not desired, but, if this be done, great care must be taken of the lens. There are one or two modifications worth mentioning. If it is desired to remove any haemoglobin present, the glass should, after drying, be placed for a few seconds in a 1 to 5 per cent, solution of acetic acid, and, after washing in distilled water, be dried again before staining. If it is desired to clear up the specimen so that the cells shall not be visible under the microscope, there can also be used the acid, or, better still, two or three drops of a 33 per cent, solu- tion of potash or soda in a watch-glass of distilled water. This leaves the contours of the nuclei still faintly visible. Masses of fat are undesirable in such specimens for they confuse the picture and are likely to give deceptive imitations of bacteria, owing to the crystals which form. This material is disposed of by heating the cover-glass after allowing a drop of the dilute potash to fall upon the specimen. The fat is then dissolved and becomes invis- ible. The same purpose can be effected by dipping the specimen in chloroform and afterward in alcohol. The specimen, when satis- factorily prepared, may be mounted in water, and Frankel strongly recommends this to be done, as the shape of the bacteria is thus pre- served and their membranes are better shown. If it is necessary to mount them in a permanent shape, the specimens can be placed in Canada balsam, dissolved in xylol rather than in chloroform, as the latter robs the bacteria of the coloring matter and the speci- men quickly fades. It is exceedingly difficult to stain spores. By the ordinary methods of staining spores remain uncolored and appear as highly- refractive bodies, which are better seen in recent cultures, owing to the contrast with the highly-colored protoplasm of the young bacilli. Spores may, however, be stained if they are exposed for some time to heat. The cover-glass containing the specimen to be stained may be placed in a hot-air oven at a temperature of 120 C for an hour, or at a higher temperature for a shorter time, or it may be passed eight or ten times through the flame of a Bunsen burner. The spores may then be stained with an aqueous solution of fuchsin or methyl-violet. This method so injures the bacilli that they do not color as well as usual. If a double staining is desired, Holler's method may be used. According to Moller, the material is placed on a cover-glass, and is allowed to dry ; it is then passed three times through a flame, or is left for two min- utes in absolute alcohol ; it is then placed in chloroform for two minutes and SO SURGICAL PATHOLOGY AND THERAPEUTICS. washed in water, and afterward from half a minute to two minutes in a 5 per cent, solution of chromic acid, and again washed in water ; a solution of car- bolic fuchsin l is now poured over the glass, which is heated in a flame until boiling occurs for sixty seconds, when the solution is poured off and the preparation is decolorized in a 5 per cent, solution of sulphuric acid and washed in water. It is next placed in an aqueous solution of methylene-blue or of malachite-green, and again washed in water. The preparation is now dried and mounted in balsam. The spores are stained dark red, and the protoplasm of the bacilli is blue or green. To prepare pathological specimens for bacteriological study the portions to be examined should be cut into pieces about half an inch square and placed in absolute alcohol. The alcohol must be changed once or twice, and at the end of a few days the specimens are ready for the section cutter. 2 The sections can be taken out of water or alcohol and placed in a dilute coloring fluid for from five minutes to an hour or more. They are then placed in acidulated water or in 60 per cent, alcohol to remove the excess of coloring matter; they are washed afterward in water, which must be re- moved by alcohol before placing the sections in oil of cloves, or, better, in oil of cedar, whence they are taken and permanently mounted in Canada balsam. If a section is overstained, washing in alcohol will remove the superfluous color better than water. Alcohol is sometimes too powerful in its bleaching effects, and it is therefore desirable to remove the water by evaporation before placing the section in oil. If it is desired to make a double stain- ing, Bismarck-brown in weak solutions or picrocarmine may be used. Frankel thinks it is better to reverse the process; that is, to stain the nuclei first and the bacteria afterward. It requires considerable experience to distinguish readily all objects which are of non-bacterial origin, but closely resembling micro-organisms. Examination with the microscope alone would not have accom- plished a great deal in the science of bacteriology. It was neces- sary at first, in order to preserve live bacteria for study, that a medium should be provided in which they could grow. Although Pasteur accomplished a great deal with his bouillon culture-fluids, it was found that there were certain disadvantages inherent in this method of investigation that offered obstacles to further progress. The facility which a fluid offers for indefinite growth in every direction makes it exceedingly difficult to separate the different varieties of bacteria from one another. This differentiation was attempted by taking an exceedingly small quantity from one flask and placing it in a fresh flask, and later repeating the same opera- 1 See page 57, Surgical Bacteria. 2 See Appendix. BACTERIOLOGY 31 tion, until finally the dilution was so great that but one organism was found in each drop, and the special form was thus obtained. The slightest error in the process, however, speedily reproduced an impure culture. It was Koch's great merit to have systematized the first rude attempts to grow bacteria on solid culture-media and to bring the art of culture to its present state of excellence, though undoubtedly we are as yet but upon the threshold of this new field of science. The great advantage of the solid-culture method lies in the opportunity which it gives to isolate the different varieties of bac- teria from one another. Having accomplished this, bacteria can now be planted rapidly from fresh growths until the organism has passed through several generations, with the certainty that there will result a growth which is not only a particular kind of bacteria, but one that has now become entirely disassociated from the orig- nal source from which it was taken. To provide a suitable soil the soil must not only contain those ingredients which bacteria need for their growth, but it must also resemble, as nearly as it can be made, the chemical constitution of those tissues which the organ- ism attacks. It is also absolutely necessary that the material used must entirely be free from organisms of any kind, and that it must be sterilized thoroughly. For fluid culture-media a watery extract of meat or a bouillon is used ; for the solid culture-media an admixture of gelatin, or a Japanese substance known as "agar- agar," or coagulated blood-serum, potato, or egg-albumin, etc., is employed. Sterilization of culture-media is a most important feature of bacteriological technique. It may be effected by heat or by filtra- tion. The former method is the one chiefly employed. Bacteria which do not form spores are killed at a comparatively low temperature. Sternberg found that the pyogenic cocci required the highest temperatures, and that they were killed by an exposure for ten minutes to a temperature of 62 C. All bacteria are de- stroyed in one or two minutes, in the absence of spores, by exposure to the action of boiling water or of steam. A very much higher temperature is required for the destruction of micro-organisms when dry heat is used. The spores of bacilli have a much greater resisting power, and in some cases are not destroyed by a boiling temperature maintained for several hours ; but the majority are killed by being subjected to the boiling temperature of water for a few minutes. Fractional sterilization is employed for certain nutri- ent media, for the reason that prolonged boiling may injure them. 32 SURGICAL PATHOLOGY AND THERAPEUTICS. This method is based upon the supposition that some of the more resistant spores may be present in the culture-material, and that bacteria may be developed from them after sterilization by the ordinary method. A repetition of the process will therefore destroy the growing bacteria which are developed from such spores. The culture-material is subjected for a short time to the temperature of boiling water ; after an interval of twenty-four hours the operation is repeated for the purpose of destroying those bacteria which may have developed in the mean time from spores. This is repeated at corresponding intervals from three to five times. Test-tubes and all glass and metal objects which it is intended to use in the laboratory are sterilized by dry heat. A hot-air oven made of sheet iron with double walls and shelves is used for this purpose. A much higher temperature is needed under these con- ditions than when moist heat is used. Micrococci and bacilli are not destroyed below a temperature of 120 C. It is necessary to raise the temperature to 140 C. to destroy spores, and the degree of heat should be maintained for an hour or more. When, there- fore, apparatus is sterilized, a tem- perature of about 150 C. should be maintained for this length of time. As moist heat acts more rapidly upon bacteria, the sterilization by steam is extensively used. Koch's apparatus consists of a copper or a zinc cylinder which is covered with a jacket of felt. There is an open- ing at the top for the escape of steam, and another through which a thermometer may be inserted. The water in the cylinder is heated by a Bunsen burner, and the steam is maintained at a temperature of ioo° C. Near the lower third of Fig. i.— Arnold Sterilizer. the vessel is a perforated shelf which is placed sufficiently high so as not to come in contact with the water. The Lautenschlager sterilizer is so arranged that a current of steam descends from above upon the objects to be sterilized and passes out through the bottom of the vessel. The Arnold sterilizer (Fig. 1), which is largely used in the United States, is convenient, as it is so arranged that steam BACTERIOLOGY. 33 can be obtained rapidly with a small quantity of water. It has the advantage also of great simplicity. The autoclave is a form of sterilizer by means of which steam can be obtained under pressure. Under these conditions a single sterilization at a temperature of 115 C. for half an hour suffices. This apparatus is, however, expensive. Test-tubes which are to contain the nutrient media are plugged with cotton, which acts as a filter, allowing the access of air, but preventing the entrance of bacteria. After sterilization in the hot-air oven the tubes are ready to be charged with the nutrient media. The bouillon peptone-gelatin is subjected to a temperature of ioo° C. for ten minutes at intervals of twenty-four hours, four days in succession. Bouillon and agar-agar jelly may be prepared in the same way or be steamed once for an hour. The sterilization of culture-material should be tested by placing it for a few days in an incubating oven at 30 to 35 ° C. The culture-media should be slightly alkaline, and should resemble as closely as possible the fluids of the body. To make a suitable bouillon, cut up 500 grammes of lean meat, place it in a pint of water, and let stand for twelve hours in a cool place. Now squeeze through a loose cloth, a little peptone being then added to take the place of albuminous substances precipitated on heating. Boil in a water-bath or in steam three-quarters of an hour, and neutralize with a satu- rated solution of the carbonate of soda. Boil again one hour, and the coagulable albuminoids will be precipitated or will float upon the surface. Filter through paper wet with distilled water. The bouillon must still be kept alkaline, or at least neutral, and should not, after repeated boiling, become in the least cloudy. The white of an egg, added before boiling, helps to clear up the fluid. The fluid thus prepared should be placed in sterilized test-tubes, and the tubes thus charged must finally be sterilized by the fractional process. Bouillon is a good material to use if it is desired to measure a given number of bacteria, as each drop will always have about the same number, or if it is desired to watch their development in the hanging drop or to obtain large numbers of bacteria. One of the first forms of solid media used was the cut surface of FlG< 2 cooked potatoes. Potato- culture. A practical method for preparing potatoes for planting bacteria is as follows : Good-sized potatoes should be selected, and the ends sliced off. They are then punched with an apple-corer. Cylinders about two inches in 3 34 SURGICAL PATHOLOGY AND THERAPEUTICS. length are thus obtained, which are split obliquely. These pieces are allowed to soak in cold water for two or three hours, and are then placed in sterilized test-tubes containing a fragment of glass to support the potatoes in such a way that they will not be immersed in the water of condensation. The tube thus charged is sterilized by the fractional method (Fig. 2). Gelatin possesses the much greater advantage of providing a solid material which is at the same time transparent. Nutrient gelatin should thus be prepared: 1000 parts bouillon, 10 parts peptone, 5 parts salt, too parts gelatin are the proportions of the ingredients. Shake and heat to melt the gelatin. Soda solution should be used for neu- tralizing. Boil the mixture half an hour to precipitate coagulable substances, and filter. The filter must be warm. The resultant fluid must be clear, and must remain so on boiling. In sterilizing it must not be subjected too long to heat, as heat injures the stiffening properties of the gelatin. Steaming fifteen minutes a day for three days is sufficient. The disadvantage of gelatin is its liability to become softened by heat, and it therefore cannot be used for making plates of those organisms requiring for their development a temperature of 30 C. Agar-agar is a substance resembling isinglass, prepared in the far East from a gelatinous form of algse. It is nearly soluble in hot water, forming a jelly which melts only at 90 C. and hardens again at 40 C. The preparation of agar is much harder than that of gelatin, on account of the greater difficulty of filtration. The addition of 6 to 7 per cent, of glycerin to the preparation makes it a suitable soil for the growth of tubercle bacilli. Agar-agar is thus prepared : To 100 parts bouillon, 10 parts peptone, and 5 parts salt are added 1 to 2 parts agar-agar. This mixture must be boiled for two or three hours before filtering. Blood-serum may be employed for the growth of a great variety of bacteria, but more particularly for those organisms which do not develop readily on other media. The blood is received in sterilized cylinders, which remain on ice for two days to allow the coagula- tion to be completed. The serum is then removed with sterilized pipettes and placed in test-tubes. Human serum, ascitic, hydro- cele, and ovarian fluids have been used in the same way. The tubes thus charged are sterilized by the process of discon- tinuous heating. They are left in a hot-water bath of a tempera- ture of 6o° C. for about an hour daily for from five to seven days. Koch has devised an apparatus for this purpose. The tubes are left in an oblique position, so that a large surface may be exposed for culture purposes. After being sterilized the serum is solidified by a careful exposure to a temperature of about 68° C, which causes it to coagulate, forming a transparent jelly-like mass. BACTERIOLOGY 35 A great many forms of organisms will not grow upon any of these cnltnre-soils or on any that are now used. This can easily be demonstrated by trying to inoculate them with a drop of saliva which under the microscope can be seen to contain a great variety hi i|, Fig. 3. — Method of Filling Test-tubes with Nutrient Material. 1 of organisms. The resulting culture will contain but compara- tively few of these forms. About 10 ccm. of the culture-media are placed in each test-tube. The gelatin is allowed to harden with the test-tubes in the vertical position, and is inoculated by thrust- ing the platinum needle, charged with the infected material, into the gelatin. This is the so-called "stab-culture" or "stick-cul- ture." The agar-agar and blood-serum are usually allowed to solidify while the test-tube is in an oblique position, thus giving as large a surface as possible for the bacterial growth. If, now, there is a great variety of bacteria growing in a speci- 1 The funnel containing the material to be used is protected from the air by a plate of glass. A rubber tube connects the funnel with a pointed glass nozzle, and the flow of fluid is controlled by a Mohr check-cock. A plug of cotton is held between the fingers of the right hand, and the tube is held in the left hand. On the right are the empty sterilized tubes, and on the left are the baskets containing the tubes which have been filled. 36 SURGICAL PATHOLOGY AND THERAPEUTICS. men (as in faeces), they can be separated by plate-cultures. Three test-tubes containing the gelatin mixture are melted in a water- bath at a temperature of from 30 to 40 C. : a very minute frag- ment of the material to be examined is placed in one of the tubes, and is thoroughly mixed with the culture-fluid ; from this " original" tube, as it is called, three drops of the liquid are trans- ferred to the second tube, and from the second tube three drops are transferred to the third. The culture-fluids are thus progressively made more dilute. The fluid gelatin is poured into Petri dishes (Fig. 4) or upon square glass plates, and is allowed to harden. The plates are then placed in a large double dish upon little trays, one above an- other. Wet filter- paper is placed in the bottom of the dish to keep the air moist. The bacteria in the fluid are thus more or less widely separated from one another, and the vari- ous colonies are given an opportunity to develop separately. There is thus an opportunity not only to determine the number of varieties, but also to contrast them with one another. Some liquefy the gelatin ; some are pigmented. If it is desired to examine a particular colony, the plate containing this growth may be placed under a microscope of low power, or, under favorable circumstances, a cover-glass may be placed upon the colony and the oil immersion may be used ; or the cover-glass with the adherent colony may, after removal, be dried and stained in the usual manner. Many bacteria that cannot be separated in any other way may be obtained by the plate method. The colonies it is desired to study must now be transferred to culture-tubes, where they are more protected from infection from outside sources and can more carefully be studied. A minute fragment is taken from one of the colonies while observing it through a lens of low power. The needle with the fragment thus obtained is thrust deeply into a gelatin culture-tube. As the cul- ture grows it is not difficult to determine whether it is pure or not. Another mode of transferring the culture from the plate is to draw the platinum needle over the surface of the agar-agar, which is Fig. 4. — Petri Dish with Colonies. BACTERIOLOGY. 37 usually allowed to harden by placing the tube in an oblique posi- tion. This allows the culture to grow upon the surface and in the presence of oxygen. As a rule, the gelatin and agar cultures will live for three or four months ; it is better, however, to renew the cultures every six weeks. The anaerobic bacteria are much more difficult to cultivate. The culture-media must be treated with substances which rob them of their oxygen. The organisms must thoroughly be mixed with the gelatin. After spreading the fluid gelatin containing these organisms on plates, they are covered, before hardening, with thin leaves of mica to cut off the oxygen, and are sealed up by paraffin poured over the edges of the mica. Or the gelatin may be boiled in the test-tube before the bacteria are mixed with it, and then quickly hardened. The boiling process drives out the oxygen, and the deeper layers in the tube are protected from oxygen by the upper layers, and anaerobic bacteria can then be made to grow. This method, which has the advantage of supplying different amounts of oxygen, is available for those anaerobic forms that can grow where there is no oxygen, but prefer oxygen. They will be found in the upper layers of the tube. Those which can only grow where there is no oxygen will be found at the bottom of the tube. If the gelatin in a tube is punctured by a platinum needle armed with anaerobic bacteria, the deeper portions only of the puncture line will show signs of growth ; as the layers are reached where oxygen still exists, the growth will stop. Bggs may be used for the same purpose. A small puncture having been made and the organisms introduced, the hole is sealed up with collodion. The small amount of oxygen existing in the egg is soon replaced by sulphuretted hydrogen. A method of cultivating anaerobic bacteria in the presence of hydrogen gas will be described in con- nection with the tetanus bacillus. If it is necessary to keep the culture medium at a high temper- ature, an oven must be provided for the purpose. That now generally in use has a double wall which contains water heated by a gas-jet. The degree of heat is indicated by a thermometer and is regulated by some automatic arrangement. The escape of heat from the sides of the oven is prevented by a felt jacket. The action of the pathogenic bacteria in disease is not yet fully understood. One of the earliest theories assumed that the presence of bacteria in large numbers in the organs acted mechanically to impair their functions. This is probably true to a limited extent only. According to Frankel, their action is explained by the 38 SURGICAL PATHOLOGY AND THERAPEUTICS. development of a specific, exceedingly poisonous substance having a very deleterious influence upon the organism. This poison, like that of the serpent, may spread itself all through the body, and, although small in quantity, may produce very marked effects. It probably varies greatly in amount in different cases. As to whether the poison is a product elaborated from the bac- terial cells as a specific excretion, or is the result of a tissue-meta- morphosis brought about by the organisms, which select from the tissues such substances as are most nutritious to them, is a point about which authorities differ. Opinions at the present time are pretty evenly divided upon this point. It can easily be understood that when one or two important elements are taken from the chemical composition of a cell or from the matrix in which it lies, an entirely new chemical compound may be the result. The chemical nature of the tissues in which the bacteria grow is there- fore an important element in determining the nature of the com- pound that will be formed. It is a well-known fact that the albu- minoids, for instance, are necessary for the development of most toxines. Poisonous substances may be developed in one case which in another fail to form, owing to the absence of some important basic substance. The result of such action of bacteria upon the cells of the body is to produce what is known as " irritation." If the action is suf- ficiently powerful, death of the cell will ensue, but if it be less powerful and continued for a certain length of time, the result will be a growth of new cells. This action is probably exerted through the endothelium of the capillaries, for we often see bac- teria enclosed within such cells. These cells exercise an important influence upon the nutrition of the organ, as they determine to a certain extent what chemical substance shall be allowed to pass through the vessel's walls for its nourishment. The result of such a disturbance of nutrition upon the organ will of course affect its functions, and this may go to the point of producing all trie phenomena of an inflammation. The production of a general con- stitutional disturbance will be found discussed at more length in another chapter. It may merely be said here that the most gene- rally received opinion is that substances are produced which have a ferment-like action and increase the tissue-metamorphosis greatly throughout the body. Baumgarten, however, believes that the growth of foreign organisms in the body is alone sufficient to account for all the phenomena of fever without assuming develop- ment of a particular virus. BACTERIOLOGY. 39 It is a well-known fact that ptomaines can be separated from their bacteria, and, if introduced into the body, can produce local or general disease. That apparent suppuration can be produced experimentally in this way has finally, after much discussion, been determined in the affirmative. Introduced in large quantities, ptomaines may excite grave constitutional disturbance. These substances are not, however, multiplied and reproduced within the body ; they exert only a passive role. Such a condition is known as ''intoxication" or "toxic infection," as distinguished from the "septic infection" of bacteria. The question of immunity of the living body to the action of certain bacteria is one which has received a vast amount of atten- tion, and is still unsettled. Leading up to this question is that of the mitigation of the virulence of bacteria and the production of a vaccine, as first broached by Pasteur. This change in the activity of the organisms may be produced by allowing them to grow for an unusually long time in their culture-media. In this w T ay the power to develop in the living body seems gradually to be lost. This change in the bacteria shows itself in a more vigorous growth upon the soil than took place at first, when it was less accustomed to its situation. The organisms of chicken cholera and anthrax were first successfully cultivated so as to produce a "vaccine" for these diseases. Another way of weakening the action of the bacteria is to mix with the culture-media certain chemical substances which' are poisons to them, but not sufficient in amount to kill them. Roux weakened the anthrax bacillus in this manner by mixing bichromate of potash with the bouillon. This experiment suggests an expla- nation of the cause of the insusceptibility of certain animals to some forms of bacteria which are passed through them, owing to the pres- ence of peculiarly hostile chemical compounds in their blood. A weakening of their power is also brought about by exposure to atmospheric pressure, sunlight, and high temperatures. The cause of the weakening of virulence is supposed to lie in a degeneration of the bacterial cell-protoplasm, but there is no marked change visible to the eye. How far this process of protective inoculation can be carried in the control of disease is a very doubtful question, but the fact has been definitely established that under certain circumstances a mitigated virus can render the most virulent poison harm- less. Bitter has shown that the bacilli of the anthrax vaccine develop only in the immediate neighborhood of the point of infec- 40 SURGICAL PATHOLOGY AND THERAPEUTICS. tion. Heuppe and Wood were able to produce the same immunity to anthrax by the injection of organisms, quite of a different nature, Fig. 5. — Bacteriological Syringe. On removal of the rubber bulb this instrument can be sterilized by dry heat. The almost capillary lumen permits great accuracy of dosage (H. C. Ernst's modification of the Koch syringe). and not even pathogenic, into animals which ordinarily were very susceptible to the disease ; and the same immunity has been pro- duced by the injection of peculiar forms of albumin in no way connected with bacterial growth. According to Frankel, the pro- tection afforded by vaccination is therefore the result of many substances which are chiefly of bacterial origin. According to Pasteur, immunity is acquired by the exhaustion of a chemical substance necessary for the growth of the micro-organisms. The " retention " hypothesis assumes that the products of tissue-meta- morphosis remain behind after the first invasion, and prevent a return of the same kind of organism. According to Frankel, this hypothesis has fewer objections than any other. It is known that in some forms of fermentation substances are developed which prevent the further growth of organisms, and may even prove poisonous to them. The phagocyte theory of Metschnikoff is still exciting great attention, and although it has already been referred to in another chapter, an allusion to it in this connection cannot be avoided. The first studies were inade upon the Daphniidae ( u water fleas"). The needle-shaped organisms which invaded the intestinal canal and the tissues of its body were surrounded by leucocytes and taken up into their protoplasm, and there were changes thus produced in them which suggested a sort of digestive process. Metschnikoff also placed fragments of liver taken from a rat, dead of anthrax, under the skin of a frog, and found them later infiltrated with leucocytes in whose protoplasm many of the bacilli were found. He found also that the bacilli, when artificially weakened and injected into warm-blooded animals, were quickly taken up by the leucocytes, but when injected with their full strength still pre- served, only a few were found in the spleen thus enclosed by leucocytes. He accordingly advanced the theory that the leuco- BACTERIOLOGY. 41 cytes, like their ancestors, the amcebce, had a certain instinctive propensity, in search of material for their nourishment, to consume the invading organisms. Hence the term "phagocyte." The protective influence of vaccination was supposed by this observer to be due to the power which the consumption of weaker forms of bacteria gave to the leucocytes to devour the more virulent varie- ties. The opponents of the phagocytosis theory, who are numer- ous, claim that the phagocytes eat up the bacteria only when the latter have been killed by other influences. It should be men- tioned that the leucocytes are not permanent bodies, therefore a capacity on their part for transmitting this acquired power to their descendants must be assumed if this theory is adopted. Although the phagocyte theory seems to play a certain role in the problem of immunity, the general weight of opinion seems at present to be opposed to this very attractive theory in its entirety, and to lean to the view that predisposition to disease means a favorable culture-soil for the bacteria in question, and immunity from disease means a soil unfavorable to those organisms. The chemical constitution of the blood-serum is therefore probably a more important factor in resisting or in favoring the invasion and growth of bacteria than any peculiar powers possessed by the white blood-corpuscles. When it is realized how hard it is to cultivate certain forms of bacteria on artificial media, it does not seem surprising that the varying condition of the chemical constitution of the blood and tissues of different animals, or the changes occurring at different periods of life of the same individual, should produce soils at times unfavorable to the growth of pathogenic bacteria. Buchner thought that this destructive power of the blood-serum lay in the amount of salts it contained and the albuminates with which they are combined. If, for instance, a rat is treated with phosphate of lime, which causes a production of acid in the body, the high grade of alkalinity of the blood will disappear and the animal will become susceptible to the anthrax bacilli. If a large number of bacilli are injected into the same kind of animal, a similar result will follow, for, although many of the bacilli are killed by the unfavorable conditions they meet with in an insus- ceptible animal, the dying organisms liberate acids and pave the way for an invasion of the system by the survivors. It should not be forgotten that an antagonism exists between the healthy living tissues of the body and bacteria. If these organisms gain an entrance into the circulation, they usually disappear rapidly. It 42 SURGICAL PATHOLOGY AND THERAPEUTICS. was at one time supposed that they were excreted with the bile or the urine, but this is now known not to be the case ; for it is established that an uninjured membrane will not allow the bacte- ria to pass through it, as a rule. Wyssokowitsch found that they were deposited chiefly in three organs, the liver, the spleen, and the bone-marrow. If, on the one hand, the organisms are non- pathogenic, they are destroyed in these organs ; on the other hand, if they are pathogenic, they have an opportunity to develop in those localities. There are three routes through which bacteria can obtain an entrance into the body : First, through the skin, generally through some wounded surface, although it has been shown by Garre that the apparently uninjured skin does not offer an insur- mountable barrier ; secondly, through the digestive canal ; and, thirdly, through the respiratory tract. The pathogenic bacteria may be defined as those which stand in a causal relation to certain well-marked morbid conditions, and they are regarded as the specific agents which produce the patho- logical symptoms. Koch lays down as a crucial test that certain conditions must be fulfilled before it can positively be asserted that a given organism is the specific cause of a disease. These are : it must be found in all cases of that disease ; it must be found in no other disease ; and it must appear in such quantity and be so distributed that all symptoms can be accounted for by its presence ; also, that the bac- teria must be capable of being isolated from the diseased tissues, and be grown upon some of the artificial culture-media, and when injected into an animal must be capable of reproducing the disease. Although all these conditions cannot be fulfilled, yet the constant presence of a single variety of bacteria in a given disease renders, it highly probable that it is the cause of the disease. II. SURGICAL BACTERIA. The number of bacterial forms found in, and fully identified with, surgical diseases is not large, yet it can safely be said, from the present standpoint of our knowledge, that the traumatic infec- tive diseases are all to be accounted for by the action of micro-organisms in the tissues. The organisms which surgeons have most frequently to contend with are those which produce suppuration. Of these there are several varieties, although the majority of them have the globular or coccus form and are called "pyogenic cocci." The staphylococcus pyogenes au- reus was first recognized by Ogston and Rosenbach, the latter of whom gave it the prefix derived from ozayuXr] (a bunch of grapes), owing to the characteristic grouping of the cocci in clusters (Fig. 6). Its shape is globular, and the developed organ- ism measures about 0.7// in diam- eter. The younger cocci are some- what smaller, the size depending to a certain extent also upon the nature of the soil in which they are grow- ing. They multiply by division in the manner already described, but the line of fission is difficult to see, owing to its fineness. They are readily stained by all the coloring agents, being well adapted to the Gram method of staining, and beine Fig. 6.— Staphylo- coccus Pyogenes Aureus. one of the varieties of micro-organ- Fig. 7. — Staphylo- coccus Pyogenes Albus. isms most easily demonstrated in this way. Although no spores are found, the aureus is a very durable form of organisrn. Its power of growth is not destroyed by drying for ten days. It requires strong chemical substances or 48 44 SURGICAL PATHOLOGY AND THERAPEUTICS. boiling for several minutes in water to kill it. On gelatin-cultures it can preserve its vitality and power of reproduction for a year. Becker first obtained growths of the staphylococcus on gelatin, to which it had been transferred from the abscesses of cases of osteo- myelitis, but Rosenbach was the first to recognize that it was not confined to this disease alone, but was common to all forms of sup- puration. It grows well at ordinary house-temperatures, but is more active when subjected to a temperature of from 30 to 37 C. It can develop activity in media which have only a very small amount of oxygen. The staphylococcus pyogenes aureus exhibits, when grown upon solid culture-media, certain peculiarities which distinguish it from all other varieties of cocci. When the gelatin is inoculated, a growth of an opaque gray color takes place along the whole length of the puncture. At the same time the gelatin immediately around the growth begins to liquefy, but more rapidly near the surface than lower down. At the end of three or four days the surface of the gelatin becomes completely liquefied, and the bacterial growth begins to sink as the softening of the gelatin proceeds downward. By this time it begins to assume a golden- yellow or orange color, and collects in a mass at the bottom of the puncture-canal. It has a peculiar odor of sour paste, particularly w T hen grown on potato. When a culture is made on the surface of obliquely-hardened agar there forms along the needle track primarily a moist glisten- ing growth, which is at first a yellowish-white, but soon becomes an orange color (Fig. 6). The growth is somewhat elevated above the surface, is from 3 to 4 mm. wide, and has a wavy border. The color may not develop at first, but it appears especially brilliant if the growth has not taken place in the high temperatures of the oven: in the latter case the luxurious growth appears to interfere with the pigment-formation, which occurs most pronouncedly when the growth is well exposed to the air. It can be prevented from occurring if the air is shut off by a film of sterilized oil or by other means. The aureus is found abundantly outside the human body. Its presence has been demonstrated in dirty dish-water, in the soil, and also floating in the air, particularly in foul hospital wards. But its commonest seat is the superficial layer of the skin. It has been found also in the respiratory and digestive tracts, in the normal mucus of the pharynx and the saliva, in the biliary ducts and the faeces, and, most important of all for the surgeon to remember, in the dirt collected under the ends of his finger-nails. SURGICAL BACTERIA. 45 The liquefaction of the gelatin appears to be due to the presence of a soluble peptonizing ferment which is excreted by the aureus. It has also the power to peptonize albumin. It has generally been supposed that poisonous ptomaines and toxines were not formed bv the staphylococci, but recent investigations have shown the contrary to be the case. The pathogenic qualities of the cocci of suppuration are described in another chapter. The aureus is the commonest of all pyogenic cocci, and it has been found in 80 per cent, of the cases of suppuration examined. Staphylococcus pyogenes albus (Fig. 7) behaves in all respects like the aureus, except that it does not develop the golden-colored pigment. It appears to be a variety of the aureus, *v. ...-' but cannot be so culti- \J v.^, #t .•"' '"'}'%"' vated as to change into .' V : . \ , '" : ,.\ the aureus. It always :* *':).: \J ^ ..["' ••.'.'.'■'■" retains its characteristic . t : :•;£'.#•*' \S. \ white growth, occurs less •. ..•*"*' '''->.., «... t \ t often than the aureus, _ . ,..--.. '•< •': \/ "••••:;.. and does not seem quite ' .-l}]-' .>' ?.jj> •„ so virulent, as the symp- ••*v. v -"*'" ;'*♦ * '*"'':;'' toms caused by it ap- ..«:' .V './ ... ..- A pear clinically less pro- *' \ 'S.\ >j " .. '-"y \ nounced in severity. : . U.:;' B% \\ (•"•{ Staphylococcus viri- '" •'' >'./.' : '' •• *"*""'" dis flavesce7lS occupies Fig. 8.— Streptococcus Pyogenes. an intermediate posi- tion between the aureus and albus (Babes). On agar it forms a delicate film. The cocci are irregular in shape, and are larger than the aureus. The staphylococcus flavescens is very rare. Staphylococcus pyogenes citreus, a variety seen by Passet in two cases, appears in all respects similar in its behavior to aureus and albus, except that it develops a lemon-yellow pigment. It lique- fies gelatin more slowly than the two varieties above named. Staphylococcus cereus albus et jlavus are two unimportant varie- ties of pyogenic cocci, also described by Passet. The cocci are cha- racterized by a dull, waxy growth on the surface of gelatin. They cannot be distinguished under the microscope in any way from the other varieties. As they are very rare forms, and later observers have failed to find them, Baumgarten suggests that it may be possible the genuine pyogenic coccus had died out, and that the cereus was a remaining form which Passet accidentally observed. 4 6 SURGICAL PATHOLOGY AND THERAPEUTICS. Micrococcus pyogenes tenuis is a name given by Rosenbach to another rare form of pyogenic coccus. It has only been seen once since by later observers. Microscopically, the cocci are somewhat more irregular in shape and larger than those of the aureus. On the surface of agar the tenuis forms a very thin, transparent deposit. This coccus obtains its name from the great deli- cacy of its growth. It is quite possible that this variety, like the cereus, was an accidental inhabit- ant of an abscess and not the genuine pus-pro- ducer. Rosenbach does not place it among the staphylococcus group of micrococci. The streptococcus pyogenes is one of the most important varieties of the pyogenic cocci. It usu- ally occurs alone, but sometimes it is found with staphylococci, and is microscopically identical with the streptococcus of erysipelas. The arrangement of the cocci distinguishes it in a marked degree from the staphylococcus group. The cocci are arranged in rows or chains (Fig. 8), instead of in bunches. There are usually from six to ten thus attached, and they appear to be grouped, further- more, somewhat in couples like the so-called "dip- lococci." The individual cocci are small globular cells from 0.3/i to 0.4/i in diameter. They grow at ordinary house-temperatures, but more actively at a temperature of from 30 to 37 ° C. They are not particularly sensitive to the absence of oxygen, but grow best upon the surface of nutrient media. They are easily colored by the different aniline dyes, and are adapted to the Gram method of double staining. In culture-media the cocci grow slowly (Fig. 9); in gelatin cultures the small white colonies appear throughout the whole length of the puncture. As a rule, there is not much growth on the surface, the growth reaching nearly its full development in four or five days. On agar the growth shows a similar tendency to collect in minute globular drops, which finally form a border at the margin of the scratch. The color of the points is white, and the growth at first has quite a transparent look, but later the centre of the colony has a- faintly brownish color. Fig. 9. — Strepto- coccus Pyogenes (culture). SURGICAL BACTERIA. M If it is desirable to obtain a considerable number of these cocci, they can be grown very rapidly in bouillon. The streptococci are found, in the normal state, in the saliva, in the secretion from the nostrils, in vaginal mucus, and also in the urethra. Thev are also found wherever the normal condition is disturbed by other diseases. We are apt to get what is called a "mixed infection" with this or- ganism in typhoid fever, diphtheria, pneumonia, tuberculosis, scarlet fever, etc., and it is therefore probably an important agent in producing compli- cations of those diseases. Bacillus pyocyanens is an organism found in green or blue pus. It occurs, however, only in open wounds, and is not, strictly speaking, a pyo- genic organism, not usually producing suppuration. It is sometimes found in the serous secretions of wounds and in the perspiration. It is a small, thin rod with distinctly rounded ends, and may occur in chains of five or six links. It .has very active movements. Spores are not seen to form. It be- longs to those organisms which can grow where there is a small amount of oxygen, and develops at ordinary house- and oven-temperatures. When grown in gelatin there develops a shallow bowl-like depression, on the border of which there forms a beautiful green fluorescent pigment (Fig. 10). The depression widens until it reaches the borders of the test-tube, and then the greater part of the bac- terial growth sinks to the bottom in thick, shining bands. The gelatin above gradually clears itself, and over the surface is formed a delicate yellowish- green film. The whole culture has a distinctly greenish tint. The pigment is deposited from the bacteria when in contact with oxygen, and it is therefore found only on the exposed edges of dressings. The substance then formed has been named " pyocyanine." According to Frankel, if i c.cm of a fresh bouillon culture is injected into the subcutaneous tissue of guinea-pigs or of rabbits, a fatal infection is produced. By begin- ning with minimum doses only small abscesses will result, the animals finally becoming able to bear doses which would otherwise be fatal. Its prophylactic character was first discovered by Bou- Fig. 10. — Bacillus Pyocyaneus. 48 SURGICAL PATHOLOGY AND THERAPEUTICS. chard, who showed that anthrax, even when already developed in the animal, could be cured by injection of this bacillus. Another variety, described by H. C. Ernst, is supposed by him to possess septic qualities, and still another is mentioned by Paul Ernst which is non-pathogenic. Bacillus pyogenes fcetidus is found, according to Passet, in the pus of perirectal abscesses. It forms on the surface of gelatin a delicate white or grayish growth. On agar and on potato it has a light-brown color and emits an offensive odor. Micrococcus tetragenus was first found by Koch in the tuber- culous cavity of a lung, and is occasionally seen in morbid and healthy expectorations. It was found by Steinhaus in an acute ab- scess near the angle of the jaw : under the microscope the charac- teristic groups of four were observed enclosed in a capsule, and in very large numbers. It was also seen by Iakowski in two cases of acute abscess, one on the finger and the other in the palm of the hand. In culture-media the cocci do not grow in any special order, but in the tissues they are arranged in groups of four imbedded in a gelatinous membrane. The organism is aerobic. It colors well with all the aniline dyes and by the Gram method. On gelatin it appears as thick, globular, whitish masses with a somewhat glistening surface. Bacillus coli communis (Escherich) was first discovered in 1885, at which time this micro-organism was reported as being constantly found in the discharges of cholera patients at Naples. Since then it has been found usually present in the normal dejecta. It is also found outside the body, both in air and in water and in putrefying fluids. Its presence in diarrhoeal discharges and its near relation to the typhoid bacillus caused it to be studied very closely in order to find some method by which the two organisms could be separated. Lately the importance of this bacillus as a pyogenic organism and as a cause of septic and suppurative pro- cesses has been fully recognized. The bacillus varies in shape with the media in which it is grown, and to some extent also with the source from which it comes. It is usually seen as a short rod, from 2 to 3// in length and from 0.4 to 0.6/i in breadth, with rounded ends. It may grow in chains of from four to six filaments, though it is most frequently combined in pairs (Fig. 11). Sometimes these various forms are associated together, giving the microscopic field the appearance of a mixed culture. Spores have not been demon- strated, but the organism possesses very numerous and peculiarly 'K <" r ' 1 K * 1 \ H* ^ ^ - 7' * \ ^ KV v '" v * make it difficult to distinguish them from the genuine gonococci. Bumm has succeeded, however, in making them grow on human ** - ;. y>--' blood-serum, but this growth is ** % *j accomplished with considerable \a '•■:* - , * \ difficulty. The materials used " V. v must, in the first place, be as free ^ .y** as possible from other organisms, ,-> '" - >s V>f otherwise the latter will outgrow the COCCUS. The gonorrheal pUS, Fig. 12.— Gonococci. containing the organism in large numbers, must be placed on the surface of the blood-serum in drops of considerable size. Scratch- or stab-cultures are of no value. The test-tube must be placed in an oven at a tempera- ture of from 33 to 37 ° C. The growth forms a delicate film with, well-defined, irregular borders. It appears like a layer of varnish upon the top of the serum. When somewhat thicker it has a grayish-white or a slightly brownish tinge. The growth is slow and scant in amount. At the end of two or three days the cocci begin to die off, and the culture must therefore be often trans- planted if it is desired to preserve the organisms. As nothing further will be said about this disease, it may be well to study here the action of the gonococci in the human epithelium. For some time it was thought that sufficient proof had not been afforded of the specific character of the gonococcus. There is no one single characteristic which distinguishes this organism from all 52 SURGICAL PATHOLOGY AND THERAPEUTICS. others, but the combination of peculiarities which have just been mentioned is such as is not found in other forms of bacteria. These peculiarities are — the diplococcus or " breakfast-roll " shape, the characteristic arrangement of the organism in the pus-cells, the bleaching caused by Gram's solution of iodide of potassium, and the difficulty of cultivation on ordinary media. Proof positive has been afforded, however, by several experi- menters of its contagious character. Bumm transplanted the twentieth generation of a gonococcus culture to the urethra of a bedridden paralytic, and produced a typical gonorrhoea. This experiment has recently been made upon the healthy urethrae of medical students. Bumm also examined the different stages of the gonorrhceal inflammation in the conjunctiva of new-born infants. Twenty-six fragments were taken from the conjunctival mem- brane at periods of the disease varying from thirty-six hours to thirty-two days. He found that the cocci, once having entered the conjunctival sac, reproduce themselves rapidly in the secre- tions, next invade the epithelial layer, and finally force their way down to the papillary layer. On the second day an enormous immigration of leucocytes takes place into the invaded layer of epithelium and the surrounding cells, pushing the epithelial cells, so as to lift them from their bed. On the papillary layer thus exposed there forms an exudation of a fibro-cellular character in which are clumps and rows of growing cocci. The bacterial growth does not invade the deeper tissue ; it does not go beyond the most superficial of the sub-epithelial layers. A regeneration of the epithelium soon covers over the denuded spots, and the cocci, after growing for some time longer on the surface, gradually disappear. It is only on certain types of mucous membrane that these organisms will grow — namely, those which possess a cylin- der epithelium or one closely allied to it. These are the mem- branes of the male and female urethra, the uterus, Bartholin's glands, and the conjunctiva. The more deep-seated secondary inflammations, such as involve the prostate, the epididymis, the testicles, the uterus, and the tubes, are frequently due to the pres- ence of some of the pyogenic bacteria ; but suppurative inflamma- tion of both tubes and ovaries has been found to be due largely to the presence of the gonococcus. The aureus has been found as a frequent companion of the gonococcus in the urethral discharge and in the pus from gonorrhceal buboes. The metastatic inflamma- tion of joints and the endocarditis which occur as sequelae of gonorrhoea have been supposed to be due to the presence of SURGICAL BACTERIA. 53 pyogenic cocci, but Councilman and others have shown that the gonococcus may be the sole organism concerned in the inflamma- tory process. Why the gonococcus should grow only in the superficial layers of certain mucous membranes, and nowhere else in the body, has not yet been satisfactorily explained. The most plausible theory seems to be that inasmuch as the gonococci possess a very marked preference for oxygen, they find a better culture-soil in the epithelium than in the subjacent connective tissue. Bumm has shown that injections of pure gonorrhoeal discharge or of pure cultures of the gonococcus into the subcutaneous tissue do not produce suppuration. That this loss of activity is not explained by the action of phagocytes is shown by the fact that the organ- isms, when the tissues are examined later, are not taken up by the cells of the part, but are nearly all to be found outside the leucocytes. After the gonococci have existed for a certain length of time in the epithelium of the part, they disappear spontaneously in a certain number of cases. This disappearance is accounted for by the casting off of the cylinder epithelium during the inflammatory processes, and its replacement by a pavement epithelium which resists the efforts of the cocci to penetrate it. In this way proper nutriment gradually fails them and they die out. It is generally accepted that cure is effected in this way rather than by the phago- cytes, for such leucocytes as are invaded by the gonococci are destroyed by the latter during the active growth and multiplication of the organisms which take place in the protoplasm of those cells. Streptococcus erysipelatis in all respects so closely resembles the streptococcus pyogenes that the majority of bacteriologists are unable to detect any constant differences between them either by the microscope or by culture. The description of the organism coincides with that already given to the streptococcus : therefore it is needless to repeat it here. Rosenbach undertakes to recognize certain distinguishing marks between the two. He thinks the cocci and the chains of the erysipelas coccus are larger than those of the pyogenic coccus. His delineations of the culture show a growth of the erysipelas coccus more transparent and more irregular and nodular in outline than is seen in the cultures of the other organisms. The brownish tint of the culture is also want- ing. The weight of evidence at the present time is, however, in favor of the identity of the two organisms. The question is dis- cussed more at length in the chapter on Erysipelas. 54 SURGICAL PATHOLOGY AND THERAPEUTICS. Bacillus Tetani. — The first observations on the nature and origin of this organism were made in 1884 by Nicolaier, who found a bacillus in garden soil, and who succeeded in producing tetanus in mice, guinea-pigs, and rabbits by injecting the soil into them subcutaneously. The same organisms were found in the diseased animals, but there was great difficulty in obtaining a pure culture of the bacilli, thus giving conclusive evidence of its power to produce the disease. This culture was finally accomplished in 1889 by Kitasato, who planted on a suitable culture-soil a frag- ment of tissue from the neighborhood of a wound in a man dead of the disease. He found that the spores of this bacillus germinated before those of the other forms of bacilli mixed with it. As soon as these spores had formed he subjected the culture to a temperature of 8o° C. , which killed off all bacteria ; con- sequently, the spores of the tetanus bacillus alone, remained, and a pure culture of this organism was obtained as soon as the bacilli had developed from them. The spores are found in garden soil, in masonry, in decomposing liquids, and in manure. The tetanus bacillus is a large slender rod with somewhat rounded ends. It resembles the bacillus of mouse septicaemia, but •v 1 ^ 1 / 1^ X! Fig. 13. — Bacillus Tetani. is longer: in fact, it sometimes grows into long chains which show very imperfectly the lines of division. The spore-formation takes place at the end of the bacillus, and, as it enlarges the cell considerably, gives it a "pin" or "drumstick" shape (Fig. 13). The spore germinates at a temperature of 37. 5 ° C. in thirty hours; in the temperature of a house, in about a week. It is motile, and belongs to the strictly anaerobic organisms, rapidly dying when exposed to the air. It is readily colored by methyl-blue and SURGICAL BACTERIA, 55 fuchsin, and is brought out very perfectly by the Gram method. It can be cultivated in gelatin mixed with grape-sugar, which aids in its rapid development. The upper portions of the gelatin remain sterile, but in the lower portions of the puncture there is an active bacterial growth which sends out innumerable little pro- longations, giving to the culture the appearance of an inverted fir tree. After the first week the gelatin begins to liquefy and to obscure the peculiar features of the growth, until, finally, the gelatin is changed into a whitish-gray, tenacious, shining mass. To obtain cultures of the tetanus bacillus from cases of trau- matic tetanus in man or from experiment animals the following method may be employed, which is a modification by Frothingham of Kitasato's method : Inoculate tubes of decidedly alkaline bouillon with pus from the wound or point of inoculation. If there is no pus, small fragments of tissue are snipped from the region of the wound and used for this purpose. The tubes should now be placed in an atmosphere of hydrogen at a temperature of from 37° to 39 C. At the end of forty eight hours a microscopic examination may be made, and if the tetanus bacilli are found, the tubes are to be heated for three-quarters of an hour to one hour in a water-bath previously heated to 8o° C. From these heated tubes fresh alkaline bouillon may be inoculated. Fig. 14. — Hydrogen Jar for Anaerobic Cultures. The stop-cock on the right allows the air to escape from the jar, while the hydrogen is passed in from the left. These fresh cultures may be allowed to develop under hydrogen at a temper- ature of 37 C. for forty eight hours (Fig 14). Pure cultures should be obtained in this way, the purity of the culture being verified by microscopic examina- tion and growth on solid culture-media, and the virulence being determined by inoculation experiments. Brieger has obtained from cultures a toxine which he named "tetanin," and in addition " tetanotoxin " and "spasmotoxin," all of which, when injected into animals, produce convulsive movements and, finally, paralysis. Inasmuch as the same group 56 SURGICAL PATHOLOGY AND THERAPEUTICS. of symptoms were obtained by the toxines as were obtained by the bacilli, and as the latter are hard to find in the blood and internal organs of individuals affected with tetanus, it has been thought probable that the symptoms of the disease are largely produced by these chemical substances. Although Rosenbach and Shakspeare have stated that the bacilli are to be seen in the central nervous system, subsequent observers have not been able to find them, and it is probable, there- fore, that the convulsions are produced by the tetanin elaborated by these organisms. Bacillus Tuberculosis. — Although experiments were made as early as 1865 by Villemin to prove the inoculability of tubercle, and as Cohnheim in the following decade decided that tuberculosis was a specific infectious disease, it was not until 1882 that Baum- garten and Koch simultaneously discovered the organism which causes the disease. Baumgarten should receive credit for first having seen the bacillus with the microscope, but it remained for Koch to cultivate it successfully and by inoculation to prove beyond question its right to be considered the cause and only cause of tuberculosis. The tubercle bacilli are small and thin rods about 2 to 4// in length ; that is, about one-quarter to three-quarters the length of the diameter of a red blood-corpuscle. The ends of the rods are generally slightly rounded, and are usually slightly bent near the middle or are more or less curved. In artificial cultures the rods are a little smaller than when growing in the tissues. The longest rods are usually seen in phthisical sputa. They are generally single, occasionally being found in pairs arranged like a V, and sometimes several are strung together. They do not possess the power of motion. Whether spore-formation takes place is unde- termined, although Baumgarten thinks it highly probable that it does occur, as a cheesy material, in which it is impossible to demonstrate the bacilli by any method of staining, when inocu- lated into animals produces the disease. Free spores have never been seen, nor have the bacilli been observed in the act of spore- formation. In the fresh state none of those bright, glistening spots are seen which are characteristic of spores. When colored, the bacilli exhibit, placed in regular order, bright spots which are very suggestive of spores. The expectorations can be kept months, and even years, in a dried state without destroying the vitality of the bacilli. The acids of the stomach and the products of decom- position have no effect upon them. Pure cultures of bacilli have SURGICAL BACTERIA. 57 been mixed with the food of animals, and have thus been passed through the digestive tract without any effect upon their vitality. This durability seems to be due to the unusually tough cell-wall which the bacillus possesses. The organism is a facultative anaerobic ; that is, it may grow without oxygen, although it pre- fers to grow with oxygen. This is one of the few bacteria which have a pathognomonic stain. Though taking the ordinary watery and alcoholic aniline stains with difficulty, yet when properly stained it does not give up its coloring material even in the presence of mineral acids — a property which the bacillus of leprosy alone holds in common with it. The following is a convenient method (Ziehl) of examining the sputa : The sputum selected is spread out upon a glass with a dark background to enable one to detect the various details, such as the fragments of the diseased lung, the secretions of the upper air-passages, and the saliva. The bacilli are usually found in the lung-fragments, which are small, tough, yellow clumps floating in the saliva. One of these clumps is removed by the steril- ized platinum needle and placed upon a cover ; a second cover-glass is then placed upon the first, and the specimen is gently pressed between the two so as to form a thin layer, whereupon the glasses are separated by a sliding motion and are allowed to dry in the air. To complete this process the glass to be stained is rapidly passed three times through a flame. A few drops of carbolic fuchsin 1 are allowed to trickle over the glass, and it is held over the flame until the coloring fluid partially evaporates. More staining fluid is now added, and the heating repeated until a satisfactory coloring is obtained, or the coloring fluid containing the specimen can be placed in a watch-glass and heated for a few moments over a water-bath. The specimen is then washed with distilled water. To decolorize the surrounding cells and other forms of bacteria a strong decolorizing agent must be used, as, for example, a 5 to 10 per cent, solution of sulphuric acid. The glass is moved up and down in this solution until the deep-red color becomes a yellowish brown. Next place the glass in 70 per cent, alcohol to wash out the dissolved fuchsin. Wash with distilled water and color again with ordinary watery solution of methyl-blue. Wash, finally, with distilled water and examine, wet or dry, the specimen, and mount it permanently in Canada balsam. The specimen is examined to the best advantage when wet, as the bacilli are not so much shrivelled as when mounted in Canada balsam. The tubercle bacilli will be found colored red, and any other bacteria which happen to be present, and which have been deprived of their red color by the acid, are stained blue, so that the different kinds can thus readily be distinguished from one another (Figs. 15, 16). The method may be simplified by dipping 1 Fuchsin 10 parts in 100 parts of a saturated aqueous solution of carbolic acid. 58 SURGICAL PATHOLOGY AND THERAPEUTICS. the red-colored specimens into a solution in which the acid and ?4 % S .4fc % # Fig. 15. — Tuberculous Sputum. the methyl-blue are both present: water, 50 parts, alcohol 30 parts, nitric acid 20 parts, and methyl-blue to saturation. This * * WW " m s* 1 % Fig. 16. — Tuberculous Urine. simplifies the process somewhat. Sections are colored very much in the same way: Place the section for half an hour in a dish of carbolic fnchsin ; allow it to float for one minute in a 5 per cent, solution of sulphuric acid ; wash in 60 per cent, alcohol. Next stain with methyl-blue for two or three minutes. Wash in water and weak alcohol, dehydrate in absolute alcohol, and, having cleared it in oil of cedar, mount in Canada balsam. SURGICAL BACTERIA. 59 Although for clinical work the short methods may be used in the hands of experts, still it must be remembered that the Ziehl solution stains a number of spores, which, unless recognized, may prove a source of error. It is not generally known that under certain conditions — for example, age — the bacilli may not be stained by the quick methods. When stained for twenty- four hours according to the now nearly-forgotten Koch-Ehrlich method the bacilli are well defined. For this reason the Koch- Ehrlich method is given. It should however, be remembered that this method shows crystalline forms which may be mistaken for bacilli: Place the section in aniline-water fuchsin for twenty-fonr hours ; decolor- ize in a 25 per cent, solution of nitric acid ; wash in 60 per cent, alcohol ; place in watery methyl-blue for a few moments ; wash and mount. Under the microscope is seen the miliary tubercle consisting of leucocytes and epithelial cells, and a giant-cell in or near the centre of the growth. The bacilli are found lying in small numbers between the leucocytes and in the giant-cell. The nuclei of the giant-cell appear to be arranged in a radiating manner at its periphery, as do also the bacilli. This arrangement is due to the fact that the centre of the cell has undergone degeneration and its contents at this part have disappeared. This appearance is quite characteristic of the tubercular giant-cell, and distinguishes it from the giant-cell of sarcoma (Fig. j6). The degenerative pro- cess is seen also in the other cells at the centre of the tubercle, while new cells and bacilli are seen on the borders. In this way the growing tubercle undergoes a cheesy degeneration at its centre. If the disease at this stage is on the surface of the skin or a membrane, ulceration will occur. The growth of the organisms is exceedingly slow, and takes place at the temperature of the human body, and very slight deviations from this point are likely to arrest their development. Koch devised expressly for this organism the hardened blood- serum. Nocard and Roux have suggested a combination of agar with glycerin, upon which it grows even better, as the bacillus seems to have a predilection for glycerin, and this being also much more easily sterilized. When cultivated in the test-tube on agar thus prepared, a well-developed growth is procured at the end of fourteen days, while on blood-serum from one to two weeks more must pass before the culture reaches the same point. It then appears as thick crusts of a dull grayish-white color, which crusts 6o SURGICAL PATHOLOGY AND THERAPEUTICS. are very dry and brittle and are made up of minute scale-like masses (Fig. 17). If the growth meets a drop of condensed moist- ure, it will form a thin film over the latter, without in the least disturbing the clearness of the fluid. To obtain materials with which to make a series of pure cultures tuberculous sputa may be injected into a guinea-pig. When tuberculosis is established, the animal should be killed, and a fragment of tu- bercle taken, with due precautions, from the lung and placed upon the culture-soil. After develop- ment takes place the fragment of lung can be seen under a low power, and surrounding it are seen S-shaped, wavy, and scroll-like masses of bacilli. The tubercle bacillus is not found growing out- side the living tissues of man and animals, the necessary conditions of nutrition and temperature not existing elsewhere. They must be regarded, therefore, as true parasitic organisms. Although they are unable to grow around us, their great power of resistance permits of their being preserved for a long time in a dried state mixed with dust, and of taking on an active growth whenever an opportunity occurs for them to become grafted again upon the living tissues. This inoculation may take place on the skin fol- lowing slight blows or bruises or cuts. The hands of attendants on the sick may be cut with a glass containing sputa. Anatomical tubercle is an exam- ple of this form of contagion. The disease known as "lupus" is but a variety of tuberculosis of the skin. As has been seen, the bacillus is extremely resistant to the action of the digestive fluids, and animals experimentally fed with this organism have succumbed to a general tuberculosis. Whether in- oculation can take place through the uninjured mu- cous membrane has not been demonstrated, but it is probable that if bacteria can penetrate the uninjured skin, they can also work their way through a normal mucous membrane. As a rule, the mesenteric glands are found first affected, and afterward the mucous membrane — a sequence which is at least suggestive that the membrane was previously in a healthy condition. Later, the spleen and liver are found infected. A very practical deduction from Fig. 17 — Bacillus of Tuberculosis on glycerin- agar. SURGICAL BACTERIA. 61 these experiments is the necessity for the supervision of food, par- ticularly the milk of tuberculous cows. It is now well known that the organisms are found in the milk. H. C. Ernst has shown that six drops of infected milk injected subcutaneously into a guinea- pig will produce a general tuberculosis even though there be no manifestations of disease in the udder. The question of an infection through the respiratory tract appears to be a disputed one. According to Baumgarten, experi- mental work seems to point against such mode of entrance into the system. Frankel, who writes with the authority of Koch behind him, takes the opposite view, and believes that breathing infected air is the most frequent mode of acquiring the disease. Experi- ment shows that the disease appears first at the point of infection, and therefore is at first local. The frequency of the disease in the lungs surely points strongly to the respiratory tract as the route through which infection takes place. Inasmuch as it has been proved that bacilli can float in the air when dry, it is probable that they are in this way conveyed from one individual to another. The durability of the organism, as already seen, protects it from the injurious influences of desiccation. As Stone has shown, it may retain its vitality in this condition for three years. How this transfer may take place has been explained by the investigations of Cornet. He demonstrated that the organisms are not found distributed indiscriminately in the air and other surroundings, but that they are found only in localities frequented by tuberculous patients, in such places as one would expect to find their expec- torations. This he demonstrated by injecting the dust of infected localities into guinea-pigs, thus producing the disease. The dust of other localities produced negative results. The bacilli are therefore frequently found in houses inhabited by tuberculous individuals. The organisms, having been expectorated on the floor or on handkerchiefs, are subsequently disseminated through the building in the form of dust. Cornet regards with suspicion hotels or hospitals occupied by consumptives, and the same may- be said of factories, prisons, or other buildings where large numbers of individuals are congregated. Cornet strongly advises that tuberculous sputa should not be allowed to dry up, but should be kept in a moist state. Bacillus mallei (bacillus of glanders ; rotz bacillus ; morve). — This organism was discovered by Loffler and Schutz, who made rheir announcement in 1882. They demonstrated the presence of the bacilli in the diseased tissues, cultivated them outside the living 62 SURGICAL PATHOLOGY AND THERAPEUTICS. organism, and inoculated them successfully into animals, thus reproducing the disease. These organisms are somewhat shorter than, and not quite so thin as, the tubercle bacilli ; that is, in length they are about two-thirds the diameter of a red blood-cor- puscle. They are frequently arranged in couples, side by side, but generally are single. In culture several of them may be linked together in a chain (Fig 18) ; in the tissues they are distributed in clusters, either parallel with one another or pointing in various directions. They possess no movements of their own. The pres- a tip «o vss^J-xv >*}K Fig. i 8. — Bacillus Mallei. ence of spores has been doubted, and the peculiar bright spots seen when the bacilli are colored are not spores, but are evidences rather of a degenerative change. Baumgarten has, however, by a special method of staining, been able to show that in some cases at least they are able to form spores. He does not think, however, the spore-formation takes place in the living tissue. The durability of the glanders bacilli is not, however, apparently great ; they do not bear desiccation more than two or three weeks ; exceptionally they may last as long as three months. The so-called " spontane- ous glanders " which occurs at long intervals after the existence of a local epidemic may be explained possibly by the presence of spores. They belong to the facultative-anaerobic bacteria, and grow best at a temperature of from 30 to 40 C. They belong to that class of bacteria which takes the staining fluid easily, but they SURGICAL BACTERIA. 63 as readily lose their color. One of the simplest methods of stain- ing is to treat a cover-glass preparation with warm carbolic fnchsin, and to wash off with a 2 per cent, solution of nitric acid. No method of double staining has yet been successful. In staining sections they should be placed six to eight hours in carbolic methyl-blue, then in acetic-acid solution, and finally in distilled water. Having been dried on the object-glass with a current of air, they are cleaned in xylol and mounted in Canada balsam. The bacilli can be grown upon a 4 per cent, glycerin-agar. When cultivated upon this soil, hardened obliquely in a test-tube at a temperature of 37 C, they form on the fourth or fifth day a white, transparent, moist, glistening film along the needle track. The growth on potato is very characteristic, it forming here a yel- low, transparent, honey-like layer which appears on the second day. In a few days it becomes deepened in hue and less transparent. For a short distance around the border of the culture the potato acquires a yellowish-green color. No other organism presents these appearances under cultivation. When seen in sections under the microscope, the bacilli are found singly or in small groups, the latter evidently having developed in a cell which has subsequently broken up. The capillary vessels do not seem to be involved, a fact which corresponds with their rare occurrence in the circulation. The greatest collection of bacilli is in the centre of the nodule or tubercle — a condition which is almost as characteristic of glanders as it is of tuberculosis. As the border is approached few organisms are found. The majority of the bacilli lie between the cells. The principal cells of the nodule are the epithelioid cells ; giant-cells are never seen. As the nodule develops leucocytes abound. The pathological changes which follow resemble the softening of sup- puration. The process seems to stand midway between the cheesy degeneration of tubercle and the suppuration produced by the pyogenic cocci. Very few of the organisms are found in the secretions from the nostrils. It has been found that the bacilli readily lose their virulence after several generations of culture have been reached, and this points to the fact that, outside the living organisms, the conditions are unfavorable for their preservation. The bacillus mallei probably does not grow out of the living tissues except under very favorable circumstances, it being for the most part a true parasite. The virus can readily be inoculated into horses, and the disease with all its characteristic symptoms may thus be reproduced. Asses are also susceptible to glanders, as are goats, cats, field-mice, 64 SURGICAL PATHOLOGY AND THERAPEUTICS. and guinea-pigs. Pigs, white mice and house-mice, and oxen, however, possess a certain immunity. Lions and tigers have suc- cumbed to the disease by infection experimentally produced by mixing the virus with their food. The virus acts first at the point of inoculation, and thence spreads slowly throughout the tissues, the blood remaining almost entirely free from bacilli. At the post-mortem examination nodules are found in the spleen, the liver, or the lungs. In examining a glanders nodule which has not yet broken down one is generally able to discover the bacilli in colored sections ; but it is well at the same* time to make a potato-culture, which will, if the bacilli are present, show the characteristic growths. If it is desired to examine the nasal secretions or discharges from ulcers, a satisfactory result will not be obtained by the above methods, for here the bacilli are not numerous, and are mingled with different kinds of bacteria which resemble them. This dif- ficulty is overcome by inoculating guinea-pigs with the material to be tested. Field-mice, which are otherwise suitable for inocula- tion, are liable to die of septicaemia. If the bacillus mallei be present, it will be found in the nodules that develop with the disease. Bacillus of Leprosy. — A few words on this organism are appro- priate in this chapter, as leprosy is a disease closely allied to tuber- culosis, and its organism bears points of resemblance both to the tubercle and to the glanders bacillus. The disease is one which also occasionally comes to the surgeon for operation. This bacillus was first described in 1880 by Hansen, whose work was later con- tinued by Neisser, a skilled bacteriologist. The bacilli of leprosy in appearance are almost exactly like the tubercle bacilli. They are long and slender rods with somewhat sharpened ends, and are, like the tubercle bacilli, without power of motion. It is doubtful also whether the clear tin colored portions seen in the bacilli after staining are or are not spores. As has already been shown, they are the only organisms which react in the same way as do the tubercle bacilli to coloring reagents, which, however, they take somewhat more readily. The readiness with which the bacilli are stained by the ordinary aqueous and weak alcoholic solutions of the aniline colors and also by the Gram method serves to distin- guish them from the tubercle bacilli. Although the bacillus of leprosy is found in all cases of the disease, it is not fully identified as the cause of the disease, it being impossible to obtain reliable cultures by any of the known SURGICAL BACTERIA. 65 methods. Inoculations by Bordoni of animals with the bacillus have been, without exceptions, failures, which Bordoni explains by the rapid weakening of the bacillus when removed from the body. Melcher and Ortmann placed fragments of nodules from a patient immediately in the anterior chamber of the eye of a rabbit, and observed the animal die of the disease several months later. At the autopsy small nodules were found in the internal organs, and the presence of the bacilli was demonstrated in them. Arning inoculated a condemned criminal in the Sandwich Islands with material cut from a leper. Some months later a nodule appeared at the point of inoculation, and at the end of five years his death took place, general leprosy having developed. The bacilli are ordinarily found in the skin and the tissue sur- rounding the nerves, and in the lymphatic glands, the spleen, and the liver, but they are rarely found in the blood. Their tendency is to grow in clusters, appearing usually inside of cells, some of which are epithelioid in character, and others apparently are leucocytes. These cells have been called i{ lepra-cells " by the Germans, but some observers denied the existence of such cells, and claimed they were merely clusters of bacilli lodged in dilated lymphatic vessels. Such clusters form a characteristic appearance in discharges from lepra sores. Syphilis Bacillus. — The question of the microbic origin of syphilis has been extensively discussed and investigated, but as yet no definite conclusions have been reached which are generally accepted by bacteriologists. The most important contribution to this study was made by Lustgarten, who in 1884 announced that he had discovered in the tissues and in the discharges from syphilitic ulcers a bacillus closely resembling the tubercle bacillus, but distinguished from other forms by its peculiar method of staining. The bacillus of syphilis usually is slightly curved or S-shaped. To color it a section should be placed for from twelve to twenty-four hours (at the ordinary room-temperature ) in a solution of aniline-gentian-violet, and for two hours be kept at a temperature of 40 C, and then placed in absolute alcohol for a few minutes ; next placed for ten seconds in a 1 per cent, watery solution of permanganate of potash, then for a moment in a strong watery solution of sulphuric acid, and finally washed out in distilled water. If sufficiently decolorized, it may then be mounted in the usual way. The same method may be used for the cover-glass preparation, except that water should be used instead of the absolute alcohol after staining, and the other steps of the process should follow one another more rapidly. A simpler method is to keep the cover-glass in a hot solution of fuchsin 66 SURGICAL PATHOLOGY AND THERAPEUTICS. for a few minutes, leaving sections for twenty-four hours in a cool solution, and then bleached in at first a weak and afterward in a concentrated solution of chloride of iron. Cover-glasses are washed in water and the sections in alcohol. The bacilli of syphilis are found always enclosed within large cells. Iyustgarten maintains that he has found these organisms in all cases of syphilis examined by him, but those who have carried out his methods have been unable co find them. They have been seen oftener in the cover-glass preparations than in the sections. Glanders and tubercle bacilli are stained also by Lust- garten's method, but .his syphilis bacilli appear to lose their color more easily. Lustgarten's attempts to cultivate these bacilli were not successful. They are said to have been grown upon a gelatin prepared from the bladder of Russian sturgeon. Transplantation of a fragment of tissue on gelatin left at the ordinary house- temperature produced a grayish-yellow growth around the frag- ment at the end of thirty-seven days. Inoculation was made also with the blood of an infected monkey, and the brownish growth produced was seen, on examination, to be composed of small bacilli. Granules were found also in the cultures which were thought to be' spores. In 1885 a discovery was made which threw a great deal of doubt upon the genuine nature of the syphilis bacillus. Two observers simultaneously demonstrated a bacillus in the preputial and vulvar smegma bearing a striking resemblance to Lustgarten's bacillus. Its appearance and reaction to staining were the same. The smegma bacilli were supposed to lose color a little more rapidly than the other form, but this difference does not appear to be constant. The only variation between the two forms is that, while both could be found in discharges from the vulvar or the preputial sores, or, possibly, also elsewhere in ulcerations of the surface of the body, the smegma bacilli could not be found imbedded in the tissues. Many authorities of note are inclined to think that some relation exists between these organisms and syphilis. But this is not the only organism which has been reported as the cause of the disease. Eve and Lingard described a bacillus cultivated from the blood and the diseased tissues in syphilis. It resembles the tubercle bacillus, but it is stained by the ordinary aniline dyes and by the Gram method, Lustgarten's method yield- ing negative results. A pure culture was obtained by inoculating hardened blood-serum with the blood or weak fragments of tissues SURGICAL BACTERIA, 67 from syphilitic patients. The growth appeared as a thin, light- yellow or greenish layer. Inoculation of monkeys from this culture were not successful. Disse and Taguchi examined the blood of patients with sec- ondary syphilis, and they almost constantly found cocci i/i in diameter, isolated or in colonies, between the corpuscles. The cultures upon the different media appeared as grayish-white masses, and all culture-media except serum were liquefied by them. This is, according to some, the only organism which liquefies agar- agar. Gram's method of staining yielded good results. The most important claim of these organisms to be regarded as the cause of syphilis was the inoculation of rabbits, dogs, and sheep, and the production of a chronic infectious disease which was transmitted to embryos developed before and after the inoculation. Inoculation of animals with the discharges of the diseased tissue of syphilitic patients has not always been attended with positive results. Klebs successfully inoculated monkeys with the liquid obtained from an excised chancre, in which liquid he had found bacilli. He made a culture in liquid gelatin and inoculated the culture-fluid. Buccal ulcerations developed in appearance some- what like plaques muqueses. Caseous deposits resembling gummata were found in the dura mater. He also implanted a fragment of a chancre beneath the skin, and obtained caseous deposits, which, however, resembled tubercle. Martineau and Hammic placed in culture-bouillon fragments of chancres, and subsequently found a growth of bacilli. They obtained, by inoculating monkeys w 7 ith this fluid, eruptions re- sembling those of syphilis. An inoculation of the prepuce in three places was followed, twenty-eight days afterward, by the develop- ment of nodules which resembled indurated chancres. Secondary symptoms were also developed. Although no satisfactory demonstration has been made, it seems highly probable that syphilis is of bacterial origin and that the organism is a bacillus ; but the necessary identification by culture and inoculation has not yet fully been worked out. Bacillus of Malignant CEdema. — This organism was first de- scribed by Pasteur as the vib?'io?i septiqne, under which name it is to be found in French works on bacteriology. Its present name was given it by Koch, and it is an organism found in one of the laboratory diseases of animals. It is occasionally also found in the traumatic gangrene of man, and therefore deserves a place here. It has often been mistaken for the anthrax bacillus, but from 68 SURGICAL PATHOLOGY AND THERAPEUTICS. which it is now readily distinguished. It is evidently a saprophytic organism, and is found in decomposing substances, in dirty water, and in dust, but is chiefly found in rich garden-mould. If such soil is injected into a guinea-pig, the animal dies in twenty-four or forty-eight hours, the oedema bacilli being found as the cause of death. They are slender rods, considerably narrower than anthrax bacilli, and are frequently seen together in bands which are often bent and curved. The bacilli have an active motion, but this motion soon ceases when the organism comes in contact with oxygen. Spores are formed in a temperature of above 20 C. They are large and are situated at the centre or the end of the rod (Fig. 19), which appears slightly distended at this point. The i/ \ \ I ' - f 1 ® 9 \ 1 Fig. 19. — Bacillus of Malignant CEdema : cover-glass preparations from the liver of a mouse. bacilli are strictly anaerobic, and are sensitive even to the slightest traces of oxygen. They take well the aniline staining-fluids, and when colored the pointed ends of the rods distinguish them from the anthrax bacilli. They do not stain well by the Gram method. They grow best in gelatin cultures to which has been added from 1 per cent, to 2 per cent, of grape-sugar. In the early stages they form varicose prolongations at the lower portion of the needle track, and on the periphery form radiating fibres. Later the gela- tin melts gradually into a cloudy, opaque mass. There is usually a gas-formation which distends the needle track nearly to the sur- SURGICAL BACTERIA. 69 face. The gas has a disagreeable odor, but it does not have the peculiar foul smell evolved by the genuine bacilli of putrefaction. If a pure culture of the cedenia bacillus is subcutaneously inject- ed into a guinea-pig, there is obtained an extensive bloody, ©ede- matous exudation of the muscular layer, but no pus nor foul odor and very slight gas-formation. The changes in the internal organs, liver and spleen, are very trivial. If, however, garden-soil is sub- stituted for the pure culture, there is then obtained an infiltration of the same tissues, with a dirty reddish serum which has a foul odor, and which may be purulent and be accompanied with an abundant gas-formation — in short, the picture of a progressive gan- grenous emphysema such as is often seen in traumatic gangrene in man. In this case there are found, in addition to the bacilli of oedema, other forms, such as the "pseudo-oedema bacilli," etc. A case of this kind is reported by Rosenbach — a compound fracture of the thigh and leg with subsequent gangrene. The thigh was amputated in the upper third. From the foul decomposing tissues of the limb a culture was taken immediately after the operation, from which culture he obtained a "saprogenic bacillus." The internal organs are but slightlv affected. If an animal be examined immediately after death, the oedema bacilli will be found in the superficial tissues of the body, but never in the blood-vessels. This arrangement is in striking contrast to that of the anthrax bacilli. But after death they rapidly spread throughout the body, and an active spore-formation occurs which does not take place during life. In the mouse inoculated with the bacilli of malignant oedema the course of events is somewhat different from that ob- served in the rabbit and guinea-pig : a rapid invasion of the entire body takes place during life, and the condition might easily be mistaken under these circumstances for anthrax. According to Chauveau, an animal which had recovered from malignant oedema was ever after insusceptible to this disease. Roux and Chamber- lain report that they obtained from the culture of these bacilli soluble substances which, when injected into animals, protected them from the action of the bacilli themselves. The ptomaine was obtained either by destroying the organisms with heat or by removing them with a filter, or the cedematous fluid from an inoc- ulated animal w T as used. An immunity was thus obtained. The ^pseudo-oedema" bacillus is described by Fliigge and Li- borius, who found it a frequent companion of the oedema bacillus. The pseudo-oedema bacillus is a somewhat thicker rod than the bacillus of malignant oedema, and possesses a very bright border. 70 SURGICAL PATHOLOGY AND THERAPEUTICS. It is distinguished also by the formation of two spores in each rod. The bacilli are strictly anaerobic. In sugar-gelatin they are ac- companied in their growth by an abundant gas-formation, which has an odor of old cheese. Small doses of the culture are not infectious ; in large doses it kills mice and rabbits. Bordoni and Uffreduzzi in 1889 obtained from the cadaver of a man who had died of a disease similar to anthrax an organism closely resembling the pseudo-cedema bacillus, to which organism they gave the name i(, proteus hominis." Tricomi, an Italian observer, found a slender, long bacillus in the blood of patients suffering from senile gan- grene, and also around the line of demarcation and in the adjacent healthy tissues. He cultivated the organism on the various media, stained it with the aniline dyes, and succeeded in producing gan- grene in animals at the point of inoculation of the pure culture. Godwin obtained from a case of gangrenous emphysema cul- tures of streptococcus and the albus. W. Koch obtained from a case of progressive gangrene in a young man a bacillus closely resembling the bacillus of glanders. Bonnome found the pyo- genic cocci in a case of gangrene of the lung in man, and by mixing the cultures with fragments of pith, as has been shown elsewhere (p. 145), he enabled the cocci to be caught in the lungs of animals inoculated, thus reproducing the gangrene of the lung. Ivingard found long bacilli in noma, and similar organisms in gan- grenous stomatitis of cattle. Ranke found in cases of noma streptococci similar to those found by Koch in his experiments on field-mice. As Senn justly remarks, there is no specific organism to blame for traumatic gangrene, which may be caused, he thinks, either by the mechanical obstruction of the vessels by large numbers of organ- isms in the capillaries, or by the chemical action of the ptomaines on the tissues, or, finally, by the excess of exudation in a part which mechanically obstructs the return of the venous blood. Those appalling forms of traumatic gangrene, which are de- scribed elsewhere, are in many cases probably caused by the bacilli of the class to which belong the oedema and pseudo-cedema bacillus, which, with the pyogenic cocci, are always present, and are ready to attack wounds occurring in foul parts of the body or in tissues whose vitality has been destroyed by some injury. Bacillus Anthracis. — This organism deserves a place among surgical bacteria, not only because it produces the malignant pustule in man, but also on account of its historical position among bacterial diseases. It was not only the first of bacteria SURGICAL BACTERIA. 7 1 found in diseased blood and tissues, but the investigation which demonstrated it as the true and only cause of splenic fever formed also the foundation upon which the science has subsequently been built up. In 1850, Davaine and Rayer announced to the Academie des Sciences that in animals affected with anthrax there existed in the blood little filiform bodies about double the diameter of a red corpuscle in length. These bodies did not possess spontaneous movements. After the subject had begun to attract the attention of the scientific world it was more carefully studied by Davaine himself, and later by Pasteur. But it was due to Koch that the existence of spores was discovered, and that cultures of the bacilli could be made and injected into animals, thus reproducing the disease. The bacilli, when grown on culture-media, are seen under the microscope as bright, transparent rods with slightly rounded ends. They are from 1 to 1.5/z in thickness and from ' , Z 1 ^— <- 3 to 6u long, and are en- % / "^^- J- X "\. . \ tirely without the power of ,* _ motion. If such bacilli are ~~ , [ \ placed in bouillon and ex- / 1 ^ / ~~~"~ .^ \ amined under the micro- C_ " y ' JS^ x ' scope, it is possible to ob- ®//S _^ / / serve the process of divis- | ^ ion, which takes place ~ /"\ N *i / rapidly under somewhat high temperatures. The _Jt / V short rod-like cells grow ^\ — \ to long staffs which stretch / -' / ' ^-' j f ''/* across the field of vision, ~" 3& "^ and which show only here „ „ .„ A A J tig. 20. — Bacillus Antnracis; cover-glass prepa- and there indications of rations f rom the i iver Q f a mouse. being made up out of sev- eral cells. They now become somewhat less transparent, and, growing to great length, the chain of bacilli becomes twisted up into characteristic coils or knots (Fig. 20). If, however, the bacteria are taken from the blood of an animal dead of anthrax, and are colored in the usual manner, there is no longer seen the rounded ends just alluded to. They now appear somewhat larger at each end than in the centre, and articulate, as it were, with the other rods of the chain, like the phalangeal bones 72 SURGICAL PATHOLOGY AND THERAPEUTICS. or the joints of a bamboo rod. This appearance is best shown with Bismarck-brown or methyl-bine. These organisms, when in the tissues, can be demonstrated by Gram's method, but they have an altered and granular appearance. The articulating enlarged ends of the bacilli are peculiar to anthrax, and distinguish these bacteria from all other forms. In using Gram's method care must be taken not to bleach too much, as the bacilli readily give up their color. If it is desired to see the spores, the bacilli must be examined in a drop of bouillon. Having reached the stage of development already described, the bacilli begin to show in the middle of the rod little accumulations of thickened protoplasm, that unite to form a large glistening body which appears as a bright spot of irregular outline in the middle of the cell. This body increases in size and brightness, is surrounded by a well-defined membrane, and is about the same width but somewhat shorter than the bacillus. It is sometimes wider than the cell, and when many of these bright egg-shaped bodies have formed in a chain of bacilli, a striking picture somewhat like a string of pearls is obtained. Presently the transparent remnant of the protoplasm, which has not been used for the formation of the spore, is dissolved and the spore is liberated. If the spores are now placed in fresh bouillon, they begin to germinate. This process can be watched in a hanging drop of liquid agar, which soon hardens and holds the spore, so that they can be observed during the different stages of their development. The spore soon loses its glistening appearance and increases in length. The tough membrane is next ruptured at one end, and the young bacillus projects from the opening. It continues grow- ing in the direction of the long axis of the spore, and finally casts off the shell of the spore and appears as a completely-developed bacillus. The growth of the bacilli is most active at a tempera- ture of 37 C, the extreme range of temperature being from i6° C. to 45 C. Access of oxygen is necessary. The spores do not germinate at a temperature below 24 C, and they need a large supply of oxygen. Spores do not form, therefore, either in the living body or in the cadaver of an animal which has died of the disease. They grow best artificially on the surface of agar or of potato, or in thin layers of bouillon, or in human urine freely exposed to the air. The bacilli have comparatively a slight resisting power : they are readily destroyed at a temperature of 6o° C. , and are unable to SURGICAL BACTERIA. 73 live more than a few weeks in the dry state. The spores, however, belong to the most durable of bacterial organisms. It is difficult to destroy them with chemical agents, and when they exist in a state of nature sunlight alone appears to have a destructive action upon them. These spores are used as a standard test of the value of disinfectants, and threads dried in spore-cultures may be pre- served for an indefinite length of time and used for this purpose. In gelatin the track of the needle is found filled with a whitish growth, from which delicate white threads project into the sur- rounding medium. On the surface the gelatin begins to liquefy, and at the bottom of the fluid is seen a slimy white layer of bacteria which gradually settles deeper as the liquefaction proceeds. On the surface of obliquely-hardened agar the bacteria appear as a ; "■'"■:" ' ; \\ v \ 1 /> x^7 /> b Fig. 21. — Section of Kidney from an Animal dead of Anthrax, showing bacilli in blood- vessels. grayish-white growth with a dull silver hue and raised somewhat above the surface. The virus may be introduced into the system in various ways. It may be inoculated even in very small quantities, and will pro- duce a fatal septicaemia, as it is reckoned among the most highly infectious of the bacteria. Buchner succeeded in introducing the spores and also the bacilli into the respiratory passages by inhala- tion. The bacilli produced much more irritation than the spores, 74 SURGICAL PATHOLOGY AND THERAPEUTICS. and pneumonia occurred. Baumgarten is doubtful whether this mode of infection occurs outside the laboratory. When taken into the stomach with food the bacilli are usually destroyed by the gastric juice, but the spores reach the intestinal canal. The alka- line character of the secretions and the high temperature give them an opportunity to germinate. They attach themselves to the epithelium and develop rapidly on the surface : the cells are then pushed aside and the bacilli reach the deeper layers of the mem- brane. Sheep and oxen are particularly sensitive to this form of infection, it being the one which under natural conditions plays the most important role. In man the infection most frequently takes place through wounds, and it forms the malignant pustule, but it has also been observed to gain an entrance through the lungs, giving rise to a pneumonia. One of Pasteur's most brilliant scientific feats was the demon- stration of the possibility of protecting an animal from the virus of anthrax by vaccination. It was found that cultures of the bacilli, carried on at high temperatures, were weakened in their poisonous action. The same result could be obtained by growing them at a moderately high temperature for a considerable length of time. Organisms treated in this way were found to produce alkaline substances, whereas the bacilli of natural strength produced acid substances. It was thought that this discovery would prove of great practical value, but experience has shown that, although sheep are protected by the vaccine thus produced from an inocula- tion with bacilli of full strength, the immunity is not permanent, but lasts only about a year, and, moreover, that it does not protect against infection through the intestinal canal. As this is the most frequent form of infection in cattle, further experiments are neces- sary to determine whether it is possible to devise a practical system of vaccination of cattle. An albuminose has been been separated from anthrax cultures in Koch's laboratory by precipitation with absolute alcohol. It was then redissolved and filtered through a Chamberland filter. Injected into animals, it was found to exert a protecting influence. According to Pasteur, the strength of the anthrax virus may be restored by inoculation into susceptible animals. Cultures from the blood of such animals will have an increased virulence. Cenkowski in Russia succeeded in obtaining an improved vaccine by passing the virus through the marmot {Zieselmaus) until a definite strength was obtained. The cultures of this vaccine were preserved in glycerin. L,ess than i per cent, of the animals were SURGICAL BACTERIA. 75 killed by the vaccine, and his tables show that during four years of its use, a larger number of animals being vaccinated each year, there was a diminution of the anthrax mortality in the herds from 8.5 and 10.6 per cent, to 0.13 per cent. An examination of the infected tissue shows the bacilli chiefly in the capillary system ; few organisms are seen in the large vessels, whereas the capillaries are crowded. They are found in the spleen, in the liver, and in the kidneys (Fig. 21), particularly the glomeruli. In the capillaries of the intestinal mucous membrane is occasionally found a ruptured vessel through which the organisms have escaped into the sur- rounding tissue. It was thought at one time that bacilli were eliminated with the various excretions, but it has been maintained that it was impos- sible for the bacilli to pass through the walls of the capillaries. Baumgarten is, however, of the opinion that the bacilli are as well able to migrate as are the leucocytes. Inasmuch as the capillaries of the kidneys are filled with these organisms, it is not surprising that the bacilli are found in the urine. It is also quite certain that they can pass through the placenta and affect the foetus, whether by penetrating through the walls of the blood-vessels or by escap- ing into the extravasations which are so numerous in the placenta. Rosenblath inoculated five pregnant guinea-pigs with anthrax. From the nine foetuses he obtained anthrax cultures in five. As the infection of the foetus does not always take place, it is probable that the bacilli pass through the placenta only under unusual conditions. The very frequent hemorrhages which accompany the disease probably give the bacilli an opportunity to escape from the circulation of the mother into that of the foetus. The bacilli are supposed to exert their pathological action in several ways: First, by so crowding the capillaries as to interfere with the nutrition of the parts; secondly, by robbing the tissues of oxygen; and, finally, by the formation of a toxine which exerts a poisonous influence. As the spores are the organisms which have preserved this disease from time immemorial, and which make it so difficult, even with our present knowledge, to prevent epidemics, it is interesting to consider how cattle are exposed to their influ- ence. During an epidemic the discharges from the intestine, the bladder, and the nostrils are scattered about on the surface of the earth in the track of grazing cattle. The organisms find a resting-place also in their hides. It was at one time thought that the bodies of buried animals might be a source of infection, but the conditions for germination at some depth beneath the surface 76 SURGICAL PATHOLOGY AND THERAPEUTICS. of the ground are not found to be favorable. The spores, there- fore, find a resting-place only in the superficial soil. They may be freed from their surroundings either by wind or by flood, and, mingled with the food of animals, may become the source of a fresh epidemic. Man is exposed to infection chiefly from contact with diseased animals or from handling their hides or wool; hence the name "wool-sorter's disease" has been given to anthrax in man. Actinomyces is a form of fungus which was first described by Bollinger in 1877 as existing in cattle, and which Israel found also in man a year later. It did not become generally understood, however, until Ponfick's article appeared in 1882. Bollinger found it in peculiar lumps about the jaws, the throat, or the tongue of animals, which lumps were supposed to be tubercle, cancer, and various other affections. In man the fungus is accompanied more or less by extensive suppuration in the same localities and also in other parts of the body. The organisms seen by the naked eye appear as a growth about the size of a millet-seed: they are yellowish, sulphur-like bodies of a tallowy consistence, which bodies, seen under the microscope, consist of a cluster of straight or of wavy branching threads, and also of radiating prolongations quite thick and clubbed- or pear-shaped, appearing sometimes like the fingers of a hand. These prolonga- tions are so arranged as to give the growth the appearance of a sunflower. The size of these colonies varies greatly, ranging from scarcely visible bodies to nodules 2 mm. in diameter. Their color may also vary from the light yellow mentioned to whitish, light brown, or green, and their surfaces may be smooth or mulberry- shaped. The club-shaped ends may be wanting, and the growth then appears very much like the streptothrix found as concretions in the lachrymal ducts of man. The radiating arrangement of the threads may also be wanting, in which case the growth is not unlike the leptothrix found in the mouth. It has been thought by some that these different appearances indicate a mixed growth of organisms, but culture-experiments prove that this is not the case — that the organism belongs to a polymorphous or cladothrix variety of fungus. The organism is colored with difficulty. The finer threads take the aniline colors well, but the club-shaped prolongations do not take the staining. They appear to be the result of a retrograde change in the growth. A portion of a nodule is spread upon a cover-glass and is allowed to dry. The glass is then heated in the SURGICAL BACTERIA. 77 flame of a lamp, and a few drops of picrocarmine solution are allowed to fall upon it. After two or three minutes the prepara- tion is washed in distilled water and alcohol and examined in water and glycerin. The fungus takes the yellow staining, while the other structures appear red. When sections are examined Gram's method of staining may be used. The actinomyces colonies are then seen stained a bright blue, surrounded by a zone of the clubbed ends colored a pale yellowish-pink; around this a zone of pus and of granulation-tissue colored pink; and, outside of all, the several tissues stained red. Sections may also be stained in Ziehl's carbolic fuchsin for fifteen minutes to half an hour, and then decolorized in a i per cent, picric-acid solution until the whole section has a yellow appearance. Dehydrate and mu. ^P # Fig. 22. — Section of Tumor of a Calf, showing actinomyces. mount. The fungus appears as a brilliant red aster, while the surrounding tissues are colored yellow (Fig. 22). According to Baumgarten, it is difficult to get a pure culture unless the growth be stirred in liquid gelatin, which is then poured upon a glass to harden. It can thus be grown upon blood- serum, gelatin, or agar. The cultures develop best at tempera- tures of from 33 to 37 C, and the growth is complete at the end of five or six days. When grown on the surface the line of inocu- 78 SURGICAL PATHOLOGY AND THERAPEUTICS. lation widens and has a granular whitish appearance. Presently small, yellowish-red nodules form in the centre of the culture, while the border is surrounded by a delicate white fringe. Finally, the nodules run together and are covered by a white velvety coat. III. HYPEREMIA. Among the most elementary disturbances in the whole domain of surgical pathology, in many cases so slight as hardly to be called kW pathological," are those changes in the circulation known as hypercrmia. From the earliest times these vascular disturbances have been recognized as the effect of some form of irritation act- ing upon the organism, as is evident from the phrase " ubi stimulus ibi affluxMs" handed down by early writers. It was not, however, until Claude Bernard gave the impetus to special research in this direction by his discovery in 1851 of the result of section of the cervical sympathetic nerve that any extended scientific study of the condition was attempted. Since then the science of angio- neurology, "one of the most important doctrines in medicine," has been evolved. The importance of a study of this subject need hardly therefore be urged as essential to a proper understanding of some of the more complicated pathological problems which will engage the reader's attention later. Hyperaemia signifies an increased amount of blood in a part. When, on the one hand, there is an increased amount of blood in all the vessels of the body, the condition known as plethora exists. On the other hand, anaemia is a term used to denote the condition existing when there is less blood than usual in the body. This term is, however, used in a medical sense to indicate certain pathological changes in the blood. Finally, ischaemia means a decreased flow of blood to a part. Hyperaemia is of two kinds — active and passive. In active hyperaemia there is an increased flow of arterial blood to the part. This condition has sometimes been called "fluxion." In passive hyperaemia there is a slowing of the blood-current ; the blood is venous in color ; a condition of stagnation exists. The condition of the circulation in active hyperaemia is well described in the account of an experiment by Vulpian on the vaso-motor effects produced by faradic stimulation of the peripheral segment of the lingual nerve in a dog. There is a considerable dilatation of all the vessels of the corresponding half of the tongue in the region in which this nerve is distributed. The mucous membrane in this 79 So SURGICAL PATHOLOGY AND THERAPEUTICS. region and also on the corresponding side of the frsenum becomes bright red. The principal vein of this part of the tongue becomes turgescent, and the blood contained in it and its tributaries is bright in color, resembling that of arterial blood, while there is a corresponding rise in the temperature of the part. In active hyperaemia there is an increased rapidity of flow of the blood, not only through the arteries, but through the veins also. If an artificial hyperaemia be produced in a dog's paw by division of the sciatic nerve, there will be found an increased tension in the femoral vein, as shown by a canula inserted into that vessel and placed in connection with a manometer. If the vein be tied, there is an almost arterial pulsation in it. There is, then, in hyperaemia an increased pulsation and dilatation of the arteries and a filling of the veins with arterial blood. Even the smallest arterioles, which do not pulsate ordinarily, begin to pulsate as soon as pressure is made upon them. The condition of the capillary vessels can con- veniently be studied in the web or the tongue of a frog. Under normal conditions the capillaries contain but few corpuscles, one or two at a time flowing through, and apparently filling out, the lumen of the vessel ; at times only liquor sanguinis is observed. Under a slight stimulus there is marked increase in the rapidity of the flow of the corpuscles, and the little vessels are distended with them, many appearing in the field of the microscope that were not before observed. Both the arteries and the veins are much dilated, and the rapidity of the flow is greatly increased. Whether there is or is not an actual dilatation of the capillaries is still a disputed question, as the absence of muscular and elastic walls in the capillaries does not permit of the marked changes of calibre seen in other kinds of vessels. Strieker, however, has an explana- tion which enables him to assume that active dilatation and con- traction of the capillaries take place. Experiments on the glan- dular vesicles of the skin of a frog, representing a single acinus and duct, show that under the stimulus of the faradic current the cells which line the acinus swell up and diminish the calibre of the acinus, and that on removal of the stimulus the same cells shrink and enlarge the cavity. A similar swelling of the cells forming the capillary walls has been observed, and the changes in the size of the lumen of these little vessels are supposed by Strieker to occur in this way. The following, then, are the principal changes seen in active hyperaemia. There is a temporary increase in the amount and rapidity of the flow of blood, and when this has subsided the circu- HYPEREMIA, 81 lation goes on as before, and no perceptible change in the part appears to take place. Ordinarily, there is no escape of fluid from the walls of the vessels, and if a canula is placed in a lymphatic of the leg of a hypersemic animal, no increased flow of lymph will be found. CEdema may, however, sometimes occur to a moderate extent, and the wheals of urticaria are supposed to be examples of such a condition. Occasionally there may even be rupture of the vessels and hemorrhage, but this only occurs when there is some pathological complication or when the vessels them- selves are diseased. Usually the effect of hyperemia is quite the opposite ; the walls of the vessels, instead of becoming thinner, are actually thicker, having undergone hypertrophy from the hypersemia, probably of the vasa vasorum. The increased warmth accompanying hyperemia is easily explained. The temperature of the surface of the body is always less than that of the interior, as considerable elimination of heat is constantly taking place. Indeed, the variations of temperature on the surface may be considerable. If now an increased amount of warm blood from the interior of the body flows through a given territory, the tissues become warmer and the temperature of the part is raised. Increased nutrition of the part, or increased activity of the muscular walls of the vessels considered as sources of heat, can hardly be sufficient to produce any perceptible local increase of temperature. The apparatus by means of which these vascular changes are accomplished is known as the vaso-motor system. The origin of the vaso-motor nerves or the vaso-motor centres has been traced to the medulla oblongata. The exact spot has variously been stated as at the boundary-line of the cervical and dorsal portions of the cord, or in the anterior portions of the lateral columns, or in the lower part of the floor of the fourth ventricle near the point of the calamus. These nerves can be divided into two groups. A large majority leave the spinal nerves with the rami communicantes, enter the sympathetic, run upward or downward, and terminate in independ- ent branches of the sympathetic or the splanchnic nerves which supply the abdominal organs; or, after entering the sympathetic, they return through the rami communicantes to the spinal nerves, and are distributed with them to the skin, muscles, and bone. Another group does not enter the sympathetic at all, but takes its course in the spinal nerves. The latter groups are called the u direct supply, " and the former the "indirect supply," of vaso- 6 82 SURGICAL PATHOLOGY AND THERAPEUTICS. motor nerves. The sympathetic does not form a separate system, but is connected with the spinal nerves. The cervical portion receives fibres from the first dorsal nerve-roots. The nerves which enter the sympathetic for the lower extremities come from the lumbar nerve-roots. The classical experiments of Claude Bernard gave the first information as to the physiological action of the vaso-motor system. The division of the cervical sympathetic in the rabbit was shown by him to be followed by marked hypersemia or dilata- tion of the blood-vessels in the ear. This was finally explained by supposing a paralysis of the vaso-constrictor nerves to have taken place. The same observer, however, discovered that stimu- lation of the chorda-tympani nerve produced dilatation of the vessels in the submaxillary gland. Here, then, was a demonstra- tion of two different kinds of nerves in the vaso-motor system, one of which by its action constricted the blood-vessels; the other, when in activity, produced a dilatation of the vessels. For a long time the chorda tympani and the nervi erigentes of the corpora cavernosa were supposed to be the only examples of the dilator nerves. Goltz, however, undertook to demonstrate the presence of the vaso-dilator fibres in the sciatic nerve of animals. He found that section of this nerve was followed by dilatation of the blood- vessels of the limb, which after a while resumed their natural calibre. Cutting off a second fragment from the peripheral portion of the nerve reproduced the dilatation. These phenomena were explained by the presence of vaso-dilator nerves which were irritated by the section. Other observers, however, showed that if the peripheral end of the divided sciatic was stimulated there took place a contraction of the vessels, which later gave way to dilatation due to exhaustion ; the nerves therefore were constrictors, and not dilators. Ostroumoff found, however, that in curarized dogs the freshly- divided nerve contracted when irritated, but that three or four days later the same irritation produced dilatation; time, therefore, was an element of importance in the problem. He assumed that both kinds of nerves are present, and that the vaso-constrictors degenerate soon after section, but that the dilators degenerate slowly. It has been noticed by all observers that the dilatation following section of the sciatic subsides at the end of a few days. This change is said to be brought about by the perivascular ganglia, which, with the nerve-plexus uniting them, are supposed to acquire HYPEREMIA. 83 gradually a higher degree of activity after separation from the nerve-centres. Such a system of ganglia and nerves has never been demonstrated anatomically ; no one has ever seen it, but there is found in the walls of the small intestine a similar plexus of nerve-cells and nerve-fibres, which plexus seems to preside over the movements of that organ, and to be subjected to excitation and inhibition through nerve-fibres connecting them with the cerebro-spinal centres. Microscopical clusters of ganglia have been seen on the arteries of the submaxillary gland, as also in the neighborhood of the large vessels of the penis. Strieker explains the phenomena supposed to be caused by the local ganglia in another way : he assumes that recovery from hyperaemia following section of the cord is accomplished by nerve- branches which are given off from the cord above the point divided, and which anastomose with the nerves going to that part. These nerve-branches gradually acquire increased power, and eventually exert a sufficiently powerful action upon the dilated vessels to cause them to contract again. This he calls " collateral innervation." In the light of the investigations which have been quoted we are justified in assuming the existence of the vaso-constrictor nerves and the vaso-dilators, which place the blood-vessels in com- munication with the vaso-motor centres. A peripheral vaso-motor mechanism also exists, presided over by the so-called "perivascular ganglia." The perivascular ganglia and the vaso-constrictors are continuous in action ; they keep the muscular walls of the blood- vessels in a state of tonic contraction, or, in other words, they give them their proper tonus. The dilators are not always in action, but are called into play only under exceptional circumstances. According to some author- ities, these nerves act like the vagus by producing an inhibitory action upon the local ganglia. Others believe them to have the ability to dilate the blood-vessels directly by their own action. Among the latter authorities is Strieker, who has shown that the dilators emerge from the cord through the posterior or sensitive roots. Most physiological and many pathological hypersemias are, according to him, produced by an irritation of the dilators. The close anatomical relationship between the sensitive and dilator nerves would explain the existence of hyperaemia in connection with many forms of neuralgia and the presence of pain accompany- ing the congestion of inflammation. He says: "It is probable that the local irritation excites at the same time both the sensory 84 SURGICAL PATHOLOGY AND THERAPEUTICS. nerves and the vaso-dilators of the implicated region. Whilst the former cause pain by centripetal conduction, the latter produce a dilatation of the vessels by centrifugal conduction." There may be found however, a vascular hyperaemia produced by purely reflex action. Goltz irritated the central end of a divided sciatic nerve, and obtained sometimes a dilatation and sometimes a contraction of the vessels in the opposite leg. Brown-Sequard and Lombard, after irritation by pricking, found a rise of temperature of a man's skin on the same side of the body, and a fall of tem- perature on the other side. These changes, though slight, were observed by Lombard's very delicate thermo-electric apparatus, and they indicated contraction or dilatation of the vessels. Numer- ous examples of this form of hyperaemia may be given. Neuralgic affection of the knee-joint with swelling is observed to be dependent upon uterine disorder. The danger of sympathetic inflammation of the sound eye following injury to either one of the eyes is well recognized. Weir Mitchell has observed a burning in the sym- metrical part following injury to a certain portion of the body. A lowering of temperature has also been observed in one hand on placing the other hand in cold water. The application of ice-bags to the heart, the abdomen, and the thighs has produced contraction of the blood-vessels in distant portions of the body. In fact, a system of treatment has been based upon the sensitiveness of the vaso-motors to heat and cold. It is a well-recognized fact that headache may be relieved, that nose-bleed may be stopped, and that the catamenial flow may be established by judicious use of these remedies, and it is not surprising that still greater claims are made for these remedial powers when there is taken into consideration the very considerable disturbances in the distribution of blood to different parts of the body, which disturbances may be produced experi- mentally. Irritation of the splanchnic nerves, on the one hand, produces contraction of the powerful abdominal blood-vessels and increases greatly the arterial tension throughout the body; on the other hand, division of the splanchnics produces hyperaemia of these vessels. Strieker says: "If this reservoir is wide open, it can contain so large a portion of the total amount of blood that the rest of the body becomes anaemic. An animal with complete paralysis of the abdominal viscera therefore bleeds to death, as it were, into its own abdominal vessels." In this condition there is dilatation of the mesenteric and of the renal arteries. At the same time on division of the portal veins an increased flow of blood is observed. No increase of temperature was found in the HYPEREMIA. 85 abdominal organs after division or irritation of the various nerves and ganglia supplying them, as they already possessed the highest temperature of all parts of the body. Such is the condition of the abdominal vessels in the frog in the well-known Goltz experiment. This experiment consists in tapping the abdomen of a frog with light but frequent blows, which result in a temporary cessation of respiration, heart-pnlsation, and muscular action, from which condition, however, the animal speedily recovers. As all local hyperemias are accompanied by compensatory local anaemias somewhere else to preserve the pressure, it can easily be seen that the blood-vessels of the abdominal viscera can become the regula- tors of the blood-pressure throughout the body. As hyperemia may be caused by paralysis of the constrictors or by irritation of the dilators, two forms of active hyperemia must be recognized. When caused by a paralysis of the constrictors it is known as hyperemia of paralysis, or neuro-paralytic conges- tion; when caused by an irritation of the dilators it is known as hyperemia of irritation, or neuro-tonic congestion (Reckling- hausen). The various elements which combine to form the vaso- motor system tend to counteract one another, and, in disturbances, to restore the normal condition. If a sudden change takes place in one direction, a reaction in the opposite direction may soon occur. After long exposure to cold there is a tendency to conges- tion of the part; to avoid this, frozen parts must be warmed slowly; conversely, the arm and hand which have been held for a long time in warm water may become paler than usual. One of the most striking examples of hyperemia of paral- ysis is observed after gunshot injury of the cervical sympathetic. A case is reported by Mitchell, Morehouse, and Keen that at the end of six weeks showed unilateral hyperemia of the face after an unusual exertion, with redness of the conjunctiva, con- traction of the pupil, secretion of tears, and ptosis. A similar injury recently occurred during the writer's service at the hospital, that was followed immediately by changes in the pupil and hyper- idrosis of the injured half of the face and the neck. Hutchinson observed, after fracture of the clavicle, paralysis of the arm, narrowing of the pupil, and rise of temperature of the injured half of the face. Such evidences of pressure on the cervical sym- pathetic in this injury he considers not unusual. A more exten- sive form of this kind of paralysis is given by Groningen. A laborer lying on his back after a full meal was playfully hit upon the stomach with a plank; in fifteen minutes he was dead, and at 86 SURGICAL PATHOLOGY AND THERAPEUTICS. the autopsy no structural lesion could be found in any part of the body. Many examples of syncope due to blows upon the chest and the abdomen, followed by death or recovery, and usually ascribed to shock, are undoubtedly caused by a reflex paralysis of the heart and the abdominal vessels. As the treatment of these cases is very different from that adapted to shock, it is important that the two conditions should be distinguished from each other. The action of the heart in cases of vaso-motor paralysis can be restored by electric stimulation or frictions and by compression of the abdominal walls to force the blood forward into the heart, whereas in shock absolute' rest is of the utmost importance. But few examples of hyperemia of paralysis are recorded as following injuries of the nerves of the extremities. An observa- tion by Waller on the ulnar nerve is worth mentioning here: The nerve at the bend of the elbow was placed on a freezing mixture until all sensation was lost. A rise of temperature with conges- tion was then noticed in the skin between the third and fourth fingers, and in some cases this condition lasted several days. Swelling of the finger-joints has been noticed following fracture of the internal condyle of the humerus causing pressure on the ulnar nerve. The same condition sometimes follows Colles's fracture, and is probably produced by pressure upon the nerves of the wrist by the displaced upper fragment. The hyperemias of dilatation are, as a rule, shorter and quicker in their action. They are accompanied by nervous symptoms, such as neuralgic pain, active secretion of the gland supplied by the nerve, oedema, and desquamation of epithelium from mem- branes. The changes of color in the cheek following disturbance of the emotions, as shame or anger, are regarded as examples of this form. The flushing following the stimulating effects of alcohol, tea, and coffee is supposed to be due also to stimulation of the dilator nerves. Redness of the conjunctiva, and even of the forehead and cheek, with flow, of tears, is an occasional accom- paniment of facial neuralgias, and is a symptom in accord with observations of Strieker on the presence of the dilators in the sensory roots. In fact, in hemicrania a dilatation of the vessels of the retina, both arteries and veins, has been observed. Perhaps the most striking example of hyperemia following nerve-irritation is herpes zoster. Not only does the eruption follow the anatomical distribution of nerves, but evidences of inflammation have also been observed in the nerves themselves by Haight and others. Cases of erythema, described by Mitchell, Morehouse, and HYPEREMIA. 87 Keen, following irritation of nerves previously severed by gunshot injury, are probably due to an active dilatation of the vessels. Redness and swelling of the joints have been observed by Weir Mitchell in cases following gunshot injury of the brachial plexus, and by Packard in a case of compression of the sciatic nerve by a tumor. The conditions described by Mitchell as erythromelalgia may be classed with these hyperaemias. The reflex hyperaemias are said by Recklinghausen to belong to this class also. Hyperaemia caused by paralysis of the perivascular ganglia may be observed in parts of the body separated from the nervous centres, as in transplanted flaps, where an unusual susceptibility to heat and cold is ordinarily shown by changes in the calibre of the vessels. A hand and forearm separated from the nervous centres by division of the nerves exhibited this increased suscept- ibility : on dipping the hand into cold water congestion with the formation of vesicles took place. A bright blush suffuses a limb after removal of an Esmarch bandage and the capillary hemorrhage from the wound is for a short time quite active if means have not been taken to prevent its occurrence. The dilatation of the blood- vessels is here evidently due to a local influence exerted directly upon them, either as the result of pressure or the removal for a certain length of time of the nutrient blood. Whether this local influence is exerted partly upon the muscular apparatus of the vessel-walls directly, and not through the perivascular ganglia, is an open question. The congestions of the walls of sacs following- evacuation of their contents belong to this class. Tapping the abdomen for ascites may be followed by heart failure or by serious hemorrhage into the peritoneal cavity if the pressure of the fluid is not replaced by external support. Too rapid evacuation of a bladder distended by obstruction from enlargement of the prostate may be followed by hsematuria and cystitis. In such a case the vessels of the bladder-wall are suddenly deprived of a support to which they have been accustomed for months or for years perhaps, and have lost the tonus which enabled them to preserve their normal calibre. This rapidly-produced hyperaemia is followed by rupture of some of the vessels or by a congestion terminating in inflammation. ' A portion only of the urine should be removed from such a bladder in order to allow the blood-vessels time to regain their tonus. A similar condition is often seen in limbs after fracture. The distention of the blood-vessels so characteristic during the first attempts to place the foot upon the ground after prolonged rest in the horizontal posture is in part due to increase 88 SURGICAL PATHOLOGY AND THERAPEUTICS. of pressure from the vertical position. The relaxing effect of moderate heat upon the vessels of the hand on placing it in warm water is familiar to every one. Very hot water will stimulate the constrictors, and is therefore useful in arresting hemorrhage from a wound. Prolonged douches of hot water have a similar astringent effect, and are used upon the cervix uteri for this purpose. The class of remedies known as rubefacients have probably a local action only on the blood-vessels ; when very stimulating they will produce primary constriction followed by dilatation of the vessels. It is supposed that many of the erythematous eruptions seen in bacterial diseases," such as, for instance, surgical scarlet fever, are produced by the local action of the bacteria or their toxic products upon the vessels. The artificial congestion produced by cupping is not a pure example of either active or passive hyperemia, as the vacuum draws the blood from all quarters indiscriminately ; that is, partly from the arteries and partly from the veins. Hyperemia is, as a rule, a passing condition, and, as already stated, leaves the part in the condition it was before ; long-con- tinued hyperemia may lead to hypertrophy of the vessels, and also of the part itself, as hypertrophy of the heart from hyperemia of the coronary arteries. When dilatation of the blood-vessels comes on suddenly and is intense in character, there may be an exudation of plasma from the vessels and oedema will take place. This is particularly noticeable in soft tissues, as the eyelids, in the neigh- borhood of inflammations, and is known as collateral oedema. It is probable, however, that in these cases there is not a pure exam- ple of hypersemia, but that other elements are at work, of which more will be said when studying inflammation. CEdema, and even hemorrhage, may, however, occur as the result of pure hyperemia, as is seen in many forms of skin eruption. At times excessive glandular secretion occurs : this is observed in the mucous mem- branes and also in the skin. It is a question whether the secretion is the result of a reflex irritation of the nerves going to the gland- cells or of the dilatation of the blood-vessels of the gland. In very chronic cases there is found, in addition to hypertrophy, an unusual growth of hair on the part. Passive hyperemia is caused by partial or by complete obstruc- tion of the flow of blood through the veins. It can be produced artificially by placing a ligature around a large vein. If this vessel be placed in communication with a registering apparatus, it will be found that there will be considerable increase of pressure at first, but that in a short time the pressure has returned to normal. HYPEREMIA. 89 The blood has found its way around the obstruction through the neighboring veins, which exist in abundance. If, however, a tourniquet is placed around a limb tightly enough to obstruct only the veins, but not the artery, there will soon be seen a rise in the pressure, which will become almost equal to that in the arteries. There may even be a pulsation in the veins. The same condition will be established after obstruction of a single vein in organs which have only one vein, as the kidney. Obstruction of the portal vein and of the femoral vein under Poupart's ligament will also be attended by such serious disturbance. In this form of hyperemia the color of the skin will be bluish or dark red. When the surface is unusually transparent, as under the nails, there is a livid or cyanotic hue. The change of color is most marked at the extremities, where the capillaries are large, or where the arterioles terminate in veins without an intermediate capillary system. The temperature of the surface is cooler than usual, this being due to the slowing of the blood-current, thus allowing less warm blood than usual to pass through the tissues. The venous color appears to be due in part also to this state of the current, for the blood remains longer in the part, and consequently becomes more highly charged with carbonic acid and more com- pletely deprived of its oxygen. In amputation wounds the venous color of the blood flowing from the surface is marked while compression is still partly exerted by the tourniquet, and the flow is more rapid than normal, owing to the increased pressure in the veins. Such hemorrhage will, however, speedily be arrested by removing the tourniquet and allowing the current to flow in its natural direction toward the heart. The minuter changes in passive hypersemia may be studied in the frog's tongue after tying the veins on either side. There is at first an appreciable slowing of the current in the small veins and in the capillaries. These vessels soon become filled and distended with blood-corpuscles, the plasma-layer in the smaller veins dis- appearing entirely. The red corpuscles now appear to lose their contour and become fused together in an almost homogeneous mass. The flow of blood ceases, and the blood-column has a rhythmical pulsation communicated to it with each heart-beat. Presently at isolated points red corpuscles appear projecting through the walls of the capillaries and small veins, and finally they are forced com- pletely through, owing to the pressure to which they have been subjected. There is at the same time also an escape from the vessels of a certain amount of fluid, which gives rise to oedema 90 SURGICAL PATHOLOGY AND THERAPEUTICS. caused by the pressure exerted upon the small vessels both by the veins and the arteries. In the arteries no increased pressure is observed, as their tonus is always higher than any pressure that can be produced by this form of hyperaemia. A study of the arteries of the retina shows that they are narrower than usual under these circumstances. This contraction of the arterioles is supposed to be either compensatory, so as to bring less blood to the congested part, or is for the purpose of making the blood-stream more powerful. The exuded fluid is poorer in albumin than the liquor sanguinis or pure lymph; and it has but slight tendency to coagulate. The reddish tinge some- times given to the fluid is due to the presence of red corpuscles. One of the most familiar examples of this form of hyperaemia is that condition of the vessels of the lower extremities accom- panying varicose veins. Here all stages of the process can be studied. At first there is only oedema, the change in color being but slight, owing to the collateral circulation. Later there is considerable pigmentation of the skin, owing to the destruction of the escaped red blood-corpuscles, and finally the disturbance in the nutrition of the part is so great that a breaking down of the tissues takes place and gives rise to ulceration. Many of these symptoms Can be made to disappear by overcoming the obstruc- tion due to the dilated and tortuous blood-channels, which can easily be done by placing the limb in a horizontal posture. Passive hyperaemia may also be produced by pressure on venous trunks from inflammatory new formations or tumors. If the force of the blood-current is naturally weakened, as in feeble individuals or in disease of the heart, there may be local congestion at points where it is most difficult for the blood-column to overcome the force of gravity. This congestion often occurs in the lungs when an enfeebled individual has been for a long time in the recumbent posture, for then the blood-pressure is always more feeble. These forms of hyperaemia are known under the name of hypostatic congestion. It is possible that such congestions may take place in other internal organs, such as the prostate and bladder. It is necessary to be on guard against complications of this kind when confining the aged to bed for any length of time. A similar condition is that which leads under similar circum- stances to decubitus or bed-sore. Light pressure on a spot for a considerable time causes an ischaemia which is followed by a relaxation of the vessels, particularly the small veins, owing to the feeble circulation, instead of the usual hyperaemia that in the HYPEREMIA. 91 normal condition should follow. The most protruding portions of the skeleton posteriorly indicate the points where these congestions are likely to occur. The feeble circulation is followed by stasis in the capillaries, the stage preceding actual death of the part, which stage may occur in the form of ulceration or gangrene. The bluish color imparted to portions of the body subjected to great cold is due to hyperaemia following an ischaemia of the part. In parts which have been in a state of chronic inflammation slight external influences will produce the cyanotic color for the same reason. The hyperaemia and swelling in legs convalescing from fracture is in part due to passive hyperaemia. In heart disease there may be general passive congestion of the whole body, as well as anaemia, and in shock the pallor, the clammy and cyanotic skin, are all due to a feeble heart-action which slackens the blood-current in the capillaries and the veins. IV. SIMPLE INFLAMMATION. i. The Process. A proper understanding of the phenomena of inflammation may be said to be absolutely essential as a basis upon which to build up a knowledge of surgical pathology. The close relation of the blood-vessels to the inflammatory process was recognized by Hunter, who says: k ' The act of inflammation would appear to be an increased action of the vessels. " He recognized the congestion of hyperaemia accompanying inflammation "as the first act of the vessels when the stimulus which excites inflammation is applied." In a study of the circulation as observed in inflammation, the experiments of Cohnheim, both on the circulation and the action of the white corpuscles, first published in 1867, added greatly to the knowledge of this process, and deserve, therefore, to be mentioned first. Such modification of his views as were sug- gested by other observers will be then considered. If a frog be par- alyzed with curare, and there is drawn through an incision made on one side of its abdomen a loop of intestine, and so spread out that the light can easily be transmitted, there will be obtained a transparent, highly vascular membraue which soon becomes in- flamed upon exposure to the air. It does not require very careful observation to perceive that the rapidity of the flow of blood is greatly increased, and that the number of the vessels is also appar- ently increased, many now being visible which were not before observed. The capillaries, through which there flowed only occasionally a corpuscle, are now quite full and their situation easily determined. The increased rapidity of the flow lasts only for a short time, however, and it is followed by a slowing of the current, which now becomes slower than normal. Thus far, the phenomena observed have not differed in any way from those seen in active hyperaemia ; but now a new element, the slowing of the current, is introduced, and from this time on the picture changes, and new phenomena are seen which have not been found to exist in hyperaemia. In consequence of the slowing of the current the corpuscles accumulate in great numbers in the capillaries, which, although distended, do not become materially increased in calibre. 92 SIMPLE INFLAMMATION. 93 Along the walls of the small veins there may now be noticed an accumulation of white corpuscles. They are no longer swept back again into the current after a temporary adhesion to the wall, but remain attached to the wall until a considerable number have accumulated. Occasionally one is dislodged, only to be soon arrested again in its progress. Finally, their number becomes so enormously increased that the entire vessel-wall appears to be lined with a layer of white corpuscles (Fig. 23). Adherence of white corpuscles to the wall is observed also in the capillaries, but there they are more freely mingled with the red corpuscles, whereas in the veins the two varieties of cells seem to have separated from one another. In the arterioles there is a tendency to ac- cumulation on the inner wall of white corpuscles, this being particularly no- ticeable during the diastole ; the suc- ceeding wave, however, sweeps them back into the current again, and they disappear. Presently slight protuberances are noticed here and there on the outer walls of some of the small veins, and they gradually increase in size. At cor- responding points on the inner side of the vessel are situated white corpuscles. At points favorable for observation one can see that an enlargement of the outer protuberance keeps pace with a dimi- nution of the size of the corpuscle pre- viously observed attaching itself to the inner wall, and that when the corpuscle has entirely disappeared there is seen on the outer wall a perfectly-developed cell, which proceeds to detach itself from the vessel and by frequent changes of shape to change its position from time to time. When at rest these cells are round, granular bodies, containing one or more nuclei, and are not to be distin- guished from white blood-corpuscles ; when in motion they possess one or more prolongations and become quite irregular in shape, resembling in all respects the ' ' wandering cells ' ' of the connec- tive tissue originally described by Recklinghausen. In the mean time large numbers of similar cells are making their way through the walls of all the veins within the field of vision until they are surrounded with several layers of white corpuscles. Fig. 23.— Blood-vessel, Mesentery of a Frog, showing diapedesis of leu- cocytes. 94 SURGICAL PATHOLOGY AND THERAPEUTICS. The white corpuscles are also seen escaping through the walls of the capillaries, but to a less extent ; and there is found here mingled with them a certain number of red corpuscles. In the arterioles no such passage of cells is taking place, the interior of the vessel-wall, as has been stated, being kept clear of white cells by the force of the current. At the same time there is consider- able exudation of fluid from the vessels into the meshes of the surrounding tissue. The mesentery is now distended by a mass of cells and fluid, which presently escapes from the tissues to the sur- face, where the fluid coagulates and forms a membrane, between the fibrils of which are imprisoned the white and perhaps also some red corpuscles. The escape of white corpuscles from the vessel was first described in 1841 by Dr. Williams in England, but it was not until Cohnheim had so clearly demonstrated the process and its bearing upon the theory of inflammation that it was accepted by the scientific world. The tongue of the frog, in which has already been observed the changes of hyperemia, is also well adapted for studying the con- ditions of the circulation in inflammation. A caustic substance of some kind applied to the centre of the organ will enable one to observe different degrees of inflammation at different distances from the point of injury. On the extreme periphery the circulation is normal ; next, a zone of dilated vessels with slowing of the current, and, still nearer, an exudation of white corpuscles is seen, particularly from the veins. As the centre is approached the circulation becomes slower and the exudation greater, until the zone of stasis is reached where the vessels are acted upon by the chemical substance and the blood has coagulated in them. The different phases of the circulatory disturbances may be produced by simply placing a ligature around the frog's tongue and removing it at different periods of time. If left on from twelve to twenty-four hours, and then removed, a passing hyper- semia is produced. This can be seen on any limb after the re- moval of an Esmarch bandage. If the ligature is left in place from thirty-six to forty-eight hours, there is caused at first a hyperemia, followed by a slowing of the current and an exudation of cells and plasma. If left on for sixty hours, the stream will become so sluggish that there will be an enormous diapedesis of white corpuscles, and many red corpuscles will also be found in the exudation. The tongue looks as if it were covered with red spots. If the ligature be not removed for two or three days, the blood penetrates into the beginning of the arteries, but not into SIMPLE INFLAMMATION. 95 the smaller arteries or capillaries or veins, and the circulation is never re-established. It is quite evident that there is here something different from simple hyperaemia ; not only is the current slower, but there is an exudation or a leakage through the walls of the vessels. This exudation is attributed by Cohnheim to a molecular change in the vessel- wall, a condition bringing about different relations of friction and adhesion between the blood and the walls due to changes in the endothelium. Cohnheim thinks that he can exclude the nerves, for he has been able to produce inflammation in the ear of a rabbit when every connection has been severed except the artery and the vein. This, however, can hardly be received as satisfactory evi- dence, for the perivascular ganglia are not excluded, and it is probable that in a case such as this they may be called into action. The dilatation is also greater than in hyperaemia ; for instance, a rabbit's ear will have a still greater dilatation and injection of the vessels after section of the sympathetic if the part be irritated with croton oil or dipped in hot water. The slowness with which the process develops is against the hypothesis of nerve-action ; some- times hours elapse after application of a caustic before any change occurs. Cohnheim argues, also, that the disturbance is not in the blood, for it may be produced in the tissues while the blood is absent. If the blood be excluded from a rabbit's ear by an Esmarch bandage, and the ear be dipped in moderately hot water, and the ligature be removed as soon as the ear has cooled off, the symptoms of inflam- mation will presently show themselves, and the ear will become swollen to several times its normal thickness. The disturbance has not been produced in the blood, but in the part itself. It is not probable, he thinks, that the cells of the part can have any influence upon the corpuscular elements of the blood, although it can be conceived that they may attract to themselves the fluid portion. He is therefore driven to the conclusion that the change is in the wall of the vessel. It has already been noted that if the blood is excluded from the vessels for a certain length of time, it will not enter them again, although the vessels are apparently open. It would not, therefore, be difficult to understand how under other circumstances these walls can hinder or retard the flow of blood. The chemical character of the fluid which filters through the wall, as compared with that observed in hyperaemia, is another reason for assuming a change in the wall. This idea of change in the vessel-wall is accepted by Burdon 96 SURGICAL PATHOLOGY AND THERAPEUTICS. Sanderson. The vessels dilate, he says, because they have lost the power they before possessed of resisting dilatation. There is a loss of vital power, in consequence of which leakage also takes place. Professor Glax of Graz showed that by keeping up the vital properties of tissues in animals by the artificial circulation of properly arterialized blood through the vessels under an absolutely constant pressure, the introduction of a small percentage of injurious substances, such as metallic salts, produced a leakage and a dim- inution in the quantity of blood flowing through a given part. Landerer contends that the primum movens in inflammation, or the first thing to-be noticed, is the much more frequent injury to the tissue-cells than to the vessels. He would not do away entirely with the view that the vessel-wall takes part in the process. The capillaries should be regarded as vascular spaces in the tissues lined with endothelium like the lymph-spaces, and not as separate tubes sufficiently strong to support all the pressure that may be brought to bear upon them from within. The greater part of the tension is borne by the tissues, which, in virtue of their elasticity, can be placed in a state of elastic tension in the same way as the walls of larger arteries. The irritant ] — or, as Landerer prefers to call it, the u innammation-excitor ' ' — exerts an influence upon the tissues in virtue of which they become relaxed ; they are thus more easily distended and their elasticity is less complete. This diminished elasticity of the tissues would act upon the momentum transmitted to the blood in the same way as the wall of an athero- matous artery. The pressure cannot be returned to the blood- column, but must be expended in stretching the tissues. The momentum of the blood-column is thus partly lost and diverted to other purposes. The amount of blood increases, but the power to move it diminishes ; there is a leakage of lymph, owing to the diminution of external pressure. Landerer thinks that the old phrase, ubi stimulus ibi affluxus, which has something mysterious about it, should be discarded, and it should be replaced with the simple physical law of "local diminished pressure or resistance, increased flow." One of the earliest theories about the circulation was called the " attraction theory," which assumed an increased adhesiveness in the elements of the blood to one another and to the vessel-wall. Another theory assumed a change in the plasma by which it became more concentrated, and thus caused resistance to the natu- ral blood-flow. Or it was thought that there was a vital attraction 1 Landerer rejects the term " irritation " as too suggestive of nerve- or muscle-action. SIMPLE INFLAMMATION. 97 of the tissues for the blood : an increase of this function would hold back the blood in the tissues and produce a determination of blood to an organ. An affinity between the fluids of the tissues and the contents of the vessels undoubtedly exists. A change, therefore, in the tissues would affect the blood and the vessel- walls. The action of the cells in inflammation and their power to attract materials from the blood was especially dwelt upon by Virchow. Recklinghausen does not accept the experimental evidence showing a slowing of the current in inflammation. At the height of the process the color of an inflamed part is scarlet. The color of the blood when drawn by leeches is arterial, and the flow after an incision is more rapid. The pulsation of large arteries is stronger near an inflamed part, and the blood flows away as rapidly as it comes, as is shown in cases of venesection, where the blood from the vein has frequently also an arterial color. The stasis seen in the web of a frog's foot as the result of an " irritation " is not, he maintains, a symptom of inflammation. The irritant always produces at first an increased rapidity of the stream. When very small injuries are produced, there is no slowing of the stream; after a few hours the normal circulation is restored. If strong irritants are used, there is always a zone of "active congestion" or increased rapidity of flow of the blood surrounding the spot. The stasis in the centre leads to necrosis, a result which does not necessarily form a part of inflammation. The purulent softening which occurs around the necrosed portion takes place in the zone of active congestion. In the mesentery of the frog, as Reckling- hausen shows, there are many complications which produce a slowing of the current. Among these complications may be mentioned the thinness of the membrane exposed to the air, the contraction of the intestine, the great hyperemia of the abdominal viscera, and the diminished heart-action and blood-pressure caused by curare. In the frog's tongue which is turned over and stretched out there are frequent obstacles to the blood-flow. Recklinghausen evidently does not regard the slowing of the blood-current as a necessary part of inflammation. He is, how- ever, willing to admit that some inflammation-excitors may act through the blood upon the vessels, and thus impair the action of their walls. At all events, it may be concluded, from the experiments described above, that there is produced a condition differing from simple hyperemia. The disturbance of circulation in inflamma- tion comes on later and lasts longer than in hypersemia. There is 7 98 SURGICAL PATHOLOGY AND THERAPEUTICS. also exudation which does not occur in hypersemia or occurs only to a slight degree. In its earliest stages the congestion of inflammation differs probably but little from active hypersemia. As the process develops there is a greater dilatation of the vessels and a dimi- nution of tension; the vessel-walls and the tissues are "relaxed" through the action of the inflammatory agent. As a consequence, the conditions of hyperemia are so far departed from as to produce a leakage of the vessels. Should the inflammatory agent occasion a more profound impression upon the part, there may be a temporary stasis in some of the capillary vessels; and there can easily be imagined permanent stasis in a very limited area with- out the occurrence of necrosis 01 even of serious disturbance of nutrition. In the average case of pronounced inflammation there probably exists the phenomena of genuine hyperaemia of the blood-vessels in the peripheral portions of the inflamed mass, with greater distention and relaxation of the vessel as the centre is approached. These causes, combined with the swelling of the parts, would undoubtedly impair the rapidity of the blood-flow. The phe- nomena of a rapid current, as arterial pulsation and color, with more rapid flow of blood from an incision, might coexist with a slowing of the current in another portion of the same part. It is a well-known fact that in certain inflammations the con- gestion may be so severe as to obstruct the circulation of a con- siderable area, and to an extent that will cause death of the part or mortification. Such severe forms of inflammation are, however, fortunately, extremely rare, and they occur usually in parts not capable of rapid distention, as the bone, or where the circulation is less active, as the extremities of the arterial circuit. The disturbances of circulation of the blood seen in laboratory inflam- mations must, therefore, be regarded as partly artificial in cha- racter. In reality, however, there is probably considerable varia- tion in the rapidity of the blood-flow. A word may be said here about the changes seen in the blood during inflammation. Much attention has been drawn of late to the so-called u third corpuscle," which is a colorless proto- plasmic disk from 1.5 to 3.5// in diameter, these corpuscles num- bering, according to Osier, about one to every twenty red cor- puscles. They are visible in the circulating blood, and on the withdrawal of blood from the circulation they tend to adhere to one another, and to form irregular granular clumps, known as SIMPLE INFLAMMATION. 99 "Schnltze's granular masses," or as granular debris so often seen in the neighborhood of blood-clots. The name now usually given them is "blood-plaques." Their tendency to agglutinate and to disintegrate has prevented their earlier recognition. They are more numerous in the infant and in the aged. They are supposed by some to be true hoematoblasts — that is, bodies from which the red corpuscles are formed ; they are seen in large numbers when blood-corpuscles are forming, but their relation to this process is still doubtful. The blood-plaques are much more numerous, however, in acute sthenic fevers and in chronic wasting disease, and probably also in «f% ,#> *■■&. V^ cm ry ^ * ** % H- # k i * Fig. 24. — Leucaemic Blood, showing various forms of leucocytes. cases of inflammation, both acute and chronic. At the crises of fevers and after the healing of acute abscesses they are seen in large numbers, and it is supposed by some that an effort at the repair of the blood is thus made by these bodies at this period, but, as has been said, the evidence on this point is yet insufficient. There is a very noticeable increase in the number of white cor- ■w puscles in the blood during inflammation. This increase is what J should naturally be expected from observation of the great in- crease in the number of these cells in the inflamed part, and from the active migration which takes place through the walls of the blood-vessels (Fig 24). The whole system thus appears to sympa- IOO SURGICAL PATHOLOGY AND THERAPEUTICS. thize with the local condition, and those organs in which leucocytes abound, as the spleen and the lymphatic glands, are found much enlarged at this time. Davidson of Edinburgh explains the increase of leucocytes in the blood by a muscular contraction of the spleen, such as occurs in digestion through reflex action from the stomach ; in inflammation the source of the reflex irritation is supposed by him to originate in the walls of the arterioles of the inflamed part. These cells appear to be quite independent of the red corpuscles, which were formerly supposed to be derived from them. It will presently be seen that they have quite different functions, inti- mately connected .with the process of repair and the protection of the body from invading organisms. Leucocj^tosis is usually seen in the suppurating forms of inflammations, and is of value as confirmatory evidence in the diagnosis of deep-seated abscesses, even the pus of a felon being sufficient to cause marked increase in white cells. According to the observation of R. C. Cabot, it is regularly, though not invariably, present in purulent but not in catarrhal appendicitis, and is of value in enabling the physician to distinguish this affection from colic or from constipation. Leucocytosis may help one to distinguish pyo- salpinx and pelvic abscess from pelvic neuralgias and small ovarian tumors. Cabot did not find leucocytosis following urethral fever or cystitis or endo- metritis. He found this condition of the blood in three cases of suppurative colangitis, but absent in two cases of gall-stones without pus. Leucocytosis was not observed in tubercular affections. In general septic peritonitis it is occasionally absent. It is seen in suppurative osteomyelitis, and also in all forms of suppuration with pocketing of pus following operations. It is the rule in en~sipelas. In new growths it is very variable, apparently accom- panying chiefly those cases in which cachexia is most marked. In old times, when venesection was a common procedure in inflammatory disease, it was well known that blood coagulated quickly when withdrawn from the body. The so-called " buffy coat," the crusta phlogistica, or white layer, which was seen at the top of the coagulum in a vessel, was supposed to be due to an excess of fibrin in the blood ; a fibrinous crasis was supposed to be evidence of an inflammatory state of the blood. It is now known that the white corpuscles play an important part in the process of coagulation. Fibrin is formed by the union of two substances, fibrinogen and paraglobulin, with the co-operation of fibrin-fer- ment. Fibrinogen is found in the blood-plasma, while the other two substances are, for the most part, found in the white corpus- cles. When the latter break down these substances are set free, and are able to act upon the fibrinogen and form fibrin. The increased amount of fibrin seen in the coagulum and in the exuda- tions must be ascribed, therefore, to the increased number of white SIMPLE I NFL. I MM. I WON. 101 corpuscles circulating in the blood and finding their way into the tissues of inflamed parts. There is now to be considered the action of the tissues of the inflamed part. Before Cohnheim's and Recklinghausen's investi- gations the increased number of cells found in inflamed tissues was supposed to be due to a proliferation or a multiplication of the cells of the part. This was the view of Virchow, who showed that the tissue-cells are placed in a condition of increased activity by the inflammatory irritant, and consequently attract to them- selves nutriment in unusual quantity for their growth and multi- plication. The vascular changes in inflammation he regarded as the result of this increased activity of the cells. In connective tissue there exist two principal varieties of cells — the fixed and the wandering cells: the former are stellate or fusiform, and lie hidden among the fibres which constitute the principal portion of the intercellular substance. In addition to these there are the small round cells, containing one or more nuclei and a gran- ular protoplasm, in all re- spects resembling the white corpuscles of the blood. It was Recklinghausen who first recognized their power to take on changes of shape, such as are characteristic of the amoeba, and by this amoeboid movement (Fig. 25) to change their location. These cells, described by him as wandering cells, are constantly moving through the meshes or lymph-spaces of the tissues, entering them from the vascular system and escaping through the lymphatics, keeping up in this way a constant circulation. In the normal tissues they are few in number, and are seen and studied only after careful methods of preparation, but when the tissues are irritated or inflamed they are found there in large numbers, and their presence is accounted for in the way which has already been described when studying the action of the vessels in inflammation. In consequence of these observations Cohnheim assumed that the old theory of cell-prolifera- tion would have to be abandoned in favor of the migration theory. He endeavored to show that the fixed cells of the part underwent Fig. 25. — Amoeboid Movements of a Leucocyte. 102 SURGICAL PATHOLOGY AND THERAPEUTICS. no active change during the inflammatory process, and for this purpose made a series of investigations upon the cornea, a form of tissue simple in composition and convenient for study, owing to its great transparency. The cornea when examined fresh in a drop of aqueous humor is seen to be absolutely transparent, and no structure can be distinguished, but when treated with a solution of chloride of gold a beautiful network of large stellate anastomos- ing cells is seen lying in a transparent intercellular substance. If, however, the cornea be treated with a solution of nitrate of silver, the cells appear as a branched system of canals anastomosing in a dark background. Such pictures as these suggest the presence of spaces through which it would be possible for wandering cells to migrate. It will be well to devote a moment to the consideration of these experiments, as the results obtained by Cohnheim have been the object of much discussion and dispute. They were, in brief, as follows: A ligature is drawn through the bulb of a rabbit's eye, and opacity of the cornea is seen in twenty-four hours, in frogs in from two to six days. Later, the cornea becomes milk- white or grayish or yellowish-white, and thicker and somewhat softer than in the normal condition. This opacity is due to leuco- cytes. On removing the cornea before the opacity is too great, and putting it into a neutral solution on an object-glass and examining it with a high power, the leucocytes are seen in all shapes, and also the corneal cells with their characteristic prolon- gations. The leucocytes may be seen moving about independently of these cells, and generally obscuring them. If, however, the cornea is treated with chloride of gold, the corneal cells are seen unchanged. Such changes as have been observed in them by others Cohnheim regards as degenerative only in nature. There is a granular condition of the protoplasm, a retraction of the prolon- gations, and the formation of vacuoles. If the centre of the cornea of a winter frog is touched with a pencil of nitrate of silver, at the end of twenty-four hours an opaque streak is seen projecting from the margin of the cornea in one or two places, generally from the upper and lower margins, at which point more or less hypersemia of the vessels is seen to exist. These opacities reach the cauterized point on the third day, and by the sixth day the opacity has localized itself around the cauterized point, while the surrounding cornea is clear. Under the microscope the corneal corpuscles were found by Cohnheim in all cases to remain unchanged, the opacity being due to the presence of large numbers of leucocytes. SIMPLE INFLAMMATION. 103 One of the peculiarities of the leucocyte, about which more will be said later, is its power to appropriate foreign substances, which thus become imprisoned in its protoplasm. Cohnheim undertook to prove that the new cells seen in the cornea were identical with the leucocytes, by injecting granules of carmine or aniline blue, held in suspension, into the lymph-sacs and blood-vessels of the frog, and subsequently producing a keratitis. In such an inflamed cornea many of the new cells are found to contain these granules, which are not seen in uninflamed tissues. These views, first propounded by Cohnheim in 1867, produced a profound sensation, altering as they did very materially the then existing ideas of cellular pathology. It is needless to say that they met with active opposition from many quarters, but by no one were they so vigorously opposed as by Strieker of Vienna. This observer not only maintained the old theory of " proliferation," but developed it still further and evolved his theory of ' k tissue-metamorphosis, "" which, in brief, is that not only the cells, but also the entire tissue, returns to an embryonic condition and separates into amoeboid masses; in other words, that the intercellular substance as well as the cells may take part in the formation of new cells in inflammation. Many other observers also undertook to show that the fixed cells were capable of proliferation, and the cornea was selected for this purpose. Burdon Sanderson, while admitting that immigra- tion plays an important part in keratitis, pointed out that changes in the stellate cells of the cornea could be observed if studied at an earlier stage than that employed by Cohnheim. Shakespeare of Philadelphia recognizes four different kinds of cells in the cornea. His studies show pretty conclusively that the fixed cells are active in the processes of destruction and repair. He goes so far as to say that slight injuries of the cornea may be repaired entirely by these cells without the assistance of the adjacent blood-vessels other than an additional supply of blood-plasma. Finally, the following experiment would seem to leave little doubt that the corneal cells can proliferate. A cornea is irritated and then excised and preserved in a moist chamber; in two or three days a formation of wandering cells takes place at the point of irritation; the appearances of ordinary keratitis follow. It is certainly fair to infer that these cells came from the elements of the cornea existing there at the time of irritation. Recklinghau- sen states that changes in the corneal corpuscles have occurred under the eye of the observer, and that fragments of protoplasm 104 SURGICAL PATHOLOGY AND THERAPEUTICS. separated from them have been seen to go through the same changes of form as wandering cells. In the omentum of young animals there is a very simple form of epithelium and one more or less remote from blood-vessels. If an artificial peritonitis be produced, Cornil and Ranvier have shown that an active proliferation of these cells will be seen at the >end of twenty-four hours. In the writer's own studies of inflamed tissue he has seen undoubted evidence of proliferation of the fixed cells. Some beautiful examples of this were observed in the skin adjacent to a carbuncular inflammation. In the inflammation of the walls of the artery of a horse, produced by the application of a ligature, the muscular cells of the media were seen in an active state of proliferation. Cohnheim in answer to observations of this kind pointed out that many of these changes seen in fixed cells were of a degenerative character and preceded the final destruction of the cell. The emigration theory still continued dominant, however, until Strassburger, Flemming, and others demonstrated the changes seen in the nucleus known as karyokinesis, or indirect cell- division,, which they observed in vegetable cells, in the tissues of the lower animals, and afterward in the normal human tissues, and finally also under pathological conditions. (See page 218.) This proved conclusively that the fixed cells did not play a passive part in inflammatory processes, and the role which these cells played in hypertrophy, repair, and tumor-growth (Fig 26) was shown to be a more prominent one than had hitherto been supposed. In any acute inflammation the tissue-cells break down in large numbers; but many of them, according to Ziegler, become wandering cells, and are difficult, at first, to distinguish from leucocytes. They do not produce any pus-corpuscles, but event- ually play a prominent part in the process of repair. Several forms of leucocytes are now recognized in inflammatory tissue, among them being the single and the polynucleated. The polynucleated are the type of the pus-corpuscle. They possess two or three nuclei or peculiarly deformed biscuit or sickle-shaped nuclei, which are supposed to be appearances which precede a breaking down of the cell (Fig 24). The single-nucleated cells are scarce in acute inflammation, but in the later stages and in chronic forms they are more common. Many of the wandering cells derived from connective-tissue cells closely resemble the single-nucleated leucocytes, and cannot always be distinguished from them. SIMPLE INFLAMMATION. 105 Regarding the origin of many of the cells seen in inflamed tissues, Grawitz has recently propounded a theory which closely resembles that already alluded to by Strieker. He claimed that the majority of these cells came from the intercellular substance. According to this theory, during embryonic development numer- ous cells change into intercellular substance and remain slumber- ing, as it were, in this condition until some irritation arouses them, when they return again to an active-cell type. This means that the fibrous tissue of connective tissue, the homogeneous tissue in cartilage, and the intercellular substance in bone are not excretory Wi w •« * Fig. 26. — Karyokinesis in the Cells of a Sarcoma. products of the cells, but that the bodies of the cells are actually changed into intercellular substance. When these cells begin to appear the nuclei are extremely small and the cells seem to have no protoplasm. They are arranged in rows, and are so deeply situated in the bundles of fibres that one must conclude that they have originated in loco from their accustomed quiescent fibrous state, and cannot therefore have been transported thither by emigration. These cells are frequently seen in numbers when there is no sign of karyokinesis, indicating that the pre-existing cells of the tissue are not in an active state of development; which fact goes to show that they are not derived from other cells. The nuclei gradually enlarge, and acquire a cell-body that forms around the nucleus from the 106 SURGICAL PATHOLOGY AND THERAPEUTICS. material of which the softening fibre is composed. When a considerable portion of the intercellular substance has changed to cell-protoplasm the fibre as such disappears, and it is replaced by a row of cells lying close to one another. These cells when once formed are precisely like those which existed before, and, like them, are capable of proliferation. Shakespeare, whose work has already been alluded to, regards the flat or spindle-shaped cells seen in the primary bundles of fibres in the cornea, the cartilage, or the intima of vessels as cells which are usually invisible and which are not susceptible to staining processes. These cells, he thinks, are Grawitz's slumbering cells. Under the influence of irritation these cells are aroused to activity, and appear to acquire their original power both to destroy and to repair. Weigert vigorously opposes this idea of slumbering cells. The fibres, he says, are absorbed, being damaged or dead, and cells appear where they were before. The new cells come from the pro- liferation of the pre-existing cells. The absence of the signs of mitosis, or indirect cell-division, is no argument against their origin from the cells of the part, as this form of division is chiefly confined, to cells that are intended as permanent cells. What are the functions of the leucocytes? and why do they crowd in such numbers to the inflamed part? Cohnheim regarded them as the active agents in the process of repair, but according to Ziegler many of them are taken up by the proliferating connec- tive-tissue cells, for which they appear to serve as nutriment. Many of these mobile cells appear to play the role of scavengers, owing to the power possessed by them of appropriating particles of foreign bodies or bacteria and transporting them to distant points. The usefulness of the leucocytes in consuming and receiving portions of the broken-down tissue can easily be under- stood, for there is here touched the principle of absorption, by means of which dead substances, blood-clots, and exudations are disposed of. A new view of the function of these cells seen in inflamed tissue has been propounded by Metschnikoff, whose first studies on the action of the daphnia when attacked by the spores preying upon that organism formed the basis of his doctrine; which is, in brief, that the cells of the inflamed part and the invading organ- isms are opposed to one another in a struggle for existence. If the white corpuscles, or the phagocytes, are enabled to appropriate and to destroy the bacteria with which they come in contact, the system is protected from the germ; if, however, the bacteria are SIMPLE INFLAMMATION. 107 more powerful than the cells, a destructive local inflammation or a constitutional disease may result. MetschnikofF describes two kinds of phagocytes — the microphagocyte and the macrophagocyte. The former corresponds to the migrating leucocyte, and the latter are larger cells developed from the proliferated fixed connective- tissue corpuscles, which in some cases consume the smaller cells after their struggle with the bacteria, thus removing the debris of the inflammatory struggle and paving the way for an absorption of its products. In other cases they attack the bacteria directly: they are, for instance, more likely to take up bacilli, as in anthrax and leprosy. In tubercle the macrophagocytes figure as epithelioid cells and giant-cells containing bacilli, but these organisms are seen also in the leucocytes. This doctrine is well illustrated by studies made by its author in erysipelas. He finds that in fatal cases of this disease only comparatively few leucocytes were seen, and none containing bacteria. In the cases recorded some of the cells contained a large number of the bacteria; other cells contained none. In some of the former there were perfectly-formed bacteria; in others the bacteria did not take the staining reagent so well, showing a degeneration of power; and in others granular debris only of bacteria was found. In gangrenous portions of erysipelatous tissue no cells containing bacteria were seen, the microbes all being free in the tissues. Experiments made with the anthrax bacillus on animals not susceptible to this disease show well the action of the leucocytes, as this form of bacteria is so large that the organisms are studied with comparative ease. In some diseases the macrophagocytes appear to be the active cells; in others the microphagocytes destroy the bacteria. Many observers have not accepted this doctrine, and they maintain that the loss of activity of the bacteria is either a spontaneous loss or one due to the antagonism of other forms of bacteria. Baumgarten points out that in relapsing fever the spirilli are not seen in the leucocytes, yet the patient recovers. The explanation of this is, probably, that the strife is not waged in this case in the blood, but in the tissues or the viscera, as the spleen. At all events, there is seen, in this doctrine, although it is as yet hardly removed from the stage of probability, a reasonable explanation of that condition known as immunity, by means of which certain animals are pro- tected from certain diseases, and by which man is also protected from a second attack of certain diseases. ioS SURGICAL PATHOLOGY AXD THERAPEUTICS. A word in conclusion regarding the action of the cells in inflammation. The number of cells found in an inflamed part is in proportion to the degree of inflammation existing there. If, on the one hand, the inflammation has been severe, the tissues will be found so filled with small round cells that it is difficult to recog- nize the original character of the tissue itself. If, on the other hand, the decree of irritation has been slight, as is often the case in wounds healing rapidly under aseptic treatment, a compara- tively small increase in the number of cells of the part takes place. Little has hitherto been said about the changes seen in the intercellular substance. In connective tissues this substance con- sists mainly of a network of fibres. In certain tissues, like carti- lage or the cornea, this substance is more homogeneous in appear- ance, although with suitable reagents the fibrous nature is made apparent. Under the stimulus of inflammation there is great increase in the number of cells which more or less obscure the intercellular substance; but it is evident that a solvent action is exerted upon it, either by the cells that are present or by the fluid which is exuded from the blood-vessels, or by both. According to Strieker, the cellular substance returns to an embryonic state and becomes separated into particles of amoeboid substances; in other words, it is broken up into cells again. According to most authorities, it is, however, simply melted down into a granular softened material, forming a matrix for the support of the vastly increased number of cells. When the cell-immigration is limited in extent there is seen but little change in the intercellular substance. In addition to the escape of leucocytes from the blood-vessels, there is found a certain amount of fluid which has leaked through the vessel-walls into the inflamed part. This fluid is richer in albumin and is more concentrated than the serum exuded in passive hypersemia. and it resembles closely the liquor sanguinis or blood-plasma. The fibrinogen it contains comes in contact with the fibrin-ferment and paraglobulin which are set free from the numerous breaking-down leucocytes, and fibrin is conse- quently formed. That this collection of fluid is not due to an obstruction of the capillaries can easily be demonstrated in a dog's leg by setting up an inflammation in the paw, exposing the lvmph-vessel, and inserting a canula into it, when it will be seen that a considerable increase in the amount of lymph naturally exuded by the vessels is taking place. The coagulation of the SIMPLE INFLAMMATION. 109 lymph thus accumulated in the inflamed part gives to it a certain firmness which is characteristic. The product thus formed, with the cells which have emigrated from the blood-vessels, constitutes what is known as the exudation. Such, then, are the changes which take place in the tissues during the origin and development of a simple or uncomplicated inflammation. The further progress of the inflammatory process will be considered in the succeeding chapter. V. SIMPLE INFLAMMATION. 2. Symptoms and Causes of Inflammation. Font cardinal symptoms of inflammation have from time immemorial been grouped together — namely, rubor, tumor, dolor, and calo)\ or redness, swelling, pain, and heat — to which modern writers have added a fifth, functio l:> Q- A Fig. 37. — Point of Origin of Sup- puration in Osteomyelitis. 198 SURGICAL PATHOLOGY AND THERAPEUTICS. canals, through which the blood-vessels pass. At other times the inflammation remains for a period localized (Fig. 37). The red color of the medulla of youth is preserved in the bones of the trunk and the head during growth and in adult life, but it is lost in the medulla of the bones of the extremities, where the tissue is of a yellow hue, due to the presence of fatty tissue. In osteomyelitis this tissue becomes reddened, but unlike the normal medullary tint, and there is an increase in the consistency of the tissue. The fat- cells disappear, and the part becomes infiltrated with granulation- cells and some red corpuscles. There is, in fact, a great increase in the number of leucocytes and of cells containing red masses and pig- ment-granules, and an increase also in the number of leucocytes throughout the organism, so that an u inflammatory leukaemia" has been said to exist. The spleen may be enlarged, and hemor- rhagic exudations are often found in the serous cavities. Ullmann found, in dogs with osteomyelitis, that the leucocytes were increased from four- to sixfold. The inflammatory exudation is not diffuse, however, but collects at numerous foci, which give to the part a mottled appearance due to local congestions and to extravasations of blood. As these foci soften they turn yellowish-gray or dark red according to the amount of blood or pus they contain. The bone, on section, shows collections of pus or of spongy tissue infil- trated with pus. The numerous abscesses are varied in form and size, and are often arranged in rows near the epiphyseal cartilage. As soon as suppuration is established there forms a line of granula- tions which separates the diseased from the healthy tissue. New tissue is formed both in the medulla and in the periosteum, con- taining many osteoblasts, which are capable of producing new bone. An absorption of tissue takes place at these points, thus separating the dead from the living bone. As the amount of pus increases, it either spreads by infiltration along the interior of the shaft of the bone or it works its way through some of the natural channels (as the Haversian canals) to the surface, and accumulates beneath the periosteum, separating it from the bone (Fig. 38). When the pus breaks through this obstruc- tion it burrows next between the muscles, and it may form one or more distinct abscesses. The pus which they contain is at first of a brownish color, occasionally has a very foul odor, and is accompa- nied by the discharge of extensive sloughs. It frequently contains innumerable drops of medullary fat, which is said to be quite a cha- racteristic feature of these abscesses, and therefore to possess a cer- tain diagnostic value. This fat is due to increased pressure in the INFECTIVE INFLAMMATION. 199 Fig. 38. Extension of Suppuration in Osteomyelitis. medullary cavity, which forces the fat-drops through the Haversian canals. In many cases the epiphyseal cartilage remains intact through all this inflammation, and offers an ef- fective barrier against the spread of the disease toward the joint. In some cases, however, it is broken through and disappears, and the disease attacks the epiphysis. One joint may be af- fected either by a direct extension of the pus in this way through the bone or by the more circuitous route from abscesses which have perforated the periosteum and eventually have pushed their way through the capsule. As the epiphyseal cartilage is absent in the adult, the joint is more likely to be affected at this period of life. The effect of this acute suppurative process is to cause necrosis or death of the bone. When the shaft of the bone is involved in the ordinary way, a few fine, needle-like particles of dead bone may be found in the medullary canal during the first few days of the process. Later, larger fragments may be found to have sep- arated, either as exfoliations from the surface or as fragments from the denser portions of the medullary bone. When the pus reaches the periosteum, it may burrow for a long distance beneath it, and a large portion of the shaft may thus be deprived of its external blood- supply. As a consequence of this com- plication considerable portions of the bone may die, and in rare instances the whole diaphysis or shaft may be destroyed (Fig. 39). There then re- sults what is called "total necrosis" of the bone. Usually, however, only a small part of the shaft suffers, and the sequestra thus formed rarely exceeds one-third or one-quarter the length of this portion of Fig. 39. — Necrosis of the Shaft and Periosteal Formation of Bone. 200 SURGICAL PATHOLOGY AND THERAPEUTICS. the bone. The extent of the necrosis is greater near the point of origin of the suppuration; that is, near the epiphyseal line, and at this point it may occupy the whole thickness of the bone. Nearer the middle of the shaft the necrosis is usually more superficial. It does not always follow that after the periosteum has been sepa- rated the portion of the bone thus exposed must necessarily die. Some of the periosteum thus separated may subsequently become reunited to the bone. The dead bone can usually be recognized, when inspected through freshly-opened abscesses, by its yellowish color and by the absence of the mottled appearance of normal bone. As the result of an extensive necrosis there may be, in rare cases, a spontaneous fracture of the bone at some point in its shaft. But this occurrence is usually prevented by the formation of new bone, which begins a few weeks after the old bone has been destroyed. Separation of the epiphysis also often occurs, but in the majority of cases the suppuration has only been sufficient to separate part of the epiphysis from the shaft of the bone. When the bone dies it becomes a foreign body, still attached to the adjacent live bone, but separated from its covering of perios- teum by a layer of pus. It lies, in fact, in the centre of an abscess. After the abscess breaks the periosteum comes more or less closely in contact with the shaft of the bone, and in a few weeks it is found that bony tissue is forming in the granulation layer lining the peri- osteal wall of the cavity. The formation of new bone takes place slowly, however, and it may be several months before sufficient bony tissue is found to supplant that which is gradually separating as a sequestrum. It is an important provision of Nature which does not permit the live bone to free itself entirely of the seques- trum until the work of the periosteum has been accomplished. Consequently, it is found that when the dead bone is fully separated and is ready to come away from the cavity in which it lies, it has become imprisoned in a wall of new bone (Fig. 40). The pus in which the sequestrum is bathed escapes through one or more fistu- lous openings in the newly-formed bone. In cases in which the periosteum has partly been destroyed by the septic process there will be no bony formation at that point, and the dead bone will then remain covered only by the soft parts, and can easily be reached and removed by the bone-forceps, or it may be forced out gradually from its bed by the exuberant granulations, or, if small in size, it may be expelled through a fistulous opening in the integument ; in rare instances large fragments of bone may be extruded in this way. The pus exerts only a slightly solvent action INFECTIVE INFLAMM. I TI( W. 20I upon the necrosed bone, but there are nevertheless frequently sepa- rated from the larger sequestra bony spiculae, which from time to time are found in the discharges upon the dressings. The seques- trum is more likely to be affected by the young growing granula- FlG. 40. — Separation of Sequestrum and Formation of Involucrum. Fig. 41. — Unhealed Abscess-cavity, with Eburnation of the Surrounding Bony Tissue. tion tissue, by which small sequestra may entirely be absorbed. The large portions of dead bone may, however, remain for years imprisoned in their bony cavities. After all sequestra have been discharged a suppurating cavity frequently remains with no tend- ency to heal, owing to the rigidity of its walls (Fig. 41). Such cavities may eventually become tuberculous. The epiphyseal car- tilage in a certain number of cases remains intact; in other cases it is partially affected, and in still other cases it has disappeared, and under these circumstances it is usually found that the epiphysis or even the joint has been involved. Occasionally, as a result of the disorganization of the cartilage, there is a complete separation of the epiphysis from the diaphysis. The regeneration of the medulla takes place from the perivas- cular connective tissue in the Haversian canals which open into the medullary cavity, and also from those portions of the marrow that still remain at the epiphyseal ends of the bone. From these points is developed a gray connective tissue which eventually assumes all the characteristics of the old medulla. On the bor- 202 SURGICAL PATHOLOGY AND THERAPEUTICS. ders of the newly-forming bone are found the osteoblasts from which the new bony tissue is developed. This new tissue is more porous and irregular in its arrangement than the old bone, and the bone-corpuscles it contains appear to be larger than those seen in normal bone-tissue. In some places an absorption of bone may occur as a result of the inflammation. Here are found in the porosities of the bony tissue the large giant-cells or osteoclasts through which absorption takes place. Occasionally there is found a bipolar ostitis, both juxta-epiphy- seal regions of the bone being affected simultaneously. The disease begins in these cases at one end of the bone, and the infective material is conveyed through the medullary canal to the other end. At times the route taken can be followed throughout the canal; at other times the infection leaves no sign of its pas- sage. In some cases these bone-inflammations may be multiple, several bones being thus simultaneously affected, such cases closely resembling pyaemia. The latter disease is not infrequently a sequel of the severer types of this form of bone-inflammation. Makin and Abbot report forty-one cases of bone-inflammation terminating fatally with symptoms of pyaemia. But many of the so-called cases of pyaemia originating from osteomyelitis are to be regarded as multiple osteomyelitis, the pyogenic cocci in such instances con- fining themselves to the osseous system. Such forms of osteomye- litis run a far more favorable course than pyaemia. In combination with such types there may be ulcerative endocarditis. Such a case has recently occurred in the hospital ward. A boy, twelve years of age, suffering from osteomyelitis of the shaft of the left tibia and the clavicle, had also marked valvular disease. The clavicle was treated by the removal of a large sequestrum involving the entire shaft of the bone, and amputation through the lower third of thigh was performed, as ^repeated operations by different surgeons failed to arrest the suppurative process in the tibia. True pyemia, however, may follow the outbreak of a violent type of osteomyelitis, and in certain cases the patient may die in a few days after the development of inflammation from septicemia. The latter complication sometimes follows the opening of a bone- abscess. Such a case recently came under the writer's observa- tion. The patient, a gentleman of about sixty years of age, had many years before suffered from osteomyelitis of the right femur, which had healed without necrosis of any extent. The abscess had been forming for about fourteen days, and when opened a large INFECTIVE INFLAMMATION. 203 amount of fetid pus and sloughs was discharged, and the patient rapidly succumbed to acute septicaemia, which supervened. This case illustrates also the tendency to recurrence, which, after years of apparent health, the disease sometimes shows. These recurrent forms are said to be due to spores which have become encapsuled, and, owing to some local disturbance, have become free again. Osteomyelitis is not always found in the long bones. It may have its seat in both the short and the flat bones. It is, however, much more rare in the latter situation, and many of these cases are mistaken for tuberculosis. In fifty-one cases reported by Frohner the clavicle was found diseased eleven times, the scapula nine times, the ileum nine times, and the os calcis seven times. The disease may occasionally be situated in the so-called "joint region," and it then constitutes what is called epiphyseal osteo- myelitis. There is in this form of the disease a primary localiza- tion of the inflammation in the articular extremity of the bone; that is, between the epiphyseal and articular cartilages. Under these circumstances the joint is involved at an early stage, for the more vascular epiphyseal cartilage offers a barrier to the spread of the disease toward the shaft of the bone, and the pus can therefore spread only in the direction of the articular cartilage. The joint affection soon overshadows the disease of the bone, and the patient presents the symptoms of a joint inflammation, the origin of which can only be brought out by a careful study of the case. Jordan, who reports two such examples, advises an early opening of the joint before it has been destroyed. Many such cases have undoubt- edly been mistaken for tubercular disease. We next come to a consideration of the symptoms of osteomye- litis. As the reader has already seen, this disease occurs most fre- quently in youth and after some slight injury or from exposure, or perhaps from no known cause. The patient suffers for several days from prostration, and complains of pain in some one joint or in the adjacent bone. Presently a severe chill occurs, which is followed by high fever, frequently of a typhoidal character. The pulse is weak and rapid and the face is flushed, the expression in the gravest cases being one of fright and stupefaction. The tongue is dry and coated, and there is frequently some delirium. The spleen is slightly enlarged, and there is often a foul diarrhoea. These are the symptoms of a grave septic infection of the system, probably from the ptomaines or toxines set free by the invasion of the bacteria. At first the only local symptom may be pain, but presently a swelling can be observed in the neighborhood of some 204 SURGICAL PATHOLOGY AND THERAPEUTICS. joint, such as the knee, the shoulder, or the elbow, followed soon by more or less oedema of the adjacent soft parts, which oedema usually surrounds the affected limb. The swelling spreads in the direction of the axis of the bone, and the skin becomes cedema- tous and the veins enlarged. Although the skin may not yet have changed color, the part is excessively painful to pressure, the slight- est movement of the limb causing the patient to cry out lustily. The pain is of a boring or almost breaking character, and at times throbbing; it is not necessarily always near the epiphyseal line, but may be near the middle of the shaft: it may exist for several days before the most careful examination can detect any local change or swelling. As the color of the skin changes to a reddish hue signs of fluctuation appear, and if the abscess is now opened the pus discharged is of varying character, according to the partic- ular conditions of the case. At times the pus may be foul and filled with fragments of slough and decaying blood. Again, the pus may be found comparatively typical in character, and it will then be perceived that there are innumerable minute drops of fat floating in it. These fat-drops arise, as has been explained, from the decomposed medullary tissue, having forced their way out through the Haversian canals. Often, at this time, it will be found that the joint has begun to sympathize, and there may simply be catar- rhal synovitis due to the neighborhood of the severe inflammation, or the joint, from having become infected, has begun to suppurate. In rare cases the disease in a bone can thus infect both articular cavities with which it is in contact. The lungs are often also the seat of inflammations at this period, which inflammations may be caused by fat-embolism, such as is often observed after extensive fractures. This complication is seen in the early stages of the disease, and appears as a diffuse catarrh with abundant expectoration or with symptoms of oedema of the lung. Later pneumonia may be found developing, caused by ^v £ emboli which have been detached from infected thrombi formed a in the rich venous network in the medullary tissue. Metastatic deposits may also be found occasionally in other organs, such as the kidneys, and the symptoms of a genuine embolic pyaemia may, in rare instances, gradually develop. In the majority of cases, how- ever, the situation is not so grave, and with the discharge of pus from the abscess the fever subsides and the case assumes a chronic type. It may then be found that the heart has been involved, and that there has been developed an endocarditis due to the attachment of the bacteria to the endocardium. INFECTIVE INFLAMMATION. 205 Returning, now, to the abscess which has just been opened, it will be found, on introducing the finger into the wound, that the bone has been denuded of its periosteum. If the pus has burrowed beneath the periosteum, the bone will be exposed for a considerable distance, and the surgeon will be somewhat startled to feel his finger gliding over the smooth and slippery surface of the shaft of the bone, which may be completely separated from the soft parts surrounding it. At other times an incision down to the bone may not liberate pus, and it then becomes necessary to open the interior of the bone before the seat of the suppuration can be dis- covered. With the discharge of pus the severity of the constitu- tional disturbance abates. As the suppuration gradually diminishes in quantity the fever disappears, leaving the patient greatly emaciated and with one or more sinuses leading to the diseased or dead bone. As has already been seen, more than one bone may be affected at the same time, and this appears to be due not necessarily to metastasis, but to the simultaneous affection of one or more local- ities ; at all events, these cases of multiple osteomyelitis must not be classified with those which succumb to genuine embolic pyaemia. The clinical picture in the two types is a very different one. The various points of inflammation develop synchronously or nearly so, and the virus does not appear to follow the laws of dissemination that hold in pyaemia. Many of these foci of inflam- mation may not come to suppuration. A tender lump may form at the end of a bone, and may subsequently disappear by resolu- tion. At some of these points there appears to be a new formation of bony tissue instead of suppuration, and cases have been reported in which an increased length of the bone has resulted from inflam- matory hyperaemia. In not a few cases — particularly in infants and in young chil- dren — acute suppurative arthritis may occur as a result of the extension of the disease through the tender tissue of the epiphys- eal cartilage. This form of osteomyelitis is frequently secondary to some of the exanthemata or to diphtheria or to pneumonia, and may be observed in many of the children frequenting the out-pa- tient department of a large hospital. The amount of bone-destruc- tion may in such cases be small, and the bone and joint may be restored to the normal state. This is the class of cases referred to by Koplik and Van Arsdale as being caused by the streptococ- cus infection. These authors recognize two forms of streptococcus osteomyelitis. In the mild form the disease is non-articular, the constitutional disturbance is slight, and it corresponds to Volk- 206 SURGICAL PATHOLOGY AND THERAPEUTICS. mann's catarrhal inflammation of the joint. The local inflamma- tion is an acute one, and the joint suppurates, but the disease yields readily to surgical interference, and the function of the joint is gradually re-established. The grave type of the disease is insidious in its onset, the first thing noticed by the mother being the consti- tutional disturbance. "The child, if brought to the physician's attention, at once awakens solicitude. It lies quietly, pale, with sunken eyes surrounded by dark rims ; its tongue is coated, fulig- inous ; its skin is dry, its temperature not being very high, how- ever." Occasionally there are symptoms of pain, indicated by sharp little cries, and when certain parts are touched the suffering of the child is very great. In later stages the swelling of the joints is more pronounced. Several joints are usually affected, and aspiration reveals pus. Many of these cases belong to the class which has incorrectly been classified with pyaemia. Closer examination shows that the suppuration has emanated from the shafts of the bones, and that this portion of the bone may at times become extensively involved in the disease. The diagnosis of acute osteomyelitis may, under certain circum- stances, be attended with unusual difficulties. Most frequently the disease is mistaken for acute articular rheumatism. If a child is attacked in one or more joints simultaneously with symptoms of acute inflammation, and, later, symptoms of cardiac complication are developed, it is not surprising that the treatment selected should frequently be the administration of salicylic acid. Occa- sionally a patient is brought into the hospital in a more or less comatose condition, and it is only with great difficulty that there can be obtained from his friends anything approaching a history of the case. If under these circumstances there is as yet little local swelling around the focus of inflammation, it is not improb- able that the diagnosis of typhoid fever might be made. The disease does not always confine itself to the long bones, for not infrequently it is found that the carpus and tarsus, and some- times the flat bones, like those of the cranium, are affected. Such cases might be mistaken for tuberculosis. Tuberculous inflammations, however, are of a chronic type, while pyogenic inflammations are always acute. In doubtful cases the local conditions must carefully be studied, particularly with reference to their history. It will then be found that the pain is first noticed near the joint, and that pressure will bring out the fact that an acutely sensitive spot exists near the epiphyseal line. It is undoubtedly the fact at the present time that the true nature IN FECI 1 1 F IX FLAM MA WON 207 of these cases is not generally understood. Attention has not yet been drawn toward this subject, particularly to the importance of an early diagnosis, which may result in saving from destruction not only the bony tissue, but also a joint. The danger both to life and to the welfare of a limb is so great that it is to be hoped that those who see these cases in the early stage will realize the importance of a correct diagnosis and the necessity for prompt treat- ment. Much harm has been done by a former generation of surgeons, who taught that these cases were the result of periostitis — a diagnosis which inevitably leads to incorrect views as to the proper treatment. The most frequent sequel of this disease is necrosis, which may be recognized by the presence of a fistulous opening leading to the dead bone. A probe introduced will readily detect the hard, smooth, bony substance lying at the bot- tom of the sinus. Occasionally the sinus is simply filled with flabby granulations, and it is probable that portions of the dead bone have been expelled by the pressure of the granulation tissue that has developed, or that the sequestra, if small, have been absorbed. The amount of bone disposed of by the process of absorption is in most cases exceedingly small, and large sequestra often remain for years unaltered (Fig. 42). Spontaneous fracture is exceedingly rare. The writer remembers having seen but two examples. Separation of the epiphysis oc- curs, according to Ullmann, not as the result of the disintegration of the epiphyseal carti- lage, but in consequence of a suppuration through the lower portion of the shaft, and it appears to occur quite independently of necrosis. In some cases the inflammatory symp- toms subside without the discharge of pus, and the patient appears to have recovered from the attack. Pain, m however, recurs from time to time, and the patient may suffer for years from attacks of neuralgic pain, arising chiefly at night. There may be little if any enlargement of the bone to indicate the seat of the inflammatory process. Finally, an operation discloses an abscess Fig. 42. — Necrosis of Femur, the result of Acute Osteo- myelitis. 208 SURGICAL PATHOLOGY AND THERAPEUTICS. situated usually near the epiphyseal end of the bone. The cavity formed in the bone has usually a smooth surface and contains true pus. The surrounding bony tissue is much denser than in the normal condition, and frequently presents the condition known as ebumation (PI. I.). These abscesses are usually small, and they contain a drachm or two of pus, but occasionally they may attain great size. Stanley describes such a bone-abscess, the opening into which was closed by a cork that the patient was in the habit of wearing to protect himself from the discharge of pus. Dislocation may occur as the result of several conditions. The joint may have become disorganized by the extension of the inflam- mation, the capsule and ligaments being then relaxed or partially destroyed. Roser has explained some forms of dislocation by an unusual growth of the ligaments due to hyperemia near the necrosed bone. In some cases the growth of the bone is arrested by the destruction of the epiphyseal cartilage. If there is an adjoining bone which continues to grow, a displacement of the head of the adjacent bone may result. Nelaton mentions such a displacement of the head of the fibula in consequence of an arrest of development of the tibia. In rare instances the granulations which protrude from the fis- tulous openings may begin to assume an active growth and the skin around becomes more or less infiltrated. The discharge is then more purulent in character, and it has an offensive odor. A new growth, which proves to be carcinoma, is taking place in the gran- ulation tissue. Volkmann has collected thirty-two examples of this complication. Prompt amputation of the affected limb is of course the only remedy, as an early involvement of the inguinal glands may take place. The prognosis of the disease varies, as may easily be judged, from the severity and the extent of the inflammation. The grave types of osteomyelitis that terminate fatally in a few days are hap- pily rare. This form is perhaps most frequently seen in young children or in infants, and it is usually due to a streptococcus inflammation. In a large majority of the cases the severe constitutional disturb- ance may subside in due time, and the chronic stage of the disease may be prolonged indefinitely. Nature does not appear equal to the task of removing the dead bone from its newly-formed cavity. The spontaneous removal of all sequestra is the exception. Even an empty cavity may be unable to heal, owing to the inability of its bony walls to shrink, and a ' ' bone-fistula ' ' may remain as a PLATE I Shaft of the Femur, showing the results of osteomyelitis. Thickening of bone with eburnation. The sequestra have long since been discharged. INFECTIVE INFLAMMATION. 209 permanent condition (PL L). In some cases when the necrosis has been extensive, and when the suppuration has been pro- longed and excessive, the patient may become greatly emaciated, and eventually amyloid degeneration of the internal organs may supervene, which condition is soon followed by a fatal termination of the case. Since the pathology of osteomyelitis has been recognized and the point of origin of the inflammatory process has been definitely determined, the question of treatment has been much simplified. This is a disease which is caused by pyogenic cocci, and which ter- minates with hardly a single exception in suppuration. It is true that a certain number of cases are reported where the symptoms- have subsided and the inflammation has terminated in resolution instead of in suppuration. Such cases are probably not true cases of acute osteomyelitis. Counter-irritation, which was a mode of treatment much in vogue in former times, may be discarded. It is known that the actual cautery may in experimental cases of inoculation with pus- cocci prevent suppuration by stimulating the absorption of these organisms before they have had time to multiply, but such an agent would hardly act upon the deeply-seated foci, the presence of which in bone is not detected until the disease has made too much prog- ress to be checked. In the early stages, before a diagnosis has been made, much may be done to mitigate the sufferings of the patient. The limb may be immobilized by a splint and pain be relieved by the application of ice-bags or of poultices. The treat- ment of this disease from the earliest moment that a diagnosis can be made is eminently a surgical one. As in cases of suppuration in the abdominal cavity, pus must be removed before it has an opportunity to effect serious or fatal injury. Although in appendi- citis some surgeons still hesitate to operate, as many cases recover without suppuration, in osteomyelitis pus is always formed, and must be removed — the sooner the better. The problem differs somewhat according to the stage the disease has reached when the patient first comes under observation. In the earliest period the pus is still confined to the interior of the bone, and a well-formed abscess may not yet have developed. It is uncertain whether the virus may not infiltrate the whole medulla and destroy the entire shaft or endanger the life of the patient. In these cases an opening should not only be made to allow the pus to escape externally, but an attempt should also be made to remove the infected area itself, and thus to arrest the inflammation. Some 14 2io SURGICAL PATHOLOGY AND THERAPEUTICS. writers advise an attempt to remove the pus by boring with a drill numerous small holes through the soft parts and the bone. This is Ullmann's method, who makes the punctures from 2 to 3 centimetres apart. Kocher not only punctures the bone, but also injects carbolic acid with a view to disinfecting the foci of suppura- tion. Such procedures seem hardly suited to ordinary cases of bone-suppuration, but might be used on some of the smaller bones, such as the alveolar processes of the jaw, where the amount of pus is exceedingly small. In typical cases of this disease a prompt incision should be made through the soft parts to the bone, which must then be opened with the gouge or with the trephine. Fre- quently no signs of inflammation will be detected until the medulla has been reached; then a few drops of pus, collected in small foci, may be revealed, or the discharge may merely be of a sero-puru- lent character, or the medullary tissue may be gangrenous. The infected portions of the medulla must carefully be scraped away, and if this operation is thoroughly performed the wound may be left in a completely aseptic condition. The wound should not be closed, but, after having been thoroughly washed out with some disinfectant, should be stuffed with iodoform gauze. The result of this treatment is subsidence of the febrile symptoms and great relief of the pain. If, however, the high temperature recurs and the bone again becomes painful, it may be necessary to enlarge the bony opening and to scrape away any portion of the medulla found to have become infected. A stout, sharp curette is the most useful instrument for this purpose: it should be made in various sizes, so as to reach all corners of an infected area. The Esmarch bandage should always be applied before operating upon the bones of the extremity, the surgeon being thus enabled to carry out with great precision all the details of the operation and to see with great ease all the pathological changes. When the pus has reached the surface the periosteum is dis- sected from the bone for a certain distance and the soft parts are invaded. This condition is readily recognized by the swelling and the redness of the surrounding integuments. In such cases the external abscess must be laid open and disinfected by curetting and by washing its walls; the periosteum must be opened freely, and a search must also be made for the point of origin of the inflammation in the bone. This is a precaution which surgeons often neglect, thinking that the case is one of "suppurative periostitis," and that it is unnecessary to search farther. The teachings of pathology must be remembered here, and search for INFECTIVE INFLAMMATION. 2ir pus must be made near the epiphyseal Hue. No operation which does not include an opening into the bone should be regarded as a completed one. French surgeons have long recognized the import- ance of this detail. Lannelongue advises that the trephine should be placed near the epiphysis, and that a second opening should be made into the shaft of the bone to open the medullary canal, which in young subjects does not always reach to the epiphyseal line. If the periosteum has peeled off for a great distance, it may be neces- sary to make a third opening. Trephining, he thinks, should also be employed in osteomyelitis of the flat bones, such as the cranium. Multiple openings are only advisable in very extensive disease of the medulla. Under ordinary circumstances an opening near the epiphyseal line should be made, and be sufficiently enlarged with the chisel or the gouge to expose the diseased area. Formerly it was advised not to open these abscesses until the last moment, when the surrounding inflammation had had time to protect the tissues from the decomposing medulla. It was found that in many cases of early opening the patient succumbed to septic infection, but this rule does not hold good at the present time. The custom serves, however, to emphasize the importance of thoroughly opening and disinfecting these treacherous abscesses. So serious were the results following these operations before the days of antiseptic surgery that amputation was freely advised as the only means of saving life. The fine specimens of bones containing sequestra in many of our museums are silent testimony to the pop- ularity of the discarded treatment. Chassaignac laid down careful rules for amputation in this class of cases, and Roux held that disarticulation was the only proper remedy, as amputation through the continuity of a bone did not avail to prevent the spread of the inflammation. Amputation is now resorted to only in exceptional cases, when all other means fail to arrest the suppuration or the case approaches a fatal issue. When such abscesses have been opened and disinfected drainage-tubes should be introduced down to the medulla, and the abscess-walls should be packed with iodo- form gauze. The whole limb is then swathed in a voluminous antiseptic dressing and is placed upon a splint. If all goes well, this dressing need not be changed for several days. But if consti- tutional disturbance continues, the dressing should be removed and the wound be thoroughly washed out with a disinfectant. A moist antiseptic dressing may in such cases be substituted for the dry dressing. A large cotton poultice soaked in a solution of sulpho- naphthol (i : 250) may be applied and changed once or twice a day. 212 SURGICAL PATHOLOGY AND THERAPEUTICS. In those cases where the joints are involved — which complica- tions occur chiefly in infants and in young children — the following rules, laid down by Van Arsdale, should be observed: As soon as the joint appears swollen and becomes painful, it should be aspi- rated under the strictest antiseptic precautions, and if pus is found the joint should be laid open, drained, and dressed antiseptically. Usually one incision will be sufficient for this purpose, but in some instances counter-openings with packing of the joint, or even resec- tion of the joint, may be necessary. Resection of the hip is more frequently performed than that of the other joints. Volkmann found the prognosis more favorable in resection of the hip for this disease than for tuberculosis. Special attention should also be given to the shaft of the bone in these cases, and incisions should be made for the purpose of exploring this portion of the bone. If it is necessary to remove portions of the shaft, Van Arsdale dwells upon the importance of working upon the two regions separately, with the view of sparing, as much as possible, the epiphyseal line, and thus giving an opportunity for the future development of the bone. Many cases of osteomyelitis resist all efforts to arrest the inflam- mation. Suppuration continues, and the shaft of the bone may become more or less disorganized. In other cases the pus may burrow so freely under the periosteum as to denude the entire shaft. Under these circumstances the question has been raised as to the justifiability of a resection of a considerable portion of the shaft of the bone. Oilier recommends this operation only as a last resort. It should be performed as late as possible, as the perios- teum may then have reached the reproductive stage. The objec- tion to this operation is the uncertainty of the reproduction of the bone; a large number of operations are reported where only a par- tial renewal of the diaphysis has taken place. Marchant reports a case of resection of the shaft of the tibia in a child sixteen years of age. This patient, when seen five years later, walked on the side of the foot. A case of resection of two-thirds of the inferior portion of the radius was followed by forced extension of the hand backward and outward. Marchant reports successful cases of resec- tion of the shaft of the humerus and of the femur, and successful cases are also reported by Holmes, Cheever, and many other sur- geons. Petersen reports the case of a sailor, seventeen years of age, who had been suffering for eight days from osteomyelitis of the clavicle. The entire diaphysis was dissected by pus and was removed. The bone was renewed in four weeks, and the wound INFECTIVE INFLAMMATION. 213 was healed six weeks after the operation. In the bones of the extremities such a condition would be, according to Oilier, extremely unfavorable for the repair of bone, and if the perios- teum is dissected off in this way by pus, its osteogenetic elements will be destroyed. The cases favorable for resection are those in which the periosteum is thick and covered with osseous plates, and this condition is found in the later stages of the disease. Certain portions of the skeleton are more readily reproduced than others ; as, for instance, the lower jaw and the lower portions of the tibia. The prognosis of resection is most favorable in children; after the twentieth year resections of the shaft are problematical. In many cases in which the operation has been attempted the amount of shortening of the limb has been excessive. In resections of the shaft of the bone care should be taken not to interfere with the epiphyseal cartilage. The incision through the periosteum should carefully be made, and this membrane should be bruised as little as possible during its separation from the bone. The edges of the periosteum should subsequently be sutured with catgut, and a small drain of gauze should be left in one or in both ends of the incision. The limb may then be immobilized on a splint during the subse- quent treatment. By far the greater number of cases of this dis- ease come under the notice of the surgeon during the stage of necrosis ; that is, after all acute symptoms subside and a fistulous opening remains to mark the site of the abscess. It is generally agreed that sufficient time must be allowed to elapse for the sequestrum to separate from the live bone before the attempt is made to remove it. It is quite difficult to determine where the line of demarcation is to form, and it often happens that a piece of bare bone of considerable size is gradually covered over by granulations and the wound heals without any loss of bone. The bone receives its nourishment from the vascular medulla, as well as from the periosteum, and the separation of the latter does not there- fore necessarily result in death of the bone. An early interference may therefore not only involve the removal of a needlessly large quantity of bone, but may also disturb the vitality of the sur- rounding bony tissue and cause the separation of new portions of the bone. The time required for the separation of a sequestrum varies greatly. At the epiphyseal line the bone may separate in a few weeks, but in the shaft of the long bones it may be several months before the sequestrum is fairly loosened. A fragment of cortical bone usually separates much more rapidly than some of the deep- 214 SURGICAL PATHOLOGY AND THERAPEUTICS. seated, spongy sequestra. There is less danger of spontaneous fracture if the sequestrum is allowed to remain until the involucrum has developed and sufficient new bone has thus been formed to replace the old. Usually, when a typical case of necrosis presents itself for treat- ment, the sequestrum is found deeply seated within a cavity formed by new bone, which has grown exuberantly and lines for some dis- tance the walls of the sinus leading to the dead bone. When a considerable quantity of periosteum has been destroyed by the sup- purative process, the dead bone will be found uncovered by new bone, and may, consequently, much more easily be reached. The cicatricial tissue about it, however, is dense and unyielding, and in any case, therefore, free incisions are necessary to lay bare the for- eign substance which is to be removed. One should always be pre- pared, therefore, for a long and tedious operation and for extensive dissection in these cases; for it is not only necessary to remove the dead bone, but the cavity must be so treated as to heal permanently. The rigid walls of an old involucrum cannot shrink together, and they are covered with feeble granulations which may contain a miscellaneous assortment of bacteria. These are the conditions which favor the persistence of a " bone-fistula." The old method of treatment, which consisted principally in fishing for fragments of dead bone with the forceps, cannot too strongly be condemned. Modern surgery demands a completed operation; that is, one which ensures rapid and permanent healing of the wound. The limb having been thoroughly cleaned and the sinus having been syringed out with some mild antiseptic for several days before the operation, an antiseptic dressing should be applied, so as to diminish as much as possible the septic condition of the parts sur- rounding the wound. The Esmarch bandage having been so adjusted as to render the limb bloodless, the sinus should be laid open to its point of entrance into the bone. In some cases it will be found impossible to do this, owing to the tortuous nature of the canal and to the presence of a large vessel or a joint-cavity in the immediate neighborhood. In necrosis of the lower portion of the diaphysis of the femur the sinus often opens through an intermus- cular space near the route of the femoral vessels, and the surgeon must proceed cautiously to avoid wounding these vessels. It may be more convenient under these circumstances to approach the bone-cavity from the opposite side of the thigh if it be necessary to chisel away a large surface of new bone. A clean and straight incision should be made through the soft parts and the periosteum, INFECTIVE INFL. I MM A TION. 215 and the surface of the bone should be exposed freely. The entire roof of the suppurating cavity should then be removed with the trephine or the chisel or with both. This operation is necessary not only to ensure complete removal of the sequestrum, but also to expose the lining pyogenic membrane, so that it may be scraped away thoroughly and nothing but healthy tissue be left behind. The same scrupulous care should be given to this part of the operation that the dentist employs in treating a carious cavity in a tooth. The wound, as now shaped, is no longer a fistulous tract, but a trough-shaped affair with a large opening. It may now be treated so as to heal by granulation or to unite by first intention. In the former case the wound, after being thoroughly irrigated with a weak solution of corrosive sublimate to wash out all particles of bone or of tissue, is stuffed with iodoform gauze, which is used in sufficient quantity to keep the upper por- tions of the lips of the wound well separated from one another, so as to allow the wound to heal slowly from the bottom to the sur- face without resuming a fistulous shape. This method consumes a considerable period of time, and may, owing to neglect on the part of the patient, terminate in a fistula which may require months to heal. Attempts have been made to hasten the healing process by plas- tic operations. Flaps of skin have been turned into the long gut- ter, so that the exposed surfaces of bone may be covered in by the yielding soft parts. Fragments of bone still adhering to the peri- osteum have been loosened from the sides of the trough, and have been pushed in so as to obliterate the cavity. Schede proposed to fill up this deep cavity in the bone with blood-clot, which subsequently becomes "organized," after the manner originally described by Lister. The wound must be made absolutely aseptic by chiselling away all diseased or infected bone and cutting away edges of skin and tissue which have been satu- rated for a long time with the discharges. Any suspicious corners must be swabbed out with strong solutions of carbolic acid or of permanganate of potash, and the wound must be drenched and scrubbed freely with milder antiseptic washes. The edges of the periosteum and integuments are now approximated by sutures, which should be made of catgut and be applied as buried sutures. A small strip of protective or rubber cloth is placed over the wound, and before the tourniquet is removed an antiseptic dressing is firmly bound on, to prevent the escape of blood which oozes from the walls of the wound and fills the cavity. This dressing should 2l6 SURGICAL PATHOLOGY AND THERAPEUTICS. not be disturbed for two weeks, at the end of which time, in successful cases, the wound will be found to have healed by first intention. It is not always easy to retain sufficient blood in the cavity thus prepared to fill it completely, in which case the delicate clot grad- ually melts away as granulation tissue forms, and the wound has to be reopened and allowed to heal from the bottom. A partial suc- cess will, however, shorten considerably the healing process. Senn conceived the idea of utilizing decalcified bone-chips as a ' ' filling ' ' for these bone-cavities. These bone-chips are preserved in an alcoholic solution of corrosive sublimate or in a solution of iodoform in ether. The most favorable cases for this method are bone-defects due to the removal of tumors, or bone-lesions other than those produced by pus-cocci. The next most favorable cases are primary circumscribed inflammations in the epiphyseal ends of long bones. This method is also applicable after operation for necrosis. After the cavity has been disinfected and dusted over lightly with iodoform the chips, previously washed in an antiseptic solution, are dried upon a gauze compress, and are then put into the cavity until it is packed with them as far as the periosteum. The periosteum is now sutured with absorbable buried antisep- tic sutures. Buried sutures may also be used for the soft parts above. The skin is finally su- tured with silk. An absorbable antiseptic drain of catgut is used at the extremity of the wound to allow the escape of the super- abundant blood, which flows in as soon as the tourniquet is re- moved. The remaining blood coagulates and forms a matrix in which lie the bone-chips (^g. 43). A voluminous antiseptic dressing should be applied to the limb, which should be con- fined in a splint, and the dressing be allowed to remain undis- turbed for two weeks. Rest should be enforced until the process Fig. 43. •Healing of Blood-clot, and Senn's Bone-chips. INFECTIVE INFLAMMATION. 217 of repair in the interior of the bone has been completed, embracing a period varying from four weeks to three months. Many successful cases testify to the value of both the above meth- ods. They cannot, however, be carried out in difficult cases except by the trained surgeon with every possible convenience at his com- mand. Many bone-cavities communicate with the exterior surface by numerous tortuous channels, whose walls contain septic material which is sure to contaminate the blood-clot. These methods are better adapted to cavities not made by suppuration or to pus-cav- ities of limited size and readily accessible to the gouge or to the curette. In some of the more complicated cases of necrosis a pre- liminary operation might so far restore the neighborhood to a cleanly condition that the blood-clot method might later be adopted with success. When, however, the cavity has been opened and cleansed in the thorough manner already described, there is every reason to hope that a permanent healing of the wound may be completed by the process of granulation in from three to four months' time, and this is the method the writer would recommend in the majority of cases. The attending physician should never undertake the care of such a case if he contemplates only halfway measures. If not prepared to go through with the labor of a com- pleted operation, it will be better for his reputation to have nothing to do with the case. IX. THE PROCESS OF REPAIR. Formerly the changes brought about in the tissues by means of which repair was effected were supposed to be caused by inflam- mation. It was thought that a smart inflammatory reaction was necessary to glue the lips of a wound firmly together. Aseptic surgery .has demonstrated the error of this view, and it is now known that the two processes are quite independent of each other. The action of the cells in repair is a question about which there has been a great deal of dispute. Some of the changes which they undergo during inflammation have already been considered. Suf- fice it to say here that Virchow adopted the view that the large number of new cells seen during the reparative process were formed by a proliferation of the pre-existing cells of the part. Cohnheim set aside this view, and replaced it by his theory of the action of the leucocytes, which were supposed to supply all the material for the new tissue that was formed. This theory held sway for nearly two decades, but a more perfect knowledge of the histology and the physiological action of cells has partially restored to the fixed cells of the tissues their former prominence in the process of repair. The old theory of cell-proliferation assumed that all cells' underwent what is now understood as direct cell-division; that is, a segmentation of the nucleus having taken place, there was a division of the protoplasm by means of which two cells were formed. The theory of indirect cell-division s or karyokinesis, has now supplanted that of direct cell-division, which is supposed to take place only in those cells having no power to form new tissue, such as the leucocytes, the role of which in repair is now regarded as quite subordinate. One of the earliest changes that is seen in the cells of a part when repair is going on is an increase in their size. At the same time peculiar changes are taking place in their nuclei. The nucleus consists, according to Ziegler, of a membrane and contents. The latter is composed of a network of nucleoli, gran- ules, and threads which are somewhat opaque, and which can read- ily be stained by pigments. This network lies imbedded in a soft material which is incapable of receiving color. During the process 213 THE PROCESS OF REPAIR. 219 of division the network of the nucleus undergoes a series of typical changes of form which give origin to the term karyokinesis (xd t ouov } nucleus ; xiuyaet;, movement) (Fig. 26). Flemming uses the term karyomitosis (jjuto^ a thread), denoting the thread-like appearance of the network. That portion of the material of the nucleus which stains readily is called "chromatin." The nucleus, in fact, is a highly organized substance by which the cell transmits its peculiarities to its descendants. The proto- plasm of the cell is the medium of communication with the sur- rounding tissues, and it regulates the nutrition. When the cell is about to undergo division there is a marked increase in the amount of chromatin of the nucleus ; the threads of the network become much thicker, and they seem to be coiled loosely together; at the same time numerous nodules appear in the network (Fig. 26 1 ). The nucleolus now disappears, and the mem- brane of the nucleus, losing its ability to take the staining fluid, is soon lost (Fig. 26 2 ). The threads become gradually thicker, and arrange themselves in a series of loops which point toward the equator of the nucleus, and form, when seen from the poles, a stellate figure known as the mother-star (Fig. 26 s ). The next change in the grouping of the threads is known as metaki?tesis, and consists in a movement by which these loops are gradually turned around so as to point toward the poles of the nucleus. As the loops which are now found in two separate groups gradually approach the poles, there are formed two stellate figures (one near each pole), which are known as daughter- stars (Fig. 26 4 ). Their stellate appearance is well seen when viewed from the poles. These daughter-stars gradually resume the thread- like coils found in the original nucleus, and eventually form a network. x\t the same time a new membrane is formed around each coil (Fig. 26 5 ), and two nuclei are thus developed (Ziegler). During nuclear division the protoplasm of the cell undergoes certain active rotary movements : as the result of these movements there is the formation of a bright zone around the nucleus and of radiating lines at the poles of the cell. Finally, there is a segmentation of the protoplasm of the cell, which segmentation begins about the time the daughter-coils are formed. Considerable variations may take place in nuclear division, but the above is the type of the process. The division of the nucleus is usually bipolar, but it may be multipolar. In this way many nuclei may form. If the segmen- tation of the protoplasm is delayed or if it does not occur, the large many-nucleated cells known as giant-cells are developed. 220 SURGICAL PATHOLOGY AND THERAPEUTICS. The cells that multiply and take part in the formation of new tissue are the fixed cells of the connective tissue and the cells forming the walls of small blood-vessels, which cells also take an active part in this process. Under these circumstances the endo- thelial cell is seen much enlarged, projecting into the lumen of the vessel and undergoing mitosis. Some of the new cells come from a distance, and belong, therefore, to the variety of wandering cells. The leucocytes wandering into the part are frequently present in large numbers, particularly when there is much inflammation, but play no active part in the formation of new tissue. While these new cells are collecting the old tissue has perhaps softened and broken down. The intercellular substance becomes more or less granular, and less is seen of it. In this way there is formed a new temporary tissue, known as granulation or embry- onic tissue. The cells found here are the leucocytes, single-nucle- ated or polynucleated, and the cells which are actively forming new tissue are called "formative cells," "embryonal cells," or "plasma cells." They have a granular protoplasm and a bright, round, and large nucleus, which stains readily, giving the cell an appearance strongly suggestive of epithelium. They are therefore usually called ' ' epithelioid cells. ' ' Owing to their power to form connective tissue they are also called "fibroblasts." They have various forms : some are spindle-shaped, others pear-shaped, and many may have several prolongations. Ballance and Edwards describe the plasma-cells seen in small glass chambers placed beneath the skin of animals, according to Ziegler's method, as mostly plate-like cells extended into so thin a film that their exact limit was hard to determine. They were distinguished from leucocytes by their larger size and coarser granules and by the constant presence of a single clear nucleus of oval figure. In specimens from chambers that had rested sevent3 T -two hours these cells showed vacuolation. In some of these vacuoles a leucocyte or red corpuscle could be found. The leucocytes near these cells appeared to serve as a pabulum for them. Not all the leucocytes were disposed of in this way : some of them were dissolved in the tissue- plasma exuded by the plasma-cells (a protolytic ferment). Grawitz believes that many cells — his so-called "slumbering cells" — develop from fibres: nuclei first appear within fibres, and the cell-body is gradually formed around them. These cells are capable of division like fixed cells, and when cicatrization takes place they pass into their fibrous condition again and become slumbering cells once more; that is, they now no longer react to staining processes. When connective tissue is formed, there is seen between these THE PROCESS OE REPAIR. 221 slumbering cells a more or less homogeneous intercellular sub- stance in which fibrillar later make their appearance. The fibril- Ice, however, may form directly without the intervention of a homogeneous material. According to some observers, these fine fibres are formed by a splitting up of the protoplasm of the cell itself: other observers, however, assume that an intercellular sub- stance is exuded, as it were, from these cells, and that in this medium the fibrils are subsequently formed. When the develop- ment of fibres has reached a certain point the formative cells or fibroblasts begin to diminish in number, those which are left being enclosed in narrow spaces between the bundles of new fibres. According to Grawitz, as already seen, the new cells are devel- oped from the so-called kk slumbering cells," which lie, undetected by staining fluids, in the fibres under ordinary circumstances, but when in a state of irritation they become active once more and are capable of forming new tissue. This view, though endorsed by many, has not met with general acceptance. Thus far, connective tissue only has been considered. The cells of this tissue, like all other cells, can of course solely produce those of their own blastodermic layer. An epithelial cell cannot produce cartilage or bone. Some cells have permanently lost their power to proliferate, such as the epidermal cells and the non-nucleated blood-corpuscles ; also, probably, the ganglion-cells. Epithelial cells, gland-cells, connective-tissue cells, periosteal and bone-mar- row cells, possess very active reparative properties. Attention will now be given to the healing of a wound through the skin and subcutaneous tissue. When there is made an incision which freely divides these structures, their natural elasticity sepa- rates the edges of the wound from one another, and the wound is said to "gape/' When only smaller vessels are cut, the bleeding either stops spontaneously after exposure to the air or it may read- ily be controlled by the temporary application of pressure-forceps. When the larger vessels have been tied and the bleeding ceases, the edges of the wound are brought together by suture. If the wound is deep, it may be necessary to pass some of the sutures to an unusual depth, or buried sutures may be applied to bring the subcutaneous fatty tissue or muscular fibres into their proper posi- tion, so that no " dead spaces M are left. In other words, the walls of the wound must be brought in contact throughout, otherwise the oozing of blood and serum that almost invariablv occurs during the first few hours may separate the walls from one another and thus delay the healing process. 222 SURGICAL PATHOLOGY AND THERAPEUTICS. If the wound has been preserved in an aseptic state, there are no symptoms of inflammation seen during the healing process. The parts appear during the next few days almost exactly as they were at the time the wound was first dressed. There is usually a certain amount of swelling and tenderness in the part. The former symptom is due to the exudation of serum, which collects in the interstices of the tissue or between the lips of the wound. In large wounds the amount of serum thus exuded may be considerable. It is estimated that the quantity of serum which flows from the wound of an amputated hip-joint may exceed a pint in the first twenty-four hours. There is also an increased number of cells in the part, and a deposit of fibrin both in the lips of the wound and in the interstices of the tissue. In consequence of this exudation the parts immediately about the wound are somewhat firmer to the touch than they were before. Firm pressure and careful adjustment of the edges of the wound will generally greatly diminish the amount of the exudation. The dressing, however, is usually soaked with a sero-sanguinolent dis- charge during the first twenty-four hours. On this account some surgeons still prefer to place a drain of some kind between the edges of the wound for twenty-four or forty-eight hours, even though they are quite confident of its aseptic character. The primary oozing of serum is thus disposed of, and undue pressure on sensitive or on vital parts, such as the brain, is avoided. A small strand of sterilized gauze or a thoroughly sterilized drainage- tube is sufficient for the purpose. If the drain is not removed before the end of the second day, it is liable to cause suppuration. Even though the dressing be perfectly aseptic, the staphylococcus epidermidis albus (existing in the deeper layers of the epidermis) may thus find its way into the interior of the wound. If the stitches are removed on the fifth day in wounds where there is no tension, the skin will remain adherent, although the union is still far from firm. The edges of the wound are, in fact, only glued together during the first two or three days by the coagulated fibrin. In large wounds coaptation of the parts on the surface is rarely so perfect that complete union of the edges of the skin takes place from one end of the wound to the other. At one point the skin may be at a slightly lower level than at another point, or the skin may be curled in by the stitches. Small fragments of skin may have been bruised or unduly constricted, and minute sloughs may form in this way. Consequently, after the dressing has been PLATE II - ) i ■ ■);■:■■■ ■ ■:'■'' .vs^- Zo '■' * Healing by First Intention of an Abdominal Wound (sixth day) : above is seen a suture mfil trated with leucocytes; below are seen the edges of a divided Iinea alba separated by a blood-clot; upper border, skin ; lower border, peritoneum. Cell infiltration is seen only ahmg the line of incision. THE PROCESS OF REPAIR. 223 removed minute scabs are found here and there along the line of the incision that do not drop off for several days. The points of exit of the suture are also marked by small crusts. During this period the wound is in a very receptive state, and any undue strain or neglect may favor the development of a minute focus of sup- puration under some one of these scabs, which may result in an abscess. The soft new tissue has feeble power of resistance to the invasion of the bacteria. A large wound cannot be said to have passed through its period of danger before the end of three weeks. This mode of union is termed healing by first intention (PI. II.). If the wound has not been kept aseptic, symptoms of inflamma- tion appear on the second day. The edges of the wound are some- what reddened, and much more tender than in the aseptic wound. By the third day a slight amount of pus may emerge from some portion of the superficial structures or from a stitch-hole. A mod- erate amount of sepsis will not interfere with a prompt healing of the wound, and if a moist antiseptic dressing is applied to favor the escape of the small quantities of pus found here and there, the wound may practically heal by first intention. In such wounds, however, it is probable that there will be left a small sinus which may not heal until the end of two or three weeks. If sections of the wound, made at different stages of the heal- ing process, are now examined, the following appearances will be observed: At the upper margin of a wound two or three days old the epidermis is usually found more or less curled in. Wherever in the deeper layers of tissue the fibres have retracted, there are found small clots of blood, which serve the useful purpose of filling out all irregularities. If the section has been stained carefully, all cell-structures stand out with great distinctness, and the line of the incision is indicated, even with a very low power, by a row of cells which have accumulated at the edges of the wound on either side. In cases running an aseptic course the number of cells is com- paratively small, and they are not seen except in the immediate vicinity of the wound (PI. II.). There is an accumulation of cells around some of the blood-vessels, and rows of small round cells may be seen extending between the bundles of fibres toward the margins of the wound. The small clots found in clefts between retracted fibres are invaded with numerous leucocytes. The number of vessels does not appear to be increased, and it is probable that in many instances the formation of numerous vascu- lar loops, so often described, does not take place. 224 SURGICAL PATHOLOGY AND THERAPEUTICS. In healing by first intention there is at first no reddening of the cicatrix, which, however, becomes red and prominent at the end of a few weeks, and it is probable that at this period new vessels have formed. In many parts of the body the scars are almost imperceptible from the beginning, and in these cases there is little if any increased vascularity. According to Thiersch, the plasma- canals communicating directly with adjacent vessels contain blood, by which the tissues are provided with nutriment until new blood- vessels are formed. When there is considerable amount of inflam- mation complicating the healing process, there is a formation of new vessels, which develop in the shape of loops projecting toward the edges of the wound. Experimentally it has been shown that in animals these vascular loops may unite across the lips of the wound in about ten days. A careful inspection of several sections usually discloses the fact that minute fragments of the edge of the wound or of the deeper structures have become necrosed and are in process of absorption. The leucocytes are markedly increased in numbers around such masses, and also around fragments of the ligature, between the fibres of which many cells make their way. It is evident that the leucocytes are endeavoring to break up and absorb all material that is in the nature of a foreign body (PI. II.). If a wound is examined near the end of the first week, it will be found that the round cells are beginning to disappear, and in their place will be seen spindle-cells or fibroblasts. These are the cells which have developed from the pre-existing cells of the part. The surrounding cells or leucocytes take no prominent part in the process of repair, but serve as nutriment for the forming tissue. Between the fusiform cells new intercellular substance is developed in the way already indicated, and thus new fibrous tissue is formed. As the fibres develop many of the fusiform cells undergo granular degeneration and are absorbed. The same fate also awaits such leucocytes as have not already found their way through the lymph- channels back into the circulation. In this way is formed cica- tricial tissue, which differs from normal fibrous tissue in that the fibres do not run parallel with one another, but interlace in various directions, forming a felt-like mass which is very elastic and has great contractile power — a peculiarity which serves a useful pur- pose in drawing the edges of the wound firmly together. The scar when gradually formed becomes prominent and red, and is a source of disfigurement on an exposed surface. The contractile nature of the scar-tissue, however, gradually constricts, one after another, THE PROCESS OF REPAIR. 225 the delicate capillary loops that have developed, so that eventually there is less blood flowing through the part than there was before the injury. This change takes place slowly, and a year or more may elapse before the red scar has faded away and given place to a line that is somewhat paler than the surrounding healthy skin. Healing by second intention occurs when the edges of the wound have not been brought together. In this case a considerable quantity of new tissue is formed, by means of which the cavity is built up from the bottom. If a w r ound is made (by the removal of a breast) so large that the skin cannot be brought together, it will be found, after the bleeding has been arrested, that in the portion which has not been closed the bottom is covered by the red muscu- lar tissue of the pectoralis muscle, and that the sides are composed of the yellow adipose tissue. The anatomical structures are some- what obscured by the formation of a thin coagulum of blood which fills out the irregularities of the surface on the bottom and around the edges of the wound. After the lapse of several hours a trans- parent film forms over the whole surface, covering it like a varnish. The wound is said to have "glazed." This appearance is pro- duced by the exudation of serum from the blood-vessels and by the coagulation of the fibrin it contains. Formerly surgeons were in the habit of waiting for this stage of the healing process before closing the wound, as it was supposed that the opposing surfaces would then quickly adhere and would not be forced apart by the exudation of serum. This film does not remain transparent a long time, for soon minute opaque spots begin to appear here and there, caused by the accumulation of leucocytes. The coagula of blood on the surface also soften, and the color runs through the transparent layer and stains it a dirty red. The normal tissues now begin to disappear, and the layer formed over them soon becomes further discolored by the liquefaction of minute sloughs of tissue which have been bruised by the knife. The surface of the wound no longer has its clean appearance, but it is covered with a dirty membrane having a mixture of ill-defined colors. This membrane remains for three days, at the end of which time it appears to have separated from the subjacent parts by the formation of a fluid beneath. The mem- brane finally floats off with a free flow of pus, and there is disclosed a layer of bright-red tissue studded with very minute elevations, known as granulations. The wound is said to have cleaned off. It will be noticed at this stage that the wound is much shallower than it was before. The tissue of which these granulations are 15 226 SURGICAL PATHOLOGY AXD THERAPEUTICS. composed is known as granulation tissue, and it is by the growth of this tissue that the cavity is filled. In a few days this layer reaches the level of the surrounding skin, and it is now seen that the area oi the wound is smaller than it was at the beoqnnincr The next stage in the healing process is the covering of the granu- lations with epidermis. If the margins of the granulating tissue be examined with a lens, the presence will be noted of a trans- parent film, through which the granulations may still be seen, although they have flattened out. As this transparent film works its way toward the centre of the wound the older layers change to a pearly-white color and become opaque. This process (Fig. 44 j v . Fig. 44. — Healing by Second Intention. consists in the proliferation of epithelial cells, by which means the new granulation tissue is eventually covered over. These cells can- not form independently in the centre of the wound, although the new epithelial cells possess amoeboid movements and may wander a short distance from the margin of the wound. The growth is not unlike the formation of ice on a pond, the water around the edo-es of which first becomes covered by a thin film of ice, which by a process of continuous formation finally covers the deeper waters at the centre. In large wounds the surrounding epidermis is unable to supply a sufficient number of cells to cover the open surface; consequently, the wound would not heal were it not for the power of the cica- tricial tissue forming beneath the granulations to contract and draw the edees of the wound toward one another. This contrac- tile power is caused by the shrinkage due to the absorption of the THE PROCESS OF REPAIR, 227 soft cellular and vascular granulation tissue and its replacement by dense fibrous structures. If the granulation tissue is studied under the microscope, there will be found a tissue crowded with small round cells and contain- ing a large number of small blood-vessels, which tend to run in a vertical direction toward the surface of the wound. An examina- tion of this tissue with a high power of the microscope shows that there are not only a large number of leucocytes, distinguished by their numerous nuclei which come out very characteristically when stained, but that there are also many single-nucleated leu- cocytes and larger epithelioid cells. Near the surface of the gran- ulation tissue the leucocytes abound (Fig. 45). L,ower down are 'o n o ffi Fig. 45. — Vascular Spaces with Tissue filled with Leucocytes near the Surface of Granulations. found the larger cells, particularly in the vicinity of the blood- vessels, from whose walls an active cell-growth appears to take place. Still lower, the cells assume a spindle shape, and the deep- est layers of all consist of bundles of spindle-cells running in a horizontal direction beneath the surface. In wounds that have remained open for a long time or in ulcers this deepest layer has become quite fibrous, and it seems to serve the purpose of walling off the surrounding healthy tissues from the imperfectly-formed 228 SURGICAL PATHOLOGY AND THERAPEUTICS. tissue above, which in many cases contains the elements of disease (Fig. 46). Many observers describe a rich growth of blood-vessels, arranged in festoons and loops, running vertically toward the surface, and Fig. 46. — Detail Study from a Deep Layer of Granulation Tissue, showing a vessel with epithelioid cells and spindle-cell growth. ascribe to the presence of these loops the little hillocks of cells so characteristic of granulations ; but a study of microscopical sec- tion does not show this arrangement. The blood-vessels are com- paratively few in number at this time, though they are much larger than those found in the surrounding parts. They have a tendency to ascend, either vertically or at a slight angle, toward the surface, where their further progress is lost. They are parallel with one another, and probably anastomose by a more or less hori- zontal system of capillaries in the upper layers of cells. (Fig. 44.) The histological changes which occur during the formation of granulation tissue have already been indicated so far as the action of the cells is concerned. There is seen at first, as the result of this action, an abundant small round-cell infiltration of the part occupying nearly all the space, so that the intercellular substance THE PROCESS OF REPAIR. 229 is difficult to find. The fibres have, in fact, undergone a soften- ing, and the intercellular substance appears as granular "material. The majority of these cells are leucocytes which have emigrated from the blood-vessels ; but many of them, principally those with single nuclei, are derived from the pre-existing cells of the part. As this tissue develops and as the cavity begins to fill, there is found, in studying with high powers, a great variety of shapes, some being club-shaped, others having a large body and a bright oval nucleus, the so-called "epithelioid cells." The epithelioid cells may be seen best near the vessels which ramify in the new tissue, and they are the principal cells relied upon for the formation of the new scar-tissue. In the deeper layers, consequently among the cells most advanced in development, are found many spindle- shaped cells running parallel with one another and in a more or less horizontal direction. This is the next stage of the process. It is between these cells that the new fibrillar are seen forming. On the surface are found numbers of broken-down cells and poly- nucleated cells enclosed in a coagulated material. This is the liquefied tissue cast off from the upper layer and seen on the liv- ing granulations as pus. The new blood-vessels form by a budding growth from the walls of pre-existing vessels. The endothelial cells of a capillary undergo division by karyokinesis, and presently there is seen a tent-like ele- vation (from the wall of the vessel) that continues to grow into a fine prolongation, consisting of granular protoplasm, which, after a certain length of time, contains nuclei (Fig. 47). This bud may unite with a similar one, or may return to the vessel again, forming a vascular loop, or may communicate with another ves- sel (Fig. 48). The vessel may also terminate in a club-shaped end. The central portion of the new protoplasm now begins to soften, and a cavity forms which subsequently communicates with the lumen of the vessel. The new tube at first has a homogene- ous wall, but later the protoplasm groups itself around nuclei that are forming, and endothelium is thus developed. Some of the tis- sue-cells of the neighborhood come in contact with, and strengthen, the vessel-wall. When the vessels are in a state of development like this their walls are highly cellular. In all granulation tissue an active cell-growth is found near the vessel, and the endothelium of the capillaries has a special reputation for its power of procrea- tion. This is the method of intracellular growth of capillaries > and is the generally-accepted theory of vascular development. The intercellular method of growth is seen in the formation of 230 SURGICAL PATHOLOGY AND THERAPEUTICS. a bundle of spindle-shaped cells in new tissue in which vessels are also forming. Some of these cells group themselves together, and form a channel which presently communicates directly with the vascular system. If these channels are traced carefully, the ex- Fig. 47. — Development of Blood-vessel in Mesentery of an Embryo. treme limits may be found to which the corpuscles have pene- trated. Inasmuch as it is known that the plasma-canals are filled with blood in fresh wounds, it is highly probable that the subse- quent cell-growth can form canals which open into the blood-ves- sels. In the writer's studies in the repair of arteries new tissue has been seen growing into a portion of a blood-vessel which has been cut off from a trunk by a double ligature, containing young vessels developing in this way. In sections of granulation tissue can be seen small blood-vessels with bands of cells branching off from their walls. In the axis of these bands the cells are separated and vessel-walls are formed from them. When the granulation tissue has been covered with epidermis, the cell-infiltration has already in part disappeared, and the poly- nuclear leucocytes have broken up and have been absorbed. The fibroblasts have formed intercellular substance. Perhaps some of the fibroblasts have been transformed into fibres to awaken once more at some future time. At all events, the scar-tissue now be- comes very rich in fibres, and few cells are seen there. The blood- THE PROCESS OF REPAIR. 231 vessels, which at first are quite numerous, and which give the cha- racteristic redness to the new cicatrix, eventually diminish very { 1 Fig. 48. -Development of Blood-vessel in Mesentery of an Embryo : formation of vascular loops. greatly in number in the way already indicated, and the scar becomes paler than the normal skin; but this change does not occur until months after the wound has healed. The healing of a wound whose edges have not been brought together may take place without the formation of pus, provided the cavity thus formed is filled with healthy blood-clot and the wound itself is in an aseptic condition. The so-called organization of the blood-clot occurs by an in- growth of cells into the gelatinous material thus furnished, which material takes no active part in the process, but serves as an admir- able "culture-medium" for cell-development. In such cases at the end of two or three days the clot is seen filled with a round- cell infiltration, the cells of which grow more numerous as the clot breaks up and disappears. The granulation tissue thus formed, in a few days more is supplied with blood-vessels. If no suppura- tion takes place, a portion of the old clot remains as a scab upon the surface until cicatrization is complete. The organization of the clot is not, however, always effected in this way. In some cases the clot may recede before the advancing cell-growth, which 232 SURGICAL PATHOLOGY AND THERAPEUTICS. occurs in the shape of granulations projecting in an irregular manner into it in the same way as upon a granulating surface. The clot shrinks greatly as the new tissue grows forward to take its place (Fig. 49). This method of healing by blood-clot occurs in subcutaneous wounds, in simple fractures, in ruptures of inter- nal organs, and, in fact, to a certain extent, in almost every wound that heals without suppuration. The granulating surfaces of open aseptic wounds (a few days old) may be brought together, and will unite by third intention. vT& Fig. 49. — Granulations compressing Blood-clot; injected specimen (tenth day). In older open wounds with moist and luxuriant granulating sur- faces the granulations should be scraped off before bringing the edges together. In this way the healing process is sometimes greatly shortened. The healing of tendon varies somewhat according to the presence or the absence of blood-clot. After the tendo Achillis has been divided experimentally in the rabbit, the sheath is found filled with a firm cylindrical clot. A few days later it will be evident that a growth of new tissue has taken place in the tendon-sheath, and that a callus has been formed enclosing the retracted ends of the tendon (Fig. 50). If the specimen is now removed, placed in alco- THE PROCESS OF REPAIR. 233 hoi to harden, and subsequently is divided longitudinally, it will be found that the divided ends of the tendon have retracted consider- ably, leaving between them a mass of blood-clot and new tissue which forms a spindle-shaped covering enclosing both ends for some distance beyond the point of division. The clot is already par- tially absorbed, and the new tissue is grow- ing into it in various directions. If the limb has previously been injected with Ber- lin blue, the rich new formation of vessels may be seen producing a highly vascular network around the borders of the clot. In such a case as this the ordinary method of the organization of the blood-clot has not taken place, owing probably to the size of the clot, but the tissue has formed granula- tions which are pushing into the clot. It is probable that large clots are usually ab- sorbed in this way by lateral pressure, rather than by infiltration with wandering cells. If the new-formed tissue be exam- ined at this time with a high power, it will be found to consist of spindle-shaped cells running mainly in a direction parallel with the long axis of the tendon. The new tis- sue appears to spring from the inner wall of the sheath, while the cut edges of the tendon, standing out in bold relief, seem to take no part in the process. The new blood-vessels form about from the tenth to the fourteenth day a rich vascular network in the provisional tissue, and some of them can be seen already communicating with vessels lying between the fibres of the old tendon (Fig. 51). In the granula- tions which surround the margins of the blood-clot there is found a rich anastomosing network of vessels, many of them form- ing loop-like prolongations; others seem to terminate in club- shaped extremities (Fig. 49). The blood-corpuscles of the clot have by this time disappeared, having become pressed together, and the clot now appears as a brownish mass of tangled fibres of fibrin. As the process of repair proceeds the fusiform cells dimin- ish in number and the intercellular substance begins to make its appearance: this process continues until a tissue is formed which, with the microscope, is difficult to distinguish from normal ten- Fig. 50. — Healing of Ten- don : callus formation with absorption of blood-clot. Granulations are seen com- pressing the clot from the sides, and, at the lower por- tion, from behind (tenth day). 234 SURGICAL PATHOLOGY AND THERAPEUTICS. don-fibre. As this new tissue develops a large portion of the pro- visional tissue is absorbed, together with the remains of the blood- clot, and the callus disappears. When the blood-clot is absent the walls of the sheath come in contact, and unite as a band which joins the ends of the tendons. Fig. 51. — Detail Study of the End of the Divided Tendon seen in Fig. 50. New tissue in many cases grows between these walls, and a tendon- cicatri* will thus be formed. According to Viering, the tendon-cells also take part in the repair, but no change is observed in them before the fourth day. All that is seen of the tendon-cells in the quiescent state is an elongated staff-shaped or double-oval nucleus bent into a gutter shape. There is but little protoplasm to be seen beyond a delicate granular mass around the nucleus and along the margin of the plasma-canals, on the sides of which lie these cells. The nuclei soon enlarge and the protoplasm becomes clearer. Nuclear divis- ion next takes place, and the cells soon become mingled with the fusiform cells produced by the granulation tissue. Viering also found cells which he regards as developed from the so-called ' ' slumbering cells" in the tendon-fibres. It is probable that the tendon-cells take only a comparatively limited part in the process THE PROCESS OF REPAIR. 235 of repair, though the new tissue formed resembles tendon-tissue more closely when the ends of the tendon have been sufficiently approximated. In some tendons the divided ends are not reunited, owing to their great displacement. This is more likely to occur near the flexure of joints and where the sheath is lined with endothelium. Tendons widely separated may be exposed by an incision and the ends may be approximated by sutures. In this case union takes place with more or less complete restoration of function. An attempt should always be made to suture the divided ends of a tendon if there is any probability that spontaneous union will not occur. When a tendon is divided intentionally by the surgeon for the purpose of lengthening it, the ends may be allowed to remain a considerable distance apart in certain localities, as, for instance, the ankle. If it is desired to elongate the tendon of the wrist or of the hand, a plastic operation should be performed. The tendon in this case may be divided by an extremely oblique incision, so that the ends will still overlap slightly when considerable retraction of the prox- imal portion has occurred. A flap may be made by partially dividing one of the ends some distance above the seat of the wound, and by incising the tendon along its central axis from this point close down to the point of injury. The flap thus formed can be reflected and be united to the other end. Repair of muscular fibre is a subject about which observers have differed greatly. It was formerly supposed that striped muscular fibres were not able to reproduce new fibres, and that the cicatrix of muscle was connective tissue. More care- ful histological study has disproved this view. Differences of opinion have, however, prevailed as to the origin of the mus- cular fibres. Some authorities believe that the new growth pro- ceeds from the muscular cells or sarcoblasts; others assume that it originates from the contractile substance which is metamorphosed protoplasm. Nauwerck has recently made a series of careful investigations to determine these various points, by experiments on rabbits. He found several preliminary changes which are not permanent. In small wounds of muscle at the end of twelve hours evidence of cell-divis- ion is seen in the connective tissue of the perimysium internum and in the endothelia of the small vessels. The height of the development of granulation tissue thus formed is reached about the sixth day. In the centre of this tissue necrosed fragments of muscular fibre and giant-cells are seen. This new tissue occupies the injured part, and extends along the perimysium for some little distance between the 236 SURGICAL PATHOLOGY AND THERAPEUTICS. neighboring healthy muscular fibres. It does not remain long, however, and at the end of two weeks there is seen in its place con- nective tissue with few nuclei separating some of the muscular fibres. In the mean time, the ends of the injured muscular fibres break up into spindle-shaped fragments, and some of them undergo fatty degeneration, vacuolation, or a vesicular degeneration. Some fibres remain at first in contact with their necrosed ends; other fibres atrophy and terminate in tapering points. The separation of the necrosed fragment is favored by leucocytes and connective- tissue cells, and during the next few weeks they are gradually absorbed. One of the earliest changes seen in the living muscular fibre is the proliferation of the muscular cells, or so-called " sarcoblasts, ' ' which appear in the form of bundles of muscular cells at the ends of the muscular fibres, either near the necrotic zone or some dis- tance away. According to Nauwerck, they do not undergo stria- tion, as some observers have supposed, but at the end of the first week undergo fatty degeneration, and at the beginning of the third week have disappeared. There is seen also, at an early period, a peculiar longitudinal splitting up of muscular fibres, accompanied by an active formation of nuclei, the disappearing fibre being replaced by a bundle of slender fibres having longi- tudinal striation and spindle-shaped cells. About the sixth day some of the living fibres begin to elongate and to grow in among the necrosed masses of fibres. The first terminal prolongations form narrow fibres composed of a proto- plasm rich in nuclei. These outgrowths occasionally surround, fork-like, a necrotic fibre. By the eighteenth day the granula- tion tissue is already invaded for some distance by the new fibres. These prolongations grow from the stumps of old fibres, forming the tapering fibres found near the wound, and from fibres which have been split up longitudinally. The prolongations are not always single: in some places two such growths are seen coming from one fibre, and these in turn may bifurcate. Later, these new fibres present at their ends club- or spindle-shaped swellings which are richly supplied with nuclei. Karyokinesis is seen in these nuclei, but more frequently multiplication is effected by the process of "indirect fragmentation." These muscular buds show a longitudinal striation, but by the end of the second week transverse striae are plainly seen. The nucleated terminal por- tions present an appearance closely resembling giant-cells. These swollen ends disappear during the fifth or sixth week. THE PROCESS OF REPAIR. *37 As the muscular fibres grow they lose their parallel arrange- ment and becomes entangled with one another. Budding may take place, not only from the ends of the fibres, but also laterally. The former method is, however, the usual one. The new-formed fibres gradually invade the connective-tissue cicatrix. They be- come thicker and cylindrical, and acquire transverse striation. Many of them do not remain permanently, but break down at an early stage of the process and undergo fatty degeneration. As the fibres grow from opposite sides of the wound they inter- lace with one another (Fig. 52) like the fingers of clasped hands £ ■ ' ' "- - *i v Fig. 52. — Repair of Muscular Fibre (Xauwerck). (Neumann). In this way the connective-tissue scar disappears. In small wounds the cicatrix is therefore entirely muscular. In large wounds the fibres may be unable to form sufficient new muscle, and the connective-tissue cicatrix persists. The great irresrularitv in the direction of the new fibres is so modified as time goes on that the horizontal arrangement reappears, but there is usually more or less interlacing of the new muscular fibres. Repair of Nerves. — It has now been abundantly proved that a spinal nerve when divided can reunite with return of its 238 SURGICAL PATHOLOGY AND THERAPEUTICS. functional activity. It has also been proved that the periph- eral end of one nerve can be united to the central end of another nerve with restoration of function. As yet there are no data which show that a purely motor trunk can unite with a purely sensory trunk, with a return of function to the peripheral portion. Up to the time of Nasse and Waller it was generally believed that nerves were united by the formation of new fibres between the divided ends, and that the peripheral end suffered no degen- eration, union taking place by first intention. This view appears to have been borne out by clinical experience in certain cases in which, after nerve-suture, there was an immediate return of motion or of sensation, or of both. Experimental researches on animals, however, have not confirmed this view. The rapid reproduction of sensibility is explained in some cases by anasto- mosis of the peripheral branches of the divided nerve with other sensitive nerves that have not been cut; other cases may be exam- ples of the so-called "supplementary " or "vicarious sensibility" and motion. The experiments of Howell and Huber, as well as those of other observers, show that in animals the peripheral end of a divided nerve degenerates completely throughout its whole length. There is also a degeneration of the terminal fibres of the central end to a limited extent. These degenerated nerve- fibres are subsequently replaced, and the repair which unites the two ends of the nerve takes place from both fragments, but chiefly from a downward growth of embryonic fibres from the central portion. The new nerve-tissue is produced from pre-existing nerve-tissue, and not from the connective-tissue structures which form a com- ponent part of the nerve-trunk. New nerve-fibres are conse- quently not formed in the granulation tissue surrounding the ends of the divided nerve, but the actively-growing embryonic fibres from the central and peripheral ends penetrate this tissue, and finally meet one another and unite. According to Ranvier, Kolliker, and others, the repair takes place from the central ends. The axis-cylinders swell and divide into several branches that eventually break through the neurilemma and ramify in the con- nective-tissue structures which support the nerve-fibres (endoneu- rium and perineurium), and cross through the granulation tissue into the peripheral end, some of the cylinders eventually finding their way into the nerve-sheaths again. In accord with this view is the theory that the axis-cylinder is a prolongation of a nerve- THE PROCESS OF REPAIR. 239 cell, and, when cut off, repair can take place only from the cell from which it originated. Howell and Hnber found that the return of function in the sutured nerve in a dog begins to appear on the twenty-first day, and is nearly perfect at the end of eleven weeks. This return of function cannot take place, however, without the previous degen- eration of the entire peripheral end, and it is attended by a total loss of conductivity and irritability. At the end of about four days after division the continuous myeline sheath breaks up into a number of segments, and this division is accompanied by, or causes, a breaking of the axis. By the seventh day a very active proliferation of the nuclei of the nerve-sheath or neurilemma has begun. It is probable that this takes place by indirect division. After division the nuclei migrate, and several nuclei are often found in one internodal space. From the seventh to the four- teenth day absorption of the myeline takes place, together with the contained fragments of the axis-cylinder, until finally the remnants of these two substances entirely disappear. Protoplasm now begins to accumulate around the new nuclei, and increases until a continuous band or fibre of protoplasm, in which nuclei are imbedded, is formed within the old sheath. These bands constitute the ''embryonic fibres" of Neumann. After the formation of this new fibre a new sheath is made by Fig. 53. — Changes seen in the Repair of a Nerve after Division: I, absorption of myelin and multiplication of nuclei of nerve-sheath near points of absorption ; 2, embryonic fibre six and a half months after section ; 3, formation of myelin tube ; 4, newly-formed myelin tube (Howell and Huber). differentiation of the peripheral layers of this protoplasmic band, and it is supposed that the old sheath becomes part of the endo- neural connective tissue (Fig. 53). 240 SURGICAL PATHOLOGY AND THERAPEUTICS. It is probable that these embryonic fibres have some of the properties of mature nerve-fibres, and that they can conduct impulses after having united with the normal fibres of the cen- tral end. Possibly this may be an explanation of the rapid return of sensation in some of the reported surgical cases. In case the ends of the divided nerves are not reunited, the degenerative changes proceed in much the same way as when the suture has been made; but the regeneration, beginning with the formation of the embryonic fibres, proceeds more slowly than in the case of suture, and never gets beyond the embryonic stage. If the reunion with the central end has been made, the regenerative changes go on to the formation of complete nerve-fibres having myelin sheaths and axis-cylinders. It is supposed that the new myelin is formed either by a myelin degeneration of the super- fluous nuclei or from the substance of the protoplasm by a process of chemical differentiation. When the myelin sheath is first formed it encloses a core which does not take the staining by osmic acid. Neumann and others assume that the new axis-cylinder arises from this core, but Ran- vier believes that one or more axes grow out from the axis of each intact fibre of the central end. In the central end the myelin and axis-cylinders disintegrate, and are absorbed for a certain distance: an embryonic fibre is formed from the new protoplasm arising from the nuclei, and in this a myelin sheath is first formed into which an axis-cylinder penetrates as an outgrowth from the end of the old axis. It is supposed, by Howell and Huber that in the normal fibre the nutrition of each internode is directly controlled by the inter- nodal nucleus — that is, the nucleus which presides over the portion of the nerve included between the nodes of Ranvier — and that the metabolic activity of the nucleus in turn is influenced by trophic impulses received through the axis-cylinder from the nerve-cen- tres. When the flow of impulses is interrupted the metabolisms of the nucleus and its dependent structures, myelin and inter- nodal protoplasm, are altered, and the degenerative changes in the myelin and axis-cylinder take place. When the embryonic fibre re-establishes a communication with the central end, the proto- plasm and nuclei are again brought under the influences of the trophic impulses from the nerve-centres, and consequently there is a new formation of myelin. According to Ranvier, every nerve-fibre consists of links united together at the "points of contraction of Ranvier." Each link THE PROCESS OF REPAIR. 241 possesses a nucleus and represents a cell. It is evident that the protoplasm and nuclei of these cells play a prominent part in the process of repair, acting as a sort of neuroblast. It is not surpris- ing that repair in the peripheral portion of the nerve should be effected after so extensive a degeneration, when it is remembered that changes of this kind are going on during the entire physiolog- ical life of the nerve almost as regularly, according to some authors, as the growth of epithelium (Recklinghausen). It is evident, from what has preceded, that the connective-tissue elements play no part in the repair of nerve-tissue. The perineur- ium and the endoneurium throw out new connective tissue about the ends of the fragments and form a sort of callus which holds the nerve together. It is the growth from this tissue, principally, that forms the so-called "neuromata" or bulbous terminations of the ends of nerves in a stump. These tumors are really fibromata, and it is due to the contraction of the cicatricial tissue they contain that nerves thus affected are so painful. In regard to the clinical symptoms following nerve-section it may here be said that, although paralysis following division of a motor or of a mixed nerve is immediate and complete, there are conditions, such as have already been referred to, which mask this symptom to a certain extent. Free anastomosis with an adjacent nerve will give to a certain cutaneous district a sensibility it would not otherwise possess. Another portion of the skin may receive nerve-supply from several nerves. There is, normally, free anastomosis between the median and the ulnar nerves on the palmar aspect of the hand. It should also be remembered that there are numerous anastomoses between the musculo-cutaneous and the median nerves. The back of the hand is supplied not only by the radial and ulnar nerves, but also by other nerves. The musculo-cutaneous nerve may supply sensation to the skin of the thumb and to the radial portion of the dorsum, the posterior cutaneous nerve may supply the middle portion of the same region, and the external interosseous nerve may supply the oppos- ing sides of the index and middle fingers. There are, therefore, two factors to deal with in estimating the difference in duration and extension of disturbances of sensibility: first, the irregularities of nerve-distribution in individual cases, and, second, the collateral nerve-supply by anastomosis. The prognosis of nerve-suture varies greatly according to circum- stances. If a nerve is immediately sutured after division and the wound heals aseptically, the conditions are most favorable for restoration of function. If there is a loss of a portion of the nerve, the prognosis is less favorable for union, and the time for 1G 242 SCRGICAL PATHOLOGY AXD THERAPEUTICS. repair is in such case much longer. The nearer the injury is to the origin of the nerve, the longer is the period required for repair to be completed. The restoration of function is, however, the more rapid the nearer the point of division is to the peripheral end of the nerve. Excess of inflammation tends to produce cicatricial tissue which may be dense and may interfere with the reunion of the ends of the nerve, and not infrequently it forms a bulbous termi- nation, chiefly to the proximal end. Old injuries are not so easily repaired as fresh injuries, as the distal portion of the nerve has undergone degenerative changes which still remain. The prognosis is not hopeless in cases in which the nerve has been divided months or even years before. The question of repair of the nerve-tissue of the brain is one about which great doubt exists. Krebs examined two cases of brain injury — one recent, the other of long standing. Whether new cells were developed from the gray matter or neuroglia does not appear to have been definitely determined. From experiments on animals he concluded that the nerve-cells proliferated. Obersteiner says: "A divided nerve-fibre in the central nervous system is ren- dered permanently useless ;' ' according to Schieffendecker, a regen- eration of nerve-fibre takes place in the cords of very young animals after division, but repair is never seen in adult animals nor in man. Nerze-suture. — There are two methods of applying nerve-suture, which are known as the direct and the indirect suture. The direct suture is applied through the nerve-tissue, but the indirect suture is \ s 5 ed through the perineurium only. The direct suture possesses the disadvantage of injuring the nerve-fibres that are to be relied upon for repair. It has, however, a firmer hold upon the nerve, and is therefore more reliable when there is any tension upon the suture. When the ends of the nerve can be brought together without ten- sion the indirect suture is preferable, as it admits of a more accu- rate adaptation of the ends to one another. Kolliker prefers the finest catgut, for, although silk and metal sutures do not prevent healing by first intention, it is not absolutely certain that so sensitive a tissue may not be irritated by a more per- manent suture. When there is too much tension an auxiliary suture may be applied to the proximal end passing transver-r to the long axis, including adjacent tissue and skin if neces- This auxiliary suture holds the retracted proximal end in position, so that coaptation sutures may be inserted. In primary suture the ends of the nerve should be refreshed if they have been bruised or torn. In secondary suture a fragment THE PROCESS OF REPAIR. 243 should always be removed from each end before they are brought together, and the bulb on the proximal end, if present, should be excised, thus removing the cicatricial tissue that has formed. In primary sutures the ends of the nerve are usually easy to find, but in secondary suture it is sometimes impossible to find one of them. When there is a considerable interval between the ends of the nerve the difficulty in bringing them together may be overcome in various ways. The simplest method, and the one which is effectual if the distance does not exceed 4 cm., is nerve-stretching. The limb should first be placed in a position favoring the approximation of the ends, and the stretching may be done with, the fingers or by dressing-forceps protected by rubber tubing. Letievant and Beach have both suggested plastic operations, the former having practised the operation upon the ulnar nerve. One or both ends are split longitudinally for some distance above the stump, and the portion thus released is reflected and united to the opposite end. Nerve-grafting has been tested experimentally by several ob- servers, and has been successfully performed by Landerer and Vogt on the human subject. It has been found that the implanted frag- ment takes no active part in the process of repair, and that the nerve-fibres undergo degeneration. It serves merely as a medium through which the nerve-fibres grow. Vanlair proposes a method called "suture tubulaire," which consists in slipping the two frag- ments into a piece of decalcified bone. He found, however, that the fragments occasionally grew past one another without uniting. He therefore lacerated the distal end to allow the new nerve-fibres to penetrate it. Assaky substitutes for the decalcified tubes catgut loops. The catgut sutures applied in this way are supposed to serve as guides to the growing nerve-fibres. In very large defects or in case the proximal end cannot be found Letievant proposed that the distal end should be implanted upon the trunk of an adjoining nerve, the trunk being opened at the point at which the nerve is sutured. When two neighboring nerves are divided, it may happen that it is only possible to bring together the distal end of one nerve with the proximal end of the other. This operation is advised in order to maintain the integrity of at least one nerve-area. Lobker in one case shortened the bone in order to bring the ends of the nerve together and at the same time to suture the tendons. The following case is interesting in this connection : A boy entered the writer's ward at the hospital for an unreduced dislocation of the elbow-joint. Attempts at reduction failing, the joint was laid open and all bands were 244 SURGICAL PATHOLOGY AND THERAPEUTICS. divided. The joint surfaces were brought in apposition, but it was then found that the ulnar nerve had been cut during the operation, and the ends were so far removed when the bones were in place that they could not be approximated. The joint was accordingly excised, and the nerve was then easily sutured. The wound healed by first intention, and at the end of two months the function of the nerve was restored and there was good motion at the elbow-joint. Kolliker prefers, above all, the method of nerve-stretching. He places Assaky's catgut loops next in order of preference and before plastic operation, as this method follows more closely the physiological processes during repair. Healing of Bone. — The cicatrix of bone is usually bone; that is, the bony tissue has the power of reproducing itself after injury, and it is only in exceptional cases that this does not occur. ■When a long bone is broken there is a great deal of injury to the surrounding parts. The Haversian canals are ruptured, and there is a considerable oozing of blood between the bony fragments and in the surrounding tissues. This oozing is usu- ally sufficient in amount to form a tumor of considerable size at the seat of injury immediately after the accident, and serves in many cases as a guide to the diagnosis of fracture (Fig. 54). The soft parts are also lacerated to a considerable extent. It is rare that the rupture of the periosteum does not occur. The sharp end of one or of both fragments may be thrust through the periosteum, or it may be pulled up from the ends of the bone by the dis- placement which takes place at the mo- ment of injury. As the result of such an injury to the part traumatic inflammation occurs at the seat of the fracture, and in a few days the tissues in the immediate neigh- borhood, if examined, are found infil- trated with blood-clot and are matted together by the exudation which takes place. The anatomical relations of the soft parts surrounding the bone are, for the time being, lost, and the upper and lower fragments are imbedded in an indurated mass of tissue, which, extending some distance above and below the seat of the fracture, Fig. 54. — Experimental Fracture (dog) at the end of the first week, showing bloodclot and detached fragment of bone. THE PROCESS OF REPAIR. 245 is known as the callus. This callus does not have any well-defined outline, and involves not only the bone and periosteum, but also the connective tissue and some of the surrounding muscular tissue. In a few days after the injury this inflamed mass begins to take on much firmer consistency than is seen in traumatic inflammations else- where. If examined during the second or third week of the pro- cess of repair, the tumor is found to consist no longer of blood-clot which has been absorbed, but of a dense tissue which has formed abundantly in and beneath the periosteum, and which in places appears to have developed into cartilage (Fig. 55). A w T eek or two later this material is transformed into a porous tissue surrounding the two fragments and holding them firmly together. In the mean time changes have been going on in the medullary canal. As the blood-clot is absorbed it is found that the fatty tissue of the canal has disappeared near the seat of the fracture, and that it is replaced by granulation tis- sue. Presently it is obvious that this tissue in turn has given place to newly-formed spongy bone, known as the internal callus. An intermediate callus is also recognized by some authorities as existing at this time between the ends of the bone, but it is clearly a development of bone-tissue from one of the other sources first mentioned. During this period but little change takes place in the sharply- defined ends of the shaft. Gradually, however, the dense cortical bone becomes more porous, so that at the end of one or two months a mass of spongy bone occupies the seat of the fracture. The newly-formed bone preserves the contour of the callus, forming a spindle-shaped swelling extending for some distance above and below the injury. From this time on, the new bone, formed from the medulla and the periosteum, is gradually absorbed, while the bone of one fragment, now continuous with the other, resumes its former density and becomes cortical bone once more. With the Fig. 55. — Experimental Fracture (dog) after forty-six days : ossification of callus. 246 SURGICAL PATHOLOGY AXD THERAPEUTICS. absorption of the provisional bone the medullary canal and the periosteum resume their former relations. When the fragments so overlap one another that the continuity of the medullary canal is broken a portion of the cortical bone of each fragment is event- ually absorbed, and in this way the medullary canal is re-estab- lished. The object of this temporary bone-formation, known as the provisional callus, is to hold the broken fragments firmly together while the slow process of cicatrization in bony tissue takes place. The histological changes which occur during the process of repair after a fracture may now be considered. Already as early as the second day there is found in the immediate neighborhood of the fracture an infiltration of the parts with leucocytes. This infil- tration involves the lacerated periosteum and the connective tissue and muscular fibres. The extravasation of blood and the inflam- matory exudation combine to obscure the normal anatomical struc- tures. At some distance from the immediate neighborhood of the fracture there is found at this time an unusual activity in the deeper layers of the periosteum and in the adjacent bone. An active cell-proliferation takes place, in consequence of which fusi- form cells and angular or stellate cells abound. This tissue is in intimate communication with the interior of the bone, and is, in fact, continuous with the medulla through the connective-tissue system of the Haversian canals. It has been called by Ranvier the "periosteal medulla/ ' In a few days there is found in this tissue a thick layer of new cells imbedded in a finely striated intercellular substance, the cells being surrounded by a halo somewhat like that seen in cartilage, and the tissue being unusually dense and firm in appearance. This is the so-called " osteoid substance." Nearer the ends of the bone, and near the centre of the inflammatory mass known as the callus, the intercellular substance has a more transparent hya- line appearance, and during the early period of repair this portion of the callus consists lar^elv of cartilaee. If the osteoid substance just referred to is examined at the moment when the transformation into bone is taking place — that is, during the second or third week — it will be found that portions of this tissue take the staining fluid more readily than other portions, so that it has a more or less mottled appearance. This appearance is due to the deposit of lime-salts, and presently it is found that trabecular of bone have formed, and that the cells which were there before have now become bone-cells (Fig. 56). These cells are therefore known as osteoblasts. The spaces found THE PROCESS OF REPAIR. 24: between the bony plates are now seen to be in communication with the Haversian canals and to contain blood-vessels. These vessels, emerging from the canals in the cortical bone, run at Fig. 56. — Ossification of Osteoid Substance in Callus, three weeks (dog) : osteoid substance above, shaft of bone below. The dark trabecule are formed of newly- ossified bone; between them are the Haversian canals in process of development. right angles to those supplying the shaft of the bone, and the grain of the new bone is consequently at right angles with that of the old (Fig. 57). This new spongy bone is now seen forming some distance from the seat of fracture, and gradually growing thicker as the ends of the fragments are approached. As this grows out from each end of the bone, it invades the cartilaginous callus, and the two but- tresses of bone developing from the ends of each fragment approach each other, and finally come together and form a bony bridge which unites the broken ends. This newly-ossified callus consists of spongy bone with a coarse meshwork, containing what 248 SURGICAL PATHOLOGY AND THERAPEUTICS. might be regarded as an anastomosing network of medullary tis- sue. If these spaces are examined with a high power of the m; •■• ;. i- • • 1: -.- v , <£ "■ ' ' ■ ; %!'# & % ^ Fig. 57. — Experimental Callus (dog), three weeks. microscope, it will be found that they contain a vascular granu- • lation tissue surrounded at the margin of the 9 g cavity by a row of cells (Fig. 58). It is evident fe that these cells are ac- tively concerned in the formation of new bone, layer by layer, as the deposition of lime-salts can be seen at certain points taking place be- tween the cells. In this way the spongy bone be- comes denser and more like cortical bone. The hyaline cartilage in the specimens examined by Fig. 58.— Detail Study of Three Weeks' Callus, show- tne writer seems to be ing osteoblasts forming new bone. absorbed as the bony A %**% &v "*m 'U: ,><» THE PROCESS OE REPAIR. 249 growth shoots out from each end of the callus. The hyaline car- tilage may, however, at certain points form bone by the calcification of the intercellular substance and a change of the cartilage-cells into bone-cells (Bruns). Meanwhile, in the medullary canal, near the ends of the bone, the granulation tissue becomes changed into red or embryonic marrow; osteoid substance is formed around the mar- row adjacent to the cortical layer of bone, and new spongy bone is thus thrown out from the sides of the medullary canal until it is filled with a porous bony tissue. Hyaline cartilage is occasion- ally seen here, but this is the exception. During all these changes the ends of the cortical bone appear to remain unaltered. The Haversian canals are filled, however, with a round-cell infiltration, and the vascular spaces are grad- ually enlarged by an absorption of the lime-salts, probably by the production of some chemical substance developed by the granula- tion-cells. The ends of the dense bone become porous, and con- sequently there takes place a transformation of the bone in the immediate vicinity of the fracture and the surrounding callus into a mass of spongy bone. In this way the ends of the frac- tured bone become firmly united to each other. This process occupies many weeks, and in some bones it may be months before the dense bony tissue undergoes the changes necessary to hold the two fragments permanently together. When union has been accom- plished the callus undergoes absorption, which first occurs in the internal callus. In the medullary spaces, which again are becom- ing enlarged, there are found numerous giant-cells or osteoclasts that appear to play a prominent role in the process of absorption. The giant-cells usually lie in little excavations of the bone-sub- stance. In this way the outer callus also is gradually absorbed, but those portions of bone that are to remain permanently become denser, and finally assume the appearance of normal cortical bone. The amount of the callus varies greatly in different cases. It corresponds pretty closely with the amount of displacement of the fragments and with the severity of the inflammation. In ordinary cases of simple fracture the callus is found only in the angles formed by the broken ends of the bone. In animals that are allowed to run about during the process of repair the two ends of the bone are imbedded in a luxuriant callus which involves a con- siderable portion of the shaft. Sometimes there appears to be an inability on the part of the bone-producing structures to form new bone. The inflammatory tissue is absorbed and no new bone is thrown out, and as a result 250 SURGICAL PATHOLOGY AND THERAPEUTICS. of this there is what is called an "ununited" fracture. If the ends of the two fragments are examined, it will be found that they have lost their sharp edges by absorption of bone, and that they are now more or less pointed. The two ends of the bone are united by a ligamentous band. In some cases nature attempts to form a new joint, and it is then found that the ends are held together by a capsule which when open is seen to contain a small amount of clear serum, and the ends of the bone are covered with a more or less perfectly formed hyaline cartilage. This con- dition is known as psend-arthrosis. In other cases the whole bone is absorbed, but this is extremely rare. The Warren Museum con- tains the arm of a grocer, whom the writer remembers to have seen, whose humerus was entirely absorbed after fracture. The causes that combine to produce non-union in bone do not appear to be under- stood thoroughly. The period of life at which an ununited fracture is commonest is, according to Bruns, between thirty and forty years. The chances of union during old age appear to be much more favor- able than has generally been supposed. Individual peculiarity has probably as much to do with the development of pseudarthrosis as any other factor. Among the constitutional causes mentioned as favoring non-union are pregnancy, syphilis, scurvy, and diabetes. It is probable, however, that pregnancy exercises but little influ- ence one way or another on the repair of bone. In syphilis it is in the later stages of the disease only that delayed union is observed. Local causes may materially contribute to the chances of non- union. Compound fractures supply twice as many cases of non- union as simple fracture. The displacement of the fragments and the presence of anatomical structures between the ends of the bone, such as muscle, tendon, nerve, or portions of the articular capsule, are conditions that seriously interfere with union. Imperfect fixa- tion of the fragments is also a fertile source of failure of the bones to unite. The femur and humerus, being single, are for this reason more likely to be the seat of ununited fracture than bones which are steadied by the presence of another bone. Unskilful treatment is not so frequent a cause of non-union as is supposed, but it is more likely to be followed by deformity at the seat of fracture. Healing of Arteries. — When the trunk of a large artery is wounded an abundant hemorrhage occurs from the cut in the vessel-wall into the surrounding tissues. If there is no open wound in the integuments, a large and tense haematoma is formed. The blood coagulates not only outside the vessel, but also in the wound in its wall and in the interior for a greater or THE PROCESS OF REPAIR. 251 lesser distance. Bleeding is thus arrested and the process of repair soon begins. As the clot is gradu- ally absorbed there is formed granulation tissue, which seals up the line of incision in the wall of the artery. The clot serves as a temporary pro- tection against hemorrhage, but it is soon absorbed, and the cicatrix which has meanwhile formed is composed of connective tissue only, and when sub- jected to arterial pressure is distended until an aneurismal sac is formed. When a ligature is placed around a large artery in continuity, the blood-current is permanently arrested, and it is possible for a durable cicatrix to be developed capable of resisting any strain that blood-pressure can bring to bear upon it. When the knot is firmly tied the intima and a variable portion of the media are ruptured, and the adventitia is gathered into a dense tendinous sheath around the constricted ends. The earliest change noticed is the formation of thrombi, the distal thrombus usually being smaller than the proximal. The size of the thrombi varies greatly. In aseptic operations they are exceedingly small, but they were pres- ent in all cases examined by the writer; in fact, a thrombus w T as seen in the ductus arteriosus of the new T -born infant, where local sepsis was highly improbable. During the first two days granulation tissue forms about the point of ligature and for some distance above and below. This tissue also varies with the amount of traumatism; it is, however, sufficient in all cases to bury the knot. If there is much trauma or if the wound becomes septic, the amount of this surrounding inflamma- tory tissue is increased and a callus of consider- able size is formed, which protects the vessels from the dangers of hemorrhage (Fig. 59). If repair progresses favorably, presently the adventitia is seen invaded by leucocytes in the neighborhood of the ligature, and the infiltration far to penetrate the thrombi. The solvent action « Fig. 59. — Carotid Ar- tery of Horse two weeks after ligature. A callus surrounds the ends of the ves- sel, between which the knot may be seen. The process of repair in the ar- terial wall has not yet begun (specimen 1048, Warren Mu- seum). goes sufficiently of this granula- 252 SURGICAL PATHOLOGY AND THERAPEUTICS. tion tissue gradually disintegrates the bundles of fibres surrounded by the ligature, and the two ends of the vessels separate from one another, leaving the knot imbedded in the centre of the callus. The ends of the vessels, once released from the ligature, begin to expand, and the granulation tissue penetrates freely into the thrombi. Conditions are now reached closely resembling the repair in fractures which have just been studied. There is at this stage both an external and an internal callus. With the development of the granulation tissue new blood-vessels are formed, which spring from the vessels surrounding the ligature: these grow into the thrombi with the granulation tissue, and the thrombi are then said to have become ' ' organized.' ' The granulations that develop in this way form irregular masses of new tissue with spaces between them, which, when the superjacent clot is absorbed, be- come blood-spaces communicating with the lumen of the vessel. These spaces in their turn communicate with the new capillaries in the granulation tissue. This completes the first stage of the healing process. In arteries of considerable size this stage is completed by the fourth or fifth week (Fig. 60). The provisional structures are now grad- ually absorbed, and as they disappear it is found that the walls of the artery have not been inactive. A growth has taken place in the intima at an early stage of the process, and many of the wandering cells found in the clot come from this layer. As the clot and the internal callus disappear there is found a permanent cicatrix, which closes the ends of the vessel. This cicatrix varies in shape according to the presence or the ab- sence of large arterial branches. When no branch is present it has the shape of a cres- cent, the horns of which project symmetric- ally along the inner walls of the vessel. If the branch is given off on the side, the horn on that side is short, reaching only to the point of junction, while the horn on the other side projects much farther into the vessel, thus so narrowing its lumen as to Fig. 6o.-^Carotid Artery of the Horse two months after ligature. The ends of the vessel have opened and the provisional tissue has grown into the thrombus. Between the ends is the ligature sinus (Specimen 1 048- 1, Warren Museum). THE PROCESS OF REPAIR. 253 allow it to taper gradually toward the mouth of the collateral branch. The cicatrix, when fully developed, consists of three layers. The inner layer is composed of endothelium formed in the way already described; below this is a layer of muscular cells, devel- oped by a proliferation of the cells of the media, and outside of all is a connective-tissue cicatrix, evidently formed by the outer walls of the vessel. There is, then, in the permanent cicatrix a reproduc- tion of the three walls of the vessel. When the cicatrix has fully formed the provisional tissue is absorbed, and in its place is found a cord uniting the two ends of the vessel. The mass of new ves- sels formed in the cal- lus has also disappeared. A small central vessel is usually seen penetrat- ing the cicatrix from the lumen and anas- tomosing with a sys- tem of capillaries sur- rounding the end of the arterial stump (Fig. 61). In large cica- trices, w 7 hich sometimes extend a considerable distance into the ves- sel, this central arte- riole may be branched or tortuous, and may give to the cicatricial tissue a "cavernous" appearance. The formation of a muscular cicatrix is generally denied, but the writer, having made extensive researches upon this point, is con- vinced that a muscular cicatrix is developed. The reason why it has not been found is easily explained. The process of permanent cica- trization is so slow that investigators have examined specimens at Fig. 61. — Femoral Artery of Man three months after liga- ture, proximal end, termination of healing process. The cicatrix, composed partly of muscular cells, is penetrated by a small vessel. Below is the fibrous tissue which unites the proximal to the distal end. 254 SURGICAL PATHOLOGY AND THERAPEUTICS. too early a period. The process requires a period of time varying from two to six months, or even longer, for its completion, accord- ing to the size of the vessel. Unstriped muscular cells proliferate much more frequently than is usually supposed. A physiological example of this is seen in the uterus, and every wound that unites involves a reproduction of these cells whenever new arterioles are formed. Some writers, as Senn, and Ballance and Edwards, advise the application of two ligatures to arteries of the largest calibre when tied in continuity. They must be drawn tight enough to approx- imate the walls without rupturing them. The object of this manoeuvre is to diminish the danger of secondary hemorrhage. When the ligature is applied in this way the ends of the vessels do not separate at once, but the vessel remains as an obliterated cord. It is probable, however, that the granulation tissue works its wav into the interior of the vessel in the manner already described. This process is clearly shown in the illustrations given by Ballance and Edwards in their admirable work. There is, therefore, no essential difference in the process of repair under these circum- stances. The walls of the vessel at the point of ligature are absorbed more slowly, however, and traces of them probably remain here and there in the cord uniting the two ends of the vessel. The old idea that the thrombus was organized is now so gener- ally abandoned that it is unnecessary here to discuss the question. The role of the thrombus is protective. In aseptic cases it is reduced to a minimum. In septic cases the whole length of a long trunk may be plugged by a clot. After the ligature of an artery in an amputation-stump the process of repair goes on in the manner described, but there are certain important modifications in it to adapt the circulation of the blood to the new conditions. The main artery of the stump so contracts that its calibre is greatly diminished. The cicatricial tissue which forms extends a long distance into the interior of the vessel, sometimes even throughout its whole extent. In this way its size is further diminished, so as to adapt it to the greatly diminished blood-supply needed for the part. The collateral branches increase in size, so that finally, instead of a large vessel ending abruptly as a cul-de-sac at the end of an amputation stump, there is a much smaller vessel which terminates in a large number of branches distributed in various directions. This diminution in the lumen of the main trunk is analogous to the change which THE PROCESS OF REPAIR. 255 occurs in the hypogastric arteries after birth. There is a so-called ''compensatory endarteritis," which in the new-born infant in- volves even the aorta. The changes seen after ligature in conti- nuity are analogous to those which follow obliteration of the ductus arteriosus. In both a substantial muscular cicatrix is secured at the point of obstruction to the blood-flow. In closing, a word about the ligature. Scarcely any subject in surgery has caused more discussion. Ligatures, usually of silk, were at first left with one long end, so that they could be with- drawn when they had cut their way through the vessel. This method was disadvantageous, as the ligature kept the wound open. Acupressure and torsion were substituted, but they were soon sup- planted by animal ligatures, which are absorbed. Since it has been understood that silk ligatures can be made aseptic, they are now used by most surgeons, as animal ligatures may become absorbed too soon, and a feeling justly exists that they are not to be relied upon. The proposition to apply two ligatures in such a way as to approximate the walls of a vessel without rupturing them is not likely to come into general favor. This method has not the merit of simplicity, and by it the dangers of suppuration are increased. If a ligature is not firmly applied, the lumen of the vessel may not be occluded. It is true that there is danger that the first half of the knot may loosen while the second half is being tied, and this accident has occasionally occurred, but its danger may be obviated by extra care in the application of the ligature. The old idea that the inner coats must be ruptured should no longer influence the surgeon. He should simply endeavor to place the ligature firmly enough upon the vessel to occlude it. A rough hempen or a braided-silk ligature may be needed to hold the first half of the knot in the largest arteries. In all other vessels the slipping of the knot need not be taken into account. Secondary hemorrhage after the ligature of arteries in continuity has become an accident of extreme rarity since the introduction of aseptic surgery. X. GANGRENE. Nkcrosis is the term usually employed by pathologists to denote death of a circumscribed portion of tissue. This term is com- prehensive in its significance and is applicable to all forms of local death. It is, however, usually limited to death of portions of internal organs where, owing to the absence of bacteria, putrefac- tion does not take place and the dead mass is absorbed, new tissue growing in from the surrounding parts to form a cicatrix. Gan- grene is a term applied to death of a part on the surface of the body, which part is readily accessible to bacteria, and therefore almost invariably is accompanied by decomposition. Mortification and sphacelus are terms also used to denote this variety of gangrene. Surgical custom has limited the use of the term "necrosis" to death of bone: it will be necessary, however, to employ the term in speaking of the death of portions of internal organs. The causes that produce death of a part are usually divided into three groups: the first group includes those causes which act directly upon the tissues by mechanical or chemical action, as when a part is crushed by violence or when a powerful escharotic is applied to the surface of the body; in the second group are those forms of gangrene caused by thermic agencies (exposure to a temperature of 54°-68° C. will produce death of a part, and cold, — 16° C, will also bring about a similar result); in the third group are those forms caused by a deprivation of the nutrition of the part, as when the blood-supply is cut ofT by the obstruction of a blood-vessel. Gangrene may be caused by the action of bacteria, either through the specific chemical substances which they liberate, or as the result of vascular obstruction due to the inflammatory process to which they give rise. A neuropathic form of gangrene has been described by several authors, who assume that the injury of the so-called "trophic nerves" is the cause of death of the part. The readiness with which decubitus, or bed-sore, appears after injury to the spinal cord is strongly suggestive of such a theory. Samuel calls attention to the fact that in spinal and cerebral affections the presence of skin rubbing against skin may be sufficient to produce gangrene, as on the labia and the scrotum, and that large doses of chloral adminis- 256 GANGRENE. 257 tered to the insane cause profound sleep, during which in one night decubitus may be produced. It is, however, probable that the com- plete immobility of the paralyzed part and the simultaneous altera- tions in the innervation of the nutritive blood-vessels are sufficient to account for the changes produced, without assuming the pres- ence of a special set of trophic nerves. Gangrene may, however, be caused by the action of the vaso-motor nerves, as will be seen later. The condition of the nutrition of the tissues is also an important factor in the development of gangrene. In old and feeble individuals, in whom the circulation is impaired by weak heart-action or as the result of fever of a low type, gangrene fol- lows readily upon slight injuries. Individuals affected with dia- betes or with scurvy are peculiarly liable to gangrenous processes. The so-called " marasmic thrombi " are due usually to a slowing of the current and a coincident defect in the walls of the blood-ves- sels, thus favoring the coagulation of the blood. One of the first changes noticeable in the tissues after death of the part is the disappearance of the nuclei of the cells. In some cases chromatin (or the substances which take the staining most readily) collects in the form of granules, and is removed from the nucleus into the protoplasm of the cell, where it is dissolved and disappears. In other cases the nucleus itself loses its power of taking the staining fluid, is dissolved, and disappears. Such changes are readily seen in the epithelium of the kidney after embolism of a vessel: at the same time the affected tissue has a pale, cloudy, yellowish-white appearance, readily discernible by the naked eye. If the necrosed tissue contains substances capable of coagulation as well as the ferment necessary for coagulation, and if there are no processes, such as suppuration, unfavorable to this change, there may arise the condition described by Weigert as coagulation- necrosis. This condition is not unlike that which occurs when blood coagulates and a thrombus is formed. The cells of the tis- sue become altered to granular or hyaline masses and lose their nuclei. The intercellular substance also undergoes a hvaline degeneration. A striking example of this change is seen in mus- cular fibre when necrosis occurs as the result of trauma or of toxic infection or a burn. The connective-tissue fibres swell up and run together as a homogeneous mass. The dead tissues have a gray- ish-white color, or they may be tinged a dirty brown by the admixture of blood; a greenish-gray color indicates the beginning of decomposition. Recklinghausen has observed the formation of hyaline thrombi 17 2 5 8 SURGICAL PATHOLOGY AND THERAPEUTICS. in the arterioles, and occasionally in the capillary vessels of gan- grenous parts. The hyaline masses appear homogeneous and, rarely, slightly striated, and fill only partially the lumen of the vessel. They appear to be formed during the contraction of the arteries, and to be connected in some way with changes in the arterial wall. In some cases the walls themselves of the capil- laries undergo a hyaline degeneration. These conditions have been observed in senile gangrene following burns, and in gangrene produced artificially in a cock's comb by the administration of spurred rye. Gangrene is in many cases so intimately connected with changes in the arterial system that it is necessary to refer briefly to some of the forms of arterial disease that are liable to produce it. The inflam- mation of the walls of arteries is almost invariably accompanied by the formation of new tissue — a condition which has an important bearing upon the circulation through the diseased channels. In the aorta an inflammation of the intima is accompanied by the production of warty, sometimes pediculated, growths which project into the lumen of the vessel. In the small arteries this growth from the intima involves a vessel through a considerable portion of its length, and it may be so extensive as to fill out the greater part of the lumen, producing a condition known as obliterating endarteri- tis (Fig. 62). This new formation is developed chiefly from the en- dothelium. Later, when the new tissue has de- veloped to a considerable extent, new vessels form in it which spring from the vasa vasorum. Many of them also communi- cate directly with the lumen of the vessel. It is by means of these ves- sels, some of which are of considerable size, that the circulation is main- tained. They are not mere blood-channels, but are supplied with a wall of their own. In cases Fig. 62.— Tibial Artery from a case of Senile Gangrene where SUCH extensive of the Foot (obiiterative endarteritis). changes have taken place GANGRENE. 259 it will be found that also both the middle and the outer coats of the artery are involved in the inflammatory process. In many cases the inflammation terminates in atheromatous degeneration of the walls of the artery. In this case the begin- ning of the process is characterized by the formation on the inner wall of soft gelatinous nodules, which later become of almost car- tilaginous hardness, the result of a growth from the intima. Later the media and the adventitia become involved, and there is next dis- covered that degenerative or atheromatous changes are beginning, and when the nodules are laid open with the knife they are found to contain whitish and yellowish masses even in their deepest por- tions. As these masses soften the surface of the nodules becomes involved and an atheromatous ulcer is formed. If, however, the focus of degeneration is more deeply seated in the wall of the vessel, a cavity is developed containing fatty granules, cholesterin crystals, and fragments of tissue, forming the so-called ' ' athero- matous abscess" (Orth). These little abscesses may eventually break and discharge their contents into the interior of the vessel. Such crateriform ulcers offer an opportunity for the development of a thrombus. In the heart or the aorta such a clot would furnish the point of departure for an embolus. In the smaller vessels these formations lead to the obliteration of the lumen. These abscesses may heal and leave scars. In some of the atheromatous foci calcification may take place. These calcareous masses may be present in large numbers in the aorta covered by epithelium, or they may be found projecting from atheromatous ulcers. Their size and shape indicate that they have developed from the calcification of thrombi which have been deposited on the wall of the vessel. When all these various changes are present in different stages of development there exists the condition to which the name u end- arteritis deformans" has appropriately been given. The pathological changes produced in the wall of the artery by syphilis, and even by tubercle, are also sufficient to impair their function of nutrition. The effect of the changes in the arterial circulation must of course be great. Occurring as they do chiefly in advanced life, they are accompanied by great enfeeblement of the circulation at the extremities. If the arterial disease has been in the smaller vessels, the diminution of the force of the circula- tion is gradual, and absolute cessation is finally brought about either by the formation of a small thrombus or by some slight injury. The arterial supply being cut off, no fluid is brought to the dead part, and the veins, being unobstructed, have not retained 260 SURGICAL PATHOLOGY AXD THERAPEUTICS. any venous blood in the part, consequently the part becomes grad- ually dried by evaporation and the form known as lk dry n or senile gangrene is produced. The coloring matter of the retained blood, being diffused through the dead tissues, imparts to them the cha- racteristic dark color of this form of gangrene. The dried tissues eventually become hardened to a leather-like consistency; hence the term mummification. When there is sudden arrest of the arterial circulation or death of the part through venous obstruction, there exists the condition known as moist gangrene. Bacterial infection soon brings about decomposition, during which gases are often developed, producing emphysema of the tissues. The blood-corpuscles are soon broken up and dissolved, and the cells become cloudy, lose their nuclei, and break down. The striations of muscular fibre disappear, and the mucin of the nerve-fibres runs into drops. Fat-cells become disorganized, and drops of fat are mingled with the swollen and softened fibres of connective tissue. In this way the tissues grad- ually become dissolved. While these changes are going on, the surrounding healthy tissue undergoes a reactive inflammation, due to the putrefactive changes which are developing in the gangrenous part. A red line of inflammation is formed at the point where the gangrene has ceased to spread, and the dark, discolored dead masses stand out in strong contrast to the bright-red color of the inflamed tissues about them. In this way the so-called u line of demarcation n is formed. When suppuration takes place the dead tissue becomes separated from the living, and the gangrenous tissue is in this way event- ually liberated. In necrosis of internal organs, of which infarction of the kid- neys or of the lungs is an example, there is rarely bacterial infec- tion, and suppuration does not take place. There is, of course, no line of demarcation in such cases, but the living tissues grow into and replace the dead substance, which is gradually absorbed. Senile gangrene occurs most frequently in people over fifty years of age, and is caused, as before stated, by arterial disease. Death of the part may take place from a thrombosis of the small vessels or in the arteries leading to it, or it may be due to an embo- lus. The immediate cause of gangrene is often a weakening of the heart's action in an individual in whom, owing to the conditions mentioned, the peripheral circulation is already very feeble. A slight injury, like the bruising of the foot or even a "hang-nail," may be the starting-point of the disease. GANGRENE. 261 The part most frequently attacked is the foot, one or several of the toes being affected, it being extremely rare to find the disease in the upper extremities. The earliest symptom is redness and swelling of one of the toes, accompanied sometimes with consid- erable pain. This condition is very apt to be mistaken for an attack of gout. The characteristic discoloration, however, appears and settles the diagnosis. It usually involves the whole toe, but does not spread beyond. A line of demarcation forms at the meta- tarso-phalangeal articulation, and the toe shrinks or it becomes coal-black in color, and the integuments become dry and wrinkled, and sometimes almost as hard as wood. The pain has by this time ceased, and the patient's general condition may not be materially affected. In favorable cases the toe is gradually separated and falls off, and the wound heals by granulation. In many cases, however, the attempt of nature to form a line of demarcation fails and the gangrene spreads to one or more adjacent toes. The surrounding tissues are now in a state of inflammation, as there is more or less decomposition in the gangrenous part, owing to the presence of bacteria, and their bright-red color is in strong contrast to the blackened toes. If the gangrene does not spread, a line of demar- cation forms along the border of the dead part, but the disturbing influences of septic inflammation are in many cases sufficient to con- tinue the process. Many of the bacteria form substances having an escharotic action upon the adjacent tissue, and the nutrition of the neighboring parts must be in good order to enable the tissue to re- sist them. When gangrene has once reached as far as the dorsum of the foot, the prognosis becomes very grave, and the patient, after nature has made several vain attempts to form a line of demarca- tion, dies of exhaustion at the end of a prolonged illness. In such cases as this it usually will be found at the autopsy that the tibial arteries have been involved in an obliterating inflammation or that their walls are rigid and atheromatous. There is, therefore, the danger that the gangrene may also involve the leg as far as the knee, and this is occasionally the case where an extensive throm- bus has formed throughout the length of these vessels, extending even into the popliteal and femoral arteries. Haidenhain, in a careful examination of a number of legs amputated for senile gangrene, found evidences of thrombosis either of the femoral artery or of its branches. In 11 out of 20 cases there was almost complete obliteration of the larger vessels by old thrombi, many of which had already become organized. According to this writer, thrombi form at the point of bifurcation 262 SURGICAL PATHOLOGY AND THERAPEUTICS. of the popliteal and fill the tibials in their whole length. Such thrombi were found quite often in diabetic cases. Gangrene of the foot and leg combined is, however, more often due to embolism than thrombus. Here the onset is more acute, and generally occurs in an individual who has had signs of previously existing heart or arterial disease. The first symptom may be a sharp pain in the foot and the calf of the leg, and when seen early the af- fected portion of the limb is blanched and cold and pulsation in the tibial artery is absent. Such a group of symptoms in an individual with a history of cardiac disease places the diagnosis beyond a doubt. The most frequent point of lodgment of such an embolus is the bifurcation of the popliteal artery. A thrombus forms immediately upon the proximal side of the embolus, and the femoral artery may be obliterated for a considerable portion of its length. The follow- ing cases of embolism of the popliteal artery will serve to illustrate the clinical features of this affection: In one case, a hospital patient, the leg was removed jnst below the knee- joint, and the patient made a good recovery. In another case embolism occurred in a patient affected with heart disease after a very exhausting polit- ical campaign. The limb when first seen was cold and pulseless ; the patient had suffered a great deal of pain for twenty-four hours. The pulse was rapid and intermittent and the general condition of the patient was bad. Ampu- tation was performed on the third day, after an attempt had been made to improve the patient's strength. By this time the limb had become discolored for some distance above the ankle, but the muscles and the skin of the calf still retained a natural color. Amputation was performed at the lower third of the thigh, and the vessels were found plugged with thrombi, so that there was no hemorrhage. A large fresh thrombus projected from the femoral artery, and it seemed to extend into the vessel for a long distance. Slight sloughing of the flaps and connective tissue of the interior of the wound occurred a few days later, but the sloughs eventually separated and were replaced by healtlry granulations. A week after the operation a sharp pain occurred in the chest, with a rise of temperature, followed by the expectora- tion of a dark clot, indicating the development of an infarction of the lung. The patient died three months later of an infarction of the spleen, which sup- purated, a large abscess being found in this region at the autopS3\ Embolism of the brachial artery may also occur, but not so frequently as in the femoral artery and its branches. Treatment. — In the mildest cases of senile gangrene, when one toe only is involved, it is advisable to refrain from interference. The metatarso-phalangeal articulation lies deep, and meddlesome surgery may cause the gangrenous process to extend. In the student days of the writer this old surgical rule existed — namely, that in spontaneous, or idiopathic, gangrene, as it is often called, GANGRENE. 263 the surgeon should wait for the line of demarcation, but that in traumatic gangrene he should amputate at once. The mortality following conservative treatment in senile gan- grene was, however, so large that the old rule has been abandoned, and it is now advised by the best authority to interfere as soon as it is evident that there is not sufficient power to form a line of demarcation. A good rule to follow is to advise amputation as soon as the gangrene has invaded the sole or the dorsum of the foot, for it is then liable to spread with much greater rapidity. The point at which amputation should be performed is a ques- tion about which authorities differ. As has been seen, the tibial arteries are usually diseased in their entire length, and the circu- lation in them is therefore almost always more or less diminished. For this reason many surgeons prefer to amputate above or below the knee-joint; that is, at a point well removed from the region of the disease. In one case the writer operated with good results, on a feeble individual who had diabetes, at the middle of the leg, but if the strength of the patient will bear it, it is better to ampu- tate at the lower third of the thigh. Before undertaking to interfere surgically it is well to ascertain the probability of similar processes occurring in other portions of the body, as the following case will show: A man fifty years of age, but in appearance much older, entered the hospital with gangrene of the great toe and a portion of the same foot. He had injured it two months before in very cold weather. The leg was ampu- tated a few days later at the point of election . The patient recovered from the operation and the wound healed well during two weeks, but he died on the seventeenth day after three days of severe illness. At the autopsy there were found, in addition to an obliterating endarteritis of the tibial arteries with calcification, obliteration of the splenic artery, thrombosis of the splenic vein, and anaemic necrosis of the liver and spleen. The immediate cause of death was thrombosis of the femoral vein and pulmonary artery. The amount of disease in this case was such as to make it doubtful whether an amputation should have been attempted with much hope of success. In case a conservative treatment is decided upon, careful attention should be given to the patient's general condition. Cardiac tonics and a nourishing diet with stimulants are indicated. The parts should be kept in as anti- septic a condition as possible, and every opportunity should be given to the gangrenous toes to become mummified. In case of embolism an effort should be made to save the limb. The parts should be elevated slightly to favor venous circulation, and be encased in warm cotton, care being taken to avoid all constriction 264 SURGICAL PATHOLOGY AND THERAPEUTICS. of the circulation by the dressings. When once the diagnosis and the extent of the gangrene are established, the sooner ampu- tation is performed the better. A condition very closely allied to senile gangrene is that known as diabetic gangrene (PI. III.), which occurs also in elderly indi- viduals. It is important, therefore, that the condition of the urine should be carefully determined in all cases of senile gan- grene. The picture of the disease so closely resembles that already given that there is little to add to it. Furuncle and carbuncle, bed-sores, pneumonia, abscess, and gangrene of the lungs also occur in diabetic patients. Diabetic individuals bear surgical operations so poorly that in general it is the custom to advise against operations in persons affected with this condition of the system. The writer would not, however, hesitate to advise amputation in a case of spreading gangrene. A gentleman sixty years of age applied to the writer for treatment of gangrene of the third toe of the left foot. The right leg had been ampu- tated two years previously for gangrene. There was found well-marked diabetes, and when the gangrene began to spread to the foot amputation was performed in the middle third of the leg with a successful result. There was marked atheroma of both tibial arteries. By careful attention to diet the patient recovered his strength, and when seen by the writer a year or two later appeared to be in excellent health. Haidenhain in a recent article undertakes to show that gan- grene in diabetes is due to arterio-sclerosis of the vessels, as in senile gangrene, and advises amputation at the thigh as soon as the gangrene has invaded the sole or the dorsum of the foot. Of 13 cases of amputation below 'the knee, including disarticula- tion of toes, Chopart's and Lisfranc's amputations, and amputa- tion of the leg, only 2 recovered; 2 cases died from gangrene of the flaps, and later, in 9 cases, amputation was made at or above the knee. Of 27 primary and secondary operations above the knee, 19 cases were cured and 8 died of diabetic coma. In none of these cases did the condition of the wound appear to be the cause of death. Haidenhain advises the cutting of very shallow flaps. It is customary to describe moist gangrene as a separate variety, but many cases of senile gangrene may be moist, this condition depending in such cases on the rapidity with which the disease has established itself and on the amount of tissue involved. A frequent cause of moist gangrene is injury to the large vessels by gunshot wounds or the complications which result from fractures. PLATE III sue M Diabetic Gangrene. PLATE IV 2*~ Gangrene of Leg, following ligature of femoral artery for popliteal aneurism. GANGRENE. 265 Traumatic gangrene is almost always of the moist variety. Gan- grene of this type may occur also from acute inflammation and from burns and frost-bite. Obstruction to the venous circula- tion from thrombosis or from pressure by bandages or dressing will retain the fluids of the body in the part and prevent any tendency to mummification. As examples of venous obstruction there may be cited strangulated hernia and severe forms of para- phimosis. The sloughing of flaps after an amputation for injury is also an example of moist gangrene. The characteristic appearances of the traumatic form of moist gangrene are best seen after an injury to some large vessel, such as the popliteal or the brachial artery (PI. IV.). For the first twenty- four hours it is doubtful whether the limb will live or not. Pul- sation of the tibial (if the lower extremity is the injured member) is wanting from the beginning. The limb is blanched and is colder than the opposite limb. The patient, who has suffered from the pain of the original lesion, is relieved of pain with the approaching death of the limb; and, inasmuch as he is still able to move his toes, he fails to appreciate the grave nature of his injury. The skin discoloration which begins at the end of twenty-four hours is usually a symptom that may be relied upon as character- istic, but extensive ecchymosis may sometimes give a misleading impression. The writer well remembers a case of frost-bite where the greater portion of both feet were of a coal-black hue: he obtained the patient's consent to a double amputation above the ankle, but at the moment of the administration of ether doubts as to the propriety of operating determined him to wait another day. The patient eventually escaped with the loss of one or two toes of each foot. The irregular distribution of color shows that the circulation has been greatly impeded, and livid spots alternating with an unusual pallor are more certain indications of approaching gan- grene. When decomposition sets in a greenish tinge is added to the variegated coloring of the limb. The part now becomes swollen and of a soft, unnatural, pulpy consistency. Pressure fails to bring about a paleness of the skin with a subsequent return of color. Blisters filled with a bloody serum form upon the surface. The swelling and discoloration are partly due to increased blood-pressure in some of the vessels of the part, for there is still a limited circulation in the veins even when mortifi- cation has set in. At this period there is an entire loss of sensation 266 SURGICAL PATHOLOGY AND THERAPEUTICS. in the part, and the patient will bear the prick of the scalpel with- out flinching. In many cases it is only by some such demonstration as this that he is convinced that there is no longer need of an attempt to save the leg. In favorable cases the gangrene is con- fined to the injured part, and in this case a line of demarcation forms, but even before this line shows itself it becomes evident from the contrast between the white healthy skin and the swollen and discolored tissues that the gangrene will not spread. The color deepens in hue, and becomes eventually either dark green or coal black. The tendency of the deeper parts to soften is very marked, and muscular tissue soon becomes reduced to the consistence of a brick-dust paste. Tougher tissues, like tendons, retain their form much longer, and bone is rarely altered by the gangrenous process. When the putrefactive changes are more acute, the chemical changes are probably brought about by more malignant forms of bacteria, as the streptococcus or malignant oedema bacillus. The saprogenic organisms also play a prominent role. In such cases the gangrene readily spreads, and it is accompanied by the forma- tion of gases which spread through the loose tissue in advance of the disease. These gases consist of ammonia, sulphide of ammo- nium, sulphuretted hydrogen, and volatile fatty acids. In the foul, discolored, and greasy fluids that ooze from the wound there are found leucin, tyrosin and fat-crystals, crystals of triple phosphate, and clumps of dark pigment. The gangrene rapidly spreads, and while the patient is endeavoring to make up his mind to the loss of a foot the whole limb may be destroyed. The changes of color in the skin are rapid and striking in their effects. The part is dark green or black, the leg a livid bronze color, and streaks of green and bronze run in long narrow bands up the thigh. The constitu- tional disturbance is profound. The patient suffers from acute sep- ticaemia; there are collapse with a small and frequent pulse, rapid respiration, profuse perspiration, and choleraic discharges from the bowels. The citation here of a few cases will serve to indicate the grave nature of the affection: A man was shot through the leg by a discharge from a fowling-piece, the posterior tibial artery being lacerated in its lower third. Pulsation could not be felt in the artery at the ankle-joint. An attempt was made to save the limb. On the third day the foot became gangrenous, and the disease spread so rapidly that twenty-four hours later amputation at the junction of the middle and upper third of the thigh failed to save his life. The whole limb was in a state of acute putrefaction, being distended with gas and emitting a foul odor. The skin presented a variegated coloring of green, brown, bronze, and black. GANGRENE, 267 An elderly woman addicted to the use of alcohol fell and sustained a com- pound Colles' fracture, the sharp edge of the shaft of the radius piercing the radial artery. When seen a few days later the arm was swollen above the elbow and was greatly discolored ; the hand was closed, claw-like, and greatly swollen. A foul discharge oozed from the wound. Amputation was performed at the middle of the arm. The softer tissues of the gangrenous portion were almost completely macerated. The patient made a good recovery. A boy fifteen years of age sustained a fracture of the bones of the forearm while trying to vault over a bale of goods. The patient was brought into the hospital a few days later with the forearm in splints and in a gangrenous con- dition. The next day the arm was much swollen and discolored, and of a deep bronze hue. Emphysema could be felt over the shoulder and the correspond- ing half of the chest. There being no wound through which decomposing fluids and gases could escape, a number of free incisions were made in the parts already dead to relieve the tension and favor drainage. In this way the spread of the gangrene was arrested, and the next day a line of demarcation formed below the shoulder-joint, and the boy eventually recovered. These cases of traumatic gangrene require the most prompt interference on the part of the surgeon. They are known as u fulminating gangrene" or "gangrenous emphysema," or, in the expressive French language, as gangrene foudroy 'ante. Gangrene may result from some of the forms of inflammation with intense congestion of the parts. In some cases of hyperaemia accompanying inflammation there is, as has already been seen, a slowing of the blood in the capillaries, and in this condition red corpuscles are often forced through the walls of the vessels, giving rise to the hemorrhagic type. This degree of congestion precedes total stasis, which, when it occurs on a large enough scale, produces death of the part. But death is still more frequently caused by the direct poisonous action of bacteria. When an inflammation is about to terminate in gangrene, the bright red color becomes a deep livid red, mottled with blue, later a purple hue, and finally black. The underlying tissues are boggy and are distended with gas and decom- posed fluids. There is great swelling of the adjacent lymphatic glands. At the seat of the lesion the muscles and tendons are mace- rated, the bone is denuded and surrounded by a putrid fluid min- gled with pus. It is in this fluid that one finds the largest number of micro-organisms. The constitutional disturbance is profound. There is great physical prostration and the signs of septicaemia are well marked. A post-mortem examination shows that the viscera are congested and cedematous, and present hemorrhagic infarctions (Park). Such gangrenous types of inflammation occur only from some of the most poisonous forms of bacterial infection, as, for example, 268 SURGICAL PATHOLOGY AND THERAPEUTICS. the bacillus of malignant oedema. Occasionally a man is brought into the hospital with an entire arm in this condition, the result of an acute phlegmonous inflammation arising from a poisoned wound in the hand. The infection occurs often after the most trivial lesions, as the prick of some dirty tool or instrument. The treatment of moist gangrene varies greatly according to the con- ditions under which it develops. The old rule, to amputate at once in traumatic gangrene, has but few exceptions. If there is no tend- ency to spread, a time can be chosen for the operation when the condition of the patient is satisfactory to the surgeon. In spread- ing gangrene the loss even of hours is sometimes fatal to life. There are but few cases in surgery that are more urgent than these. Free incisions may sometimes relieve tension and permit the escape of foul gases and fluids, but such a resort is not to be depended upon to arrest the process, and it should only be employed when amputation is not permissible on account of the low state of the patient. The process, once fully developed, may leave the patient in such a state that life can only be saved by amputation. It is hardly necessary here to remind the reader that good food and stimulants, both alcoholic and cardiac, may be needed to develop all the strength which the system can command. Alco- holic stimulation is about the only form of treatment that can be depended upon in this grave condition. Gangrene from frost-bite may result partly from the effects of cold and partly from the enfeebled condition of the patient. A temperature of — 16° C. is sufficiently low to produce this condition. Exposure to cold in a drunken sleep is the commonest way in which this form of gangrene is acquired. The parts — usually the feet — at first are blanched, and later become purple or marbled, running in shade from a deep black in the toes to a mottled purple which may extend above the ankles. The effect of cold upon the small arteries is to cause them to contract to prevent the flow of blood. If this condition of spasm is maintained too long, the arteries will not dilate and the blood will never return. If kept up for a certain length of time, they will dilate to such an extent that the part will become engorged with blood, and gangrene may be produced in the same way as in the acute congestion described above. There will be an intense passive hypersemia with stasis in the vessels, that may lead to death of the part or to a chronic inflammatory process. The blood must therefore be allowed to come back gradually, and it is for this reason that treatment by cold is so often used. The Esquimaux C. INGRENE. 269 place a frozen man in a room at the temperature of zero Fahren- heit, and gradually raise the temperature to the desired point. The practice of bringing a case of frozen feet into the warm ward of a hospital should, if possible, be avoided. The part, at all events, should be kept in an atmosphere cooled by ice-bags while the skin is kept dry. Usually the threatening color will gradually disappear, or will prove to be due chiefly to extravasated blood beneath the epidermis, and the gangrene will be found quite lim- ited in extent. The use of poultices to warm the dead parts should be avoided r as they promote suppuration and favor burrowing of pus. After the warmth has fully been restored an antiseptic dressing should be IfefeK X. Fig. 63. — Gangrene of the Toes from Frost-bite. applied until the line of demarcation is established, when the dead parts can be removed by an operation if necessary (Fig. 63). A not uncommon cause of gangrene is extravasation of urine. 270 SURGICAL PATHOLOGY AND THERAPEUTICS. The effect of an ammoniacal urine laden with bacteria is to cause an extensive slough of the connective tissue and occasionally of the scrotum. Free and early incisions are indicated in such cases. When a portion of the scrotum becomes gangrenous and separates, the remainder retracts, and the loss of integument appears to be much greater than it really is. Although the testicles and cords may be exposed in their entire length, they will eventually be covered in by the granulating wound. The treatment of such cases consists in free incisions through the whole extent of the extrava- sated area. An incision on the median line, dividing the scrotum into halves as far down as the point of rupture in the urethra, is usually called for. A rare occurrence, which the writer has seen only once, is gan- grene of the urethra and glans penis due to obstruction of its nutrient artery. In this case the gangrenous parts were carefully dissected away and a clean external wound was left, but the patient succumbed to a gangrenous cystitis. Noma, or cancmm oris, is the result of gangrenous stomatitis affecting the cheek. Noma occurs most frequently as a compli- cation of one of the eruptive diseases of children, such as scarlet fever; it may also affect the pudenda. It is evidently produced by a septic inflammation, although Samuel regards it of neurotic origin, as it does not pass the middle line and is developed without preceding inflammatory symptoms. Schimmelbusch has examined one case for bacteria, and found small bacilli, often in pairs and sometimes in long filaments, growing along the boundary-line of the living tissue. These bacilli grow in gelatin without liquefying it at the temperature of the room, and injected into rabbits they cause abscesses. They did not stain by Gram's method. Lingard examined five cases and found a bacillus 4-8// long; when injected into rabbits it caused inflammation, and death on the tenth day. Foote examined one case of noma and found bacilli, but he failed to obtain cultures of them. Sections taken from the skin at the edge of the ulcer covering the malar bone, and stained by Gram's method, showed an outer zone of necrotic tissue and an inner zone of normal tissue. At the edge of the necrotic zone bacilli were found packed closely together to the exclusion of all other bacteria along the line of necrosis : this gave the impression that they were eating directly into the sound tissue. They were, in fact, seen infiltrating the healthy connective tissues, though in much less abundance than along the line of necrosis. Thus far, there is not sufficient evidence to show that an organism which GANGRENE. 271 may be regarded as specific has been obtained by a number of independent observers. The cheek is usually affected, and the loss of substance is so extensive that the whole side of the month is frequently exposed. The bones of the superior and inferior maxilla may be laid bare, and the teeth may frequently drop out. After the slough has sepa- rated the wound appears like a sharply-cut gigantic ulcer, involv- ing the side of the nose and the entire cheek. After cicatrization takes place a large opening still remains, and the case requires an elaborate plastic operation for its relief. At the pudenda the dis- ease usually begins at the labial margin and extends to the clitoris, the nymphae, and the hymen, and sometimes to the urethra. The disease may spread to the perineum, to the anus, or to the thigh (Hamilton), and, as in the mouth, the sloughing is deep and fre- quently extends quite to the bone. The constitutional treatment in noma is of the greatest import- ance, and it is chiefly through this treatment that life may be saved. Quinine and iron may be given in full doses, and stimu- lants also. Disinfecting gargles may be used for the mouth and antiseptic dressings for the pudenda. A few drops of an emulsion of sty rone 3ss, glycerin £iv, water giij, added to a glass of water, forms an agreeable and efficient disinfectant for the mouth. In the use of antiseptics care should be taken to avoid poisoning by the absorption of the drugs used. Ergotism, or gangrene produced by eating grain containing ergot of rye {Secale comutum), was a disease of the seventeenth and eighteenth centuries, and at one time produced great havoc among the farmers in France, Switzerland, and other countries of Europe. It has been denied that the drug could produce this effect when used experimentally upon animals; but according to Recklinghau- sen the characteristic effect was produced in a cock's comb, where a spasm of the arterioles was observed after its administration, and the contractions were severe in degree and of long duration. At one time the mortality of ergotism is said to have been very great, entire hands and even whole limbs being affected by the gangren- ous process. Decubitus, or bed-sore, is a form of gangrene produced by pres- sure. When the slough separates it leaves a large ulcer, which has already been described. Many believe decubitus to be an example of neuropathic gangrene, as it occurs so readily after injuries to the spine. The rapidity with which sloughs form on the heels after such injuries is certainly suggestive of trophic 272 SURGICAL PATHOLOGY AND THERAPEUTICS. changes. There is no direct proof of this theory, however, and the general opinion appears to be that the gangrene is due to enfeebled circulation with uninterrupted pressure. Continued pressure, even when too light to cause pain, as from a tightly- applied tourniquet or from splints, produces the same effect. Bed- sores form readily in patients affected with low forms of fever, and they are in such cases partly due to enfeebled heart- action. In the treatment of decubitus great care should be taken to prevent pressure on the parts liable to be affected, such as the heels and the sacrum. The skin should be kept clean and dry, and one of the chief advantages of a trained nurse in such cases is the care given to the condition of the integuments of the back. Daily friction with alcohol, keeping the parts dry with toilet-pow- der, and the use of ring pads to remove pressure are the principal means of prevention. Since the days of trained nurses bed-sores have greatly diminished in number, and their development is a source of much less anxiety to the attending physician. The same cannot be said, unfortunately, of the use of hot-water bottles. It has been the writer's lot to see, as the result of their careless use, extensive sloughs form upon patients while still under the influ- ence of ether. It is a good rule not to allow any hot-water bot- tles in the bed of a patient coming out of ether: the bed can be heated sufficiently before he is placed in it. A rare form of gangrene, but one which is nevertheless occa- sionally seen at the present time, is that known as symmetrical gangrene or Raynaud's disease. It is a variety of dry gangrene characterized by two prominent features — the absence of any ana- tomical lesions of the blood-vessels, and the symmetrical develop- ment of the disease in the two halves of the body. It may be found in both an upper and a lower extremity, or in all four extremities, and occasionally the ear, the cheeks, and the nose are affected. Mills reports a case in which the tip of the tongue was slightly affected. A somewhat similar condition is that pop- ularly known as " dead finger," which comes on after exposure ta cold, and which is not unfrequently seen in young ladies after a cold bath. The affected finger is distinctly paler than the others and is cold; the circulation, however, soon returns. In the con- dition associated with symmetrical gangrene the disturbance of the circulation is more profound, and there occurs what the French call "local asphyxia." The pallor is succeeded by a cyanotic color of varying degrees of intensity. On pressure the color disappears, and returns very slowly, showing great feeble- GANGRENE. 273 ness in the circulation. When in this condition the ends of the fingers, the parts most frequently affected, are often quite painful. The color later becomes almost black, and minute blisters appear on the tips of the fingers. The blisters become filled with a sero-purulent fluid, break, and leave excoriations which may remain several days. The color now begins to return, the excoriations heal, and a little conical tubercle is left just be- neath the edge of the nail. The improvement is, however, only temporary; the same changes recur, and may be repeated during a period lasting one or two years. In an advanced stage the ends of the fingers are covered with a number of little white scars, the skin being indurated, and they have a thin, sharp, withered look, as if they had been pinched in a vise and had preserved the shape thus given to them. When the vascular disturbance reaches that point which is sufficient to cause death of the part, the transparent cyanotic pulp of the finger has at its central part a small black mass of tissue which subsequently separates as a slough. No cardiac disease is found in cases of symmetrical gangrene, and the general condition of the patient gives evidence of no form of organic disease anywhere. The vaso-motor disturbance remains at its height for about ten days, and convalescence is established at the end of from three weeks to several months. Occasionally,, after one or two attacks, the condition becomes more or less perma- nent, and the part affected is continually cold and torpid. At times the skin of the backs of the hands and the fingers becomes thick- ened and rigid, and the fingers are held semiflexed and ankylosed. The two affections most likely to be mistaken for this disease are chilblains and senile gangrene. In chilblains all the extrem- ities are not likely to be found affected, and the disease is limited to certain periods of the year. Senile gangrene is rarely bilateral: it is much more extensive, and the characteristic condition of the arteries is usually present. Owing to the predominance of pain it has sometimes been mistaken for gout. The prognosis of sym- metrical gangrene is favorable. If the stage of gangrene develops itself at the end of a week or ten days, it is probable that a com- plete recovery will follow the separation of the eschars. If, how- ever, the disease does not reach this point, but comes and goes, there is danger that it will settle down into a chronic condition. In four-fifths of the cases the disease is found in women. In the great majority of cases it occurs between the ages of eighteen and thirty years. As a low temperature is an exciting cause, the dis- ease is more frequently found on the approach of the winter 18 274 SURGICAL PATHOLOGY AND THERAPEUTICS. months. Not infrequently there may be premonitory symptoms for one or two winters, with return to health in the summer season, and a final termination in gangrene. The following case is the only example of this affection which the writer has seen: A rather feeble woman, twenty-five years of age and a native of Scot- land, presented herself at the hospital in June, 1878. She had been in good health until four months previously, at which time she suffered frequently from nose-bleed. Soon after this she noticed that the tips of the fingers and toes became red. At the time of entrance to the hospital the pulps of the fingers and toes were discolored. The borders of the affected area resembled the semi-transparent purple of a grape. There was none of the reddish tint seen in strangulated intestine. The lightest shades were also essentially purple in tint: near the centre the hue deepened until it was difficult to determine whether or not the tissues were gangrenous. The patient did not complain of much pain, but was totally incapacitated for work, owing to the condition of her hands. On two of the finger-tips were patches of gangrene. In a few daj-s several sloughs separated from the fingers as dry, black eschars, the largest being about the size of a ten-cent piece. The treatment consisted in administration of iron internally and good food, and the application of resin cerate to the parts, About two months later, when the patient left the hospital, the fingers had healed and presented a red and shrivelled look. There was no gangrene of the toes. Symmetrical gangrene, according to Raynaud, is a form of ischaemia due to contraction of the arterioles, which contraction may sometimes extend back as far as arteries of considerable size (radial pulse). In the lighter forms of spasm there occurs ' ! local syncope " or " dead finger. ' ' The veins probably are also con- tracted. When the reaction following the spasm is incomplete there is " local asphyxia." The veins having the smallest amount of muscular fibres relax first, and the venous blood flows back into the capillaries, but stops here, as the arteries are still contracted. As a result of this condition there is a certain amount of stagnation in the larger veins, and sometimes slight oedema. The arterial con- traction was demonstrated in the retina in a case where there was disturbance of vision during the attacks. It is evident, therefore, that the disturbance lies in the vaso-motor apparatus. The sym- metrical character of the lesion is explained by an irritation of one of the vaso-motor centres of the cord which brings about a spasm of the vaso-constrictors. As the disease is situated in various parts of the body, the centre of irritation is not always at the same point, and as there exist several vaso-motor centres, different points may become the seat of the contractions. The vaso-motor nerves are affected not GANGRENE. 275 only by direct irritation, but may also be susceptible to reflex action. An example of the latter is the contraction of the vessels of one hand when the other hand is suddenly plunged into very cold water. Inasmuch as symmetrical gangrene follows occasionally the puerperal state or may show itself periodically at the menstrual epoch, it is but reasonable to suppose that the reflex irritation may take its origin in the uterus. Some of the cases described by Mitchell as erythromelalgia have a resemblance to this affec- tion, and some of them undoubtedly appear to be symmetrical congestions. Although this arterial spasm shows itself at the most peripheral portions of the body, it probably is to be found elsewhere, but the parts being less exposed to the loss of heat, gangrene does not occur. The treatment of symmetrical gangrene consists principally in the administration of tonics and in placing the patient under the best hygienic conditions. Raynaud recommends the use of con- stant descending currents to the spine. The use of some local stimulating application may serve to restore the tone of the cir- culation of the part after the arterial constrictions have ceased. During the separation of the sloughs a careful antisepsis of the part should be maintained. The action of chemical agents as the cause of gangrene has been noted. There is one drug (now so universally used as an antisep- tic agent) which occasionally exerts such a powerful local action that it is desirable for the writer to warn against its use under cer- tain conditions. Watery solutions of carbolic acid when applied to the fingers on compresses have in a number of cases been fol- lowed by gangrene of the entire finger. Several such cases have come to the writer's knowledge. Strong solutions of this acid have a numbing influence upon the part, and, in the early days of its use, strong carbolic acid was experimented with as a local anaesthetic for minor operations. A prolonged application of a compress wet in a carbolic solution is followed by the evaporation of the water and a corresponding concentration of the agent. The surgeon should therefore avoid entirely the use of solutions of this drug on the extremities of the body. The danger of " carbolic ga?i- grene" is one that should always be kept in mind. Ainhum (a native word meaning to saw off) is an affection which occasionally terminates in gangrene, although spontaneous amputation of the part affected may occur without gangrene. It is a disease characterized by a constriction of the integument of 276 SURGICAL PATHOLOGY AND THERAPEUTICS. the little toe at its plantar fold, producing a deep fissure which gradually encircles the toe until the latter is attached to the foot by a narrow pedicle. Ainhum, which occurs almost exclusively in negroes, is found in Africa and the West Indies ; it has also been met with among the Hindus. It is seen more frequently in men than in women. Cases are reported in which the finger was affected, but they are rare. It is said to be hereditary. There is apparently little if any ulceration during the constrict- ing process. Ainhum has been compared to scleroderma, and Eyles describes a thickening of the deeper layers of the cutis vera. Accord- ing to Duhring, it may be grouped with " degenerative fibromata. n The epidermis is much thickened. The bones undergo an osteo- porosis or a rarefying ostitis. The condition known as ' ' obliterat- ing endarteritis ' ' has been observed. As the constriction deepens the end of the toe enlarges, and appears as if it had been encircled by an elastic ligature. The disease may last from one to ten years. A healthy male negro, fifty-three years of age, suffering from this affection, presented himself at the Massachusetts General Hospital. His family resided in the British Provinces. His grandfather, father, brother, and two sisters had all lost the little toe of the left foot. The toes of all had been removed by a surgeon, except that of one sister, who pulled off her toe. In the case of the patient the disease began four years before in the same toe. There had been no pain, although sensation was felt in the affected part. The disease when first seen resembled a soft corn, in which a deep furrow existed. The furrow gradually increased until the toe was only attached by a pedicle about one-eighth of an inch in diameter. There was a slight exco- riation at one point, but no distinct ulceration, the toe being much enlarged. On removal the toe was placed in alcohol, and after hardening was divided by a horizontal incision, the knife easily cutting through the bone. The phalanx had almost entirely disappeared, and the bulk of the tissue appeared to be made up of a mass of adipose tissue. The cutis and epidermal layers did not appear to be hypertrophied. The patient made a good recovery. No cause has yet been assigned for this affection. It has been suggested that the constriction has intentionally been produced by a ligature. Possibly it may be due to mechanical friction, owing to some peculiarity in gait or in footgear. Sudan noticed in sev- eral cases that lumbar pains preceded the local affection, and he does not regard the disease as local in origin. It has been sug- gested that division of the constricting bands of fibres at an early stage of the disease might check its progress. In the majority of reported cases amputation was performed. This can be done usu- ally with a pair of scissors, as the bone has disappeared from the pedicle. XL SHOCK. "i\.LTHOUGH the fact of death ensuing upon injuries of parts not essential to life, even when unattended by hemorrhage, and upon operations not usually esteemed hazardous, has not escaped observation, writers and teachers seem to have contented them- selves with the bare statement of it, either from an impression that, being an equivalent in effect to death on the spot or being due to an idiosyncrasy moral or physical, the further consideration of the subject in a practical view was unavailing." Thus writes Travers, the senior surgeon of St. Thomas's Hospital, in 1826. Previous to this time the term "shock," as now used, had rarely been employed as a surgical expression. Guthrie, however, speaks of the "shock of the injury," and Sir Astley Cooper says in his lectures, "The most severe injuries by shock to the nervous sys- tem cause death without reaction." James Latta, in 1795, is said to have been the first to have used the word to describe this condition. This profound but somewhat obscure disturbance of the system, although probably recognized by the practical surgeon from time immemorial, has only received the somewhat tardy attention of medical writers, and even at the present time its pathology is but very imperfectly understood. At all events, the most diverse views have been held by those who have studied the condition of the sys- tem in shock. Its importance was first recognized by English writers, to whose efforts no doubt much of our present knowledge is due. Travers, Jordan, Savory, and many others have given the subject special study. It seems strange that the progressive Ger- mans should have allowed shock to have passed almost unnoticed until 1867, when Billroth and Neudorfer first called attention to it. The nomenclature of the affection is not a large one. The terms "traumatic torpor" and "stupor" have been used by Pirogoff; 1 ' prostration without reaction ' ' is spoken of by Travers ; Savory uses "collapse" as the title to his article; and " neuroparalysis " has been employed by those who have attempted to explain the nature of shock in this way. In Germany Wundschreck and Erschiitterung are terms that have been used to a limited extent, 277 278 SURGICAL PATHOLOGY AND THERAPEUTICS. but they have given way, as in France, to the very expressive English phrase which is now almost universally employed. Though the literature of the subject is considerable since it received a place in surgery, yet few writers attempt to define the nature of shock. Its pathology is usually passed over briefly, and the term may be said to have been employed indiscriminately to describe all cases of sudden death following injury without hem- orrhage. In America and in England the condition has been regarded as a general depression of the nervous system without any very well-defined idea as to what the nature of the change was. Mansell-Moullin has defined it a little more accurately as a reflex paralysis or inhibition of the nervous system. In France, Blum explains shock as an arrest of the heart's action, due to reflex irri- tation of the pneumogastric nerve. In Germany many writers have adopted the theory of Fischer, who attributes the weakness of the heart's action and the other phenomena of shock to a reflex vaso-motor paralysis whereby the abdominal vessels are hyperae- mic, and the heart, brain, and other organs are correspondingly ischsemic. Before going more deeply into this question let there be a mutual understanding of the clinical picture which this subtile condition produces in the human organism, when, as Gross graphi- cally puts it, " the machinery of life has been rudely unhinged." A patient is brought into the hospital with a compound commi- nuted fracture or with a dislocation of the hip-joint added to other injuries, where the bleeding has been slight. As the litter is gently deposited on the floor he makes no effort to move or look about him. He lies staring at the surgeon with an expression of com- plete indifference as to his condition. There is no movement of the muscles of the face ; the eyes, which are deeply sunken in their sockets, have a weird, uncanny look. The features are pinched and the face shrunken. A cold, clammy sweat exudes from the pores of the skin, which has an appearance of profound anaemia. The lips are bloodless and the fingers and nails are blue. The pulse is almost imperceptible; a weak, thread-like stream may, however, be detected in the radial artery. The thermometer, placed in the rec- tum (it would be useless to attempt to take the temperature in the axilla), registers 96 or 97 ° F. The muscles are not paralyzed anywhere, but the patient seems disinclined to make any muscu- lar effort. Even respiratory movements seem for the time to be reduced to a minimum. Occasionally the patient may feebly throw about one of his limbs and give vent to a hoarse, weak groan. SHOCK. 279 There is no insensibility (coma is not observed in cases of shock), but he is strangely apathetic, and seems to realize but imperfectly the full meaning of the questions put to him. It is of no use to attempt an operation until appropriate remedies have brought about a reaction. The pulse, however, does not respond; it grows feebler, and finally disappears, and "this momentary pause in the act of death " is soon followed by the grim reality. A post-mortem examination reveals no visible changes in the internal organs. The two principal theories as to the nature of shock are based on certain functional disturbances in the vascular and nervous sys- tems respectively. Fischer takes the ground that shock produces a paralyzing effect upon the heart in a manner similar to that pro- duced upon the frog in Goltz' s experiment, which consists in the infliction of repeated slight blows upon the abdomen (p. 85). When the heart begins to pulsate again it remains small and pale, and receives in the diastole very little blood, and is there- fore able to throw out only a small quantity into the system. This condition was ascribed by Goltz to a lack of tonicity in the vessels of the abdominal cavity, but later he w T as convinced that there was a very general vaso-motor paralysis. It was shown also that the same condition could be brought about by blows received in other parts of the body. This lack of tonicity Goltz subsequently showed was not confined to the arteries, but might affect the veins also, and in this way such large quantities of blood might be received in the vessels of the abdominal cavity, as has been shown experimentally to be the case after division of the splanchnic nerves, that the heart and large vessels elsewhere could receive but an extremely small quantity of blood. According to Fischer, then, the great mass of the blood stagnates in the abdominal veins and arteries during shock. This, he thinks, is a sufficient physiological explanation of the symptoms of shock. As the skin is anaemic, it is pale, cold, and without sensation. Experiment has shown that muscles deprived of their blood are rigid and unable to perform their func- tions, and the great muscular weakness is therefore accounted for. The irregularity and the temporary cessation of the heart's action account for the small, irregular, and absent pulse. The cerebral ansemia explains the mental phenomena of shock and the nausea and vomiting. Schneider also adopts the theory of a reflex paralysis of the vaso-motor nerves, as based upon the views of Falk and Sounen- burg on the cause of death after extensive burns. According to Schneider, every extreme irritation produced by surgical operations 28o SURGICAL PATHOLOGY AND THERAPEUTICS. or by injuries causes at first contraction, and subsequently general dilatation, of the blood-vessels. ' ' The heart is unable to force the small amount of blood through the empty vessels. Its own mus- cles are insufficiently supplied with oxygen, and it gradually ceases to beat. The great lowering of the temperature of the body can be explained by the diminished blood-pressure, and consequently the increased difficulty in providing oxygen for the tissues, or by the retarded flow of blood and the consequent increase of the loss of heat, or finally by the direct influence upon the heat-centre. ' f Thus the theory of Fischer is extended so as to include a vaso- motor paralysis of the whole vascular system. This view is accepted by Mansell-Moullin, who considers it an enormous advance on all previous views, but still cannot accept it as thor- oughly sufficient to explain all the phenomena of shock. He assumes these vaso-motor changes to be produced by inhibition, rather than by simple reflex paralysis, and, arguing on this basis, suggests that the same power may be the direct and immediate agent influencing the nerves that govern sensation, motion, and volition as much as those that control the walls of the blood-ves- sels. The molecular action which constitutes nerve-force may be interfered with, perhaps even interrupted, not only in certain cen- tres that control the heart and vascular system, but also in other centres. " Shock is to be regarded as an extreme and general man- ifestation of that inhibition with the power of which, as regards a few organs, physiology has made us acquainted. ' ' "In short, ' ' he concludes, ' ' shock is an example of reflex paralysis in the strictest and narrowest sense of the term — a reflex inhibition, probably in the majority of cases general, affecting all the functions of the nervous system and not limited to the heart and vessels only." The vaso-motor theory is also held by Gross, for he states that shock is essentially dependent upon reflex paralysis of the entire circulatory system, but especially of the heart and abdominal ves- sels. It has gained numerous adherents in Germany, among whom may be mentioned Kulenburg and Schede. Grceningen, however, takes exception to the vaso-motor- paral- ysis theory, and shows that Goltz himself did not regard this as shock, but rather as syncope or ' c fainting. ' ' Many of the symp- toms of shock can, he acknowledges, be explained by this theory, particularly those belonging to the circulation — not those, however, connected with motion and sensation. The anaesthesia and paresis produced in the posterior extremities of a rabbit after ligature of the abdominal aorta do not correspond to those symptoms produced SHOCK. 281 by shock. The return of blood to a part thus rendered anaemic is usually exceedingly painful, and there are also peculiar creeping sensations. No anaesthesia is produced by the Esmarch bandage. In shock there is no sensation whatever in the muscles. Anaemia of the brain is one of the symptoms of syncope, not of shock. If Fischer's theory were correct, the signs of shock and hemorrhage would be the same, but, as will be seen later, there are important differences in this respect. In rabbits subjected to the Goltz exper- iment Grceningen was unable to demonstrate an anaemia in the peripheral arteries and muscles. In rabbits dying from shock he found the abdominal arteries and veins empty. All possibility of hyperaemia of these vessels may be removed by administering Cal- abar bean to these animals, and yet the symptoms of shock may be produced. Many claim that in the mammalia sufficient blood can- not be made to collect in the abdominal vessels to produce this so-called "intravascular hemorrhage." Division of the splanchnic nerves in animals does not produce the symptoms of shock. Cases of sudden abdominal plethora following premature delivery, or of sudden emptying of effusion from the abdominal cavity, are incor- rectly called "shock," according to Grceningen, being in reality brain-anaemia. In addition to these arguments, there may be adduced the prac- tical experience of those surgeons who are accustomed to operations in the abdominal cavity. It has certainly been the writer's expe- rience that the symptoms of shock are not accompanied by any marked change in the blood-supply to the abdominal vessels. A careful analysis of this theory shows, therefore, conclusively, that it does not account satisfactorily for all the symptoms of shock. Many surgeons regard shock as a sort of heart failure, a tem- porary paresis of the muscles of the heart. Savory, whose arti- cle has long been an established authority on shock, says: "The heart is powerfully affected through the nervous system, and its action is arrested." Blum has endeavored to explain the func- tional disturbance of the heart in shock by the action of the pneumogastric nerve similar to that caused by experimental irri- tation of the nerve, which produces either a diminution in the num- ber of beats or a sudden interruption of the heart's movements. This explanation would not account for those cases of shock in which the rapidity of the heart's action is increased. Irritation of this nerve does not always produce the same changes in blood- pressure, whereas in shock there is always a general and considerable diminution in the blood-pressure. This theory, moreover, does not 282 SURGICAL PATHOLOGY AND THERAPEUTICS. explain the weakness of muscular action and the diminished sensi- tiveness and many other symptoms of shock. In cases of irrita- tion of the pneumogastric nerve produced in man by pressure upon the carotid region the number of pulse-beats per minute is dimin- ished one-half, but the beats continue to be strong, as does also the action of the heart. The arterial pressure was temporarily dimin- ished, but afterward was above normal. Grceningen observed the case of a hussar who was kicked on the left side of the neck by a horse. In addition to a paralysis of the left vocal cord, there was, for several days, a remarkable reduc- tion of the heart-beats to thirty per minute. The pulse was, how- ever, strong and the heart's action good, although slightly irregu- lar. Meyer found that by electric stimulation the heart's action could be arrested for a minute in warm-blooded animals, but he was unable to produce any permanent impression upon the motor apparatus of the heart. Finally, post-mortem examinations show that irritation of the pneumogastric causes arrest of the heart in diastole. In cases of death from shock the heart is often found contracted and empty. It need hardly be added that paralysis of the heart produced by irritation of the pneumogastric nerve cannot be accepted as the cause of shock on such evidence. Many of those authors who have been inclined to accept the vaso-motor theory of shock have nevertheless not been fully satis- fied with its capacity to account for all the symptoms. Mansell- Moullin's opinion on this point has already been quoted. The same view is held by Mitchell, who says: " Either the shock of a wound causes paralysis of vaso-motor nerves and sequent conges- tion, with secondary alterations, or it destroys directly the vital powers of a centre. Now, there is no reason why if shock be com- petent to destroy vitality in vaso-motor centres or nerves, it should be incompetent to so affect the centres of motion and sensation." Cooper was clearly of the opinion that death in some injuries was caused by both direct and indirect shock to the nervous sys- tem. Billroth undertook to explain the change thus produced as a molecular disturbance of certain portions of the brain. Brown- Sequard recognizes an irritation of the cervical cord, the medulla, and the neighboring central structures as shown by the effect upon the vagus, the sympathetic, and sensitive nerves. There is, he thinks, a weakening also of the nerve-power at the respiratory centre. One of the most thorough and complete studies of the action of the nervous system in shock has been made by Grceningen. An SHOCK. 283 indication of this action is given by Leyden, who ascribes the phe- nomena of shock to a powerful irritation either directly upon the cord or indirectly through a peripheral sensitive nerve, by which a profound molecular disturbance is produced in the nerve-tissue, which is thereby incapacitated from receiving less intense stimuli. The functions of the cord may thus be paralyzed or be reduced to a minimum. Among these functions there must be included not only sensation and motion, but also those which preside over the heart, the vaso-motor nerves, and the respiration. "The brain," he says, "does not participate, the mind is clear: it is rare that stupor, coma, or delirium is present." Let us see for a moment what the result is of the functional activity of the nerve when subjected to a mechanical irritation. If a sensitive nerve is irritated, a change takes place in its equilibrium which is transmitted peripherally and centripetally. As to the centrifugal change nothing is known. The centripetal irritation brings about a change which is called "sensation." In the nerve as well as in the nerve-centre there is a certain amount of consump- tion of tissue, perhaps also a molecular change. In fact, it is known that after repeated irritation there is a chemical change in the nerve, and that its power of responding to further irritation is diminished. The mere act of function, therefore, brings about a change which is called "fatigue," and, when extreme in degree, " exhaustion." The fatigue disappears after a certain interval with rest, and the nerve resumes its former power of responding to irri- tation. In the case of the motor nerve the irritation expresses itself centrifugally in muscular action. Here also both nerve and muscle may become exhausted by repeated irritation. As Savory puts it, "Action involves exhaustion, and repose is needed for repair. The greater the effort, therefore, the greater the exhaustion." The exhaustion of the peripheral nerve de- pends partly upon the degree of the irritation, and partly also upon the suddenness with which it is exerted. It follows, therefore, that a single sudden maximum irritation produces the highest degree of exhaustion. Experiment shows that the irritation is not confined to the nerve alone, but spreads from its point of origin to certain portions of the central nervous system. So far as the amount of the irritation goes, Grceningen recog- nizes four degrees: (1) The lowest is without perceptible action on the nerve; (2) the second disposes of the sense of feeling, such as touch, sight, hearing, taste, and smell; (3) a stronger irritation effaces more or less the acuteness of these perceptions, and brings 284 SURGICAL PATHOLOGY AND THERAPEUTICS. out prominently the sensation of pain or of such disagreeable sen- sations as loathing, disgust, etc. ; and (4) the highest degree of irritation destroys all sensation either temporarily or permanently. Bach lower degree of irritation leads insensibly up to a higher one. The sensation of heat and cold may merge into that of pain. So with the other senses: a strong light may blind, an intensely loud noise may cause deafness. Again, a higher degree of irrita- tion prevents the perception of one of lower grade : the lips are bitten to suppress the pain of an operation. A maximum of irritation may be reached when all special senses are destroyed, and even pain itself is not felt. With all these changes of func- tion the nerve remains anatomically the same, to all appearance. The paralyzed nerve and the nerve afflicted with the most intense neuralgia may have no marks to distinguish one from the other. The disturbances recorded are therefore considered purely func- tional. Let us now look at the nerve-centres. The change in them produced by irritation is usually called "reflex inhibition," but the phenomena thus produced can as readily be explained by the theory of fatigue of these centres caused by over-irritation. Reflex paralysis is an example of fatigue of the nerve-centres. I^ewisson showed that if the kidney of an animal was seized and squeezed by the hand, a temporary paralysis occurred in the posterior extremities and reflex irritability was for the time destroyed. Mitchell reports numerous cases of reflex paralysis following injuries to nerves. Here exists paralysis of the motor apparatus as the result of irritation of a sensitive nerve. These paralyses were in remote regions and unconnected with the injured limb, and they appeared after the first shock of the injury had subsided. Langenbuch showed that after nerve-stretching the pulse was smaller and more frequent or slower, the breathing more super- ficial or changed in rapidity. From these examples it is seen that during the simple process of innervation the nerve-centres may become fatigued to a greater or lesser extent, and that when the irritation of the peripheral nerves is very intense the functions of those portions of the cord receiving or transmitting these impressions may be temporarily interrupted. A condition of fatigue or exhaustion is thus pro- duced that shows itself in a weakening or suspension of the sen- sitive and motor functions of these portions of the cord. The changes which are due to exhaustion must not be con- founded with inhibition. The reflex centres are a portion only SHOCK'. 285 of those that are affected. The motor centres are also paralyzed, sensation is weakened, the perception of pain is benumbed, the temperature falls, respiration is less active, the vaso-motor centres are enfeebled, and the strength of the heart fails. As Grceningen says, the spinal cord up to its point of origin from the brain is sud- denly overwhelmed, as it were, and can only regain its vitality after a complete rest. It has hitherto been supposed that the nature of this condition of the cells of the cord was not demonstrable by any method of examination, and the change which takes place was therefore regarded as molecular, such as one might expect to find in a purely functional disturbance. The observations of Hodge, how- ever, are very suggestive in this connection. This observer has made a microscopical study of changes due to functional activity in nerve-cells, hoping to find alterations corresponding to those seen in the cells of a gland which is performing its functions. The gland-cell during rest becomes filled with granules, and dur- ing secretion these granules pass out, generally leaving the cell shrunken. " The necessity for rest in a gland-cell is made appar- ent by its loss of substance. If nerve-cells do not lose substance or change in some way, why are we tired at night?" To test this question Hodge subjected the spinal ganglia of frogs and cats to electric stimulation for several hours, comparing the changes observed in the cells with the normal cells and with stimulated cells after a period of rest. He also studied the effects of normal daily fatigue in sparrows, swallows, and bees. The ganglia of birds obtained in the early morning were compared with those of birds killed at the close of a hard day's work. He concludes that metabolic changes are as easy to demonstrate microscopically as similar processes in gland-cells. These alterations consist in a marked decrease in the size of the nucleus, and a change from a smooth and rounded to a jagged, irregular outline. There is a loss of the open reticulate appearance of the nucleus, and it takes a darker stain. There is a slight shrinkage in size with vacuolation in the cells of the spinal ganglia, and considerable shrinkage with enlargement of pericellular lymph-space for cells of the cerebrum and cerebellum. The protoplasm does not take the staining mate- rial so well as when in its normal condition. There is a decrease in the size of the nuclei of the cell-capsule when present (Fig. 64). These interesting results seem to throw new light upon the condition of the ganglia of the cord and medulla in the condition known as shock, and render the supposition highly probable that 286 SURGICAL PATHOLOGY AND THERAPEUTICS. in this profound functional disturbance similar changes may be found which may gradually disappear after an interval of rest. Some writers undertake to distinguish several varieties of shock. That variety of which a brief clinical picture has already been given is the most frequent, and is called by some the ' ' torpid form of Fig. 64. — Ganglion-cells from the Cord of a Cat : a, cell stimulated seven hours ; b, resting cell. shock. ' ' Travers in his account of shock uses the term ' ' prostra- tion with excitement," which was intended to describe a particu- lar form of shock. About this variety, which has frequently been mentioned by subsequent writers, there has been much discussion. Mansell-Moullin thus describes it: " The patient tosses wildly and vaguely from side to side as if frantic, complaining of a fearful oppression and want of breath, with presentiments of death and a feeling of total annihilation; often shouting again and again the same thing Xo encouragement is of any use: the conscious- ness is unclouded," etc. Cheever thus concisely defines this condi- tion: " Typhoidal delirium, a dusky flush over the malar bones, dull eyes, intermittent pulse, jactitations, exhaustion, death." Travers in his account of this condition quotes two illustrative cases, one of which appears to be an attack of acute mania follow- ing injury to a person who had previously been insane. The other, a rapidly-fatal case, closely resembles one of fat-embolism. In severe hemorrhage there is a peculiar restlessness which might show itself notwithstanding the accompanying shock, but hardly to such an extent as in this form of shock. There are, how- ever, cases where little or no bleeding has occurred when after an injury there is immediately great excitement. Mitchell has described graphically several such cases in his article on "Inju- ries of the Nerves." In one case of gunshot wound of the right SHOCK. 287 wrist-joint, injuring the ulnar and median nerves and causing cere- bral excitement, the patient, who was a colonel, ran along the line of his regiment "half crazed,' ' in a state of wild excitement, and presently fell insensible, but not from loss of blood. In another case of shot-injury to the right median nerve the patient, also an officer, was helped to the rear, talking somewhat incoherently about matters foreign to the time and scene. He was very feeble, but lost little blood, and he had not the least remembrance of hav- ing been shot or. of any event which followed an hour afterward. Grceningen, although inclined not to accept this form of shock, suggests that it may be one following a condition of exaltation occurring after injury, and Roberts, speaking of delayed shocks, says: "Another explanation I venture to offer for some of those cases is the reactionary mental exhaustion that may occur after mental excitement and simulate shock." It is probable that some of these cases may be ascribed to that condition known as "delir- ium nervosum" or "delirium traumaticum." The so-called secondary or delayed shock may be due to sec- ondary complications ; it is probable that the term originated at a period when the pathology of fat-embolism or septic infection was less understood. In certain cases of shock the patient may some- times linger for one or two days before finally succumbing to exhaustion, and in this sense there may be such a condition, but it is usually called "protracted shock," and is hardly to be classed as a separate variety. Gross describes a variety known as insidious shock, which the writer thinks many surgeons will recognize as characteristic of true shock. The symptoms are of a marked character, however, and well calculated to deceive both patient and practitioner. "The person, though seriously injured, congratulates himself upon having made an excellent escape, and imagines that he is not only in no danger, but will soon be about again The countenance in this form of shock has often a peculiarly melan- choly expression, as if foreshadowing the fatal event; a sad smile plays upon the lips and illumines the lower part of the face, while the upper part wears a gloomy aspect in striking contrast with the other." It seems to the writer that in such cases there had been an attempt at reaction which had failed. The cheek may be flushed slightly and the skin be dry and warm; but the pulse, although stronger, is easily compressed, and it is evident to the careful observer that the patient's condition is most critical. He may greet you w T ith a cheerful ' ' Good-morning, doctor, ' ' and when 288 SURGICAL PATHOLOGY AND THERAPEUTICS. asked how he feels will respond, ' ' Fine ;' ' and yet the fatal end may come only a few hours later. Several writers speak of local shock. Pirogoff mentions u la stupeur locale." Grceningen defines it as peripheral shock. It should not be confounded with the bruised and benumbed frag- ments of tissue in the immediate neighborhood of a wound. It seems to consist in diminution of sensation and of motion in the adjoining apparently healthy tissues, which is probably of central rather than of local origin. Gussenbauer claims to have seen this condition even when the symptoms of general shock have been very slight. It is analogous to some of the reflex paralyses so often observed, but in this case it is near rather than remote from the wound. Berger has noted in some cases a complete hemi-anaes- thesia involving not only the skin, but the adjacent mucous mem- branes. This anaesthetic condition is in some cases so marked that operations have been performed without pain. Many acts of hero- ism of this nature on the battlefield are mentioned by surgical writers. Among the most frequent causes of shock are the severe injuries which surgeons are accustomed to see in hospital practice. Among these injuries are the compound comminuted fractures of the bones of the extremities that are so frequent among railroad employes or machinists. Penetrating injuries involving the viscera are nearly always accompanied by considerable shock, though this primary condition must not be confounded with the septic disturbance which ofteii follows with great rapidity. Injuries of certain organs, as of the testicle and bone, are supposed to produce shock more readily than in other parts. A blow on, or the crush- ing of, the testicle may produce a certain amount of shock. Bris- towe reports a case of severe shock following a blow by a shot which grazed the testicle. Hunter mentions a sudden death dur- ing castration. Fischer reports the case of a fine healthy man who was attacked by an enraged horse. The testicle was seized by the animal, and the scrotum was held for a considerable time between the animal's teeth and severely lacerated. The man died in a few hours from shock. Operations upon the testicle, as conducted at the present time, are rarely followed by the symptoms of shock. Operations upon the urethra, such as catheterism, are often followed by syncope, but it is not in accord with the writer's experience that genuine shock can be produced by this cause. The very extensive operations which are now performed for necrosis do not seem to be followed SHOCK. 289 by shock more frequently than any other operations of the same magnitude. All capital operations, particularly those prolonged over a considerable period of time, produce shock. Primary ampu- tations at the hip-joint were almost invariably fatal during the War of the Rebellion. The method then employed involved serious hemorrhage, which always greatly aggravates the condition of col- lapse due partly to the injury and partly to the operation. This operation was finally prohibited by the surgeon-general. According to Billroth, the evulsion of an arm or a leg is usually followed by a fatal shock. Fischer, however, relates the case of a lion-tamer whose whole left arm was torn from the shoulder-joint by a lion. The loss of blood was very slight, and the patient was so little affected by shock that he was able to walk to the hospital. Loss of blood is a powerful factor in the production of shock, and many of those cases which have terminated fatally may have been largely due to hemorrhage. The present "completed" operation for removal of cancerous breasts is likely to be followed by serious shock if this detail be not attended to. "The more sudden the loss of blood, the greater will be the immediate prostration and the less are the chances of recovery ' ' (Gay). Blows upon the chest are usually not followed by much shock, which is of short duration, and which is due as much to the gen- eral effects of the injury as to the local lesion. " The pit of the stomach ' ' or the abdomen is a much more sensitive region. Examples of shock from this form of injury are innumerable. Vincent relates the following case: "A man received a blow from a stick upon the epigastrium. He had an anxious expression and suffered from oppression, irregular heart-action, and shivering, symptoms which gradually disappeared during the day. In the evening his appetite returned, and he felt well: during the night he died without a struggle. At the autopsy there was absolutely nothing abnormal to be found." Blows received during football or baseball matches have termi- nated fatally with the same symptoms. Such cases remind one of the frog experiments of Goltz, and of Fischer's vaso-motor theory of shock. Doubtless many of these cases may be shown to owe their fatal termination to a weak heart. Grceningen attributes the shock in such cases to the peculiar anatomical distribution of the nerves to the abdominal viscera. Here are found the rich plexuses of the sympathetic system with the large ganglionic masses, most prominent among which is the semilunar ganglion, named by Bichat " le cerveau abdominal." A very powerful irritation may 19 290 SURGICAL PATHOLOGY AND THERAPEUTICS. suddenly be transmitted to the cord and the medulla oblongata, and the subsequent exhaustion of the vital nerve-centres may thus be produced. The writer is inclined to think, however, that a cer- tain number of these cases may be due to the vaso-motor disturb- ance produced by a temporary paralysis of the splanchnic nerves. This theory seems at least more closely in accord with physiologi- cal experiments. Such cases, therefore, should not be regarded as cases of true shock. Blows upon the neck often produce sudden collapse. There has already been alluded to the effect of a blow upon the pneumogas- tric nerve and the symptoms thus produced. In those cases under consideration, however, the patient drops vertically to the ground in an unconscious condition. Prize-fighters are well aware of the opportunity which a blow " upon the jugular " offers to save them- selves, perhaps, from a threatening defeat. Various theories have been offered to explain the nature of this injury. To some path- ologists it is known as concussion of the larynx. Fischer assumed that spasm of the glottis was thus produced. By Claude Ber- nard and others it is supposed that an inhibitory action is exerted upon the respiratory centre through an irritation of the superior laryngeal nerve. It is known that swimmer's cramp is produced by some such powerful stimulus sent to the respiratory centre, and it is probable that the sudden unconsciousness caused by garotting is produced in the same way. A blow in this region would also bruise the cervical sympathetic plexus of nerves, and it is possible that a sudden cerebral anaemia could thus be produced. It seems to the writer that many of these cases should be interpreted in this way and be removed from the category of shock. That true shock may, however, be thus produced seems apparent from cases reported by Maschka, of which the following is an example: A boy, twelve years of age, received a blow from a stone upon the anterior por- tion of the larynx. He fell lifeless to the ground. At the autopsy no local lesion was found and no injury elsewhere. The sudden death may be attributed in this case, in part, to shock and in part to cerebral anaemia. In severe burns which have affected more than one-third the sur- face of the body the symptoms of shock are always well marked. It has been suggested that extensive dilatation of the blood-vessels upon the surface of the body causes diminution of blood-pressure, and that the heart's action is thus weakened. Billroth attributes the symptoms to shock produced by the severe irritation of the nerve-centres through the peripheral nerves, and it is probable that SHOCK. 291 the condition of such individuals is one of true shock. Similar results, according to Gay, may be produced by swallowing irrita- ting poisons, as oxalic acid or corrosive sublimate. The constitu- tional effects of such poisons as prussic acid or nicotine or the poison of serpents should be regarded as collapse due to the action of the poisons rather than to true shock. Sudden death from light- ning is also due to shock. Grceningen reports the case of a sol- dier who recovered from lightning-stroke in whom the symptoms of shock were well pronounced. Cases of sudden death often follow the tapping of cysts, particu- larly in the abdominal cavity. Many of these cases should be regarded as local hyperemias due to the sudden removal of pressure from the abdominal blood-vessels. In some cases when the aspira- tor has been used air has unintentionally been forced into the veins and an embolism thus produced. Moullin reports a case of death in five minutes after tapping the liver for hydatid disease. The only sign of organic disease found at the autopsy was a slightly granular condition of the kidneys. The sensitiveness of the abdominal cavity has already been mentioned. In abdominal operations shock may be produced and he aggravated by prolonged handling of the intestines and the breaking up of extensive adhesions, and the exposure of the viscera to the air, whereby a great amount of heat is rapidly lost. Great shock is caused by a rupture of the viscera, particularly of the intestines. In strangulated hernia the symptoms of shock are often present in a marked degree. Even after the constriction has been relieved fatal shock may supervene. This peculiar condition has been recognized by French writers under the name of peritonisme or cholera herniare. According to Mansell-Moullin, the strangula- tion of a portion of the small intestine, whether in a hernial sac or "by some band within the abdominal cavity, is attended at once by symptoms of the most complete prostration, and may of itself, if left unreduced, be sufficient to occasion death without the produc- tion of peritonitis. The relation of pain to shock has been noticed by many writers. Before the days of anaesthesia such a case as the following, reported by Sir Astley Cooper, seems to have been a not unusual occurrence: A brewer's servant, a man of middle age and robust frame, suffered much agony for several days from a thecal abscess occasioned by a splinter of wood penetrating beneath the nail of the thumb : a few seconds after the matter was discharged by a deep incision the man raised himself by a convulsive effort from his bed and instantly expired. 292 SURGICAL PATHOLOGY AND THERAPEUTICS. If it is recalled for a moment what has been said about the dif- ferent degrees of nerve-irritation, it will be found that very power- ful nerve-irritation, such as usually produces shock, is painless. The higher degree of irritation destroys function. For this reason wounds received during battle are not painful. Stromeyer states that nothing is so surprising to the novice in military surgery as this absence of pain. ' ' Perfect quiet reigns in the hospital ward the first night after a battle. ' ' That anaesthesia has served to lessen shock after operations is probably due to the fact that the nerve-centres are thus protected to a certain extent from powerful irritations from without, rather than to the mere absence of pain. L,e Gros Clark says: "I think the shock of pain is much overestimated: .... it is certain that great and almost continued pain is compatible with protracted life." Grceningen maintains that the theory that shock is caused by pain has not been proven. Mental emotion is accepted by many writers as a cause of shock, but the theory is received with doubt by others. The following case, reported by L,auder Brunton, has been much quoted: Many years ago the janitor of a college had rendered himself obnoxious to the students, and they determined to punish him. Accordingly they pre- pared a block and an axe, which they conveyed to a lonely place, and, having dressed themselves in black, some of them prepared to act as judges and sent others of their company to bring him before them. He affected at first to treat the whole thing as a joke, but was solemnly assured by the students that they meant it in real earnest . He was told to prepare for immediate death. The trembling janitor looked all around in the vain hope of seeing some indication that nothing was really meant, but stern looks met him everywhere. He was blindfolded and made to kneel before the block ; the executioner's axe was raised, but instead of the sharp edge a wet towel was brought smartly down on the back of the culprit's neck. The bandage was now removed from his eyes, but, to the astonishment and horror of the stu- dents, they found that he was dead. Such a case may be due to heart failure from fear and excite- ment. It is generally conceded, however, that all depressing influences, whether moral or physical, contribute to the aggrava- tion of shock. Soldiers exhausted from great fatigue or from star- vation or demoralized by defeat succumb much sooner to shock than do their victorious opponents. The effect of individual temperament is often strikingly shown after severe injuries. Soldiers of the most undaunted courage turn pale and tremble like a leaf after a comparatively trifling accident (Gross). Mitchell reports the case of an officer wounded in the heel SHOCK. 293 who was instantly thrown into a condition of the utmost trepida- tion. His character for courage was undoubted, and a court of inquiry, for which he asked, cleared him on the surgical evidence. Railway injuries are supposed to be a prolific source of shock even in cases where there has been no well-defined external or internal injury. This class of cases, formerly regarded as due to concussion of the spine, has been more recently interpreted by Page as a shock to the nervous system in which a condition is eventually arrived at where the seat of the disturbance seems to be centred in the will-power rather than in any lesion of the nervous system. Cases of this kind may or may not at the time of the acci- dent present the symptoms of true shock. "It is a singular fact that cases attended by symptoms of shock immediately after an accident seldom present the symptoms peculiar to ' shock to the nervous system ' ' (Gay). The subsequent chronic state of the patient should not be confounded with true shock, but is more closely allied to the condition now known as neurasthenia. Age and sex are supposed to have an influence in producing shock, but it is not probable that there is any material difference in this respect. In youth, as in old age, the nerve-centres probably yield more readily to powerful irritations, and this may also be said of persons whose constitutions are enfeebled by alcohol or by disease. Great precautions should be taken during the performance of capital operations upon very young children as well as upon the aged, and the condition of the heart and kidneys should always be inquired into in all cases before operation. At one time it was supposed that individuals in robust health were not so well pre- pared to undergo a severe operation like amputation of the hip- joint as those who were already somew T hat invalided by disease. In the former class of cases there is usually the history of a severe accident with its attendant shock and hemorrhage. Obviously in the second class of cases the operation would be performed with all the advantages that a previous preparation of the patient could give. There have already been briefly alluded to the symptoms of shock in a typical case. The most striking of these symptoms to the observer is the sickly-white hue of the skin, the thin, pale lips, and the contracted features: the expression of the face is frequently so altered that it is difficult to recognize a friend. The pupils are but slightly altered, but the eyes are sunken in their sockets. The sur- face of the body is cold everywhere to the touch, the hands are 294 SURGICAL PATHOLOGY AND THERAPEUTICS. blanched, and the fingers and nails exhibit a bluish color. The sensation of pain is more or less diminished, but a disturbance of the crushed limb will cause the patient to emit a feeble and hoarse cry. Muscular action is greatly enfeebled, so that voluntary move- ments are made but seldom. The excito-motor functions in severe shock are gravely impaired. The lids do not close when the con- junctiva is irritated. Deglutition is difficult. The anal sphincter is relaxed, while the urine is retained. ' ' Under such circumstances, especially when the fifth and glosso-pharyngeal nerves fail to excite any response in the nerve-centres, the gravest fears may be enter- tained that respiration itself will momentarily yield" (Jordan). The inspirations are shallow, but are occasionally accompanied by sighing and convulsive tremors. There is no coma, but the mental condition is one of more or less sluggishness, due doubtless to the central anaemia. The con- dition of the pulse varies with the degree of shock. In the milder forms it is frequently slower than normal, but it is more compres- sible. In the graver forms it is small, fluttering, and at times almost imperceptible. The thread-like pulse is under these circumstances usually more rapid than normal, the heart apparently endeavoring to compensate by frequent action for the feebleness of the current. The strength of the pulse is a most important guide to the surgeon in estimating the severity of the shock. A more accurate gauge of the degree of shock is to be found in the temperature. To determine this point the thermometer should be placed in the rec- tum, and if a fall of two degrees below the normal point is regis- tered, the amount of shock is sufficient to contraindicate operative interference. Much lower temperatures have been recorded from observations taken by placing the thermometer in the axilla. The secretions are often much diminished or are altered in their cha- racter. The urine is scanty; the catamenia may suddenly cease or may appear. Many writers relate instances of suppression of lac- tation. A woman suddenly threw herself between two soldiers to save the life of her husband. The chemical condition of her milk was so altered immediately after that the child at the breast was poisoned by it. The great amount of cold sweat upon the forehead has been explained by the relaxation of the mouths of the sweat- ducts. Vomiting is regarded by some as the primary sign of reaction. One of the first evidences of this change is the return- ing color of the face and the strengthening of the heart's action. Formerly it was supposed that the symptoms now recognized as SHOCK. 295 traumatic fever were simply due to the rebound of the system from the condition of shock, and that they were to be expected as a natural sequence. Reaction is, however, in reality, simply a return of the system to its normal condition. The various functions should therefore, in a case which has been treated antiseptically or where no wound was present, reappear in their natural state of activity. The pulse becomes stronger and fuller, the skin dry and warmer, and the respirations are deeper. The mind regains its self-possession, and the temperature returns to the normal standard. In making the differential diagnosis there are many conditions formerly attributed to shock to be considered which now are recog- nized as due to other causes. It is only in the gravest forms of hemorrhage that the patient's condition is likely to be mistaken for one of shock. The anaemia from loss of blood can readily be distinguished from shock, as it comes on gradually, perhaps, from recurring hemorrhages, and is an affection of a more chronic type. When, however, the patient succumbs to bleeding from some large vessel or in consequence of the laceration of numerous vessels in some extensive wound, his condition very closely resembles that of shock. John Bell has given a vivid picture of such a case: "The face becomes all at once deadly pale, the circle around the eyes is livid, the lips are black, and the extremities are cold. The patient faints, recovers, and faints again, with a low, quivering pulse; he has nausea, and his voice disappears. There is an anxious and incessant tossing of the arms with restlessness, which is the most fatal sign of all. He tosses continually from side to side; his head falls down in the bed; at times he suddenly raises his head, gasping for breath, with inexpressible anxiety; the toss- ing of the limbs continues; he draws long and convulsive sighs; the pulse flutters and intermits with the breathing more and more, and he expires." The prominent distinctive features of hemor- rhage are the anxious expression of the face, the tossing about of the arms, the great restlessness, and the frequent attacks of syncope. Acute septic poison, particularly that occurring after operations or injuries of the abdominal cavity, presents frequently a group of symptoms which might readily be mistaken for shock. A per- foration of the intestine may have taken place, or a gunshot injury of the bowel has permitted the escape of the contents of the intes- tine into the peritoneal cavity. In a few moments' time the appearance of the individual changes and the symptoms of col- lapse are well marked. 296 SURGICAL PATHOLOGY AND THERAPEUTICS. In fat-embolism there exists another cause of sudden death after injuries. Fluid fat may be taken into the open vessels and be carried by the lymphatics into the circulation. Fractures of bones furnish the most typical example of this complication, as do also ruptures and contusions of the liver and severe contusions of the skin and subcutaneous fat. Acute suppurations in tissues rich in fat may also produce fat-embolism. It is also found in a greater or lesser degree in acute osteomyelitis. The most frequent seat of these emboli are the lungs. After reposing for a brief time in the vessels of the lung, the fat-drops are carried onward and dis- tributed to various organs, such as the heart, capillaries, skin, brain, muscles, and kidneys, whence they finally disappear. It is only when large amounts of fat accumulate in this way in the capillaries of the lung that a fatal result is brought about. The symptoms of this complication, which occurs within twenty-four or forty-eight hours after an injury, are sudden pallor, irregular heart-action, dyspnoea, perhaps haemoptysis, or convulsions and death. Fat will be found in the urine. The presence of air in the vessels in small quantities has been shown by experiment not to be injurious, but when a large quan- tity has been introduced during a surgical operation the heart may be filled with air, and then is unable to contract. Death under such circumstances will be instantaneous, and will be attended with the symptoms of syncope. This extremely rare occurrence can only happen, according to Hare, when a pint or more of air has been introduced at once into the circulation. Fainting or syncope is regarded by Travers as differing only in degree from shock. It has already been shown that syncope is due to disturbances of circulation only. Preliminary nausea, ringing in the ears, and dizziness, followed by a fainting fit, during which the patient is temporarily unconscious, are symptoms of acute cere- bral anaemia, and not of shock. In concussion of the brain there are, according to Fischer, an arterial anaemia and venous stasis. The experiments of Koch and Filene showed no central lesion, and they conclude that the vaso-motor centre is not only affected, but that all other cerebral centres of activity are temporarily ex- hausted and paralyzed. There is here a condition closely resem- bling that which in the cord and medulla is called "shock." Some writers, however, point out that there must be some phys- ical change, for the brain is never fully restored to its former con- dition, as the memory of what has happened immediately before the injury never returns, and in this respect concussion differs SHOCK. 297 from shock in its nature. Duret has, in fact, observed a lacera- tion of the floor of the fourth ventricle, due to the forcing of the cerebral fluid from the lateral ventricles through the aqueduct of Sylvius, which is thus dilated, into the fourth ventricle. The symptoms of concussion are, however, essentially different from those of shock: there are both insensibility and a slow and full pulse, symptoms which are sufficiently characteristic. The prognosis of shock is uncertain and doubtful. Shock may be fatal within the space of a few seconds, or the patient may live one or two days and finally die. According to Cheever, if reaction does not set in within eighteen hours after the injury, it never comes. Among the symptoms that enable us to judge best of the patient's condition may be mentioned, first, the pulse, which can be examined with the least disturbance of the patient. A patient may live in a pulseless condition for several hours, but if appro- priate remedies and nursing fail speedily to restore a semblance of pulsation at the wrist, the condition of the patient may be regarded as most grave. Perhaps a more accurate guide, on account of its independence of the emotions of the patient, is the temperature. To determine the temperature properly the thermometer should be placed in the rectum. A temperature of 96 F. is regarded by Redard as indicating severe shock, and is one which contra- indicates any surgical operation. Loss of power in swallowing is considered a symptom particu- larly unfavorable. This indicates, according to Mansell-Moullin, an inhibition of the glosso-pharyngeal centre, which is in the immediate vicinity of other vital centres. The same import may be attributed to insensibility of the conjunctiva, indicating that the fifth pair of nerves is also implicated. Persistent vomiting, showing great irritability of the stomach, and relaxation of the sphincters, are signs that a fatal termination is close at hand. Fortunately, in many cases much can be done toward the pro- phylactic treatment of shock. Cheever calls attention to the relation of the operative procedures of modern surgery to shock, and raises a warning voice against many of its attendant dangers. Operations under anaesthetics, often needlessly prolonged, are ex- hausting, and modern dressings are apt to be tedious and chilling. Great care should be taken against exposure of the patient, and a special costume is often advisable for the proper protection of the trunk or of the extremities. Wet cloths and irrigations favor evaporation and rapid loss of heat. The axillae, the thorax, and, above all, the abdomen, are 298 SURGICAL PATHOLOGY AND THERAPEUTICS. especially prone to deleterious chilling. The prolonged exposure or the handling of certain organs, such as the brain or the intes- tines, is liable to produce shock. If a capital operation is to be performed upon a feeble subject, even* detail of the operation should carefully be planned beforehand, and a systematic effort should be made to reduce to a minimum the time consumed in moving the patient from his bed to the operating table and back again. Many details which on ordinary occasions seem important should be sacrificed to the more important element of time. The scale may be turned at the last moment against a patient who has successfully endured the ordeal of an amputation at the hip-joint by. too much attention on the part of the surgeon to some elaborate detail of suture. kk The old method was a matter of minutes : now it is one of hours" (Cheever). Inasmuch as many of the features of aseptic surgery have been simplified, may we not aspire to add to modern skill the speed of a former generation ? The moment when to operate in a case of shock is a point in which the practice of different surgeons differs greatly. In cases of severe shock it is manifestly bad surgery to add the shock of an operation to that already existing, but it is often a question whether the presence of a mangled and bleeding limb does not retard or pre- vent reaction. While waiting for operation the patient lies upon the table, the limb is encircled by the tourniquet, and the repose and care so important to him at such a crisis cannot be obtained. More harm, however, is done by early operations than by prolonged waiting. A few hours of such rest and treatment as can be obtained often enables the patient to regain sufficient power to carry him safely through the ordeal of an operation. Whatever is done at this time should be so planned as to avoid scrupulously all unnecessary fatigue. Rough handling and fre- quent shifting of the patient are manifestly out of place ' ' when a feather turns the scale." Paget says : " There is perhaps no case in the management of which the courage to do little is more needed. Great energy of treatment may do great mischief." The patient should be placed as quietly and as gently as possible on the bed where he is to remain permanently until reaction is established. The foot of the bed should be raised, so that the weak heart may be able to nourish the exhausted vital centres with blood. Next in importance to perfect rest is the application of heat to the body. Hospital operating tables should be so arranged that diffused heat may be brought in contact with the patient during the opera- tion and the previous period of waiting. Heat should be applied SHOCK. 299 to the extremities and to the neighborhood of the heart. Great care should be taken, particularly in the case of the patient under anaesthesia, to avoid burning the skin. An arrangement by which dry heat could be conveyed from the hot-air register to the bed itself would accomplish this object better than in any other way, and would have the great advantage of avoiding disturbance of the patient. In cases of severe shock it is thought advisable by some to per- form u auto-transfusion;" that is, to bandage the extremities so that the circulation may be limited to a confined area where the organs most essential to life are situated. Such a method involves dangerous handling, and its employment should be advised in exceptional cases only, when other and better remedies are not available. Transfusion is now abandoned, but there may be resorted to, in cases of shock attended with great loss of blood, infusion of a warm salt solution: Sodii chlorid., 3iss. Sodii bicarb., gr. xv. Aq. dest, Oij.— M. The salt solution may be introduced either into the median cepha- lic vein or into the loose subcutaneous tissue of the abdominal walls. Patients endeavor to supply the deficiency of fluid at the vital centres by drinking large amounts of water. If the water is well borne, there is no objection to its use, but in an irritable condition of the stomach it is not likely to be retained. Enemata of water are very valuable under these circumstances. Mumford recommends hot enemata of a weak salt solution. A quart might be given, and be repeated in half an hour. The solu- tion in the exsanguined state of the patient is absorbed with aston- ishing rapidity from the lower bowel. Lange administers a pint of water of the temperature of the body, with the addition of some stimulant, mostly claret, during long operations. This allows of absorption before it is too late. L,ater, there may be given nutrient enemata largely diluted — peptonized beef-juice, milk, and eggs — up to four or five ounces, with the addition of half a pint or more of warm water. The enema should be administered through a flexible catheter attached to a short rubber tube and funnel. By this means high injections may be given. Stimulants given by the stomach should form an important ele- ment in the treatment of shock. To strengthen the heart's action, 300 SURGICAL PATHOLOGY AXD THERAPEUTICS. and at the same time to relieve nausea, black coffee should be given in small and frequent doses; it may be given alone or in conjunc- tion with brandy. In giving alcohol care should be taken not to overload the stomach. Champagne or brandy and soda is often well borne. Brandy may be injected hypodermically when the emer- gency is great, but it should not be regarded as a matter of routine, and should only be used when other and more efficient means of stimulation, such as have already been mentioned, cannot safely be employed. The writer is somewhat sceptical as to the absorption of remedies injected into the subcutaneous tissue of an extremity during severe shock. The thick fatty layers which underlie the integument of the thorax and abdomen are more suited for hypo- dermic medication. Of drugs, opium is probably the most valuable. In small doses it is stimulating, and it brings about a condition of repose which is of the utmost value. It should be given subcutaneously or by the rectum. Digitalis is also a powerful cardiac restorative: as it is not usually well borne by the stomach, it may also be administered subcutaneously or by enema. It should be given in large doses if used at all. Xitro-glycerin also strengthens a failing heart. It may be given in doses of -^inr g r - an d is often of service when digi- talis fails to produce the desired result. Strychnine may be placed upon the list of drugs available in such emergencies: it is highly prized by Grceningeu. A good diffusible stimulant is aromatic spirits of ammonia, which has the advantage of being well borne by the stomach. It is a useful drug to employ in the least grave forms of shock. Remember alwavs that the condition the surgeon has to deal with is one of exhaustion, and that rest is needed for repair. XII. FEVER. To have a clear understanding of the nature of the process known as fever, it will be necessary, first, to study the laws gov- erning the mechanism which maintains the human body at a con- stant temperature. The normal temperature of a human being in a state of health is 37 ° C, or 98. 4 F., and it possesses this pecu- liarity, that under most varied conditions, in the tropics and in arctic regions, there is an extremely slight variation from these figures. The stability of temperature observed in man is shared by birds and mammals, and the arrangement by which this standard is preserved is known as thermotaxis or heat-regulation. The body constantly produces heat by a process of combustion, oxygen being introduced into the tissues and carbonic acid being eliminated. Enough heat is thus manufactured to raise the tem- perature of the body i° C. in half an hour. Were there not at the same time a corresponding loss of heat, the temperature would rise 48 ° C. in twenty-four hours — a height which would be incom- patible with life. To maintain a proper temperature it is necessary, therefore, that there should not only be a given production of heat and provision made for a continuous dissipation of the same, but there must also exist a mechanism by which the two processes are balanced, so that the temperature shall remain at its normal height. If the production of heat should at any time exceed the loss, the temperature would immediately rise; if the production should happen to be less than the amount given oft, there would be a fall of temperature. As a matter of fact, both of these processes are subject to considerable variation. After taking food there is an increase in the amount of heat produced, and a still greater increase after muscular exercise; during rest and sleep the amount produced is somewhat diminished. Under similar conditions there is a cor- responding change in the amount of heat that is given off from the body. The flushed face of one who has just risen from a luxurious repast, the warmth and moisture of the skin and the increased res- piration following active exercise, are indications that the regu- lating process is at work, and that the increased heat-production is 301 302 SURGICAL PATHOLOGY AND THERAPEUTICS. being offset by the cooling down of the unusual amount of blood exposed on the surface to the influence of the surrounding air and by the increased evaporation. In estimating the temperature of the body, particularly when making scientific experiments, it is important to remember that all parts are not equally warm. The body may be likened to a heated globe whose centre has a uniform temperature: a thermometer introduced gradually will grow warmer until it reaches this central point, when the temperature will become constant. The surface will have a considerably lower temperature, owing to the cooling process which is going on, and between the two there will be an intermediate layer whose breadth will vary according to the amount of cooling down the globe is subjected to. These inequalities are greatly modified by the circulating blood. If there has been an increased amount of heat produced, the warmer blood will, on coining to the surface, expend some of its heat in warming up this layer, and will further be cooled by contact with the surrounding cooler medium. It appears, therefore, that there is an automatic arrangement which seems to protect the human body from the ordinary changes to which it is daily subjected; but that this works only within cer- tain limits is evident from the artificial aids which are necessary to man to keep the temperature normal. Light clothing and cooling drinks favor heat-elimination when the atmosphere is unusually warm : the cool water taken internally not only lowers the tempera- ture of the interior slightly, but also furnishes abundant fluid to facilitate evaporation from the surface. Further protection is given also to animals in the varying thickness of their furry coats or in their adipose tissue according to the necessities of the climate or the season. Some animals are less able to preserve their normal temperature than others, cats and rabbits being killed easily by cold baths. The equilibrium is less stable in children than in adults. It will be seen that the change in the calibre of the vessels on the surface of the body is an important factor in the regulation of the temperature in man. In a heated atmosphere the vessels are dilated, the skin becomes unduly warm, and active perspira- tion takes place. If the air be dry, evaporation will be favored greatly, and man is thus able to bear for a short time tempera- tures so high that it was at one time supposed that the power to produce cold existed in the body. If an animal is placed in a chamber heated to from 32 ° to 36 FEVER. 303 C great increase of respiration and heart-pulsation will be observed; also dilatation of the vessels of the skin, as may be seen in its ears and in other places. In a temperature of from 42. 2° to 42. 8° C. there is an enormous increase of respiration, the pulse cannot be counted, all the vessels are dilated, and all the muscles are relaxed; the pupils are also dilated. If kept long in this temperature, death occurs from paralysis of the heart and the vessels. Removal of the animal to a cooler atmosphere before death will be followed by sinking of the temperature below nor- mal. This fall of temperature is due to the great dilatation of the superficial vessels, causing an excessive loss of heat. The low temperature observed after excessive burns is caused in this way, the dilatation of the cutaneous vessels being very complete, owing to the destruction of all muscular action in them. It is probably some such disturbance of the circulation that occurs previous to "catching cold," the dilated vessels on the surface allowing the blood which goes to the internal organs to become suddenly cooled. Anything that tends to weaken the contractility of the vessels^ like too great care in protecting the surface of the body, would favor catching cold; whereas cold bathing exerts a protective action by restoring the tonus of the vessels. The time of the year when sudden changes of temperature occur, as in the early spring, is prolific in such affections, rather than in winter, when the cold is continuous. Although the symptoms produced by the long-continued high temperature resemble fever, yet the condition is not fever, for the temperature found to exist in these experiments is due to the storing up of heat in the body owing to a diminished loss, and not from an increased production. The increased chemical changes of fever are also not present. On exposure to cold under ordinary conditions the skin becomes cooled and the heat-dissipation is considerably interfered with, as less moisture is now exhaled; and when the degree of cold is unusual the shivering bears evidence to marked muscular con- traction taking place, notably in the muscles of the skin and in the blood-vessels, the skin becoming shrunken and the condition known as goose-flesh being produced. If the loss of heat is not sufficiently checked in this way, active muscular exercise will favor a restoration of the normal temperature by an increased production of heat. If a large amount of heat is suddenly abstracted from the body, as in a cold bath, the usual mechanism which regulates the heat-loss will not be sufficient to maintain the temperature, and it is interesting to find that under these circum- 304 SURGICAL PATHOLOGY AND THERAPEUTICS. stances as much as three or four times the normal amount of heat may be produced. The prompt reaction that follows the cold bath in healthy individuals is probably due to this fact. The regula- tion of heat-dissipation is effected by the vaso-motor apparatus: this is partly accomplished by the direct action of the changes of the temperature upon the surface of the body and partly by reflex action through the sensitive nerves. The dilatation of the vessels in a heated skin is evidently due to a vaso-motor paralysis, but the profuse perspiration which accompanies it is not so easily explained. Whether to ascribe it to hyperaemia of the sudorip- arous glands or to stimulation of special nerves presiding over their functions remains still to be determined definitely. Given a steady production of heat, regulation is effected by varying the amount of heat eliminated from the body; but if there is a long-continued or excessive loss of heat, as in the experiment of the cold bath, then regulation must be effected by increasing the amount of heat-production. L,et the atten- tion therefore now be turned to the sources of heat-production in health. Many experiments show that muscular action is followed by an increase of temperature in the muscles. They constitute nearly one-half the whole mass of the body, and are said to produce four-fifths of the heat in health, and even more in fever. A comparison of the electrified and the quiescent nerve indicates the power of nerve-tissue to produce heat. Glands at the time of their function are a fruitful source of heat. It is generally conceded also that in all tissue heat is produced during the assimi- lation of nutritious material. Of these tissues, the muscles must be regarded as the chief source of heat, for in them the oxidation is most active. Even when at rest a large amount of carbonic acid is found in the venous blood which comes from them, and during severe muscular action the amount of carbonic acid exhaled may be increased five-fold. There has already been mentioned an increased production of heat in the cold bath; that is, when a large amount of heat is sud- denly abstracted from the body. This has been explained by an irritation of the peripheral nerves through change of temperature of the skin, producing a reflex action on the nerves going to in- ternal organs, which nerves probably bear some relation to the oxidation-processes. The tissue-metamorphosis — or metabolism, as it is sometimes called — in the muscles at rest is not only affected by cold, but it can also be increased by strychnine and other irritants, FE VER. 305 and can be diminished or stopped entirely by curare. This drug paralyzes the terminal fibres of the nerves and thus deprives the muscles of their innervation; hence the bright arterial color of venous blood and the diminished gas-changes in curarized ani- mals. In cases of paralysis the tissue-change in muscles is markedly affected. The idea of an increase in the amount of heat-production through the nerves is not a new one. It is a well-known clinical fact that injuries to the upper part of the cord have been followed by a fall of the temperature below normal: in a case of crushing of the cord at the fifth cervical vertebra, reported by Hutchinson, the temperature fell to 93 F. In a case of injury in the me- dulla the temperature rose as high as no° F. In cases of paral- ysis trifling disturbances, such as those of digestion, will cause an excessive rise of temperature for a short time. In cerebral hem- orrhage and tumors of the brain there occasionally is a rise of temperature without other evidence of inflammation: just before and immediately after death there may be an excessive rise, the temperature exceeding 108 F. Urethral fever has long been cited as an example of febrile dis- turbance produced by reflex action as the result of local irritation. When the vaso-motor nerves were studied by Claude Bernard, he thought that the sympathetic was a check-nerve to heat-produc- tion, and that the chorda tympani had the opposite function. He therefore called them "thermic nerves," supposing them to influ- ence directly the production of heat going on in the tissues. Brown- Sequard showed, however, that the local rise of temperature in Bernard's experiments was due to the increased flow of blood to the part, and that no production of heat consequently took place. These observations led to a series of experiments to determine whether there existed a special set of nerves which presided over the production of heat, the so-called " excito-caloric nerves." The vaso-motor centre has been placed in the lower part of the floor of the fourth ventricle by Wood and others, and it is also said by some writers to be situated in the anterior portion of the lateral columns. The best authorities are as yet divided on the question of the existence of a special set of thermic nerves, to say nothing of thermic centres, but the general drift of opinion is at present set- ting strongly in favor of such an apparatus presiding over the pro- duction of heat. Ott claims to have discovered four heat-centres. Some recent observations in England have thrown light upon the mode of action of these nerves in producing heat in the muscle. 20 306 SURGICAL PATHOLOGY AND THERAPEUTICS. MacAlister has succeeded in separating the heat-producing or ther- mogenic function of the muscle from its motor function. By elec- tric stimulation of the sciatic nerve of a frog he was able to record the rise of temperature produced simultaneously with motion. It was found after repeated stimulation that the thermometer showed no rise in temperature, while the motive power was still unimpaired. The same independence of the thermogenic from the motor func- tion was observed in warm-blooded animals by experimenting with the influence of cold on the muscles. He concludes, therefore, that the metabolism by which motion takes place and that which results in the thermogenic function are different. The ' ' contrac- tile, stuff " of the muscle is not the same as its " thermogenic stuff." They act differently to stimulation, to repairing influences, and to cold. The thermogenic material which a muscle contains is conse- quently acted upon by nerves which keep up a process of innervation hi the muscle whether at rest or in motion. Gaskell has undertaken to show that this process of innervation is of a double character. He found, on the one hand, that the action of the motor nerves on the muscular fibres of the heart produced contractions (by means of chemical changes in the muscle) which are of a destructive nature ; repeated action exhausts the "contractile stuff." On the other hand, stim- ulation of the vagus or inhibitory nerve is restorative : there is a repair of function of the muscle ; the chemical changes are in this case constructive. The former action is called " catabolism," the latter " anabolism," or assimi- lating or trophic action. It is the stimulation of these nerves by change of air, agreeable surroundings, and other favorable conditions that promotes repair of the tissues and increases the appetite and weight. He infers that the thermogenic tonus of the muscle is preserved in the same way by two opposing innervations, the one tending to build up the thermogenic stuff, and the other disintegrating it by the process of oxidation. Further, Gaskell found, on stimulating the motor nerve of a quiescent muscle, that the con- tracted muscle assumed an electrical condition different from that of the uncontracted or negative variation, and that when the inhibitory nerve is stimulated the muscle exhibits a positive variation. It is possible that fur- ther experiment will show that on stimulating the motor nerve there will be an evolution of heat, and on stimulating the inhibitory nerve the muscle will become cooler. From these observations MacAlister concludes that the muscles of the body have their double nerve-supply. ' ' The one set of fibres are essentially cata- bolic : they set up disintegrative changes in the muscle, which are manifested first by thermogenesis, and secondly by contraction. The other set of fibres, whose path is perhaps anatomically different, are essentially anabolic : they set up reconstructive changes in the muscle which are manifested by inhibi- tion of motion on the one hand and absorption of energy on the other. ' ' It is thus seen that the normal temperature of human bodies is FEVER. 307 maintained by the heat produced from the chemical changes which result from the innervation of the tissues, and particularly the mus- cles, consisting mainly in the absorption of oxygen and the elimi- nation of carbonic acid. The nervous mechanism presiding over this function is probably somewhat analogous in its action to that of the vaso-motor system, by means of which the elimination of heat from the body is effected. The stability of air-temperature is largely maintained by variations in the amount of heat-dissipation, consequently by changes in the circulation in the surface of the body and by evaporation from the skin and the lungs. Changes in heat-production are occasionally also brought about by reflex action. Whether this action is accomplished through a special regulating centre is doubtful: it is more probable that the nervous action thus aroused is exerted through thermic nerves than through the vaso-motor system, as many good observers still suppose. The reader is now prepared to consider the nature of that form of constitutional disturbance which is accompanied by the group of symptoms associated with the name of fever. The most promi- nent and constant of these symptoms is the rise of temperature. Although it has long been recognized that the body was warmer in fever, and although as early as the last century it was discovered, by means of a Fahrenheit thermometer, that the temperature was raised even during a chill, it is only within the recollection of the present generation of physicians that systematic measurements of the temperature were undertaken, and that the relation of pyrexia to fever became generally recognized. Perhaps the earliest symptom of fever is that general sense of lassitude and discomfort known as malaise; but if the patient be examined by the physician at this time, it will be found that there is already a slight rise of temperature and an increase in the rapid- ity of the pulse. The skin of the head and the body feels warmer to the touch, although the extremities may be cold. If the febrile attack is severe and the temperature is rising rapidly, this condi- tion will quickly be followed by the group of symptoms known as the chill. These symptoms are a sense of cold, with coolness of the skin, particularly the extremities ; paleness and sometimes cyanosis of the face, accompanied with involuntary movements of trembling and chattering. The duration of this period may be one or two hours, and will be followed by a sensation of undue warmth. The face will be found flushed, and the sur- face of the body will be considerably warmer to the touch. The patient, who at first crouches over the fife or covers himself ::-5 5 VRGICAL PATHOLOGY AND THERAPEUTICS. with many blankets, now seeks relief by removing the clothing. If the rise of temperature — or the stage of invasion, as it is called — is mz:i :::-.'. the mili is rsrmly zbser: The 5 1 : i; ;. srme ::" fever. :: -v\:.. . is mm rzrirr. vxrith the temremmre remzirs i: its highest point. This stage may be reached in a few hours, or it may be several days before the period of invasion has been completed. The semrz stmze is r:zrz::er:ze i : hem mm zryress :f the skin. by dryness of the tongue, by thirst, by scanty urine, and by head- mhe — izh mme rims zlisrzrbmme :f the rermrs system :":".". :~ ez by the period of defervescence^ during which the skin becomes rrrls: z: times mme is rmfzse rersrirztizr zmz the mmzerzrzre rerzrrs :■: mrrml Tzmirv ::mmles:er:e mere zre irremtmriries ir me termerzr :re — hi:h rrzy be slirhtly rmisez ir : he everirr. :: rmy :':: z my :: : - : mm be". :~ the r :rmm z mzr the temr-ermrre heir,: i mmy mmmlesterte s rsrez title t: slirm: irri:z:i:r.s Ir: fzzm mses there rmy be z rzzm fm". :f :emz«erzrzre. even be'.:™ the r:z- mal, or in the moribund period there may be an excessive rise, ---'.v.:'. : ~iii ever zzrrirre f:r r- sh:rt rime mter fez::: Tire tem- yr:.;:: -.varies ir mm mrzls : ir milzrer mere me rrez: fmrres zmz i: frezyzertly rzrs him: ir :iz petrle me rise :f temr-ermrre is r :: s: rrezt Z m mr me ztmzk the tzztier: mii hzve its: m:i::. the ermrizzim — iii be m:re :r less mrrker m:::v: :: me mmrm :: me rever. The mm: termerrtrre is zs ~mi ':e seer yzsry remzrzez rs me yizmz symr::m :f fever, rs :: is m:re mzsmz: mm zzy ::her syrrrtztr There zre zzmiztemy zrses ir -v'mizh me temrerzmre :s temporarily -; :she: zz zb:ve zz z:zzh by .: zerriem e.imirz- ri:r : :' hem zs ir exmerhmerzs :: —him zztertim hrs zirezzybeer zmie: —him mrrz: be rermzez zs fever zrz :he:e zre ms: i:ss :f her: m :: :'z:zi zzzzzz:z the remremrme mm fm". be".:— me r: rzr.il r-:ir: zrrhm me rrzrress :f zhsezse bz: these mrzmms zre exzerti.mzl There zre zis: s:me :zses :f excessive :: term-miry rise ir remr-ermrre ::: rervzrs ziseises "him. by szme. zre m: remzrzez rs febrile ir rzvzre. K:~ :her shili the rise :f temr-ermrre m zm.zmez f:r- Ore ■:z the eirlies: zttemrts :: exrizir mis rise t^s rmze by Trzzbe ~h: mr z ri:reer ir :he mm : f the temz-erzvzrz ir fever. His :he:r- -z-s :: — z zvzzzzz: izvz'zrz ^zzz: he szrr-:sez. zzzsez z ::rtrz:ti:r : f the zrterizies m the szrfzm ::' the b:-fv rimirishixr rreztiy the hem-elimirmi:r 7mer the ryr> :zz: mztenz. m mv t: rs zm zz: :::: the sersiti*. eress : the FE I r ER. 309 vaso-motor system, makes an unusually intense impression, a rapid rise of temperature follows : in this case there would be a great dif- ference in temperature between the central and peripheral portions of the nerves, and a chill would be the result. The fall of the temperature would be caused by a relaxation of the vessels and a consequent increase in heat-dissipation. According to this theory, no increased production of heat takes place. Since then it has, however, repeatedly been shown that there is not only an increased production of heat, but there is also an increased elimination. The warmth perceived by the hand or by more accurate thermometrical tests shows that more heat is given off than is usual. If in the mean time the temperature remains the same or increases, more heat must necessarily have been produced. The actual amount of heat produced can be determined by calorimetric test, the amount of heat-dissipation within a given time being thus determined, and the heat-production calculated after allowing for certain changes of temperature occurring during the experiment. It may, how- ever, be determined by observing the oxidation process, as will be seen presently. There was at first much opposition to Traube's view, but later there has been a disposition to accept the theory of a diminished loss of heat as an important factor in the production of fever. Rosenthal has recently shown that in experiments upon animals heat-loss is diminished and heat-production is not increased in fever; Maragliano found that antipyretics act by causing a dilata- tion of the superficial vessels, and that when the action of the drugs ceases and the fever returns this relapse is preceded by a new con- striction of the vessels ; Walton has shown by experiment that the symptoms of fever can be produced by a primary shutting in of heat, but he accepts, nevertheless, the view of increased heat-pro- duction in fever. During the chill it may be assumed that there is a greatly- increased amount of heat produced, while the loss of heat is diminished, owing to the contraction of the vessels of the skin. By this contraction the heat-supply is also prevented from reaching the terminal branches of the nerves in the skin, which is the ther- mic apparatus by which heat or cold is perceived. According to Cohnheim, the variations of temperature are perceived by the warming or the cooling of this apparatus, and, owing to the cooling of these nerves, the sensation of chilliness is thus pro- duced. As the heat-loss is diminished, heat must consequently be heaped up in the interior of the body, and the temperature 310 SURGICAL PATHOLOGY AND THERAPEUTICS. must rise rapidly. A change of several degrees within an hour is a not uncommon occurrence under these circumstances. Individuals whose regulating apparatus is easily disturbed are subject to slight chills from various causes. Excessive muscular action, as in mountain-climbing, may increase the heat-production three- or four-fold, and if the heat-elimination is not sufficiently active or if it is too suddenly arrested, a rise of temperature with chill may result. Such a disturbance may prove to be temporary only, but serious congestion may be caused in this way. By the time the second stage of fever is reached it will be found that the temperature has ceased to rise; that the regulating process is not entirely suspended; that the spasm in the superficial vessels passes off; and that there is a free flow of blood through them. In this way the active elimination of heat is re-established. Some authorities look upon heat as an excretory product, like urea. Maclagan says: "Increased formation of any excretory product leads to a stimulation and increased activity of the organ by which it is eliminated;" consequently the increased heat-dissipa- tion soon balances the increased heat-production, and no further rise of temperature takes place. A more careful observation of a patient at this time will show that there are great irregularities in the heat-dissipation, the surface temperature changing from hour to hour, but on the whole the amount of heat lost is much greater than that produced. It will also be found that the heat-production varies somewhat at this stage. The height of the temperature is, consequently, the result of the balance between the two. Heat-production must not be confused with high temperature. The temperature may be high with a moderate production of heat only, owing to diminished loss of heat, and it may be low when the production is high, owing to an excessive elimination of heat. It may be surprising to learn that the amount of heat produced in fever is really not much greater than that produced by a strong healthy man on full diet: it is, however, much greater than that produced by a well man on fever diet and at rest; but the chief point of difference in the heat- production of the sick and of the well man is, that in the latter the extra heat-production is limited to periods of active exercise or following hearty meals, whereas in the sick man the increased production is going on continually. The heat-elimination in fever is most active when the heat-pro- duction is least; that is, during the early stages and height of the fever it is irregular in its action, whereas in health the increased amount of heat produced at any time is rapidly disposed of by free FEVER. 311 perspiration; the insensible perspiration is also more abundant and constant than in fever. The two factors of heat-regnlation are, therefore, acting more or less independently of one another in fever. Coming now to the stages of defervescence, it is seen that the temperature is beginning to fall: this appears to be due chiefly to the fact that the production of heat is now less active. The elim- ination of heat is, however, greater than at any other period of the fever. Whether the perspiration seen at this time is due to the flooding of the cutaneous vessels with warm blood or to an irri- tation of nerves presiding over this secretion is not satisfactorily determined. Under certain circumstances the temperature runs to an unu- sual height, and the condition is then known as hyperpyrexia, the temperature ranging from 108 F. to no° F. This condition is explained in different ways : by some it is supposed to be caused by imperfect elimination of heat, which function has become so profoundly disturbed that the heat-production cannot stimulate it into action. The question now naturally arises, What is the cause of the increased heat-production in fever? It was supposed at one time that local inflammation — of a wound, for instance — was the source of heat-production. The amount is, however, far too little to pro- duce any material change of temperature. It has already been shown that the oxidation-processes are a source of heat in health, and it has long been known that the amount of carbonic acid exhaled from the lungs and of urea excreted by the kidneys is greatly increased in fever. Experiments on fever patients have shown that the amount of carbonic acid eliminated may be increased from 70 to 80 per cent., and that during the chill two and a half times the normal amount may be given off. It is only quite recently that it has been definitely determined that there is an increased absorption of oxygen going on at the same time. Elaborate observations by Lilienfeld showed that both of these gases were proportionately increased in fever — that the change was not qualitative, but quantitative. He proved also that this increase is greatest with the rise of temperature, that the inter- change of these gases is somewhat less active at the height of the fever, and that during the defervescence it sinks somewhat below the normal. He further finds that the oxidation is not most active when the temperature is highest, but is most active before the latter is markedly raised and in the early stages of a rapid rise; moreover, 312 SURGICAL PATHOLOGY AND THERAPEUTICS. that these processes go on just the same in fever if the temperature is kept down by some artificial means, such as a cold bath. He therefore concludes that the increased combustion in fever is not the result of increased temperature — that it can, indeed, take place independently of the latter — but that it is one of the factors which combine to cause the rise of temperature. There is also an in- creased amount of urea usually excreted before the rise of tem- perature begins, which is additional proof that metabolism precedes fever. L. ..... ! &. --™»*>f r .■■--■•/$* •A %'' A ■ *a;\.^ w.. - . A jr 1G> 67.— Infiltration of Muscular Tissue with Streptococci in a case of Septicaemia of Man. The blood-vessels contain numerous leucocytes, but none are found in the surrounding connective tissue. taneous tissues of the thigh (Fig. 8). Sections of the muscles of the thigh showed that all the intermuscular spaces were distended by a mass of bac- teria, and there was no infiltration of leucocytes into the tissues, though the blood-vessels seemed to contain an unusually large number of white blood- corpuscles (Fig. 67). In sections of the kidney the bacteria were demon- strated with considerable difficulty, in spite of the fact that the amount of kidney-substance that could be picked up with a small wire loop gave over one hundred colonies when planted. When found the cocci were in the SEPTICAEMIA. 341 intercellular spaces. Neither in the kidney nor in the muscular tissue was there any suggestion of arrangement of the cocci in chains. This was to be seen only when cultivated outside of the body. The next point to be considered is the mode of entrance of the poison into the body. Of course by far the most frequent route of introduction, as the surgeon sees it, is through a wound which has become infected by the failure of antiseptic precautions in an ope- ration or from the exposure which necessarily accompanies a severe injury. The conditions in a wound favorable for septicaemia are those which accompany gangrene or sloughing of the tissue, although some of the most malignant types of the disease may occur when the wound has been insignificant in size. Septic infection may accompany other traumatic infective diseases, such as erysipelas and hospital gangrene, particularly the latter, and sudden putrefaction of the contents of a wound, such as is likely to occur in an infected wound containing blood-clots or imprisoned pus. Such cases as these would probably be followed by that variety of blood-poison- ing known as saprczmia. But it is not through wounds alone that the virus finds its way into the body. The skin is indeed a sure protection, when in its normal condition, against the invasion of microbes or ptomaines. The mucous membranes are not so protective in character. The intestinal canal is filled with bacteria of various kinds in its entire extent, and under conditions favorable to them they will often make a raid upon the interior of the body. In individuals of broken-down and enfeebled constitutions it is not improbable that an examination of the blood at intervals would show the presence of micrococci. As Cheyne has shown, a local injury or an inflam- mation will furnish a lodging for these wandering organisms, and a focus of infective inflammation will at once be established by which a general infection of the system may be produced. Chau- veau has, in fact, artificially imitated such a disease by injecting putrid material into the veins of animals, and in then producing a local inflammation, such as fracture of a bone. Such cases as these are occasionally seen arising apparently spontaneously in man, and they were at one time supposed to be examples of "spontaneous septicaemia." In these cases an acute or infective inflammation is usually found somewhere to account for the constitutional symp- toms. In former times these foci were often overlooked, perhaps partly on account of the violence of the constitutional symptoms, and it was therefore supposed that a sort of miasmatic infection had 34 2 SURGICAL PATHOLOGY AND THERAPEUTICS. taken place. The origin of such forms can now be traced to various well-recognized surgical affections. One of the commonest of these affections is acute osteomyelitis, which occurs in the long bones of the young following slight injuries or following exposure in individuals of enfeebled constitu- tion. The onset of such inflammation is exceedingly violent, and the conditions for absorption of the virus are unusually favorable. A certain number of such cases die in the early stages of the dis- ease before even suppuration is established. Similar inflammations may occur in other parts of the body, as will be seen presently. It can only be assumed, by way of explanation of the origin of these cases, that an invasion of bacteria has taken place through the intestinal canal, and that they have obtained lodgment at some bruised or weakened or inflamed spot, or that the organisms have obtained an entrance through some minute wound. But in some cases there is direct proof that an infection takes place through the intestinal mucous membrane. Sepsis intestinalis is now a well-recognized affection, resulting usually from the absorption of poisonous substances in food. Vaughn gives an excellent description of the result of poisoning by eating canned meats, sausages, ice-cream, and cheese. In the latter substance he found a ptomaine that he named tyrotoxicon, which is now generally regarded as the active principle in many of these cases of poisoning. This observation would place this group of affections in the class of sapraemia or poisoning by a chemical substance — an "intoxication." It seems difficult to believe that the numerous intestinal bacteria play no part in the process, and that in addition to the "intoxication" there is not also, to some extent, "mycosis" of the system. This is, indeed, the view of many observers, but Vaughn's studies led him to relegate the intes- tinal bacteria to quite a subordinate role in the process. With regard to the respiratory tract as an avenue of entrance for the poison of septicaemia, it does not, at first view, seem prob- able that an example of such a mode of infection should ever occur. Ogston, however, recognizes as one of the mildest forms of sapraemia the sickness and nausea produced by a bad smell, which, as he says, is but a ptomaine of putridity, and which under certain contingencies may produce serious symptoms. Some of the cases of fever supposed to be due to sewer gas do not differ essentially from the more strictly surgical forms of blood-poisoning. Gussenbauer suggests that the inhalation of such gases may predis- pose the system to the invasion of bacteria. A curious fact in this SEPTICEMIA. 343 connection is the supposed immunity acquired against infection of this kind by individuals who are habitually exposed to foul odors, as those who work in the sewers or in the dissecting-room. To the surgeon such a mode of infection is comparatively rare; the physi- cian, however, meets with it in many of the epidemic forms of disease. Examples of infection through the genito-urinary tract occur rarely when this region is still in a normal condition. The follow- ing is perhaps such a case: A man thirty years of age entered the hospital with symptoms of stone of a few months' standing. A phosphatic calculus of about 80 grains was removed 03- litholapaxy, the operation lasting tw T enty minutes. No blood flowed in the urine after or during the operation. Examination of the urine showed no disease of the kidneys. The patient's general health had always been good. The temperature, however, ranged in the neighborhood of 105 F. for a week, during which time the urine was loaded with bacteria. The fever gradually subsided, the bacteria disappeared, and the man made a rapid recover}- at the end of that time. Imperfect asepsis had been preserved during the operation in all probability, and infection through the urinary tract had conse- quently taken place. The danger of operating upon those whose kidneys are in the condition known as ' ' surgical ' ' is familiar to all surgeons. In this case an organ already contending with bac- terial inflammation of a chronic character suddenly ceases to resist invasion as the result of the shock and depressing influence of a surgical operation or of a fresh infection. Passing now to the symptoms of septic infection, the purely toxic form will first be considered, inasmuch as some authors, par- ticularly recent writers, dwell upon the importance of distinguish- ing cases of saprsemia, or pure ptomaine-poisoning, from the other forms, although the writer does not feel that we are yet fully justi- fied in recognizing this as a separate disease in the present state of our knowledge. The most typical example of saprcsmia is usually found in the obstetric wards, and is there due to the putrefaction of retained clots or placental fragments in the uterus. The poison may be absorbed from the mucous membranes of the vagina or the uterus with their rich lymphatic connections, or through open wounds in the vaginal mucous membrane, or at the point of attachment of the placenta, or through the uterine sinuses directly into the circu- lation. The preliminary chill, which usually marks the onset of many acute forms, is generally wanting. There is, however, a 344 SURGICAL PATHOLOGY AND THERAPEUTICS. rapid rise of temperature to ioi° or 103 F. , rarely higher. The changes in the blood are marked, the patient becoming anaemic; there is some leucocytosis, but the chief change is in the number of red corpuscles, that varies directly with the degree of blood- poisoning. In the early stages there is headache with nausea and vomiting, and later diarrhoea and purging. The blood, the nervous system, and the intestinal canal appear to be the parts chiefly attacked by the poison. The inflammatory condition of the intestinal canal may be due in part to an effort of the system to eliminate the virus. The temperature is contin- uously high, and delirium supervenes, followed by coma in fatal cases. In no disease are the results of treatment more striking and satisfactory than in this, a prompt removal of the putrefying con- tents of the uterus being followed in a few hours by a fall of tem- perature, a disappearance of all alarming symptoms, and a return to a comfortable condition. The removal of the clots or placental remains can be effected either manually and instrumentally or by an antiseptic douche, which should carefully be introduced into the interior of the ute- rus, care being also taken against the introduction of air into the uterine sinuses. This douche should consist, according to Duncan, in cases where the state of putrefaction is advanced and the lochia consequently are exceedingly foul, in the injection of a solution (1 : 40) of carbolic acid. The writer takes occasion, however, to warn the surgeon that solutions of this strength are liable to pro- duce symptoms of carbolic poisoning if used in large quantities or in repeated doses, and that in surgery such solutions are now used less frequently than formerly. Often a dose of ergot may alone be sufficient to evacuate the uterus, in which case it will be well to be content with a vaginal injection. The writer has dwelt upon a subject not strictly surgical because there occurs in the puerperal state the best example of this type of poisoning, and the lesson it conveys as to treatment is so obvious as not easily to be forgotten. The surgeon cannot always expect, however, to accomplish so satisfactory a cure, for not infrequently the poison of septicaemia will be mingled with that of sapraemia, and the improvement will therefore be but temporary, unfavorable symptoms reappearing when the period of incubation has passed and when the virus is beginning to act upon the system. Unfortunately, cases of the pure sapraemic type are rare in sur- gery. The condition most favorable in the wound for the develop- SEPTICAEMIA. 345 ment of the disease is the presence of unusually large quantities of blood-clot or serum, or of gangrenous or sloughing tissues, particularly in such situations as prevent an easy access of the pent-up materials to the surface. Such conditions occasionally occur after opening a deep-seated abscess, when large veins have been exposed, or in the peritoneal cavity after the removal of abdominal tumors. All such fluids, if they are preserved in an aseptic condition, will produce nothing more than a slight rise of temperature (aseptic fever) if absorbed, but if allowed to remain stagnant they are, in certain situations — as in the vicinity of the intestinal canal — extremely liable to bacterial invasion, even though external asepsis has been successfully carried out. It is, therefore, highly important that thorough drainage should be provided when a tendency to oozing of blood is liable to occur, particularly in the peritoneal cavity when the wonderfully rapid absorbing action of the perito- neum has been impaired. The accompanying chart represents the fever-curve in a case of resection of the knee-joint. On the fourth day an infection of the wound occurred from a concealed sinus : opening and disinfection of the wound and sinus were promptly followed by a fall of temperature (Fig. 68). 104 103 10 10 100 99 98 96 A 1 2 3 4 5 6 7 8 9 10 II 12 4- 'J / A / \ I / 1 J i J \ /■ 1 J u L- 8- 7 -^= \i / C Fig. 68. — Sapraemia. The constitutional disturbance in true septicemia does not differ materially from that just mentioned in the initial stages. The main difference consists in the more gradual onset of the disease, a period of incubation existing before the presence of the virus makes itself felt. Usually after a capital operation there will be considerable elevation of temperature even in favorable cases. At the end of 346 SURGICAL PATHOLOGY AND THERAPEUTICS. forty-eight hours, however, an improvement is usually expected T and for this reason, probably, there has arisen the popular belief that by the third day the surgeon is able to tell whether the patient is going to make an uncomplicated and rapid recovery or not. If at this time the temperature still remains high, or even increases, some unfavorable conditions are liable to be discovered existing in the wound, and on removing the dressing it will probably be found that a septic infection has taken place, and that one or more of the symptoms of infective inflammation are present. Occasion- ally the removal of stitches, or the effective disinfection and drain- age of the wound, may be sufficient to arrest further constitutional disturbance, but if genuine septicaemia develops, whatever may be done to the wound will be of little avail. With the access of fever which marks the beginning of the dis- ease there is, as in saprsemia, rarely a chill. Great prostration with headache and loss of appetite are soon followed by a typhoid- like indifference to all surroundings, a sort of stupor which renders the patient disinclined to make complaint as to his condition or feelings. The variations in the temperature correspond more or less accurately with the local condition of inflammation in the wound, but in some of the most malignant types the wound itself may be a trivial one and the amount of local septic disturbance may be comparatively small. There is a slight morning remission, but the fever is essentially a continued one, and it increases in degree, with perhaps a rapid rise at the end of a fatal case (Fig. 69). \r\A 1 2 3 4 5 6 7 8 9 10 II 12 IU4 mo / ^1 + lUo- ino 1 f / ^ y' \C\\ / / IUI inn f IUU C\C\ 99 J 98- 97- Fig. 69. — Septicaemia. Gussenbauer calls attention to a certain class of cases in which there is subnormal temperature caused by the absorption of ammo- nia compounds, to which he gives the name "ammonsemia." Such a condition may be seen in connection with gangrenous hernia, and SEPTICEMIA. 347 it has even been mistaken for shock. Many such cases doubtless belong to the sapraemic type of blood-poisoning, and, coming immediately after the operation or injury — such, for instance, as a penetrating gunshot wound of the abdomen — might readily give rise to such an error of diagnosis. Until Marion Sims called attention to the importance of laparotomy and to the toilet of the peritoneum in such cases, many a patient was undoubtedly allowed to die of supposed shock who otherwise might have been saved from a rapid poisoning. The effect which the poison has upon the lymphatic system is often well marked. In some cases there is seen from the begin- ning an acute lymphangitis, but this symptom belongs to a class of cases that will be considered later. In those cases which do not run a very rapid course an enlargement of the lymphatic glands may be noticed, particularly in the parts communicating directly with the wound. The entire lymphatic system will be more or less affected, and this condition will show itself in an en- largement of the spleen, which occasionally may become so hyper- trophied as to produce a distinct area of dulness. This is usually considered one of the characteristic symptoms of septicaemia, and should always be sought for. Another symptom characteristic of the disease is diarrhoea, which is usually not troublesome, and which can without difficulty be controlled by appropriate remedies. It is, however, frequently present, and may aid in the making of a diagnosis. At times the symptoms of gastro-enteritis are more acute, and sometimes there are rice-water discharges and vomiting, even when the route of the infection has not been through the intestinal canal, as in cases of canned-meat poisoning. A slight discoloration of the skin, with a faint yellow tinge of the conjunctivae, is sometimes seen in this disease, but the icterus is far less marked than in pyaemia. It is probable that the icterus is haematogenous, and is dependent upon the breaking down of the red corpuscles. In addition to this change in the blood there will probably also be found an increase in the number of white corpus- cles and the presence of micrococci, if the blood is examined during life. The pulse is rapid, and in dangerous cases is weak. Heart fail- ure is a complication that the surgeon must be prepared to meet. Symptoms of ulcerative endocarditis or of pericarditis are not likely to be observed. Scarlet eruptions of the skin are not uncommon, as has been shown in the remarks on surgical scarlet fever in the preceding chapter. The character of the rash may vary greatly 34 8 SURGICAL PATHOLOGY AND THERAPEUTICS. from simple erythema to a pustular or hemorrhagic eruption. Hoffa has obtained from the skin of patients thus affected micro- cocci which were not pyogenic. The eruption is explained by him as being caused by them, their presence bringing about a capillary thrombosis in the vessels of the skin. It is hardly probable that the bacteria are present in sufficient numbers to produce an actual plugging of the vessels, but they probably act upon the fibrin-ferment in a way to produce a considerable coagulation of blood in the capillary vessels. A similar condition of the vessels of the retina gives rise to retinitis, which, however, does not make itself perceptible as a symptom, but it may sometimes be detected with the ophthalmoscope. These are the principal symptoms to be observed in severe examples of the disease. In milder forms many of them may be wanting. It is of course difficult to determine precisely when a case of surgical fever reaches that degree of severity which justifies the surgeon in giving a diagnosis of septicaemia, but undoubtedly many cases of genuine septic infection of the system are seen that eventually recover. In such cases the disease may assume a chronic form, running a course of two or three weeks' duration. A marked feature of this type is enlargement of the spleen, which may become a tumor of considerable size. The temperature does not rise so high as in the acute form. In the more malignant cases of septicaemia as the disease pro- gresses the wound will become unusually foul. Heuter, indeed, thought that the smell of a septicaemic patient was characteristic, and that a good surgeon ought to be able to make the diagnosis with his nose. With the powerful antiseptics of to-day he could hardly be expected to rely upon any such symptom. The temperature continues to rise, and the skin, which is first hot and dry, later becomes bathed in perspiration. The icteric hue will now be more marked. The prostration is at this time very great, and the patient has a listless expression. Septicaemic patients are not usually troublesome; they make but few com- plaints even when questioned as to their feelings. Their condition has been described as one of " euphoria." There is a dull expres- sion on the face that finally gives place to a sort of death stare, so familiar but unwelcome a sign to the unsuccessful operator. Bron- chial symptoms, with quickened respiration, make their appearance, diarrhoea continues, and the stools are offensive; the urine is con- centrated and scanty. Stupor is succeeded by delirium, and with the appearance of coma the patient becomes moribund. SEPTICEMIA. 349 The post-mortem appearances of septicaemia show but little evi- dence of gross change in the internal organs. A more careful study of them, however, has shown that considerable alterations exist. Putrefaction of the cadaver takes place more rapidly than in the bodies of those who have died from any other disease. The blood is of a tar-like consistency and shows little tendency to coag- ulate; it contains innumerable bacteria, both micrococci and bacilli. Cultures taken from the interior of the heart and from the juice of internal organs often yield a growth of streptococci. Congestion of the pia mater is often found, and sometimes also punctiform extravasations in the deeper portions of the nerve- centres. As a rule, however, there are few changes seen in the nervous system. The muscles sometimes present a brownish dis- coloration. In chronic septicaemia there may be some evidence of endo- carditis in a thickening of the endocardium, but the ulcerative form of inflammation is not usually seen in this disease. Slight effusions in the pericardium and in the pleura are, however, found. There may be some oedema or passive congestion of the lung, and some increase in the secretions of the bronchi. The principal change is found in the alimentary canal: here the evidences of a gastro-intestinal catarrh are marked. There is a cloudy swelling of the submucous tissue of the stomach, particularly in puerperal cases. The principal points of inflammation of the intestines, according to Gaspard, are in the duodenum and the rectum. The membrane is swollen, of a mottled color, and is dotted over with punctiform hemorrhages. According to those who have experi- mented upon animals, this is one of the most constant symptoms of blood-poisoning. The spleen and lymphatic glands, particularly those of the mesentery, are enlarged. The enlargment of the spleen is generally well marked, its parenchyma being much darker than usual and greatly softened. The liver shows signs of putrefaction earlier than any other of the viscera, and at times the appearance known as e7nphyse?na of the liver indicates an advanced stage of decomposition, with the evolution of gas. This was very marked in a case the writer once saw, in which septicaemia followed the production of an abortion produced by inserting a dirty catheter into the uterus. A slight cloudy swelling of the liver is usually all that is seen. The kidneys are somewhat cedematous, and the tubuli uriniferi are more or less affected by a catarrhal inflamma- tion. Most observers agree that bacteria are abundantly found in the glomeruli — an evidence of the effort upon the part of nature to 35° SURGICAL PATHOLOGY AND THERAPEUTICS. excrete the poison. The capillaries of an infected region are often plugged with streptococci, and the walls of larger vessels are infil- trated with them. Large numbers of these organisms are also found in the lymph-spaces of the connective tissue (Figs. 70 and 71). Fig. 70. — Capillary Embolus of Streptococci in a Sarcoma. A round-cell infiltration is seen in the sarcomatous tissue about the embolus. (Case of fatal septicaemia.) The condition of the wound, as might be expected, is of the foulest description. Evidences of congestion or oedema of the sur- rounding tissues are apparent, and all these tissues are crowded with micrococci, and they are found also in the adjacent lymphatic glands, which are considerably enlarged. The writer has attempted to sketch the disease as it is usually seen after injuries or operations. There are, however, several variations in type which cannot be passed by without mention. Prominent among these variations is that form of septicaemia which usually follows a dissecting wound. Gussenbauer looks upon this as a form of ptomaine-poisoning, but Horsley does not accept this view. The rapidity with which symptoms make their appear- ance is due not to the absorption of a chemical poison, but rather to the unprotected nature of the tissue into which a fluid in a state of active decomposition is inoculated. Then the virus selects a SEPTICAEMIA. 351 special route, by which it is rapidly carried to a distant point. More than one case of such a poisoning has occurred to a student 1 ^ ^ v > ^ v # * •- Fig. 71. — Infiltration of Vessel-wall in Sarcoma. (Case of fatal septicaemia.) of the school during the writer's experience as a teacher. The fol- lowing account gives the salient points of one of these cases: A young man, tall and slender, about twenty-one years of age, had wounded himself slightly in the dissecting-room. He applied the next day to one of the surgeons at the hospital, complaining of pain in the shoulder. His condition was such that he was admitted to the hospital, and a consulta- tion was held the following day upon his case. At that time the whole arm was swollen ; red lines were seen running from an insignificant wound in the finger to the axilla. There was no sign of suppuration in the axillary glands, but the whole pectoral and scapular region was enormously swollen and cedematous. There was an anxious expression of countenance, high fever, and great prostration. Ether was given, and free incisions were made over the whole pectoral region, permitting the escape of a thin, slightly turbid serum. No pus was found anywhere. The patient was not benefited by the operation, and died the following day. At the autopsy no pathological changes of interest were recorded. Happily, cases of such malignant poisoning as this are not often met with. They bear a close resemblance to malignant oedema. Usually the poison gives evidence of its presence by an inflam- mation of the finger extending up the hand and invading the lymphatics, as shown by red markings upon the anterior aspect of 352 SURGICAL PATHOLOGY AND THERAPEUTICS. the forearm and arm. An infective, followed by a suppurative, inflammation of the glands of the axilla occurs, and with the open- ing of the abscess further progress of the inflammation is arrested. The fever which accompanies this attack is rapid in its onset, and may be attended with sensations of chilliness, although a chill does not usually occur. There is great mental depression, and usually there is the appearance of anaemia with great loss of strength. The constitutional disturbance yields rapidly upon arrest of the inflam- mation, and in the milder types cannot be called a genuine "blood- poisoning;" that is, it hardly belongs to the forms of the septi- cemic or sapraemic type, but rather to the variety known as sur- gical or suppurative fever. Serious forms of septicaemia accompany such diseases as hos- pital gangrene and traumatic gangrene. In the latter case the acute type is found in its most characteristic form, but a descrip- tion of this complication is reserved for the chapter treating of Gangrene. There has already been alluded to the so-called ' ' spontaneous sep- ticaemia," and it has been shown that such a disease does not exist, but that in all cases a focus of inflammation is to be found some- where to account for the blood-poisoning. Many cases of suppu- ration of the appendix have doubtless passed in former times for spontaneous septicaemia. The absorption of the products of an inflammation around the appendix tainted with gangrenous and fecal extravasations must produce grave constitutional disturbance, particularly when the peritoneal cavity is invaded and this power- ful absorbing surface is exposed to the poison. The conditions for acute septicaemia are here exceptionally favorable. Undoubt- edly, a certain number of cases of perinephritic abscess could be rescued from this category. An individual in robust health is attacked with fever; there are no localizing symptoms; typhoid fever or pneumonia is suspected, but no characteristic signs of either of these diseases show themselves, and the patient succumbs in a few days, the strength of the poison having benumbed the senses to that extent that symptoms of local inflammation in the loin have not been complained of. Even at the present time, when a more generally diffused know- ledge and frequent autopsies have helped to clear up many obscure forms of disease, cases will occur that are still not easy to explain. The writer remembers one of this kind: A hard-working and temperate Irishman was attacked with subacute rheumatism in the ankle. The administration of salicylic acid did not SEPTICEMIA. 353 serve to check the disease, and, as symptoms of polyarticular rheumatism with increased fever began to develop, he was removed to the hospital. A temporary improvement followed, but just as the rheumatic joints were improving an intense inflammation in the neighborhood of the right hip developed, reaching from the right iliac fossa halfway down the thigh. Acute septicaemia developed, and the patient was dead before forty-eight hours had elapsed. Unfortunately, an autopsy was not permitted. Acute osteomyelitis, which the above history suggests, has already been spoken of as a cause of septicaemia. In making a diagnosis of septicemia there must first of all be taken into consideration the condition of the wound. If there is found only an accumulation of blood-clot, the surgeon may have reason to hope that he has simply to deal with sapraemia. The high continued fever, the indifference of the patient to his sur- roundings, the absence of chills, and the symptoms of a general disturbance in the alimentary canal are the most important of the constitutional symptoms. The detection of an area of dulness in the region of the spleen, and of the presence of albumin and bac- teria in the urine, would aid in the diagnosis. But it must be confessed that there are no constant or very characteristic local symptoms, and that our opinion must be arrived at rather by a process of exclusion. The treatment of septicemia may be either local or general. The local treatment is largely prophylactic, and consists, it need hardly be said, in a strict observance of the principles of aseptic surgery. When once the diagnosis of septicaemia has been made, it will be the surgeon's duty carefully to examine the wound and to undertake as thorough disinfection as the strength of the patient will permit. Occlusive dressings must be abandoned; the wound must be opened sufficiently to expose all infected parts and to ensure free drainage of all putrefying discharges. A thorough washing of the wound may have considerable effect upon the fever if the poisoning be largely from ptomaines absorbed from the secretions, and some of the older methods invented by sur- geons who had a large experience in septic diseases should not be forgotten. Among these " the drip " has often done useful service — a device by means of which a constant current of fluid is carried over or through the wound. Over the part is suspended a cup from which depend a few strands of wick-yarn, and this will often prove sufficient for the purpose when a more elaborate arrangement of tubes is not possible. The antiseptic fluids applied in this way must be exceedingly weak, for a large quantity of a poisonous 23 354 SURGICAL PATHOLOGY AND THERAPEUTICS. substance would be absorbed, even though the solution were not strong; in fact, it would be desirable to use milder remedies, like boracic acid, and to rely chiefly upon the flow of pure water. If the wound is so situated that it can be submerged in water, weak antiseptic solutions will often prove most serviceable in finally overcoming the septic infection. Carbolic solutions, in the strength of i : iooo of water, or of sublimate, i : 50,000, will be sufficiently strong, or these solutions may be applied by means of hot fomentations or "antiseptic poultices." Strong solutions of carbolic acid (1 : 20) or peroxide of hydro- gen may be used in moderate quantities to disinfect the wound before the dressings are applied. It is probable that a very con- siderable amount of bacterial growth can be removed by thor- oughly scraping or curetting the surface of the wound, for the most superficial growths are not only removed, but the deeper tissues also are more thoroughly exposed to the action of the dis- infectants. Iodoform, which as a dressing is at its best on such occasions as this, may be applied freely to a sloughing wound, for the danger of poisoning is less than when directly in contact with healthy granu- lations. It can be applied on cotton or on gauze. Whether the agent be sublimate, carbolic acid, or iodoform, a careful watch, to avoid poisoning by these agents, should be kept upon disturbance of the bowels and on the condition of the urine. The more minute details of local treatment will be found in the chapter upon Infec- tive Inflammations. In the general treatment of the disease the surgeon has to deal with a fever accompanied with marked prostration of the strength and a deterioration of the blood. With the introduction of the antipyretic treatment of fever this method was also employed for surgical fevers, but with most unsatisfactory results ; at least, that has been the writer's experience. The relief from fever is exceed- ingly brief; at times no result whatever has been produced, and antipyretics do not appear to add in any way to the comfort of the patient, as is the case in typhoid fever. The disturbance of the fever-curve may also mislead the surgeon as to the patient's condition. These remedies are, however, not contraindicated in the milder forms of septicaemia, and they may often be productive of great relief to sleepless subjects. In the acute form valuable time may be wasted in watching their effect upon the disease. Great reliance must be placed upon nourishment and alcoholic stimulants. Nourishment must, of course, be of a nature suited SEPTICAEMIA. 355 to the condition of the digestive system, and must be adminis- tered in small quantities and frequently. It is astonishing how much alcohol a patient in this condition is capable of absorbing without bad effects. The flushing of the face is a signal for its discontinuance or for its administration in smaller doses. The condition of the pulse will also be a good guide. Whether alcohol acts simply as a food or possesses antiseptic qualities has not been proved. According to Sternberg, the micrococcus requires the presence of 20 per cent, of alcohol for its destruction. The amount necessary to produce this action in the blood of a patient weighing one hundred and sixty pounds would be more than a quart — " a much larger quantity than the most enthusiastic advocate of its use would deem safe to administer." Alcohol to this amount has not infrequently been given in the course of twenty-four hours without ill effect, even in patients wholly unused to its action. This, of course, does not imply the presence of so large a quantity at any one time in the system; but it may be that in the living tissues the organism would find a less favorable soil for exerting its resisting powers against drug-action than when taken fresh from active artificial cultures. Heart failure must be guarded against, and heart-tonics may often be given with advantage when the pulse is weak and rapid. The tincture of digitalis, which may be tried in increasing doses for this purpose, is a drug that should perhaps be employed more freely by surgeons than it has been. The diarrhoea can be treated best with opium if it proves troublesome, and bismuth or tannin may be employed if necessary. In dealing with septicaemia it must be remembered that it is an essentially different disease from the surgical fevers. The latter are due to the absorption of virus constantly generated in the wound, and it is to this point, therefore, that attention should be directed. But in septicaemia there is, except in the case of saprae- mia, a constitutional disturbance which has become quite inde- pendent of its local origin — a disease in which the whole sys- tem, both blood and tissues, is involved, and which calls for the employment of all the resources at the surgeon's command. XV. PYAEMIA. This disease always accompanies suppuration, and, as will be seen, is nothing more or less than a complication of that disorder. The name pycemia, which is attributed to Piorry, was not given to it until the present century (1828). It is derived from the Greek (nvov, pus, aljua, blood). Velpeau described the disease under the name infection piiriilente, which term is still employed by the French. Although the nomenclature is of recent origin, the dis- ease itself was well known to the ancients, and it presents such marked clinical symptoms and pathological changes that the descriptions of the old writers leave no doubt in the mind as to the correctness of their observations. Hippocrates described that most characteristic of symptoms, the chill, and also the existence of icterus. Paracelsus described the inflammation of the joints. Ambrose Pare recognized the fact that compound fractures of the skull were sometimes followed by abscesses of the liver. Morgagni and Petit in the eighteenth cen- tury attempted to show that metastatic abscesses were caused by an actual penetration of pus into the blood. The next observation worthy of note was that of Hunter, who recognized the existence of phlebitis as one of the links in the chain of pathological events. Hunter supposed that there took place an adhesive phlebi- tis which prevented the entrance of pus into the blood, although the rupture of an abscess might occasionally cause this to occur. Suppuration of the inner wall of the vein he thought was the usual result of phlebitis, by which this protective influence would be pre- vented, and pus would be carried away in the blood-current, or inflammation might extend along the walls of the vessels to the heart, and thus cause death. He did not, however, express him- self clearly as to the relation of the metastatic abscesses to the inflammation of the veins. Cruveilhier was among the first to point out that the result of phlebitis was the coagulation of blood in the veins. The discussion at this time turned upon the question of formation of pus by the inflamed lining membrane of the vein or by a sort of endosmotic absorption of pus through the healthy walls of the vessels. Up to this time it was pretty generally believed that the phe- 356 PYsEMIA. 357 noinena of pyaemia were produced by the presence of pus in the blood, by whatever route it may have obtained an entrance; but as early as 1822, Gaspard made experimental observations on ani- mals which led him to believe that the metastatic abscesses were due to the presence of putrid materials in the pus. Observations on the condition of the blood in pyaemia were numerous at this time, and the view was even advanced that inflammation of the blood itself, a haemitis, occurred. Rokitansky described a class of cases in which, apparently, a large number of pus-corpuscles were seen in the blood, but Virchow and Bennett recognized in these cases the affection which is now known as leukaemia. A great impetus was given to the advancement of the knowledge of this disease by the investigations of Virchow upon thrombosis and embolism. That which had been supposed to be pus found in the veins near an infected wound he showed was a collection of white corpuscles; that the masses which were mixed up with them were the remains of a softened thrombus; and that embolism resulted from detachment of the fragments of such a thrombus and their arrest in some distant capillary district. If a terminal arteriole was thus occluded, infarction took place, and a metastatic abscess might be the result of the irritating nature of the materials of which the embolus was composed. This explanation fully disposed of the old idea that pus penetrated the lumen of the vein by the rupture of an abscess. At that time a great distinction was made between " laudable " pus and "infected " or foul pus, and Virchow thought to emphasize his new views on the spreading of suppura- tion through the body by substituting the term " ichorrhaemia " (r//i)p, gore, corrupted matter) for "pyaemia." What this poison- ous substance was which produced such formidable complications had not yet been discovered, but light was soon thrown upon this point by the work of Pasteur on fermentation. From this time on the question of the bacterial origin of the disease gave rise to a vast amount of experimental investigation, which, however, did not succeed in clearing up this point until the methods of bacteriologi- cal study had become sufficiently perfected to give reliable results. A variety of experiments were made to determine whether the poisonous agent existed in the fluid or solid constituents of pus. Burden Sanderson, as early as 1865, injected the purulent fluid from an ankle-joint of a patient, ill with pyaemia, into the subcu- taneous tissue of animals, producing metastatic abscesses. In experiments made in 1872 he found in the pus artificially-produced bacilli and micrococci, to which he gave the name microzyme. 35 8 SURGICAL PATHOLOGY AND THERAPEUTICS. Finally, a systematic study was made upon the microscopic appearance of organisms found in the pus of pyaemic patients. Doleris was one of the first to recognize in the lochia of infected puerperal patients what would probably now be called the "strep- tococcus," and the same organism was observed by Pasteur in fatal cases of puerperal pyaemia — the microbe en chapelet. He formu- lated the theory that the disease was due to this organism passing through the blood and lymph-channels to different parts of the body, thus producing metastatic inflammations. These organisms were reproduced by cultures taken from the blood and pus during life and after death. Koch injected fluid from putrefying flesh into the subcutaneous tissue of a rabbit and produced metastatic deposits; from the heart of this animal blood was taken and injected into another rabbit, and the disease was thus reproduced. The organisms observed were chain-like micrococci measuring about 0.25/* in diameter. These organisms were observed adherent in small clumps to the walls of capillaries of the kidney and other organs; each little mass of bac- teria enclosed several blood-corpuscles, and appeared to possess the peculiarity of causing the blood-corpuscles to adhere and form thrombi. If this is a characteristic of the streptococcus, which was probably the organism he saw, then an explanation is pre- sented of the origin of the most characteristic feature of pyaemia. Near the wound numbers of micrococci were found in the tissues and around the subcutaneous veins, and even in the walls of the veins, through which their passage could be demonstrated in many places. Owing to their peculiar adhesive properties, Koch found they did not remain long in the circulating blood, because they were soon deposited in the capillaries of the organs. No micro- cocci were found in the lymphatics. Ogston's work contains a number of interesting facts bearing upon pyaemia. His idea of a single poison for all forms of surgical fever is a simple and attractive one. He says: " Between a simple localized acute inflammation on the one hand and the severest case of pyaemia on the other there exists only a difference in degree, a difference in intensity." He shows that the swelling of joints, so characteristic a symptom of pyaemia, is produced by the effusion of serum, which, when examined, does not show the presence of micrococci, but these cocci are found in the coverings of the joint or in the synovial fringes around the cartilages, and, according to Ogston, the effusion takes place from a spot where a colony exists. Rosenbach thought that Ogston went too far in assuming that PYsEMIA. 359 pysemia is purely a secondary affection. He examined 6 cases of pyaemia in man by making blood- and pus-cultures during life and inoculating animals with the organisms thus obtained. In 5 of these cases he found the streptococcus both in the blood and in the metastatic abscesses of the lungs. In 2 of these cases the staphylo- coccus was associated with the streptococcus. In 1 case he found the staphylococcus only, and this case recovered. As the result of his investigations he divides pyaemia into two varieties. The first is that which has already been described as suppurative fever; that is, a fever accompanying severe and extensive suppurations and fre- quently terminating fatally in the acute stage. Such cases are said to have died of exhaustion. In these cases he thinks the blood- poisoning is due to the presence of the staphylococcus, much as Og- ston describes, and that this kind of fever should be called "true pysemia." It may be said here that Heuter described this form of fever as "pyaemia simplex" in contradistinction to the embolic form, which he called "pysemia multiplex." The latter was Ro- senbach's second form of pysemia, or the " thrombo-embolic " form with metastasis, which, as he shows, may be quite independent of the condition of the wound and in active development, even after the wound has healed, and which is usually caused by the strepto- coccus. A good many observations have been made upon the bacteria of pysemia. Besser, for instance, examined the blood, pus, and parenchymatous fluids in 23 cases of pysemia. In 8 the staphylo- coccus was found; in 14, the streptococcus; and in 1 both kinds of cocci were seen. During life the cocci were found in the blood in 11 out of 12 cases. Out of 46 cases, in all, collected by him, the staphylococcus was found in 22, the streptococcus in 21, and both were found in 3 cases. He concluded that there was no difference b>etween the cocci of pus and the cocci of pysemia. Pawlowsky examined 5 cases of pysemia in man, and found the staphylococcus in 4. In the fifth case, which had an unusual number of joint- complications, he found the streptococcus. He believed the staphylococcus is the usual cause of pysemia, and particularly in cases of abscess of the internal organs. Pawlowsky, perceiving that pure cultures of the pyogenic cocci when introduced into the organism disappeared rapidly, made sim- ultaneous injection of sterilized cinnabar particles and staphylococcus cultures into the circulation, and produced a typical pysemia with metastatic abscess. Injections of the coccus without the cinnabar were not sufficient to produce the disease. The particles of cin- 360 SURGICAL PATHOLOGY AND THERAPEUTICS. nabar were supposed to have favored the formation of minute thrombi, impairing the local nutrition of the tissues and favoring impaction. Bonome also succeeded in getting metastatic abscesses by intravenous injection of fragments of sterilized pith with pure cultures of staphylococci. An important addition to the experimental investigation of pyaemia is that intended to throw light upon the origin of the nodular and ulcerative endocarditis found in this as well as other diseases. An acute endocarditis was produced by Wyssokowitch by introducing an instrument through the jugular vein and bruis- ing the valves, and subsequently by injecting bacteria of different kinds directly into the circulation. If the bacteria were injected into the connective tissue, or an interval of two days was allowed to pass after the lesion of the valves had been produced, or a very weak dose of bacteria was employed, the endocarditis did not take place. Ribbert succeeded in infecting the endocardium without previous injury by introducing fragments of potato with the cul- ture. These small particles enabled the bacteria to become, me- chanically, more easily arrested, and the injury inflicted upon the endothelia at the same time offered a soil more favorable to bacte- rial growth, owing to its impaired condition. The process by which the endocardial lesion appears to be formed in the human subject is as follows : The micrococci become attached either to some old lesion of the valve or to some point on the valve favorably situated to receive them, owing to the pressure of the blood-column against it when the valves are closed. A coagulation- necrosis of the inner wall of the vessel takes place at the point of attachment. A rough surface is thus presented to the blood-cur- rent, and numbers of white corpuscles or blood-plaques become attached to the little clump of micrococci and necrosed tissue, and a thrombus is thus formed. If the destruction of tissue is not great, the granulation tissue may cover in the micro-organisms and a nodular mass will be found in the valve; but if there has been extensive necrosis, when the protecting thrombus is swept away an ulceration will be observed in the wall of the valve. Baumgarten suggests that the tuberous form of endocarditis is produced by the staphylococcus, and the ulcerative form by the streptococcus. Having thus glanced over the most important experimental investigations in pyaemia, the reader is now prepared to form an opinion as to the nature of the micro-organisms and the route which they take in infecting the system. PYAEMIA, 361 Both the staphylococcus and the streptococcus have been observed, and, although at one time it was supposed that the former was the principal agent in producing the disease, the data afforded by observers up to the present time do not permit one to decide in favor of either: so far as can be judged, therefore, it is probable that accidental anatomical and pathological conditions determine the question of a successful resistance on the part of the tissues, rather than the presence or the absence of either of the above varieties of micrococci. Enough is known of the vary- ing degree of virulence of pathogenic bacteria to enable one to realize that they may act very differently under varying conditions. This can easily be proved by clinical observation as well as by laboratory experiments. The route through which an infection of the system takes place from a wound is almost invariably the blood-vessels, although occa- sionally the infection may follow the lymphatic system. When the micrococci are not restrained in their growth in an infected wound, they soon reach the blood-vessels, and when they come in contact with the walls of a vein an inflammation is set up and thrombo- phlebitis results. As they reach the intima a disturbance of nutri- tion in the endothelium takes place, and rough places are thus formed on the inner surface of the vein. If, now, the descriptions of Osier and Zahn are recalled, it will be found that a number of leucocytes become adherent to such a spot and form a little mass attached to the inner wall, which mass after a while becomes more or less homogeneous, so that the individual corpuscles cannot be discerned. The white thrombus of Zahn is formed in this way, and it becomes the starting-point of a thrombosis which may so enlarge as completely to fill the lumen of the vein. The blood- plaques, as well as the leucocytes, will also be seen collecting about this rough spot, and aid in the process of coagulation. Such an event would seem to serve as a protection to shut off the damaged vein from the general circulation. The street has been closed for repairs, as it were, and doubtless in many a case such is the result of this effort on the part of nature. Unfortunately, the thrombus affords an unusually good soil for the micrococci, and an infection and puriform softening of the clot eventually take place. Inasmuch as thrombosis may occur throughout the extent of a large vessel — as, for instance, the femoral vein (Fig. 72) — a large mass of soft material, looking like blood-clot and pus mixed together, is contained inside the vessel, extending far beyond the limits of the wound and in more or less direct communication with 362 SURGICAL PATHOLOGY AND THERAPEUTICS. the circulation. The mode of progress of the micrococci from the wound to the adjacent vessels seems merely to be a process of ger- mination and growth. It was at one time thought that they were transported into the thrombi already formed by the white corpus- Fig. 72. — Thrombus of Femoral Vein. cles, in the interior of which cells numbers of cocci are often found; but this theory has not been sustained. Thrombo-arteritis may also occur; that is, the micrococci may penetrate the arteries as well as the veins, but the denser walls and the more vigorous current do not favor development of thrombi; and when thrombi are found they do not, of course, spread to distant points, but fragments detached will remain in an adjacent capillary district. Fragments from the infected venous thrombi when detached are arrested in the capillary system of the lungs, where they form new foci of infec- tion, and favor the formation of a metastatic abscess (Fig. 27). Very small emboli may, however, pass through the lung capillaries, as the vessels are much larger than those of other capillary systems, and in this way the whole arterial system will be exposed to a sim- ilar infection. Cocci may also be found free in the circulation inde- pendent of emboli. Their direct penetration into the circulating blood is impeded by the thrombosis which occurs at the point of entrance in the vessel-wall. Small masses of micrococci may, how- ever, be detached before coagulation has taken place, and be swept off into the current. Single organisms are not likely to cause sup- puration, as the resistance of the tissues neutralizes their pathogenic action, and they quickly disappear from the circulation. The micrococci, when circulating through the blood, are lodged in and become attached to the endothelium of capillaries where the circulation is slow, or in the lumen of vessels with an anatomical arrangement favorable for a lodgment, as in the glomeruli of the kidney. Having reached a stationary point, they begin to grow either in the lumen or in the wall, and spread through a consider- able capillary district. A necrosis takes place around the mass of micrococci, and suppuration occurs at its border. As the cocci PYsEMIA. 363 from the centre and the pus-cells from the periphery break into the necrosed tissue, it melts down and a miliary abscess is thus formed. If the bacterial growth is of slight intensity and is not extensive, necrosis will probably not occur, but suppuration may take place without it. Free micrococci may also become attached to the valves of the heart and to the veins by the blood-pressure forcing them into the soft endothelium while the valve is closed, causing nodular or ulcerating endocarditis. Fragments of emboli laden with micrococci are more likely to become attached in this way, as has already been shown experimentally. If the embolus is arrested in the terminal artery of an organ, a wedge-shaped infarction will result. The tissue, thus lowered in vitality, is soon invaded by the micrococci: leucocytes also wander in, a softening takes place, and there arises a wedge-shaped abscess situated near the surface of an organ. If the lodgment takes place in a tissue with free anastomosis, the cocci invade the intermediate tracts of tissue or parenchyma, or they may spread backward along the inner wall of the artery to a collateral branch, and may thus be carried to an adjacent capillary district; in this way a more or less diffused abscess will be formed. From the above examples it will readily be seen that the great variety of suppurations occurring in pyaemia can be accounted for by the spreading of micrococci from the origi- nal wound into different parts of the body. It will be perceived that the old idea that pyaemia was due to the presence of pus in the blood has been abandoned. It occa- sionally happens, however, that an abscess may be situated in the neighborhood of a large vein, and that perforation of the vessel- wall may take place, the abscess actually emptying itself into the cavity of the vessel. Schuh reports a case of a man suffering from an acute abscess behind the peritoneum. He was suddenly taken ill with symptoms of pyaemia, and died in two days. At the autopsy it was found that the abscess had broken into the ascend- ing cava and that metastatic abscesses existed in the lungs. Numerous balls of pus were found floating in the blood, and about two ounces of pus were collected from the blood-vessels. Gussen- bauer reports a number of such cases. Infection may also take place through the lymphatic system, although the chains of lymphatic glands offer a protection which is not found in the veins. Gussenbauer reports a case of gangrene of the lower extremities in which foul pus was found in the thoracic duct; Schuh records a case of lithotomy, with death three weeks after the operation, in which case the lymphatics over the 364 SURGICAL PATHOLOGY AND THERAPEUTICS. sacrum and in the lumbar region were filled with purulent mate- rial, and the thoracic duct was distended to the size of a pigeon's egg with thin green pus which was found extending up to its opening in the vena cava. Pus may be found in the lymphatics of the broad ligaments of the uterus in cases of puerperal pyaemia. In such a class of cases the richness of the lymphatic connection and the direct communications with the venous system render a general infection more probable than in the case of suppuration in more superficial regions which have access only to the peripheral lymphatics on the surface of the body. All these forms of infection, which take their departure from a wound, have been called "types of extravascular infection," to distinguish them from a class of cases in which no wound is pres- ent; nevertheless, pyaemia exists. The cases of intravascular infection, or the so-called "sponta- neous pyaemias," have long been recognized, but their etiology has been but little understood. An otherwise healthy individual receives a trifling wound or catches cold, and after suffering from severe chills and fever, and perhaps swelling of the joints, dies, and metastatic deposits are found in the internal organs. A young man or a boy stays too long in the bath, and the next day he has a severe chill; symptoms of acute osteomyelitis of the femur develop, and he eventually dies of pyaemia. An interesting feat- ure of these cases is that they are frequently associated with acute ulcerative endocarditis. More will be said about their clinical features in discussing the symptomatology of pyaemia. How does infection take place in cases like these ? It has been pointed out that micrococci are found in the circulation even when no suppuration takes place. All that seems necessary is a lowering of the general tone of the system or the existence of some weak or diseased spot, in order that these organisms may break down the bar- riers which the normal tissues afford. Under such conditions there may arise a marked disturbance of function or circulation of an organ, as the kidney, perhaps from getting chilled, or an inflamma- tion may occur which will favor the localization of micrococci in that neighborhood, and a perinephritic abscess may be the result. A starting-point is thus established from which an extensive infec- tion of the system may occur. The changes in the nutrition of a rapidly-growing long bone, and its anatomical peculiarities, account for the fact that such tissue is a favorite seat of infective inflamma- tion. The rich anastomosis in the medullary cavity favors the accu- mulation of micrococci in a given capillary network. A rapid PYsEMIA. 365 multiplication of the organism occurs: the vessel endothelium is first attacked, and then the intravascular tissues, and there is soon a considerable space undergoing necrosis and forming the central point of an acute suppurative inflammation. There are cases, however, in which no preliminary abscess is formed. The attack may be accompanied with no characteristic symptoms of local dis- ease, yet an autopsy will show metastatic abscesses in the inter- nal organs. In these cases marked evidences of ulcerative endo- carditis are pretty sure to be found, and it is supposed that the micrococci have obtained a lodgment in the valves of the heart. According to Osier, the number of primary cases of ulcerative endocarditis is limited, this lesion of the heart being more fre- quently associated with some other affection, even with such a disease as pneumonia. Pneumococci have been found in such cases. In pre-antiseptic days, when pyaemia was a much commoner disease in hospitals than it is now, it was thought that certain seasons of the year were favorable for epidemics of the disease. The writer has observed such an epidemic. Having had one or two deaths from pyaemia in his hospital wards, attention was given to the search for a local cause. To his surprise, he learned that a neighboring lying-in hospital had been closed on account of a similar "epidemic," and that several cases of puerperal pyaemia had also occurred in a suburban hospital. It was at the time of the year, the early spring, when erysipelas and other traumatic infec- tive diseases have long been dreaded by the surgeon. In some of these affections, as erysipelas, climatic influences seem to be an etiological factor, and the writer sees no reason to doubt the exist- ence of conditions in the atmosphere that are more favorable to the development of an unusual activity in the staphylococcus and streptococcus than at other times. So acute an observer as Sir James Simpson says: "There are epidemic states in which puer- peral and surgical fevers are frightfully common. Some localities and towns are far more frequently their seat than others." The enthusiasm for antisepsis should not allow the surgeon to forget the teachings of an earlier school, founded as they were on abundant experience. In a report made to the Pathological Society of London the statement is made that during ten years (1869 to 1878), within which period all cases of pyaemia in the London hospitals were recorded, the mortality of 1874 and 1875 was decidedly in excess of that of other years. These two years were noted for their marked 366 SURGICAL PATHOLOGY AND THERAPEUTICS. meteorological conditions. In 1874 there was a remarkable defi- ciency of rain during the whole year. On the contrary, 1875 was characterized by its excessive rainfall. The most fatal months during this series of years were February and March. As to the influence of age and sex, it may be said that children and old men, and women at all times of life, are less frequently affected than men in the prime of life. This immunity is perhaps partly due to less exposure to traumatism, but so far as children are concerned this is probably not the reason. Wounds in children usually heal rapidly, the reparative process is more active, and it effects more perfect results than in maturer years. The blood and tissues of young children are, as a rule, purer and healthier, and the resisting power against infection is consequently greater. In the adult there is present all the ailments due to advancing years, which ailments handicap him in the struggle for life; and in cer- tain conditions of the system, such as alcoholism and diabetes, there exist conditions peculiarly susceptible to traumatic influ- ences. Pyaemia does occasionally occur in infancy: Savory reports cases in children ten months old, and one even as young as four days old. Among the kind of wounds which predispose to metastatic inflammation may be mentioned contused wounds, wounds of joints, compound fractures (supposed to favor pyaemia by fat-em- bolism), particularly fractures of the head, osteomyelitis, injuries of the veins or of the vascular regions, and wounds received in war or by individuals in an enfeebled condition. The disease usually makes its appearance about ten days after the injury — that is, at the height of the suppurative process — but it may begin at any time during the suppurative process. The most prominent of the symptoms of pycemia is the chill. This chill, however, may not accompany the first onset of fever, which is usually severe. At other times the chill may be the only symptom which first arouses the surgeon's suspicion, for the febrile disturbance may be slight or may be of a degree which has existed for some time; as, for instance, in a case of suppurative fever. An examination of the wound may reveal local infection and symptoms of infective inflammation. The lips of the wound are, in this case, red and swollen, and the interior of the wound may have a discol- ored or grayish, sloughing appearance, but, even though the wound be far advanced in the process of repair, a typical pyaemia may develop itself: indeed, some cases have been reported where the disease first made itself manifest after the wound had actually PYsEMIA. 367 healed. In such cases the wound is probably situated near some rich venous anastomosis, as the hemorrhoidal veins or the sinuses, in which thrombi are readily formed. The chill may be either a slight shivering or of the severest type, followed by profuse per- spiration and considerable exhaustion. Usually after the chill is over the patient appears very much as before. There is no men- tal disturbance, although there may be at the same time consider- able fever. Ordinarily the surgeon does not observe a second chill until the following day; although Billroth, who has made a special study of the chills of pyaemia, states that as many as three chills may occur in the course of a single day. He also noticed that chills were less likely to occur during the evening and night than in the morning or afternoon. He lays special stress upon the marked difference between septicaemia and pyaemia so far as this symptom is concerned, as in the former disease, except perhaps at the onset, chills are never seen. The explanation of the chill is to be found probably in the existence of multiple suppurations throughout the body. The surgeon is aware that when in the course of an acute inflammation, as in cellulitis, a chill occurs, there is every reason to expect the appearance of pus. In the chapter on Fevers the writer endeavored to explain the cause of a chill and its relation to sudden elevations of temperature. With the formation of each new metastatic abscess there is probably a liberation of fresh pyrogenous material, which may have a more or less specific action on the blood and tissues, or possibly the nerves controlling heat-regulation, thus producing this special form of disturbance. A no less striking peculiarity of pyaemia are the variations of temperature. Billroth, who made a careful study of fever-curves in various fevers, first called attention to the curve of pyaemia. Heu- ter, who has also studied this question, speaks of the pyaemic curve as most characteristic. The fever-curve which pyaemia most nearly approaches is that of intermittent fever, but it varies from the latter in lacking regu- larity of change. It differs from all fevers in not having a regular evening exacerbation and morning remission, although this may occur. Heuter describes it as an "irregular intermittent type" (Fig. 73). Its irregularities are certainly great. The usual course of events is as follows : There is, at the beginning, usually a sharp rise, which may reach almost the highest point of the curve. If the temperature is already high at the time of the appearance of the disease, there will be a sharp rise to mark its onset. There will 3 68 SURGICAL PATHOLOGY AND THERAPEUTICS. be a period of pyrexia of longer or shorter duration, and then a fall, but not to the normal line, followed by a succession of similar exacerbations. During these periods of high fever the temperature remains at no fixed point, but there will be constant variation of 104 103 102 101 100 99 98' 97 I 23456789 10 k / \? J A h \ l v.- A V \a i VI \t \A \ \ \r v \ v v l 1 I n \ ■/■ Fig. 73. — Pyaemia. fractional portions of a degree. These variations may occur almost hourly, so that it is necessary to take thermometric observations very frequently. It is customary, when the existence of pyaemia is suspected, to take a record every two hours, which is pretty sure to bring out varying undulations in the fever-curve. At the same time the daily record of temperature carried through the period of the disease shows also the greatest irregularities. In general it might be said that the curve of pyaemia consists of an irregular series of sharp rises- and falls, with an intervening zigzag outline to the curve. During all this time the normal line is not reached, yet in exceptional cases the temperature may return to normal, and may remain there for a day or two. Occasionally there has been observed a sharp rise post-mortem. The reasons for these remark- able changes are naturally to be sought for in the diverse patholog- ical appearances which are found at the autopsy. There may not always be an abscess to account for each chill or a chill to corre- spond to each abscess. Individual susceptibilities doubtless play an important role in the development of this symptom, but the multiple foci of embolism, infective inflammation, and suppura- tion, some visible and some almost imperceptible, amply account for the greatest irregularities in the fever-curve. After the first febrile phenomena have abated somewhat symp- toms of respiratory disturbance usually show themselves. A number of small metastatic abscesses may exist without indicating their PYsEMIA. 369 presence by any symptom, but if they are superficial and are situ- ated near the pleural surface, the patient will generally complain of a sense of oppression and pain at that spot. Symptoms of pleurisy will develop, and auscultation may later reveal an effu- sion into the pleural cavity, and probably, also, the existence of pneumonia at the base of one or both lungs. With dyspnoea there will be cough with the expectoration of sputa, at first frothy and mucous, later rusty and perhaps purulent. In rare cases only haemoptysis occurs. Braidwood lays stress upon a peculiar "sweet- ish," u hay-like" "purulent" odor of the breath, of which he says : ' l This character of the breath in suppurative fever is very remarkable and of easy recognition." Metastatic abscesses of the liver cannot readily be recognized unless near the peritoneal covering, in which case localized peri- tonitis will be indicated by the presence of a sharp pain at that spot. Gussenbauer has recognized the presence of such lesions twice during life by auscultation, a slight crepitus being noticed. The discoloration of the skin that has gradually developed has now assumed a hue deep enough to be recognized as an icterus. It is described by Braidwood as " a yellowish tinge intermixed with the dull leaden or ashy color which accompanies wasting disease. ' * Its origin is not probably due to metastatic inflammation of the liver, which frequently is absent, but is either haematogenous or is caused by the presence of micrococcus growths in the capillaries of the skin. The facial expression, though not specially characteristic of the disease, is different from that of septicaemia. The marked emaciation which has already set in gives the eyes a hollow, sunken look. At the same time they show by their anxious expression that the intelligence is as keen as ever, and it may remain so until the final stages of the disease. The dryness of the skin occurring with the initial rise of temperature will be followed by profuse perspira- tion, a marked symptom as the disease progresses, appearing inde- pendently of the chill as well as immediately after it. Later in the course of the disease erythematous patches are seen, or there is a scarlet rash extending over the greater portion of the body. This rash assumes in pyaemia a most markedly papu- lar or even pustular form, and it is undoubtedly due to colonization of micrococci in the upper layers of the skin. Toward the end purpura spots are seen, and the pustules may coalesce and give rise to foul discharges, or vesicles filled with puriform fluid develop. There is not found so marked a disturbance of the digestive organs as in septicaemia. At first the bowels may be constipated. 24 370 SURGICAL PATHOLOGY AND THERAPEUTICS. The tongue is furred, the thirst is great, and, as the fatal issue approaches, the tongue becomes dry and brown and is coated at last with a heavy crust, while the gums and teeth are covered with sordes. Occasionally foul and bloody stools occur, but diarrhoea is a more characteristic symptom of septicaemia. Another marked symptom of pyaemia that develops itself as the disease progresses is general hypercesthesia. The patient complains of a sharp pain, first at one point, then at another. Many of these pains are undoubtedly due to metastatic inflammation, but the gen- eral tenderness which manifests itself on the surface of the body cannot be explained in this way. Such patients are extremely dif- ficult to handle or to move about in bed, and if, in addition, there is a severe wound or a compound fracture of the bone, the situation is extremely trying and painful for the nurse as well as for the patient. Where so much suppuration is going on one would naturally expect enlargement of the glands of the lymphatic system, and with them the spleen; but there is not found that pulpy softening of the spleen which is characteristic of septicaemia. Metastatic abscesses and infarctions may occur in this organ, as elsewhere, in which case there will be an enlargement that can be made out by percussion. As an indication of the state of the kidneys the condition of the tirine rarely affords much information. It will, of course, be some- what scanty and high-colored, particularly at first, and urates may be deposited in excess. A considerable amount of albuminuria with fibrinous casts would indicate a hyperaemia of these organs, possibly due to the ' presence of metastatic deposits, but possibly also to the febrile disturbance only. Pus-corpuscles are occasion- ally seen, and at times also bacteria in considerable quantities, due to the effort on the part of the system at elimination of the poison. Hofmeister has accounted for the presence of peptone, which is found in this as well as in certain other diseases, by showing that the active leucocytes in pus possess the power to retain peptone, so that the amount of it can greatly be increased. He regards, therefore, the presence of this substance in the urine as an indica- tion of the breaking down of pus-corpuscles in the body. Haema- turia has occasionally been noticed, but it is an extremely rare symptom. Not only are there complications in the internal organs during pyaemia, but on the surface of the body there is also much to occupy the attention of the surgeon. Among the most important PYjEMIA. 371 of the complications are those found in joints. Early in the dis- ease the surgeon may have complaints of pain in the knee or in the shoulder-joints, and an examination of the knee will enable the surgeon to detect readily the presence of an effusion. The surrounding tissues may also be swollen and inflamed for a con- siderable distance. An incision into such a joint may disclose the presence of turbid serum or pus, which may collect with great rapidity. The sterno-clavicular articulation is often affected, but all joints, small as w r ell as large, are liable to be the seat of inflam- mation. Phlegmonous inflammations are also seen, but they more fre- quently accompany puerperal pyaemia. The surrounding tissues are cedematous and the muscles are of a brawny-red color. Meta- static inflammations of bones are not likely to occur, but in acute osteomyelitis of long bones accompanying some forms of ' ' sponta- neous pyaemia ' ' there are signs of most acute and extensive inflam- mation, accompanied by severe pain. The inflammation of joints may, however, be accompanied by inflammation, and even by sup- puration, of the adjacent bones. In amputation-stumps the signs of bone-inflammation are often present. There is an increased dis- charge of foul pus, and an examination discloses the presence of a sequestrum and of a protruding mass of granulation tissue from the medullary cavity. At a later period "the medulla is found dead, blackened, and encysted, but within it is a putrid mass of bone debris and pus. A probe passes down the entire length of the shaft." If the blood be examined during life, there are found, in addi- tion to the presence of micrococci already mentioned, an increased number of white blood-corpuscles and blood-plaques. The red corpuscles are, however, diminished in number, and many of them have a crenated or shrunken appearance, which may account in a measure for the anaemic pallor of the patient. (See page 100.) Symptoms of heart-lesion are rarely noticed, although in those cases in which ulcerative endocarditis is a prominent feature paiu in the region of the heart is occasionally mentioned. The ptrfse is fairly strong, but is more rapid than usual; in the later stages of the disease its weakness and rapidity are, however, very marked. The prostration at this period becomes a striking feature, as is also the great emaciation, w r hich at times becomes extreme. All these symptoms will be aggravated greatly by secondary hemor- rhages, which are not infrequent, and which are usually hard to Z12 SURGICAL PATHOLOGY AND THERAPEUTICS. control, as they may be repeated even after the ligature of a large vessel. In the later stages of the disease the mind begins to fail, and there occurs for the first time delirium, which, as the end approaches, gives place to coma. The presence of paralysis, stra- bismus, sudden deafness, or priapism may point to the existence of metastatic meningeal inflammation. Subsultus tendinum will almost always be present. The usual duration of pyaemia is from ten to fifteen days. Bill- roth's tables give ten cases which lasted from ten to eighteen weeks. It is probable, he thinks, that the thrombi form in the second week, and are most dangerous from softening in the third and fourth weeks. The writer has seen a case which lasted nearly two months. The pyaemia which has just been described is that form in which the virus finds an entrance into the system through the surface of a wound. But it has long been recognised that pycemia may occur although no wound exists. The etiology of this form of pyaemia has already been discussed, and the reader is therefore aware that the micrococci can get into the system by means of an intravascular infection. It remains for the writer merely to mention some of the cases which belong in this category. The most striking, perhaps, of all, and the one which the surgeon is most likely to see, is the case of acute osteomyelitis, generally of the long bones. Such a case is always ushered in by a chill. Symptoms of the most acute inflammation soon show the origin of the fever, and when finally suppuration is established and the abscess breaks, great injury has been done to the bone. A pyaemic complication is not, therefore, to be wondered at when the severity of the affection is considered. A good many of the cases of ulcerative endocarditis belong in this category, as has been shown. In some the lesion seems to be the primary — that is, the point of entrance of the micrococci into the tissues; in others the endocarditis may be but one of a series of secondary changes starting from an inflamed lung or kidney or from a rheumatic joint. The symptoms will vary considerably according to the disease of which the embolism and metastasis are complications. In the cardiac group, or those which supervene usually in cases of chronic heart disease when weak spots in the shape of fibrous scars exist upon the valves, there will be symptoms of pain in the cardiac region and palpitation, with a sense of dis- tress, and auscultation will disclose a murmur. PYEMIA. 373 In some cases cerebral symptoms seem to predominate from the beginning; suppurative meningitis may coexist with a patch of pneumonia at the apex of one lung and with endocarditis of the mitral valve. Different portions of the body have been examined carefully to find the door through which the virus has entered in these forms of obscure origin. The following case, occurring in the writer's practice, fairly illustrates the type of pyaemia that develops without a wound : E. L , a female thirty-four 3-ears of age, entered the medical wards of the hospital with pain in the right lumbar region, which pain had existed for six weeks and which was ushered in with a rigor. She had been in poor health during the winter, and had recently suffered from one or two epileptic seiz- ures. The signs of suppuration growing more marked and pus appearing in the urine, a diagnosis of perinephritic abscess was made, and, as her condi- tion was grave, she was transferred to the writer's wards and the abscess was opened, ten ounces of pus being removed. Chills and increase of fever had developed before the operation. At the time of the evacuation of the pus a gelatin culture was taken, which in a day or two developed into the staphylococcus. No improvement followed ; the breathing became labored; involuntary dejections occurred ; the pulse ran up to 180, and the patient died on the fifth day after the operation. At the autopsy there was oedema of the lungs. Miliary abscesses were found on the surface of the heart and in the papillary muscles, and the edges of the aortic valves were thickened. There was hemorrhagic infarction of the spleen and acute purulent nephritis of the right kidney, and miliary abscesses in the central portion of the left kidney had occurred. A small metastatic abscess was found in the intestine, and one the size of a horse- chestnut was found in the liver. A microscopic section of one of the abscesses of the heart showed the typical microscopical appearances, a clump of micrococcus growth occupying the centre. At the demonstration before the class the original aureus culture was shown at the same time with the microscopical sections and the fresh organs in which metastasis had occurred. In puerperal pyaemia there is pretty much the same chain of events that occur in traumatic pyaemia. According to Baumgar- ten, the streptococcus is often found in secretions from the vagina, which seems to constitute a sort of lurking-place for it, and the lochia furnish a most admirable culture material. After par- turition the uterine contractions, the free flow of the lochia, and the rapid epithelial formations that cover the denuded surface do not give the cocci an opportunity to obtain an entrance. If, how- ever, the contractions are feeble and the lochia are retained, the sinuses are not securely closed, and if epithelial formation is pre- vented by placental remains, which are very favorable spots for bacterial development, or if the deeper layers of the uterine walls are torn, the door is at once opened to puerperal infection. The 374 SURGICAL PATHOLOGY AND THERAPEUTICS. form of endometritis which results is usually a diphtheritic one, for the streptococcus has only a feeble peptonizing influence; but during a more prolonged stay in distant parts its capacity to cause inflammation may be strengthened, and it is then fully capable of causing suppuration. It may follow the route of the lymphatics or of the blood-vessels, causing parametritis, ulcerative endocar- ditis, and metastatic abscess in the various organs. Puerperal pyaemia is said by Billroth to be relatively less malignant than surgical pysemia. Of a series of 50 cases tabulated by him, 5 recovered, and these 5 were all cases of puerperal pysemia. Surgical pysemia is sometimes divided into acute and chronic forms. The form usually described as chronic is that which has already been studied under the head of Suppurative Fever. The diseases are, however, of quite different character, presenting not only different causes, but different symptoms and pathological changes; they have only this in common: they are both compli- cations arising from a suppurating wound. As has been seen, pysemia may kill rapidly in a few days, or it may last weeks or even months. In the latter case the symptoms are not so pronounced as in the acute type: chills are less frequent, as metastatic inflammations are fewer in number. The chances for recovery is such cases are correspondingly greater. Such a case is the following, an example of true chronic pysemia: W. C , twenty-seven years old, a healthy brakeman, received a com- pound comminuted fracture of the left leg from a car- wheel. Amputation of the thigh was performed through the condyles . Extensive sloughing of the flaps followed, and on the seventh day a hemorrhage occurred from the popli- teal artery ; the vessel was secured in the wound, but four days later a second hemorrhage occurred, and the femoral was tied at the point of election. Three days later swelling and tenderness of the left parotid showed itself, and event- ually an abscess formed, which was opened. At this date there was also increased respiration with bloody sputa, and at times the patient became delirious. By this time the patient had become anaemic, emaciated, and greatly prostrated in strength. An offensive dis- charge oozed from the wound. The thigh was shrunken and the wounds were pale and blue. A day or two later a sharp pain in the right side at the level of the fifth rib ushered in a local pleurisy. Two slight hemorrhages occurred from the point of ligature of the femoral about a month after the patient's entrance to the hospital, and the artery was again tied higher up. He seemed now to be failing ; emaciation was extreme, and the sensitiveness of all parts of the body was so great that it was with difficulty that his wounds were dressed. Under stimulants and nourishment he rallied, however, and by the sixtieth day the temperature remained on the normal line for the first time. Pyrexia in a milder form returned later, and on the ninetieth day an abscess formed in the middle of the thigh, PYAEMIA. 375 although the wounds by this time had nearly healed. After this no further suppuration occurred, and he was discharged from the hospital with two small granulating surfaces at the end of the stump four months from the time of entrance, the temperature having been normal for a week only previous to his departure. So much has already been said about the pathological changes seen in pyaemia that it would be difficult to give a detailed account of the post-mortem appearances without much repetition. Decomposition in the cadaver does not set in nearly so quickly as in septicaemia. The surface of the wound is of a blackish-green color like gangrenous tissue^ the granulations are smooth and glazed, and there is usually little discharge in the wound. Large arteries may be seen occasionally, partly open so far as their walls are con- cerned, but they are plugged by a protruding clot which is still firmly attached to them. Thrombo-phlebitis exists in veins lead- ing from or adjacent to the wound. The puriform softening may have broken down the entire thrombus, and nothing remains but a soft muddy puriform material, extending sometimes for a long dis- tance beyond all signs of local inflammation. Excellent examples of thrombosis can be seen in the sinuses after injuries to the bones of the cranium. An examination of the internal organs brings to light the presence chiefly of metastatic abscesses. But it must not be supposed that they are dotted about in the profusion seen in the beautiful anatomical plates of Cruveilhier and others. In the large proportion of a series of cases reported by a committee of the London Pathological Society a post-mortem examination showed the presence of abscesses in the lungs and such a swelling of the spleen and kidneys as one would expect to see in any severe febrile disturbance. The presence of abscesses of the lungs can easily be accounted for, the ramifications of the pulmonary artery being naturally the first lodging-place of a wandering embolus. They are more frequent in the lower lobe, as the branches of the artery are somewhat larger there. They are not usually of large size, but several may run together and form a cavity as large as a hen's &gg. Catarrhal pneumonia may surround them. Infarction may also occur. A serous effusion is often found in the pleural cavity; more rarely it is purulent. The liver is usually in a state of cloudy swelling. Occasionally it is the seat of abscesses, which arise from several sources. They may be the result of thrombosis of the pulmonary veins following abscesses in the lungs, or they may be dependent upon the soften- ing of thrombi in the portal system, or, finally, they may be caused 37 6 SURGICAL PATHOLOGY AND THERAPEUTICS. by minute emboli which ha've passed the lungs. They are sup- posed to follow, frequently, injuries to the head, and they are not numerous, and frequently are quite superficial. Occasionally a single large abscess will be found in the liver. The liver is said to be, next to the lungs, the most frequent seat of metastatic deposits. The kidneys are often the seat of miliary abscesses or small emboli (Fig. 27). The metastatic deposits are more frequently seen in the cortical portion, for the reason, as already noted, that the Malpighian bodies are particularly favorable for the lodgment of masses of micrococci. On section, the organ appears swollen and cedematous. The metastatic abscess is the lesion most fre- quently seen, but infarction may be found also. Morbid lesions of the heart are not so frequent in the surgical forms of pyaemia as they are in the class of cases that have been described. The mitral or the aortic valve may be affected, but, according to Hutchinson, more frequently it is the mitral, and this author mentions two cases in which the lesion was recognized before death by a mitral murmur. The lesions consisted in nod- ular growths upon the valves, which subsequently break down and leave the so-called "ulcerations." This process may be so extensive sometimes as to leave an ulcer of considerable size; according to Osier, perforation of the septum has even occurred. Metastatic abscesses may also be found in the muscular substance of the organ. The existence of slight pericarditis may be indi- cated by the presence of an increased amount of fluid in the peri- cardium. The intestinal canal, as already seen, is not so likely to be affected in pysemia as in septicaemia, and frequently no patho- logical changes whatever are found. A miliary abscess may, how- ever, occasionally be found in the submucous tissue, and the latter membrane may occasionally also be affected and break down, thus forming ulcerations. The latter may appear as small ulcers pene- trating the mucous and vascular coats, and they are occasionally seen near the pyloric orifice of the stomach in puerperal cases. According to Braidwood, the large intestine appears to be more frequently affected, and the ulcers, when of any size, are situated with their long diameters across the axis of the canal. The brain may be passively hyperaemic, when the heart and lungs are affected, with some effusion in the ventricles. The pres- ence of metastatic abscesses is rare: when seen they are small and are in the cortical portion. One would more likely find patches of congestion in different portions of the brain, or suppurative meuin- PYsEMIA. 377 gitis. Metastatic deposits have not been found in the spinal cord, perhaps because the lack of well-defined symptoms does not lead to an examination of that organ. Inflammation of the connective tissue with suppuration is occa- sionally seen. Gussenbauer has found it more frequent in puerpe- ral pyaemia. Infection may occur through the arterial system, or local metastasis may occur in the neighborhood of the wound, as in one of the cases first reported. Joint-inflammations are also supposed to be more frequent in puerperal pyaemia, but they are certainly a characteristic also of surgical forms of the disease. The knee and shoulder are the parts most frequently affected, but inflammation is often found in the wrist and in the sterno-clavicular and temporo-maxillary articula- tions. An inflammation of the latter joint might easily be mis- taken for suppurative parotitis. The condition found on opening the joint in the milder form of inflammation is congestion of the synovial membrane accompanied by a more or less abundant effu- sion of synovial fluid. Later, pus forms, ulceration of the cartilage takes place, and the joint may become completely disorganized. In other cases a large quantity of pus may form in a joint, and on washing it out only very slight traces of morbid action may be observed (Savory). When the joint-inflammation has been severe and acute in type the surrounding tissues are often extensively involved. It is in these cases that the muscles, when cut into, exhibit the brawny condition so often described. Metastatic abscesses are more often found in muscles of the extremities than in those of the breast. Purulent exudation is sometimes found even in the sheaths of the tendons. Bristowe mentions the presence of metastatic abscess in the tongue. Perhaps much of the hyperaesthesia complained of by pyaemic patients may be due to congestions or to inflammations in the soft parts, which at the autopsy escape notice. The bones are more frequently the seat of inflammation, from which pyaemic poisoning may originate, than the seat of secondary abscesses. The medullary tissues are so constituted, anatomically, as to favor absorption of the products of infective inflammation. The bones in the neighborhood of the wound are likely to show signs of periostitis and osteomyelitis in pyaemic cases. Metastatic abscesses are seen, however, in the diploe of the cranial bones. The parotid gland is not unfrequently the seat of metastatic abscess. A metastatic panophthalmitis is sometimes caused by an embolism of the retinal and choroidal vessels. Such an inflamma- 37§ SURGICAL PATHOLOGY AND THERAPEUTICS. tion is of course very destructive, and the contents of the globe usually slough and escape. Gamgee has seen metastatic abscess three times in the prostate. Rarer seats of abscess are the thyroid gland, the mediastinum, the testicles, and the ovaries. The diagnosis of pyaemia is not difficult after the disease is well established, for the intermittent type of fever and the chill are sufficiently characteristic, particularly if there be a suppurating wound. The presence of mental disturbance with a sudden chill and fever, and the existence of sloughing tissue in the wound, would be suggestive of septicaemia. If there were considerable digestive disturbance coincident with a chill, the surgeon might suspect the approach of an attack of erysipelas. Emaciation, hyperaesthesia, diaphoresis, and great prostration are symptoms sufficiently characteristic to aid in establishing the diagnosis, which will be confirmed when the existence of a metastatic abscess has been established with certainty. Speaking of the prognosis of pyaemia, Savory graphically says: " Seldom giving any warning of its approach, it will at once con- vert a case which just before seemed full of promise into one past all hope of recovery ; for it cannot be denied that, with rare excep- tions, to pronounce a patient the subject of pyaemia is to say that he is a doomed man." Nevertheless, the number of cases of recovery that have been reported is a respectable one. In the first place, there is a relatively high percentage of cures in puerperal pyae- mia. In surgical pyaemia most writers report cases of cure. In one case an account has been given of the autopsy performed upon a man who had recovered from pyaemia the year before: the cicatrices of the metastatic abscesses were plainly visible in the internal organs. Ac- cording to Guerin, these patients do not long survive their recovery. The treatment of pyaemia is of course chiefly preventive. The results obtained by the introduction of the antiseptic treatment of wounds are probably more brilliant than those which the history of any other affection, medical or surgical, can show. When once the disease is established, it has been suggested that amputation of the injured limb, if the wound be in that region, would cut off the source of the poison. This expedient the writer tried in one case, but without success. At the autopsy it was shown that the puriform softening of the thrombus extended to Poupart's ligament. Still, a number of cases have been reported wherein pyaemia has been arrested by amputation. Ligature of the infected vein has been advised, and more recently opening the vein and removing the infected thrombus. PYAEMIA. 379 The investigations of Macewen have given a strong impetus to this mode of dealing with the lateral and sigmoid sinuses in eases of infection following suppuration of the middle ear. As the result of this infection, thrombosis occurs not only in the sinuses mentioned, but the internal jugular vein, espe- cially its upper third, not infrequently also participates in the inflammatory action. When disintegration of the thrombus takes place systemic infection may occur, the emboli lodging themselves in the lungs principally, and occa- sionally in the liver and kidneys. If an extensive thrombosis has been set up in the sinus, a portion of it may be placed beyond the limits of the infected area, so that while the centre of the thrombus undergoes puriform softening, the extremities may still remain aseptic. As the result of this infection the w T all of the sinus may break down and pus may collect between the wall of the vessel and the bone. On opening the bone at the point of the sigmoid groove granulations are often seen covering the sinus, and often along with these there is an oozing of pus. If the vein-wall is still intact, it may be laid open, and the contents of the sinus may thus be exposed to view, when the disintegrating clot ' ' may be removed by the aid of a small spoon or gently washed out : the former is the safer." In manipulating the contents of the sinuses, especially when removing the thrombus from the side nearest the jugular bulb, care is neces- sary against admission of air, more especially if aseptic washings be em- ployed. Macewen does not recommend the ligature of a large sinus. Bal- lance and Horsley have, however, recommended the ligature of the internal jugular in addition to the curetting of the sinus, and this operation may be performed in cases where the infection has extended to this vein. If it is necessary to ligature the vein, it should be done before clearing out the sinus. It must not be forgotten, however, that the internal jugular is not the sole channel between the sigmoid sinus and the lungs. In the United States the operation of curetting the sinus has been per- formed successfully by Mixter. About an inch and a half of the sinus was exposed, and, as it showed no pulsation, it was incised and an inch and a half of softened thrombus was removed with an ordinary dressing-forceps. Jack has also performed this operation, without, however, succeeding in saving the patient. Macewen recommends that infective pustules on the face or lips should be excised and that the main veins should be tied. " In infective wounds of the orbital cavity, rather than permit the formation of infective thrombosis of the cavernous sinus, the serious question of extirpation of the eyeball and clearing out of the contents of the cavity may arise." The success of this method has been sufficiently great to author- ize its employment in other regions of the body, as, for instance, in the femoral vein. It is only radical measures like these that will offer any hope of relief after infective thrombosis has once been established. Complete disinfection of the wound should of course be attempted if putrefying discharges are retained, and its walls should be curet- ted thoroughly to remove the layer of germinating bacteria. Meta- static abscesses should promptly be opened and disinfected when 380 SURGICAL PATHOLOGY AND THERAPEUTICS. possible; and if suppuration is established in a joint, it should not be allowed to go on without an attempt to arrest its progress by surgical interference. Incision and free douching with antiseptics are advised, and in cases of chronic character this procedure may be sufficiently successful to save life. The administration of antipyretics is not advisable, as most of them have a rather debilitating effect upon the heart. If any drug should be thought desirable to combat the fever, quinine is to be preferred. Alcohol is probably the surgeon's mainstay in the dis- ease, and it should be given freely even to patients who are not accustomed to its use. Their temperate habits will now stand them in good stead. The amount should be so adjusted as not to cause flushing of the face at any time. Easily-digested food of the most nutritious kind should be given with all the care that skilled nurs- ing can devote to its administration. The hygienic surroundings should of course be considered. If the patient is in a hospital, he may be moved into the open air for several hours a day if the disease is not running too acute a course or the exhaustion caused by the moving is not too great. If the case becomes chronic, a complete change of room and of clothing will often produce the same effect upon the course of the disease that a change of climate does to an invalid. The weakened condition of the blood should not be overlooked during convalescence. The administration of iron would probably be indicated to repair the damage done to the red blood-corpuscles. It is to be hoped, however, that few surgeons will ever see cases of pyaemia in the future. XVI. ERYSIPELAS. One of the most frequent of traumatic infective diseases, and one which antisepsis has not yet succeeded in banishing entirely from our hospitals, is erysipelas. It may be defined as an acute inflammation of the skin spreading along the surface, and rarely to the deeper parts, with a tendency to spontaneous recovery. It is accompanied by acute febrile disturbance; it may involve mucous membranes ; it may recur. The name is said to owe its origin to ipodpoz, red, and netta, skin. There is, however, no good Greek authority for the latter word. 'Epuaoc; and 7isAa<; are suggestive words, but have no meaning which would justify their use. The disease was known to the ancients, but reliable reports of epidemics date back not farther than the latter part of the eighteenth century. Erysipelatous angina was epidemic in Great Britain in 1777 and 1800, and extensive epidemics occurred also in that country in 1821 and in 1832; there was an epidemic in France in 1750. According to Tillmans, during 1843 the disease visited Scotland, Denmark, and Germany, and numerous American authori- ties bear testimony to the fact that it prevailed in America in 1842. Hall and Dexter give a description of ' ' erysipelatous fever " as it appeared in 1842-43 in the northern section of Vermont and New Hampshire. The accounts of these epidemics paint pictures of a much severer type of disease than the surgeon is accustomed to see to- day. The inflammation began frequently in the throat. In Indi- ana the tongue was noticed to become very much swollen, assum- ing a blackish-brown color, and deglutition was almost impossible. In New England the phlegmonous form was common. One prac- titioner writes: " The whole surface, under the pectoral muscle extending to the axilla, frequently under the latissimus dorsi run- ning up under the muscles of the shoulder, is, in not a few cases, one extensive abscess." In many cases the muscles and bones were involved, and the discharges were said to be so acrid that the hardest steel was "directly penetrated by it as by nitric acid," and the instruments used in opening an abscess were found, after being laid aside for a few hours, to be entirely unfit for further use. The epidemic prevailed in the greater portion of the Northern States, 381 382 SURGICAL PATHOLOGY AND THERAPEUTICS. and large numbers of lives were sacrificed. This appears to have been the last expiring effort of the disease as an epidemic type, for since that time no such accounts are preserved in literature, and during the writer's own experience the disease in that form has practically been unknown. The origin of the virus of erysipelas has always been a matter of much dispute, many having thought that no specific poison existed, but that the disease was caused by exposure to cold or by meteorological influences. The early experiments made to test the possibility of transmitting the virus to animals, and of thus prov- ing the inoculability of the disease, did not meet with such success as to settle the question definitely. Prominent among these experi- ments were those of Tillmans, who inoculated rabbits and dogs with virus taken from the large vesicles which form upon the dis- eased skin, and also with blood, lymph, and pus. Out of 25 experi- ments conducted in this manner, 5 only were successful. In these 5 cases the disease was subsequently transmitted to other animals. Tillmans concludes that the disease is only mildly contagious, and this was also the opinion of other observers. Fehleisen, who was one of the first to isolate the streptococcus of erysipelas, succeeded not only in transmitting the disease to ani- mals, but also from man to man. The human inoculations were justified by being used for the purpose of curing chronic forms of ulceration of the skin, such as lupus or rodent ulcer and also sar- coma. Of seven persons thus inoculated, six developed erysipelas ; the single failure was probably due to the fact that the patient inoculated had passed through an attack of the disease some three months previously, and was therefore supposed to be protected from a second attack. The period of incubation was found to be from fifteen to sixty-one hours. The coccus was found in the lymphatic vessels of the skin and in the lymph-spaces, and when the culture was pure it never produced suppuration. Fehleisen concludes from his observations that the erysipelas coccus is a specific microbe which will always reproduce the disease when inoculated even in the smallest quantities, differing thus from the staphylococcus, which must be administered in a sufficiently large dose. These experiments upon man were based upon the experience that an attack of erysipelas often exerted a curative effect, but in the cases mentioned the inoculation failed to cure the malignant growths. Finally, a death having occurred from erysipelas in the hands of imitators of this method, further experimentation in this line was very properly abandoned. ERYSIPELAS. 383 The bacteriological studies of Koch, Rosenbach, and other observers fully confirmed those of Fehleisen as to the nature of the organism which is the cause of erysipelas. The single cocci are from 0.3// to 0.4// in diameter. They grow in serpentine chains, the links of the chains forming pairs of cocci, as in most forms of streptococci. When each coccus is about to divide it becomes larger and oval, and two cocci result from the fission of the old one. The organism is readily stained with the usual aniline reagents. The question of the identity of the erysipelas coccus with the streptococcus pyogenes has frequently been raised, and authorities are not yet entirely agreed upon this point. The coccus of erysip- elas is somewhat larger than the streptococcus. The culture on the surface of agar appears as a very delicate grayish-white film com- posed of great numbers of minute colonies closely crowded together. When the gelatin is inoculated fine white granular masses form along the line of puncture, but at the surface there is usually not much growth. The culture shows after twenty-four hours, and reaches its full development in four days. It does not have a sol- vent action upon the gelatin. The cultures die out at the end of four months. Baumgarten thinks that the erysipelas coccus and the streptococ- cus show different degrees of activity in the same species — that they are the same organism, which under different external conditions act differently. The organism when situated in the superficial firm layers of the skin acts with less virulence, causing sero-cellular or fibrinous exudation, while in the loose structures of the subcu- taneous tissues it acts more vigorously, causing suppuration. Many modern observers concede that the erysipelas coccus causes not only erysipelas, but also abscess, but many others believe that when sup- puration occurs, it is due to pyogenic cocci which have become inoculated secondarily, and that suppuration is therefore merely a complication of the disease. Experimental inoculation with ery- sipelas cocci has, in the hands of one observer, always produced erysipelas, while inoculations with the streptococcus produced phlegmonous inflammation. If the organisms are situated in the skin the inflammation will be erysipelatous, but if in the deeper tissues it will be phlegmon- ous. Tillmans would group all progressive types of inflammation in the same class. Such a classification would place not only cel- lulitis, but also lymphangitis, malignant oedema, and even fulmi- nating gangrene, in the same group with erysipelas ; but our pres- 384 SURGICAL PATHOLOGY AND THERAPEUTICS. ent knowledge of the bacteriology of these affections would hardly authorize such a wholesale grouping. The cocci are found in the capillary lymphatics of the skin and in the lymph-spaces chiefly, but they are sometimes also seen in the capillary blood-vessels and in the small veins. They may be found even beyond the lines of the inflammation in parts as yet unchanged. Near the red border the growth of organisms is most active. The lymphatics are so crowded with them that leucocytes are hard to find. Chains of cocci may be seen at this point in the adjacent connective tissue, and here also will be observed the signs of active inflammation as indicated by hypersemia of the vessels, emigration of leucocytes, and swelling of the fibres of the connec- tive tissue. According to Baumgarten, the cocci lie between the leucocytes in the lymphatics, but in the tissues they are occasion- ally found in the cells. Nearer the centre of the inflamed parts, where the process has been going on longer, the infiltration is greater, but the cocci have, according to Baumgarten, disappeared. They are found in small numbers only in the vesicles. Baumgar- ten does not agree with Metschnikoff that the disappearance of the cocci is due to phagocytes. The cell-exudation does not take place until after the coccus growth has reached its height, and only a few cocci are found in the cells. The cocci do not spread through the body in the vascular circuit, although they may occasionally be found in the blood-vessels at a distance from the inflammation. The constitutional disturbance accompanying erysipelatous inflam- mation is undoubtedly due to their presence in the circulation or to the presence of ptomaines. The appearance of the disease at a point distant from the seat of the inoculation is clinical proof that the virus may be transmitted through the circulation. If the erysipelas cocci are identical with some of the chain-like cocci found in decomposing substances, this accounts for the fact that the disease may be acquired both by contagion and by mias- matic infection, as in epidemics; also for its occurrence at certain seasons of the year; and also for Billroth' s clinical observations that it is in wounds chiefly discharging decomposing secretion mixed with blood that erysipelas is most likely to occur. The most frequent point of entrance of the virus is through the wound, and from this point it spreads rapidly through the lymph- capillaries of the surrounding skin. In the so-called "cases of idiopathic erysipelas" the disease was supposed to develop itself quite independently of any trauma, but even in these cases it is not difficult to imagine that some minute wound, abrasion, or diseased ER YSIPELAS. 385 spot 011 the surface of the skin may offer a suitable soil for the inoculation of the microbe. The routes taken by the pyogenic cocci in producing boils and carbuncles could readily be followed bv the erysipelas coccus. The disease does not always manifest itself at the point of entrance, but it may appear first at some dis- tant portion of the body, thus necessitating transmission of the organism through the circulation. It is possible that the lungs or the digestive tract may allow the passage of the microbe, and that the infection of a certain locality may be through the circulation instead of through the integuments. Whether a slight trauma of the mucous membrane is necessary for such invasion cannot easily be decided. It is, however, highly probable that healthy skin offers a sure protection against infection. The clinical evidence of the contagiousness of erysipelas is abundant. Fortunately, the material to be obtained on this point belongs to a period that has already passed. The occurrence of erysipelas following vaccination has at certain periods become so serious and so frequent a complication that the operation has for the time being been abandoned. This was the case in Boston in the winter and spring of 1850. In the records of the Boston Society for Medical Improvement, Morland, the secretary states: " Of late, however, cases have multiplied to such an extent, and the result has been so often fatal, that many members of the society have refused to vaccinate except when it has been absolutely necessary, and have almost wholly given up revaccination." Cabot reported the case of a gentleman sixty-nine years of age who was revaccinated, and at the end of a week phlegmonous erysipelas developed. The disease invaded the chest and the right arm as well as the left. The sup- puration was severe about the left shoulder, and the pectoral muscle was thus separated from the parietes of the thorax. Numerous openings were made about the elbow and shoulder for the discharge of pus. The patient was con- fined to his bed for two months. Bigelow reported a case of a healthy child five months old. On the eighth day there was taken from the vesicle matter with which he vaccinated three other children. On the next day the arm became erysipelatous, and the child died in a few days. All the patients vac- cinated from this child had typical vesicles and no anomalous symptoms. Bigelow regarded this as evidence conclusive against the transmission of erysipelas by vaccination. Tillmans, however, has no doubt that in many cases the vac- cine lymph has conveyed the virus of erysipelas. Barbieri vac- cinated forty-nine children with virus from a child who had ery- sipelas at a distance from the vesicle, without his knowledge, and, out of twenty-one children who had a vesicle, twelve contracted erysipelas and four died. This, however, does not prove that the 25 386 SURGICAL PATHOLOGY AXD THERAPEUTICS. vaccine lymph necessarily contained erysipelas poison, for the points may have become infected after having received the lvmph. Whether such a mode of transmission of erysipelas cocci is pos- sible could be determined only by a series of experiments in which all the conditions considered necessary for a reliable bac- teriological experiment had been complied with. There is little doubt, however, that inoculation might take place by unclean instruments, so that the pustule might become infected bv the virus emanating from a concurrent epidemic of the disease. The close relationship of erysipelas and puerperal fever has long been well recognized, and it is of especial interest in view of the fact, which is now known, that both these diseases are caused bv the streptococcus type of bacteria. Dr. O. W. Holmes, in a paper on the contagiousness of puerperal fever, reports an epidemic of that disease in the practice of a physician who made the autopsy in a case of oedema and gangrene of the thigh, and received an injury to his ringer which confined him to the house. Several cases of erysipelas occurred in the house where the autopsy was performed, and two of the nurses who cared for the puerperal cases died of erysipelas. Stille reports the experience of a Philadelphia physician who had 95 cases of puerperal fever in rapid succession, and of the children born in these cases no less than 15 died of erysipelas. But perhaps the most striking example of the close relationship of the two diseases is the following: There was an epidemic of puerperal fever in the Hopital St. Louis in January and Februarv, 1861: no new cases could be admitted. The puer- peral patients already in the hospital were transferred to a derrna- tological ward, while the patients with disease of the skin — thirty- two in number — were placed in the puerperal ward, whereupon an epidemic of erysipelas broke out among those patients, and several of them died. The question of the transmission of the disease from case to case has been much discussed, and, although the contagiousness of ery- sipelas has been recognized by many writers, still there are high authorities to-day who are not prepared to accept this view. Gross says: "The question of the contagiousness of this disease is not yet fully settled. Much may be said both against and in favor of this view. My own opinion, founded on considerable experience, is that the affection at times possesses such a character. " Stille says: "But direct clinical proof is also abundant that erysipelas itself is communicable bv contagion." The occurrence of several cases of the disease in a certain locality or in a hospital ward is not ERYSIPELAS. 387 necessarily evidence of its contagiousness, for such a concurrence of events may be due to a common cause from which each case has taken its origin. But when a case is brought to a given point and it becomes the focus of an epidemic, the evidence in favor of con- tagion is much more conclusive, as the following examples show: In 1852 a man arrived in Platte county, Missouri, with facial erysipelas. The farmer who nursed him fell ill with the disease; a second farmer who nursed and slept with these two individuals was taken with erysipelas; sub- sequently six other persons who helped to nurse these cases were themselves attacked. No other cases occurred in the neighborhood (Stille). A young man visited an intern of the Lariboisiere in Paris who was ill with erysipelas ; on returning to his home in Guise he was taken with the disease, and died in thirteen da3 r s. His servant had erysipelas. A relative, who visited him from a distance, two days after his return home was taken ill. His wife also had erysipelas, and likewise three neighbors who visited them during their illness. A relative of the latter who came from a neigh- boring village to see them was the next victim; also three Sisters of Charity who nursed them, and who, on their return to the convent, infected several other sisters. The physician who attended these cases died of erysipelas, as did also his daughter. Previous to this time there had been no cases of ery- sipelas in any of these localities. It was the common experience of many a hospital surgeon, in times past, that a single case of the disease, allowed to remain in the open ward of a hospital, has given rise to no other cases. Such facts as these have caused many to doubt the theory of contagion, and it is highly probable that the average case of erysipelas is but feebly contagious. There are, however, undoubtedly cases which are contagious in the highest degree, particularly when gangrene or phlegmonous inflammations occur as complications. In former times diseases of this type could be followed from bed to bed, and there often existed a certain ward or some bed where the occupants were generally expected to have the disease. At the present time, when antiseptic dressings isolate a patient so much more effectually from his neighbors, it is probable that a case allowed to remain in a ward where other wounds existed might not communicate the disease. The more complete know- ledge of the virus of erysipelas has, however, given rise to greater care to bring about isolation. The old view that the disease may be caused by exposure to cold or by climatic conditions is generally discarded, although these conditions may undoubtedly act as pre- disposing causes. The season of the year and the state of the atmosphere may at times be more favorable to the development of the erysipelas cocci than at others, and the greater activity of these organisms at certain periods is thus accounted for. Certain 388 SURGICAL PATHOLOGY AND THERAPEUTICS. it is that in the winter and early spring months this disease is more likely to be epidemic than at other seasons. The presence of de- composing materials provides a soil favorable for the development of the cocci, as has already been seen. The presence of any decay- ing substance, imperfect drainage, and bad hygienic surroundings are therefore to be regarded as predisposing causes of the disease. So far as age is concerned, it may be said that in children the disease is comparatively rare. Erysipelas neonatorum is, however, frequently epidemic in badly-arranged lying-in hospitals, and it is usually associated with puerperal fever. This disease does not appear frequently during old age. Whether certain constitutional affections, such as scurvy, alcoholism, diabetes, and tuberculosis, predispose to erysipelas is still a doubtful question. Some individ- uals have frequent attacks of the disease, and they are supposed to have an hereditary disposition. The idea that persons with a lymphatic constitution, or, as Heuter suggests, those with large lymph-capillaries and broad lymph-spaces in the skin, are more susceptible, is certainly suggestive. Attention must now be turned to the symptoms of erysipelas. When in the course of the healing of a wound there is found a sudden attack of febrile disturbance, ushered in usually with a chill, which has been ascribed by the friends or the attendants to indigestion or to gastric disturbance of some kind, the possibility of an attack of erysipelas should at once suggest itself. Long before any of the characteristic local conditions about the wound are noticed, the presence of prodromal symptoms make themselves manifest. The tongue becomes heavily coated; there is a sense of oppression in the epigastrium, with malaise by day, and possibly with delirium at night. There may also be noticed occasionally some enlargement of the lymphatic glands, particularly those lead- ing from the part, indicating the route through which the absorp- tion of the poison is taking place. A day or two may pass before the local symptoms appear. In the mean time there is no percept- ible change in the condition of the wound — certainly not enough to account for the constitutional disturbance. Occasionally there may be an indisposition so slight that the patient is hardly conscious of it, and then the earliest manifestations noticed are in the wound itself. By far the most characteristic feature of this disease is the inflammation of the skin. The local inflammation is recognized by an increased feeling of tension in the wound, with increased heat and usually with an itching or a burning sensation. The ER YSIPELAS. 389 ervthema often seen about a wound, and caused by hot poultices, bv tight stitches, or by other irritating features of the dressing, is easily distinguished from erysipelas, as the former is chiefly hyper- emia, and not accompanied by exudation, and is also limited entirely to the part irritated. Slight pressure will show that there has been no organic change in the tissues. As true erysipelas develops there is diffused redness and swelling more or less uniform in the centre, but at its edges showing a zigzag irregularity of out- line that is quite characteristic, one writer having likened it to the burned edges of a sheet of paper. The color is not of that rosy tinge which pure hyperaemia produces, but it has a somewhat more dusky hue. There is mingled with the red a yellowish tinge which becomes more evident on pressure, for then there is noticed a dis- tinct yellowish staining of the skin during the brief moment that the blood is absent from the capillaries. Pressure also shows that there is considerable hardness of the inflamed part; there is usually no perceptible pitting on pressure, except in anatomically loose tis- sues like the eyelids or the scrotum. There is, in fact, a picture of inflammation, of a very superficial character, of the cutis vera, with an exudation of considerable amount in that structure and in the underlying looser tissues. As the inflammation increases in severity there can be detected with a lens minute vesicles situated here and there or in large numbers. Many of these vesicles run together and form bullae of considerable size, which are filled first with a clear and slightly yellowish serum that subsequently becomes turbid or at times becomes even purulent. The smaller vesicles soon dry and form yellowish or brownish scabs, so that during the resolution of the inflammation there may be consider- able desquamation. As soon as the local inflammation is once developed it shows a tendency to spread in various directions. The outline continues to be well marked, and, as has been shown, it is strikingly irregular or zigzag, this peculiar appearance being due to the anatomical arrangement of the lymph-channels along which the cocci spread. The general direction of spreading is, when on the extremities, toward the trunk; when on the face, toward the scalp; but at times the route which the disease takes when starting from a wound may vary greatly. It may meander over a great extent of surface. The writer has seen it invade the entire surface of the body. Such forms of erysipelas have been called "wandering" erysipelas (am- bidans or migrans). The disease does not usually remain more than three or four days in any one place: it moves along, involving neigh- 390 SURGICAL PATHOLOGY AND THERAPEUTICS. boring parts. Occasionally it may appear at a distant point, and it is then called "metastatic;" but this is a form seen chiefly in pyse- mic complications of the disease. The parts originally involved may become inflamed a second time after the inflammation has passed on to distant regions. This tendency to recur is quite cha- racteristic of erysipelas. Volkmann says: " It is like a fire over which one has no control; it burns on wherever it finds material, and it suddenly breaks out afresh in a spot where it was supposed to be extinguished." The duration of the disease is from one to two weeks. It is well to remember that there is always a tendency to recovery. It might even be called a "self-limited" disease. As the inflamma- tion fades away there is an abundant desquamation; the swelling subsides, and, inasmuch as in the ordinary typical cases of erysipe- las there is no suppuration, there is a complete return of the skin to its normal condition. But even after the disease has entirely disappeared there may still be a relapse even more severe than the original attack. The writer remembers the case of a lady who had erysipelas during the healing of a wound from amputation of the breast. The attack was severe, but she entirely recovered, and four months later, long after the wound had healed, a second attack occurred, from which she died. There may be repeated recurrences : PirogofTsaw from six to eight such cases, with a fatal termination in one case. Some patients have what is called " habitual erysipelas, " coming on at certain periods of the year or occurring always on certain parts of the body. In such a case there is usually considerable permanent thickening of the skin and subcutaneous tissue, giving rise to a condition resembling ele- phantiasis. During the progress of the attack there is generally a more or less marked change in the condition of the wound. If the healing process has only been going on for a few days in a case of union by first intention, the wound may reopen partially, and its edges will have a grayish, sloughing aspect. The lips of the wound will be swollen, and a thin, serous, purulent fluid will exude. At other times the healing process appears in no wise disturbed during the attack. In open granulating wounds the closing in of the edges may even proceed faster than before, owing to that so-called "curative" or stimulating action which erysipelas exerts. But usually the granulations lose their brilliant color and become dull and glazed, exuding a small amount of thin, sero-purulent fluid. Here and there hemorrhagic extravasations are noticed, and in cer- ERYSIPELAS. 391 tain spots the granulations lose their vitality and adhere to the wound as a rind or diphtheritic membrane. In deep wounds which are in the early stages of healing considerable sloughing of the underlying connective tissue may occur, and, if important vessels lie near, there may be some danger of secondary hemorrhage. Such a complication occurred once to the writer after ligature of the popliteal artery for aneurism. The hemorrhage, though quickly stopped by the nurse, was sufficient to prove fatal to a patient already exhausted by the disease. More rarely the wound may be attacked by true hospital gangrene, but such a complication is extremely rare at the present time. The constitutional disturbance which accompanies an attack of erysipelas is usually well marked. The gastric symptoms and the chill have already been alluded to. With the chill there is a rapid rise of temperature, which at times may reach as high as 105 F. With the first onset of the inflammation there is no marked remis- sion of the fever, a slight fall only being noted in the morning. The temperature varies in a most erratic manner, corresponding pretty closely with the local progress of the disease, but the tend- ency of the fever-curve is to assume the remittent type, and in the later stages this tendency is quite marked (Fig. 74). With 2 3 4 5 6 7 8 9 10 II 12 13 14 15 16 17 i{ 9 20 21 106 105 104 103 102 101 100 99 98 ! (\ 1 k I V f ^ \/ / k h 1 / V V \ A / u '\ \ 1 1 / V \y / vi \ \ \A J 1/ A /\ \ j V-—' \J ./... u s S, ^ Fig. 74. — Traumatic Fever followed by Erysipelas in a case of Lithotomy. subsidence of the erysipelas there will be a defervescence with speedy return to the normal temperature, but occasionally the febrile disturbance continues, although the local inflammation has disappeared. There is usually in these cases a considerable rise of temperature in the evening, with a fall to the normal line in the morning. Such cases are apt to experience a recurrence of 392 SURGICAL PATHOLOGY AND THERAPEUTICS. the local inflammation, and it is the writer's habit to have the patient thoroughly disinfected and removed to a different room, when all febrile disturbance speedily subsides. It has always seemed to the writer that in such cases there took place a sort of auto-inoculation by which the patient was reinfected by the micro- cocci that had been disseminated through the clothing and the apartment. After a severe attack of erysipelas the defervescence will often be followed by a subnormal temperature lasting at times for a week or two. There are, however, no other symptoms of collapse, and such a temperature is probably due to the feeble condition in which the patient is left. The other varieties of erysipelas that are usually recognized as such in America are the phlegmonous and the facial. In the phlegmonous variety the disease usually begins, as in the ordinary form, in the skin, and it extends subsequently to the deeper parts. The spreading downward of the process is usually indicated by an increased swelling of the part. The skin becomes more tense and harder. Vesicles and blisters form, which are some- times filled with a bloody fluid. The surrounding parts are swollen and cedematous. In the mean time the constitutional disturb- ance is greatly increased, and the fever is more continued in type and at times is of a typhoidal character. The formation of pus may be ushered in by chills, and at the point of suppuration the tense tissue will become soft and more or less fluctuating. A free incision gives vent to a thin and discolored pus in which may be found shreds of sloughing connective tissue. There does not appear to be a circumscribed collection of pus, but rather there is a purulent infiltration of the subcutaneous connective tissue. L,arge masses of sloughing tissue are eventually discharged, which masses have been likened to wads of wet chamois-leather or to wet blotting-paper. Usually several incisions are necessary to give free drainage to the pus and ichor and the masses of sloughing tissue. In the milder form the inflammation is usually confined to one region of the body, as the leg or the thigh or an arm and forearm. Occasionally, however, the disease assumes a more malignant type. The suppurative process spreads between the muscles, which may be dissected away from the adjacent parts for a considerable dis- tance. The periosteum may be attacked and the bones be laid bare to an extent that gives rise to necrosis. Ashurst, Volkmann, and Gos- selin describe a suppurative synovitis which appears to be caused by direct invasion of the joint by erysipelas cocci. The result ER YSIPELAS. 393 of such a complication is of course a more or less complete disor- ganization of the joint, and when more than one joint is involved the termination of the case could hardly be otherwise than fatal. If the synovitis occurs late in the disease, when other symptoms are subsiding, the patient may escape with ankylosis. More fre- quently it is found in these severe forms of erysipelas that the intensity of the inflammation is expending itself upon the skin, and the disease then assumes the gangrenous type, although occa- sionally a most extensive burrowing of pus may take place beneath the skin without involving its vitality. Stille cites such an instance where the skin of the entire abdomen was dissected off the abdom- inal muscles. When, however, the gangrenous type develops, the skin becomes of a dusky red color which does not disappear on press- ure. Large bullae filled with bloody serum form, which, when dis- charged, have an offensive odor. At times the skin may become gradually pale and white or marbled. The sloughing process will extend more or less deeply, and fasciae, muscles, or arteries will be exposed and be involved. At times the gangrene will be limited to certain isolated patches of skin whose vitality has been impaired by the violence of the inflammatory process; at other times the gangrene will involve large areas and will develop at an early stage of the inflammation. The tendency to form pus is slight, and on incising the parts a foul, discolored serum will ooze from the wound. The constitutional symptoms will become graver at the same time. Such types are most frequently met with in old subjects enfeebled by disease or by intemperance, or in young chil- dren affected with tubercle. They are found also in the course of malignant epidemics such as occurred in 1843 ^ n America. Some of the malignant types of inflammation associated with felon and palmar abscess are distinctly erysipelatous in their nature, and are caused by wounds from infected instruments, or they follow injuries received during the handling of a cadaver. Medical stu- dents are occasionally subjected to this affection, and also those who may come in contact with meat or food in a state of decom- position, as butchers and cooks. The inflammation, starting from a slight prick or abrasion on the finger, spreads rapidly up the hand and arm. The lymphatics are usually at first involved, as indicated by red streaks extending up the inner side of the arm. The whole limb, however, may become the seat of an acute and rapidly-ex- tending inflammation. The tendency to suppuration is slight, but the amount of exudation is excessive, and the oedema may spread even over the shoulder and chest. Although such cases would not 394 SURGICAL PATHOLOGY AND THERAPEUTICS. be classed by every surgeon in the category of erysipelas, yet Till- mans regards them as such, owing to the tendency of the disease to spread. The conditions found correspond with what one would expect to result from the action of a malignant streptococcus growth — namely, rapid spreading with slight tendency to suppuration. Such cases resemble closely the so-called "malignant oedema" of Pirogoff. As to the gangrene fondroyante of Maissonneuve, which is also looked upon by Tillmans as a malignant form of erysipelas, it may be said that there are types of erysipelas where there occurs extensive sloughing of the skin as well as of the parts beneath; but the condition of rapidly spreading gangrene of an entire limb with acute putrefaction, which follows injury to blood- vessels or nerves, can hardly be classed with erysipelas merely be- cause of its tendency to extend itself quickly over a large surface. The acute inflammations of the fingers and hand, although usually terminating speedily in suppuration, as in felon or in palmar abscess, may occasionally assume a distinctly erysipelatous type. They are accompanied with great pain and constitutional disturbance, the patient usually seeking relief as soon as possible, and they should be promptly dealt with. It is important to remember that a hand or even a life may be saved by active inter- ference. In the case of a laundress such an inflammation, involving the finger and a portion of the back of the hand, was immediately arrested by free incis- ions a few hours after the first symptom of trouble had been noticed. No pus escaped, but a turbid serum oozed from the wounds. Inflammation of the scrotum and penis of a severe type is described arising independently of any urethral complication. The liability of this region to great distention in acute inflam- mations would make it a favorite seat of the gangrenous type of erysipelas. In other regions, when the tendency to oedema is great, serious complications may result. In a case of erysipelas of the face and neck following a rhinoplastic operation the swelling of the neck was excessive, and pressure upon the glottis produced a dyspnoea that could be relieved only by tracheotomy. Facial erysipelas has sometimes been called ' ' idiopathic erysip- elas, ' ' the idea having generally prevailed that this form of the disease was non-traumatic in origin. Although the possibility of an infection through the mucous membrane has already been con- sidered, the opinion has of late years been gaining ground that the majority of cases arise from some slight solution of continuity in the skin itself. It may even happen that at the moment of the ERYSIPELAS. 395 breaking out of the disease the little wound may have already healed, and the erysipelas takes its origin from the germ contained in the freshly-formed cicatrix. The attack is usually ushered in with a chill which is sometimes of great severity, but the presence of enlarged glands, which may appear before the blush upon the skin, is considered quite characteristic. The most frequent point of departure of the inflammation is the root of the nose. Accord- ing to Raynaud, the spot where erysipelas first appears is one of the lachrymal ducts, through which the disease emerges from the corresponding nasal fossa, which is endowed with lymphatic ves- sels emptying themselves into the submaxillary lymphatic glands. Under the circumstances one would expect to find the lymphatic glands enlarged and painful. Starting from the bridge of the nose, the inflammation spreads laterally across the cheeks toward the ear, rarely involving the tip of the nose. It is said to have a preference for the right cheek. The characteristic irregular outline marks its progress as it gradu- ally spreads over one or both cheeks and finally involves the entire face. The color is a scarlet-red, tense and shining, shading off into a darker hue at the ears. The eyelids are the seat of an cedematous swelling which completely closes them, and the expres- sion of the face is so changed as to render the latter unrecogniz- able. The nostrils are obstructed so that the patient is confined to mouth-breathing. The swelling of the ears is also sufficiently great to impair the hearing. The chin is rarely involved, this being accounted for by the fact that the lymph-stream carries the virus from the upper lip directly to the submaxillary region. The sur- face of the skin is roughened by the presence of minute vesicles which may run together and form bullae whose contents may at times be mixed with blood or with pus. The inflammation may involve a portion of the neck, but more commonly it invades the scalp, in which region the color is much less marked, and might be over- looked when the hair is abundant. There is, however, considerable swelling, pressure is painful, and the glands at the back of the neck are enlarged and sensitive to the touch. An aggravated form of the disease will be accompanied with a high temperature which is more or less characteristic. During the early stages of the inflammation the pyrexia will be of the con- tinued type with slight evening exacerbations, the temperature varying from 103 to 104° F. At the end of four or five days there will be a defervescence which is usually quite rapid. Before the temperature becomes normal, however, there will be one or more 39 6 SURGICAL PATHOLOGY AND THERAPEUTICS. exacerbations which are caused by local outbreaks of erysipelas. During the height of the fever there is, in most cases of this variety, more or less delirium, which is explained in the majority of cases by an irritation of the cortical substance of the brain due to reflex nerve-action or disturbance of the vaso-motor sys- tem, or by the sepsis which causes the fever. The extension of the disease to the scalp is accompanied by an aggravation of the brain symptoms, but it is rare that any pathological changes are found in the brain or its meninges to account for them. Suppurative men- ingitis, when it exists, is usually caused by direct extension of the erysipelas into the orbit — a locality where abscess may occur — and thence by a continuation of the suppurative process to the mem- branes through the orbital fissure. The delirium, therefore, is not necessarily a dangerous symptom, and ordinarily it disappears with the subsidence of the fever, The tendency of the inflammation to involve the tissues of the orbit is a characteristic symptom of the graver form of facial erysipelas. The distention of the eyelids is so great as to cause, in rare cases, gangrene. Considerable disturbance of vision may be caused by conjunctivitis, by congestion of the sclerotic, by cloudi- ness of the cornea, and by oedema in the orbit, but the latter symptom will disappear with the subsidence of the inflammation. If there is deep-seated pain and protrusion of the eyeball, with dis- turbed or complete loss of vision, an extension of the erysipelas to the eye itself may be feared. Blindness, which is occasionally seen as the result of facial erysipelas, is caused by atrophic degen- eration of the optic papilla or by panophthalmitis with suppuration and destruction of the eye itself. Erysipelas neonatorum, which is a very fatal malady, is rarely observed outside of hospitals. The close connection between this disease and puerperal fever has already been alluded to. The period at which it is most frequently seen is at the time of separa- tion of the umbilical cord, and it is from the granulating surface of the stump that it takes its origin. At first there is but little fever, and the slight blush about the navel or the pubes is often regarded as an unimportant symptom. The skin, however, soon becomes a brighter red, and the subcutaneous cellular tissue is indurated and swollen. The next day the inflammation has spread to the genitals and the thighs, below and over the abdomen. The constitutional symptoms now become strongly marked: there is high fever with great prostration; the child cries, and there is great restlessness. The skin in the later stages may become gan- ERYSIPELAS. 397 grenous, or phlegmonous inflammation may occur. Finally, the patient falls into a state of collapse, and succumbs to the disease on the sixth or the tenth day. Inflammation of the tissues and the navel is well marked. There may be found both periarteritis and periphlebitis. The tendency of the arteries to become involved is due to the great thickness of the periadventitial tissue, which is nearly double that seen in the veins. The inflammation extends to the point at which the hypogastric arteries are reflected upon the walls of the bladder. When phlebitis occurs, it will extend along the walls of the veins and into the liver. Pus may be found in the surrounding cellular tissue, and peritonitis may also be a complica- tion, and even the pleura may be affected. A peculiar sclerosis of the cellular tissue of the affected parts has been described, particu- larly of the lower extremities and the pubes. Patches of brown and discolored skin mark the seat of this lesion, but the question whether this affection is to be regarded as a complication of gen- uine erysipelas is considered by Tillmans as doubtful. Erysipelas is found not only in the skin, but occasionally also in the mucous membranes. Attention has already been called to the fact that nasal erysipelas is one of the most frequent points of departure of facial erysipelas. Raynaud states that the advent of the latter affection may be foretold by the swelling of the lachrymal duct caused by the passage of the inflammation through that canal. When the pharynx is involved there is seen in the beginning a marked enlargement of the submaxil- lary and cervical glands. There is a burning sensation in the throat, with dryness and a tendency to dyspnoea or difficulty in swallowing. The color of the throat is a dark red, diffused or in patches, and the swelling is considerable, involving more or less the tonsils. Later, vesicles form, which vesicles soon break and evacuate a serous or sero-purulent liquid, leaving behind little yel- lowish-white patches which are easily removed. The disease lasts five or six days. Occasionally the throat may become the seat of a gangrenous or diphtheritic inflammation, or there may form an abscess somewhat similar to the retropharyngeal abscess. In some cases there is an extension of the inflammation to the mouth, the tongue in this event becoming more or less swollen. In malignant epidemics, such as that described as occurring in 1842 in America, the enormous swelling of this organ gave rise to the name given to the epidemic itself — "black tongue." The inflammation may make its way from the pharynx through the Eustachian tube to the external auditory canal and thence to 39§ SURGICAL PATHOLOGY AND THERAPEUTICS. the head and scalp. The mucous-membrane inflammation may also be secondary to the facial erysipelas, the disease finding its way in through the mouth, nose, lachrymal duct, or auditory canal. The disease does not stop at the pharynx, but may extend down as far as the glottis; it usually stops here, and only occasionally extends and gives rise to oedema of the glottis. Such a complication is of course nearly always fatal. Finally, the inflammation may be traced as far as the lungs, in which case all the symptoms of pneu- monia may develop. Trousseau described erysipelatous pneumonia, or pneumonia migrans, which differs from the common form in not involving an entire lobe, but, beginning insidiously and involving a circumscribed area, it moves from place to place, an apparent resolution taking place in the parts successively involved, until the entire lung becomes affected, and even double pneumonia may result. This form runs its course slowly, and there are frequent improvements with relapses. Raynaud does not accept the identity of this form with true erysipelas unless a distinct extension of the disease from the skin or the mucous membrane has taken place. Without a coexisting erysipelas it would not be justifiable to make such a diagnosis. That erysipelas may involve the female genitals has already been shown. The rectum is occasionally also the seat of the dis- ease by extension from the nates. The writer had an opportunity of observing this form in a case of cancer of the rectum, the dis- ease breaking out after a digital examination. Both nates were extensively involved. Complete relief of the symptoms of stric- ture followed, and an examination later showed that the cancerous mass had disappeared. Unfortunately, there was eventually a return of the carcinoma. The principal anatomical seat of the disease is in the skin. If this organ be examined, the cells of the epidermic layer will be found much swollen or raised up by fluid in the form of blisters. The cells of the rete are enlarged and swollen, and there is a serous infiltration of the lining membrane of the hair-follicles and the sweat-glands. In the upper layers of the true skin there is a rich capillary network of lymphatic vessels, and this region is the prin- cipal seat of the coccus growth. The cocci are seen crowding these capillaries and spreading also into the connective-tissue spaces. The bacteria are most numerous near the margins of the erysipe- latous blush. In the neighboring parts, which have not yet been attacked, cocci are more or less numerous in the lymphatics of the skin, and even in the subcutaneous tissue. Near the red border ER YSIPELAS. 399 they have already reached their highest degree of development. The lymphatics are so crowded here with cocci that the leucocytes are not visible. The cocci may also be found between the bundles of connective-tissue fibres. Within the border-line there are greater hyperaemia and exudation of leucocytes, which are seen emigrating from the blood-vessels in large numbers. Proliferation of the cells of the connective tissue is also going on, but these cells do not appear to take any active part in the process. Nearer the centre of the diseased area the cocci are no longer to be seen, but the inflammatory exudation has reached its highest point. The vesicles on the surface are filled with a turbid serum, but the cocci are seen here only in small numbers. When the growth of the cocci is unusually active the surrounding tissue undergoes necrosis and minute abscesses may form. Undoubtedly many such abscesses develop, and they are subsequently absorbed without any external indication of their presence. In the more malignant types of ery- sipelas suppuration occurs on a larger scale, and it is probable that this process is due to the activity of the erysipelas cocci, which occasionally seem to possess true pyogenic qualities. After an active growth in various directions the organisms cease to continue their development, and the further progress of the disease is thus arrested. The micrococci are not found in the capillary blood-vessels of the part affected. That a certain number of them find their way into the circulation has been abundantly proved. The reason why metastatic foci of inflammation are not thus established is to be found in the fact that after leaving the original seat of their devel- opment the organisms are speedily destroyed. Masses of micrococci are occasionally found in distant organs and in the enlarged glands. Although bacteria are found in the blood only in small numbers, the peculiar changes seen in the blood-corpuscles have been attributed by Heuter and others to the presence of the micro-organisms. The precise reason for these changes is not yet clear. The red blood-disks assume a peculiar crenated appearance. They not only shrink, but readily dissolve and run together, looking, as Stille says, like streams of yellow fluid crossing the microscope. Fatal hemorrhages occurring during the progress of the disease have been ascribed to this condi- tion of the blood. The white corpuscles are usually increased in. number. Endocarditis may occur, involving the bicuspid and mitral valves, and also pericarditis. A slight systolic murmur is frequently heard, which usually disappears with the erysipelas. 400 SURGICAL PATHOLOGY AND THERAPEUTICS. The condition of the heart-action may largely be due to the state of the blood and to some fatty degeneration of the muscular tissue. Fatty degeneration of the diaphragm is sometimes also noticed. The gastric disturbance so characteristic of this disease is not explained by any well-marked local changes. It is probably due to the general septic condition of the system. Ulcerations of the small intestines, such as are seen following extensive burns, are occasionally found. They are probably of catarrhal origin, and may be the cause of the bloody diarrhoea which is occasionally observed. The cerebral symptoms which occur in facial erysipelas would lead one to expect marked changes within the cranial cavity; but this is not the case. The brain and the membranes may be some- what hyperaemic and cedematous, and the large sinuses and the veins may be filled with dark serous blood and thrombi in a lim- ited number of cases. Suppurative meningitis, which is extremely rare, results from the invasion of a phlegmonous inflammation through the orbit. Among the other material changes may be noted enlargement of the spleen, parotitis, and cloudy swelling of the kidneys. Neur- itis may be found in rare cases in the nerves of the parts affected, which affection may give rise to muscular contractions. In grave cases, when pysemic infection has become a complication, there may of course be found the numerous pathological changes result- ing from sepsis. The curative influence of erysipelas when it occurs in the course of other chronic diseases has already been mentioned. Occasionally the Wound itself will seem to heal more rapidly, and the granulations to have a more ruddy and vigorous appear- ance than existed previous to the attack. Chronic inflammations of the skin, particularly those of a tuberculous or syphilitic cha- racter, have been known to yield to an attack of erysipelas that resisted all kinds of treatment. Volkmann, Grivet, and others report quite a number of cases of lupus permanently cured in this way. Chronic ulcers of the leg have been stimulated to heal, and also old sinuses connecting with joints or bones. The therapeutic use of the products of the organism will be discussed elsewhere. (See Appendix.) Raynaud reports, in Ricord's clinic, a case of phagedenic chancre which for two years resisted all kinds of treatment. Finally, Ricord suggested that an attempt be made to bring on erysipelas. All kinds of irritating dressings were tried in vain, as well as charpie saturated with pus. Two ERYSIPELAS. 40 1 months later, erysipelas appeared spontaneously, and the chancre was healed in a few days. Old neuralgias often improve after an attack of erysipelas, and likewise in the insane a temporary improvement has been observed. The disappearance of tumors has been frequently noticed. The writer has already called attention to a case of cancer of the rec- tum in which the growth melted away before an attack of erysip- elas. Tillmans and Coley have collected a number of cases of sarcoma cured in this way. (See Sarcoma.) A woman forty-three years old, having a sarcoma the size of an apple on the left cheek and two other sarcomatous nodules on the face, was operated upon by W. Busch for the removal of a lobe of the larger tumor. Two days later erysipelas appeared and considerably diminished the size of the tumors; after a relapse they disappeared entirely. A man twenty-eight years of age, having a large incurable lympho-sar- coma of the left side of the neck extending from clavicle to parotid, after entering the hospital had facial e^sipelas which involved the neck. During the illness, which lasted eight days, the growth diminished one-half in size. Two days later the patient died, and at the autopsy an extensive fatty degen- eration of the cells of the tumor was observed. The observation made in the latter case probably explains the process by which absorption takes place. The feebly resisting power of the diseased cells renders them less able to resist the action of the micro-organism. It must not, however, be supposed that erysipelas always has this effect upon morbid growths on the surface of the body. The writer has more than once seen epi- thelial ulcers of the face which had passed through an attack of the disease with their vitality unimpaired. The diag7iosis of erysipelas is usually not difficult when the inflammation of the skin is fully developed, lu the early stages, however, before the local symptoms appear, there is no sure guide. Gastric symptoms with febrile disturbance which cannot be ac- counted for after careful examination of the patient strongly sug- gest the near approach of erysipelas. Enlargement of the glands adjacent to the part affected is usually alluded to as an important sign, but it would not, in the writer's opinion, be wise to rely upon a mere enlargement unless the swelling be manifestly acute and be accompanied with indications of an adjacent skin-inflam- mation. The erysipelatous blush is sufficiently characteristic. The doughy swelling of the skin, the yellow infiltration, and the peculiar zigzag outline slightly raised above the level of the adjacent healthy skin are all sufficiently constant to avoid con- 2G 402 SURGICAL PATHOLOGY AND THERAPEUTICS. fusion with erythema, with inflammation due to abscess in the wound, or with irritation from tight stitches. In abscess there should be a rise of temperature, but in the other conditions the constitutional disturbance would probably be so slight as to show dearly their nature. There may be some difficulty in recogniz- ing erysipelas in certain regions, as in the scalp. The presence of inflammation on the face or the ears, together with enlargement of the occipital glands, will then help to establish the diagnosis. The difference between phlegmonous cellulitis and phlegmonous erysipelas is one w T hich in some countries is not recognized at all, and in general it is regarded difficult to distinguish between them. The cellulitis usually starts from a severe wound, owing to the failure of antisepsis in the early stages of the healing process. The most frequent example is that accompanying compound frac- ture. The inflammation in this case is essentially deep-seated, and the skin is not the seat of a distinct and independent inflammation, but it is involved only to such an extent as could be accounted for by the inflammation of the deeper-seated cellular tissues. The appearance of the suppurating tissues shows less tendency to gan- grene in cellulitis than in erysipelas. The prognosis of erysipelas is, on the whole, favorable. After a few days of inflammation there is a marked tendency to resolu- tion. The experience of different surgeons and physicians, how- ever, varies greatly. Stille never met with a fatal case of facial erysipelas where supporting or palliative treatment had been tried. He had, however, seen it fatal when evacuant, sedative, or altera- tive measures had been employed. Trousseau and Chomel, both of whom had a large experience in medical erysipelas, had hardly ever seen a fatal case of the disease. Gosselin, however, had a mortality of 20 per cent, in facial erysipelas. In surgical erysipe- las it was as high as 43 per cent. This is certainly an unfavorable showing — far more so than the experience of the majority of sur- geons of to-day would give. The sanitary surroundings of the hospital patient were probably far inferior to what they are at present, and it is possible that many of these cases may have occurred during the period of an epidemic, which always exerts an unfavorable influence upon the prognosis of the disease. The nature of the wound is supposed to be a factor in the ques- tion of mortality. Large or fresh wounds are considered as more likely to be followed by graver forms of the disease than small or granulating wounds. If the disease attacks the mucous membrane, as in the throat, it will probably be severe; if the vagina is the ERYSIPELAS. 403 point of origin, as in puerperal cases, there may be reason to fear pyaemia or septicaemia. The deeper-seated types of the disease, such as the phlegmonous or the gangrenous, have undoubtedly a higher mortality than the cutaneous forms. In individuals enfeebled by long-standing suppuration, and in alcoholic subjects, the disease will prove a formidable complica- tion. The same may be said of a number of organic diseases, such as diabetes and Bright' s disease. For similar reasons youth and old age are periods of life when the patient is less resistant to its influences than when in the prime of life. Velpeau said that the disease was not dangerous in itself, but only through its complications, and in this opinion the writer's experience would lead him to agree. Secondary hemorrhage and oedema glottidis have led to a fatal termination in two cases which might otherwise have recovered. Even a mild form of the disease, without complications of any kind, may carry off an aged person. As a rule, however, it may be said that erysipelas is in the large majority of cases a mild disease, and one which has a strong tend- ency to get well of itself, quite independently of treatment. The writer's experience of fatal cases has been exceedingly small, and since the antiseptic system has been so highly perfected in all its details, the cases that do occur seem to run a milder course. At the present time the hospital surgeon has only to dread those cases which are imported into the hospitals, and which occur usually in neglected and enfeebled subjects. The cases of facial erysipelas which the writer has met with in private practice have nearly always been severe. The fever, the facial deformity, and the cer- ebral symptoms make a formidable group. The writer does not remember, however, to have seen but one fatal case. The treatment of erysipelas may be divided into local and con- stitutional. Of the latter form there has always existed two prin- cipal varieties, which, in general, may be divided into supporting and depletive. Depletion is an inheritance from ancient times, when venesection, emetics, and purgatives were the fashion. The object of bloodletting, and the reason that it at one time became a more or less popular treatment in the disease, was the effect pro- duced upon the circulation of the brain and the consequent relief given to cerebral symptoms. It may have acted also as a ready method of eliminating the virus from the system, although the number of cocci found in the circulation is not sufficiently large, so far as our knowledge at present goes, to enable one to say that they would be removed in any considerable number in this way. It can 404 SURGICAL PATHOLOGY AND THERAPEUTICS. be conceived that occasionally the conditions existing in a particu- lar case would justify venesection. In a case of facial erysipelas in a plethoric individual with violent delirium a resort to this mode of treatment might be justifiable, but the surgeon should hesitate to advise it in other than exceptional cases. Apart from the pos- sible infection at the point of puncture, and the possibility of the formation of a septic thrombus, the danger of lowering the vitality in a disease which not infrequently has a typhoidal tendency is not lightly to be regarded. Emetics are now so rarely given for any disease that it seems hardly necessary to say a word about them. They may, however, be classed with cathartics as a method of eliminating the virus, for it is probable that the only benefit that could be derived from a cathartic would be this. A laxative might be given at the outset if there is reason to believe the bowels are overloaded. Caution should be observed in this disease to avoid any form of treatment that would act in a depressing way upon the system, and, as a rule, it would be prudent, therefore, not to adopt any of the measures which have just been alluded to. A great variety of internal remedies have been suggested that were supposed to possess special virtues in this affection, the most prominent of these being iron. By English writers iron has at times been regarded as almost specific in its action. It was first recommended by Hamilton Bell, who gave 25 drops of the tincture of the chloride of iron every two hours day and night. The theory of the action of iron is probably based upon the influence which the cocci are supposed to have upon the red corpuscles. The readiness with which they assume a crenated or shrunken appearance has been ascribed to the loss of haemoglobin removed from them. Iron is also supposed by Stille to have a constricting action upon the blood-vessels. A large number of English writers endorsed the treatment of Bell, but in all the latest publications the writer finds the statement of Pick quoted, that, although he has used it in drachm doses every two hours, he has failed to obtain any benefit from it. In the writer's experience iron has not seemed to have exerted any special action upon the disease, although he has not given it in so frequent doses as is advised by the English school. Iron has received endorse- ment from other nations as well as England, both French and Ger- man writers having used it with satisfactory results. Stille also gives the drug his endorsement, although he believes the measure of its utility is not always the same. It seems to him best adapted ER YSIPELAS. 405 to the less sthenic forms of the disease or to those cases where marked debility is present. Cerebral symptoms do not appear to contraindicate its use. PirogofF strongly recommends camphor: he finds immediate results on the use of frequent doses during the first twenty-four hours. It is said not only to diminish the fever, bringing on a profuse perspiration, but also to lessen the delirium. It must not be used continuously for any length of time, as ''camphor delir- ium 1 ■ may be produced. Digitalis and aconite are among the remedies that have had their day in the treatment of this disease. The drug used perhaps more frequently than any other is quinine. It has been supposed to exert an action on the cocci through its power to arrest the migration of the white corpuscles. But as this does not afford an adequate explanation, it has been supposed also to act in virtue of its antipyretic power. According to Stille, it seems to act as well in small and moderate doses as in large anti- pyretic doses. The writer is in the habit of omitting it when the cerebral symptoms are urgent, but he gives it usually in 5- to 10-grain doses, in combination with iron, three or four times a dav. Its tonic action gives it a decided advantage over manv other drugs. "The use of alcoholic stimulants in ordinary cases of the dis- ease is not only unnecessary, but injurious," according to Stille. Tillmans, however, recommends the administration of alcohol as a most valuable remedy both as a stimulant and as an antipyretic, and he is in the habit of prescribing a mixture of sherry with champagne. Under the action of the alcohol, he thinks, with suitable nourishment, one sees the disappearance of cerebral symp- toms. Pick advises the use of stimulants in almost all cases, even from the commencement, and occasionally in large quantities. In the milder forms of erysipelas it is the writer's habit to relv chiefly upon food to preserve the patient's strength. In old or feeble subjects, in the typhoidal types of the disease, or in cases when the amount of nourishment is insufficient from any cause, alcohol is clearly indicated. It is important to remember that delirium does not necessarily contraindicate its use, and that, on the contrary, in many cases nervous disturbance may disappear as the action of alcohol upon the system begins to be felt. Should it be necessary to use other measures to keep the patient quiet, the bromides, chloral, and even opium, can be employed without dan- ger. The antipyretics have but little influence upon the course of the fever, as their action is but temporary, and they do not belong 406 SURGICAL PATHOLOGY AND THERAPEUTICS. to the class of drugs which would be used appropriately in a sup- porting treatment. There is hardly any disease upon which such a vast array of salves and lotions have been expended as erysipelas. In the writer's student days, when erysipelas was the constant companion of the hospital patient, local applications were confined chiefly to the margin of the blush, the adjacent healthy skin being painted with a narrow stripe of nitrate of silver to prevent the further prog- ress of the inflammation. Fresh applications were made as the disease crossed the line thus drawn. Tincture of iodine was used in the same way, but it was also painted extensively over the inflamed surface, and it probably exercised an antiseptic action upon the micro-organisms in the skin. As a local application car- bolic acid is probably used at the present time more than any other drug. White thinks that he can obtain absolute control over the disease by an application of an evaporating lotion of \ drachm of crystallized carbolic acid to 4 ounces each of alcohol and water, the part being kept wet with this solution either constantly or on alternate hours during the day and evening. The disease should yield to this treatment within forty-eight hours. Heuter first recommended subcutaneous injections of carbolic acid in 2 per cent, or 3 per cent, solutions. The injection should be made near the border of the diseased part, and about two Pravaz syringefuls should be used at one time, the dose being repeated at intervals of one or two days. The material injected should be spread over as great a surface as possible by passing the point of the needle in various directions. This precaution is taken to avoid abscesses, which have been observed to form at the point of puncture. The number of doses is subsequently increased to four or five daily. The erysipelas usually spreads over the first points of injection, but it is arrested on the third or the fourth day. A simple and comfortable way to apply carbolic acid is with liquid vaseline as a vehicle. It can be painted on the diseased surface with a soft brush. If a considerable area is to be cov- ered, it would not be advisable to use a stronger solution than 1 per cent. In the early stages, when a small patch of the disease exists, a 5 per cent, solution may be used to advantage. The part can be protected by covering the vaseline with a film of gutta- percha tissue or with oiled paper. Whatever way the drug be used, it is hardly necessary to say that in the earliest period of the disease the treatment is likely to be far more effective. This rule applies with especial force to subcutaneous injections. ER YSIPELAS. 407 Carbolic acid in a mild form can be brought to bear upon the disease through the agency of the class of preparations to which belong creolin and phenyl. These preparations can be applied in a strength of 2 per cent, on hot poultices of cotton or other mate- rial. Such a method is well adapted to erysipelas of an extremity. The treatment can be made more effective by holding the hand or the foot for an hour thrice daily in a hot bath of the same solution. The advantage of these preparations is that they are not liable to cause carbolic-acid poisoning — a complication which should always be kept steadfastly in mind when applying this drug over large surfaces. Concentrated solutions of salicylic acid have been injected subcutaneously around the borders of the diseased tis- sues, and a solution of sulphocarbolate of soda has also been used in the same way. The discomfort caused by the swelling of the skin is greatly relieved by any soothing material which can be so applied as to exclude the air. Dusting on starch or burnt flour accomplishes this exclusion, but it is soon brushed off or is caked up into dry masses. The frequent application of oil or of vaseline to the face with a soft camel' s-hair brush relieves the sensation of burning and stiffness, and it is generally a very soothing remedy. White paint has been used in the same way. A drug which involves the adjustment of a dressing to the face is much less agreeable to the patient. Frequent changes of temperature should be avoided, and exposure to cold, it is needless to say, is liable to aggravate the symptoms of inflammation. The treatment of the wound, if there is one, should vary greatly according to the changes which have taken place in it. Occasion- ally no change of dressing will be necessary, but if there is much sloughing of connective tissue, free drainage must be secured and appropriate antiseptic remedies must be supplied. In phlegmonous erysipelas, it is important to recognize pus as early as possible, and to give it free drainage by multiple incisions if necessary. It is in these cases that prompt surgical interference may be productive of the best results. The tendency of the poison to spread along the loose connective-tissue spaces must be checked promptly, no mat- ter how long or how numerous the incisions. Very hot and large antiseptic poultices are now indicated, and they should be changed several times a day, combined, if necessary, with antiseptic baths, as every opportunity should be offered for a discharge of the slough- ing tissues. The graver forms of gangrenous erysipelas or malig- nant oedema must be dealt with promptly and heroically by long 408 SURGICAL PATHOLOGY AND THERAPEUTICS. and deep incisions. Many a life has been saved by the prompt interference of the surgeon. Small incisions, under these cir- cumstances, are worse than useless. In phlegmonous erysipelas of the face pus forms in the orbital fat, necessitating an incision between the eye and the orbital margin. In scrotal erysipelas of a phlegmonous or a gangrenous character a free incision should be made through the raphe, com- pletely dividing all the tissues involved. This incision usually results in a prompt arrest of the inflammatory process, and the wound heals rapidly. In the treatment of erysipelas of the mouth, the nose, and the fauces the practitioner must be guided by the general principles that govern the antiseptic treatment of septic inflammations of that region. Applied in the form of spray, antiseptic drugs may not only control the activity of the coccus, but they may help also to ward off the complications that may arise from cedematous swelling. In the vagina iodoform powder may be used freely, and antisep- tic douches should frequently be given. As soon as the diagnosis of the disease has been made the patient should be removed from a ward containing other cases, and complete isolation of the case should be preserved. This point should be strongly insisted upon, as, until very recently, erysipelas has not been regarded as a contagious disease. The thorough demonstration of its bacterial origin ought at the pres- ent time to leave no doubt in any reasonable mind upon this point. It is important also to realize that with the desquamation, which sets in early, the apartment is soon filled with the germs of the disease, and that thorough ventilation and frequent change of clothing and sheets are therefore matters to receive especial atten- tion. The tendency to relapse, so characteristic a feature of the disease, may find its explanation in the infection of the wound from the patient's own surroundings. The writer has not infre- quently seen a chronic and relapsing type of the disease arrested, or a tendency to undue prolongation of the pyrexia cut short, by removing the patient to another room. During the period of con- valescence the treatment should be tonic and supporting, and care should be taken to avoid exposure to cold, to draughts, or to fatigue. So long as desquamation lasts isolation should be con- tinued, and in private practice the patient should not be allowed to mingle freely with other members of the household, especially during periods of epidemics, until it is tolerably certain that the diseased organisms have been eliminated from the system. XVII. HOSPITAL GANGRENE. The task devolving upon the writer in this chapter is one of unusual difficulty, for the disease to be considered is one with which few teachers of to-day have had experience and which students never see. The impress of the antiseptic treatment of wounds having been sufficiently strong to stamp out, at least for the present time, one of the most baneful of the traumatic infec- tious diseases, hospital gangrene has become a historic disease. It is not improbable, however, that many students of to-day may be brought in contact with it, for, although the discipline of hos- pital surgery has banished the disease from the wards, it is pos- sible that cases may be brought into hospitals for treatment in the future, as they have in time past, or, what is more probable, that the disease may be met with in private practice. Paradoxical as it may seem, it is nevertheless true that hospital gangrene dur- ing the past decade has been seen only in private practice. As complete a disappearance of the disease has, however, been re- ported in former times, and it is highly probable that the occur- rence of war, of great epidemics, or of any disaster which may profoundly affect the present well-regulated system of hospital service or of surgical aid to the sick poor in large centres of population, will bring back this unwelcome guest. Hospital gangrene is a contagious traumatic disease character- ized by a diphtheritic wound-inflammation produced by a poison the precise nature of which is not yet fully understood, and it is usually accompanied by more or less profound septic constitutional disturbance. It has been known from the earliest times under various suggestive names, such as "wound-typhus," "wound- cholera," "pourriture d'hopital," "sloughing phagaedena," "nosocomial gangrene," etc. One of the earliest descriptions of the disease is by Pouteau in 1783. He describes it as ime maladie qui jiisqtt* a present rt a occupe la plume de personne. The most classic clinical descriptions of the disease were given by Dussaussoy in the latter part of the last century, and by Del- pech in 181 5, based, as they must have been, on an experience which could have been obtained only under the peculiar condi- 409 410 SURGICAL PATHOLOGY AND THERAPEUTICS. tions of that historical period. Indeed, "history" and gan- grene may be said to be coeval, and it is to the medical reports following great wars during the present century that surgeons are indebted for the most valuable data bearing upon the etiology and the treatment of the disease. Crowding of hospitals alone does not appear to be a sufficient cause, but when overcrowding follows the infliction of great privation and fatigue, the conditions most favorable for an outbreak of the disease seem to be obtained. A brief reference to some of the campaigns of late years will illus- trate these conditions. With Napoleon in Egypt the disease was reported as very fatal. According to Macleod, in the English army in the Crimean War the development of hospital gangrene resulted from the lowered general health rather than from specific causes. "It was in many cases a veritable child of the typhus." The French suffered much more severely than did the English. u The system they pursued of removing their wounded and operated cases from the camp to Constantinople at a very early date, the pernicious character of the transit, the crowding of their ships and hospitals, all tended to produce the disease and render it fatal when pro- duced." Many of their cases commenced in camp. On one of their transports sixty bodies were thrown overboard during the short passage of thirty-eight hours to the Bosphorus. The disease raged in the hospitals on the Bosphorus, and followed the returning wounded soldiers even to the hospitals in the south of France. " Both in the French and in the Russian hospitals gangrene was often combined with typhus, and in such cases the mortality was fear- ful." Men who had been wounded after unusual exertion seemed more susceptible to the disease. Macleod states that after the assault on the Redan not a few cases of amputation of the thigh were lost from gangrene of a most rapid and fatal form. In the camp at Scutari the wounds generally assumed an unhealthy aspect when the dreaded sirocco prevailed. During the Civil War the total number of cases reported by the Surgeon-General was twenty-six hundred and forty-two. The conditions under which some of the epidemics occurred are very suggestive. Keen reports one of the earliest which took place in 1862 in Frederick, Maryland, after the battle of Antietam. He says: "The old general hospital, which had contained six hundred beds, was so crowded with patients that one thousand were of necessity placed in the wards, and one thousand eight hundred men were fed at tables and slept some- where." About the middle of October, after some days of cold, HOSPITAL GANGRENE. 411 rainy weather, the first cases were noticed. In December, when Keen left the hospital, fifty cases in all had occurred, with but two deaths. In 1863 an outbreak of hospital gangrene occurred in Annapolis, Maryland, among men who had recently been brought from Rich- mond, Virginia, all of w T hom had been closely confined in the prisons and prison hospitals of that city. "In the prisons they were much crowded, and the majority were unprovided with beds or cots, sleeping on straw which was foul and infected with ver- min." In the epidemic at Nashville, Tennessee, in the same year, the disease appears to have been of an indigenous origin. The cellar under the hospital had passing under and opening into it by several apertures the common sewer of that part of the city. The soil-pipes of the several wards emptied into the sewer without traps. The cellar opened upon an alley from which the infected ward derived its ventilation. The emanations from the cellar were most offensive at all times. Surgeon Goldsmith in his report states: k( I think that the records of surgery do not afford a more unique or striking example of one of the methods of the production of hos- pital gangrene." A still more striking example of the conditions favoring the development of hospital gangrene is to be found in the experi- ences of the Union soldiers in the Confederate prison at Ander- sonville, Georgia. The site of this prison, which was simply a stockade, and which afforded no protection of any kind, was selected by General Winder and was enclosed in November, 1863. The ground covered was about fifteen acres, but the space taken up by the various walls and the dead-line reduced the space to about twelve acres. The ground, which sloped toward the centre on either side, was divided into equal halves by a small, muddy brook. A part of the valley thus formed was a swamp. The refuse from the cook-house and the sewage from the guards' camps w T ere emptied into the brook, and thus rendered it unfit for drinking purposes, so that the prisoners relied chiefly upon wells which they made for the purpose. Every tree had been cut down and no shel- ter was afforded. No provision was made at first toward carrying off the refuse and sewage of the prison, and no sanitary regulations were put in force. " The only living things that seemed to thrive in this place were the flies, and they swarmed. Everything was covered with them, and they were responsible for the maggots that kept the swamp a moving mass of corruption " (Mann). Accord- ing to Jones, a morass of human excrement lined the banks of the 412 SURGICAL PATHOLOGY AND THERAPEUTICS. stream. The greatest number of men accumulated at any one time is said to have been thirty-five thousand, and, although the mortality was enormous, this number was maintained by the fre- quent arrivals of fresh squads of prisoners. In the summer of 1864, Lieut. -Col. D. T. Chandler of the Confederate service, who officially inspected the prison, begged the Richmond government to send no more prisoners. His report states : There is no medical attendance provided within the stockade ; small quantities of medicine are placed in the hands of certain prisoners of each squad or division, and the sick are directed to be brought out by sergeants of squads daily at "sick call " to the medical officers, who attend at the gate. The crowd at these times is so great that only the strongest can get access to the doctors, the weaker ones being unable to force their way through the press ; and the hospital accommodations are so limited that, though the beds (so called) have all or nearly all two occupants each, large numbers who would otherwise be received are necessarily sent back to the stockade. Many — yesterday twenty — are carted out daily who have died from unknown causes and whom the medical officers have never seen The sanitary condition of the prison is as wretched as can be, the principal cause of mor- tality being scurvy and chronic diarrhoea. Nothing seems to have been done, and but little if any effort made, to arrest it by procuring proper food — .... a place the horrors of which it is difficult to describe and which is a disgrace to civilization. The report of Crews Pelot, Asst. Surg. C. S. A. , states, in regard to the hospital accommodations : " A majority of the bunks are still unsupplied with bedding, while a por- tion of the division tents are entirely destitute of either bunks, bedding, or straw, the patients being compelled to lie upon the bare ground." After describing the insufficient supply of food and medicine, he adds: "Our wards — some of them — were filled with gangrene." During the month of August (1864), about the time when these reports were written, there were 31,678 prisoners in the stockade, and the number of deaths in that month amounted to 2993. About this time Dr. Joseph Jones was sent to inspect the condi- tion of the men at this prison. From his extensive and painstaking report are quoted the following details : " In the depraved and depressed condition of the system of these prison- ers, in the foul atmosphere of the stockade and hospital reeking with nox- ious exhalations, small injuries — as the injury inflicted by a splinter running into a hand or foot, the blistering of the arms or hands in the sun, or even the abrasion of the skin in scratching the bites of insects— are sometimes followed by extensive and alarming gangrenous ulceration." Dr. A. Thornbury reports to Dr. Jones that in Ward No. 5 at the Ander- sonville Hospital 325 cases of gangrene were treated during the months of July, August, and September (1864), and that out of that number 208 died. HOSPITAL GANGRENE. 413 Gangrene first made its appearance in April of that year, and in many cases it was difficult to decide at first whether the ulcers were scorbutic or gangrenous. Small-pox also broke out at this time, and several thousand were vaccinated. As was to be expected, in every case affected with scurvy gangrene supervened in the vaccination-wound, and many of these cases died. The origin of the gangrene appeared to depend in a great measure upon the state of the general system. " In such a filthy and crowded hospital as that of the Confederate States Military Prison of Camp Sumter, Andersonville, it was impossible to isolate the wounded from the sources of actual contact of gangrenous matter. The flies swarming over the wounds and over filth of every description ; the filthy, imperfectly washed, and scanty rags ; the limited number of sponges and wash-bowls (the same wash-bowl and sponge serving for a score or more of patients), — were one and all sources of such constant circulation of the gan- grenous matter that the disease might rapidly be propagated from a single gangrenous wound In many cases gangrene attacked the intestinal canal of patients laboring under ulcerations of the bowels Amputation did not arrest hospital gangrene : the disease almost invariably returned. Almost every amputation was followed finally by death, either from the effect of gangrene or from the prevailing diarrhoea and dysentery." The exhalations from the gangrenous wounds of the Federal prisoners in the hos- pital and stockade appeared to extend their effects to a considerable distance outside of these localities. Thus the Confederate soldiers guarding the pris- oners, who did not enter the stockade or hospital, were in several instances attacked with hospital gangrene supervening upon slight abrasions or injuries. " In the gangrenous stumps examined after death the disorganiza- tion of the vessels and muscular tissue was widespread. Stumps from which gangrene had apparently disappeared, and which were thought to be doing well, were discovered after death to be thoroughly rotten within, notwith- standing that there was but little discoloration of the skin and comparatively little swelling. In the decayed state of the blood and in the depressed state of the forces gangrene appeared to affect the tissues with great rapidity and with but slight external marks of inflammatory action." The extent of mortality of this epidemic of hospital gangrene will probably never be known accurately; but, as the testimony of Col. Chandler shows that many cases of severe illness never came under the eye of the surgeon at all, and as Dr. Jones concludes that scurvy directly or indirectly caused nine-tenths of the deaths among the prisoners, and inasmuch as it is known that for one month alone the death-roll amounted nearly to three thousand, and that it was often difficult to distinguish in the beginning between scorbutic and gangrenous ulcers, and that when the epidemic was at its height nearly every abrasion become gangrenous, — some faint idea may be gained of the enormous number of cases of gan- grene that occurred. It is hardly necessary for the writer to say more about the role which bad food, unhealthy surroundings, and depressing influences play in the etiology of this disease. 414 SURGICAL PATHOLOGY AND THERAPEUTICS. The Franco-German War, with all its greatly perfected medical equipments in both armies, was not exempt from this plague. It will serve no useful purpose to go into any of the particulars of this campaign: a single example will suffice: In the hospital at Brest three separate epidemics of gangrene occurred, each one fol- lowing the arrival of a convoy of wounded from the front. It was not alone in time of war that this disease flourished, and, although Joseph Jones makes the statement that it was un- known in the South previous to the Civil War, the writer cannot help feeling that the disease nevertheless existed, but was unrec- ognized. The following statement, taken from Jones's report, at least suggests such a possibility. Writing from the general hospital at' Staunton, Virginia (in 1863), Dr. Merillat says: "Fortunately, I have never had an opportunity of observing in this hospital the disease described in the books as hospital gangrene." He then proceeds to give an account of certain conditions of the wounds in his wards, which account is evidently a description of the ulcerat- ing form of gangrene. Certain it is that the disease was familiar to hospital surgeons in Boston and in Philadelphia, as the writer can testify from personal knowledge. A most malignant epidemic at the Massachusetts General Hospital is one of the earliest recol- lections of his professional career. This epidemic occurred at a period when the river flats adjoining the hospital grounds were filled in. One of the peculiarities of this epidemic was the fre- quent complication of erysipelas. The following case is taken from the records of October 1, 1864: Amputa- tion of leg at junction of middle and upper thirds for osteosarcoma ; on October 6, sloughing aspect of wound with exposure of both bones ; on the 7th, chill ; on the 14th, complete separation of flaps by sloughing. The muscles are separated for some distance from the integuments. Some hem- orrhage from the main artery. Death occurred October 15. Many cases of amputation presented about this time very typical examples of the pulpy form. The wounds of stumps were enormousty swollen and everted. Second- ary hemorrhage was of frequent occurrence, and in several cases ligature of the femoral artery in Scarpa's triangle for hemorrhage was followed by gan- grene of the ligature-wound, and death. But few cases have been seen in the hospital since the introduc- tion of the antiseptic methods. A case of the ulcerating type the writer saw, however, in the summer of 1889, ^ n the wards, but failed to obtain from the surgeon in charge of the case a specimen for bacterial study. Unfortunately, at the time of the disappear- ance of hospital gangrene bacteriology had not reached that point of perfection which it since has, so that no satisfactory scientific HOSPITAL GANGRENE. 415 work on the relation of micro-organisms to the disease has been accomplished. The experimental work of Koch, although it is confined en- tirely to animals, is of sufficient value to be recorded here. In Koch's experiments on septicaemia in mice he found in certain cases, in the neighborhood of the place of injection, in addition to the septicaemia bacillus, a micrococcus growth which produced a disease resembling gan- grene. By using field-mice instead of house-mice he was enabled to elimi- nate the bacillus, as this organism would not grow in the blood of the former animal. The micrococcus growth, however, developed at the point of inocu- lation just as well in field-mice as in house-mice. He found the ear of the mouse the best place to study the influence of the coccus upon the tissues and its mode of growth. He says: " Spreading out from the place of inocu- lation one can see extremely delicate and regular micrococcus chains, here pressed together so as to form thick masses, there arranged diffusely, the individual elements of these chains, as can be understood from the measure- ments of the longer ones, having a diameter of 0.5//." These organisms can be traced all through the gangrenous portions of the ear ; here neither red blood-corpuscles nor nuclei of lymph- or of connective-tissue cells can be seen. Even the exceedingly resistant cartilage-cells are pale and unrecog- nizable. "All the constituents of the tissues look as if they had been treated with caustic potash: they are dead, they have become gangrenous. Under these circumstances the bacteria develop all the more vigorously, the micro- cocci penetrate in numbers into the damaged blood- and lymphatic vessels, and here and there the cocci fill the vessels so completely that they appear as if injected." Just beyond the point reached by the cocci is a densely agglom- erated mass of nuclei, forming a wall, as it were, against the invasion of the micrococci. This wall has no great breadth, and immediately beyond it comes the normal tissue. The micrococci do not quite reach up to this layer of leucocytes. Between the two there is a layer of considerable breadth con- sisting only of gangrenous tissue, in which neither micrococci nor leucocytes are found ; the cells of the layer of leucocytes adjoining this gangrenous tis- sue appear to be in a state of disintegration. Koch thinks that the organisms excrete a soluble substance which comes in contact with the surrounding tis- sues by diffusion. When greatly concentrated this product has such a dele- terious action on the cells of the tissues that they perish. [A sort of coagu- lation-necrosis evidently takes place.] At a greater distance from the micro- cocci the poison becomes more diluted and acts less intensely, only producing inflammation. "Thus it happens that the micrococci are always found in the gangrenous tissue, and that in extending they are preceded by a wall of nuclei which constantly melts down on the side directed toward them, while on the opposite side it is as constantly renewed by lymph-corpuscles deposited afresh." The close resemblance between the membrane of diphtheria and certain forms of hospital gangrene has raised the question of the identity of the two diseases. The diphtheritic inflammations, how- ever, do not necessarily have any connection with the infectious 41 6 SURGICAL PATHOLOGY AND THERAPEUTICS. disease known as " diphtheria." The diphtheritic membrane, such as is seen on mucous membranes or elsewhere, is due to a combina- tion of necrosis and inflammation. It is an anatomical process which may be caused by the Klebs-L,6frler bacillus, the organism that produces true diphtheria, or by the streptococcus, and possibly by other organisms. The action of the diphtheria bacillus is quite superficial, and it does not show a tendency to invade the deeper tissues. The presence of a diphtheritic membrane on an open wound does not therefore necessarily imply true diphtheria. The presence of streptococci in all other forms of membranous inflam- mations is a possible indication of what may be found in the diph- theritic form of hospital gangrene. The latest microscopical studies of specimens of gangrene, taken from the recently-dead subject, are those of Heine, made probably about 1870 — a period when little was known of the proper methods of bacteriological research. Sections examined with high powers of the microscope showed on the surface a finely granular homo- geneous layer, varying greatly in thickness, which contained large numbers of chain-like organisms resembling " those described bv some authors as micrococci. n These organisms were seen some- times in many-branched chains and sometimes in masses closely packed together. In the deeper portions of this layer were seen fragments of leucocytes (Eiterzelleii), and deeper still were found masses of leucocytes closely packed together, the same organisms being found either in the cells or in chains intertwined between them. Wherever the leucocytes had broken down the micrococci were more visible. In this layer was also seen a fine network of fibres which at places were continuous with broad bands of coagu- lated fibrin running between the cells. Lower still he found a layer of granulation tissue rich in blood-vessels, in many of which coagulation of the blood had taken place. In places the walls of the vessels appeared to have broken down, and they were sur- rounded by circumscribed clots or by diffused infiltration of the surrounding parts with blood. The tissues near the wound ap- peared to be infiltrated for a considerable distance with leucocytes which were collected between the fat-cells, the muscular fibres, and the tendons, so that these structures were fairly buried in the infil- trating tissue, and their nuclei appeared to be undergoing a degen- eration (coagulation-necrosis). The principal conditions observed by Heine were the larger numbers of micro-organisms, the marked tendency to coagulation of the intercellular substance and exuda- tion fluids, the enormous accumulation of leucocytes, and the HOSPITAL GANGRENE. 417 tendency to degeneration of the cells and coagulated intercellular substance in the final putrefactive changes. The latest article on hospital gangrene is by Rosenbach. A careful study of two specimens sent to him from the Army Medical Museum at Washington showed that the preparations, preserved since the Civil War, were too old to make it possible to detect the presence of bacteria. Rosenbach reports in his earlier monograph two cases of traumatic gangrene in which the disease originated in a slight injury to the finger. Rapidly-spreading gangrene of the arm followed, and cultures taken from incisions made into the gan- grenous portions showed the presence of the streptococci. In two cases of traumatic gangrene, with emphysema, of a most malig- nant type he was able to find, microscopically, a bacillus, but no streptococci. The cultures failed. The writer mentions the following cases of traumatic gangrene — although clinically the disease is widely different from hospital gan- grene — because they have a bearing upon a personal experience: In 1883 the writer was summoned into the country to a case of traumatic gangrene following a gunshot injury of the leg. The disease had in forty- eight hours spread from the foot to the middle of the thigh, and the odor showed that putrefactive changes were well advanced. The operation of amputation in the upper third was performed at midnight. Proceeding on his journey the next morning, the writer met a physician in consultation in the afternoon, and explored a sinus communicating with a carious rib. A few days later a well-defined type of hospital gangrene was developed in the wound, which was not larger than would admit a good-sized drainage- tube, and before the disease could be checked an ulcer the size of a dessert- plate had formed. The only instrument employed in both operations was a pair of scissors, as, with this exception, the instruments of his colleague were used in the second operation. The scissors were employed to lay open the sinus where gangrene subsequently supervened. That they were the vehicle by which bacteria were transferred from one case to the other seems highly probable. So far as the evidence goes, it would seem to favor strongly the assumption of a streptococcus bearing the same relations to gangrene that the streptococcus erysipelatis does to erysipelas. But the bac- teriology of gangrene, after all has been said, from a modern point of view may still be regarded as almost a terra incognita. As has already been explained, the disease is not confined to hospitals, but may occur in private practice. The records of nearly all hospital epidemics show that many of the cases were brought into the hospital with well-developed gangrene. At the present time it is much more likely to be met with outside the hospital, where antiseptic surgery has no control. Why cases are 27 41 8 SURGICAL PATHOLOGY AND THERAPEUTICS. not brought into hospitals is a difficult question to answer. None are reported, although probably such occurrences do happen. It might be assumed that no epidemics exist at present, but with the present knowledge it is known that such surgical epidemics take their origin from favorable combinations of bad weather, filth, and crowded quarters. These combinations are not so difficult to obtain in every large city as to make the origin of sporadic cases of gangrene impossible. The presence of extra-mural cases of gangrene in the city during a hospital epidemic may be accounted for by contagion, for the route which the virus takes is often a very circuitous one. An example of this is given by Brugmanns, who states that in 1799 a quantity of charpie was sent from France for use in the Dutch hospitals. Wherever these dressings were used gangrene occurred. Inquiry brought out the fact that the charpie had already been used for dressing wounds, and that it had been cleansed and bleached for the trade. Much has been said about the contagiousness of gangrene. Medical literature contains too many examples of successful inocu- lation from man to animals and from man to man for the question to admit of any doubt. Joseph Jones experimented upon a large pointer dog: about half an ounce of gangrenous matter was taken from the wound of a dead subject and was buried between the lips of an incision. The wound subsequently took on a typically gangrenous condition. Fischer made wounds in five rabbits and rubbed into the wounds the discharges from a gangrenous wound. In all cases gangrenous ulcers were produced. Dussaussoy treated an ulcerated carcinoma of the breast in a man fifty years of age with inoculation of gan- grenous matter, the patient having refused to submit to the actual cautery. He dressed the sore for several days with charpie soaked in the gangrenous discharges, but without effect. He then decided to bruise the granulations and make them bleed, and then applied the matter to the freshly-made wounds, and in three days the ulcer had become gangrenous. This coincides with clinical observation that fresh wounds are more susceptible to the disease than those that are suppurating freely. Ollivier in 1810 had his arm inoculated with gangrene during an epidemic in Spain. He visited for this purpose a locality where the disease existed. The matter was taken from the wound of a young soldier who finally died of the disease. It was inoculated with a lancet into the skin of the deltoid region, after which HOSPITAL GANGRENE. 419 Ollivier immediately returned home, distant a two-days' journey on horseback. Gangrene established itself in the puncture, and could only be controlled by the actual cautery. The following is an example of contagion from patient to patient reported by Act. Asst. Surg. Cleveland: In the officers' hospital an officer with gangrene occupied a room alone. The carpenters wished to put in a water-pipe, and he was removed to a room in which were three other officers with wounds not then gangrenous. All four had their wounds exposed and dressed, and the gangrenous odor pervaded the apartment. Although the officer was returned to his own room in an hour, the next day gangrene appeared in the wounds of the other three who had been exposed to the infection. Many clinical observations are cited where cases in hospital wards have not communicated the disease to patients with wounds in the adjoining beds, while patients in distant parts of the ward were attacked. This inoculation can easily be explained by trans- portation of the virus by dressers and attendants. More difficult to explain, however, is the existence of two wounds in the same indi- vidual, one of the wounds being gangrenous, the other being healthy. Asst. Surgeon Thomson reports the case of a soldier wounded by a frag- ment of shell which passed across the right thigh below Poupart's liga- ment, through the scrotum, destroying the right testicle, and behind the left thigh. The thigh-wounds were both superficial. The wound in the left thigh was attacked with gangrene. At this time there was in the right thigh a granulating surface, three by two inches in dimensions, level with the integument and cicatrizing rapidly. A smaller equally healthy surface remained unhealed upon the scrotum. The gangrenous ulcer continued to spread until it had involved the perineum and was eight inches in diameter, when it was finally controlled by treatment. In spite of the profuse dis- charge, the other wounds continued to cicatrize rapidly. Surgeon Thomson remarks: "If, therefore, the disease be propagated by inoculation, all the circumstances were favorable, since the proximity of the thighs at their upper part and a denuded surface on the scrotum, that might act as a link, render it certain that a portion of the great discharge from the left must fre- quently have been placed in contact with both of the other sores." Such a case seems not difficult to explain on the theory of the protective influence of the granulations. A bruising of the sore on the posterior aspect of the body led to its inoculation from some outside source. The healthy state of the granulations of the other wounds served as a protection to them. Probably most examples of this sort, when analyzed, can be explained in some such way. They were usually made to serve as an illustration of the theory that hospital gangrene is a "constitutional disease;" that is, a disease not due to local contagion. 420 SURGICAL PATHOLOGY AND THERAPEUTICS. The question of the possibility of inoculation through the uninjured skin has been raised by Rosenbach, who points to Garre's experience with the inunction of cultures of the staphy- lococcus pyogenes aureus on the sound skin (p. 138). Very slight bruises are sufficient, as has already been seen. Gangrene is said to have occurred in the days of slavery after the use of the lash. Jones states: l ' Gangrenous spots followed by rapid destruction of tissue appeared in some cases in which there had been no pre- viously existing wound or abrasion." It is not probable, how- ever, that clinically gangrene is found developing in the unin- jured skin. . That meteorological influences favor the outbreak of an epi- demic of gangrene need hardly be said after the testimony of Macleod, of Keen, and of others already quoted. The hot sirocco was always dreaded at Scutari, and the peculiar climate at Andersonville had undoubtedly much to do with the progress and virulence of the epidemic. The heat of a camp exposed to the full rays of a summer sun in Georgia, and the heavy rains of that region, combined to favor the growth of a bacterial poison. In the North the sudden advent of cold and stormy weather is frequently noted as immediately preceding an epidemic. The period of incubation does not appear to be of certain dura- tion. The observation of Cleveland quoted above would place it at as short a period as twenty-four hours. Rochard cites a case where one week is supposed to have elapsed between the perform- ance of an operation with an infected instrument and the outbreak of the disease. In Ollivier's case of inoculation of his arm with the virus the characteristic appearances showed themselves first on the third day. The principal forms which are described by modern authorities are the ulcerating and pulpy forms. The term "diphtheria of wounds" is also frequently used to denote a milder type which appears to affect the granulations only. Some regard this simply as a milder form of ulcerating or " phagsedenic " gangrene; others are opposed altogether to the use of the term " diphtheria " in con- nection with gangrene, as the two diseases should not thus be con- fused with each other, they being two entirely distinct affections. Heine takes strong ground in favor of the identity of the two dis- eases. He bases his views partly on the frequent occurrence of diphtheria of the throat during epidemics of gangrene, and of cases of diphtheria following the reception of gangrene into hos- HOSPITAL GANGRENE. 421 pital wards. During an epidemic at Heidelberg, Heine dressed the wounds for several weeks, during which time he had not seen a case of diphtheria. At the end of a month he was taken ill with diphtheria. During Heine's illness O. Weber, the noted surgical pathologist, took charge of his cases, and a few weeks later he also was attacked with diphtheria, which terminated fatally, although he had not previously been exposed to the disease. The present knowledge of diphtheria would enable one to deter- mine in a similar case whether the disease was a form of infection with the Klebs-Loffler bacillus, or, what is more probable, was a mixed infection of other organisms. A strong argument against the identity of the two affections is the alleged absence of paralytic symptoms following gangrene. Heine explains this by the relative nearness of the throat inflam- mation to the base of the skull, and by the ease with which such inflammation would extend to the nerves usually affected. Rosen- bach thinks that this paralysis is not produced in this way — that from the present standpoint of our knowledge the paralytic phe- nomena must be regarded as the result of a ptomaine-poisoning, and that the absence of such symptoms in gangrene implies the action of a different virus. Heine quotes, however, certain cases of gangrene where symptoms of paralysis have actually occurred, but his opponent regards these cases as not genuine gangrene, but as diphtheria of the wound. Felix inoculated wounds with the poison of diphtheria by dressing granulating wounds with charpie impregnated with fragments of membrane and secretions from cases of diphtheria. In two cases diphtheritic inflammation of the wound, of a moderate degree of severity, was produced. It is not denied that gangrene may not affect the mucous membranes, but it is claimed that in such cases the deep ulcerations and the charac- teristic conditions of the surrounding parts present a very dif- ferent appearance from ordinary diphtheria. Finally, the prevalence of diphtheria for nearly a score of years since the disappearance of gangrene is strongly suggestive of a radi- cal difference in the exciting causes of the two diseases, and, inas- much as it is known that a diphtheritic membrane can be formed by organisms which bear no relation to true diphtheria, there is now but little evidence to produce in favor of their identity. In the mean time, guided by clinical appearances only, it will be best to distinguish a diphtheritic form of gangrene. This form may be regarded as the mildest type of the disease, and as one in which the granulations are chiefly affected, and in which there is an arrest 422 SURGICAL PATHOLOGY AND THERAPEUTICS. of the healing process rather than destruction and enlargement of the area of the wound. The earliest change to be noted — and one which, in the writer's student days, the dresser was cautioned always to watch for carefully in every case — was a change of the granulations from their healthy red color to a grayish tint. There is at first a loss of color. The surface of the wound becomes glazed and somewhat opaque, forming a thin veil or membrane through which the contour of the granulations is still seen. The increasing opacity and thickness of this layer finally forms a sort of u rind," which occasionally develops without any accompanying symptoms of infective inflammation. This membranous condition of the wound may be caused by some accidental source of irritation, such as the retention of foul discharges, mechanical irritation, or the presence of a foreign body in a fistulous canal opening into the wound. What has occurred is chiefly a change in the character of the discharge from the wound with coagulation of the exudation on the surface. When, however, the disturbance in the healing pro- cess is more profound, as shown in alteration of the granulation tissue with distinct increase of irritation in all parts of the wound, in greater readiness on the part of the granulations to bleed, and in a more inflamed appearance of the margins of the wound, the surgeon may look for coagulation-necrosis involving the upper layer of the granulations, and consequently the development of a diphtheritic membrane. This membrane may involve a depth of tissue sufficient to produce necrosis of the surface to a con- siderable extent and the formation of sloughs, or there may be seen here and there small extravasations of blood due to the breaking down of the walls of the vessel which supplies the dif- ferent granulations. The secretion of the wound is at first diminished; later it changes in character and becomes more watery, and it is then much more abundant, so that in some cases the dressings become quickly saturated with the discharge and require to be changed frequently. The margins of the wound are not materially affected in the milder cases, but when the granulating surface becomes more deeply infected the edges of the ulcer are found thickened and raised, while at the same time portions of the membrane melt down or are thrown off as small sloughs. The wound assumes a crater-like appearance, and occasionally the edges of the skin begin to break down and have an appearance as if they had been gnawed by some rodent. Usually the process is arrested by treat- ment, and as the membrane melts away or is cast off the healthy HOSPITAL GANGRENE. 423 granulations appear, and the swollen and somewhat injected lips of the wound resume their natural size and color, the cicatrizing pro- cess proceeding once more. The type to be placed next in point of severity, but which writers generally regard as less frequent than either of the other varieties, is the ulcerating form. Here the formation of a membrane is not so apparent: the granulations, however, have an unhealthy appearance, are paler than usual, and have lost their plump, exuberant character. On closer inspection it is found that a number of them are the seat of minute dark-red or light-gray patches, which are sprinkled about over the surface of portions of the wound. These points soon break down and leave behind them clean-cut circular excavations in each granulation. Some of these patches look like small pustules, which, when they break, expose a grayish surface. These minute ulcerations subsequently run together and form an ulcer in the granulating surface. Several such ulcerations may develop in different portions of the wound, and when the process has extended to the outer border, the skin becomes involved and breaks down, leaving semi-circular defects which give the lips of the wound the appearance of having been bitten out. At this time the surface of the wound becomes dis- colored and assumes a grayish or a brownish hue, the discharge becoming thin and streaked with blood and having a foul odor. The process is not usually a rapid one, and the breaking down and enlargement of the wound may be an affair of several weeks. In this way the wound may increase in size indefinitely both in area and in depth. The extent to which the ulcerating process will penetrate depends somewhat upon the anatomical nature of the tissues. A dense fascia will exert a limiting influence, but when loose connective tissue is involved muscles may be dissected out or be eaten through. In the case reported by Thomson, already quoted, the condition of a wound of the posterior portion of the thigh is thus described: " An ulcer three by two inches in extent was found, oval in shape, covered with an ashy-gray slough upon its margin, thickened and everted, surrounded by a livid areola, and, instead of normal pus, discharging a thin fetid serum mixed with debris." This description portrays fairly well the diphtheritic type. Attempts to treat it with applications of nitric acid were unsuccess- ful, and the report continues : "There was the characteristic margin preceded by the areola of livid stasis preparing the tissues for their rapid destruction. The connective tis- sue beneath the skin had been destroyed, so that the skin for an inch from its margin was perfectly movable. The muscles, separated from each other by 424 SURGICAL PATHOLOGY AND THERAPEUTICS. the death of their connective tissue, lay in the wound, bathed in its discharge, but rosy and florid and resisting the advance of the disease. This sore was so unmistakably hospital gangrene that several pictures of it were taken by direction of Surgeon Bristow, which represent well the surface of the ulcer dripping with its thin, serous discharge, mingled with threads of dead con- nective tissue, its ' piled-up,' thickened, and everted margin surmounted by a thin line of vivid redness, and its broad zone of purple congestion shading away into a bronze hue, the depth of color in the areola indicating the en- gorgement of the small vessels, and its hue the feebleness and slowness of the movement of the blood But little change had taken place in the character of the ulcer, which was eight inches in length by seven in breadth, extending to the perineum and irregularly oval in shape. The muscles exposed (the semimembranosus and biceps) had yielded, and were now almost divided. ' ' The interval of time which had elapsed during which the changes described had taken place was a little over two months ; from this time on convalescence took place. A case like this may be regarded as a somewhat severe example of the ulcerating form, but the appearances of the skin around the wound are such as are to be expected when the ulcerating type has reached its full degree of development. Frequently, however, the disease is confined to a superficial form of ulceration, and then there would be seen but little sloughing or membrane-formation. The wound has a dirty, unhealthy, or sometimes only an irritated look, and is constantly growing larger until arrested by treatment. The different phases of phagsedena are well portrayed by this type of gangrene. The striking results of phagsedenic ulceration are well shown by Plate xxvii. of the Surgical History of the War of the Rebellion, where a portion of the calf of the leg has been eaten to the bone, laying bare the popliteal artery at its lowest portion. The wound looks as if it had been produced by the teeth of some wild animal. These examples are, however, suggestive of those forms which may be said to come between the ulcerating form and the character- istic and commonest type of hospital gangrene — " the pulpy form." This variety includes all the graver cases with extensive and deep- seated loss of tissue. The pulpy form may begin with a diphtheritic infiltration of the granulations, which infiltration rapidly swells to a thick and cedematous covering of the wound, or the color of the granulations deepens, owing to an intense hyperemia of the part. Under the increased blood-pressure many of the tender walls of the blood- vessels give way and diffuse extravasations take place, or, as Piro- goff describes, hsematomata may form rapidly, owing to profuse bleed- ing in the granulation tissue at certain spots. This form is some- HOSPITAL GANGRENE. 425 times called the " hemorrhagic.' ' Whatever the preliminary changes may be, the surface of the wound soon becomes enor- mously swollen, and it is changed into a dirty gray or a greenish mass of putrefying sponge-like tissue. The secretion of the wound, which was at first arrested, now begins to run again. It wells up through the pulpy mass in the form of fetid ichor, the odor of which is thought by many to be quite characteristic. The edges of the wound become extremely sensitive, and they are everted and raised and of a deep-red or purple tint, shading off, when the dis- ease is spreading, into a bronzed hue. Changes as profound as these may occur within from twenty-four to forty-eight hours. The swollen membrane thus formed soon begins to putrefy, but it does not readily separate. Its color changes frequently, and it is difficult to describe. It is often distended with gas from the decomposing substance, and it finally breaks up into soft, gelatin- ous sloughs or moist, cheesy debris, and is thrown off, only to be followed by new formations beneath it. In the mean time the deeper tissues have been attacked, and the advance of the infec- tion is indicated by the increased amount of inflammatory reaction, as shown by the great swelling, the discoloration of the surround- ing integuments, and the profound constitutional disturbance. At this time secondary hemorrhage from some large vessel frequently takes place, speedily terminating the case fatally or necessitating the ligature of the femoral or brachial or other vessel of largest size, thus involving the formation of a wound in which gangrene may develop itself anew. The changes described are taken from personal memory of cases which occurred in the epidemic of the hospital to which reference has already been made. The differences that may occur in the form of the exudation are of course very great, each epidemic showing peculiarities of its own. Rosenbach describes a gelatinous membrane which occasionally forms enormous colloid vegetations. When in a state of putre- faction such voluminous masses have been likened to decomposing foetal brains. The discharge from the wound is enormous; it may be orange- colored or may be brownish, or — what is a more generally fitting description — it may be foul and dirty. Pitha says of it: " No mat- ter how deep the infiltrated surface appears to be, it always seems insufficient to account for the great quantity of the discharges The foul pus pours in such cases as if it came from an inexhaust- ible spring. ' ' As the infection advances no tissues are spared: the muscles are 426 SURGICAL PATHOLOGY AND THERAPEUTICS. laid bare, and they often so swell and soften, as they are rapidly eaten through, as to suggest the presence of a sloughing sarcoma. The nerves are dissected out, but they generally retain their ana- tomical form and distribution. The fasciae are more resistant, but they do not long resist the advance of these graver types of the dis- ease. Articulations may be laid open, and even the bones may not escape necrosis. In some of the most malignant types the greater portion of a limb may thus become disorganized, but these cases, fortunately, are rare. The skin has a marble hue, the parts are distended by emphysema of the connective tissue, and mortifica- tion of the limb may ensue. The great swelling which takes place in the different layers of the wound is often deceptive as to the amount of tissue which has been lost. This is shown after the membrane separates and the wound rapidly contracts. The disease does not always advance with the rapidity indicated. Even cases which eventually may terminate fatally may begin and advance with great deliberation until, as the vital powers become lowered, the gangrene seems to gain new strength and to assume a more malignant type. The early writers generally state that at first constitutional symptoms are wanting, but this is probably due to the fact that thermometric observations were not taken. It is not, however, until the second week that the symptoms become marked. The fever-curve is of course variable, corresponding more or less with the local manifestations. It is. quite irregular — more, as Heine says, like an outline of the Alps. The constitutional symptoms are probably produced by the absorption of the toxic products, or possibly by the bacteria themselves, and the fever does not differ clinically from that of septicaemia. But, although the typhoid- like condition with diarrhoea is characteristic of both affections, in gangrene there is a marked clinical feature in the great sensitive- ness of the wound. The pain and nervousness attending the dress- ing of the wound are such, in some cases, that few men possess the fortitude to go through the ordeal. The bare idea of a change of the dressing may bring on, according to Pitha (whose patients were probably Southern Germans), convulsive trembling, perspiration, and palpitation of the heart. It is often necessary to etherize the patient at these times, especially when escharotics are applied. It is not surprising that many cases are followed by relapse, or that patients who have been discharged from the hospital as apparently cured have returned with the disease in full bloom again. Such a HOSPITAL GANGRENE. 427 reinfection could easily take place from germs concealed in some part of the patient's person. Among the most frequent complications of the disease is ery- sipelas; and if it may be supposed that they are both caused by the streptococcus group of organisms, it is certainly not surprising. With such a severe infective form of inflammation as gangrene, it is also to be expected that pyaemia may occasionally be met with, but this complication would probably not supervene unless local phlegmonous inflammations had followed or complicated the origi- nal disease. A few selected cases may perhaps give a clearer idea of the cause and peculiarities of the pulpy form of gangrene: Thomson reports a case of amputation of the thigh for a fracture of the tibia caused by a Minie-ball at the battle of Fredericksburg. The wound had healed, except a narrow strip of skin, on February 18, when it was found covered with a gray slough and had the characteristic odor. The cicatricial tissue soon yielded to the sloughing, and the subcutaneous connective tissue had been destroyed for two inches beneath the skin at the outer angles of the original incisions. The destruction was limited to the connective tissue until the nineteenth day, when the skin became involved. The constitu- tional symptoms became grave; the mental despondency was marked; a free diarrhoea also began. The whole surface of the stump had now a margin of black mortification of the skin, outside which was the usual areola of purple congestion, the complete stasis of to-day becoming the sphacelus of to-mor- row. The end of the femur, protected by rosy granulations, now protruded from the black mass of sphacelus, the integument having become loosened by the destruction of the subcutaneous connective tissue, and retracted. The presence of this mass of putrefaction seemed to add to the nervous prostra- tion, if, indeed, the absorption of such peccant material is not its sole cause. On the thirty-first day the symptoms had been typhoidal for several days: emaciation had gone on rapidly; there had been subsultus tendinum and muttering delirium with extreme prostration until this date, when death occurred. The limb was removed after death, and the specimen sent to the Army Medical Museum (Specimen 1000, Surg. Sect.). The sphacelus had involved all the tissue for five inches above the divided bone, and there seems to have been a faint effort to form a line of demarcation. An interesting point illustrated by this case is the presence of healthy granulations at the end of the bone in the centre of the gangrenous mass. This is a peculiarity noticed by many writers — namely, that a portion of a wound may be affected with the dis- ease, and in another part the granulations may be in a perfectly healthy condition. Jones reports a large number of cases in great detail. The following case is illustrated by two colored plates: A man twenty-two years of age, who had been in the Confederate service nearly four years, was wounded in the middle of the left thigh (Aug. 17, 428 SURGICAL PATHOLOGY AND THERAPEUTICS. 1864) by a piece of lead, weighing about a pound, from a rifle-shell. He was removed from Atlanta to Macon, and the disease appeared four days after his arrival at the latter place. On the fourteenth day the wound in the thigh was eight inches in diameter, was nearly circular, and was deeply and irregularly excavated; the edges were everted and the surface was coated with a dirty grayish, purplish, and dark-bluish leaden-colored laver. There was a most fetid, irritating, and sanious discharge from the wound, but no pus. Temperature 105. 6° F. The next day the large muscles of the thigh were exposed by the gangrenous excavation, and they were fre- quently observed, quivering, especially after the application of nitric acid, which causes intense pain. On the twenty-fifth day the wound began to assume a healthy appearance, and on the thirty-fifth day it was cicatrizing. The next case, which is an example of the ability of gangrene to lay open joints, is quoted from the same author: The patient was thirty- seven years of age. A Minie-ball struck the flesh}- part of the forearm about the middle : no bones were injured. This injury- occurred July 20, 1S64, the patient being transferred from Atlanta to Macon. At the end of a month, when the wound was healing, it took on gangrenous inflammation, became swollen, and was surrounded by a red, livid areola and burned most painfully. By the middle of September the muscles of the arm and forearm in the region of the elbow-joint were extremely denuded and the gangrene was spreading. Application of nitric acid did not arrest it. October 1. the gangrene had denuded the condyles of the humerus and had penetrated the joint. The muscles exposed presented red, purplish, and greenish colors in different portions. The odor of the wound was insupportable. There were great prostration, dejection, and nervousness with muttering delirium. Tongue was dry and of a dark pur- ple-and-blue color. October 4. hemorrhage from the brachial artery, near where it divides, took place at sunrise, and the patient died in twenty minutes. Dr. Jones dwells upon the sallow hue of the complexion and the livid-blue color of the tongue as derangements manifestly induced by the gangrenous poison on the constitution of the blood. Per- haps the most striking examples of the severest type of the disease are related by Macleod: " In the Crimea, during the summer of 1S55, after the taking of the quar- ries and the assault in June on the Great Redan, not a few cases of amputa- tion of the thigh were lo?t from moist gangrene of a most rapid and fatal form. In the case of a few. who lived long enough for the full development of the disease, gangrene in its most marked features became established, but most of the men expired previous to any sphacelus of the part, overwhelmed by the violent poison which seemed to pervade and destroy the whole economy." Two cases under Macleod' s own care, in men who had a limb utterly destroyed by round-shot or by grape, are thus described : ' ' During the night previous to death the patient was restless, but did not complain of any par- ticular uneasiness. At the morning visit the expression appeared unaccount- HOSPITAL GANGRENE. 4^9 ably anxious and the pulse was slightly raised. The skin was moist and the tongue clean. By this time the stump felt, as the patient expressed it, heavy like lead, and the burning, stinging pain had begun to shoot through it. On removing the dressings the stump was found slightly swollen, and the dis- charge had become thin, gleety, colored with blood, and having masses of matter like gruel occasionally mixed with it. A few hours afterward the limb became greatly swollen, the skin tense and white, and marked along its surface by prominent blue veins. The cut edges of the stump looked like pork. Acute pain was felt. The constitution had by this time begun to sympathize. A cold sweat covered the body, the stomach was irritable, and the pulse was weak and frequent. The respiration became short and hurried, giving evidence of the great oppression of which the patient so much com- plained. The heart's action gradually and surely got weaker till, from four- teen to sixteen hours from the first bad symptom, death relieved his suf- ferings." In regard to the pathological anatomy of the disease little remains to be said. The post-mortem appearances are those which are the result of septicaemia, unless pyaemia has occurred as a com- plication. In this case it is probable that in trie neighborhood of the wound there would be evidence of phlegmonous inflammation. One would hardly suppose that there would be any difficulty in the diagnosis of the disease, yet in its early stages there are con- ditions of hospital wounds which might be mistaken for gangrene. The mechanical or the chemical irritation of the granulations may be the result of unsuitable dressings, such as were frequently applied in former times. There may be obtained in this way capillary hemorrhage with oedema of the granulations, and even the forma- tion of a croup-like layer. The writer has at the time of this writing a wound of the bursa of the elbow that has assumed such an appearance from hardening of the secretions in the dressing, which had been kept on a week. The presence of a foreign body or of a piece of dead bone, especially if the sequestrum consist of a fragment of cancellated bone with decomposing matter retained in its meshes, may also cause doubtful appearances of the wound, and even the formation of a rind upon the surface of the granula- tions. Such a rind is not infrequently seen in feeble or in aged individuals, or it may be due to the presence of a scorbutic or tuber- culous taint in the tissues or in the system. Occasionally bed- sores will counterfeit closely the appearances of hospital gangrene in the spreading of the wounded surface and in its sloughing con- dition. The writer has seen carbuncular sloughs transform a wound into one of this appearance, and show a tendency to spread which could only be checked by thoroughly cleansing and disin- fecting the wound. This condition occurred in a feeble old man. 430 SURGICAL PATHOLOGY AND THERAPEUTICS. The ' ' gray look ' ' of a wound which has hitherto been healing kindly must be regarded as suspicious, particularly in times of epi- demics, and formerly it was a condition that was always regarded with great distrust. The prognosis of the disease is very variable. It must not be supposed from the clinical description given above that the mor- tality is greater than septicaemia, pyaemia, or tetanus, for instance. It is undoubtedly as serious a wound-disease as erysipelas, and per- haps more so, although such epidemics of erysipelas as occurred in America about fifty years ago have been of the gravest character. The ulcerating form is much less dangerous than the pulpy form, and the latter type varies greatly, according to its locality, in its effect upon the system. Penetration of the great cavities, such as the peritoneum or the pleura, by gangrenous ulceration is almost invariably followed, according to Packard, by a fatal termination. The opening of a joint during the progress of the disease cannot be regarded in any other light than as a most serious complication. In the epidemics observed since the beginning of the present cen- tury the mortality has varied from 18 to 80 per cent. In some of the more recent campaigns the mortality has probably been at a much lower figure. The number of cases of gangrene reported in the Surgical His- tory of the War of the Rebellion was 2642. Of these cases, 1142 were fatal, making a mortality of 45.6 per cent. The percentage of fatality (with the exception of penetrating wounds of the trunk) of cases of gangrene after flesh-wounds was larger than that after fractures. In one of the more recent epidemics, which occurred in the barracks at Berlin, the mortality was only 6 per cent. In undertaking the treatjnent of hospital gangrene it is import- ant to remember that the agent employed must come directly in contact with the diseased tissue — that it will be of no avail to dress the wound simply with applications containing an efficacious drug. The dead portions on the surface must first be removed, the mem- brane be scraped away, and sinuses be laid open, in order that the remedy may be enabled to exert its influence directly upon the dis- eased part. It is pre-eminently a disease where heroic treatment is clearly indicated. The actual cautery has always been popular with the French surgeons. Pouteau was the first to endorse it. He says: u Cette pratique etait familiere aux anciens: osons la retablir dans tout son lustre." Rochard says: u The actual cautery is more terrifying than painful. At a white heat and passed rapidly over the tissues HOSPITAL GANGRENE. 43 1 it is less painful than applications of perchloride of iron. The cautery may be followed by the use of cold compresses removed from time to time until the pain ceases." At the present time the most suitable dressing to follow this would be an antiseptic poul- tice frequently renewed and alternating with an antiseptic bath until the separation of the sloughs has taken place. Nitric acid in full strength, which has been much used, seems to have been the favorite application by Southern surgeons during the war. Jones advises a liberal and thorough application of the acid: "It should not merely coagulate and alter completely the gangrenous matters, but also come in contact with the sound parts In most cases one thorough application of the acid will be sufficient If, however, the patients be retained in the crowded wards or tents, the most energetic treatment will fail entirely of arresting the disease." The patient, as in the case of cautery, should be placed under the influence of an anaesthetic and all gangrenous tissues should carefully be cut away. All sinuses found under the skin or in the connective tissue should be laid open freely and the dead tissues be removed. As Keen says: "Stumps must be laid bare and appa- rently ruined; sinuses must be fully exposed and the disease relentlessly pursued to its farthest refuge." Rochard well adds: "II faut du courage." For milder cases an acid wash may be used consisting of solu- tions of hydrochloric acid of greater or lesser strength; the one in use for many years at the Massachusetts General Hospital during epidemics was the following: 1^. Potass, chlor., 3ss; Acid hydrochlor., 3j; Misce et adde. Aquse, 3vii It can be applied on charpie. Keen used chiefly in the West Philadelphia epidemic the acid nitrate of mercury, preferring it to nitric acid, as it caused less pain and often saved time by enabling the surgeon to dispense with an anaesthetic: "The pain continues for a shorter time, the slough appears to be destroyed and disintegrated more thoroughly, and it separates in from twelve to thirty-six hours sooner than that from the acid." He continues: "The constitutional treatment is, I take it, of far less importance than the local, just as the consti- 432 SURGICAL PATHOLOGY AND THERAPEUTICS. tutional symptoms are less grave than the local. Frequently they will subside entirely after the vigorous local treatment advocated. The fever will abate, the patient will sleep well, the tongue clean, the bowels relax, and he will tell you the next morning that he has eaten an excellent breakfast and 'feels first-rate.'" The 'application of pure or fuming bromine was advocated strongly by Goldsmith. This drug should be applied with great thoroughness. It at once obliterates all gangrenous odor; its ready vaporization permits its application to the bottom of the sinuses and sulci which cannot safely be laid open with the knife. Its action is almost instantaneous. Surgeon Cleveland was in the habit of applying bromine to all cuts or injuries of his fingers, and he had no trouble with such wounds, although coming into daily contact with the disease. Goldsmith advises for milder cases the following solution of bromine: i». Brominii, 5; Potass, bromid., gr. 1 60; Aquae, ad 3iv.— M. Lint saturated with this solution should be applied to the part; over this a dry piece of lint; over this a sheet of lint spread with simple cerate; and outside of all a piece of oil-silk, which is intended to retain the vapor as long as possible. If the sloughs are thick and they cannot well be trimmed, the bromine may be intro- duced into the thickness of the slough by means of a hypodermic syringe. The irritating effects of the vapor of bromine upon the eyes and the air-passages of the dresser were such as to give a great deal of unpopularity to this remedy. It was employed, however, with great success in many of the army hospitals during the war, and afterward in civil practice, and those who had occasion to give it a fair trial were enthusiastic over its thorough work. The French used perchloride of iron in their last war with suc- cess; it was the most successful remedy at Brest. Charpie soaked with it should be applied to the cleansed wound, and be renewed at the end of every twenty-four hours for a longer or shorter period. Its application appears to have been quite as painful as that of the much more powerful remedies. Packard recommends the use of sugar — a carbohydrate not giv- ing up its oxygen — which prevents oxidation and which acts as a preservative. Powdered white sugar may thoroughly and thickly be dusted over the wound or be applied as a thick syrup. "The HOSPITAL GANGRENE. 433 cure consists in the removal of all sloughing and dead tissues, and in opposing oxidation by means of a dressing with any substance which either contains no oxygen or will not give it up." At the present time the vast array of modern antiseptic reme- dies, among which we may mention iodoform and peroxide of hydrogen, will be at hand for the surgeon's use. Of these reme- dies, carbolic acid has already been employed in several epidemics. In weak solution it does not penetrate sufficiently deep. Heuter used 5 to 10 per cent, solutions, and reapplied them several times a day. In this shape it has a caustic action, but it was apparently not adapted to severe cases. It goes without saying that the most powerful prophylactic treatment is the application of the laws of strict asepsis so far as they can be carried out. If a single case occurs in a hospital ward, it should immediately be isolated; if a number of cases occur at once, the ward should be evacuated. An epidemic at the Chestnut Hill Hospital, near Philadelphia, was arrested in twelve hours by placing all those attacked with the disease in tents in an adjoining grove. A chronic case which has obstinately resisted local treatment will often improve rapidly after a complete change of room, of bedding, and of clothing. Amputation for hospital gangrene of stumps was a frequent resort in pre-antiseptic days. There is no doubt that the presence of gangrene is no contraindication to such an operation at the pres- ent time. With thorough antiseptic precautions the case ought to do well afterward. In 1870 such an attempt was made by a Ger- man surgeon for gangrene of the foot involving the tarsal joints. The wound was soaked with a strong solution of carbolic acid, and the foot was carefully wrapped up in cloths wet with the same solu- tion. The leg was thoroughly washed with " phenyle-water ' ' before the operation. The dressing for the stump consisted of carbolic compresses. The healing was slow at first, but after the opening of a small pus-cavity cicatrization rapidly took place. 28 XVIII. TETANUS. Tetanus (from TtTdivco, to bend) is an infectious disease, gen- erally traumatic in origin, characterized by painful tonic contrac- tion of the muscles, beginning with those of the jaw or the neck and affecting progressively the muscles of the trunk and the limbs. It is accompanied by convulsive paroxysms and an irritation or inflammation of the nerve-centres in the upper portions of the cord. It is due to the presence of a bacterial poison in the blood and tissues. The etiology of the disease has received a vast amount of study by modern as well as by ancient writers, and its origin has been attributed to various causes. One of the causes to which the dis- ease has most frequently been attributed are sudden changes in the weather, particularly change from heat to moist cold. After the battle of Prague there was said to be as many as a thousand cases of tetanus among the wounded who were left upon the field of bat- tle without shelter. In the Austrian campaign of 1866, Stromeyer saw thirteen cases after a cold storm which followed a period of heat. At Strasburg, Poncet did not see a single case of tetanus during the early period of the siege, but in September, after a sudden fall of the thermometer, a dozen cases occurred in the military hospital in which he was stationed. In tropical coun- tries the disease appears to be much commoner and to favor cer- tain regions. Negroes are supposed to be peculiarly susceptible, among whom, in Brazil and Peru, the disease is said to be very common. In Algeria the Arabians are supposed to enjoy an immunity to the disease; such at least is the experience of French surgeons. Idiopathic tetanus is said to be common in the Southern United States, in Central America, and in the West Indies: in Europe tetanus has most frequently been ob- served in connection with military surgery. It has also been supposed that the disease might originate from an injury to some nerve-trunk. One of the most acute and typical forms of tetanus under the writer's care followed a lacerated wound of the arm with exposure of the median nerve for several inches in its length, in a way that rendered it impossible to cover the nerve 434 TETANUS. 435 with the integuments; but Weir Mitchell reports that tetanus from injury to the nerve-trunk occurred in only one case out of all that he observed during the late war, and he believes that the source of irritation is in the peripheral branches of the nerves in the majority of cases. Such a reflex origin of the disease has been assumed by several authorities, and the sometimes almost instantaneous relief of symptoms by the division of painful cicatrices or other sources of nerve-irritation gives ground for this belief. In the report of a case in the Surgical History of the War the symptoms were appar- ently due to such a cause, following amputation of the finger. Several months after there appeared tetanic symptoms, which were immediately relieved by the removal from the cicatrix of a neuroma about the size of a buckshot. The history of this case renders the diagnosis doubtful, but the association of the symp- toms with the peripheral irritation is at least suggestive. In another case, where the median nerve was caught in the cicatrix, intense pain was suffered and there was great nervous irritation after the wound had healed. Partial trismus occurred finally, that was somewhat relieved by an incision which freed the nerve from the cicatrix. The tetanic symptoms recurring were not relieved by resection of the nerve, and amputation was resorted to, after which the man recovered. Larrey divided certain cica- trices of the shoulder that gave rise to cramp-like pains and tetanus, the operation being followed by immediate relief of all the symp- toms. "The patient opened his mouth and was cured." Rose refers to such cases, which he calls u scar- tetanus. " Following out this idea, some writers thought that the situation of the wound played an important part in the origin of the disease, and an endeavor was made to establish the fact that it was as a complication of wounds of the hands and the feet that tetanus was almost invariably found; but examination of statistics shows that this view is not borne out by the facts of the case, that the disease may follow injury in almost any region of the body, and that it may arise spontaneously when no perceptible wound is to be found. The view that tetanus was of humoral origin has been advocated by Travers, Billroth, and others for a long time. This theory assumed an intoxication due to the formation of a poison de- veloped either in the wound or in the perspiration — in other words, a ptomaine. An attempt was not made, however, to associate this chemical product with the development of bac- teria. It was not until 1885 that the bacillus tetani was discovered. It 43 6 SURGICAL PATHOLOGY AND THERAPEUTICS. is a long-, slender rod, in one end of which a spore forms, distending the cell into a "drumstick" shape (p. 54). It is one of the most marked types of anaerobic bacteria, and it is usually found min- gled with several other varieties, from which it has been separated with great difficulty. For this reason pure cultures have only quite recently been obtained. The organism is found principally in the tissues near the wound, and it has not been satisfactorily demon- strated in either the blood, the internal organs, or the central nervous system. Injected into animals after cultivation, the or- ganism produces symptoms of tetanus in twenty-four hours. At the autopsy a slight infiltration is seen at the point of injection, but no coarse changes are seen elsewhere. A few bacilli are found near the point of injection, but none in other parts of the body. In no case do their numbers stand in any proportion to the severity of the symptoms. For this reason it has been assumed that the organisms manufacture at the point of inocu- lation an extremely active poison which disseminates itself throughout the body. Betoli mentions the fact that slaves died of tetanus after having eaten the flesh of a bull which had per- ished from that affection. Brieger has, in fact, succeeded in obtaining from the culture of the bacteria ptomaine which he called ' ' tetanine. ' ' The same substance he also obtained from the freshly-amputated arm of a. man afflicted with the disease. Under what special conditions infection takes place in man cannot yet be stated with any certainty. The tetanus bacilli are found in large numbers in the world about us — in garden soil, in the dust and sweepings of our streets and dwellings, in crumbling masonry, in putrefying fluids, and in manure. In connection with the latter source it may be mentioned that French writers, and par- ticularly Verneuil, regarded persons who are brought in contact with horses as particularly susceptible. Considering the great numbers of tetanus bacilli that are constantly to be found about us, it might seem surprising that tetanus is so rare a disease. This is explained by their anaerobic nature. The presence of free oxygen prevents the development of the bacteria. The bacilli are there- fore unable to find an opportunity to grow upon small and super- ficial wounds except in rare instances. Punctured wounds lodge the organisms deep in the tissue, a soil better fitted for their growth. If the penetrating foreign body, such as a splinter or a nail, should carry in with it dirt from the skin, grains of sand, or fragments of stone, the conditions are peculiarly favorable for the inoculation. TETANUS. 437 and development of the bacilli. Among the predisposing- causes of tetanus may be mentioned age. Yandell shows that the disease is peculiarly fatal to persons under ten years of age, and that this period included 7 per cent, of all the cases collected by him, but did not include trismus nascentium. The disease is said to be rare in later life, but the same author noted fifteen cases occurring in individuals over fifty years of age; and one case is reported in a man aged eighty-nine. The condition of the patient's health is an important factor in his ability to resist the inroads of the micro- organisms. The enormous number of cases reported after the battle of Prague, although doubtless greatly exaggerated, indi- cates that exhaustion and exposure produce an enfeebled vitality peculiarly favorable for the origin of tetanus. Doubtless meteor- ological conditions favor the growth of the bacillus of tetanus, and under certain combinations it can easily be imagined that the dis- ease might assume an epidemic form. Epidemics of the disease have not only been reported in literature, but it is probable also that every hospital has had several cases occurring within com- paratively short periods of one another. Such has certainly been the writer's experience. Tetanus may be traumatic or be idiopathic, according to the current authorities of the present day. In view, however, of the latest investigations, there may be reasonable doubt of the exist- ence of the latter variety. As in erysipelas, it is not difficult to assume the presence of some small wound in which the organisms may have effected a lodgment. Cases of tetanus arising from so trifling an injury as a hang-nail have been reported, and the disease may become a complication of an internal injury, as a simple frac- ture. It is not improbable, therefore, that in the form of dust the organisms may be inhaled or be swallowed, and that subsequently an intravascular infection of the injured tissues may occur. A more important distinction is that made between acute and chronic tetanus. Puerperal tetanus and trismus nascentium are varieties usually considered as a group by themselves, but they are in reality not distinguished etiologically from traumatic tetanus. Acute tetanus usually appears during the first week of the period of the healing of a wound. Yandell found that of 415 cases the disease supervened in two weeks in 196 cases. In the remainder — that is, those in which the disease appeared after the fourteenth day — the recoveries exceeded the deaths. As chronic tetanus is much more liable to terminate in recovery than the acute form, it is probable that in most of those cases in which the symptom appeared 43 8 SURGICAL PATHOLOGY AND THERAPEUTICS. late the disease ran a chronic course. Of 367 cases reported in the Surgical History of the War, 287 occurred during the first two weeks after the injury or the amputation. Sometimes, then, during the first or the second week of the con- valescence from an injury, without any warning as shown by the state of the wound or the general condition of the patient, the first stage of the disease makes its appearance. After a comfortable night's rest, probably the last the patient will have, he awakes with a sensation of having taken cold. He complains of a stiff neck, but thinks little of it. Such a complaint on the part of the patient should put the surgeon on his guard, for, although it may be a symptom of a slight ailment only, it is almost the invariable precursor of the other symptoms of tetanus. During the day there is in the muscles of the jaw a slight stiffness, which renders it dif- ficult for the patient to open his mouth. This stiffness is not pain- ful, and it may still be regarded by the patient as a trivial matter; but this stage of comparative comfort does not last long, as the disease progresses apace. There is soon pain in the muscular con- tractions, which now become so powerful and continuous that the jaw cannot be opened and considerable difficulty is experienced in swallowing even liquids. In the mean time the "stiff neck" has included all the muscles that hold the head and the neck to the body. On examination of the jaws the masseters are distinctly felt in a state of rigid contraction, as hard as iron and with well- marked borders. Attempts to approach the chin to the sternum directs attention to the rigidity of the muscles at the back of the neck. If the hand is now passed down to the abdomen, the parietes are felt as firm and rigid as a metal plate; before the day closes the muscles of the back may already be affected, and the patient is unable to lie upon his back owing to the arching of the spine, or the opisthotonos, thus produced. There is already reten- tion of urine, which, when drawn with the catheter, appears to be abundant and of a normal color. The distress of the patient has now become great, owing to the painful nature of the muscular spasm, which is not only extensive, but is also continuous ; that is, u tonic." Attempts to swallow cause pain and distress, owing to paroxysmal increase in the muscular contraction. After a sleepless night the patient the next morning is found well advanced into the stage of full development of the disease. The locking of the jaws is as complete as before, and nearly all the voluntary muscles of the body except those of the upper extremities are involved. The arms may also be involved, but only to a partial extent. The lower TETANUS. 439 extremities are rigidly extended. The patient is now extremely sensitive to disturbance of any kind: attempts to move him in bed, to administer nourishment, or to pass the catheter bring on a par- oxysm of convulsive action of a most painful character. Even the muscles of the face are affected ; the eyelids are seamed, the nostrils are raised, and the mouth is puckered in a peculiar way, while its corners are drawn back by the contraction of the cheeks. The eyes are drawn in and partly closed, and occasionally there is strabis- mus. The expression, which is peculiar to itself, can be likened neither to that of pain nor that of mirth. The so-called "sardonic grin" (risus sardonicus) is perhaps the best term that can be applied to it. Once seen by the surgeon, it is never to be for- gotten. The writer remembers having seen the typical risus in one only of the cases that have been under his care. Poncet remarks that the surgeon in charge would never be able to recognize his patient after recovery. Poland mentions a case where the disfigurement remained after convalescence, and was still quite marked after a period of eleven years. While all the muscles mentioned are still in a state of tonic spasm, there will be waves of convulsive spasm throughout the body, produced by any disturbing influence: these spasms now become more frequent and violent. The muscular contraction at this time is extremely painful, and any attempt to prevent it or to straighten the limb may lead to rupture of the muscular fibre. Larrey reports rupture of the rectus abdominis muscles owing to violent spasms brought on by putting the patient into a cold bath. The same accident is mentioned by Curling, and Dupuytren has observed rupture of the muscles at the back of the neck. Des- portes records double fracture of the neck of the femur from mus- cular action, and Poncet mentions a case of rupture of a fatty heart in an alcoholic subject. The reader must not gain the impression that the patient tosses wildly about in bed: on the contrary, he keeps as still as possible, and such a patient might easily be passed in the ward without appreciating the fact that he was the victim of so terrible a disease. On closer inspection, however, he will be found lying upon his side, with his head drawn rigidly backward and with a deep hollow in the curve of the spine, which curvature becomes greatly exaggera- ted on turning down the bed-clothes. His mind is perfectly clear, but the rigidity of the muscular contractions of the mouth and in the chest does not enable him to emit more than muffled groans. The spasm of the sphincters renders movements of the bowels or of the 440 SURGICAL PATHOLOGY AXD THERAPEUTICS. bladder very difficult. There is at this time but little fever; the temperature-curve is iu no way characteristic iu this disease, but as death approaches, and even post-mortem, the rise may be exces- sive. There will be found, however, after each convulsion a tend- ency to perspiration, which may become quite a characteristic feature of the case. With each active and extensive innervation of muscular fibres there is without doubt an increased heat-produc- tion, and the diaphoresis is therefore a means by which a corre- sponding heat-elimination may be maintained. The post-mortem hyperpyrexia which is occasionally seen, the thermometer running to ioc/, ii2 c , and 113° F., may be in part due to the cessation of active heat-elimination, but it is probably due also to the action of the ptomaine on the thermic centres. During the height of the disease — that is, on the third or the fourth day — exhaustion becomes marked from loss of nourishment and of sleep. Short periods of sleep may be obtained by drugs, during which there is some relaxation of the muscular spasm; but no complete remission ever occurs, and the patient is soon startled out of a disturbed slumber by renewed convulsive movements. Attempts to give food may bring on spasm of the glottis, death having occurred during such a crisis. Attempts to expectorate the accumulated mucus may also produce the spasm. The convulsion usually lasts a few seconds only, during which there is also cya- nosis of the face and its muscles are contracted; the pupils are nor- mal; there is some foaming at the mouth; and the lips have a deeper hue. Dyspnoea is increased, and the patient makes forcible attempts to get his breath; the abdomen is pushed forward, and the patient may rest upon his occiput and heels in the position of opisthotonos. The pulse is greatly accelerated, and it may reach to 160 (Poncet). Death from heart failure may also occur during this period of prostration. In the last stages of the disease the mind continues clear, delirium is extremely rare, and the patient is fully sensible of the agonizing spasms to which the slightest noise or disturbance in the room gives rise. The face is pale and ema- ciated, and if not convulsed there is an expression of great appre- hension. The voice is feeble and the skin is constantly bathed in sweat. It is in this period that the temperature may rise, and in some cases may reach a very high point. During the last moments the tetanic spasms may relax, but they are usually maintained until the end. In tropical climates the period of acute tetanus may greatly be TETANUS. 441 shortened, and cases are reported in which death has supervened a few hours after the onset of the attack. Contraction of the muscles of one side of the trunk may occur occasionally, but pleurosthotonos is rare. When the symptoms are continued beyond the fifth day, there is hope that the disease may assume the form known as chronic tetanus. The cases of recovery from acute tetanus that occasionally occur usually go through a chronic stage before convalescence takes place. In chronic tetanus the first symptoms usually appear at a later date after the injury or operation than in acute tetanus. There is hope, therefore, if no symptoms are seen until the third week, that there may be this type to deal with. The order in which symptoms appear is the same as that in the acute form. The stiff neck, the locked jaws, and the rigidity of the muscles of the trunk are all present, and they may be of great severity; but, although the development of the disease may be rapid, there are periods during which the patient experiences relief from muscular contrac- tions. An entire day may pass without relapse. The periods of quiescence between convulsions may, at all events, be more pro- longed than those in the acute type; nourishment can be given, and the strength of the patient may correspondingly be main- tained. As time passes che interval between the convulsive seiz- ures becomes more prolonged and the convulsions are less severe; deglutition becomes less painful. The prostration, however, is extreme, and any unusual excitement or irritation, such as the pas- sage of the bougie, will bring back the spasms. Sleep, however, becomes more prolonged and more refreshing. Convalescence finally sets in, though it is liable to be accompanied with several relapses. The disease may be thus extended over a considerable length of time. Cases of six weeks' and of two months' duration are occasionally seen; Yandell reports one case in which the duration of symptoms was two hundred and forty days. Head Tetanus, or Tetanus Hydrophobicus, an affection first described by Rose, occurs after injuries in the region of distribution of any of the twelve cranial nerves; consequently it is chiefly con- fined to the head. It is characterized by spasm of the pharyngeal muscles and paralysis of the facial nerve, as well as trismus, and occasionally tetanic contractions of the muscles of the neck and abdomen. Rose explains the paralysis of the facial nerve by com- pression in the petrous portion of the temporal bone, due to swell- ing of the nerve. According to Brunner, the reported symptom of facial paralysis is due to an error of observation. Brunner 442 SURGICAL PATHOLOGY AND THERAPEUTICS. injected pure cultures of the tetanus bacillus at different points on the heads of rabbits and guinea-pigs, and succeeded in producing head tetanus. Paralysis of the affected side of the face was, how- ever, absent. The asymmetry of the two halves of the face was caused by tetanic contractions. If the injection was made in the median line, both sides of the face were affected; if one side was inoculated and the facial nerve of the same side divided at the same time, the contractions of the muscles were prevented. Klemm by a careful analysis of twenty cases disproves Brunner's theory, it being evident that paralysis of the facial nerve occurs in the majority of cases with its characteristic symptoms. The sequence of symptoms in this form of tetanus resembles that described by Rosenbach in tetanus produced experimentally in animals, in whom the muscular cramp begins at the point of inoc- ulation and spreads to other muscles. The paralysis is due to infec- tion, probably by a toxine, in the same way that paralysis occurs in diphtheria and other infectious diseases. Albert, in fact, places this affection in the class of the paralysies infectieuses. Cephalic tetanus occurs usually after a wound in the face. Rose reports the case of a coachman who received a blow from a whip- handle below the left orbit. In another case a blow was received in the temple during a street-brawl, and the patient was left uncon- scious in the gutter for several hours. In a case reported by Bern- hardt the disease followed the removal of a wen from the neighbor- hood of the left orbit. The paralysis of the facial nerve almost always occurs on the same side as that on which the injury is received. There is usually marked paralysis of the lower lid, the eye of the affected side remaining open after an attempt is made to close the lids. There is generally trismus, and occasionally spasm of the abdominal muscles is also mentioned. A marked feature of this form of tetanus is difficulty in swallowing, which symptom has given rise to the term tetanus hydrophobicus. This symptom, however, is not always present. Head tetanus is not always fatal. As in the ordinary form of tetanus, many of the chronic cases recover. Gueterbock and Bern- hardt collected seventeen cases with four recoveries. Klemm found that recoveries occurred almost invariably in the chronic cases, which lasted from four to twelve weeks. In a collection of twenty- four cases of head tetanus seven recovered, and of these six were cases of chronic tetanus. As to the character of the wound in a case of tetanus, there is little to show that the bacilli produce any marked local effect TETANUS. 443 during their growth. Poncet speaks, however, of a peculiar con- dition of the wound at the outbreak of the disease. The suppura- tive process is less healthy in character and the tissues appear to be irritated. Occasionally there is a slight blush around the edges of the wound, and sometimes evidences of lymphangitis are seen near a wound of the extremity. There may also be a slight pricking sensation in the affected member, which may even be painful. Wounds of the extremities are said to be followed more fre- quently by tetanus than those in other regions. This statement is in accord with Yandell's figures. He says: "The popular belief that injuries of the foot are more liable than those of other parts to be followed by tetanus is quite confirmed as to punctured wounds in this situation, the large majority being inflicted by nails run into the foot. ' ' Of the 505 cases reported in the Surgical His- tory of the War, all but 76 were wounds of the extremities. It is probable, however, that the nature of the injury is a more important etiological factor than is its situation, and that tetanus more fre- quently follows wounds of the extremities is due to the fact that punctured wounds are more frequent in those regions. The pres- ence of the bacillus tetani on dirty hands and feet may also form an important factor. Occasionally the disease will be found to follow the infliction of a certain kind of injury. The " deadly toy pistol," so well known to Fourth-of-July celebrations, has been responsible for many cases. Here it would seem that there is a combination of predisposing causes — youth, anatomical situation, a lacerated or a penetrating wound, dirt from the street, and finally fragments of gravel from the detonating composition. The presence of for- eign bodies in wounds has always been supposed to be a frequent cause of tetanus. The wound, however, may be extremely slight, as a contused wound of the toe with or without fracture, a trivial affair; but if the bacillus has found a suitable lodging and is well protected from oxygen, the development of the organism will be possible. The penetrating nature of gunshot wounds, such as are inflicted in battle, combined with certain predisposing causes, ex- plains the relative frequency of tetanus in military surgery. That there should be a certain amount of inflammatory reaction in the wound is to be expected when infection has taken place; but the moderate number of organisms found probably accounts for the fact that more marked symptoms of inflammation are not present. The existence of such symptoms of a septic inflammation as Poncet describes can probably be accounted for by a mixed infection. The testimony as to the post-mortem changes in tetanus is quite 444 SURGICAL PATHOLOGY AND THERAPEUTICS. conflicting. As a rule, evidence of inflammation of the brain and its meninges is wanting, but a number of observations point to inflammation in the upper portions of the cord. The great diffi- culty in preparing so delicate structures for microscopical study- throws doubt on many of the reports, but enough remains to prove that inflammation of nerve- tissue,. both central and peripheral, is generally present. Doubtless a fresh study of the field in the light of the present bacteriological knowledge will bring out many inter- esting morbid changes hitherto unobserved. Larrey, after the battle of Waterloo, performed a great number of autopsies in cases of tetanus, and found evident traces of inflam- mation of the cord and the membranes. Grinelle (1857), in a sum- mary of 52 cases of tetanus, reports that 29 presented lesions of the cord and the membranes. In 3 changes were noticed in the brain, and in n in the nerves and muscles. Lockhart Clarke, the best authority of the time, found in six cases lesions of the cord of different kinds and of surprising extent. He says: (< It seems to consist precisely of disintegration and softening of a portion of the gray substance of the cord, which appeared in certain parts to be in a state of solution." Ranvier, however, examined four cases from four to twelve hours after death, and prepared the cords for microscopical exam- ination with the greatest care, but failed to find anything abnor- mal. Verneuil believes that the lesions are dependent entirely upon reflex action, and Brown-Sequard expresses the theory that the morbid changes are due to an ascending neuritis ; and indeed in many cases there is a redness of the neurilemma of the nerves corresponding to the locality of the wound. Both Michaud and Aufrecht found lesions in the lumbar portions of the cord. Laveran examined the nerves of a patient who died of tetanus following amputation of the leg. He found proliferation of connective tissue in the tibial nerve, but no changes in the cord. In America, Amidon claims to have found extensive changes in the nervous system; small thrombi and exudation in the dura mater; degenerative changes in the brain; evidences of inflamma- tory changes at the points of origin of the cerebro-spinal nerves ; and lesions in the cord. Jewell thinks there is little doubt that there is usually irritative disease in certain not very well defined tracts of the gray matter of the spinal cord and the medulla oblon- gata, more especially of the latter. ' ' From these central diseased parts excitations are propagated along the motor tract, down the medulla and cord, and thence along the motor nerves to the TETANUS. 445 affected muscles." In the spinal cord the chief seat of the dis- order, he thinks, appears to be in the posterior cornua and the contiguous central gray matter, the disease at times invading the related white columns. Such changes are more frequent in the cervical portion, but the appearances observed depend greatly upon the duration of the case. Neither the motor nor the sen- sory tracts are invaded alone, but the precise point of irritation appears to be in an intermediate region through which transfers in reflex action are made, and there is consequently great exaltation in the reflex irritability in this disease. This brief review of the question is enough to satisfy one that the virus acts with more or less power chiefly upon the nervous centres of the cord and the medulla, but the data do not yet seem to be sufficient to establish the fact of multiple neuritis or irritation of the trunks or branches of the nerves over and above that of other tissues to which the virus may be conveyed. The diagnosis of tetanus is usually not difficult in the fully- developed stage of the disease, but it is in the earliest stages that the surgeon should be warned of what is about to come. Stiffness of the jaws may be due to inflammatory affections of the mouth or the teeth or to abscess of the cervical glands. When the external signs of inflammation are wanting, the latter source of disturbance might be overlooked. Rheumatic inflammation of the temporo-maxillary articulation may also prevent the patient from opening his mouth, but the signs of local inflammation are not difficult to discover if carefully sought. Hysterical contraction of the masseter muscles is not likely to give rise to a mistake in the diagnosis, for the surgeon's attention is not usually called to such a condition until time has long since solved the question. Colles of Dublin undertook to describe the different forms of reflex contractions which may be mistaken for tetanus. Temporary spasms following the dressing of a painful wound men- tioned by him would not probably lead to a mistake in diagnosis. Tetanic spasms due to peripheral irritation of the nervous sys- tem, such as by a scar or a foreign body, are at times severe, and, according to some authors, may be fatal. Some of these cases are probably true infective tetanus ; others may be examples of severe reflex irritation, and Larrey's case of sudden cure following the division of a scar may have been one of this type. The question of death by tetanus or by strychnia-poisoning has been raised in medico-legal cases. In the latter condition, however, there is usually no lock-jaw, and if the masseters are affected at all, 446 SURGICAL PATHOLOGY AND THERAPEUTICS. it is toward the end of the scene. In strychnia-poisoning there is hyperesthesia of the retina and objects seen are colored green. During a paroxysm the mouth foams, the jaws are joined together, and the teeth lacerate the tongue. There is also spasm of the mus- cles of the limbs and body, with arching of the back, which symp- toms with laryngismus are first in order to appear. When the dose is small and is repeated, there will be a corresponding intermission and a return of all the symptoms. In tetanus the disease begins with mild symptoms, and it is progressive and continuous. In acute poisoning the symptoms may last only for a few minutes. In temperate climates the most acute forms of tetanus last from two to three days. Tetany, which it might be supposed would resemble tetanus, is a disease not often seen in America: it affects chiefly young persons, and consists in tonic spasms of various groups of muscles, most frequently those of the upper extremities. The attack is preceded by vague tingling pains, followed by a sense of stiffness in the affected group. The position of the hand during the spasm is peculiar, resembling the posture of the accoucher's hand when about to make a vaginal examination. Opisthotonos may occur, but there is never trismus. The attacks are short and are more or less localized, and Trousseau's symptom, seen in no other convul- sive disease, is always present. This symptom consists in the peculiarity that pressure upon the nerve-trunk leading to the affected group of muscles always brings on a characteristic attack. The febrile nature of meningitis and the frequency with which it is accompanied by pain in the back of the head, as well as by the absence of the great reflex excitability, serve to distinguish that affection from tetanus. Hydrophobia is supposed by some authors to resemble tetanus, owing to the difficulty of swallowing which occasionally arises in the latter disease. Any one who has once seen both diseases would find no difficulty in distinguishing them. The portraits of the two diseases are indeed strikingly different. The countenance and bearing of the hydrophobic patient are those of excitement and mental distress. In the early stages of hydrophobia the patient does not take to his bed, and the so-called "spasm" appears only on attempting to swallow, and it is limited to the muscles of deglutition and respiration. The facial paralysis is a sufficient guide to diagnosis in tetanus hydrophobics, where there is diffi- culty in deglutition. External muscular spasm is the characteristic TETANUS. 447 feature of tetanus. There is no mental excitement; although the muscles of the face are distorted, the expression of the eye is natural. It is the endeavor of the tetanic patient to keep as still as possible, whereas the hydrophobic patient is constantly moving about. In the later stages mania is present in hydrophobia, but in tetanus the mind is clear to the last. The prognosis of tetanus depends almost entirely upon the acuteness of the symptoms. Acute tetanus is one of the most fatal of diseases. In chronic tetanus the percentage of mortality is very much lower. According to Hippocrates, the patient dies on the third, the fifth, the seventh, or the fourteenth day. If he survive this period he recovers. According to the tables of the Surgical History of the War, of 337 deaths, 287 occurred during the first week of the disease. On the eighth day there were but 7 deaths. In Yand ell's 415 cases there is a marked falling off in deaths on the fifth day, when there were but 11 deaths, from which time the percentage steadily diminished. Traumatic tetanus appears to be more fatal than idiopathic tetanus. Those cases occurring after injury received upon the field of battle appear to be the most fatal of all. In the Civil War 505 cases are recorded, of which 451, or 89.3 per cent., died. Poncet found a mortality of 90.6 in 713 cases; of Yandell's cases, which were collected from various sources, 213 recovered and 182 died. The date of invasion of the disease is an important element in the prognosis. In Yandell's cases the disease supervened in two weeks after the injury in 196 cases: of these, 62.5 per cent. died. 11 But when tetanic symptoms are delayed until the fourteenth day recoveries are notably in excess of deaths — 23 per cent." Tetanus is seen more frequently in the male sex, and it is a disease of early life: cases are rarely seen in patients over fifty years of age. The gravity of the wound does not appear to have any influence upon the severity of the disease. It must not be forgotten that the figures mentioned above do not take into consideration tetanus of the tropics. There the disease is not only much more fatal, but is also much more frequent. According to Poncet, the num- ber of deaths from tetanus in England amounts to 0.0031 of the total mortality, but in Bombay the figures rises to 3.9 per cent. The disease in that locality may prove fatal in a few hours after the most trivial injuries or even when produced by a sudden chill. 44^ SURGICAL PATHOLOGY AND THERAPEUTICS. The treatmeitt of few diseases has been the object of such varied medication as tetanus. Not only is the number of remedies too great to attempt even an enumeration, but such a variety is also used in most cases as to render it difficult to judge of their respect- ive values. Yandell, after a careful study of this question, concludes that no one agent can justly be said to possess a decided superiority over any other. No attempt is made to draw any conclusions from the treatment employed in the cases which occurred during the Civil War. Yandell places chloroform at the head of the list in cases of acute tetanus, but also makes the significant statement that when tetanus continues fourteen days recovery is the rule and death the' exception, apparently independent of the treatment. Among the internal remedies which have enjoyed a more than usual reputation may be mentioned Calabar bean, chloral, cannabis indica, curare, nitrite of amyl, quinine, and opium. Calabar bean, or its active principle, when given in small doses, relieves the mus- cular contraction, the jaws relax, the head reposes quietly upon the pillow; if given in large doses, the spasm appears greatly aggra- vated. Poncet explains the favorable action of the drug by its effect upon the conductibility of the motor nerves, by which the muscular system is, as it were, isolated from the nerve-centres. He prefers to give it by the mouth rather than by subcutaneous injection, as the dose can more carefully be regulated and the action of the drug can better be observed by this method. From i to \\ grains of the extract may be given by the mouth every four hours, or from 15 to 20 drops of a 1 per cent, solution may be injected subcutaneously. The statistics of Knecht give a mortality of 45 per cent, in 60 cases in which this drug was used. Chloral seems to be most efficacious in chronic tetanus: it relieves pain and prevents spreading of the muscular spasm and recurrence of the convulsions. It appears to act by diminishing reflex excitability in the nerve-centres. It may be continued for one or two weeks at a time, and in this way an almost uninterrupted sleep may be maintained, which paves the way to convalescence. In large doses (from 100 to 200 grains a day) chloral will relieve muscular spasm in acute tetanus, but it does not appear to have any appreciable effect upon the mortality. According to Jewell, as much as n 20 grains have been given in twenty-four hours. Ore of Bordeaux cured one of his patients by the intravenous injection of chloral: 10 grammes of chloral dissolved in 20 grammes of water were injected into the right cephalic vein in the space of TETANUS. 449 nine minutes; cyanosis disappeared at once, and all muscular con- traction ceased at the end of the operation; the patient fell into a quiet sleep. The relief was in another case only temporary, and in fifteen minutes the symptoms had returned. Chloroform may be administered by inhalation. Poncet relates a case where anaesthesia was produced six times, and at the last administration respiration suddenly ceased, but it was restored by artificial means, and the patient finally recovered under the con- tinuous treatment of opium. Simourin administered chloroform by keeping upon the breast of the patient a napkin upon which chloroform was dropped. The room was a small one, and the patient was thus exposed to the influence of the drug during twenty-two days. The patient recovered. Certain it is that the weight of evidence is in favor of the sedative action of this drug on the nervous system in cases of tetanus, as compared with that of other remedies of this class. Its action is said to be not so enduring as that of chloral. Opium does not appear to enjoy the popularity of chloral and chloroform. Large doses are required, and the digestive disturb- ance caused by the drug is a contraindication to its use. Adminis- tered hypodermically, it gives, however, great relief in some cases. The dose required is sometimes enormous, considering that the patient has but a short time to become habituated to the drug. The writer has known a young man to receive, before relief from pain was obtained, one hundred grains of morphine in the twenty- four hours. Bromide of potassium may be used in connection with chloral or, in the convalescent stage, as a substitute for that drug, but it is altogether too mild a remedy to produce any appreciable effect in the more active stages of the disease. The writer should hardly advise the surgeon to waste time in experimenting with any of the other drugs that have been used in the treatment of the disease. Those already mentioned are of use only by virtue of their sedative qualities, and they cannot be regarded as curative agents. They relieve the most overpowering of the symptoms, and in this way give the patient strength to live through the period during which the virus is in an active stage of development. So far as local treatment is concerned, it is important to remember that antiseptics, to be of any use, must reach the bacilli, which are already deeply imbedded in the recesses of a punctured wound. Those exposed to the air, being anaerobic, are not likely to develop. Punctured wounds, therefore, should 29 450 SURGICAL PATHOLOGY AND THERAPEUTICS. thoroughly be laid open and disinfected if there is any reason to suspect that infection has taken place. This infection is more likely to occur, as has already been shown, when dirt or dust is driven in with the penetrating foreign body. The large majority of punctured wounds recorded in Yandell's cases were inflicted by nails penetrating the foot. Any dressing applied should be so arranged that free drainage will be possible. A dry dressing, which might seal up a small opening, would in such case become a source of danger. Many a case of tetanus has doubtless been warded off in pre-antiseptic days by an old-fashioned poultice, which has favored suppuration and the discharge of the dangerous bacilli. In those cases to which attention has already been called, where nerve-irritation is a prominent feature, the reflex excitability has been greatly diminished by nerve-section. Some cases seem to have been cured by this operation, but in true tetanus the most that can be expected from this method is the removal of a power- fully disturbing influence on the nerve-centres. Permanent paral- ysis may of course result, but union may subsequently take place between the divided ends of the nerve. Nerve-stretching has also been tried, but the results have not been encouraging, although in isolated cases it has produced marked relief. Nerve-stretching is not to be thought of except in special cases when local indications seem to demand this operation. When a nerve is bound down by a cicatrix, it should be dissected out and thus be freed from a source of painful irritation. In certain cases when the wound is foul or is irritating, or when great laceration has exposed and mangled nerve-trunks, amputation may be necessary. The great sweating which is so characteristic of tetanus has suggested the use of warm baths and of other diaphoretics as a means of imitating Nature's method of relief. It is possible that some of the ptomaines may be eliminated in this way: it is unlikely that many of the bacilli would find their way into the sweat-glands, as bacteria are not usually so eliminated. The hot bath gives relief to the spasms while the patient is immersed, but removal from the bath brings the patient in contact with cooler media, which, together with the necessary disturbance, excite new con- vulsive movements. A. vapor bath may be administered to the patient while in bed. The vapor bath constitutes one of the clas- sical forms of treatment handed down from early times. The writer has seen it thoroughly tried without other result than to increase the patient's distress. In 1890, Behring and Kitasato published some experiments with TETANUS. 451 reference to the origin in animals of immunity to diphtheria and tetanus. According to these investigators, the acquired immun- ity depended upon some property of the blood-sernm developed bv protective inoculations, and with this curative serum they were not only able to render animals insusceptible, but also to cure already infected animals. This immunity was brought about bv the injection of cultures of the tetanus bacillus, whose activity had partially been destroyed by the addition of trichloride of iodine. By diminishing the amount of the iodine the strength of the viru- lent culture could be increased. The serum of animals thus rendered immune could be used on other animals as a protective or curative agent. Tizzoni and Catani produced a protective result in animals by injecting very small doses of tetanus culture at first, and later by gradually increasing the amount of the culture. They were not able, however, to produce any therapeutic results on ani- mals with the serum of the animals so treated. The active princi- ple of the culture they called a "tetanus antitoxine," which may be obtained by precipitation by alcohol, and when used it is dis- solved in water or in glycerin. (See Appendix.) The curative effect of this blood-serum does not seem to have proved so pow- erful as was at first anticipated, and it is denied altogether by some observers. Other observers have succeeded, however, in curing animals when the treatment was begun soon after the onset of the symptoms of tetanus. Fourteen cases of the disease in man have been treated by the methods of Tizzoni and Catani; of these, ten were adults, who were all cured. There were four cases of tetanus neonatorum, three of which terminated fatally. This method consisted in in- jecting a watery solution of the antitoxine and in repeating the dose daily. No unfavorable symptoms followed the administra- tion of these doses in any of the cases. An analysis of the favor- able cases shows, however, that the majority of them were exam- ples of chronic tetanus. The cases reported by Roux and Vail- lard were also mild in type. It is therefore doubtful whether this new treatment is efficient in the acute type of the disease. Perhaps in no disease should the comfort of the patient so carefully be studied. Before active symptoms have set in the patient should be placed alone in a room so situated as to be quite free from disturbance of any kind, if that be possible. The light should be dim and the temperature should carefully be regulated. Officious nursing should be avoided. Nourish- ment is needed to sustain strength, and stimulants may be given 452 SURGICAL PATHOLOGY AND THERAPEUTICS. in such combinations as to be least irritating to the throat. It may be necessary to use the catheter or to produce an action of the bowels. Skilled nursing should accomplish these tasks without undue excitement of the hypersesthetic nerves. With such minute care and attention to details as these rules imply treatment may, as Nicaise justly says, make chronic some cases of tetanus that began as acute. Every day added to the patient's life after the first week of the disease increases greatly his chances of recovery. Even the most acute cases sometimes get well, so that the surgeon should be encouraged to exert all the skill in his power or bring to bear all the resources of a great hospital, even in the most desperate cases, with some hope of saving life. XIX. HYDROPHOBIA. Hydrophobia is a disease of man caused by inoculation from a rabid animal due to a specific virus in the saliva. Hydrophobia, which principally affects the nervous system, is characterized by peculiar paroxvsms of suffocation, brought on chiefly by attempts at swallowing, by a catarrhal affection of the fauces, by a more or less pronounced febrile disturbance, and by an acute mania. The term rabies — or less frequently lyssa — is applied to the same disease in animals. Rabies is frequently observed in herbivorous animals, such as the ox, the horse, or the sheep. It is more commonly found in the car- nivora, such as the cat, the fox, the jackal, the wolf, and the dog. More rarelv it is observed in the skunk, in swine, in birds, and even in domestic poultry. Rabbits are susceptible to the virus, and they are used principally in experimental inoculations. The disease is always communicated by inoculation from animal to animal or from animal to man, and does not arise de novo. Infection does not always follow the bite of a rabid animal: the large majority of persons bitten are supposed to escape, but in most cases this immunity is due to protection by the clothing or the fail- ure to penetrate the epidermis, or, more probably still, to the fact that the supposed rabid animal did not suffer from rabies. Bites on exposed portions of the body by animals undoubtedly mad are probably followed by hydrophobia in the large majority of cases. The disease is not always caused by a bite, for a previously existing wound or an abrasion may be inoculated by the saliva conveved by the tongue of the animal while licking the skin of its master. In the dog the disease presents two types, the dumb and the furious rabies. In the furious form a change is first noted in the habits of the animal. He becomes uneasy and depressed, and is dull, wandering aimlessly about and hiding in obscure corners. In this early stage his saliva is already poisonous, and, as he occasion- ally exhibits a tendencv to be affectionate to some other animal of the household or to his master, his caresses are dangerous. Fre- quently, however, if disturbed, he growls and shows no inclination to move, but will still obey the voice of his master. He is subject to hallucinations, and will snap and snarl at imaginary objects. 453 454 SURGICAL PATHOLOGY AND THERAPEUTICS. Doleris mentions the case of a bull- terrier which was observed to peck, like a hen, at the hay scattered about the floor of the stable when there were no other symptoms. He was isolated and died of rabies. The symptom of hydrophobia does not exist in the dog: on the contrary, the dry and swollen state of the mucous membrane of the fauces causes him to seek water to slake his thirst. The animal will plunge eagerly into the water and bury his head beneath it to relieve this symptom. Rabid animals have been known to swim a stream to attack animals on the opposite bank. At first the dog takes his nourishment as usual, but he soon becomes voracious in his appetite, and in intense forms of the dis- ease he often exhibits a depraved taste, avoiding ordinary food, but tearing all kinds of objects and swallowing the fragments. He may even swallow his own excrement. The quantity of the saliva is not great at first, but it is more abundant in the earlier stages than later. It then becomes tenacious, adhering to the gums, and appears almost as white as snow. The dog's bark is quite cha- racteristic: it is at first husky, and in some cases ends in a plaintive howl somewhat like that of a dog barking at the moon. The sight of another dog generally brings on a paroxysm of rage — a symptom sufficiently marked and constant to be of value in cases of doubtful diagnosis. The affected brute will pass by other animals and man to attack another dog. He is usually quite insensible to pain: a red-hot poker may be grasped and held in the mouth. He can be beaten without exhibiting signs of pain, and often commits self- inflicted wounds. There may be great sensitiveness of the scar of his cicatrized wound. As the disease progresses there is marked inability to swallow either fluids or solids, and loss of strength is often progressive and rapid. The respiration is hurried. During the later periods of the disease delirium becomes a marked symptom. The animal is now seized with a desire to escape from the house, and it is during this stage that he becomes dangerous. His pupils are dilated, and his expression is terrible in its fierceness. He now attacks all ani- mals within reach, and also man. While biting and tearing he is, according to Suzor, always silent; unlike the non-rabid dog, which fights and barks at the same time. This stage is followed by one of great prostration. His gait is now tottering and his senses are dulled. After wandering about for a few hours, or it may be days, paralysis of the hind-quarters supervenes, and he dies of exhaus- tion and asphyxia. The disease usually lasts from six to eight days, but it may be prolonged for several days. HYDROPHOBIA. 455 The period of incubation of rabies varies from three to four weeks. It is occasionally very much longer. In nearly every case the disease terminates fatally. Dumb rabies is commoner than the furious form. The initial svmptoms closely resemble those of furious rabies. The voice in dumb rabies is much altered from the first, and in the later stages it is lost. The expression is sad and startled: the mouth is open, owing to the paralysis of the lower jaw, and the tongue hangs out drv and discolored and covered with dirt. Persons not acquainted with these symptoms might suppose the animal to be suffering from a bone lodged in the throat, and would, in making efforts to remove it, certainly expose themselves to inoculation. Paralysis of the hinder extremities supervenes, and it is soon followed by death. The symptoms in rabies appear to vary according to the regions of the cord which may be chiefly affected. On post-mortem examination the mucous membrane of the mouth and the tongue is found to be of a livid color. Ulcera- tions of the mucous membrane, supposed to be due to vesicles characteristic of the disease, are frequently caused by the swal- lowing of foreign bodies of various kinds, such as stones, straw > hair, and glass, with which the stomach is found to be filled. There is great congestion of the tracheal and bronchial mucous membranes, and there is a marked contraction of the bladder. Congestion of the central nervous system is also found. The etiology of hydrophobia in man is not yet fully explained. Pasteur has been unable to demonstrate any form of bacteria which can be identified with the disease. Fol and Rivolta have lately described a coccus in this disease, but their observations have not been confirmed by others. The virus is probably never absorbed through the mucous membrane: Doleris mentions cases of persons who had eaten with impunity the flesh of rabid animals. The bites of certain species are said to be more dangerous than those of other animals. In Russia it is believed that wolves are more dangerous than any other animals, and in America the bite of the skunk is greatly dreaded. There is probably no difference in the strength of the virus in these animals, the more frequent poisoning being probably due to their sharp teeth and to the greater certainty of inoculation through the penetrated skin. The period of the year is supposed to exert a favorable influence upon the development of an epidemic of hydrophobia. The results of the work of Pasteur's Institute show that the disease is not con- fined to any one period of the year, and that, contrary to the com- 45 6 SURGICAL PATHOLOGY AND THERAPEUTICS. mon belief, it is not a disease of the summer months. Two at least out of four cases which have come under the writer's observation occurred during the summer. Pasca of Milan found the disease occurred more frequently during the spring and autumn months. The period of incubation of the disease in man is quite variable, although the first symptoms usually make their appearance in the second month after exposure. According to Brouardel, the disease rarely occurs after the third month, and quite exceptionally after the sixth month. The symptoms manifest themselves earlier when the bites are numerous and severe, and they appear also earlier in children than in old people. Cases are quoted where the disease is said to have supervened several years after infection, but the exten- sion of the period of incubation beyond those above named is to be received with caution. The disease appears to be very much commoner in France than in America. Further reference will be made later to the number of cases occurring in France. In the city of New York there were, during a period of thirty -five years, only 76 deaths from hydro- phobia. In 9 of these years there were no deaths, and it has twice happened that for two years in succession there was not a death. In Boston and its vicinity H. C. Ernst reports an epidemic of rabies among dogs during 1889 and 1890, some 60 cases being observed at the Harvard Veterinary Hospital. During the summer of 1890, 3 cases in man were observed at the Boston City Hospital, from 2 of which material was taken by Ernst and successfully inoculated into rabbits, which died with the usual symptoms. The disease may appear either as a delirious or as a paralytic form, precisely as in the dog, but the delirious form is the variety by far the most frequently observed. The first stage of the disease is characterized by melancholia. It is marked by insomnia, by loss of appetite, and by great depres- sion of spirits, and occasionally there are shooting pains found radiating from the seat of the wound or in the affected limb. In a case reported by Shattuck the patient first complained of severe pain in the back of the head and in the neck; on the next day he went as usual to his business, but he returned home at an early hour much depressed, saying, u I have come home to die." Dif- ficulty of swallowing appeared on the same day. This stage does not last more than twenty-four or forty-eight hours, although some authors have described cases in which headache, insomnia, and anorexia were observed for three weeks previous to the outbreak of hydrophobia. HYDROPHOBIA. 457 The cases seen by the writer had all reached the stage when that most striking- symptom of the disease — difficulty in swallowing — was plainly marked. The appearance of the patient at this time, although not presenting symptoms likely to attract the attention of the casual observer, is most characteristic. The picture thus presented is one not likely to be forgotten or to be mistaken for any other disease. On entering the apartment one looks around invol- untarily to find the patient, for the individual, quietly seated with his back partly turned to one, is dressed in his ordinary clothing and gives no indication of suffering from any abnormal condition. A brief conversation, however, soon brings out the peculiarities of the case. His speech is perhaps the first function to betray the disease. The patient appears to be slightly out of breath, frequent short inspirations so altering his conversation as to give to it the so-called "sobbing " tone. It is, indeed, not unlike the speech of a child who has recently been crying and is endeavoring to control itself. The expression of the face at this time varies from one in no wise differing from a perfectly normal condition to a more or less wild or a haggard look about the eyes. Usually there is an appear- ance of depression or of anxiety, like that of a prisoner waiting for the verdict. But the most crucial diagnostic test is the glass of water. The following account of the attempts made by a patient to drink is given by Curtis, with whom the writer saw the case in consultation : " A glass of water was offered to the patient, which he refused to take, say- ing that he could not stand so much as that, but would take it up from a teaspoon. On taking the water in the spoon he evinced some discomfort and agitation, but continued to raise the spoon. As it came within a foot of his lips he began to gasp violently, his features worked, and his hand shook. He finally almost tossed the water into his mouth, losing the greater part of it, and staggered about the room, gasping and groaning. The respiration seemed at this moment wholly costal, and was performed with great effort, the elbows being jerked upward with ever} 7 inspiration. The paroxysm lasted about half a minute. The act of swallowing did not appear to distress him, for he could go through the motions of deglutition without any trouble. The approach of liquid to his mouth, however, would at once cause distress." It will be noticed that the "spasm," as it is called, does not involve the muscles of the pharynx and the oesophagus, but affects rather the mechanism of the respiratory apparatus. It is true that many authors report spasms of the muscles of the pharynx, and even of the jaws and the extremities, but these are secondary to the overpowering sense of suffocation. The palpita- 458 SURGICAL PATHOLOGY AND THERAPEUTICS. tions of the heart are also violent, and the cardiac disturbance has been described by Doleris as a spasme circulatoire. Of the nature of the hydrophobic paroxysm something further will presently be said. Distress is also caused by fanning the patient or by exposing him to a draught of air {aerophobia). In one case, on gently passing the fan to and fro behind the patient's head while other persons were conversing with him, the writer produced a disturbance sufficient to cause the patient to spring from his chair and to walk rapidly to the other side of the room. The patient did not appear, how- ever, to be conscious of what had disturbed him. In another case, a lump of ice being placed in the patient's hand, he flung it from him with expression of great pain; on being asked what his sensa- tions were, he explained that it felt like a red-hot coal. Already at the end of the first day the mental condition of the patient is evidently impaired, the expression of the eye has grown more wild, and the speech has begun to be somewhat incoherent. Cephalalgia is a frequent symptom, and it is occasionally of great intensity. In one of the paroxysms of the case already referred to the patient would exclaim, " For God's sake, hold my head or it will burst !" There is at this time a secretion of viscid saliva, which can be seen accumulating about the teeth and the lips. The irritation of the fauces is great, and in the effort to expel from them the adherent secretions there is developed a loud and abrupt cough, which has probably given rise to the tradition that such patients "bark like a dog." Presently the paroxysms appear to come on spontaneously. The patient, who by this time has become fatigued by the nervous excitement, by the exhausting paroxysm, and by the inability to take food, has been persuaded to go to bed. The accumulation of saliva causes attempts to swallow or to expectorate, and the contact of the secretions with the fauces or with the lips causes irritation sufficient to bring on an attack. The paroxysms are doubtless caused also by mental apprehension of an impending attack. On the approach of the paroxysm the patient, who a moment before has been quietly lying in bed, may suddenly spring out of bed and grovel on his hands and knees in a distant corner of the room. Violent attempts at expectoration may occur. At this stage of the disease there will probably be more or less marked mental disturb- ance. The patient's opinion of the manner in which he has passed the night is quite unreliable. Acute mania may supervene, and in HYDROPHOBIA. 459 one of the cases which the writer saw the patient escaped from his room early in the morning, and was found to have scaled a high fence and to have concealed himself at some distance from the hos- pital. Marked sexual excitement is frequently observed: in men the talk is obscene and painful emissions may occur; in women nymphomania may be present. During the period of mental ex- citement the patient may struggle fiercely with his attendants. Occasionally he may attempt to bite, but this is in no way cha- racteristic of his condition. In some cases during this stage mel- ancholia is present in a marked degree: the patients are the prey of nameless terrors, and many cases of suicide are recorded. After each paroxysm prostration becomes more marked, and in some cases coma may supervene temporarily. At the end of the second day, usually, the prostration is so great that the attacks are much feebler, and toward the close of the scene the patient may become comparatively quiet. The transition from prostration to coma is rapid, and the moribund stage is usually short. Febrile disturbance does not appear to be a marked feature, although occa- sionally it may appear with the outbreak of the disease; but pyrexia is present in the later stages, and in one case which the writer saw the temperature ran above 104 F. on the last day. The pulse usually is not greatly accelerated. There may also be a paralytic form of rabies in man, although this form is much rarer than is the furious form. Gamaleia of Odessa published an account of thirty cases. He found that the disease is the result of deep and multiple bites. At the onset there is considerable fever, malaise, headache, and vomiting. There is also pain in the extremities, particularly in the part bitten. Paresis and numbness appear in the group of muscles near the injured parts, these disturbances being followed by more or less complete paralysis. The paralysis then spreads, preceded or accompanied by sharp pain in the muscles invaded; the remaining limbs, the trunk, the rectum and the bladder, the face, the tongue, and the eyes, are all paralyzed, and finally there is paralysis of the respi- ratory centre, with more or less difficulty in swallowing liquids. Gamaleia says: "When well marked this respiratory lesion is the cause of dyspnceic convulsions in the muscles which are not yet paralyzed, then frequently return of breathing to the normal, but spread of the paralysis to the heart and death by syncope." This form of rabies has a duration of about one week. Dana says : "In questioning the many general practitioners from various parts of the country with whom I come in contact, I 460 SURGICAL PATHOLOGY AND THERAPEUTICS. have found that many could recall cases of mysterious acute pro- gressive fatal paralyses whose nature and cause have completely puzzled them. It may be that the paralytic rabies in man is there- fore not such an extreme rarity." Gray believes that the symptoms of the so-called ' ' dumb rabies ' ' may be caused by simple purulent meningitis and meningo-encephalitis. Lyssa falsa seu nervosa, which is a term applied to a condition produced by the fear of rabies, is occasionally seen in hysterical subjects. It is not difficult to distinguish it from the true disease, as the period of incubation is too short, and a few days' or even hours' observation will decide the question, owing to the rapid development of the symptoms of true hydrophobia. Cases of lyssa falsa are said to have terminated fatally, but such a result may have been due to complications, such as an acute mania or some infec- tious disease. Birdsall saw a number of such cases, in none of which the patient died, but he would not say that death from fright of this kind was impossible. According to Curtis, "the hydrophobic paroxysm is to be likened to the shock of the shower-bath. The regulation of the respiratory centre is accomplished by an inhibitory influence. One of the most striking examples of this action is observed in the superior laryngeal nerve. Irritation of the divided central end of this nerve causes an immediate suspension of the respiration, the diaphragm, paralyzed and relaxed, being thrown into an attitude of extreme expiration." The same result may be produced, according to Brown-Sequard, by direct irritation of certain parts of the me- dulla. A similar influence is exerted by a variety of peripheral stimuli: powerful excitations of the nerves of general sensation, particularly the fifth pair, cause slowing of the respiratory move- ments. A similar effect is produced by psychical impressions pro- ceeding from the emotional regions of the brain and the medulla, as shown in the breathlessness experienced under circumstances of great alarm or excitement or grief. The superior laryngeal nerve supplies sensation to the mucous membrane of the base of the tongue, of the upper part of the anterior wall of the oesophagus, of the epiglottis, and the laryngeal mucous membrane. When stimulated by the irritating contact of foreign bodies, liquids, irri- tating vapors, and gases, paralysis of the diaphragm takes place with extreme respiratory relaxation, so that inspiration is for the time being rendered impossible. The same protective agency is brought into play in every normal act of swallowing, or even in inspiration itself, which is thus rendered, as it were, self-inhibiting. H YDROPHOBI. I. 46 1 The breathlessness in the shower-bath or in cold sea-bathing is another example of the same inhibitory action. Similar sensations are produced by the attempt to swallow a glass of hot, steaming punch, which will sometimes "take one's breath away" by the same mechanism. Swimmer's cramp is probably also another example, resulting in sudden death from apncea, and is not due to " cramp" of the muscles, as is generally supposed. The hydrophobic paroxysm is not to be regarded as a convul- sion, unless, as Curtis graphically puts it, ik a drowning man unable to swim and thrashing about in the water, or a man clutched bv the throat and struggling frantically for life, can be said to have con- vulsions. " The paroxysms are rather to be regarded as sudden attacks of paralytic apncea due to temporary, partial, or complete inhibition of the respiratory centre taking place under the influence of peripheral impressions. The inhibitory stimulus may proceed from the area of distribution of the superior laryngeal nerve, being originated by attempts to drink and by accumulated saliva, or from the area of the fifth pair as a result of wetting the lips or the face or of fanning; or it may be due to an irritation of the nerves of sensation of the trunk and limbs or the nerves of special sense. The origin of the respiratory inhibition does not appear to Curtis to be due so much to an increase of inhibition as to diminished resistance of the respiratory centre, due to the structural changes which Gowers has shown are most intense in the respiratory centre of the medulla. All that is required, therefore, is a slight inhib- itory stimulus to reduce the activity of this centre to zero. Accord- ing to Putnam, it must either be assumed that the respiratory centre is abnormally susceptible to inhibitory influences or that the inhib- iting impulse is extremely powerful. As the structural lesions found in the medulla show an impairment of the nutrition of the respira- tory centre, the theory of over-sensitiveness to inhibitory influences must be rejected. There is no evidence that the impressions made on the skin or the mucous membrane are abnormally intensified: there is, however, the stimulus of emotional excitement which is always present in such cases. The paroxysm is therefore directly due, Putnam thinks, to the reaction on the respiratory centre of the morbid mental state of the patient. Gowers maintains that the phenomenon is not one of inhibition, but of irritability of the respiratory centres, particularly that por- tion which has to do with the process of extraordinary breathing; that is, the costo-superior respiration. According to this author, the nature of the symptoms and the lesions in hydrophobia seem to 462 SURGICAL PATHOLOGY AND THERAPEUTICS. suggest that the poison has an action on the nervous centres in the following order: the medulla oblongata, the cerebral hemispheres, and the spinal cord. The effect on the medulla is the first, the most intense, and the most constant, especially in the early stages. The action on the spinal cord is rarely marked except in the latest stage. The action on the cerebral hemisphere is chiefly shown in the delirium which is so conspicuous in some cases in the later stages. Gowers carefully studied the microscopic condition of eight cases of hydrophobia in man and of one in a dog. The changes found in the spinal cord were comparatively slight. There was some hypersemia of the gray substance, but no cell-infiltration. The region in which the pathological conditions were most intense is what is known as the respiratory centre of the medulla, the region in which are situated the hypoglossal, pneumogastric, and glosso- pharyngeal nuclei. Then, in addition to the great distention of the minute vessels seen in the cord, there was found an aggrega- tion of cells in the perivascular lymph-sheaths. The cells were found sometimes in a single layer, and sometimes so densely packed as to compress the vessel they surrounded. In some instances they had extended beyond the perivascular sheath and had infiltrated the adjacent tissues. Here and there were patches of tissue infiltrated with leucocytes in this manner. In one case such an area was found between the hypoglossal and the pneumogastric nucleus. Gowers describes them as miliary abscesses. There was also a number of small round cells scattered through the adjacent tissue in greater numbers than in health. Many vessels, especially the veins, were distended with blood-clots (showing prob- ably the septic nature of the inflammatory stimulus). The nerve- cells presented comparatively little change: many of them had a granular appearance, which was more marked in some than in others that lay near them; others had a somewhat swollen appear- ance. The changes around the auditory, facial, and fifth nuclei were not so marked. The higher part of the pons was much less affected. Miliary abscesses had previously been observed by Kol- esnikoff. Fitz found the most extreme alteration in the part correspond- ing with the calamus scriptorius. The appearance most frequently met with was an infiltration of the adventitia of the veins with small round cells. Extravasation of blood was found in the peri- vascular spaces. The u miliary abscesses " were also seen, and in two instances actual abscesses were found (Fig. 75). So far as H YDROPHOBIA . 463 other organs were concerned, Fitz found numerous slight hemor- rhages in the septum of the heart: no abnormal appearances were observed in the pharynx and in its submaxillary glands; the % ..• • .r . ^ • » • . 1% ,*.-. ■'. • ••■•■ . ■. * ,: .fvi ■■ ' m : & : ■■■:■ % ■ ■ v. . S . Fig. 75. — Extravasation or "Miliary Abscess" in the Cervical Cord in a case of Hydrophobia. oesophagus from the bifurcation of the trachea downward was extensively cedematous. In one case examined by Wickham hegg the kidneys showed cloudy swelling, but, as a rule, no pathological changes of import- ance appear to have been discovered in the thoracic and abdominal viscera. Hyaloid masses have been found in the medulla by sev- eral observers, but as these are met with also in normal specimens, it is not certain whether in these cases they were of any patholog- ical significance. Although in the microscopical appearances above mentioned there is nothing that can be regarded as specific of the disease, still Gowers is of the opinion that "the distribution of the lesions, their intensity in the lower part of the medulla and in the neigh- borhood of certain nerve-nuclei are, as far as I am aware, pecu- 464 SURGICAL PATHOLOGY AND THERAPEUTICS. liar to the disease and constitute a distinguishing anatomical character. ' ' Vesicles on the inferior surface of the tongue, once thought to be characteristic of the disease, are rarely found, and no special importance is now attached to them. The nerves of the part in which the bite is situated have been observed to present patho- logical changes: the myelin is found in a diffluent condition, the structure is softened, and the axis-cylinder is at times absent in many of the nerves. The same observation is recorded in the nerves arising from the medulla, such as the glosso-pharyngeal and the hypoglossal (Blodgett). Occasionally there is some hyper- semia about the region of the cicatrix, but in most cases no special change is observed. The writer has already intimated that treatment of the disease is futile. Powerful drugs of various kinds have been used, but no authentic cases of cure have ever been reported. It was claimed at one time that curare had cured a case, but, although Shattuck and Curtis report a most systematic course of treatment with this drug in two cases, no favorable effects were observed; and this has been the experience of others who have tried the drug. Until something in the nature of an antitoxine has been discovered, it is hardly worth while to discuss the therapeutics of the already- established disease. ^^prophylactic treatment so wonderfully carried out by Pasteur merits, however, the most careful scrutiny. Pasteur's attention was first called to hydrophobia in 1880, having visited a case in one of the hospitals under the care of Lannelongue. In Pasteur's earlier experiments on animals he found that the virus existed not only in the saliva, but also in the brain, and that the period of incubation could be shortened greatly by inoculating the trephined brain of a healthy animal with the cerebral matter of a mad dog. Symptoms appeared in one or two weeks: by other routes the inoculation may not be followed by symptoms for one or two months. In fact, he soon found that the principal seat of the virus was in the central nervous system, where it may be obtained in great quantity and in a state of perfect purity. Virus obtained from this locality was therefore far preferable to the saliva, which contained quantities of micro-organisms. He later found that the virus existed in the whole nervous system of animals and in the salivary glands. Pasteur next discovered that a given virus had its virulence modified by passing it through different species of animals. Inocu- H YDROPHOBIA . 465 lation from monkey to monkey attenuates the virus. Conversely, the strength of the virus is increased by passage through rabbits: the period of incubation is also shortened, so that by the time the one hundred and twenty-fifth passage had been reached this period is reduced to seven days. The spinal cords are virulent through- out their entire substance, and there is obtained by this method a virus of sufficient strength and reliability to be used for purposes of inoculation. By cutting up the spinal cord into fragments a few centimetres long and suspending them in a dry atmosphere their virulence gradually diminishes until it is lost, so that there can thus be obtained virus of any desired strength. If a dog is to be made refractory to the poison of rabies, it is first inoculated with a cord so old that the virus is very feeble. The strength of the inoculation is gradually increased from day to day, each virus preparing the animal for the succeeding stronger dose until cords are used which have been drying only one or two days. The dog has now been successfully inoculated with very strong virus, and, feeling no bad effects from it, has become refrac- tory to the ordinary "street rabies." The brains and cords of rabbits used for these inoculations are prepared as follows : Having been removed from their bony casing, they are laid upon a plate with the basal surface upward. The parts which are necessarily handled should first be wrapped in paper. All instruments and utensils used are carefully sterilized by heat. The cords are dried by suspending them in bot- tles with a hole near the bottom for the purpose of ventilation ; the two apertures are closed with cotton-wool plugs, and caustic potash is kept in the bottom of the flask to secure a dry atmosphere. On drying, the cords become crumpled and brittle and darker in color. The cord is used in pref- erence to the medulla, as being more convenient to handle. The virulence is the same in both. The emulsion is prepared by beating up fragments of the cord about the size of a pea with sterilized veal -broth or with water in a half- ounce conical glass, which is afterward covered with filter-paper. The nerve- tissue is triturated by means of a glass rod, and the broth is added until a thick, turbid liquid amounting to about half a tablespoonful is produced. The broth used for this purpose is kept in a pipette bottle. The inoculation experiments upon animals are carried out by trephining and inserting a drop or two of the emulsion beneath the dura mater. In this way absolute certainty of result is obtained as well as an exact period of incubation. It was in July, 1885, that Pasteur first applied his protective inoculation in man. He had at that time rendered fifty dogs refractory without a single failure. A hypodermic syringeful of the emulsion is injected into the subcutaneous tissue of the region of the hypochondrium, as the tissue is here loose and is more 30 466 SURGICAL PATHOLOGY AND THERAPEUTICS. rapidly absorbent than elsewhere. The patients are first inoculated with a cord fourteen days old, and the inoculation is repeated daily for nine days, each time with a cord one day fresher. In winter the oldest cords used are five days old, and in summer cords which have been drying- for four days are also employed. The preceding is the ordinary treatment. The so-called "intensive treatment n is used for patients who have been bitten on the hands or on the hare feet, or for patients who have been bitten so long beforehand that it is necessary to complete the course of treatment more rapidly. The intensive method consists in the omission of certain cords — for example, the weakest — and of some of the intermediary cords, and in the administration of the inoculations at shorter intervals than once in the twenty-four hours. If the first dose is given at 8 A. m. from a cord ten days old, the second dose would be given at 2 p. m. from a cord eight days old; the third at 8 p. m. from a cord six days old; and the fourth at 2 A. m. from a cord four days old. This series may be repeated at the same intervals, or, if the case be desperate — that is, if the patient has been bitten so long before treatment that the average period of incubation has already elapsed — the inoculation is carried even further, and the virus of only one day's drying may be used in the first twenty-four hours. By this intensive method it is claimed that better results are obtained than by the older, apparently safer, but slower, method. The first case upon which this method was tried was Joseph Meister, a child nine years of age. He had been severely bitten on the hands, the legs, and the thighs, and when rescued from the dog was covered with blood and saliva. The animal was undoubt- edly mad. Sixty hours after the accident (July 6th) the boy was inoculated in the right hypochondrinm with half a syringeful of the emulsion of the cord of a rabbit which had died on June 2ist. The cord had been kept fifteen days suspended in a bottle as above described. On the following day he was injected with a fourteen- days'-old cord, and so on daily or twice daily until, on July i6th, the thirteenth sitting, he was injected with a cord one day old. Healthy rabbits were inoculated with each preparation, and it was found that the older cords did not produce rabies, but the cords of July ii, 12, 14, 15, and 16 were all virulent, and the disease was therefore reproduced; Meister survived. A child of ten, who had been bitten in the axilla and on the head, and who was not subjected to treatment until thirty-seven days after the accident, died of hydrophobia appearing eleven days after the end of the treatment. The question arising which HYDROPHOBIA. 467 of the viruses had killed the child, that of the mad dog or that prepared by Pasteur, her skull was trephined near the wound and a portion of cerebral matter was taken out and inoculated into rabbits, which died fifteen days later. Had the deaths of the rabbits been the result of the preventive inoculations, the incu- bation period would have been only seven days. Of those who succumbed after treatment the majority were chil- dren who had been bitten in the face and who had only received the simple treatment, which Pasteur does not now consider suf- ficient for such cases. For those he now uses the intensive treat- ment, giving three or four inoculations daily, and reaching the one-day-old cord on the third day. Three courses are given during a period of ten days. The difference in virulence of the cords is not considered by Pasteur to be due to a diminution of degree, but to a diminution in quantity of the virus contained in them. He is inclined to believe that the rabies virus is made up of two distinct substances — the one living and capable of multiplying in the nervous sys- tem; the other not living, but capable, when present in suitable proportions, of arresting the development of the former. In other words, he believes in a "vaccinal" matter associated with the microbe, the latter dying more rapidly in the dried cords than the former. Vaccine inoculation for protection from small-pox is sufficient if performed three days after exposure, as the period of incubation of the vaccine is only nine days, while that of small-pox is twelve days. So with the vaccine of rabies: it must be given sufficient time in order to do its work more effectively. The death-rate, according to French statistics, amounts to 30 per cent, after efficient and early cauterization. When these pre- cautions are not used it rises to 80 per cent. According to Gowers, when no preventive measures are adopted at least half, perhaps two-thirds, of persons bitten escape. A moderate estimate of the death of all persons bitten by rabid animals except wolves is prob- ably 20 per cent. , whether the bites have been cauterized or not. The death-rate from wolf-bites is as high as 65 per cent. , and when the face and head are bitten it reaches 88 per cent. Indeed, in Russia it is believed that every person bitten by a mad wolf dies. The incubation period following the bite of this animal is quite short, owing to the number and the nature of the bites. It is not probable that there is any difference in the viruses of a mad dog and a mad wolf. The results obtained by the work as carried on in Paris at the 468 SURGICAL PATHOLOGY AND THERAPEUTICS. Pasteur Institute since the beginning of the employment of this method are summarized and discussed very carefully and fairly in the Annales de V Institul Pasteur. All cases are placed in one of three categories: Class A consists of those bitten by animals shown to have been rabid by experimental inoculation; Class B consists of those bitten by animals declared to be rabid by veterinary authority; Class C includes those bitten by animals supposed to have been rabid. The following table gives the figures of these different classes for 1893: Bites of Head. Bites of Hands. Bites of Body an d Legs. Total. £c £g >>c e c c c '^u .22 T3 U V ,22 H3 T3 .a X) « p, 0. .2i p. .22 p, Ph Q s P-> ft S P< Q s Ph Q S A, 12 O 80 40 132 O B, 89 O 534 3 0.56 385 IO08 3 0.30 C, 34 O 243 1 0.41 23I 508 1 0.20 135, *V, 4 0.46 656, 1648 4 0.24 Total. Total. Total, The statistics for each year from the beginning up to the present time are given below: Years. 886 887 888 .. . 889 890 891 892 893 Total Patients Treated. 2,671 1,770 1.622 1,830 1,540 1,559 1,790 1,648 14,43° Died. 25 14 9 7 5 4 4 4 72 Mortality, per cent. O.94 O.79 o-55 0.38 0.32 0.25 0.22 0.24 0.50 These figures apparently afford ample proof of the success of the Pasteur method. Tizzoni has experimented with a protective substance produced by treating the cords of infected rabbits with peptones. An emul- sion of the cords in peptones parts with its virulence entirely in twenty-four hours. The flocculent deposit obtained is preserved in glycerin. Tizzoni has been able not only to render rabbits immune, but also to check the symptoms of rabies after they had already developed. This method of treatment has not yet been applied to man. (See Appendix.) XX. ACTINOMYCOSIS. Actinomycosis (axn'c, ray, /zwoyc, fungus) is an affection charac- terized by the presence in the tissues of a vegetable parasite (acti- nomyces) which gives rise to a chronic inflammatory process. This disease is found both in animals and in man. In the former it gives rise to a granulation or sarcoma-like tumor, and it has been described, before its true nature was understood, under a variety of names, such as "big jaw," "swelled head," and "lumpy jaw." Many cases described as sarcoma in cattle were undoubtedly forms of this affection. In man the growth is accompanied by a suppu- ration, which is not due, however, to the organism, but to a mixed infection with pyogenic cocci. Langenbeck was one of the first to notice the presence of the parasite in a case of vertebral caries. Lebert was, however, the first to publish, in 1848, a description of the same organism, which he found in an abscess of the thorax. He did not, however, recog- nize its significance. Robin observed similar bodies also in pus, and Rivolta in 1868 and Perroncito in 1875 found the organisms in the jaws of diseased cattle. The first scientific description of these organisms came from Bollinger, Israel, and Ponfick in 1877, I ^7^> and 1879, respectively. Since then a large number of cases have been observed and described in man. In America, Belfield first recognized the parasite in cattle, and Murphy reported the first case of actinomycosis hominis. According to the latter, up to January 1, 1891, there had been reported two hundred and fifty cases of the disease in man. A description of the organism will be found on page 76. It may be briefly stated here that the organism is known as actino- myces, or the ray fungus, and it appears in pus or on granulations as minute granules varying in size from a grain of sand to a pin's head (Fig. 22). These granules, which are yellow in color, are easily seen by the naked eye. If pressed down with a cover-glass, they readily flatten out, while possibly a distinct gritty sensation is transmitted to the finger, owing to the presence of calcareous mat- ter. With a low power of the microscope the fungus will be rec- ognized scattered over the field in the form of irregular patches, 469 47° SURGICAL PATHOLOGY AND THERAPEUTICS. which might at first be mistaken for granular debris, but which, by more exact examination with a higher power, will be observed to have the characteristic appearance. The rosettes of clubs min- gled with pus-cells and fragments will then be found. By pressing upon the cover-glass the rosette is broken up and the club-shaped masses are seen separately. If the yellow granule is picked apart in water, the central portion of the fungus appears to be a struc- tureless core. Cultures of actinomyces are made with great difficulty. Agar- agar and egg-albumin, blood-serum, bouillon, and gelatin are the media used for the purpose. The growths taken from plates and grown in blood-serum develop at the end of four or five days. According to Babes, cultures obtained by him grew mostly in the depths of the culture medium and rarely on the surface. Attempts to transfer the actinomyces from one animal to another by mixing them with the animal's food have not succeeded, but inoculations have successfully been made by introducing the granules into the peritoneal cavity of rabbits ; also by introducing the infective mate- rial beneath the skin, into the veins, and into the abdominal cavi- ties of calves. The cow appears to be the most susceptible of all animals. Although the disease is found in cattle, yet in reported cases it does not appear that it has been transmitted to man in his food, and the disease has not been observed in carnivorous animals. The few observations that have been made, tending to show that the meat of animals is the source of disease in man, have not suf- ficed to demonstrate this satisfactorily. Hence it has not been the custom in many places to condemn the entire animal when a part only is affected. There are no observations which prove that it can be transmitted by milk. According to Bostrom, who carefully analyzed a series of cases, the disease appears to begin in the autumn, and the ears of grain in which the fungus probably grows are the carriers of the disease to man and to animals. In one of this author's cases the patient acknowledged that he was in the habit of chewing ears of barley or of rye, and in the much-quoted case of Soltmann the patient, a boy, swallowed an ear of barley, which caught in the oesophagus and could not be coughed up. Perforation occurred, and mycotic abscesses formed around the vertebral column and elsewhere. Johne found frequently in the tonsils of hogs ears of grain containing unmistakable growths of actinomyces. Jensen observed an outbreak of the disease in cattle due to feeding them with grain which had been taken from a soil reclaimed from the sea. It seems probable that the most ACTINOMYCOSIS. 471 frequent route of infection is the mouth and the pharynx, the organism becoming attached to and growing in some of the numerous inflammatory processes common to this region. The cavities of carious teeth and the follicles of the tonsils appear to be localities that afford a soil favorable to the growth and develop- ment of this organism, from which foci it is subsequently distrib- uted throughout the system. After once having gained a foot- hold, the parasite is said to be conveyed to distant parts of the body through the blood-current and not through the lymphatics. In man the disease presents two salient features — the formation of abscesses and the presence of yellow granules in the pus, and granulations of these abscesses. The swelling does not have a well-defined border, as seen in cattle, in which it resembles a tumor, but it is more or less flattened and disseminated, and is accompanied by the growth of an indurated connective tissue which is very characteristic. There is usually, later, a false fluctuation at certain points, due to the presence of the soft, fungous mass of granulation tissue. Presently the skin becomes a deep red and the abscess opens. The granulating surface has a yellowish or a violet color. Pressure brings a small quantity of thin sero-purulent or cheesy material. In some cases a few drops of thick pus will ooze out after lancing the abscess, and with them a number of striking sulphur-colored granules. On probing a sinus thus formed it will be found that the disease has involved the adja- cent muscles, which are so infiltrated and matted together as to impede their movements. The nerves are also involved in the induration, and in later stages the bone becomes affected and in it cavities form. The jaw is usually the part most frequently attacked, and later the teeth drop out and the pus-cavity com- municates with the mouth. In the mean time new fistulae form and communicate with the original focus. The disease does not attack the interior of bone as in cattle, forming a spina ventosa, but rather confines itself to a multiple caries with the formation of osteophytes (Partsch). If the inflamed mass is laid open at a post-mortem examination, the sinuses are found to resemble those seen in connection with tuberculosis of bone. There is a lining pyogenic membrane com- posed of fungous granulation tissue of a yellowish or a reddish- gray color, which tissue is readily scraped away. A central pus- cavity is rarely found. A number of minute abscesses, however, are seen in the walls of the inflamed mass. Other abscesses may be found in the immediate neighborhood, either entirely inde- 472 SURGICAL PATHOLOGY AND THERAPEUTICS. pendent of the original focus or communicating with it by fis- tulous tracts. The yellow grains are to be found in the secretions of all these various cavities and also in the walls. A cross-section of the abscess-wall shows it to consist of a sar- coma-like tissue. It has been said to resemble so closely round- cell sarcoma as to be almost indistinguishable from it were the yellow grains absent. In other places spindle, epithelioid, and giant-cells are seen. In the peripheral portions of the disease the abscess-wall consists of a dense fibrous tissue surrounding a cluster of cells, in the centre of which is the actinomyces (Babes). When once the parasites begin to develop in the tissues a growth of sarcomatous connective tissue is built up around them, forming a barrier which probably tends to retard their growth. The cells near- est the centre of this nodule undergo fatty degeneration, and break up and leave a more or less fluid substance in their place, and in this way .a miliary abscess is formed. Large abscesses form by fusion of several smaller ones. The progress of the disease is slow, as the inflammation is of a chronic type. Infection takes place most frequently through the mouth and the pharynx, but the organism may find an entrance to the system through the air-passages or through the skin. In any case a wound, however small, is necessary for inoculation to take place. When infection takes place by the mouth in the less severe forms of the disease, the patient comes with a history of toothache, with swelling at the angle of the jaw, and with difficulty of swallowing and of opening the jaw. The external tumor reddens and softens, and fluctuation is followed by an opening and discharge of pus containing the characteristic yellow granules. After some tem- porary improvement the swelling continues to spread and the abscess opens into the cavity of the mouth. Many cases can be arrested at this point by a radical operation which removes the entire diseased mass. A very characteristic symptom, according to Partsch, is the rigidity of the jaw caused by the induration of the surrounding muscles. If the affection is allowed to continue untreated, however, the bone of the lower jaw becomes involved, the teeth drop out, and several of the adjacent muscles are destroyed. As the disease works its way downward it follows the line of the sterno-mastoid muscle to the clavicle, involving on its way nearly all the struc- tures of the neck, including the vessels. The pus, which burrows about inside the diseased mass, finds its way to the surface at vari- ACTINOMYCOSIS. 473 ous points in the neck, and even into the oesophagus, so that food may be discharged through the fistulse. A muco-purulent expec- toration from the lungs shows that the disease has reached these organs, and on its way it may have destroyed the clavicle. If portions of the fungus find their way during this process into the circulation, the heart may become involved in the disease, and small tumors may form in the substance of its walls and in the pericardium. Metastatic deposits may be found in the spleen, the liver, the brain, and the kidneys. When the upper jaw is the seat of the disease the prognosis seems to be still more unfavorable. Here the cheek is involved in the inflammatory process, and abscesses may form and break as high up as the lower eyelid, which probably will be very much swollen and oedematous. Here also the disease appears to begin in a carious tooth. With the discharge of pus there may be symp- toms of nasal catarrh, showing that the disease is spreading in the direction of the nose. The swelling soon involves the whole cheek, and then spreads backward to the region of the ear and the temple. The jaws are often difficult to open at this stage, and the fetor of the breath may be well marked. If an inspection of the throat can be made, the tonsil and the fauces are often found swoll- en and red; the gums are also swollen, and many of the teeth are loose. These changes follow one another slowly, and there are periods when the disease, after surgical treatment, appears to be improving; but although, superficially, there is a diminution in the severity of the symptoms, there is a gradual spread of the infection in the deeper parts, where nothing seems to be allowed to stand in the way of the progress of the disease. In working upward it may penetrate the base of the skull and the membranes, and even invade the brain itself. From the pharynx or oesophagus it may reach the posterior mediastinum, and so affect the bones of the spine that they appear to have undergone an extensive caries. Abscesses forming in this locality may perforate the intercostal spaces and may break externally in the dorsal region. In rare cases the disease may begin with an infection of the tongue: Hochenegg reports such a case. The patient was a young man who looked after cattle and who was in the habit of chewing ears of grain. On one occasion he thought he had wounded his tongue with the edge of a carious tooth. Two months later there was a swelling in the right half of the tongue about the size of a cherry. This swelling was excised with a wedged-shaped piece of the tongue, and the patient was cured. 474 SURGICAL PATHOLOGY AND THERAPEUTICS. Infection through the respiratory tract is supposed to be due to the inhalation of colonies already forming in the mouth or the throat. A case is reported in which a tooth was inhaled into the lung and became the starting-point of the disease in that organ. The direct infection of the lung by inhalation is doubted by many, but cases are reported in which it is probable that the fungus or its spores were inhaled directly into the lung with the inspired air. The left lung is said to be more often affected than the right. The first symptom of the disease may be a pain in the side ushering in an attack of pleurisy. In a case reported by Bostrom there appeared soon after the pain a redness and swelling at the level of the eighth rib. On making an attempt to excise this swelling the tissue was found to be almost of sole-leather hardness, but pus eventually was reached. This inflammatory induration gradually spread up and down, so that six months later, when the patient died, it had invaded the thorax-wall and had worked its way through the diaphragm into the liver and along the spinal column to the pelvis. The expectorations in this case were peculiar, and were regarded by Bostrom as pathognomonic of the disease. On washing the muco-purulent sputa in water they were found to be branched in a way that showed them to be casts of the finer bron- chi, and to contain the actinomyces granules. This author ob- served the same condition of the sputa in another case. The effect upon the lung parenchyma is to produce a prolifera- tion of round cells which undergo fatty degeneration. Patches of pneumonia and peribronchitis are thus formed, or, if the infection is near the surface of the lung, pleurisy may develop. Abscesses eventually form which break into the bronchi. The apices of the lungs are usually unaffected. There is considerable resemblance in the clinical course of the disease to chronic or fibroid phthisis. At the autopsy the tissues about the diseased part are found to be exceedingly dense, beneath which are found abscesses opening into the pleura or into a pulmonary cavity. It would be difficult, says Babes, to distinguish the disease from tuberculosis of the lungs were it not for the presence of the yellow granules. There is often great contraction of the thorax when the disease has existed for some time in that cavity. Intestinal actinomycosis is due to the swallowing of the organism with the food. Colonies are said to form upon the epithelium of the intestinal wall, and there follows infiltration of the deeper layers. The mucous membrane may in this way become covered with white patches, and in such cases small nodules, about the size ACTINOMYCOSIS. 475 of a pea, may be found in the submucous tissues. In the mucous membrane these nodules soften and form ulcers which may eventually perforate into the peritoneal cavity. In a case reported by Bostrom such a complication resulted in the formation of two abscesses — one in each iliac fossa — that broke and discharged exter- nally. At the autopsy it was found that the left abscess had in- volved the ovary. Murphy reports a case of a large abscess in which the spleen was floating, and which probably was caused by actinomyces. Several cases are mentioned in which the pro- cessus vermiformis has been found attached to or opening into an actinomycotic abscess. The fungus may be found, in cases of intestinal actinomycosis, in the evacuations. The symptoms of the intestinal form of the disease are those of acute catarrh fol- lowing a digestive disturbance with diarrhoea in recurring attacks. The complications are those of chronic localized peritonitis. Invasion through the skin occurs occasionally. A number of cases are reported of inoculation through trivial wounds and also after surgical operations. Partsch describes a case of the develop- ment of the disease in the cicatrix which formed after an amputa- tion of the breast. Hochenegg records a case of a girl who slept in a stable with cattle, and who apparently inoculated a suppurat- ing wen of the cheek with the parasite. The same author reports an actinomycotic abscess of the abdominal walls due to the blow of a hammer. Many cases are reported in which the source of the infection could not be detected. A striking example is the primary actinomycosis of the brain reported by Bollinger. The prognosis of the disease when it is situated superficially is not unfavorable. If the mass is promptly removed the danger of return is not great, and a large number of cures have been reported. When internal organs become involved the disease is almost certain to terminate fatally. It is essentially a chronic dis- ease, and the patient may live from one to three years. The treatment of actinomycosis consists in an attempt to remove as completely as possible the entire mass of affected tissue. In the small primary nodules about the neck and the face this removal may satisfactorily be accomplished. If the disease has progressed any dis- tance downward into the neck, a free incision should be made along the line of the sterno-mastoid from the ear to the clavicle, and all the tissues should carefully be dissected out. The operation should be as thorough, if possible, as that for cancer. Decayed teeth should be removed; the bone of the jaw should be cut away or be so laid open as to make it possible to scrape away all evidences of diseased 47 6 SURGICAL PATHOLOGY AND THERAPEUTICS. tissue. When it is impossible to excise the mass and leave a clean wound, all sinuses should be laid open and followed relentlessly to the end, and their walls should be scraped thoroughly with the curette. The exposed surface should then be washed with a solu- tion of corrosive sublimate. Solutions of nitrate of silver, which are supposed to exert a poisonous influence upon the fungus, may be injected into suspected nodules in a strength of 1:1500 or be applied to the granulating surface of a wound. Internal medica- tion appears to exert no influence whatever upon the growth of the parasite. In a case recently operated upon by Mixter, the first reported case in man in Boston, the disease was found to be situated in the neighborhood of the umbilicus. The patient was a chVv laborer, fifty-six years of age. He first noticed, three months before, a lump in the abdominal wall that had grown slightly at the time of the operation. There was on examination an indu- rated mass surrounding the umbilicus about the size of a Mandarin orange. At the operation the peritoneal cavity was opened, and the growth was found adherent to the omentum and intestine. In the interior of the mass removed were found cavities containing a thin whitish fluid. On la}ung open the growth freely, two fish-bones, the size of knitting-needles in thickness, were found. The pus contained opaque white granules which proved to be actino- myces. The patient made a good recover}'. The disease in cattle has much less tendency to cause suppura- tion. In Europe the disease is prevalent in river-valleys and in marshes and on land reclaimed from the sea, and it appears to occur more frequently in the young than in the old and more often in winter than in summer. It appears in the form of tumor-like masses without indications of an inflammatory process, and many of the cases of " osteo-sarcoma " of the jaw in animals reported in former times were undoubtedly cases of actinomycosis. The tongue is often affected in animals, and the infiltration of this organ is accompanied by the subsequent induration often seen in this disease, but which in this case is more marked than else- where. The condition known as "scirrhous tongue" (or H0I2- zunge, wooden tongue) is thus produced. This disease of cattle is not limited to Europe, but it has been found quite extensively in cattle in the United States, particularly in the West. XXI. ANTHRAX. The nomenclature of this disease is somewhat confusing. It is known in England as ' ' splenic fever, ' ' and in Germany as MHz- brand. In France the term "anthrax " is applied to another affec- tion (carbuncle), and " charbon " is substituted. In man the dis- ease is known as "malignant pustule" in all countries. Anthrax prevails in various portions of Europe, particularly Russia, Hun- gary, France, and Saxony. It is known to exist also in Siberia and in India. Anthrax does not prevail in the United States, but isolated examples of it are occasionally seen in man. It appears at times as an extensive and fatal epidemic. Thus, according to Gronin, there perished from this disease in Novgorod, Russia, alone during four years (1867-70) more than 56,000 cattle and 528 men. The greatest losses are incurred during the summer season. The domestic animals most susceptible are cows, sheep, and horses, the ass, the goat, and swine being less often attacked. Mice, rabbits, and guinea-pigs are also particularly susceptible, and consequently are used in laboratory experiments. Anthrax can be communicated only with difficulty to dogs and poultry. The epi- demics in animals occur most frequently in swampy regions where decomposing vegetable material abounds. Saline elements in the soil, combined with warmth and moisture, seem to favor the devel- opment of the virus. The disease consequently is found along the borders of rivers and in malarial districts. The organism which Davaine demonstrated to be the cause of anthrax is known as the "bacillus anthracis. " Owing to its size it was easily seen with comparatively low microscopic powers in the blood, and was therefore the first of the pathogenic bacteria to obtain recognition. A description of the organism is given on page 70. One of the most striking peculiarities of this organism (Fig. 20) is the formation, when in contact with the air, of spores which have remarkable powers of resistance to the external agencies that ordinarily destroy bacteria. These spores do not form in the body of the diseased animal, the bacillus here reproducing itself solely by division. The organisms are released from the body in the 477 47§ SURGICAL PATHOLOGY AND THERAPEUTICS. bloody discharges of the animal. It is probable that the milk of diseased animals does not contain bacilli, but, as contamina- tion is easy by mixture with blood or with dirt, such milk should not be used. After the death of the animal the liberated bacilli elongate and spores are formed. The bacilli are easily destroyed, remaining alive but a few days. Fluids containing bacilli can retain their infective properties only a few days, unless spores are produced. These spores are called "durable spores," owing to their great vitality, and they eventually, under favorable conditions, grow to rods and long threads: this is the complete cycle of their develop- ment. The spores are found in surface soil, or, according to Pas- teur, in deeper soil when the animal is buried, and subsequently they are brought to the surface by earth-worms. Koch, however, does not accept the earth-worm theory. According to him, the spores cannot develop at any great depth, as they need a tempera- ture of over i8° C, and at the depth of ground at which the ani- mals are usually buried the temperature rarely rises above this point. Karlinski examined the carcass of a sheep dead of anthrax that had been dug up by wolves. He found on it a number of snails. Thinking that snails might spread the virus, he made a series of examinations which showed that the snails were insusceptible to the virus, that the bacilli passed through the intestinal canal without diminution of their vitality, and that they re- mained eleven days in a healthy condition in the intestine. Koch has shown that infusions of hay are not favorable for the development of the bacilli, owing to the acidity of the solution. The addition of an alkali so neutralizes this condition that growth takes place. In localities where epidemics suddenly break out there is probably an alkaline soil and a dead vegetation. After a damp season with an overflow of the banks of a river a favorable culture-fluid is formed, and the growth of the bacilli from the spores, which have up to this time been blowing about as dust, begins to take place. When once the spores have developed the disease is with difficulty exterminated from a neighborhood. The organism obtains an entrance into the body in one of three ways — namely, by inoculation through wounds of the skin, by inspiration through the air-passages, and with food through the intestinal mucous membrane. In infected districts the dust of the air is filled with the organisms, and this dust is grimed into the hair and the hide, whence the bacteria can readily be rubbed into any abrasions on the surface of the body. It has been supposed that ANTHRAX. 479 the virus when taken with the food found its way into the system solely through wounds of the mucous membrane. It has, how- ever, been demonstrated that the spores develop readily in the upper portion of the intestine of sheep, but not in the lower portion. The bacilli are destroyed by the gastric juice, while the spores pass unharmed through the stomach. Food con- taining spores was given by Koch to sheep, with the result that all succumbed to the disease, whereas portions of the spleen of a diseased guinea-pig, containing only bacilli, did not affect them. It is probable, therefore, that the organism can penetrate the healthy mucous membrane. Koch also demonstrated the possibility of infection through the respiratory organs. A mouse placed under a bell-glass, where dust containing bacilli had been deposited, succumbed to the disease. Malignant pustule is the name of the disease as it is found in man. It is known also as u wool -sorter's disease," but this desig- nation is said by some authors to be given to that variety which is unaccompanied with an external primary lesion. Infection occurs by direct inoculation into either a scratch, an abrasion, or a small wound of the skin in the great majority of cases. Individuals who come in contact with the diseased animals or with their hides, and operatives who are at work in factories where goods made from the hair or the hides of these animals are manufactured, are most liable to contract the disease. In the neighborhood of Boston the disease has been observed among operatives in curled-hair factories and among the longshore-men who handle the hides imported from infected districts. The hands in this way come in contact with the spores, and inoculation takes place later by scratching the skin. The virus may also be con- veyed by flies. Infection by the consumption of diseased meat is possible, but it rarely happens, as the mucous membrane of man is insusceptible. Contagion from man to man is also very rare. Koranyi men- tions a case of a woman who, while afflicted with the disease, vis- ited her daughter at a place where no case of anthrax had been known for thirty years. After the departure of the mother the daughter developed symptoms of the disease and died. Koranyi had never seen a case of inoculation direct from surface to surface, as in syphilis. The period of incubation lasts from one to three days. The most frequent seat of the primary lesion is the face. The first noticeable symptom is a sensation of itching, which accompanies 480 SURGICAL PATHOLOGY AND THERAPEUTICS. the appearance of a small red spot or papule resembling closely a flea-bite; twelve or fifteen hours later there forms a small vesicle, which is not distended, and which contains a brownish or a bluish fluid. If the vesicle is not scratched, it gradually dries up and forms a scab. The surrounding skin is somewhat reddened, indu- rated, and swollen. This change is the precursor of the gangrene which follows. The affected area enlarges in depth and width, the color darkens, and finally there is formed a black eschar, which, at first superficial, gradually involves the deeper layers of the skin. This black spot varies somewhat in size from 2 mm. to 2 cm. ; on the surface it is hard and dry, and there is no indication of suppu- ration. The slight burning sensation which existed during the formation of the vesicle now disappears, and the lesion is charac- terized by an entire absence of pain. Presently a circle of new vesicles forms around the eschar, giving to it the appearance of the seal of a ring set in pearls (Bourgeois). In some cases it looks not unlike a vaccine vesicle. The vesicles run together, and the fluid within them is more or less discolored by the presence of blood- corpuscles. In the mean time the surrounding skin may become reddened, although it does not always change color. There is con- siderable swelling in the immediate neighborhood, so that there forms a circular tumor distinctly raised above the level of the sur- rounding skin. It becomes later more or less reddened and indu- rated, and the so-called " carbuncular tumor" is thus formed. If the disease continues to progress, the surrounding parts become affected, and an cedematous swelling makes its appearance, which may in some cases be very extensive. In a case of malignant pus- tule of the neck in a robust young man under the writer's care the whole side and front of the neck became so swollen that prepara- tions for tracheotomy were made in case dyspnoea should develop- The tumor, however, subsided and the patient made a good recovery. If the oedema continues, fresh crops of vesicles often appear, and the skin becomes more or less affected and the adjacent lymphatic glands are enlarged. The development of these local symptoms occupies from three to nine days. Finally, a line of demarcation forms around the eschar and the slough separates, leaving a granulating surface, or cicatrization may take place under the scab without any suppuration. According to Raimbert, the striking peculiarities of the malignant pustule are the absence of pus or sanies in the initial lesion, the absence of pain, and the existence of a vesicular areola, not purulent and of limited dimensions. ANTHRAX. 481 In less favorable cases the inflammation of the surrounding tis- sues is more marked and it assumes an erysipelatous appearance. Bullae form which are filled with bloody fluid, and the parts below are ecchymosed. Suppuration and gangrene finally supervene. Malignant pustule is found almost always on exposed surfaces of the body, such as the face, neck, hands, and shoulders. It is very rarely found elsewhere. In rare cases the eschar may be wanting, and an ©edematous swelling is then the only symptom of the local condition. In such cases it has been suggested that an internal infection has taken place. This swelling may sometimes be very extensive. The lips, the eye, the eyelids, the tongue, the chest, and the upper extremities may become involved in this oedema. The swelling is soft and diffuse, and is without change in the color of the skin. It is accompanied by grave constitutional disturbance. For a day or two after the beginning of the disease there may be no marked disturbance of the general health, and the patient may even continue at his work. In some mild forms of pustule there may be no fever. At the end of a few days the patient begins to complain of malaise, nausea, pain in the muscles, and headache,, which symptoms are accompanied with a rise of temperature. In severe cases the heart's action is weak and rapid, and there is an oppressive anxiety, with rapidity of the respiration. There is slight icterus and other symptoms of septicaemia. The prostration is very great, and in the last stages of the disease the condition of the patient is like that of one in the algid stage of cholera. In some cases tetanic convulsions and trismus precede coma. When infection takes place through the intestinal canal, the dis- ease begins with debility, depression of spirits, and malaise, and probably a chill. In addition to these symptoms of constitutional disturbance there are symptoms pointing toward the intestines as the disease develops. Hemorrhages may occur from the mouth and the nose, and vomiting is followed by a bloody diarrhoea. Difficulty of breathing and cyanosis, with great restlessness, are also seen in this form. An eruption of small phlegmonous or car- buncular inflammations often occurs on the skin. The diagnosis in such cases is often extremely difficult, particularly in isolated cases occurring independently of an epidemic. Microscopic exam- ination of the blood or an inoculation of an animal furnishes the only conclusive evidence of the disease. The pathological appearances are well shown in an examination of a section taken from a fresh pustule of three days' duration. 31 482 SURGICAL PATHOLOGY AND THERAPEUTICS. An eschar is seen situated beneath the epidermic crust and the rete mucosum, involving the upper layers of the cutis vera and surround- ed at its lower border by a round-cell infiltration. A few anthrax bacilli are found in the superficial scab and in the rete. In the -eschar the bacilli are very numerous; the papillae are distended and filled with them, but they were not found in the hair- follicles, the sebaceous glands, or the blood-vessels. The periphery of the eschar is occupied by micrococci and other forms of bacteria (Straus). At a later stage of development the eschar involves the whole thickness of the cutis. The bacilli may be found in and near the eschar in some cases for eight or ten days, but not always, for the putrefactive bacteria which are found surround- ing the eschar appear to have destroyed the anthrax bacilli. In two very acute cases reported by Cornil and Babes a post- mortem examination failed to show the bacilli in the neighborhood of the pustule or in the adjacent tissues. There were no bacilli in the blood of the heart nor in the blood of the cutaneous vessels, but sections taken from the different organs gave positive results. The bacilli were found in the fibrous tissues which accompanied the vessels of the lungs and in the subpleural connective tissues. A section of the mucous membrane of the stomach showed the bacilli crowding the mucous follicles, while but few organisms were found in the blood-vessels. Rosenblath reported a case of a boy eight years of age who died of malignant pustule on the seventh day. An examination of the blood and the organs showed the existence of only a moderate number of bacilli, and those apparently not in an active state of development. The number of cocci found in the blood and in the fluid of the peritoneal cavity was very great. In intestinal anthrax an examination of the mucous membrane showed, in a case reported by Cornil and Babes, oedema and ecchy- mosis in the jejunum, as well as ulcers. The mesenteric glands were enlarged. The bacilli were found in the blood-vessels, in the tissue comprising the bases of the ulcers, and in the mesenteric glands. In the Dupuytren Museum there is a specimen of a stomach, taken by Verneuil from an individual who died of anthrax, containing gangrenous patches and inflammation of the intestine. Decomposition of the cadaver begins rapidly. The blood is thick, tarry, and shows no tendency to coagulate. There is a tendency to hemorrhages in the serous and mucous membranes. The spleen is often enlarged and ruptured, but not invariably. The prognosis of anthrax in man varies greatly. In general man ANTHRAX. 483 maybe said to be an insusceptible animal; consequently in most cases seen in young and healthy individuals in America the dis- ease runs a mild course. When the pustule tends to remain local- ized and is uninflamed, the general disturbance of the system is caused by the toxic products of the organism, but when once a general infection of the system takes place the disease in all prob- ability will terminate fatally. Although occasionally some of the mild cases of malignant pustule recover without treatment, it would be unsafe to allow any case to pursue its course without interference. The treatment should be radical, and it should aim to remove the infected area as thoroughly and promptly as possible while it is still localized. One of the most effective methods of effecting this removal is excision. The knife should be carried well outside the areola surrounding the eschar. The wound should then be washed or mopped with a solu- tion of corrosive sublimate (1 : 1000), and an antiseptic dressing, or, better, an antiseptic poultice, should be applied to the wound. The character of the dressing will be determined by the nature of the wound. The best substitute for the knife is the actual cautery, which should be applied deeply around and beneath the edges of the eschar. Small pustules may be treated by the application of liquefied crystals of carbolic acid. A small incision would favor the deep application of the acid. Larger pustules may be incised freely, and be dusted with powdered corrosive sublimate, which favors the destruction of the entire mass (Whittaker). Cutaneous injections of carbolic acid (from 5 to 10 per cent, solution) around the edges of the eschar may arrest the progress of the disease, but this form of treatment is less thorough than those already mentioned. The employment of toxines may eventually be made successfully in the treatment of this disease. Ogata's experiments are suggestive in this connection. This author states that he succeeded in eliminating immunizing substances from the blood of animals insusceptible to anthrax. This substance he describes as a ferment which, when injected into animals, acts as a curative and a protective agent. The bacillus pyocyaneus has been found to exert an inhibitory influence upon the development of the anthrax poison, and it is possible that this organism may in consequence eventually be employed as a therapeutic agent. Inter- nal medication is probably useless when once general infection is established, but a liberal and judicious use of alcoholic stimulation may enable the system to battle successfully against the generaliza- tion of the disease. 484 SURGICAL PATHOLOGY AND THERAPEUTICS. Anthrax in Animals. — The disease may develop in animals either with or without local manifestations. The latter form occurs more frequently in sheep and cows. It comes on some- times with great violence, and it is then known as the "apoplec- tic" form. A healthy and robust animal may be taken suddenly with convulsions, foaming at the mouth and nose, and may die in a few minutes, or it may rally for a time and the attack again begin. The breathing is increased in rapidity and is irregular, and the heart's action becomes weak and rapid. Symptoms of anaemia of the brain show themselves. There is dilatation of the pupils, trem- bling, convulsions, foaming at the mouth and nose, and bloody evacuations of bowels, and in a few hours the animal is dead (Koranyi). The disease may, however, last longer, in which case there is a chill with high fever, swelling of the eyelids and the nasal mucous membrane, and attacks of colic. This is the true splenic fever. Anthrax may develop in animals with a carbuncular swelling or swellings, which are often seen in horses. They appear as cir- cumscribed swellings (hot and tender), which, as they grow, become softer, cooler, and less sensitive. If they are deeply situated, the skin is not discolored and there is a good deal of surrounding oede- ma. In the skin the carbuncle is reddened or dark-colored. Occa- sionally the local swelling assumes an erysipelatous character, and emphysematous gangrene eventually develops. The carbuncular swellings are seen on the head, the neck, the belly, and the extrem- ities. A. post-mortem examination shows the blood to be thick, tar- like, and incoagulable. The vessels of the subcutaneous tissue, the mucous membranes, the alimentary canal, and the mesenteric glands are distended with blood, and there are numerous blood- extravasations which seem to break up the muscular tissues and the parenchyma of organs. The spleen is enormously enlarged. Its parenchyma is softened to a semifluid mass of a violet or almost black color. The capsule at times is ruptured, and the contents escape into the peritoneal cavity. The mortality of this disease in animals is placed at 70 per cent., and by some authors as high as 75 to 80 per cent. The thorough study that has been given to the organism which is the cause of this disease should leave the sanitary authorities no excuse for not adopting the most scientific means of disinfection for infected districts, for on no other basis can there be any hope of stamping out the disease when it has once established itself. XXII. GLANDERS. Glanders is an infectious disease, characterized by the forma- tion of nodules and ulcers in the mucous membranes, principally of the nares, and in the skin. It is found in the horse and other domestic animals and in man, and it is caused by a specific patho- genic organism. The term farcy (farcio, to stuff) is applied to that variety which involves the lymphatics and is seen principally in the skin. Equinia is a name which has been employed also to a limited extent to designate this disease. Its Latin name is mal- leus} The French call it morve, and the Germans Rots and Wur)n. Glanders is found not only in the horse, but also in asses and mules, sheep, goats, and rabbits; mice and guinea-pigs are sus- ceptible to the disease when inoculated, but mice are not suit- able for inoculation-tests, as they are apt to die of septicaemia. Dogs are but slightly susceptible. Glanders appears to occur among horses in all climates and in all countries. According to Virchow, this disease should be classed with tu- bercle and syphilis under the general head of granulomata: in many respects it resembles these diseases closely, and has often been mis- taken for them. The granulation-like tumors which are so cha- racteristic are caused by the presence in the tissues of the bacillus mallei. This organism was first described in 1882 by Lofner and Schiitz, but the organism was also discovered simultaneously by Babes and Israel. A description of this bacillus will be found on page 62 (Fig. 18). Though always due to the same organism, glanders manifests itself in many ways in different individuals, so that in an epidemic in one stable dissimilar types of the disease are seen in different cases. There may be infection of the lymphatic glands or of the nasal mucous membrane, or an inflammation of the lung or metastatic abscesses, with general febrile disturbance. The attempt formerly made to separate the disease into several 1 A name given by the ancient Latin writers on veterinary medicine to various diseases of the horse. The original meaning is ha??i??ier : the connection is obscure — perhaps from the painful and fatal character of such diseases, or from malleus, meaning the mallet of the butcher at a sacrifice; also (in the diminutive form malleolus) a fire-dart. The alleged Greek word jua/.ig or fiakia is probably a corruption of the Latin. 485 486 SURGICAL PATHOLOGY AND THERAPEUTICS. varieties should therefore be abandoned. Experiments show that the bacilli gain an entrance into the body through slight wounds, and that inoculation takes place through scratches and abrasions of the mucous membrane of the mouth and the digestive tract. Frankel adopts the view that horses acquire glanders by inhala- tion, but the nasal symptoms which are so prominent a feature of the disease are attributed by Baumgarten to the general systemic infection which has previously taken place. The disease can be transmitted from mother to foetus in utero. Babes and Nocard succeeded in obtaining an infection of guinea-pigs through the intact skin, but it is probable that the dis- ease, clinically, is not propagated in this way. It is more probable that infection takes place through the intact mucous membrane, and it appears that infection probably does take place in the horse frequently through the air-passages hy the inhalation of the dried organisms in the form of dust. In this way glanders may be communicated from one animal to another. It is said that glan- ders has been transmitted to menagerie animals by feeding them with the flesh of diseased horses. Decroix, however, disproved this theory by eating with impunity the meat of a glandered horse, both cooked and raw. In man the usual mode of infection is through some slight wound of the hands that is inoculated while grooming or feeding diseased horses or while handling the carcasses of dead animals. The disease may also be acquired by contact of the virus with the mucous membrane of the eye, the nose, or the mouth. This may happen by the animal snorting, by which small particles of pus or of mucus are blown into the face of an individual in attendance. In making experimental inoculations with the secretion, placed in contact with the mucous membranes of animals, it has been found that considerable quantities of the material are necessary to ensure infection. This fact is accounted for by the small number of bacilli found in these secretions, they being easily destroyed by other bacteria. It is therefore often difficult to recognize the dis- ease by a microscopical examination of the discharges from mem- branes or from abscesses. The disease may also be transmitted from man to animals, and in very rare instances from man to man. Cases are reported where an entire family, one after another, has been attacked. It said to have been communicated by eating from the same dish with a dis- eased individual or by drinking from a pail which had been used by a diseased horse. GLANDERS. 487 Berard reports the inoculation of a medical student from a patient in the hospital, and more than one experimenter has fallen a victim to the disease during scientific inoculation-expe- riments. Man, in fact, appears to be highly susceptible to the disease. Glanders in Man. — In 90 per cent, of the cases the disease is observed in individuals who come in contact with horses — coach- men, horse-dealers, soldiers, farmers, veterinary surgeons, students, and blacksmiths. According to Bollinger, only 6 out of 120 cases occurred in women, and these for the most part were employed in stables or belonged to the families of individuals thus employed. The period of incubation lasts from three to eight days (Koranyi). There has been a great variety of classifications, which, now that the etiology of the disease is understood, it is better to discard. The types of the disease, therefore, will simply be divided into acute and chronic. At the end of the incubation period an inflammation appears at the point of inoculation, which inflammation frequently becomes severe and assumes an erysipelatous character, and an unhealthy ulcer forms. The adjacent lymphatic glands are swollen, and running toward them there are frequently red lines, indicating accompanying lymphangitis. Around the point of inoculation there appear often minute vesicles, which enlarge and become hem- orrhagic, and which later suppurate or are accompanied by gan- grene of the parts beneath. If the wound has already healed, it may reopen and ulcerate. This ulceration may eventually heal after a long time, or it may be followed by constitutional symptoms, leading to a fatal result without other local manifestations. Con- stitutional disturbance is, however, not always present, but there are often malaise, headache, and prostration, and more rarely a chill; but when the local inflammatory symptoms develop there is a cor- responding amount of fever, which gradually subsides as the local symptoms improve and the patient recovers. In the greater number of cases, however, the disease progresses farther. In the severe cases there are prodromal symptoms fol- lowed by an outbreak of fever. Nose-bleed is often an accompani- ment of the fever; also severe pain in the muscles and joints, par- ticularly in the lower extremities, but they may exist also in the neck and the chest; usually no swellings are seen at the painful spots, but at times there arise (Edematous tumors, nodules, and boils, which may, however, disappear with great rapidity. Some of these swellings may suppurate and form abscesses. 488 SURGICAL PATHOLOGY AND THERAPEUTICS. After the fever has lasted from six to twelve days an eruption makes its appearance. Small papules, isolated or in clusters, form on the face, the trunk, and the extremities, and they gradually develop into pustules with an inflamed base. These pustules dry up or ulcerate while others are forming, and frequently bullae appear with hemorrhagic or gangrenous contents. The face now begins to swell, either on account of the presence of pustules or from the condition of the nose. A dark bluish-red tumor forms, which is firm in consistency and which is covered with vesicles, presenting an appearance somewhat like that of the anthrax car- buncle, The eyelids are swollen and a thin muco-purulent dis- charge flows from the conjunctiva. At first there is dryness in the nasal mucous membrane, and almost always there is hemorrhage. Later there is a feeling of ten- sion about the root of the nose and the mucous membrane swells. The discharge at first is scanty, and is followed by a thin, tenacious bloody mucus, which later becomes a dirty yellow, and which is extremely foul in odor. Pustules and ulcers may be seen upon the mucous membrane, and perforation of the septum may occur. The discharge flows back into the throat, whence it may be expec- torated. Inflammatory changes also occur in the mouth, the pharynx, and the palate. The mucous membrane ulcerates, and the gums easily bleed. The breath of the patient becomes offensive; swallowing is difficult. In some cases the inflammation extends to the lungs and symptoms of bronchial catarrh occur. The expectoration strongly resembles that secreted from the nostrils. There may be pleuritic pains with difficulty of respiration, and occasionally oedema of the glottis supervenes. There is often gastric disturb- ance with symptoms of intestinal catarrh, and diarrhoea often oc- curs. In the mean time the development of pustules, boils, and abscesses continues, and suppuration may extend as deep as the muscles or even to the bones. These different symptoms do not appear in any regular order. During the progress of the disease the patient becomes greatly weakened and the fever assumes a typical character. The pulse is rapid, but it becomes weaker as the disease progresses. Toward the end the skin is cold and clammy, the ulcers are much enlarged, and they discharge foul secretions. The evacuations are involun- tary, and death may be preceded by coma or by tetanic convul- sions. The course of chronic glanders varies greatly: it may last GLANDERS. 489 months or even years, and many of the usual symptoms may be wanting. The same local changes in cases of inoculation may develop as those in acute glanders. In case no obvious primary lesion is visible, there may only be vague and ill-defined symptoms of debility, combined with recurring febrile attacks and pains in the limbs and joints. Presently a cough appears; there is tender- ness about the root of the nose, with muco-purulent discharge mixed with blood; and the patient may finally waste away with symptoms of hectic fever. In many cases of chronic catarrh there may be considerable destruction of the septum and of other bones of the nasal passages. When the cutaneous affections are a feature of the case there is less of the nasal catarrh. There are, however, numerous boils and abscesses, accompanied more or less with lymphangitis. The abscesses may break and discharge thick pus, and finally may heal or may remain as sinuses, discharging a thin, foul secretion. The favorite seats of abscesses are in the flexures of limbs, particularly of the lower extremities, and in the neighborhood of joints. The abscesses often become ulcers with everted borders. In addition to these abscesses there are often circumscribed or diffused swellings which are accompanied with considerable pain, but without much change in the skin, and which after a time disappear. The chronic form of glanders may continue indefinitely, appear to improve greatly, and then perhaps become acute, or the chronic symptoms reappear and the patient gradually succumbs to the disease. Pathological Anatomy. — The characteristic features of this dis- ease in man as well as in animals are the glanders nodules, or the so-called ' ' farcy buds, ' ' which are found everywhere on the skin. Lesions are found also in the nose, in the subcutaneous and sub- mucous tissue, in glands, in muscles, in the periosteum, and in bones. In the skin the pustules are a characteristic feature. They are found to be due to a breaking-down of the corium and to the for- mation there of a cup-shaped depression filled with broken-down material. Appearing first like a flea-bite, the skin is raised in a papular elevation, on the apex of which the pustule develops; later the pustules are discolored by extravasations of blood, and, when the scales fall off, they may form ulcers. These ulcers evi- dently result from the breaking down of minute glanders nodules in the true skin. The nodules are seen also in the mucous mem- brane of the nose, and the changes here are so characteristic as to establish the diagnosis in doubtful cases. There is also catarrhal 490 SURGICAL PATHOLOGY AND THERAPEUTICS. inflammation and ulceration, which condition may extend into the antrum and sphenoidal sinuses. In the later stages there is often extensive destruction of the bones, and the cranial cavity may be invaded, pus being formed beneath the dura mater. Miliary nodules and little abscesses are found in the gums, the pharynx, the larynx, the trachea, and the bronchi, and there are found in the lungs numerous small areas of consolidation, some of which have suppurated. The muscles also are frequently the seat of nodules. These nodules are found in the biceps, in the flexors of the forearm, in the rectus abdominis, in the pectoralis, and, finally, at the point of insertion of the deltoid. A species of capsule is formed by the inflamed perimysium, which capsule encloses nodules the size of a pea. Abscesses develop here also, and they may find their way to the surface through the skin or they may burrow down and cause necrosis of the bone. The synovial membrane is often studded with miliary nodules, and the cavity is filled with an exudation. The lymphatic glands are less affected in man than in horses. There is also a fatty degeneration of the liver, a swelling and possibly infarction of the spleen, minute abscess of the kidney, and sometimes of the parotid gland. The testicle may become inflamed, and nodules with abscesses or fistulae may eventually develop. The diagnosis of glanders is often difficult, owing to the varieties of the disease and, in many cases, to the absence of an external point of entrance. When the constitutional disturbance has been profound the disease might at first be mistaken for typhoid fever. The presence of the multiple abscesses, both exter- nal and internal, makes up a picture which bears a striking resem- blance to pyaemia. In both cases the presence of nasal symptoms, together with a consideration of the patient's occupation, would aid in the recognition of the disease. Some of the chronic types with implication of the lungs might readily be mistaken for tuber- culosis, and the appearance at the autopsy even might in some cases be misleading. In the chronic form of nasal glanders the ozcena bears a close resemblance to the later stage of syphilis, and in some cases only by a course of scientific treatment might it be possible to make a differential diagnosis. The disease, however, can definitely be recognized by the demonstration of the bacillus and its culture, which on potato is most characteristic. As it is often difficult to obtain bacilli in the secretions, recourse must be had to inoculation of guinea-pigs in a manner presently to be described. GLANDERS. 491 The prognosis of acute glanders is extremely unfavorable, the disease usually terminating fatally in from one to three weeks. In the chronic form, according to Bollinger, recovery takes place in about 50 per cent, of the cases. According to Koranyi, the chronic variety, formerly known as "farcy" — that is, the nodular form — runs a more favorable course than the nasal form of chronic glanders. The period of incubation of the disease in animals lasts from three to five days. The nasal form of glanders is more frequent in horses than in man. In the chronic form the catarrh of the nasal mucous membrane is usually one of the first symptoms, and an eruption of nodules in the membrane occurs at the same time. The disease may at first be confined to one side. An inspection of the nares will show the presence of nodules and ulcers. The sub- maxillary glands of one or both sides are enlarged. When the ulcers form, the discharge becomes purulent, and the disease grad- ually spreads from the nose through the air-passages to the lungs. Later, nodules or farcy-buds may appear beneath the skin. The animals gradually waste away, and they may ultimately die a year after the appearance of the first symptoms. Acute glanders may occur primarily or it may come on at any time in the course of a chronic case. The disease begins with some febrile disturbance and with violent inflammation of the nasal mucous membrane. In a few days glanders nodules make their appearance in the nose, the throat, and the lungs. At the same time there is general engorgement of the lymphatic glands and lymphangitis. Nodules and cords are felt beneath the skin, which in places is cedematous. Swellings may subside suddenly and others appear at different points (flying farcy). These external symptoms show themselves at first about the head and the neck, and later they spread to other portions of the body. The animals begin to cough and to grow thin, and after an illness of from eight to fourteen days death occurs. The prognosis of the disease in animals is most unfavorable. In a case of doubtful disease, whether in man or in animals, a bacteriological examination will settle the question of diagnosis. A small amount of pus from an ulcer or of the nasal secretion is spread over a cover-glass and stained by the ordinary method. When bacilli cannot be demonstrated in this way in the secre- tions, experimental inoculation may be made in animals for this purpose. Straus recommends an inoculation of the secretions to be 492 SURGICAL PATHOLOGY AND THERAPEUTICS. examined into the peritoneal cavity of guinea-pigs, or to obtain cultures from these secretions and then to inoculate the animals with these cultures. An inflammation of the testicles shows itself in the animal two or three days after the inoculation. The skin of the scrotum becomes tense, reddened, and shiny, and there is desquamation of the epidermis. An abscess event- ually forms. These animals die in from twelve to fifteen days. The same symptoms occur after subcutaneous inoculation, but somewhat later. Kalming prepared a mixture of a pure culture of the bacilli in water, and subjected it to a temperature of 120 C. ; it was then filtered and injected into horses which were suspected of having glanders, and also into healthy horses. In the diseased animals it invariably produced a rise of temperature. Preusse and Pearson and others repeated these experiments with the same results. It may be concluded, therefore, that this substance (inalleiii) possesses a diagnostic value. The treatment of glanders, in man consists principally in the treatment of symptoms as they arise. If a wound is suspected of being infected with the virus, it should be allowed to bleed freely, and it should then be disinfected with a strong solution of corrosive sublimate or of carbolic acid, and be cauterized with the actual cau- tery. The external abscesses should be treated on antiseptic prin- ciples as far as possible. They should be laid open and thoroughly disinfected, and an attempt should be made in this way to arrest the progress of the disease. If the initial lesion is taken in time, such attempts may prove successful. Bayard Holmes recommends thorough curretting, followed by swabbing the cavity with a saturated solution of sulphate of zinc. The cavity is then packed with iodoform gauze wet in a saturated solution of iodide of potassium. Excision of small nodules is recommended by him. In a case reported by Holmes a patient during two years and a half was anaesthetized twenty times, and new foci were opened or old ones scraped out. A permanent cure was finally effected. The strength of the patient should be main- tained by judicious stimulation. The nasal ulceration may be treated by mild antiseptic washes and douches, and the condi- tion in the mouth be treated by appropriate gargles. In acute cases there is little prospect of doing anything more than to relieve the sufferings of the patient. The only approach to an attempt at a specific treatment of this disease is the employment of the so-called "mallein." It is pre- GLANDERS. 493 pared somewhat after the manner of Koch's tuberculin. Bonome prepares mallein as follows: A culture may be made from the blood or from the fresh viscera of animals who have undergone experi- mental inoculation with the virus, or from glanders nodules. The active principle of the glanders bacilli is precipitated by treatment with large quantities of alcohol. The fluid is afterward evaporated in a vacuum of 35 ° C. This first precipitate is dissolved in water, and is sterilized for three minutes at a temperature of ioo° C, and is again precipitated and subjected to evaporation. In this way Bonome obtained, after the addition of sterilized water, a yellow- ish-gray, sometimes whitish, odorless, neutral fluid, which was preserved in a sterilized vessel with a 2 per cent, solution of car- bolic acid. Healthy guinea-pigs were not affected by the drug, but guinea- pigs which had been inoculated with the glanders virus were made worse by large doses of mallein (10-15 m &-)> but were cured by re- peated small doses (0.5 to 1.00 mg.). They thus gradually acquired immunity to larger doses. Rabbits wasted away and died from the effects of the mallein, their glanders being made worse. It was concluded, therefore, that mallein had a therapeutic value for guinea-pigs, but only a diagnostic value for rabbits. Mallein had only a diagnostic value for horses, producing fever in those that were affected with glanders. In guinea-pigs mallein appeared to act very much as tuberculin acts. These animals, when healthy, reacted to large doses of both drugs in the same way. In the case of glanders guinea-pigs react to small doses of mallein in the same way that tuberculous guinea-pigs react to small doses of tuber- culin, minimal doses of these two drugs having a therapeutic value for these animals. Bonome experimented also with cadaverin, thymus extract, and neurin. When these substances were mixed with cultures of the bacillus mallei they appeared to restrict its development, but the experiments made on animals do not appear to have been suf- ficiently complete. Fortunately, epidemics of the disease do not flourish to any great extent in America. In Boston there have been six deaths from glanders in man during the years 1885 to 1891, inclusive. During 1891 there were but twelve cases of glanders in animals reported to the Board of Health. The animals were promptly killed, and the premises on which they had been stabled were thoroughly disinfected by the authorities. In the State of Mas- sachusetts the regulations for the control of contagious diseases 494 SURGICAL PATHOLOGY AND THERAPEUTICS. in cattle are made by the Board of Cattle Commissioners, and failure to comply with the law is punishable by fine or by im- prisonment. Epidemics of glanders were in 1887 reported to Washington, D. C, from the States of Georgia, Virginia, Texas, Pennsylvania, Louisiana, and the District of Columbia; also from Oowala, Chero- kee Nation. The Minnesota State Board of Health reports that from March, 1885, to April, 1886, it had isolated over 450 horses affected, or suspected of having been affected, by glanders. XXIII. SNAKE-BITE. Among the great variety of bacterial poisons which have thus far been studied there is hardly one which can compare in viru- lence with the venom of poisonous snakes. It may be regarded as the acme of the type of animal poison, which in the rapidity and the disastrous effects of its action is without a rival. Deaths from snake-bite are not very common in the United States, although rattlesnakes are still very numerous in certain portions of the country. In India, however, the mortality is frightful, which is due partly to the enormous number of ser- pents and partly to the careless habits of the natives and to the exposure of the person from scanty clothing. A series of careful returns compiled by Fayrer shows that in 1869 the number of deaths from snake-bite in the Bengal Presi- dency was 11,416. He estimates that deaths in India from this source alone amount annually to 20,000. In 188 1 the number of snakes killed for the bounty offered by the British government amounted to 254,968. According to Yarrow, there are in America no less than twenty- seven species of poisonous serpents belonging to four genera. The first genus is the Crotalus, or rattlesnake; the second is the Caudi- sona, or ground rattlesnake; the third is the Ancistrodon, or moc- casin, one of the species of which is a water-snake; and the fourth is the Elaps, or harlequin snake. There is also a poisonous lizard known as the Heloderma suspectum, or Gila monster. In India, of the twenty-one families of snakes known to nat- uralists, four are poisonous ; these are the Elapidcs, the Hydroph- idcz, the Viperidce, and the Crotalidcs, and they are known by the appropriate name of Thanatophidia. Among the Elapidse, of which there are five species, is the Naja tripudians, or cobra. It is a most deadly snake, and it is found in many parts of India. It grows to the length of 5^ feet or even more. It is most active at night, but it is often seen moving about during the day. It is, like the Ophiophagus, a. hooded snake. The Ophiophagus, another species of this family, is probably the largest known venomous snake, growing to the length of from 12 to 14 495 496 SURGICAL PATHOLOGY AND THERAPEUTICS. feet. It is not only very powerful, but is also very active and aggressive. The Hydrophidse, as their name implies, inhabit the salt-water estuaries and tidal streams. They are all venomous, and are very poisonous. The Viperidae, which are terrestrial snakes, are more poisonous than the Crotalidae. The latter genus has not, as has its American namesake, a rattle, and it is less poisonous ; it is also a smaller snake, measuring about 3 feet in length, the American snake reaching at. times the length of 5 or 6 feet. The heads of these serpents are so constructed as to admit of a large amount of movement in the component bones. The superior maxillary bones are united by ligaments only to the intermaxilla- ries, and the lower maxillary bones are so arranged as to be sepa- rable from one another anteriorly and to permit motion of one side only if desired. The mobility of the superior maxilla is essential to the movements of the fang, which is firmly attached to it. This fang, in the rattlesnake, is sometimes quite large, measuring three- quarters of an inch in length. In the cobra it is decidedly smaller. In the rattlesnake the fang is somewhat conical and scythe-shaped and has a sharp point. It has a deep groove, due to the folding of its edge, which gives it the appearance of being hollow. The fang communicates with the duct of the poison-gland, which is situated behind the eye and beneath the anterior temporal muscle. The walls of the duct are supplied with an unstriped muscular fibre forming a sphincter muscle, which enables the serpent to control the discharge of the fluid. The duct-opening lies at the base of the tooth, where it communicates with the fissure in the fang. In the pulp-sac in the jaw lie the nerve-fangs, and when the fang is lost by a natural process it is replaced within a few days ; but when violently removed the new fang does not appear for several weeks. When in repose the fang is folded back and covered by a fold of mucous membrane which retracts when the fang is erected. The amount of venom contained in the gland varies greatly: when perfectly fresh and healthy the snake throws out at first from ten to fifteen drops. But if the snake has recently excreted the fluid, only three or four drops can be obtained from the glands. The color of the venom of the rattlesnake varies from pale emer- ald-green to orange- or straw-color, and it is more or less glutinous in consistency. In the Indian snake it is a clear viscid fluid, solu- ble in water and slightly acid in reaction. It is equally virulent whether dry or preserved in alcohol or in glycerin. The active - SNAKE-BITE, 497 principles of the virus have been found by Mitchell and Reichert to consist of two proteids, a globulin, and a peptone. Prolonged boiling seems to convert the peptone into a coagulable albuminoid which is not destructive to life. It is generally supposed that rattlesnake poison, if swallowed, is harmless, but, according to Fayrer, the poison of the cobra can be absorbed through the mucous membrane, though with much less dangerous effect than when it is introduced into the blood: Mitchell and Reichert state if enough of the poison is taken into the empty stomach death may ensue. According to Mitchell, the venom exerts a powerful local effect upon the living tissues, and induces more rapid changes than any known organic substance. It renders the blood incoagulable, and it so acts upon the capillary blood-vessels that their walls are unable to resist blood-pressure, thus allowing the corpuscles to escape into the tissues. The swelling produced is not due to inflammation, but is due to hemorrhage. The bodies of the red blood-corpuscles lose their shape and fuse together into irregular masses, acting like soft elastic colloid material. Death occurs, according to Mitchell, through paralysis of the respiratory centre, paralysis of the heart, hemorrhages into the medulla, and possibly from the inability of the red corpuscles to perform their functions. Cobra-poison does not produce the marked lesion of the crotalus-poison, because it is lacking in globulin. Fayrer states that the poison acts through the circulation upon the nerve-centres, paralyzing them and thus destroying the vital force. The experiments made by him and Brunton also show impairment of the respiratory centre. According to Feoktistow, whose experiments were performed at Dorpat, the poison acts solely on the nerve-centres, and it has no effect whatever upon the blood. According to Wall, the symptoms of cobra-poisoning are due to a slowly-advancing general paralysis, death being caused by convulsions due to asphyxia, the poison acting upon the respiration. The effect of the cobra-poison on the blood, he thinks, is not great. It will thus be seen that European observers dwell more upon the action of the virus upon the nervous system and less upon the blood. The mechanism by which the act of striking is accomplished, and by which the virus is thrown into the system, is thus described by Yarrow: " The snake prepares for action by throwing itself into a number of superimposed coils, upon the mass of which the neck and a few inches more lie loosely curved, the head elevated, and the tail projecting and rapidly vibrating. At the approach of the 32 49 8 SURGICAL PATHOLOGY AND THERAPEUTICS. intended victim the serpent by sudden contraction of the muscles upon the convexity of the curves straightens out the anterior por- tion of the body and then darts forward the head. At this instant the jaws are widely separated, and the back of the head fixed firmly upon the neck. With the opening of the mouth the spheno- palatines contract, and the fangs spring into position, throwing off the sheath as they leap forward. With the delivery of the blow and penetration of the fangs the lower jaw closes forcibly, the muscles that execute this movement causing simultaneously a gush of venom through the tubular tooth into the wound." As the ser- pent withdraws his head the fangs are forced more deeply into the tissues, and the jaws are finally loosened from their hold by a shak- ing movement of the head, which liberates the teeth. The wound is inflicted by the rattlesnake, in almost every case, upon an ex- tremity. In India, according to the reported cases, the patient is often struck upon the shoulder or the neck. The symptoms vary greatly according to the severity of the wound inflicted. Many cases recover simply because a complete inoculation has not taken place, but when the act has thoroughly been accomplished in the way above described, and the hypodermic injection of a full dose of virus has occurred, the sequence of events follow in a characteristic and almost inevitable course. The pain in the wound varies greatly. Sometimes it is hardly observed; at other times it is described as a sharp, stinging pain. In most cases the wound is more or less painful. The puncture is sometimes so small as to be hardly perceptible. The succeeding local symptoms are swelling, discoloration, and increasing pain. This swelling is regarded by [Mitchell as not due to inflammation, as described by several writers, but to the effusion of blood. If the progress of the poison has not been arrested by a ligature after a period varying from minutes to hours, the swelling and discoloration extend up the limb, accompanied by severe pain. Vesicles soon form, and the disorganization of the tissues is so rapid that the part becomes gangrenous if the patient survives long enough. The direful effect of serpent-poisoning upon the tissues is graphically de- scribed by Lucan [Pharsalia, book ix.), who records the somewhat exaggerated stories of Cato's soldiers in their march through the Libyan desert. (This passage is also interesting as being probably the first occasion in which the peritoneum is mentioned in poetry.) Wretched Sabellus by a seps was stung ; Fixed to his leg: with deadlv death it hunsr : SNAKE-BITE. 499 Of all the dire destructive serpent race, None have so much of death, though none are less. ****** The spreading poisons all the parts confound, And the whole body sinks within the wound. The brawny thighs no more their muscles boast, But, melting, all in liquid filth are lost ; The well-knit groin above, the ham below, Mixed in one putrid stream together flow ; The firm peritoneum, rent in twain, No more the pressing entrails could sustain ; It yields, and forth they fall ; at once they gush amain. The necessity for prompt action was recognized, as is shown by the experience of Murrus: Along the spear the sliding venom ran, And sudden from the weapon seized the man : His hand first touched, ere it his arm invade, Soon he divides it with his shining blade : The serpent's force, by sad example taught, With his lost hand his ransomed life he bought. (Rowe's translation.) The constitutional symptoms of crotalus-poisoning do not appear immediately, but after an interval of a few minutes or of hours there is prostration of the most severe character. In the case of cobra-poisoning a considerable interval of time — one or two hours — has been reported before the advent of constitutional dis- turbance. There is sometimes reported a feeling of intoxication or of elation, but this is rare. Some of the early symptoms are probably due to fear. The patient, after walking some distance, feels his limbs give way beneath him, and he staggers and falls. The skin is bathed in a cold, clammy sweat; the expression is anxious; the pulse becomes rapid and feeble. The breathing is usually hurried and is more or less labored. In some cases it is diaphragmatic. The patient sometimes complains of a pain in the chest and a sense of suffocation. Foaming at the mouth is occa- sionally observed. Ewart speaks of the breathing becoming slower and slower as death approaches, but this is probably in the last stages of coma. If the patient lives long enough, the local swell- ing and discoloration of the arm continue to increase, and they may spread on to the chest and back. The pathological changes found upon man after death seem chiefly in the brain and its membranes. In Fayrer's cases conges- tion of vessels on the surface of the brain is reported, and there is occasional softening of the cerebral substance. The latter may, 500 SURGICAL PATHOLOGY AND THERAPEUTICS. however, have been due to a post-mortem change, which would occur rapidly in the Indian climate. Fluid was often found in the lateral ventricle. The pia mater is reported as engorged in several cases. In Horner's case, reported by Mitchell, the brain was found to be of a healthy consistence, but so congested that the cortical substance was of a deep brown tint. A drachm of transparent serum was found in each lateral ventricle. The veins of the pia and the vertebral veins were full of blood. In two other cases recorded by Mitchell the same conditions of the brain were found. In some of Fayrer's cases the lungs were reported as congested, and dark sanious fluid was occasionally seen flowing from the mouth, but in many the lungs appear to have been quite normal. In one of the cases quoted by Mitchell the walls of the trachea and the bronchial tubes were congested and the trachea and bronchi were full of a frothy mucus. As regards the stomach and intestines, congestions of the mu- cous membrane were occasionally reported, but more frequently they were found to be normal. No pathological changes appear to have been found in the great majority of the cases in the liver, the kidneys, or the spleen. The blood in almost all cases is found to be fluid and non-coagulable. The changes in and about the wound vary greatly from infiltra- tion by a dirty-brown serum or extravasations of blood to extensive disorganization. Fayrer reports in one case that when the left, hand was cut into, the muscles were found disintegrated and of a dark color, and in the upper arm the muscles were found to be soft and infiltrated with serous effusion. In Sir E. Homes' s case, reported by Mitchell, a large abscess existed in the arm and fore- arm, and the cellular tissue between the muscles had sloughed extensively. After experimental inoculation in animals Mitchell found the tis- sues around the point of injection soaked with extravasated blood, and if death had been postponed for some length of time, the tis- sues at some distance from the point of injection were also affected in this way to a certain extent, but not so extensively. Pro- nounced and frequent ecchymoses were found beneath the serous membranes, and there was general congestion of the blood-vessels throughout the body. The blood coagulated imperfectly, and then only after being exposed to the air, " resembling in this particular the state of that fluid observed in conditions of asphyxia." In no form of disease or injury, except hemorrhage from the great vessels, is promptness of action so important. The first thing SNAKE-BITE. 501 to be done is the application of a ligature. Every minute, even every second, is of value, because in many reported cases life seems to have been saved chiefly by the prompt application of the ligature. It must be applied tightly. The clothing, a piece of twine, any- thing at hand, should be used for this purpose, and a second liga- ture, broader than the first, may be applied higher up on the limb. A stick may be inserted into the top of the ligature to twist it, so that an improvised tourniquet may be formed. The bites should then be laid open and an effort be made by cupping or by suction to withdraw the venom from the tissues. A more effective way of accomplishing the removal of the virus before it has had time to spread is an excision of the part in which the venomous fluid lies. A portion at least of the poison is thus certainly removed and the dose correspondingly diminished. It is recommended to wash the wound with a 1 per cent, solution of permanganate of potash or of aqua ammonia. The use of the actual cautery is probably more efficient, as it is only by intense heat that the virus seems to be destroyed, experiments having showm that the permanganate and the ammonia are not to be depended upon to affect its viru- lence. It is the custom of Indians and hunters to flash powder on the wound for this purpose. An ember of hot coal would be more efficient still. If the bite is not on an extremity, the injured skin should be cut out ruthlessly by any one present. The danger of bleeding would probably be slight in any case. Care should be taken not to expose the open mouth of a vein or a serous sac to the venom. The use of stimulants still holds its popularity, and the wmiskey cure is to-day probably the one most resorted to in the United States. As prostration is one of the most prominent symptoms, the use of alcohol is undoubtedly indicated to strengthen the flagging heart. It should, however, be given in moderation at first, particularly in the young, as it is not improbable that some patients have actually succumbed to the heroic nature of the treatment. As the ligature cannot be allowed to remain permanently for fear of gangrene, it must be released momentarily from time to time. It is at this period that the alcoholic stimulant will be of advantage to sustain the strength of the patient, as fresh doses of the venom are thus unavoidably allowed to work into the system. A careful watch upon the pulse will be the guide for treatment. A great variety of drugs have been recommended from time to 502 SURGICAL PATHOLOGY AND THERAPEUTICS. time, and have eventually proved to be worthless. Lacerda of Rio Janeiro found that an injection of a i per cent, solution of permanganate of potash into the wound of an animal that had been inoculated was an absolute antidote. The remedy has been tried with varying success. The use of aqua ammonia has also had its advocates, and this drug was at one time supposed to be a specific in its action upon the venom. As a cardiac stimulant it has undoubtedly done good work, but no more decided benefit can now be claimed for it. The gall of serpents, " snake-stones" (a fragment of bone washed in blood, dried, and polished), and a great variety of other local remedies are mentioned in the litera- ture of this subject. It is probable that many cardiac stimulants might be used with advantage, such as nitro-glycerin, digitalis, and strychnine. Dr. Mueller of Sydney, Australia, has recently published a monograph advocating enthusiastically the use of large doses of the latter drug given subcutaneously, basing his method on Feoktistow's theory of the action of the poison on the nerve-centres. He recommends that as much as \ a grain of strychnine should be given in divided doses, 16 minims of the liquor strychnia^ (P. B.) being injected at a time. If under these large doses the symptoms abate or if the latter are comparatively mild at first, smaller doses should be injected, as -^ or -^ of a grain; but under all circumstances the rule that distinct strychnia symptoms must be produced before the injections are discontinued should never be departed from. Many cases apparently at the point of death seem to have been revived and finally cured by this treatment. It has, however, met with much adverse criticism in Australia, and has had thus far only a very limited trial in India. Calmette has studied the serum of animals rendered immune to the venom of serpents. According to this observer, animals can be rendered immune in two ways : either by repeated injections of venom of full strength in very small and gradually increasing doses, or of venom which has been modified by combination with chloride of gold or chloride of lime. The serum of animals thus treated has also an immun- izing and antitoxic action. This action exerts itself not only when brought in contact with the venom with which the ani- mals in question have been previously treated, but also with the poison of other serpents. It was found that the serum of a rab- bit that was immunized by cholera virus exerted an antagonistic action to the venom of the French viper and that of several Aus- tralian serpents. SNAKE-BITE. 503 Calmette found that 4 ccm. of antitoxic serum, injected into a rabbit an hour and a half after 1 mg. of cobra-poison had been injected into the same animal, was sufficient to save the animal. In rabbits which had not received the serum death occurred in twelve hours after the injection of 1 mg. of the cobra-venom. If the poisoned animal was treated with chloride of lime, a cure was effected without resort to the serum. The solution, which is of the strength of 1 to from 12 to 45 parts of water, should be injected in doses of 5 ccm. subcutaneously around the wound. From 20 to 30 ccm. of a more dilute solution may be used in the same way. This method, when employed twenty minutes after inoculation with the venom, saved animals which would otherwise have died in two hours. Whatever the treatment may be, the patient should be kept quiet. All his spare strength should be kept in reserve. He should be encouraged and soothed. Hot bottles may be applied to the heart, and the general rules for the treatment of shock might well be resorted to with advantage. It is most important to remember, in estimating the value of any particular line of treatment, that a careful estimate of the dose of the venom should be made in each case, for in inflicting the injury the serpent often fails to accomplish its purpose, and only a drop or two of the poison may come in contact with the exposed tissues. XXIV. TUBERCULOSIS. Tuberculosis did not until recently especially interest sur- geons, but it now covers a large field in surgical pathology. The surgeon has, in fact, more to do with the disease to-day than the physician. The inoculability of tuberculosis was first recognized in 1826 by' L,aennec, who became infected by an injury to his finger from a saw during an autopsy upon a case of disease of the ver- tebrae. Eventually he died of phthisis. Villemin in 1865 was the first, however, to demonstrate experi- mentally the possibility of transmitting the disease from man to animals. He showed that the cheesy products of tuberculous inflammation when introduced into the tissues of rabbits and guinea-pigs produced a miliary tuberculosis. He, however, did not identify the microscopical characteristics of the new formations thus produced with tubercle, nor did he undertake to show that other products might not produce the same results. Cohnheim and others, however, endeavored to show that any cheesy mate- rial, whatever its origin, would produce the same appearances of tuberculosis when inoculated. It was attempted also to produce tubercular nodules by intro- ducing different kinds of foreign bodies into the tissues. But, although minute tubercles closely resembling the genuine tuber- cle were thus produced, yet they did not appear capable of spread- ing to distant organs or of being transmitted from one individual to another. The recognition of the characteristic giant-cells and epithelioid cells of tubercle, and of the tendency of the tubercular masses inva- riably to undergo cheesy degeneration, helped to throw light upon the investigations which were then being made. Cohnheim, whose experiments on the cornea enabled him to study the development of the tubercle after inoculation, found that a considerable space of time intervened between the inoculation and the development of the disease — that, in other words, there was a distinct period of incubation. A great variety of experiments followed. Tuberculous perito- 504 TUBERCULOSIS. 505 nitis was produced by the injection of diseased sputa into the peritoneum of guinea-pigs ; infected food was proved to produce ulcerations of the intestinal canal and the subsequent involvement of the mesenteric glands ; the dried sputa, when inhaled, produced pulmonary tuberculosis. The old belief that tuberculosis was caused by a weakness of the tissues gradually yielded to the conviction that it was a genuine infectious disease. These views received their confirmation in the discovery of the bacillus of tuberculosis, and in the demonstration by Koch that by it alone could the phenomena of the disease be produced. Koch's discovery in 1882 fairly revolutionized a great depart- ment of surgery. He made his first observations of the bacillus of tuberculosis in the expectorations of phthisical patients and in sections taken from miliary tubercles. He succeeded, also after many trials, in producing a culture of the bacilli on blood-serum, his skill as a bacteriologist enabling him to overcome the unusual difficulties that surrounded the cultivation of the organisms. With these pure cultures he made a series of inoculation-experiments upon rabbits, guinea-pigs, and field-mice, introducing the virus subcutaneously or into the various cavities of the body, and also by intravenous injections, and in this' way he was able to obtain acute miliary tuberculosis. The tubercles taken from such animals contain large numbers of bacilli, and they are much better suited for microscopical examination than the specimens taken from human subjects. From these animals, finally, he was able to reproduce the cultures, and then to establish fully the identity of the organisms with the disease. The bacillus of tuberculosis, which is a thin, staff-shaped body from 3 to 4/i in length, will be found more fully described else- where. The submiliary tubercle is the pathological structure from which are developed the tubercular nodules found in diseased organs or in tissues. It is composed of a globular mass of small round cells, in the centre of which mass is found one or more giant-cells. The giant-cells, which are a very characteristic feature of the miliary tubercle, enable one to make an almost positive diagnosis even when no bacilli have been discovered. The peculiarity in this form of giant-cells consists in the arrangement of the nuclei, which are found chiefly in the periphery, arranged with their long diameters radiating from the centre of the cell. At the centre there is more or less evidence of a degenerative process. Surrounding this cell are seen one or more large cells rich in pro- toplasm, with large nuclei and nucleoli, which are known from 506 SURGICAL PATHOLOGY AND THERAPEUTICS. their size and appearance as epithelioid cells. According to Cheyne, the epithelioid cells are the most characteristic, as they are more constant than the giant-cells. They are, in his opinion, more fre- quently the seat of the bacilli which lie between them. These cells may be derived from the epithelium, as, for instance, in the lung, or from the endothelium of a vessel, or from tissue-cells. They are more numerous at the periphery of the tubercle. The remaining cells of the tubercle are round or are slightly spindle-shaped, and the cell-cluster is supported in a fine reticu- lum of connective tissue which in some cases is quite dense at the periphery (Fig. 76). The bacilli are found scattered here and there Fig. 76. — Submiliary Tubercle, showing giant- and epithelioid cells. The prevalence of the spindle is probably due to the locality (the tongue) from which the specimen was taken. in varying numbers between the smaller cells, and also in the body of the giant-cell. In the experimental forms of miliary tubercle the bacilli are usually very numerous, and they are then seen, in stained specimens, forming an ornamental border near the fringe of nuclei in these large cells. Very few are found in the interior of the cell. In pathological tubercle in the human subject it is not at all an easy matter to find bacilli, and several specimens are often searched through with great care before a single bacillus is dis- covered. TUBERCULOSIS. S°7 In infiltrating tubercle the epithelioid cells are not collected in small clusters, but are seen through the tissue in broad tracts, or they are simply scattered irregularly among the other tissue-ele- ments. The tissue which is the seat of the infiltration presents two chief types — namely, granulation tissue and gray fibrous tissue. The latter type shows less tendency to break down (Cheyne). The origin of the cells of the tubercle has been a subject of much dispute. According to Baumgarten, the cells found in the early stages of the development of the tubercle are not leucocytes, as has been supposed, but they originate by the process of indirect cell-division from the fixed cells of the part, whether they happen to be of connective-tissue origin or are derived from the epithelium of a gland or from the endothelium of a minute blood-vessel. The giant-cell does not develop from a fusion of several epithelioid cells, but it is the product of the nuclear proliferations of a single cell. Under the moderately stimulating action of the tubercular virus the cell does not receive sufficient irritation to undergo prolifera- tion. The protoplasm remains, therefore, undivided and increases in size, while the nuclei continue to accumulate in large numbers. In many cases of very acute tuberculosis, for this reason, giant- cells are not to be found. The centre of the cell is without nuclei, as the protoplasm has here already begun to undergo that change so characteristic of the disease — namely, cheesy degeneration. After the virus has thus affected the fixed cells of the part, it produces also an irritation upon the walls of the small vessels ; consequently exudation takes place, and the tissue is found infiltrated with leu- cocytes, but this occurs usually in a later stage of the development of the tubercle. The reticulum of fibres in which the cells lie is not usually a new formation, but is merely the remains of the pre-existing inter- cellular substance. As the cell-growth is most active at the centre of the mass, and a certain pressure is thus exerted from within out- ward, there is seen at the periphery a thickening of this network amounting at times almost to the formation of a capsule. In some cases the reticulum seems to be formed, at least to a large extent, by the processes of the epithelioid cells. The vascular supply is usu- ally very slight, the smaller vessels disappearing altogether. The consequence is, that the vitality of the diseased mass is soon affected, and an anaemic necrosis occurs, which, accompanied by a granular disintegration and a fatty degeneration of the cells, produces the condition known as cheesy degeneration, which is found in the mid- dle of the nodule, and which may gradually extend so as to affect 508 SURGICAL PATHOLOGY AND THERAPEUTICS. the whole mass. The bacilli also appear to exert an influence which brings about a chemical change in the cells. The nuclei disappear, the cells refuse to take any coloring reagents, and coag- ulation-necrosis takes place. The result of these changes is the formation of a mass of dead tissue and of cheesy debris in the centre of the tubercle. Where this formation is extensive ulcera- tion, or even abscess-formation, may take place. Occasionally lime- salts may be deposited in these central portions of the tubercle, resulting in calcification. The tubercle may be surrounded by a well-marked zone of granulation tissue, or the tissue of the tubercle may pass into the surrounding tissues without any well-marked line of demarcation. A dissemination of tubercle can take place only when the original focus is broken down and in a state of ulceration. When inflammatory reaction occurs around the tubercle, incapsula- tion may take place, and the system may in this way be protected from invasion. The entrance of the tubercular virus into the body is through various channels. The question of the transmission of the disease from mother to child through the placenta has been much dis- cussed since the discovery of the bacillus. Baumgarten is one of the most prominent advocates of this source of the tubercular virus, and, according to this investigator, it may be received during fcetal life only to manifest itself perhaps many years later. Tuber- culosis of new-born infants is, however, an exceedingly rare occur- rence, and in the reported cases of early tuberculosis the possibility exists of the acquisition of the disease from the breast of the mother or in other ways. It is true that there are recorded cases which illustrate the possibility of such transmission from animal to ani- mal. Cornil reports the case of a fcetal calf whose lung contained a tubercular nodule. The foetus was taken from the uterus of a tuberculous cow. Inoculation experiments on pregnant guinea- pigs have not, however, been successful. Hereditary tuberculosis, then, is an occurrence so extremely rare that it cannot be regarded as one of the ways in which the disease is acquired by the human subject. Many authorities still main- tain, however, that a predisposition exists which may have been inherited — that in certain families the tissues and fluids of the body furnish a more favorable soil for the growth of the bacillus. The difference in susceptibility to the virus may be the same in different individuals as it is in different kinds of animals. Frankel does not accept even this possibility, although he admits that a delicate con- stitution and a catarrhal condition of the air-passages, with feeble TUBERCULOSIS 509 respiratory action, would present conditions favorable for infection. It is generally found that tuberculous patients have a family his- tory of tuberculosis. Certain individuals, however, are peculiarly exempt. It is well known that nurses in attendance upon the sick in hospitals for consumptives may remain there years without in- fection, and that surgeons constantly wound themselves with tuber- culous bone without danger. The family physician will tell you that in his private practice he rarely sees tuberculosis in healthy families. It is probable, therefore, that a predisposition to tuber- culosis is inherited by children from their parents, but the disease must nevertheless be looked upon as one which is acquired during life by infection. Probably the most frequent route through which the virus is introduced into the body is through the lungs. The durability of the organism and its power to retain its vitality in the dried state make possible its introduction with the inspired air. The expec- torations of consumption, therefore, are a source of danger, as has abundantly been shown, not only when injected experimentally into animals, but also when allowed to dry upon the carpets or the linen. Cornet has shown that the dust of rooms occupied by such patients contains an abundance of the bacilli of tuberculosis, and Prudden and others have also found them in the dust of the streets. If the sputa are preserved in a moist state, the bacilli are im- prisoned, and hence do not become a source of danger. When introduced experimentally by inhalation, broncho-pneu- monia is produced at the extremity of the tubes, and the bronchial glands become infected later. According to Bollinger, not every tubercular disease of the lung is due to the inhalation of the virus, for it may occur there secondarily by metastasis. It is, for ex- ample, a well-known clinical fact that caries of the wrist is very often followed by pulmonary tuberculosis. Contagion may take place also through the digestive tract. It may be transmitted from mouth to mouth by a kiss, or by the spoon or the glass used by the consumptive. It should not be for- gotten that the spatula or the dentist's instruments may, if not properly disinfected, become a source of danger to the patient. The susceptibility of the mucous membrane is increased by inflam- matory processes, such as rhinitis and pharyngitis, and the virus may thus be transmitted to the submaxillary and cervical glands. The intestinal canal of animals is readily infected by tuberculous food. In man is found also primary tuberculosis of the intestine from vitiated food. The milk of tuberculous cows is now a well- 510 SURGICAL PATHOLOGY AND THERAPEUTICS. recognized source of danger. Water may also be the vehicle of the virus, experiments in Cornil's laboratory showing that the bacillus could live seventy days in sterilized Seine water of the ordinary temperature. Even meat that has been roasted may be a source of danger, for the central portions may not have been subjected to a sufficiently high temperature. Secondary tuberculosis of the intestine depends upon auto-infection, the sputa often being swallowed. The mem- brane of the bacillus is sufficiently tough to withstand the gastric juice; consequently the bacillus arrives unaltered in the intes- tinal canal, where it attacks Peyer's patches and the solitary folli- cles. The mesenteric glands are subsequently affected, and tuber- culosis of the peritoneum may thus be developed, particularly in man. In women, however, the peritoneum is more frequently in- fected through the urogenital tract. As the result of such infec- tion tuberculous peritonitis occurs. Infection through the skin is, according to Bollinger, underestimated, although the bacilli do not appear to be able to enter the pores of the skin like the pyogenic cocci. Tscherning reports the case of a servant who cut his finger while cleaning the spit-cup of his master, a consumptive. There formed a small cutaneous ulcer, which afterward became a nodule: a few months later the finger and the tendons of the palm of the hand became swollen and the cubital and axillary glands were enlarged. The finger was amputated and the glands were excised, and they were found to be tuberculous. The patient remained well. Middledorff reports the case of a man who wounded his knee-joint with a cutting instrument, and bound the wound with his handkerchief, which probably contained dried sputa. Two weeks after the accident the knee began to swell and excision of the joint for white swelling was ultimately performed. An exam- ination of the tissues showed the presence of bacilli. "Anatomical tubercle " is an example of infection received by those who are in the habit of handling infected bodies. Cheyne reports a case of a student who injured the fold of the nail at an autopsy. A wart formed, which remained as an ulcer after three years of treatment: an abscess on the back of the hand finally formed, and the finger was amputated. Death from tubercular meningitis occurred six years after the injury. The oft-quoted example of infection of the prepuce in the rite of circumcision by the mouth of the operator, who was tuberculons, is another instance. Certain portions of the body appear more easily infected than TUBERCULOSIS. 5 r l others: the face and the head are peculiarly liable, and even certain organs and tissues appear to be predisposed. Many inflammatory skin affections, which are at first purely benign, may subsequently become tuberculous. No example of infection with tuberculosis during vaccination has been reported: it is probable that the bacilli are unable to live in the vaccine lymph. Lawrence, indeed, reports two instances of remarkable recovery from advanced stages of tuberculosis after an attack of small-pox of a virulent type. Cases are reported of tuberculosis of the internal organs of gen- eration, which cases, it is possible, may have been due to infection during coitus. A large number of tuberculous diseases owe their origin to intravascular infection, the virus gaining an entrance at some unknown point. Thus, it may appear first in a chain of glands, as in the neck, or in some portion of the osseous system. Acute infectious diseases, like measles and scarlet fever, often pave the way for tuberculosis. Susceptibility to the disease is not the same at all periods of life. Individuals who have been the sub- jects of tubercle in youth often enjoy a particularly healthy exist- ence in later life. The tuberculous process may spread in different ways and by different routes. The original nodule may invade the neighboring parts by a simple process of growth. Distant portions of the body are reached usually through the lymphatic system. The lymphatic glands, however, exert a protective influence: they may not only retard the advance of the bacilli, but may also be indirectly the cause of their destruction. When the last of a chain of glands has been traversed the bacilli are conveyed through the thoracic duct into the general circulation. A thrombus may form in a vein adjacent to a tuberculous nodule, and metastatic foci may be established through embolism, or the wall of a large vein may become involved by invasion of the virus from a neighboring nodule, and bacilli may then be let loose into the circulation. They are conveyed eventually to some arteriole or capillary, where they become attached to the endothelium, and the conditions favorable for the development of a miliary tubercle are established. In this way acute miliary tuberculosis may occur. The disease may also spread by an invasion of an adjacent serous sac, by the growth of the nodule, or by suppuration, and it may discharge into the sac. If the integrity of the sac is still maintained, it will be in communication with the lymphatic sys- 512 SURGICAL PATHOLOGY AND THERAPEUTICS. tern, and the danger of dissemination will be much greater than when the membrane has changed into a wall of granulation tissue which has blocked up the lymphatics. When the bacilli gain access to cavities lined with mucous membrane, such as the bron- chial tubes or the intestines, they pass over long surfaces, increas- ing the opportunity for infection. Tuberculous affections are apt to be multiple. The multiple form may occur in the primary stage of the disease, as in spina ventosa, where several fingers are usually involved, or there may be sepa- rate infections at different times. A familiar example is that of a patient who had scrofulous glands in childhood, later had white swelling of the knee, and eventually died of pulmonary tubercu- losis. It is probable that in a case such as this the different mani- festations have some connection with one another, and that they are examples of periods of latency of the disease followed by meta- static deposits. The original tubercular focus may, however, be absorbed in con- sequence of the influence of the inflammatory process which has been set up around it. The tubercle becomes encapsuled. The cells undergo cheesy degeneration or calcification, and cicatricial tissue finally occupies the seat of the tubercle; or ulceration of the neighboring parts occurs and the tubercle is thus removed. If any bacilli remain behind, there is always danger of a renewal of the tubercular process, as the organisms are exceedingly tenacious of life, and either they or their spores, if such exist, may be able at a favorable moment to begin again an active development. The danger of relapse in this disease, therefore, is always great. Mili- ary tubercles may be found in nearly every portion of the body. They develop readily in the connective tissue, in or around minute blood-vessels, in the parenchyma of organs, or on the surface of membranes. Tuberculosis probably affects more individuals than any other form of infectious disease, for it has roughly been estimated that out of every five deaths one is due to this cause. Notwithstanding a very large proportion of those affected recover their health, it will readily be seen that the bacillus of tuberculosis is one of the greatest scourges of the human race. In 384 autopsies of children who died of acute infectious disease in a hospital in Copenhagen between 1884 and 1887, 198 showed undoubted evidences of tuberculosis. Almost without exception these children had no sign of the disease during life: in all cases the disease occurred in the lymphatic glands. TUBERCULOSIS. 513 In the Aledical Institute of Munich, in 500 autopsies on chil- dren under fifteen years of age, tuberculous disease was found in 150 cases. In other words, 30 per cent, of those who died at that hospital were tuberculous. Statistics of the autopsies performed 'upon adults in that city during a period of nearly thirty years, a city renowned for the stringent rules in regard to the examination of the dead, showed that tuberculosis existed in 29.4 per cent, of the cases. It is found, therefore that, although not always the cause of death, tuberculosis existed in one-third of those who died during a very considerable period of time. Tuberculosis of Bone. — One of the commonest of tuberculous diseases, and one of great importance for the surgeon to understand, is tuberculosis of the bones and joints. Common as this affection is, it is nevertheless one which suffers greatly from the ignorance and indifference of many who are called upon to treat it. The great advance in the knowledge of its pathology has placed the surgical treatment on an entirely new basis, and the extent and limitations of tubercular bone disease and the possibilities of intel- ligent operative interference are not yet fully appreciated. Tuberculous disease of bones and joints, in the great majority of cases, follows slight contusions and sprains. Spondylitis, or Pott's disease, usually occurs, in a susceptible individual, after a fall or a sprain. A bruise of the spongy tissue of one of the bodies of the vertebrae or of the head of the tibia, or in one of the tarsal bones, is followed by a laceration of some of the delicate vessels of the spongy tissue, and an effusion of blood consequently takes place between and around the cancelli of bone or into the synovial cavity of a joint. The result of such an injury impairs for the time being the nutrition of the part affected, the circulation does not go on so actively, and there is a period during which absorption of the effused blood and exudation does not take place. The point of injury and the surrounding tissues are momentarily disabled by the damage that has been done, and they are in a less resistant state to the invasion of bacterial poison. Individuals predisposed to tuber- culosis may already have, as has been shown, the seeds of the dis- ease temporarily imprisoned in the lymphatic gland. The bacilli may reach the injured spot as single organisms floating in the blood, and thus find ready access to the extravasated clot through the open mouth of the blood-vessels; more rarely they may reach the region in the interior of an embolus which may have become detached from a degenerating gland that had discharged its contents into a vein, or which may have communicated with the pulmonary 33 514 SURGICAL PATHOLOGY AND THERAPEUTICS. capillaries, and thus have directed the embolus into the arterial system. When such an embolus is caught in a terminal artery, wedge-shaped infarctions and wedge-shaped sequestra are not un- common in the articular extremities of long bones. These light forms of injuries are a more frequent source of tuberculosis than are more severe accidents. The French government at one time called attention to the large number of cases of amputation for tubercu- losis of the ankle-joint following sprains, and enjoined special care in the treatment of this injury. All writers bear testimony to the fact that it is extremely rare to find tuberculosis of the bone follow- ing fracture. In dislocation the rupture of the capsule appears to be a fortunate circumstance, for the effused blood can escape from the articular cavity, which blood would be likely to remain for a long time unabsorbed and to furnish a soil for the growth of the bacilli — a process which very probably occurs in many of those cases of tuberculosis following sprains. The tension is thus re- lieved and absorption more readily takes place. The majority of cases of bone-and-joint tuberculosis occur in children and in youth. According to Billroth, of all the cases one-half occur before the twentieth year. This is true of certain joints only, for disease of the wrist and of the shoulder is found occurring almost invariably in adults. These joints are more fre- quently the seat of primary tuberculosis, whereas children are more liable to that form of the disease where the lesion is first found in the bone and subsequently breaks into the joint. These primary nodules often remain in the ends of the bones for a long time without giving any indication of their presence, and Volkmann has appropriately called this the "prodromal stage of joint dis- ease." Hip-joint disease usually begins as a bone disease, and this affection is therefore more commonly seen in childhood. In youth, males appear to be more frequently affected than females, but later in life there does not appear to be any essential difference between the sexes. It is probable that only a small portion of the tuberculous nodules in joints and bones are primary in origin, the majority of them being secondary to some diseased gland in the bronchial or the mesenteric group, infection taking place through the mucous membrane. Landerer examined post-mortem 150 cases of tubercu- losis of the bones and joints, and with one or two exceptions found tuberculous disease of the bronchial glands that evidently ante- dated the bone affection. The hereditary tendencies of this disease are shown in the fol- TUBERCULOSIS. 515 lowing hospital statistics: According to Brandenburg of Basle, of 141 children with tuberculosis and 162 with bone tuberculosis, all being under four years of age, 34 per cent, were children of dis- tinctly tuberculous parents. Bollinger of Budapest reports 250 cases of bone-and-joint tuberculosis, in 97 of which either the parents or the grandparents were tuberculous. A considerable amount of experimental work has been per- formed upon animals to demonstrate the tuberculous nature of the so-called "scrofulous" bone-and-joint diseases. Watson Cheyne was one of the first to perform this work with pure cultures of the bacilli obtained directly from Koch's laboratory. A number of experiments were made upon goats, the nutrient artery of the tibia being injected by entering the tibial artery from below and injecting upward, a ligature having been placed on the vessel above the point of injection. Three minims of the cultures were thus introduced into a young goat, and the animal died on the fifty-second day. In about three weeks from the time of the injection the ankle- and the tarso- and the metatarso-phal- angeal joints began to swell, cheesy deposits being found in the lower end of the tibia and the metatarsal bones. The synovial membrane of both joints was swollen and gelatinous. The dis- ease in the joint appeared to be synovial, the epiphyses being but slighly affected. Krause performed a large number of inoculations upon guinea- pigs and rabbits. The material used was a pure culture of the hacillus suspended in a 0.6 per cent, salt solution. The fluid was introduced either through an incision in the skin, or an injection was made into the peritoneal cavity or into the circulation, as the vein in a rabbit's ear. The culture was also injected into the joint itself. Immediately after the injection the bones were fractured or the joints were bruised and twisted or were dislocated. In the guinea-pigs, out of 44 joints thus treated, 15 became tuberculous, and the joints of 72 rabbits were treated in the same way, of which 29 became infected with tubercle. A microscopical examination of the synovial membrane showed the presence of large numbers of leucocytes in the tubercles, and occasionally epithelioid cells, but no giant- ceils. The articular cartilage was rarely affected. The number of bacilli both in the joints and in the bones was in all cases, as in man, exceedingly small, and this was in striking contrast to the great numbers found in tubercle of other organs. There appeared to be no tendency to the formation of tubercles in the bones and joints when not subjected to trauma. All the 516 SURGICAL PATHOLOGY AND THERAPEUTICS. cases of fracture healed without the slightest trace of tuberculous infection at the seat of fracture. In this respect the contrast between the action of the bacilli of tuberculosis and that of the pyogenic cocci is very striking, for it is a well-known fact that when an animal is infected with the latter organisms a fracture of the bone will always be followed by suppuration. Tuberculous nodules were occasionally found in the epiphyseal ends of the bones, but not in any large number of cases. It did not appear that the bacilli were disseminated through the system in emboli, for an embolus was discovered in only a single case. Krause was of the opinion that the bacilli, after being intro- duced into a vein, were carried through the vessel, and, finally, being taken up by a leucocyte, made the passage through the wall of a vein, or in the bruised tissues passed out at the end of a rup- tured capillary vessel into an cedematous tissue or a clot which offered a favorable soil for their growth. The presence of a wedge- shaped infarction of the bone was not observed in any of the cases. W. Muller was able, however, to obtain tubercular infarctions in bone by injecting tuberculous material into the tibial artery of goats. He obtained typical wedge-shaped infarctions. Many of them were, however, round or irregular in shape — a circumstance which coincides with the shape found occasionally in the human subject. The disease begins as a tubercular ostitis, and its commonest seat is in the centre of the epiphysis or just beneath the articular cartilage. Volkmann re- marks that these chronic tuberculous inflammations of bone have a tendency to form in the ends of long bones near the joint, just as pulmonary tuberculosis does in the apex of the lung. On making a sec- tion of the bone the tuber- cular nodule appears as a well-defined mass of a reddish-gray, yellowish- white, or pure yellow color (Fig. yy). The surround- ing bony tissue is usually red and hypersemic, and the trabecular may be somewhat thickened. The cancellous spaces are devoid of Fig. 77. -Tubercular Nodule of the Head of the Tibia (Sp. 1456-2, Warren Museum). TUBERCULOSIS. 5 J 7 fat-cells, and they contain a swollen semi-fibrons material. With a magnifying glass the miliary tubercles are seen at the periphery of the nodule, its centre being composed of broken-down cheesy mate- rial. The size of these nodules varies greatly. As they grow, the tubercular virus attacks the trabecular and leads to their absorption, and the bone becomes softened and breaks up into a mass of greasy, cheesy material containing crumbling fragments of bony tissue. When complete softening has taken place, the material of which the nodule is composed becomes puriform, and it may be washed away, leaving a cavity lined with granulation tissue. In case the trabecular have not completely been destroyed, in the infected part the cancelli between them will become filled with cheesy debris, and as the vitality of the part has been destroyed granulation tissue will form around the diseased mass, and absorp- tion of the connecting trabecular occurs: the spongy sequestrum which has thus formed separates from the living bone. These so-called " cheesy sequestra" are quite small, not exceed- ing in size that of a walnut, and are more or less globular in form. The surrounding bone may become somewhat thickened, and the interstices are filled with gray fibrous tissue, or eburnation of the bone may in some cases take place (Fig. 78). When the nodule has softened completely into pus the surrounding bone is either cov- ered by a tubercular membrane, which will be described presently, or its surface is infil- trated with granulation tissue, which usu- ally contains miliary tubercles on its inner aspect, affording, nevertheless, protection to the adjacent bone. These small sequestra lie firmly imbedded in a thick layer of blue- gray transparent granulation tissue dotted with yellow spots. Large amounts of pus rarely accumulate around these nodules. When removed and macerated the sequestra are seen to be round or irregularly-shaped bodies, consisting of thickened spongy tis- sue, and they differ in this respect from the sequestra of osteomyelitis that come from cortical bone, and they are consequently much denser and have usually sharply- serrated edges. The sclerosed bone which develops around Fig. 78. — Tubercular Abscess- cavity, being the point of ori- gin of disease of the hip- joint (Specimen 1282, War- ren Museum). 518 SURGICAL PATHOLOGY AND THERAPEUTICS. the diseased area forms, with the granulation tissue, a sort of cap- sule which may arrest the further progress of the disease, and such sequestra or pus-cavities consequently may remain a long time without giving any sign of their presence. The surrounding bone may, however, eventually be invaded by the tubercular growth, and the thickened trabecular may be absorbed, but this rarely occnrs. The tubercles have usually disappeared from the nodule by the time the degenerative changes are well established, and it is with great difficulty that the presence of bacilli can be demonstrated. The difficulty in finding the bacilli is attributed by Cheyne to the fact that they are more numerous in the earliest stage of the disease and decrease later, or they rapidly pass into the spore stage. It is not always possible, he thinks, to stain them. In double staining some are found red and others blue, which result is probably due to the different stages of development. Very small tubercular nodules may be absorbed, the surrounding bone throwing out granulations that permeate and destroy the broken-down tissues. This action occurs only when the process has not gone on to suppuration, but this rarely happens in chil- dren. Some of these nodules are of embolic origin, and in this case an infarction occurs which, terminating in necrosis, leaves a wedge-shaped sequestrum of bone whose base is usually found just beneath the cartilage. These infarctions are found in the articular extremities of the long bones. In its early stages of development the infarction has a gelatinous grayish transparency, and with a lens it will be found studded with submiliary tubercles. It is usu- ally about the size of a bean, but it may occasionally be as large as a pigeon's egg. The amount of suppuration which these sequestra cause is very slight: it may, however, be sufficient to dissect off the cartilage, and then the base of the sequestrum, being exposed to the articular cavity, may become eburnated and polished by friction. The tuberculous nodules in bone may frequently be multiple. Sometimes both ends of the bone may be involved simultaneously, or separate bones and joints may be affected. There are certain seats of predilection, as the olecranon and acetabulum, the inner condyle, or the neck of the femur, where nodules are more likely to be found than in other bones composing a joint, but these points are not yet well determined by statistics. It rarely happens that the tuberculous nodules give rise to secondary nodules or infiltra- tions in the surrounding spongy bone. There may be diffused TUBERCULOSIS. 519 miliary tubercles in a bone as a part of an acute miliary tuber- culosis, or in cases where the end of the bone has been freely exposed in the later stages of an aggravated form of tuberculous joint disease. Where the confluent masses of tubercle in the centre of a nodule begin to break down, there is formed a collection of caseous material surrounded bv tuberculous tissue. This material becomes infiltrated with fluids and leucocytes, and thus there is produced a cavity containing fluid fatty material, fragments of cells, and leu- cocytes, around which there is granulation tissue filled with tuber- cles; and in this way a tuberculous abscess is formed (Cheyne). It seems, at times, to be quite a matter of accident whether the abscess breaks into the joint or finds its way by a more circuitous route into the surrounding connective tissue. As the tubercu- lous masses spread, caseation takes place at different points in the wall, and the masses are discharged into the cavity of the abscess; but the spread of the abscess is effected generally by what is termed "burrowing of pus." This burrowing occurs in various directions, and large collections of pus, altogether out of proportion to the original lesion, are formed, and are known as cold abscesses. The pus which they contain is so characteristic that it can always readily be recognized after seeing it once. It is of a pale white color, and it frequently contains masses of cheesy material, like coagulated casein, sometimes of considerable size, which makes the aspiration of these abscesses often a difficult operation. It is for this reason called "grumous. nl It has a very thin serum, much thinner than that of the pus of acute abscesses. Occa- sionally the pus may be mingled with blood, in which case it will have a dirty brown color. Not infrequently small bony par- ticles are found in the pus, feeling to the finger like grains of sand, particularly in abscesses resulting from disease of the vertebrae. The presence of the bacilli in such pus is not easy to demonstrate microscopically, but on culture the pus of cold abscesses yields a quantity of the characteristic bacilli. The pyogenic cocci are rarely seen in the cold abscess before it is opened: according to many authorities they are never found in them. Rapid rise of temperature and increase of hectic fever accompany the infection of such an abscess by the pus-cocci when an abscess is allowed to break or is opened without the strictest antiseptic precautions. The walls of such abscesses have a very characteristic appear- ance, being covered by the so-called tuberculous membrane y 1 From grume, a clot (grumus, a little heap; npu/uat;, a heap of stones). 520 SURGICAL PATHOLOGY' AND THERAPEUTICS. described originally by Volkmann. This opaque membrane is several millimetres thick, and is of a violet-gray or a yellowish- brown color, and is very feebly vascular on its inner surface, which comes in contact with the pus. It contains innumerable clusters of miliar\- tubercles, so that it often appears to be formed exclu- sively by them. They are supported by a matrix of coagulated fibrin. This membrane can easily be scraped off with the ringer or even be removed by a stream of water, and frequently during an ope- Tation it peels off from the surface in sheets several inches square. IBelow this membrane there is found a fibrous indurated tissue which separates the abscess from the surrounding healthy parts. This tis- sue is the result of a slight reactive inflammation, and it contains no tuberculous material. In over a thousand cases examined care- fully by Volkmann, on two occasions only did he see the tuber- cles invading the surrounding muscular tissue. If on opening an abscess ~::h cheesy :::::e:::- the inuscviliir tissv.e is :h'.:::d :: h.r.e undergone a cheesy degeneration, the abscess is probably syphilitic. In this case no tubercular membrane can be found, and it will not be possible to scrape away the wall of the abscess The presence of the tubercular membrane is considered by Volkmann as an abso- tutely certain diagnostic sign of the nature of the abscess. After all the tubercular membrane has carefully been scrape I awav one ran generally find in the subjacent layer of light-colored indurated tissue a small clump of red granulations. These gran- ulations protrude from the mouth of a fistulous opening leading either to diseased bone or to a tuberculous joint. Such a fistulous tract must be followed up to its source, and then there will be found somewhere in the bone a small cavity which gives rise to the more superficial suppuration. Only when this cavity has also been curetted thoroughly can the surgeon feel at all sure that the tuberculous disease has thoroughly been removed. When the abscess breaks spontaneously it communicates with the surface by an opening, the walls of which are also tuberculous, for whenever the tuberculous pus comes in contact with the healthy : ssue infection is bound to occur. Cheyne does not accept the Ger- man theory, which assumes that a wall of fibrin has been poured out around the tubercles. He thinks that the granular material of the wall of the tubercular cavity is derived from degeneration of the preformed tissue. Many of these abscesses were at one time supposed to be formed independently of the original nodule or joint disease; consequently they were called i4 peria^ticula^. ,, S :h Ab- scesses occasionally do occur as a result of the transportation of TUBERCULOSIS. 521 infected material through the lymphatics to an adjacent area of connective tissue, but more careful study of these abscesses, such as has been made since the system of thorough curetting has been established, reveals the presence of the minute fistulous tract which communicates with the original seat of the disease. As already pointed out by the writer, the tubercular deposit is almost entirely confined to the ends of the long bones, and this pathological fact helps greatly in distinguishing between this form of disease and the necrosis following acute osteomyelitis ; occasion- ally, however, there is seen tuberculosis of the diaphysis or shaft of the long bones. When the disease does occur in this locality, it is found only in quite young children. Such a case the writer saw recently in a boy about four years of age. The presence of a white swelling of the knee-joint of the same limb greatly facilitated the diagnosis. There were a series of sinuses opening at different points along the course of the femoral artery; an exploratory operation disclosed the presence of tuberculous granulations, but no large sequestrum. This condition is somewhat more frequent in the shaft of the tibia, the humerus, and the ulna than in the other long bones, and in these cases it is found to be secondary to some other tubercular focus, as in the case quoted above. Tuber- culous deposits are still more common in the shafts of the shorter long bones, such as the phalanges and the metacarpal and meta- tarsal bones. Miliary tubercles accumulate in the medullary tis- sue, which is gradually converted into the characteristic granu- lation tissue; and this tissue, as it grows, absorbs the inner layers of cortical bone and accumulates in considerable quantity. Partly from this accumulation and partly from a deposition of new bone by the periosteum, which is stimulated to a formation of new bone, there is obtained the characteristic flask-shaped bone which was known to ancient writers as spina ventosa. This name was given by them to all affections that produced such distention of bone, whether of tuberculous, syphilitic, or other origin: it was suggested partly by the cavities left in the distended bones after the granulation tissue had broken down and melted away, and partly by the appearance of the macerated bones, which appeared to have been distended with air. Gradually the surfaces of the bones yield at the end of weeks or months, and the thinned cor- tical bone is distended more and more by the growth of the gran- ulation tissue until here and there it entirely disappears. The bones crackle with a parchment-like sensation under the fingers, and fluctuation is finally established at one spot. In the mean ,522 SURGICAL PATHOLOGY AND THERAPEUTICS. tfh time the surrounding skin becomes reddened and swollen, and at some point softens and breaks down, the characteristic tuberculous pus being discharged. These bones may, however, remain for a long time in the granulation stage, and they may eventually heal without suppuration, so that no trace of the disease is left behind. The disease is generally confined to the shaft of the bone, and the neighboring joints may remain perfectly healthy. Although the epiphyses may also es- cape injury, the intermediate cartilage will probably be destroyed, and the future growth of the bone w r ill conse- quently be arrested, or the entire shaft of the bone may be absorbed. As the result of the destructive changes great deformity to the fingers or the toes will necessarily result (Fig. 79). Among the short bones is found tu- berculous disease of the bones of the carpus and tarsus both in childhood and in adult life. According to Krause, disease of the carpus is not so common in children. At this period of life the disease has less tendency to spread. Whether it be that a bone is affected ease - i'-ii which does not communicate with the articular cavity or that an adhesive inflammation shuts it off from the other bones, there are often found only a single fistulous open- ing and a tendency to heal without operative interference. This is particularly true of the carpus. In adults, however, there is a tend- ency of the disease to spread from one bone to another. The whole wrist is transformed into a spindle-shaped swelling perforated by numerous openings. A sound may be introduced in various direc- tions without detecting a sequestrum. The disease appears to be the expression of a general infection or to be one of numerous local deposits of tubercle, pulmonary tuberculosis being already devel- oped or soon to follow. In the tarsus a sequestrum is rarely found, except in the os calcis. This region may be infected secondarily to the ankle-joint, or the disease may originate primarily here as a nodule in one or more of the bones. It should not be forgotten that the synovial membrane may be affected primarily as well as the bones. The disease spreads eventually from one bone to another, until the Fig. 79. — Deformity from Absorption of Phalanx due to Tubercular Dis- TUBERCULOSIS. 5 2 3 whole tarsus is involved. After long duration of the disease the trabecular of the spongy tissue are more or less absorbed by a rare- fying ostitis, and the bones become so soft that they can easily be cut with a knife. The whole ankle becomes transformed into a spindle-shaped swelling, from which tuberculous pus is discharged through various openings. The fistulse and the skin surrounding their mouths are also infected. This disease of the wrist- and the ankle-bones usually receives the name of caries of the carpus and tarsus. By caries was meant, originally, an inflammation of the bone, with solution or ulceration of the bone, for bones so affected have, when macerated, the characteristic worm-eaten ap- pearance. The term is falling somewhat into disuse, now that it is known that most cases of caries are, with the exception of the syphilitic forms, due to tubercle. The term "caries" may be applied to tuberculosis of any of the bones or joints. One of the commonest seats of tubercular disease, especially in children, is in the bodies of the vertebrae. Billroth, in a collection of autopsies of nearly two thousand cases of caries of different por- tions of the skeleton, found that in 35.2 per cent, of the cases the disease was situated in the vertebral column. The disease begins here, as in other bones, where the growth is greatest; that is, near the periosteum and intervertebral substance. It exists, therefore, frequently as a tuberculous periostitis. In this form it is found in the anterior surface of the bone, just beneath the anterior longitu- dinal ligament. Here the vessels, which run into the bone more or less perpendicularly to the surface, are surrounded with granula- tion tissue, and the absorption of the bone is therefore greatest at these points; and when the ligament is peeled off from the verte- brae the tuberculous granulations are found adhering to it as small red nodules which have been torn away from the bone, the latter presenting the characteristic worm-eaten look of caries. Less frequently the centre of the bone is affected, and the tend- ency to suppuration is then not so great. Two or more foci may exist in the same body. Not unfrequently these nodules contain sequestra. Primary disease of two vertebral bodies in different non-adjacent parts of the spine is rare, though it has been recorded. But no extensive destruction of many of the adjacent vertebrae from primary disease of one may be said to be the rule in Pott's disease (Bradford and Lovett). The disease may become arrested in its earliest stages, and in this case bone-formation takes place beneath the ligament, and ankylosis of the vertebral column at this point will occur. If the 524 SURGICAL PATHOLOGY AND THERAPEUTICS. nodule extends between the bodies of the vertebrae, the interverte- bral cartilage becomes affected. This generally occurs, indeed, at an early stage of the disease. In rare instances the intervertebral cartilage is affected primarily, and the affection of the bone is sec- ondary (Koenig). As the process advances the bodies of the ver- tebrae are gradually converted into granulation tissue containing cheesy debris and possibly a sequestrum, and the interarticular cartilage disappears entirely. The bodies of the vertebrae are not only rendered incapable of sustaining the accustomed pressure by the growth of granulation tissue, but they are also much weakened by a rarefying ostitis, which often precedes the spread of the tubercular infiltration. As the disease advances small prevertebral abscesses form, which, as the pus comes in contact with the inter- vertebral substance, aid in its destruction. The intervertebral car- tilage may, however, in rare instances be destroyed by granulations m mm'fJ : 1'-^.. '-hi 1 , v \ * Fig. 80. — Angular Deformity from Pott's Disease. A tubercular nodule may be seen in the arches of the vertebrae (Sp. 1109, Warren Museum). without suppuration. As the bodies of the vertebrae yield to pressure the characteristic deformity of Pott's disease is produced (Fig. 80). The vertebral body may thus be so nearly destroyed that only a TUBERCULOSIS. 525 wedge-shaped mass remains to mark the former site of the bone: in this way angular curvature is produced. When several inter- vertebral cartilages are melted down and the intervening bodies are converted into wedge-shaped masses, the curvature has a more bow- shaped outline. The older writers recognized the fact that the angular curvature indicated disease of but a single vertebral body (Kranse). As suppuration goes on the pus burrows at times for a consider- able distance, as in the case of the "psoas abscess," so called, the pus following the sheath of the psoas muscle in working its way to the surface at the groin. Such abscesses originate from tubercu- lous disease in the dorsal or the upper lumbar vertebrae. Abscesses originating from disease of the lumbar vertebrae may, however, point posteriorly in the lumbar region. Retropharyngeal abscess is caused by disease of the cervical vertebrae. Abscesses arising from the upper dorsal region may involve the pleural cavity, and may even break into the lungs; occasionally the oesophagus and the aorta are bathed in the pus of these abscesses. Such collec- tions of pus may sometimes find their way into the vertebral canal, and spread beneath the meninges and bring about a compression of the cord. The adjacent ostitis may also set up meningitis, and in this case the cord may be compressed by the inflammatory exu- dation. As a result of this pressure paraplegia may be produced. Pressure of the spinal nerves may occur occasionally as the result of connective-tissue growth around the roots of the nerves. During the period of convalescence ossification of the bones at the seat of the disease may occur as the result of the reparative efforts of the periosteal and osseous tissues, and the fragments of the bodies of the diseased vertebra may thus become firmly ankylosed. The commonest seat of the disease is in the dorsal region; it is found also in the upper lumbar region and, less frequently, in the cervi- cal region. In rare instances the transverse and spinous processes may be the seat of the disease. The flat bones are also the seat of tuberculosis, although much less frequently. In the scapula it may occur with or without formation of a sequestrum; usually there is a carious softening of the part affected. In a case that came under the writer's care the caries affected the greater part of the scapula. By laying open the various sinuses it was possible to curette the bone satisfactorily. Tuberculosis of the ribs and the sternum is somewhat more fre- quently seen than that of the scapula. It is usually a disease of adult life. Tuberculosis or " caries of the ribs," as it was 526 SURGICAL PATHOLOGY AND THERAPEUTICS. formerly called, is either primary or secondary. The latter form occurs after empyema, or other suppurative processes in the thorax, in individuals predisposed to the disease. The general condition of patients with tuberculosis of the ribs is usually good: in many cases, however, there is marked anaemia, and the prognosis is then unfavorable; but these cases are not com- mon. The disease produces in the bone either periostitis or osteo- myelitis. In the latter case a red nodule forms in the centre of the bone, and later the periosteum participates in the inflammation. The trabecular and the cortical portion of the bone are absorbed, or if the progress of the disease has been rapid necrosis occurs, and there are found sequestra which, however, are usually not large. Several foci may be established in one rib or several ribs may simultaneously be affected. As the nodules break down suppura- tion takes place and the pus endeavors to escape in different direc- tions. Usually there forms at the seat of the disease a fluctuating, colorless tumor, on opening which tuberculous pus escapes, and the walls of the cavity are found to be lined with the characteristic tubercular membrane. On scraping this membrane away a small opening will be found communicating with the cavity of the bone. A careful examination will show that the periosteum is thickened and that the shaft of the bone appears to be distended at this point; occasionally the bone is destroyed and a complete solution of con- tinuity takes place, but the formative power of the periosteum usually produces sufficient new bone to preserve the rigidity of the part. The pus does not point so near the seat of the disease, and it may take a most circuitous route to reach the surface. Riedinger reports a case where an abscess over the rectus abdominis was found to originate from the fifth rib. A fistulous opening over the spinous process of one of the dorsal vertebrae the writer found communi- cating with a tuberculous cavity of one of the ribs beneath the scapula. This patient eventually died of phthisis. If the peri- osteum is primarily affected, the disease may spread over a large surface of the rib. In some cases the pus burrows inward, but it rarely breaks through the costal pleura. A pus-cavity of con- siderable size may, however, occasionally be found projecting into, but completely shut off from, the thorax. Tuberculosis may also affect the cartilaginous portion of the rib. The disease takes the form of perichondritis, but it may also involve the cartilage, which then undergoes mucous degen- eration, and which may be replaced by connective tissue. Tuber- TUBERCULOSIS, 527 culosis of cartilage is an unusually obstinate affection, as parts are involved which lie near vital organs and the reparative power of the cartilage is feeble. The pathological changes in the sternum are very much the same as in the ribs. Owing to the vicinity of the heart and the large vessels, the complications may occasionally prove alarming. The membrana sterni posterior may, however, prove a protection to the mediastinum against the invasion of an abscess. A case of very extensive tuberculosis of the sternum entered the writer's ward some years ago. The patient was in a cachectic condition. Presently a hsematoma formed near the site of one of the many fistulous openings, and it soon became evident that a hemorrhage was taking place, from time to time, from a vessel of considerable size. On etherizing the patient, laying open the tumor, and removing the clots, blood spurted from a large artery in the interior of the thorax, possibly the internal mammary. The hem- orrhage could only be controlled by plugging the cavity. At the autopsy, a few days later, extensive amyloid disease of the viscera was found. The source of the hemorrhage could not be discovered. The greater portion of the sternum was involved in the disease, and perforation had taken place at several points, but no extensive collection of pus was found in the medi- astinum. Ordinarily, these cases of sternal disease present themselves for treatment with a small fluctuating tumor over the sternum or with a sinus which marks the site of an abscess that has opened and dis- charged. These abscesses and sinuses, when carefully explored, under ether, are found to communicate with diseased bone. The minute opening leading to the bone-cavity may easily be over- looked, and in some cases is impossible to find, but tubercular abscesses in this locality almost invariably originate from bone disease. The opening of the cavity, as is customary with many surgeons, is not sufficient to effect a cure. Extensive dissection is sometimes needed to expose the tuberculous nodule, and the diseased tissue should be removed thoroughly either by the curette, the chisel, or the trephine, as the case may demand. It is only by such radical treatment as this that a cure can be effected. By the older methods of treatment these sinuses usu- ally lasted for years before healing, or the patient died of pul- monary tuberculosis. In many cases of tuberculosis of the rib a cure cannot be effected without resection of the diseased por- tion of the bone. The iodoform treatment, which is described in another chapter, is adapted to these cases, but it cannot be depended upon to effect a cure without operative interference. Among other flat bones that are affected are those of the pelvis. 528 SURGICAL PATHOLOGY AND THERAPEUTICS. The most frequent spot is the acetabulum, but the crests of the ilia and the sacro-iliac synchondrosis are also points whence cold abscesses may originate. Tuberculosis of the cranium is found chiefly in the frontal and temporal bone, always excepting the bones of the ear and the mastoid process. A mass of granula- tion tissue, with possibly a small sequestrum, is found at the site of the disease: in either case a perforation of the inner table and possibly a slight infection of the dura may take place. The disease manifests itself as a fluctuating tumor, which when opened dis- charges pus and discloses the pulsation of the brain beneath the dura. Syphilis — for which this disease may be mistaken — does not have so great a tendency to form abscesses, and it usually affects a much larger surface of the bone. That portion of the face most likely to be affected is the infra- orbital ridge. Disease in this locality occurs usually in children, although the writer has seen cases in adults. Suppuration occurs, and ectropion and unsightly scars may be the result of a chronic suppuration lasting for months. A case of tuberculosis of the malar bone caused an extensive suppuration which finally ended in ankylosis of the jaw, for which osteotomy was performed a year after the old sinuses had healed. Tuberculosis of the bones of the nose is usually secondary to disease of the mucous membrane elsewhere. It may also result from an extension of lupus of the alse or the septum into the nostril. Isolated patches of lupus are, however, seen in the nasal mucous membrane. It appears as exuberant granulations which at times have a typical papillary growth, or as an ulcer. The cartilag- inous portions of the nose are more frequently affected with the lupous type of tuberculosis. Riedel described large tuberculous tumors growing on the car- tilaginous septum in adults, and Koenig saw similar growths in children. Tuberculosis of the nose may also follow tuberculosis of the hard palate, the disease breaking through the floor of the nostril. In a case seen a year or two ago the mucous membrane of the anterior portion of the hard palate and the adjacent alveolar process was in a state of ulceration which had already extended into the nostril. Several members of the patient's family were tuberculous. The diseased portion of the bone was excised and a permanent cure was effected. The lower jaw is very rarely affected by this disease, and the same may be said of the clav- icle, although the sterno-clavicular articulation may be the seat of tubercular suppuration. XXV. SURGICAL TUBERCULOSIS OF JOINTS. There are two forms of tuberculous disease of joints. In the more common (or osteopathic) form the disease begins in the epiphyseal ends of the bones, as has already been described. The nodule eventually softens down, and, instead of breaking externally and forming an abscess, it finds its way into the joint, either through a fistulous opening or by gradual involvement of the articular car- tilages. In the second variety, the arthropathia the synovial mem- brane is the seat of the disease. In the first form there exists a preliminary or prodromal stage of joint disease during which the bone only is affected. The nature of this process, having already been described, need not be repeated here. As the inflammatory process approaches the artic- ular cavity it not infrequently occurs that a reactive inflammation of an entirely non-specific character is set up within the joint. The joint becomes swollen and tender, and it is filled with a serous exudation which may last for some time, and finally disappear (hydrops tuberculosus); or the synovial membrane may become infected and granular without showing any evidence of tubercular infection ; or a fine layer of vascular tissue may grow out over the cartilage, closely resembling the pannus growth of the cornea. This tissue may involve the lining membrane of the joint, and it may lead to adhesions and cicatricial contractions to such an extent as to obliterate nearly the whole cavity of the joint. In such an extreme case the severe symptoms of tuberculous inflammation do not make their appearance in the joint, but the tuberculous disease remains confined to the bone. It is often the case with the knee- joint that when the tuberculous nodule which has formed in the bones finally breaks into the joint a greater portion of the inner cavity is shut off by adhesion; consequently the articular surface of but one of the condyles may become affected with the disease. Such an obliterating synovitis may occur in the hip-joint, the result of which is that the head of the bone becomes sometimes ankylosed to the acetabulum. Such changes are not unlike those adhesive inflammations seen so frequently in the pleura, the peri- toneum, and in other serous cavities, and they seem to protect the 34 529 530 SURGICAL PATHOLOGY AND THERAPEUTICS. joint, to a certain extent, from the tuberculous infection with which it is threatened. This kind of inflammatory reaction is more often seen in the knee than in the hip; consequently suppu- ration with caries of the articular surfaces is less likely to occur in the knee. If, however, tuberculous material finds its way into a perfectly healthy joint, it is readily spread about by the movements of the limb into all parts of the synovial capsule, which soon becomes infected: this is well shown by Cheyne's experiments upon ani- mals. Tuberculosis of the joint of a goat was produced by injec- tion of tuberculous sputa directly into the synovial cavity, and also by boring a hole into one of the bones of the joint and introducing the same virus into the cavity thus made. Emulsion of tubercu- lous pus in distilled water was also injected into a joint with the same result. The same emulsion injected into the femoral artery produced an infarction in the tibia. Pure cultures injected into the knee-joints of rabbits yielded typical results in eleven cases out of twelve. The infection of the joint from bone occurs by the gradual spread of the tuberculous process through the connective tissue of the Haversian canals, and by gradual absorption of the bony trabecular, until finally the tubercular material breaks into the joint by a free opening in the articular surface or by the forma- tion of granulation tissue, which gradually dissects off the articu- lar cartilage. In other cases the deposit may reach the surface at the margin of the synovial membrane, which becomes thickened and shuts off the deposit for a time from the joint-cavity. This thickened patch subsequently becomes infiltrated with tubercles. When an osseous growth of tubercle has broken into a joint we know the disease is at first confined to the synovial membrane, and the tubercular layer can easily be scraped off without sac- rificing the ligaments of the joint. Therefore, when the dis- ease has not spread from this point, all that may be necessary is to remove the original nodule or sequestrum and a margin of synovial membrane without resecting the joint. If the tuberculous nodule communicates freely with the cavity of the joint, the infection of synovial membrane rapidly takes place. The masses of miliary tubercles run together at the point first infected, and thence spread gradually over the synovial mem- brane, which soon becomes infiltrated with the diseased tissue. In some cases the membrane retains its continuity, the surface is moist and smooth, and is studded with tubercle, which, however, does SURGICAL TUBERCULOSIS OF JOINTS. 531 not have a tendency to disorganize the membrane. When there is an exuberant growth of vascular tissue there may be an extensive formation of granulations, producing the so-called "fungous" type of joint disease. In still another form there is a tendency to the breaking down of the tubercular masses and to the formation of pus. This type is more frequently seen in elderly people, and the prognosis is usu- ally unfavorable. The membrane is readily perforated, and peri- articular abscesses are formed which may or may not communicate with the joint by a fistulous opening. As a result of the entrance of this large quantity of broken-down material into the joint the cartilage and the bones are generally left in a carious condition. Instead of pus there may occasionally be a turbid serum in the joint which may be slightly hemorrhagic. This tuberculous hydrops is, however, not very common. The bone type of joint disease is the commonest form of the two, and it is found chiefly in children, whereas the ordinary synovial tuberculosis is more frequently seen in adults. It seems somewhat to be a matter of chance whether the joint becomes infected with tubercle from the bone, or whether the broken-down products may not find their way to the surface without involving the joint. The cartilage is readily affected by the growth of granulation tissue into the joint, or by the presence of pus, owing to its feeble resist- ing power. The first change seen is the spread of a fibrous vas- cular tissue over the surface of the cartilage, the so-called ' ' pan- nus n growth, which becomes thinner and thinner in passing from the edge of the synovial membrane or from the opening of the tuberculous fistula. Subsequently the cartilage softens, loses its bluish-white color, and changes to a fibro-cartilage, and later to fibrous tissue, which finally becomes infiltrated with tubercle. When the tuberculous material breaks down the softened cartilage may be washed away, and the so-called ' ' ulceration of the cartilage ' ' is produced. At other times the growth of the tubercular granulations from the subjacent bone is so exuberant that the entire cartilage may be dissected off the head of the bone. This result is occasionally seen in the hip-joint, where the cartilage may be lifted off cap-like. In the primary synovial form of tubercular disease the tubercu- lous infiltration of the bone is usually comparatively superficial. A peculiar form of joint disease, described by Volkmann as caries sicca, occasionally attacks the shoulder-joint, but it may also be seen in other joints. It is characterized by a growth of scanty, 532 SURGICAL PATHOLOGY AND THERAPEUTICS. tough, and feebly vascular granulations from the synovial mem- brane, which growth penetrates the cartilage and gradually eats into and destroys large portions of the head of the bone without the formation of pus. There is often considerable atrophy of the remaining portions of the head and neck of the bone. The usual external signs of tuberculous disease of the bone are of course wanting. It is most frequently seen between the age of puberty and thirty years. It runs its course slowly over a period of one or two years, and terminates in ankylosis of the joint. Volkmann also described large isolated tubercular nodules (sometimes the size of a pigeon's ^gg) which project as a pedicu- lated tumor into the joint. The fibrous nodule is composed of dense tissue which contains but few miliary tubercles, or, again, it may contain numbers of tubercles which show a tendency to break down. The adjacent synovial membrane is at first unaffected, but later it is infiltrated with tubercle. Volkmann recommends for these cases extirpation of the nodule with temporary drainage of the joint. A rare form of polypoid growth in the joint is that con- taining adipose tissue. It may grow to considerable size, and the surface is usually studded with tubercle, which appears to occur secondarily. In some cases of tuberculous joint disease, particularly those in which there is a sero-fibrinous effusion, rice-bodies are found in large numbers. They appear to consist of coagulated fibrin and of fatty degenerated cells. They are not always associated with tuberculosis, but it is found in certain cases that the synovial mem- brane is infiltrated with tubercle. In many cases when the rice- bodies are first removed no tubercular disease is found, but the dis- ease may appear later. Their presence in the joint, therefore, is a suspicious circumstance. The exudation of fibrin which occurs with the formation of tubercle seems to be connected in some way with their growth. As in the sheaths of tendons, they may, how- ever, be independent of tubercular disease. They are usually found in joints which have still retained their motion. They may sometimes be felt in the lateral folds of a joint, and their presence may also be recognized by a peculiar crackling sensation like that produced in compressing snow. The changes in the soft parts connected with the joints are very striking in this disease. The capsules and the surrounding con- nective tissue, and even certain structures within the joint itself, are transformed into a gelatinous mass. So characteristic is this appearance that it was given the name "gelatinous disease of the SURGICAL TUBERCULOSIS OF JOINTS. 533 joint'' by Brodie. Even the muscles and tendons appear to be subject to this peculiar change. In a case the writer remembers seeing the muscular tissue of the entire lower third of the thigh was affected. In some joints the tendons are so matted together by this condition of the tissues that motion of the joint is seriously impaired. According to Krause, this gelatinous change is not tuberculous in character, but it is due to a venous stasis resulting from the increase in the contents of the joint-capsule and the extra-capsular growth. As the result of the consequent oedema, the mucin, which normally exists in the tissue, is dissolved. A similar development of mucous tissue occurs, according to Koster, in the development of a myxoma. There is found, however, a similar growth of gelatin- ous material around and in the sheaths of infected tendons when no such obstruction to the circulation exists, and it seems prob- able, therefore, that the peculiar formation seen so rarely in other forms of disease, and so characteristic of tuberculosis of the joint, must be the result of chemical changes brought about directly by the presence of the bacilli in the surrounding tissues. The inflammatory reaction may extend from the original nodule to the periosteum, and it may produce an abundant growth of osteophytes which mark the limits of the cari- ous ulceration of the bone. This bony growth is analogous to the callous edges so often seen in chronic ulcerations of the skin in the lower extremities. (Fig. 81). Among the numerous patholog- ical changes brought about during the course of the disease are those due to pressure caused by the spas- modic contraction of the muscles. This contraction, which is due to reflex irritation of the nerves, fur- nishes one of the most marked clinical symptoms of the disease. In this way the ulceration of the cartilage is greatly increased, and even the carious bone is absorbed, and the spread of the tubercular process is favored by the pressure. By this muscular action not only great deformities of the spine are brought about, but joints are also dislocated and great deformity is produced. FIg. 81. — Tuberculosis of the End of the Humerus, showing caries of the articu- lar surface and osteophytes due to inflam- mation of the periosteum (Sp. 1399, War- ren Museum). 534 SURGICAL PATHOLOGY AXD THERAPEUTICS. When the disease takes a favorable turn, cure may be brought about by the absorption of the tubercular tissue and its replace- ment by healthy granulation tissue. Cicatricial contraction occurs also in the inflamed periarticular tissues. This contraction brings about an impairment of motion which may amount to false anky- losis. In many cases where the anatomical structure of the joint is fairly well preserved there is a diminution in the area of the articular cavity by the formation of adhesions and the obliteration of some of the synovial pouches. When ossification of the cica- tricial tissue occurs, true ankylosis results. In the bones the tuberculous masses — even the sequestra — may be absorbed and be replaced by healthy bony tissue. Cheesy foci, however, mav remain for years unabsorbed without showing signs of their presence. These foci are often discovered during operations for correcting deformity. Such a condition shows the possibility of a recurrence of the disease long after the patient is supposed to have been cured. It should be said, however, that these nodules tend to remain local in the majority of cases, and that it is only after an unsuccessful surgical operation that general miliary tuberculosis is more likely to result. Disturbances in the normal growth of the bone may be produced by the irregular pres- sure which is often exerted in a diseased joint. In the so-called " dislocation of the knee-joint backward n the anterior portion of the condyles of the femur may develop more rapidly than the pos- terior portions. The reduction of such subluxations is prevented by the lateral ligaments, which are insufficiently long to permit the tibia being placed beneath the condyles. A rare occurrence is an actual elongation of the shaft of the bone, due to chronic inflammatory irritation. Atrophy of the bone is much commoner. The fatty tissue in the cancellated spaces of the bone is increased in quantity, the trabecular become thinner, and the amount of medullary tissue in the epiphyses and shaft is increased, while the cortical bone is much thinner than usual. Not only is there rarefying ostitis in the interior of the bone, but its dimensions mav also be diminished, the bone being shorter and thinner than its fellow. With the return of the natural physiolog- ical action the bone regains its normal strength and density, but it will probably never be quite so large as it would have been if atrophy had not occurred before it reached its full growth. If the epiphyseal line is prematurely destroyed, the growth of the bone will be arrested, and then the future use of the limb will seriously be impaired. SURGICAL TUBERCULOSIS OF JO/NTS. 535 Some of the peculiarities of the disease in individual joints may now be studied. In the hip-joint, in the greater number of cases, the disease is found originally in the bone, but, according to Cheyne, it does not so extensively occur there as authors are disposed to think. At all events, a large number of cases are examples of primary disease of the synovial membrane. The tubercular deposits more frequently occur in the acetabulum than in the femur. In the latter case they are seen in the head as well as in the neck, and even in the trochanter. The farther they are removed from the joint the less likely are they to involve it. When this cavity becomes affected the disease spreads from the point of reflection of the synovial membrane and from the ligamentum teres over the cartilage. The granulations are filled with miliary tubercles, and they lie on the surface of the synovial membrane or they infiltrate its substance. The fluid in the joint is only slightly increased and altered; it is somewhat turbid and is streaked with pus or with blood. At times the fluid may be distinctly purulent. The ligamentum teres as the disease advances is attacked, and it becomes softened to a pulp. The bone becomes involved first at the edge of the fold of the synovial membrane. The tubercles multiply in the super- ficial layers of the bone, and they dissect off the cartilage at several points, giving the latter a sieve-like appearance. The same process goes on in the acetabulum, and in well-marked cases of the dis- ease the femoral and acetabular cartilages may lie completely sepa- rated between the ends of the bones. Before separation, the cartilage may already have ulcerated in several places, particularly where the head of the bone and the acetabulum press against each other: the effect of this pressure is to increase the amount of ulceration of the bone, and consequently the acetabulum may become enlarged bv caries at this portion of its circumference. In the mean time the capsule of the joint is perforated and periarticular abscesses are formed. These abscesses may develop without perforation of the joint, but such abscesses are comparatively rare. In later stages of the disease the tubercular process, after destroying the liga- mentum teres, attacks its point of insertion in the acetabulum, and, the bone being gradually eaten away, an accumulation of pus may form within the pelvis. This complication, however, is infrequent. The pus in different cases varies greatly in amount, but in the primary synovial form of the disease it is always certain to be found. In caries sicca pus is not formed, but this type of the disease rarely attacks the hip-joint. 53 6 SURGICAL PATHOLOGY AND THERAPEUTICS. In the later stages of the disease the joint looks about the same whether it was originally attacked by the synovial or the osseous form of the disease. At this time absorption of the bone has taken place. The head of the femur is partly destroyed by caries, and its bony structure is so softened by rarefying ostitis that when pressed against the acetabulum more or less absorption of the bone occurs. This process is described by Volkmann as "ulcerating decubitus." There is also, from the same cause, an enlargement in the diameter of the acetabulum, due to pressure of the head of the femur after the protecting cartilage has been destroyed. As this pressure occurs with the limb in a state of adduction and flexion, the enlargement of the cavity takes place chiefly in the posterior and upper margins of the acetabulum. This condition is known as the wandering acetabulum. As the head of the femur is also greatly atrophied, its displacement from the original portion is therefore considerable, and the resemblance to a dislocation is consequently very close. This displacement in many cases is a cause of shortening of the limb. In other cases the capsule and the ligaments, owing to the distention of the joint by fluid and to the relaxation of the liga- ments, are unable to withstand the action of the muscles, and the head of the bone is forced completely out of the socket, or it rests upon the edge of the socket so that a deep groove is worn in its articular surface. The displacements occur very gradually; the relaxed ligaments permit motion in various directions; the joint "wabbles," and a slight accident may therefore result in a sud- den dislocation of the bone. The amount of destruction of bone tissue is sometimes enor- mous. The head and neck, and even a portion of the shaft, of the femur may be destroyed. In such cases the shortening and dis- placement of the limb are so great as seriously to impair its use- fulness. After the disease has once fully developed there is little probability of a cure without ankylosis, as the structures of the joint have been destroyed before the tubercular virus has been thoroughly eliminated by suppuration. In some of these cases tubercular nodules may remain unabsorbed after the disease is supposed to have been cured. Bradford reports tetanus occurring in a case of cured hip disease, and at the autopsy there was found a large tubercular focus, which was the only source to which the tetanus could be assigned. In the knee-joint at the period of life when the disease is most common — namely, in childhood — the origin of the disease is as frequent in the bone as in the synovial membrane: as age advances SURGICAL TUBERCULOSIS OF JOINTS. 537 the bony form is more common, and the frequency of sequestra in old people makes the disease more obstinate (Cheyne). In old peo- ple wedge-shaped sequestra are often seen after injuries. When tubercular nodules are found in the bones the internal condyle of the femur is the point most frequently attacked, but these nodules are often found also in the epiphysis of the tibia. Tumor albiis, or white swelling — which term is applied chiefly to disease in the knee-joint — is due to the formation of granulation tissue in the joint, to the gelatinous change in the tissue about the joint, and to the enlargement of the ends of the bone. The simultaneous atrophy of the muscles of the limb serves to make the swelling more prominent. The whiteness of the skin is due to the absence of all inflammation in the integuments in the early stages of the disease. The development of tumor albus is ascribed by Roser to the frequent use of the knee-joint by a patient who has not yet received treatment. He thinks the thickening of the para- articular tissue is due to the irritation brought about by frequent motion. The minute tuberculous changes which occur in the joint have already been sufficiently described. In no joint can the spread of the tubercular tissue and its destructive effect upon the cartilages be better observed than in the knee. Occasionally the amount of pus formed is considerable, and, as it may not perforate the capsule, it distends the joint, giving a sense of fluctuation like that of hydrops. This condition has been called "cold abscess of the joint." It is not, however, a frequent complication. On opening a joint in well-advanced stages of the disease there is found more disease than might be supposed to exist from the clinical symp- toms. The ulceration of the cartilages is well advanced and the synovial membrane is infiltrated with tubercle. Several periartic- ular abscesses are usually disclosed by the incision, and they may or may not communicate with the joint. It is rare to find a case where there is not considerable disease also of the bone. In the early stage of the disease there is flexion of the knee- joint from muscular contraction. This flexion brings the head of the tibia in contact with the posterior aspect of the condyles of the femur. The pressure of the bones favors ulcerative decubitus of the cartilage and bone at these points. As the result of the absorp- tion of the bone, which is thus brought about, the head of the tibia slips backward over the femur. This displacement is of course favored by the relaxation of the diseased capsule: it is not caused wholly by muscular contraction, but is due in part to the cicatri- cial contraction of the diseased and atrophied tissues behind the 53$ SURGICAL PATHOLOGY AND THERAPEUTICS, joint. In addition to flexion there is also a certain amount of external rotation of the leg upon the thigh, which rotation appears to be produced by the position of the contracted limb upon the bed. The shoulder-joint is not a very frequent seat of tuberculosis ; when the latter does occur, it is found chiefly in adult life. Pri- mary synovial disease of the shoulder-joint is rare. In fungous tuberculosis of the joint with suppuration there is generally found a primary deposit in the end of the humerus. The greater tuberos- ity is the most frequent seat of such a nodule, but the head of the bone may also be affected. Disease of the neck of the scapula is uncommon. The wedge-shaped infarction is a type of the disease not infre- quently found in the head of the humerus. These nodules may remain some time without causing suppuration. Krause reports a case of a man, forty years of age, who suffered from rheumatic pains in the left shoulder. The pain had been so severe that he had been unable for three months to use his shoulder, in the external appear- ance of which there was little change be3*ond a slight emaciation. There was, however, marked pain on pressure over the lesser tuberosity. An exploratory incision disclosed a large tuberculous nodule in the head of the bone, which was accordingly resected. As the disease progresses the localized pain becomes more marked and the patient instinctively holds the arm at rest; the contour of the joint becomes enlarged, and the natural depressions in front and behind the joint disappear. Large cold abscesses may accom- pany the disease in its later stages. They follow the route of the intermuscular spaces. The most interesting form of disease of the shoulder-joint is caries sicca, which has already been described. The small amount of granulation tissue which develops at any one time and the chronic course of the infection are peculiarities that cause the dis- ease to pass unrecognized. There is great atrophy of the muscular surroundings of the joint, and the head of the bone gradually sinks away and disappears. There is no suppurative inflammation, and, in fact, no sign of inflammatory change. The shoulder is stiff and the arm is held close to the side. The pain is usually severe and radiates down the arm, it being often mistaken for rheumatism. The deltoid prominence disappears and the coracoid process be- comes unusually prominent, the condition sometimes closely resem- bling a dislocation. The writer has seen several of these cases, mostly in young children, and they usually terminate in bony ankylosis. SI r RGR \ 1 1. Tl r BERC '( 7. ( )S/S ( >F J( )INTS. 539 Tuberculosis of the elbow-joint may occur spontaneously or as the result of slight injuries, particularly in children. According to Billroth's statistics, of 1996 cases of caries of the boues, there were 93 cases of disease of the elbow and 239 cases of disease of the knee-joint; in 198 cases the hip, in 150 cases the ankle, in 41 cases the wrist, and in 28 cases the shoulder, were affected. Accord- ing to Billroth, disease of the elbow holds the fourth place in point of frequency. The disease more frequently begins in the bone, a favorite spot being the spongy tissue of the olecranon. Volkmann describes such a case where pus was discharged both into the joint and externally. The removal of the sequestrum, with thorough curet- ting of the bone, was followed by a restoration of the functions of the joint. Nodules may also develop in the epiphysis of the humerus, but they rarely occur in the radius. In certain cases the synovial membrane may first be affected, and the bones will be attacked when the disease spreads to the point of insertion of the membrane in the articular ends of the bone. Suppuration is usu- ally slight. When the bones are affected the presence of the nodule will be indicated by localized pain and by some enlargement of the bone. If the synovial membrane is first attacked, an elastic swelling usually shows itself between the head of the radius and the olecra- non. The movements of the joint are impaired early, as indicated by inability to extend fully the arm. As the joint gradually becomes disorganized the surrounding tissues are swollen, and they undergo the characteristic gelatinous changes, and in extreme cases there is a well-marked tumor albus with the spindle-shaped swelling. As pus forms numerous sinuses open, and the tuberculosis may eventually extend even to the skin. In old persons and in those who have been treated unsuccessfully by some operative procedure the disease of the soft parts may be- come very extensive, necessitating amputation. The prognosis in tubercular disease of the elbow is not favorable for the re-establishment of motion unless the affection is treated at a very early stage. This joint is so complicated that the disease involves a large and a comparatively widespread surface of synovial membrane before its presence is discovered (Bradford). In studying the clinical symptoms the point of origin in the bones must be sought for chiefly in the early stages of the disease. The period during which the morbid process remains confined to the bone is often a long one. In some rare cases several years may elapse before the disease advances beyond this stage. It will read- 54-0 SURGICAL PATHOLOGY AND THERAPEUTICS. ily be seen that the beginning of the affection is very gradual and insidious. The patient experiences an inability to use the joint, and there is some slight stiffness. If one of the joints of the lower extremity is affected, there will be slight lameness. If it is a super- ficial joint, such as the knee- or the elbow-joint, there may be slight swelling of some portion of the bone, pressure upon which gives rise to pain. As these nodules enlarge pus may form and a frag- ment of the bone with pus may be discharged. The adjacent joint may at this time suffer from non-tubercular synovitis due to its proximity to the tubercular inflammation. As the result of such changes there is an enlargement of the joint. The anatomical outlines disappear and the joint may assume a more or less spindle shape. The veins are more or less injected, and the skin becomes somewhat thin and shiny like the top of a bald head (Krause). The enlargement of the joint is emphasized by atrophy of the muscle. In tumor albus of the knee the muscles of the thieh and the calf are affected in this way. The adipose tissue is largely absorbed, and even the skin in some cases seems thinner than normal. Meas- urements of the limb will show a diminution in its circumference at an early stage. In the later stages of the disease the muscle may undergo degeneration and absorption of the contractile sub- stance. Muscular fixation is a symptom of nearly all forms of tubercular joint disease. The joint is usually flexed or adducted, and is more or less rigidly held in that position. This abnormal position of the joint has been attributed to distention with fluids, it being supposed that the flexed position gives the most room for fluid; but the flex- ion is undoubtedly due to muscular spasm from reflex irritation. In hip disease spasm is one of the earliest symptoms, and it has been said that there can be no disease present if there is no limita- tion in the motion of the joint. When the joint is more or less disorganized this contraction of the muscles may lead, as has been seen, to subluxation. Pain is a prominent symptom of joint disease, although occa- sionally it may entirely be wanting. Reference has already been made to rheumatic pains accompanying caries sicca in the shoulder- joint, there being frequently a painful point anterior and external to the coracoid process. In hip disease the pain is almost invariably situated in the knee, and there is great sensitiveness to jarring of the limb. There is an unconscious protection of the joint in the movements of the patient. The reference of pain to the knee is attributed by Bradford and others to the intimate relations and an- SURGICAL TUBERCULOSIS OF JO/NTS. 541 astomoses of the sciatic, obturator, and anterior crural nerves. According to Sayre, the pain is the result of the struggle between the adductor muscles and the distended capsule. The so-called 41 night-cries " which occur in the early stages of hip disease, and more rarely in knee-joint disease, are described by patients as caused by an extremely sharp and severe pain suddenly inter- rupting sleep, and leaving an ill-defined sense of aching in the thigh and hip as if the hip had sustained a blow. The next important point of tenderness on pressure lies in the groin just external to the femoral vessels. Tenderness is detected in the knee on the inner surface of the head of the tibia. Pain is not, however, severe in the knee except in acute exacerba- tions. The anterior and lateral portions of the ankle-joint are the tenderest spots. Pain on pressure is felt at the elbow-joint over the head of the radius and the neighboring part of the capsule. Pain in Pott's disease is generally referred to the back of the head, the shoulders, the chest, and the abdomen. In the latter case the child usually complains of " stomach-ache." Tenderness on pressure over the spine is not a symptom of this disease. Heat is a symptom that can be relied upon in certain stages of disease or in certain joints. In the knee when the disease is well developed heat is usually present, especially if any exacerbation takes place. There is usually little if any febrile disturbance during the early stages of the disease and while it is confined to the bone or joint. Even when a cold abscess is present the rise of temperature is only slight, varying from 1 to 2° F. Fever may occur, however, if pul- monary tuberculosis supervenes or if there is tuberculosis of the intestinal canal or basilar meningitis. In cases of miliary tubercu- losis there may be considerable fever, and it may be of the con- tinued type. There is great exacerbation of both local and consti- tutional symptoms when a cold abscess breaks. The joint swells, the skin is reddened, and the discharge assumes the character of a phlegmonous suppuration. There is high fever, and generally there is increased emaciation. These changes are due to a mixed infection with pyogenic cocci. Eventually this fever is of the hectic type, consisting of an evening rise of temperature, with a return to the normal in the morning. Pronounced anaemia is regarded by some as an unfavorable symptom in different forms of tuberculosis, as it is an indication that generalization of the tuberculous virus has taken place. Cure may take place spontaneously even in most aggravated 542 SURGICAL PATHOLOGY AND THERAPEUTICS. cases, but generally with ankylosis or deformity. Even abscesses of considerable size may be absorbed. A fair amount of motion often remains in some joints after recovery, a portion only of the joint having been destroyed by the disease. It is not uncommon for relapses to occur several years after apparent cure has taken place, the new infection being derived from the cheesy material remaining imprisoned in the cicatricial tissue. In unfavorable cases there is apt to be found albuminuria, which is usually caused by the presence of amyloid degeneration of the kidneys. These changes are probably brought about by chemical substances which are taken up into the lymphatic sys- tem, and occasionally the lymphatic glands are seen thus affected. Although the statement is made that such degeneration perma- nently destroys the function of tissues or the organs thus affected, it is possible that after cure of the joint has taken place the amyloid degeneration may disappear. In a case of tuberculosis of the neck and trochanter of the femur of several years' duration, followed by purulent synovitis of the knee-joint, there was evi- dence of an amyloid degeneration of the kidneys and spleen and some enlargement of the liver, the signs of which degeneration disappeared after a successful amputation of the hip-joint. Pulmo- nary tuberculosis may occur as a complication, particularly in con- nection with caries of the carpus. Children are more likely to be affected with miliary tuberculosis in unfavorable cases, especially after operations have been performed. From what has been said about the pathology of tuberculosis of bones and joints it will be gathered that all the affections hitherto known as caries of the joints, scrofulous disease, gelatin- ous disease, fungous or strumous affections, spina ventosa, etc. are, almost without exception, forms of tuberculosis. As the cachectic condition marked by anaemia, emaciation, and hectic fever does not develop until the later stages of the disease, the student must not be led into supposing that a good general condition of the patient precludes the diagnosis of tubercular disease; for a nodule may remain for a long time concealed in the cancellated tissue of the bone without producing any constitutional disturbance what- ever. There are a number of other forms of infectious bone dis- ease, which, however, begin, as a rule, as acute infections, and which subsequently become chronic. The most frequent of these infections is acute osteomyelitis, which may often lead to suppura- tion of the joint and to destruction of the articular cartilage. This affection begins as a very acute inflammation of the bone, and fre- SURGICAL TUBERCULOSIS OF JOINTS. 543 quently with profound constitutional disturbance. After necrosis has taken place and the abscess has broken and fistulous openings have formed, the acute stage passes away and the patient is left with chronic suppuration of the bone. This condition is, however, read- ily distinguished from tuberculosis, as the inflammation involves the shaft of the bone instead of the epiphysis. The previous his- tory of the case and the presence in the shaft of a large sequestrum which has the shape of the original bone will enable one to make the diagnosis of osteomyelitis in most cases. The appearance of the fistulous openings will also be a guide, for in this form of bone disease the tubercular granulations are absent. In those rarer forms of osteomyelitis found in the epiphyses of the bones the difficulty of diagnosis is greater. An effort should be made in such cases to demonstrate the presence of tubercle bacilli, although their absence will not definitely settle the point, as they are difficult to find even in well-marked types of osseous tuberculosis. The tubercular sequestra are, as a rule, smaller and more irregular and are filled with cheesy material. Many forms of syphilis of the bones are not readily distinguished from tuberculous disease. There is not the same tendency to suppuration in syphilis, and the disease usually affects certain localities. Syphilitic caries of the bones of the cra- nium is usually very extensive, and it often runs its course without suppuration. It is so typical a form of the disease that when once seen it is not likely to be mistaken for anything else. There is sometimes a tendency to the formation of sequestra. The writer has seen extensive disease of this kind in the frontal bone, but in such cases the history points so distinctly to a syphilitic origin that a mistake in diagnosis is not likely to be made. When sup- puration does take place the pyogenic membrane is tough, and it cannot be scraped off the subjacent tissue, whereas in tuberculosis the membrane is removed with great ease. A syphilitic gumma may sometimes form in the capsule, and may closely resemble an isolated tubercular nodule. These cases will of course yield to treatment with iodide of potassium. Metastatic inflammations of the joints occasionally occur as complications of acute exanthemata, a portion of which inflam- mations are the result of septic or pysemic infection, and a cer- tain number of them are cases of tuberculous infection which has developed during the favorable conditions offered by the diseased state of the system. Volkmann suggests that some of them may- be due to the action of the virus of the exanthema. Serous effusion into the knee-joint, hydrops articnli, or " water 544 SURGICAL PATHOLOGY AND THERAPEUTICS. on the knee," occasionally assumes a type which may suggest the possibility of tuberculosis. There is, in such cases, a so-called "arthritic atrophy" of the muscles, with impairment of the nutrition of the limb that is suggestive of organic disease. A careful examination, however, will clearly show the true state of affairs. The "fluctuation" of the patella, the absence of pain on pressure or of grating of the joint or of any infiltration of the soft parts, are sufficiently characteristic symptoms of this affection. Neuralgic or hysterical joints often disable persons who have sustained a slight injury, and they cause much anxiety. An examination in these cases shows an absence of all pathological changes. The shifting character of the pain and the presence of nervous or hysterical symptoms will aid in the diagnosis. Such symptoms yield readily to massage. Arthritis deformans occurs chiefly in elderly people. The cha- racteristic changes in the bone are so pronounced that a mistake in diagnosis is not likely to be made. The changes in the soft parts are much less marked than in tuberculosis. Periosteal sarcoma may sometimes be mistaken for tubercular disease. The writer has opened a supposed tuberculous knee-joint to find sarcoma of the femur. Myeloid sarcomata are usually found in well-recognized spots, such as the head of the tibia, or more rarely in the condyles of the femur and in the carpal extremity of the radius. In the advanced stage of tuberculosis the disorganization of the cartilages or the capsule enables one to obtain crepitus by free lateral rubbing of the articular surfaces against one another. Even when crepitus cannot be obtained the abnormal mobility of the joint is a suggestive symptom. The prognosis of these diseases is far more favorable in children than in adults, and in estimating the value of any special mode of treatment it is important to bear this fact in mind. It should not be forgotten also that the severest types of bone-and-joint disease may heal spontaneously, as the conditions for limiting and subse- quently for absorbing the tuberculous foci are more favorable in bone than in the internal organs; as, for instance, the lungs. In the former case the disease is shut in at first by a dense wall of bone or by the tough envelope of a joint capsule; in the latter case the infective products of the disease spread over the mucous mem- branes for a long distance before they are expelled, and in this way the disease is readily generalized. This localization is more marked in children. A diffuse suppuration of the carpus or of the tarsus SURGICAL TUBERCULOSIS OF JOINTS. 545 is rare at this period of life, and a minor operation usually suffices for the cure of the affection. Caries of the wrist in adults is almost always followed by pulmonary tuberculosis. Resection of the ankle- joint for the disease in adult life is generally considered a useless operation, and amputation is practically the only resource in tuber- culosis of the carpus and tarsus at this age. The statistics of this disease do not show a very large percent- age of cures. Billroth estimates the mortality of cases observed by him during a period of sixteen years to be 27 per cent. ; Koenig records a mortality of 16 per cent, in 177 operations extending over a period of four years. Even if a local tuberculosis is successfully removed, it does not prevent the possibility of a later infection of the lungs or other organs, as the susceptibility of the individual still exists. It will remove, however, the danger of miliary tuber- culosis starting from this point. A local return shows that the operation has not thoroughly been performed. It is important to remember that even when the original focus has been removed the secondary abscesses and sinuses, if allowed to remain, are equally a great source of danger. In adults these secondary complications are even more dangerous than the original affection. The difference in the prognosis in the diseases of different joints is very great. The destructive processes which proceed in the hip- joint are more extensive and are more likely to be followed by sup- puration than those that take place in the knee, where a tendency to cicatrization often sets in early. In the most favorable cases it is unsafe to promise a cure in less than two or three years, and it should be borne in mind that there is always danger of a relapse even after several years of health. The constitutional treatment of tuberculous disease of the bones and joints differs little from that employed for other forms of tuber- culous disease. The great majority of the patients afflicted with this form of tuberculosis are unable to avail themselves fully of one important feature of the treatment, which consists in the selection of a suitable climate or of suitable surroundings. In European countries great importance is attached to a sea climate, many of the largest cities being situated in the interior of the continent. The important point to be obtained in most cases is a liberal supply of healthful air. A country life is therefore, as a rule, most favorable for a tuberculous patient, particularly a child, if the patient is not thereby deprived of too many home comforts. A liberal supply of fresh milk and eggs is one of the 35 54 6 SURGICAL PATHOLOGY AND THERAPEUTICS. principal points to be insisted upon in the diet. Among drugs cod-liver oil takes the first rank; the refined preparations of to- day have deprived this drug of many of its obnoxious qualities. It is well to advise the pure oil, to be obtained from as reliable a source as possible, and to enjoin the greatest care and cleanli- ness in the preservation of the bottle and cork and of every arti- cle used in its administration. In this way it may be adminis- tered in moderate doses for a long time without disturbing the digestion: one to two drachms for a child and three for an adult are usually sufficiently large doses. Preparations of phosphate of lime are supposed to favor bone-repair. Whether this sup- position be true or not, they serve as exceedingly valuable tonics in this disease. The syrup of the lactophosphate of lime may be administered in teaspoonful doses to children, and it is a preparation which they all like. The compound syrup of the hypophosphites, containing potassium, sodium, iron, manganese, quinine, and nux vomica, is equally useful for adults: it may also be given in drachm doses. Preparations of iron are indi- cated when in the more advanced stages anaemia begins to make its appearance, the syrup of the iodide of iron being considered one of the best. When amyloid degeneration of the kidneys and albuminuria make their appearance the administration of iodide of potassium internally is said to be of great benefit, the amount of albumin diminishing markedly during the use of the drug (Krause). One of the earliest forms of local treatment to be applied to a joint is fixation, which should be employed during the acute stage when the tubercular process is exciting surrounding inflammatory reaction. In this way inflammation is not aggravated, and many of its symptoms, such as pain and swelling, are immediately relieved. This alleviation can be accomplished in most joints by the use of the stiff bandage, which also possesses the great advan- tage of exerting gentle and continuous compression. Compression is a most effective agent in producing absorption, and it is particu- larly valuable during the granulating stage of the disease and before suppuration is established. The use of the stiff bandage on the knee-joint may sometimes be continued through a series of years with the most satisfactory results. At first a thin layer of plaster of Paris may be used, with a coating of silicate of potash or of dextrin. But later in the treatment a light dextrin or a silicate bandage may be applied and be renewed two or three times a year, and in this way the compression can be kept up over a long period SURGICAL TUBERCULOSIS OF JOINTS. 547 of time. This treatment is more applicable to the knee than any other joint, but it is employed also in disease of the hip, the ankle, and the wrist, and more rarely in disease in the elbow; in the shonlder-joint it can be of little use. The advantages of the plas- ter jacket in Pott's disease are great, and its cheapness makes it a useful substitute for apparatus when expense is a matter to be considered. Another important element in the treatment of joint disease is extension, which is employed to overcome the spasmodic action of the muscles by which the pressure of the inflamed bones upon one another is increased. This increase of pressure not only favors the spread of the tuberculous disease, but produces in many cases also, as has already been seen, an absorption of the bone (ulcerative de- cubitus), which adds greatly to the deformity. Extension at one time was supposed to separate the diseased bones, but experiment has shown that the actual separation that occurs is but slight and under conditions which do not exist clinically. This mode of treatment is more applicable to the hip and knee than to any other joints, and it prevents or corrects flexion or abduction or subluxa- tion, besides relieving many of the symptoms of inflammation. Those forms of extension apparatus which oblige the patient to lie in bed are suitable only when the symptoms partake of an acute type, but for the more chronic forms the traction splints, such as have been devised by Sayre and Taylor, are to be preferred, as they permit locomotion. In the later stages of the disease, particularly of the hip and knee, traction may be replaced by protection. Protection is obtained by the use of crutches and by a high sole on the opposite foot, so that the diseased limb may swing clear of the ground during locomotion, or by means of the so-called " peri- neal crutch," an apparatus which may be worn beneath the cloth- ing for the support of the limb. The support should be continued for a considerable space of time after all active symptoms have dis- appeared. The malposition occurring in the knee-joint must be overcome by extension or by forcible reduction by flexion. If the joint does not yield to extension by weight-and-pulley in bed, the patient should be etherized and sufficient force be exerted to straighten the limb. Occasionally there will have been so much muscular con- traction that many of the tendons near the popliteal space must be divided before the limb can be straightened. After straightening has been accomplished it is advisable to keep the limb in a stiff bandage or in some form of apparatus to prevent a return of the 54 8 SURGICAL PATHOLOGY AND THERAPEUTICS. deformity. Bony ankylosis in an unfavorable position can be relieved only by osteotomy. Malposition from ankylosis occurs occasionally in hip disease, but an excellent result may be ob- tained by cutting the femur just below the trochanters or through the neck, thus making it possible to straighten the limb. In the knee-joint the patella is occasionally ankylosed to the femur. If the patella offers an obstacle to the correction of a deformity, it may be separated from its attachment to the bone by the chisel. The treatment of cold abscess has varied greatly during recent years. When the antiseptic treatment was introduced, some of its most beneficial effects were supposed to be illustrated in the treat- ment of this affection. iVlthough septic infection with pyogenic bacteria was thus prevented, no effect was produced on the tuber- cular process, and the abscess was simply converted into a tubercu- lar sinus. A great step in advance was made when the tubercular nature of the pyogenic membrane was recognized. The method was then adopted of scraping away the membrane after laying open the abscess by a free incision. But the difficulty remained of not always being able to reach all the folds of the abscess-cavity, and small sinuses leading to concealed foci of disease were often over- looked; consequently the source of the whole trouble would remain untreated. The healing properties of iodoform in the treatment of tubercle having long been recognized, a method was finally devised whereby this drug could be brought in contact with all the ramifications of such a pus-cavity. Among the first to introduce this method were Billroth and Mikulicz. The following is Krause's description of the method: The abscess is first tapped under antiseptic precautions. It is best to use a good-sized trocar, so that clots of cheesy material and fragments of abscess-membrane can be removed readily through it. The cavity is then thoroughly irrigated with a 3 per cent, solution of boracic acid, and the iodoform preparation is injected. Solu- tions of iodoform in ether or in alcohol are more readily absorbed, but they may cause poisoning, and they have the disadvantage of leaving but a small quantity of the iodoform in the cavity. Krause objects also to iodoform oil on the same grounds. He uses a 10 per cent, solution — or, rather, suspension — of iodoform in glycerin. Another preparation is a 10 per cent, suspension of iodoform in water with 20 per cent, glycerin, 5 per cent, gum-arabic, and 1 per cent, carbolic acid. The finely-powdered iodoform is rubbed up with a few drops of glycerin, and is gradually added to the mix- SURGICAL TUBERCULOSIS OF JOINTS. 549 ture, which must be well shaken before using. When properly prepared it can easily be injected with a hypodermic needle. As this drug is only in suspension, it is not absorbed, and it remains in contact with the pyogenic membrane. A gradual absorption does of course take place, but not with sufficient rapidity to cause poisoning. It is well to act with caution in cachectic subjects. For adults about 3 ounces of such a mixture may be introduced. Smaller doses are, however, more frequently used. The abscess- walls should be so manipulated as to bring the mixture in contact with all the folds of the membrane. It is not usually necessary to put a stitch in the puncture wound, a light dressing being all that is needed. If the trocar is plugged with cheesy clots, an incision may be necessary, which must of course be sewed up before the injection is made. After the first injection the swelling subsides, and in some cases it disappears entirely in a few weeks. Two or three injections are, however, usually necessary at intervals of a few weeks. If the abscess refills, it must be washed out again with boracic acid. In this case several months may elapse before a cure is effected. At the second puncture the discharge through the canula is of a more mucous character and of a darker color, and it is mixed with par- ticles of iodoform powder. Later the fluid becomes clear and ropy, containing under the microscope round cells in a state of fatty degeneration. Occasionally a fistula forms which discharges a sim- ilar fluid, sometimes in considerable quantity, but the healing pro- cess does not appear to be disturbed. Iodoform appears to cause a breaking down of the tuberculous tissue, which is then thrown off. If fragments of the wall of such abscesses are examined microscopically from time to time, it will be found that the bacilli have disappeared soon after the beginning of the treatment. The tubercles are seen infiltrated with round cells and serous exudation, and many of the cells of the tubercle are in a state of fatty degeneration. The subjacent fibrous layer throws out granulations which destroy and throw off the tubercu- lar membrane. When all the broken-down material has disap- peared the granulations cicatrize and the abscess heals. In tuberculous joints the same treatment may be carried out. If there is pus in the joint, the treatment is the same as for abscess, a smaller quantity of the mixture being used: about an ounce is suf- ficient. A trocar about 2 mm. in diameter is better than a hypo- dermic needle. Passive motion may be employed to spread the mix- ture through the joint. It has no bad effect upon healthy cartilage. 55° SURGICAL PATHOLOGY AND THERAPEUTICS. In the wrist the best point to select for puncture is just below the styloid process of the radius and ulna. In the elbow-joint the head of the radius is considered the most available spot. In the shoulder-joint the trocar may be introduced externally to the cora- coid process, just outside the spot where the spine of the scapula becomes continuous with the acromion. In injecting the hip-joint along trocar should be used; the limb should be extended, slightly adducted, and rotated inwardly. The instrument, which is inserted just above the trochanter major, should be pushed until it comes in contact with the head of the bone. In tapping the knee-joint care must be taken to insert the instrument beneath the patella. In the ankle-joint the point to enter is under the tip of either malleolus. Anaesthesia is usually unnecessary, but a i or a 2 per cent, solution of cocaine may be used for the skin. A slight rise of temperature occurs for one or two days after the injection, but it is of no patho- logical significance. Three injections performed at intervals of about four weeks are usually necessary. There is considerable relief of pain after the first injection, but the swelling does not subside with rapidity. The tissues become, however, somewhat firmer in favorable cases. If there is pus in the joint, it generally returns after the first injection, but after the third or fourth injec- tion it disappears. The restoration of motion to the joint will depend upon the amount of change which has already taken place, but cases of complete return of the normal movements are reported. This mode of treatment appears best suited to young people and children, though adult life does not constitute a contraindication. The treatment is well adapted to tuberculous wrists, even when pulmonary disease is present. The method should be tried even in severe cases before resorting to operation. It may be tried in cases of primary epiphyseal disease as well as in tuberculosis of the synovial membrane. It should always be employed in cases of suppurating bone disease so situated that the bone cannot easily be reached by the operator. If, however, the bone can readily be reached through the abscess, an operation is to be preferred, for in this way the surgeon is in a position to leave the parts in a condi- tion favorable for permanent cure. Balsam of Peru has largely been used in the same way, but not with such brilliant results. Billroth lately adopted a combination of the old method of scraping an abscess and the iodoform-glycerin treatment. The abscess is first laid open by a long incision, and the lining mem- brane is thoroughly scrubbed off with iodoform gauze or some similar material, and, after the bleeding has been stopped, SURGICAL TUBERCULOSIS OF JO /NTS. 551 fistulous openings are sought for and traced to their source, coun- ter-openings being made, if necessary, for the purpose. The pri- mary nodule, being found, is then thoroughly curetted away. The whole cavity is now washed out with 1 : 3000 corrosive sublimate and is stuffed with iodoform gauze. The Esmarch bandage, if ap- plied, is then removed. The gauze is left in for one-half to three- quarters of an hour or until the next day, and is removed after being wet with a sublimate douche: the surface is dried, and the wound is sewed up with a sterilized continued suture under the most careful antiseptic precautions. An opening of some size is left through which the iodoform-glycerin is injected. If the gly- cerin does not flow well, it must be forced through a tube into all parts of the cavity, which should be filled sufficiently to expose the inner wall to the fluid without over-distention. The stitches should not be drawn too tightly, because they prevent healing by first intention. Finally, the wound is entirely closed and a dressing with gentle compression is applied. Those parts of the body where compression cannot easily be applied are not suited to this method, as slight hemorrhages from the walls of the cavity are apt to take place. Usually there are three or four days of fever with a high even- ing temperature. The dressing is allowed to remain, if all goes well, for two or three weeks. In other cases the fever and pain are so great that the dressings have to be removed, and the emulsion, mingled with blood, will be found oozing up between the stitches. In this case the emulsion must be pressed out and drains be inserted between the stitches, or the wound may be opened slightly and the blood be pressed out, and healing without suppuration may still occur. Billroth adopts this treatment also to open abscesses. Iodoform-poisoning is rarely seen. A 10 per cent, emulsion of iodoform in olive oil, or equal parts of iodoform and olive oil, may be used in many cases: such treat- ment is well adapted to open sinuses, and can safely be carried out by the patient himself. It is of course not so effective as one applied before the abscess is opened, but it gradually brings about an improvement in cases not amenable to treatment in any other other way, and it is useful in healing a sinus that may have re- mained after operation, or it is adapted to the preliminary treat- ment of open sinuses before attempting operative interference. In fact, the iodoform treatment is a valuable preliminary treatment to any operation that is intended, and the success which it has thus far met with, and the ease with which it can be carried out, even 552 SURGICAL PATHOLOGY AND THERAPEUTICS. by those who have not the conveniences of a large clinic, recom- mend it strongly for general trial. In dropsical forms of tuberculosis of the joints (hydrops tubercu- losus) the effusion may be treated by the method sometimes em- ployed for non-tuberculous dropsy of the joint. This method con- sists in the introduction of a canula, and, after drawing off the fluid, injecting a solution of carbolic acid of the strength of i : 60. After manipulating the joint so that the fluid shall come in contact with the entire synovial surface the solution is drawn off and the puncture is covered with an antiseptic dressing. Great care must always be taken to procure strict asepsis during such an operation. There are a large number of cases of bone or joint disease which are not relieved by any of the methods of treatment hitherto mentioned. Formerly all these cases eventually came to excision or to amputation, but the present knowledge of the pathology of these affections, and the extent to which the differ- ent parts of the joints are involved in different cases, and the great security and precision offered by bloodless and antiseptic modes of operating, enable one to choose from a much greater variety of operative procedures. Resection of the joint will obviously be unnecessary where a tuberculous nodule exists in one of the epiphyses which it is desired to remove. It may be sought for and readily be found if a fistulous tract is present; otherwise an exploratory incision must be made for the purpose. A flap of skin with the peri- osteum may be reflected from the bone, and an exploratory punc- ture may be made with the chisel in several places until the nodule is discovered. In removing the disease care should be taken, if suppuration or cheesy degeneration has not already occurred, to cut into the healthy bone, and to avoid, if possible, bringing the diseased mass in contact with the healthy tissues. If the nodule has softened and broken down, the cavity must be scraped out thoroughly with a curette, and if there is a sequestrum present it must be pried out with an elevator. The walls may, if neces- sary, be chiselled down to healthy bone even at the risk of mak- ing an opening in the joint. The cavity thus made can then be disinfected with a solution of 1 : 1000 corrosive sublimate, or, if it is doubtful whether all disease has been removed, it may be seared by the actual cautery. Some operators, relying upon the thorough- ness of their operation, allow the space to fill with blood-clot after removing the Esmarch bandage, and then seek to obtain union by first intention; but there is always danger that a local return may SURGICAL TUBERCULOSIS OF JOINTS. 553 thus be facilitated, for if there be any of the infectious material left behind, the blood-clot offers a most favorable soil for its devel- opment. It is better, therefore, to fill the cavity with iodoform gauze and allow it to heal by granulation. Senn suggests the introduction into such cavities of fragments of decalcified bone that have been covered with iodoform. These fragments offer a suitable scaffolding for the development of the granulations, and at the same time the iodoform diminishes the danger of local or of general tubercular infection. The danger of general infection must always be borne in mind whatever operation is being per- formed, for acute miliary tuberculosis may result from an infection of the surrounding healthy tissues of an operative wound. Tubercular nodules in parts of the skeleton remote from joints may be treated in the same way. A portion of the rib may be resected if necessary, or the surface of a flat bone may be trephined or chiselled until all diseased bone has been removed. When the diseased nodule or sequestrum projects into the joint, it may be necessary to open the joint to facilitate its removal. The operation to be performed in this case is arthrotomy. A number of such operations have been successfully performed. Arthrotomy consists in making an incision into a joint for the removal of a foreign or diseased body. It may be in the form of a large trans- verse cut which lays the joint open freely for inspection, or it may be a simple linear incision, or, finally, a flap of integument and perhaps of periosteum may be reflected for the purpose of expos- ing the seat of the disease. After removing the diseased bone, and, if need be, curetting some adjacent infected portion of the joint and dusting with iodoform powder, the wound is closed and a small drain or tent of iodoform gauze is allowed to remain be- tween the lips of the wound. After any such operation in or near a joint the limb should be placed upon a splint, so as to secure complete fixation during the early stages of the healing process. Such nodules are found in the anterior or in the lateral portions of the epiphysis of the tibia, in a condyle of the femur, in the neck or the trochanters of the femur, and in the olecranon process of the ulna; in nearly all of which cases it is not impos- sible to make an opening into the diseased cavity without involv- ing the joint. Several cases of exploratory incision into joints have resulted in their cure, very much as in laparotomy for tuber- cular peritonitis. In deciding upon some of the more serious forms of operation it should be remembered that the functional results after excision 554 SURGICAL PATHOLOGY AND THERAPEUTICS. of the joint are inferior to those obtained by conservative treat- ment. Moreover, any operation which involves the epiphyseal line interferes seriously with the growth of bone. Although in tumor albus there may be an arrest of the growth of bone, the shortening after an extensive incision, as of the knee-joint, is far greater than after a spontaneous cure (Bradford). These operations should therefore be attempted only when, in children, considerable collections of pus are found in the joint and more or less profound constitutional disturbance exists, as shown by the presence of fever and weakness and loss of appetite. Con- siderable displacement of the bones also indicates an advanced stage of the disease. In adults, after a trial has been made of the various forms of conservative treatment, it is better to adopt a mode of treatment that will lead to rapid healing, rather than to run the risk of pulmonary tuberculosis or amyloid degeneration of the internal organs. The advent of suppuration with the formation of an abscess communicating with the joint that can- not be controlled by the usual treatment is apt to be followed by the establishment of fistulous openings of a tuberculous character and a hectic fever. Under these circumstances it would be unwise to postpone too long resection of the joint. The presence of a dis- location or subluxation in the hip must be an indication for resec- tion. In the knee a subluxation could probably be remedied by other means unless extreme in degree. The patient's station in life will influence the surgeon some- what in the selection of a mode of treatment. In a laboring man an operation leading to a cure in a few weeks' time may be selected in preference to a more conservative treatment, although the latter might be successful in the course of two or three years. Arthrectomy is an operation designed, as its name implies, for the removal of the structures forming the inner surface of the articular cavity. In its narrow sense it is limited to an excision of the synovial membrane, cartilage, or bone. The latter opera- tion has sometimes been called "atypical resection" or partial resection of the joint. The term " erasion of the joint" is used by English writers, but all these distinctions are confusing. The principal difference between this method and the typical resec- tion of the joint lies in limiting operative interference solely to the diseased structures. In arthrotomy the ligaments and even considerable portions of the synovial membrane may be preserved. In arthrectomy the periosteum and the contour of the bones are preserved, and, if new bone-formation takes place and the repair SURGICAL TUBERCULOSIS OF JOINTS. 555 is all that could be desired, the joint retains it normal outline and sometimes its mobility. It is, moreover, not supposed to interfere with the growth of the limb. The objections to this operation are that it is not thorough, and that it fails oftener than excision to eradicate disease. In twenty-two operations for arthrectomy col- lected by Muller two patients died of general tuberculosis some months after the operation, in fifteen the wound healed by first intention, there was no shortening in six cases, and in two only was there a certain amount of motion possible. Senn reports two cases of arthrectomy of the elbow-joint, in both of which the "functional result was satisfactory." The technique of the operation consists in so laying open the joint, as performed in the operation for resection, that its interior shall freely be exposed. This opening is accomplished in the knee- joint by a transverse incision which divides the lateral ligaments. The patella should also be reflected back by free lateral incisions through the capsule, so as to expose the pouch which lies beneath it. The curette is usually not sufficiently effective in removing the tuberculous disease of the synovial membrane, as the diseased layer does not lie loosely over the surface as in cold abscess, but is part of a dense membrane from which it cannot be scraped. Every fragment of diseased tissue must carefully be dissected off with the forceps and scissors. Particular attention should be paid to the various folds of the capsule, and especially to the posterior layer which borders on the popliteal space, taking care to avoid the large vessels that lie very close to the external condyle of the tibia. If the bones are healthy, the synovial membrane alone should be excised; but if sequestra or fistulae leading to diseased bones are found, it may also be necessary to remove portions of the cartilage and bones. The patella should be allowed to remain if not dis- eased. Such an operation should of course be performed by the bloodless method and under the strictest antiseptic precautions. After removing the Esmarch bandage the oozing should be arrested by temporary pressure with corrosive sublimate gauze or with iodo- form gauze packed into the joint. A few vessels will require liga- ture, however. If the operator is satisfied that all diseased tissue has been removed, the joint may be closed, a small drain being allowed to remain a day or two in the corner of the wound. Some opera- tors after removing the bandage allow the blood to accumulate within the wound in order that healing by aseptic blood-clot may take place; but this should be tried only when it is desired to fill a space left by the removal of diseased bone, and when it is certain 55 6 SURGICAL PATHOLOGY AND THERAPEUTICS. that all diseased germs have been removed. In doubtful cases Krause's method seems the most prudent. This method consists in the tamponade of the synovial cavity with iodoform gauze. All the pouches of the cavity should be filled with gauze which has been freshly rubbed in iodoform powder, and which may remain in sitic for a few days or even for two or three weeks. If it is desired at any time to remove the gauze permanently, the joint, if it is still aseptic, can be closed by secondary suture. The dressing may be changed from time to time if the secretion is excessive. Krause adopted this method in two cases of men over fifty years of age in whom there were extensive abscess-formation and burrowing of pus. In both cases healing took place without fistulse, and the patients reported themselves well a year and a year and a half, respectively, after the operations. Owing to the diffi- culty of laying open the joint thoroughly, arthrectomy is not well suited to all cases. It is best adapted to the knee-joint, and per- haps also to the elbow-joint, but in the shoulder, and particularly in the hip, the anatomical conditions make it no easy matter to gain access to the more remote portion of the synovial capsule. The preliminary treatment with iodoform, oil, or glycerin paves the way, however, for these more conservative methods of opera- ting, and although they cannot be considered as well established methods at the time of this writing, they have nevertheless a future and deserve a careful trial. Resecticm of the joints may be illustrated by a description of the operation upon the knee. The joint is opened by a trans- verse incision running from condyle to condyle. This cut may be made directly across the centre of the patella, which can be sawn through, or it may curve with the convexity either above or below that bone. Senn makes a curved incision through the skin above the patella, and, after reflecting the flap downward, cuts through the patella, which is united again by suture after the operation. The patella is, however, usually removed even when it is in a healthy condition. After the crucial ligaments have been divided the ends of the bones are made prominent by forced flexion of the limb, and they are sawn off at some point sufficiently removed from the surface to include all the dis- eased bone. In children the epiphyseal line should carefully be avoided, for, if this is removed, the growth of the bone will greatly be impaired. A thin section, sufficient to include the articular car- tilage, is usually all that is needed. Any remaining nodule can subsequently be curetted. The bones must be so cut that the limb SURGICAL TUBERCULOSIS OF JOINTS. 557 will be straight when they are placed in apposition with one an- other, and care must be taken that the posterior edge of the tibia does not press against the popliteal vessels. After removing the elastic bandage the hemorrhage should be arrested by pressure, by elevation of the limb, and by tying such arteries as require the ligature. The bones can be held firmly together by a silver suture cut short and allowed to remain permanently. It is safer to em- ploy some form of drainage, as in the majority of cases union will be favored by conducting off the serous and bloody discharge of the first few days. In resection of the hip- and shoulder-joints the operator should not be satisfied with removal of the head of the femur or the hume- rus, but careful attention must be given to all other portions of the articular cavity, and all diseased tissue must carefully be removed, the incision being made sufficiently large for the purpose. In resection of the elbow-joint it is better to remove the bone freely and to avoid too careful preservation of the periosteum; otherwise ankylosis may occur. The results of such operations are usually excellent, and it is rare that a flail-like joint is obtained. XXVI. TUBERCULOSIS OF THE SOFT PARTS. i. Tuberculosis of the Skin. The identification of many forms of skin disease with tubercu- losis has been so satisfactorily demonstrated that no doubt exists at the present time of their true nature. Among the most prominent of these affections is lupus, which is now universally recognized as a tubercular disease, but, before Koch demonstrated the presence of the bacillus of tuberculosis in the lupus nodules, clinical observation had demonstrated the strong probability of its relation to tubercle. Brock found in 79 per cent, of the cases of lupus examined by him complications with other forms of tuberculosis, and Besnier showed that 21 per cent, of his lupus patients died of phthisis. Inoculations in animals have been made successfully from fragments of lupus, and Koch succeeded in obtaining a culture of the bacillus on blood-serum from a case of lupus hypertrophictis. Lupus is characterized by the formation in the skin of minute nodules of a reddish-brown color, more or less transparent and covered with epidermis. They appear to lie just beneath the sur- face, and they are well defined in outline. A cluster of papules about the size of a pin's head is first observed, and as the organ- isms grow they gradually approach one another, finally becoming confluent and forming nodules of considerable size. According to the direction which the growth takes there may be an almost infinite variety of forms. The varying degree of involvement of the upper layer of the skin gives rise to differences in the clini- cal appearances of the disease. These nodules are situated on the cheeks, on the nose, or on some other parts of the face; that is, in an exposed situation. They are very rarely found in the scalp, but are seen occasionally upon the limbs and trunk. Pathologically, the nodules consist of little granulation tumors in the true skin, in which tumors may be found all the elements of the miliary tubercle. The papillary layer is generally somewhat enlarged. The cutis vera and the papillae are infiltrated with leucocytes. The collection of cells in the true skin contains well- marked giant-cells. The infiltration in more advanced cases ex- tends sometimes to the adipose tissue. The bacilli are usually hard 558 TUBERCULOSIS OF THE SOFT PARTS. 559 to find. Cornil and Babes examined microscopally twelve cases, and found a bacillus on only one occasion. In the ulcerating form of lupus there is a more intense inflam- mation of the superficial layer of the cutis and the papillae. The large numbers of leucocytes bring about a softening of these layers, and they break up the attachments of the cells of the rete mucosum. The epidermis, consequently, is thrown off and suppuration of the papillary layer takes place. The evidence that lupus vulgaris is a form of tuberculosis of the skin is sufficiently conclusive. As the disease progresses in the non-ulcerative form the growth takes place from the periphery, and there can occasionally be made out minute tubercular nodules in an early stage of formation. The older portions show a tendency to get well ; they lose their peculiar color, the swelling disappears, the epidermis peels off, and cicatricial tissue is left behind. When the infiltration is not deep the disease appears as a yel- lowish-brown discoloration of the skin without any elevation of the surface. The diseased part is somewhat softer than the healthy structure, and a probe can easily penetrate the tissue. This form is called " lupus maculosus." Later the nodule may be soft and gelatiniform, or it may contain little masses of colloid material in the form of cysts. In other cases the morbid tissue is very firm and extends deeply into the skin. This form is very slow in its growth, and never breaks down. It is a peculiarly obstinate form of the affection to deal with. In some cases the tubercular nodules seem to be surrounded with an almost cartilaginous induration. As cicatrization goes on and the upper layers of the skin are destroyed, considerable desquamation occurs: this may be a suf- ficiently marked characteristic of the affection to receive a special name. This condition is sometimes known as squamous or exfo- liating lupus. When the lupus nodules break down and the cheesy degenerated material is thrown off there is presented the ulcerating type, or lupus exedens. The ulcers are covered with thin brownish crusts and the surrounding skin has a brownish-yellow color. The mar- gin of the ulcer will be raised if the tubercular growth has been an active one. In this type the growth is somewhat more rapid. When, however, the infiltrated tissues of the skin break down gradually, cicatrization may begin in the centre of the diseased area; and, as the process continues to infiltrate and destroy the sur- rounding healthy skin a serpiginous ulcer is formed. As the disease proceeds there is sometimes an exuberant formation of tissue which 560 SURGICAL PATHOLOGY AND THERAPEUTICS. produces a papillary growth. These papillary growths may be de- veloped from granulations which have become covered with epithe- lium. The names lupus hypertrophicus and lupus framboisioides are given to these forms. When lupus is situated on the lower extremities, the formation of this tissue is so excessive that the limbs are greatly enlarged, forming a species of elephantiasis. These two principal forms of lupus are not necessarily distinct: the non-ulcerating form may in time ulcerate. The parts become inflamed and softened and ulceration takes place. If ulceration occurs with great rapidity, there may be phagedenic lupus, but this type is exceedingly rare. Although lupus is principally confined to the skin, it may spread to the deeper parts and the periosteum may be attacked. The dis- ease may spread along the lymphatics and involve the adjacent glands; it may become multiple, attacking several portions of the skin at once. Pulmonary tuberculosis may eventually develop as a secondary complication, but this affection of the skin is a very chronic one, and it usually remains confined to that structure; it may spread, however, to the mucous membranes. Lupus of the face may spread to the mucous membrane of the mouth and the nostrils. The nostrils may become contracted, and sometimes may nearly be obliterated by the cicatricial tissue. The disease may reach the auditory canal and attack the membrana tympani; the conjunctiva, and even the cornea, may become involved in the disease. Lupus presents certain aspects peculiar to certain localities. On the face the disease begins as the macular variety, and finally forms one or more separate nodules. As these nodules spread and cica- trization takes place extensive surfaces may become involved, and the whole face may be transformed into a cicatricial and discolored tissue. Lupus of the nose generally occupies the tip and the alse. The reddened and hypertrophied tissue is covered with ulcers and crusts and gives rise to great deformity. The disease is found also on the lips and the external ear. On the limbs and body it assumes the warty and serpiginous forms, and it is frequently accompanied with great hypertrophy of the tissues. Lupus usually begins in childhood, and with such trifling lesions that it often passes unnoticed until at the period of puberty it springs into new life, and a rapid development of the disease with destruction of the affected part is observed (Van Harlingen). Tuberculosis vera cutis, which is a rare affection, is usually sec- ondary to disease elsewhere. It starts always from one of the TUBERCULOSIS OF THE SOFT PARTS. 561 mucous membranes and spreads over the adjacent skin. It begins as minute nodules in the skin that soon break down and ulcerate. A circular or an oval ulcer of variable size is formed. There are usually several ulcers, which may run together and assume a ser- piginous form. They are found most frequently near the anus, on the lips, near the nostrils, and on the upper extremities. They are seen only in individuals in advanced stages of pulmonary tu- berculosis. They are usually devoid of pain. Esmarch describes such ulcers near the anus, which are, however, very painful, par- ticularly at the time of a movement of the bowels, if they encroach upon the mucous membrane. They may sometimes be quite large and may be multiple. They are usually associated with pulmonary disease, and are probably the result of intestinal infection. The lupoid ulcers described by Allingham are probably of this variety. Leloir lately reported a hybrid affection of lupus and syphilis. In certain cases he found a nodule which healed to a certain point with specific remedies, and then for its entire disappearance re- quired treatment appropriate for tuberculosis. Scrofuloderma, which is an affection of more frequent occur- rence, corresponds to the gommes scrofuleitses dermiques of French, writers. It is always associated with some other unmistakable signs of general tuberculosis, such as affections of the glands, the bones, or the joints (Zeisler). It is the ulcerated form which is usually said to be tuberculous. The commonest seat of these nodules is on the face, in the submaxillary region, on the neck and thorax, and on the extremities. They are often found near a softened lymphatic gland. They appear at first as a discoloration of the skin, which becomes raised and forms a nodule that spreads slowly, and finally softens at one or more points; or it may appear subcutaneously and gradually involve the skin. Finally small col- lections of pus form beneath the surface of the diseased skin, which is much discolored. When these cavities open a thin yellowish or sanious pus is discharged, leaving pouches covered with a thin layer of skin. A flat superficial ulcer or a deep fistulous cavity may form in this way. The granulating surface is gelatinous and is of a pale yellowish color. Extensive serpiginous ulcers may thus de- velop that leave behind them disfiguring scars. Occasionally they coexist with deep-seated nodules of a tubercular nature. They occur at all periods of life, but chiefly at puberty. There is another class of tubercular lesions of the skin that appear to be the result of direct local inoculation. These types are not usually associated with generalized tubercle, and are essen- 36 562 SURGICAL PATHOLOGY AND THERAPEUTICS. tially local affections. Zeisler classifies under this head four varie- ties : namely, (a) Verruca necrogenica, or anatomical tubercle ; (b) Tuberculosis verrucosa cutis (Riehl and Paltauf); (c) Tuberculosis papillomatosa cutis (Morrow); and (d) Tuberculous ulcerations. (a) Anatomical tubercle, which is found on the fingers and the dorsal surface of the hand of persons in the habit of handling dead bodies or in performing autopsies, is undoubtedly the result of local inoculation. It begins as a small red nodule, which becomes pus- tular and is soon covered with a scab. Gradually it spreads on the surface, becomes thicker, and is covered with papillary growths, giving it a warty appearance. It has a well-defined margin. Here .and there on its surface are seen small points of pus which can be squeezed out from the deeper layers. In some cases it is quite pain- ful; at times it is very indolent in character. It may spread through the lymphatics to the forearm and the axilla, and in some instances may give rise to a fatal visceral tuberculosis. (b) Tuberculosis verrucosa cutis is classified by most writers with anatomical tubercle. It is situated on the dorsal surface of the hands and the fingers and in the interdigital spaces. It varies in size from a dime to a silver dollar. When fully developed a patch consists of three concentric zones. The peripheral zone is erythe- matous, the color disappearing under pressure of the finger. The second zone is formed of* little pustules or of scales covering pus- tules ; the skin is of a reddish-brown color and is somewhat infil- trated. The central zone, which is raised 2 to 3 millimetres above the level of the skin, is covered with papillary growths which are largest at the centre. Between the warty growths are fissures and small skin-abscesses from which can be squeezed a few drops of pus. The growth is very sensitive. The lesion is situated in the superficial layers of the cutis, and it rarely extends to the level of the sudoriparous glands. Riehl and Paltauf found large numbers of the bacilli of tuberculosis in the diseased tissue. The affection is seen in vigorous individuals who are brought by their occupation in contact with domestic animals. It is very slow in development, and it may last from two to fifteen years. Bowen has described examples of this affection. In one case infection occurred in one of the Transatlantic cattle-ships. He also describes a number of cases of this disease occurring in young subjects and on different portions of the body, as on the elbow, the wrist, and the knee. In all cases there appeared to have been a local inoculation. Micro- scopical examination of specimens taken from some of the lesions showed the characteristic giant-cells and bacilli. TUBERCULOSIS OF THE SOFT PARTS. 563 {(■) The tuberculosis papillomatosa cutis is an isolated case described by Morrow, the result of an infection of the skin of the face from pre-existing tubercular disease of the bone. The case was remarkable for the extent and the amount of the warty tuber- cular growth, which involved the cheeks, the upper lip, the nose, and the eyelids. The hypertrophic condition of the growth and the papillary excrescences were marked features of this case. (d) Tuberculous ulcerations produced by inoculation appear on any infected locality. An example of this form occurs in the pre- puce after the rite of circumcision when the fresh wound is sucked "by the operator and is infected with the saliva. Repeated instances of this form of inoculation have been reported. Infection may occur while washing the linen of consumptives. Brown describes a case of tuberculosis verrucosa cutis on the back of the finger of the right hand of a woman. The disease appeared at the time of the death of a daughter whose soiled handkerchiefs and clothing the mother had been in the habit of washing. Ulcerations have formed after piercing the ears. In all these ulcerations an exami- nation has shown the characteristic giant-cells and bacilli. Most tuberculous affections of the skin, except those seen in advanced general disease, can be cured. Lupus, however, is distinguished from all other tubercular diseases of the skin by its marked tend- ency to relapse. The general treatment of tuberculosis of the skin is the same in many cases as that adopted for the disease in other parts of the body. Although the general condition of the patient may be good in lupus, in some forms of cutaneous tuberculosis there is more or less cachexia. In any case it is of importance to sustain the patient's health. Cod-liver oil is one of the best remedies for this purpose. Bucq, who considers it the most important internal rem- edy for this disease, recommends from four to eight tablespoonfuls daily. Among other drugs, arsenic may be mentioned as one of the most efficacious. It may be administered in the form of Fowl- er's solution. For local treatment antiseptic agents have been recommended since the nature of the disease has been recognized. White em- ploys a solution of bichloride of mercury, 1 or 2 grains to the ounce, applied half an hour every morning or evening on compresses kept continually wet, or the same drug may be used as an ointment in a strength of 2 grains to the ounce, applied continuously and renewed twice a day. Care must be taken to avoid salivation, which, how- ever, is unlikely to occur if the patient is watched. White noticed 564 SURGICAL PATHOLOGY AND THERAPEUTICS. rapid improvement at first, and he obtained permanent cures by this method, in some cases after several months of treatment. He also used with satisfactory results from 2 to 4 per cent, solutions of salicylic acid in castor oil. The objection to this antiseptic mode of treatment is that the agents are not always brought in direct contact with those parts in a stage of active growth. To accomplish this contact it may be necessary to use caustics as a preliminary treatment. Among these caustics pyrogallic acid is supposed to have a mild but effective action. It may be used with ether in a saturated solution on a compress ; or it may be sprayed on and afterward covered with collodion; or it may also be employed as an ointment. After the tubercular nodule has been melted down in this way, mercury in the form of a plaster or an ointment may be applied. Iodoform, one of the most effective poisons to tubercle, may be employed locally. It may be applied in the form of a powder or an oint- ment or in an emulsion with glycerin, or it may be forced into the soft tissues by boring, or it may be injected with a hypo- dermic needle. Now that the nature of the disease is known, attempts should always be made to treat it as if it were a malignant growth. Operative procedures are therefore indicated in a large number of cases. There are of course certain regions where excision cannot be performed, as on the alse of the nose or in extensive disease of the face. The curette or scarificator or the actual cautery may be used in these cases, either alone or as an aid to other forms of treatment. The soft nature of tuberculous tissue enables the curette to sink easily into it, so that it may thoroughly be scraped away in many cases. It is well to follow up the sharp spoon with some form of caustic. The mildest of caustics is nitrate of silver, which in the form of a pointed stick can be made to search out the various rami- fications of the disease. When the diseased tissue is firm and unyield- ing, it may be exposed by means of scarification, which can be per- formed with the lancet or by an instrument specially devised for the purpose. After the deeper parts of the diseased tissue have thus been laid bare they may be treated with the antiseptic remedies already mentioned. Scarification is said to leave a better scar than the cautery. In certain parts of the face the actual cautery is one of the most efficient agents for removing the disease immediately without too great loss of tissue. The cicatrization prepared by nature often leaves less deformity than when excision has been TUBERCULOSIS OF THE SOFT PARTS. 565 performed and an attempt has been made to bring the edges of the wound together by sutures. Whenever the disease can be excised it is undoubtedly the most efficient way of dealing with it, and is the one least likely to be followed by relapse. The reputation lupus has for relapse is due to the imperfect methods of eradicating the disease. Even when the wound is so large that the edges cannot be brought together, the surgeon should not hesitate on this account, as there is presented in the Thiersch method of skin-grafting an efficient way of covering the solution of continuity. Large operations of this kind necessitate anaesthe- sia, but the smaller forms of tuberculous nodule may be excised after local anaesthesia has been produced by subcutaneous injection of a 1 per cent, solution of cocaine. 2. Tuberculosis of the Mucous Membranes. Only a certain number of these affections are accessible to the surgeon. Primary lupus of the mucous membrane is compara- tively rare. In by far the greater number of cases it is second- ary to disease of the skin, and proceeds thence to the mouth, the pharynx, the conjunctiva, etc. The small reddish-brown nodules are not observed in the mucous membrane; instead, there are seen minute white points in the livid red and slightly- thickened membrane. There is a superficial loss of cells which can hardly be called ulceration: later these white spots disap- pear and the surface becomes papillary. Lupus of the pharynx may be seen independently of cutaneous lupus. Ulceration may finally take place, and the ulcers, which last a long time, after partially healing break down again. The ulceration may ex- tend until it involves almost the whole thickness of the mucous membrane. There are forms of tuberculosis of the throat and soft palate that are not regarded as lupus. This form of the disease is seen as a large superficial ulcer, or ulcers which eventually run together. They have a yellow surface, and they may extend over a large portion of the posterior wall of the pharynx and soft palate. Miliary nodules may be seen lying in the membrane between the ulcers. It closely resembles syphilis, for which it may be mis- taken. The extensive adhesion of the velum to the pharynx and the occlusion of the posterior nares are more frequently due to tuberculosis than to syphilis. These cases are often combined with pulmonary tuberculosis, but many cases are amenable to 566 SURGICAL PATHOLOGY AND THERAPEUTICS. treatment with the curette, with caustics, or with the actual cau- tery, combined with the local application of iodoform powder. Tuberculous ozcena occurs independently of lupus, and it ap- pears in the form of ulcerations. This affection is not to be con- founded with the ordinary so-called "scrofulous ozcena." The formation of ulcers occurs chiefly on the turbinated bones. They are irregularly shaped with a yellowish purulent surface. They appear to be caused by infection from the pocket handkerchief con- taining the dried sputa of the patient. Tuberculous tumors of a polypoid shape are occasionally found attached to the septum. They resemble sarcomata, but they are infiltrated with tubercular nodules. As they grow they may per- forate the septum. Their point of origin usually enables one to distinguish them from polypi. Tuberculosis of the tongue occurs partly in the shape of ulcers which sometimes are torpid and sometimes are of the fungous variety. It appears also as a nodule which breaks down in the centre. Isolated ulcers may be mistaken for cancer, but they can generally be distinguished from that disease by the inflammatory infiltration of the tissues which always accompanies tuberculosis. Volkmann, however, has twice extirpated such growths under the impression that they were cancerous. The nodular form may also be mistaken for syphilis, but in the later stages the cheesy suppu- ration serves to distinguish it. With the aid of cocaine fragments of tissue can always be removed from the tongue for the purpose of microscopic investigation: the exploratory punch is particularly well suited for this purpose. Examples of this affection are not common in America. The writer has seen but one well-marked case of tuberculosis of the tongue. The apex and about one-third of the lateral half of the tongue were involved in an inflammatory swelling, a portion of which was ulcerated. This case was under observation for several months while the patient was treated with injections of tuberculin. On the borders of the ulcer minute whitish tubercles could be seen during the periods of exacerbation of the disease. In this patient there were slight rales at the apex and a tubercular abscess at the anus. The improvement in the general health was marked during the treatment, and, although after several months of treatment the nodule had not diminished in size, yet a permanent cure was finally effected. The disease may be treated by excision of a wedge-shaped piece of the tongue or by the actual cautery. In several cases reported by Volkmann there was subsequent pulmonary tuberculosis, TUBERCULOSIS OF THE SOFT PARTS. 567 although other cases were permanently cured by the operation. In two cases, which he examined post-mortem, the whole surface of the tongue was covered with small flat ulcerations the size of a pin's head, which ulcers in many places became confluent. Dur- ing life these ulcerations were supposed to be aphthous. Volkraann has seen non-lupoid tuberculous ulceration of the lip on two occasions. In one case, that of a young girl with multiple cutaneous tuber- culosis, the ulcer was removed by a V-shaped incision . In the second case, that of an old woman, the disease had been mistaken for cancer and had been treated with superficial cautery. This ulcer was also excised. A case is reported of a woman, thirty-two years of age, who contracted an ulcer on the inner and outer surface of the lip from her husband, who was suffering from a tubercular ulcer of the gum. A considerable number of cases of fistula in ano are of a tuber- cular nature. As is well known, this affection is often associated with pulmonary tuberculosis. These fistulse can be distinguished from the non-specific variety by their tendency to form fungous granulations and sinuses in the mucous membrane and the skin. When these sinuses develop externally their tubercular nature is apparent by the pale, gelatinous character of the granulations and by the reddish-purple color of the thin skin which covers them. They may at times be very extensive, extending out for a consid- erable distance into the nates. The skin is thin, discolored, and undermined for a considerable distance. On pressure cheesy-like masses and a thin serous pus ooze from the fistulous opening. As long as the disease is confined to the mucous membrane there appears to be no increase in size of the glands in the inguinal region, but as soon as the margin of the anus or the skin is affected these glands are sometimes found to be enlarged. This affection usually begins in the mucous membrane of the rectum as the result of an infection through some slight bruise or fissure. An ulcer rarely forms here, as is usual in other parts of the intestinal canal when tubercular infection takes place, but the result of this local inocu- lation is an ischio-rectal abscess. The bacilli are carried through the intestinal canal, as has already been seen, and they are thus brought to this locality. Occasionally a primary infection of this perirectal tissue may occur through an intravascular route, but the disease is most commonly developed secondary to pulmonary or buccal or intestinal tuberculosis. The disease must be treated with the same attention to the necessity of removing all tuberculous tis- sue as in case of tuberculosis in the bones. The membrane should be curetted away thoroughly, and each sinus should carefully be followed to its termination. The wound should then be stuffed 568 SURGICAL PATHOLOGY AND THERAPEUTICS. with iodoform gauze. Attempts at excision with subsequent sutur- ing of the wound are more liable to be followed by a recurrence of the disease. The presence of disease in the lungs is not necessa- rily a contraindication to the operation. In incipient pulmonary phthisis there is no objection to surgical interference, as it is now known that distant parts of the body are not affected by any such operations, as was formerly supposed to be the case. A somewhat analogous form of tubercular infection is observed in the region of the appendix and caecum. Here also there is a certain amount of stagnation of the intestinal contents, and therefore slight injuries to the mucous membrane are likely to occur. Another peculiarity common to both regions is the presence of loose connective tissue immediately outside the intestine. This tissue is found behind the caecum as well as around the lower portion of the rectum. For this reason, perhaps, the disease is less confined to the mucous membrane, and it takes the form of an abscess which breaks and leaves a fistulous opening. A certain number of the cases of appen- dicitis that come to suppuration are of tuberculous origin. In these cases is found a fistula containing fungous granulations which may involve the skin, and it heals with difficulty. Tuberculosis of the mucous membrane of the rectum may occur in the form of small tubercles which break down and form small round ulcers. These tubercles run together, forming ulcers, often of considerable size, that may be recognized by their eaten-out edges, by their irregular surface, and by the presence of fresh gray and yellow softened nod- ules in the borders, base, and neighborhood of the ulcer. As the disease progresses there may form a circular or girdling ulcer of the rectum which leads to stricture if an attempt is made at cica- trization. In most cases the process spreads slowly and involves the muscular tissue, and perforation may take place into the peri- toneal cavity or into the surrounding connective tissue, forming abscesses and sinuses. Tuberculosis of other portions of the intestinal canal is not infrequent as the result of a primary infection of the membrane by impure food or as the result of a secondary infection from the lungs through tuberculous sputa which have been swallowed. This form of tuberculosis rarely falls to the surgeon's lot to operate upon unless perforation or obstruction should occur, in which case laparotomy, and even intestinal resection, might be called for. One or two such cases have been reported. The result of intestinal tuberculosis is not infrequently an infection of the peritoneum. TUBERCULOSIS OF THE SOFT PARTS. 569 3. Tubercular Peritonitis. Tubercular peritonitis occurs at all periods of life. It is com- mon in childhood, but is seen most frequently between the ages of twenty and forty. This disease is most prevalent among females, although of 21 cases reported by Osier 15 were males, and in 46 cases examined post-mortem in the Munich Pathological Institu- tion $$ were males and only 13 were females. There are three types of this form of peritonitis : (1) acute mili- ary tuberculosis of the peritoneum, characterized by a sudden onset, a rapid development, and a serous or sero-sanguineous exudation; {2) chronic caseous and ulcerating tuberculosis, characterized by larger tuberculous growths, which tend to caseate and ulcerate, leading often to perforations between the intestinal coils, and by a purulent or sero-purulent exudation, often sacculated; (3) chronic fibrous tuberculosis, in which the process may be subacute from the outset, or it may represent the final result of the miliary form. Little or no exudation occurs in this variety, and the tubercles are hard and pigmented (Osier). The peritoneum may be infected, secondarily, through the in- testines, the Fallopian tubes, and possibly from the pleura through the diaphragm or from the mesenteric glands. It may also become infected, secondarily to pulmonary tuberculosis, through the circu- lation. The disease may also occur primarily in the peritoneum, but this is rare. From the intestine infection may take place through tubercular ulcerations, as there is always a formation of miliary tubercles on the surface of the peritoneum over the ulcers when these reach any considerable size, and from this point a general infection may take place. The bacilli often develop in the lymphatic vessels of the intestine without causing ulceration, and they are carried by these vessels to the mesenteric glands. In many cases the infection remains localized in some portion of the peritoneal cavity. The commonest seat of this limited tuber- culosis is the region of the pelvis in the recto-vaginal or recto- vesical fossae. When the tubercular virus enters the peritoneum it may be spread about by the peristaltic movements of the intestines or it may tend to gravitate to some one of the pelvic pouches. Localization may be maintained by adhesions of the peritoneal surfaces, which adhesions are sometimes very extensive. The Fallopian tubes are probably a frequent source of tubercular peri- tonitis, although the tubes may be infected from the peritoneum. Tubercular salpingitis is a complication often found in this disease, 57° SURGICAL PATHOLOGY AND THERAPEUTICS. for Osier estimates that in from 30 to 40 per cent, of the cases the tubes are affected. In many cases of laparotomy for removal of the tubes these organs are found diseased, while the peritoneum is still healthy. In some cases the disease spreads through the diaphragm and involves the pleura. This complication occurred in only three out of seventeen cases. When infection takes place through the mesenteric glands they become enlarged, the tubercles making their way through the capsules of the glands, or the diseased glands undergo cheesy softening, and some of the broken-down material is discharged into the peritoneal cavity. Such enlarged glands in young chil- dren are often accompanied with distention of the abdomen and marasmus, the condition being known as tabes mesenterica. In most of these cases there is probably more or less tubercular peri- tonitis. Some of these glands may grow so large as to give the appearance of an abdominal tumor. Gardner reports such a case in a man aged twenty-one. Colin describes three cases in soldiers, in whom were found enormous tubercular tumors of the mesen- teric glands. In the majority of cases the extension of the process in the peritoneum goes on slowly, and it is accompanied by a for- mation of connective tissue: in this way thick and extensive adhe- sions form. When the omentum is involved in the process the contractions which accompany the formation of adhesions cause the omentum to be retracted into a thick, firm lump, which lies transversely across the abdomen just above the umbilicus. A more or less abundant effusion takes place at the same time. The fluid is either greenish-yellow and turbid, or in more acute cases it may be serous or sero-sanguineous. In some cases the exudation may be purulent in character. Owing to the simultaneous development of adhe- sions these exudations become sacculated. The omental enlarge- ments and the encysted collection of fluid often give rise to the appearance of a tumor growing at some point in the abdominal cavity. In ninety-six cases collected by Osier of this kind 3 per cent, were supposed to be cases of ovarian or other form of tumor. These sacculated exudations may be found in the upper part of the abdominal cavity, emanating from the region of the liver, the gall-bladder, or the spleen. They may be seen also in the middle part of the abdomen. Here occasionally a cystic accumulation occurs between the layers of the omentum, assuming at times enormous dimensions. Such an accumulation would probably be mistaken for an ovarian tumor. TUBERCULOSIS OF THE SOFT PARTS. 571 These exudations may occur also within the pelvis, in which case the disease almost always starts from the Fallopian tube: the coils of intestine immediately become glued together about the dis- eased spot and shut it off from the general peritoneal cavity. In this way there form extensive pus-cavities which give rise to symptoms of acute inflammation. When the abdominal cavity is opened to relieve these symptoms the intestines are found studded with tubercles. A number of such cases have occurred in the writer's practice, of which cases the following is an example: A woman twenty-seven years of age had been slowly losing weight for two years when an attack of menorrhagia, with the formation of a tnmor in the right iliac region, brought her to the hospital. She remained in the hos- pital for two months under medical treatment, during which time she improved so much that she was discharged. Eight months later she returned in a bad condition. There was general abdominal distention, a temperature of 102 F., and fluctuation in the right iliac and pubic regions. An incision on the median line showed the intestines everywhere matted together and studded with gray and yellowish nodules, some of which on removal were found to be true tubercles. There was no serous exudation. On separating the pelvic adhesions a pint of very foul pus was evacuated. A drain was left in, and the patient made a good recovery. There was no sign of tubercu- lar disease in any other part of the body. When seen a year later she re- ported that she was in good health and had married. The matting together of several coils of intestine may form an almost solid movable tumor not unlike a uterine fibroid. The dif- ficulty of diagnosis in such cases is very great. Owing to the distortions of the coils of intestines by the pres- ence of adhesions the mucous membrane may ulcerate and per- foration may occur. It is quite possible also that symptoms of obstruction may be produced by extensive adhesions of this nature. Many cases of supposed tubercular peritonitis are not really tubercular. Welch describes fibroid or lymphomatosis nodules occurring in chronic serous peritonitis. J. F. Payne describes a case of minute fibrous granulations of the peritoneum associated with growths throughout the liver, possibly syphilitic. A careful examination of the nodules should therefore always be made if possible, and the presence of the bacilli be determined either by the microscope or by inoculation experiments on animals. Tubercular peritonitis is an affection which shows itself by no well-marked and constant clinical symptoms. Its onset is often very insidious. The infection may take place so slowly and so painlessly that the patient may not have presented a single symp- 572 SURGICAL PATHOLOGY AND THERAPEUTICS. torn of abdominal disease. The onset may, however, be sudden and be accompanied with all the symptoms of acute peritonitis. Slight fever, occasional vomiting with alternate constipation and diarrhoea, may be the first group of symptoms. On examination of the abdomen the intestines are found distended with gas, and the presence of ascitic fluid may be recognized in the lower por- tion of the peritoneal cavity. When the exudation takes place rapidly it is often mixed with blood. When the gastric symp- toms are very marked the disease may simulate cancer of the stomach. There is often a typhoidal condition which, with con- tinued fever, may lead to the supposition that the patient has typhoid fever; but occasionally there is found a subnormal tem- perature throughout the course of the disease. The prognosis of the disease is exceedingly unfavorable. It is either an indication that the system is suffering from a general tubercular infection or that disease of other organs may follow in its track. Thus there may be pulmonary tuberculosis as a sec- ondary infection. In the graver forms there may be found exten- sive amyloid degeneration of the internal organs. It is now a well-recognized fact that many cases recover spon- taneously; it is even possible that the disease may run a latent course, and a cure may take place without a sign of the exist- ence of peritonitis. There is certainly no improbability in the involution of tubercles of the peritoneum as in other portions of the body. The tubercles undergo fibroid and pigmentary indura- tion and the exudation is absorbed. A certain number of adhesions are all that is left to mark the site of the disease. The cases most likely to terminate favorably are those in which the infection is limited to the peritoneum and is of only moderate extent. The good effects of laparotomy in the treatment of this disease are now generally recognized. In 1862, Spencer Wells performed laparotomy for what was supposed to be an ovarian tumor. He found a tubercular peritonitis. The effusion was withdrawn and the patient recovered. Since then cure has followed many such mistakes in diagnosis. In 1884, Z. B. Adams opened the peri- toneum for purulent peritonitis, probably of tubercular origin, and evacuated a large quantity of pus, the patient being alive and in good health ten years later. In a case of explora- tory laparotomy performed by Halstead tubercular peritonitis was found, and the cavity was washed out with a sterilized salt solu- tion and drained. The patient made a good recovery. Several months later, the patient having died of pneumonia, an examina- TUBERCULOSIS OF THE SOFT PARTS. 573 tion showed the tubercles still present and containing bacilli, but undergoing a fibroid change. The cases best suited for operation are those in which the dis- ease is confined to the peritoneal cavity — those with fresh eruptions and considerable effusion. When the Fallopian tubes are exten- sively diseased and the tuberculosis has involved the uterus or has spread through the diaphragm, or there is any evidence of pul- monary disease, the conditions are unfavorable. When the puru- lent stage is reached the chances of recovery are in many cases poor, but the evacuation of circumscribed collections of pus is always indicated unless there is grave constitutional disturbance. Why laparotomy with drainage produces such a radical change in the peritoneal cavity has not yet been explained. It has been suggested that the curative action is due to the removal of the ptomaines which accumulate in the ascitic fluid. The operation undoubtedly produces a profound disturbance in the processes of nutrition of this membrane, and under these circumstances the soil may no longer be favorable for the growth and dissemination of the bacilli. The absorbent action brought about by traumatic inflammation, so common elsewhere, may make itself felt on such an occasion, and it may favor the removal of the broken-down products of the disease. 4. Tuberculosis of the Genito-urinary Organs. Disease of this region in women occurs in about 1 per cent, of all cases of autopsies for tuberculosis (Winckel). Tuberculosis of the Fallopian tubes can occur primarily, but it may also occur secondarily to uterine or to peritoneal disease, or it may accom- pany disease of the lungs and the intestines. It is found in child- hood, but it occurs most frequently in early adult life, and it may follow the puerperal state. Usually both tubes are involved. When both uterus and tubes are affected the tubes are generally more diseased than the uterus. It appears that in most cases the disease begins at the peritoneal end of the tubes, and works its way down- ward through the uterus to the vagina. The affection begins as a catarrh of the mucous membrane, in which are seen minute gray or yellowish-gray nodules. The canal is more or less distended with muco-purulent material. Ulceration takes place later, and with the breaking down of tissue the tube is filled with cheesy masses. The ulceration may result in perforation of the wall of the tube. In advanced stages the tubes appear coiled and dis- 574 SURGICAL PATHOLOGY AND THERAPEUTICS. tended and much thickened and indurated. Calcification may- take place in the degenerated tissue. The uterus, as has been seen, is usually affected secondarily to the Fallopian tubes, or the bacilli may enter from the peritoneum through the tubes without involving the latter. In a certain number of cases the disease is undoubtedly primary in the uterus, and it is said by some to result from the entrance of bacilli during coitus. In a case described by Post the patient with a tuberculous testicle had a purulent discharge from the urethra, which on examination was found to contain large numbers of the bacilli of tuberculosis. Tuberculosis may follow the puerperal condition, and it is then found at the site of the placental inser- tion. In this case it is probable that the disease is transmitted to this region from some point in the interior of the body. Many writers concede an intravascular infection of the genital organs in both sexes. The disease is found in the early stages at the fundus, and it works downward in nearly all cases. In some advanced stages the uterus is enlarged and the cavity is filled with caseous material. The surface of the membrane is roughened and ulcer- ated, and, although miliary tubercles may be invisible to the naked eye, a microscopical examination reveals the presence of giant-cells and epithelioid cells. The cervix is rarely affected. Cornil and Babes found in six autopsies of cases of tuberculosis of the uterus three in which the bacilli were abundant ; they were difficult to find in the other three cases. Their experience in the examination of the tubes was about the same. The disease in the vagina is most frequently the result of an infection through the secretions which form in the tubes or uterus. It may, however, follow a tubercular peritonitis without infection of the tubes or the uterus. A few cases of primary tuberculosis of the vagina have been observed, but they are exceedingly rare. If the uterus is not involved, the urinary organs or the intestine will probably be found diseased. The vagina may become infected by a perforation of a tubercular ulceration of the rectum through the recto-vaginal septum. Cornil and Babes found bacilli in tuberculous ulcerations surrounding a recto-vaginal fistula, but were unable to find the bacilli in two other cases of tuberculous ulcer of the vagina. The tubercles are seen in the early stages of the affection on the mucous membrane of the vagina as small gray nodules or as larger masses with cheesy, ulcerated surfaces. They are situated in the middle or upper portions of the vagina. Tuberculosis of the vulva does not appear to be a common TUBERCULOSIS OF THE SOFT PARTS. S75 affection. Cay la reports a case of tubercular ulceration of the labia and the ostium vaginae in a case of advanced pulmonary tuberculosis. Cases of lupus of the vulva have also been de- scribed. It is conceivable that infection might take place from tubercular discharges both from the vagina and the rectum. In many cases of tuberculosis of the lungs and the intestinal canal the vagina has been found affected, while the uterus and the tubes were in a healthy condition. This fact suggests an infection from the rectum through the anus and the vulva. When an organ is affected with tuberculosis, surgeons are accustomed, in deference to tradition, to assume that the disease has been transmitted to it from the lungs or the intestines. Hegar suggests, in addition to the possibility of a direct infection of the sexual tract during coitus, an infection by fingers and instruments during a vaginal examination. Gonorrhceal infection of the mucous membrane robs it of its epithelium, and a favorable soil is thus offered for the growth and spread of the bacilli. Such gonorrhceal inflammation may spread through the uterine mucous membrane to the Fallo- pian tubes. In this and in other ways the virus may gradually spread from the original point of infection through the genital tract. It may also be transmitted from the primary lesion through the rich uterine lymphatic plexus to the peritoneum, and thence find its way through the Fallopian tubes into the uterine cavity. If disease of the uterine tract were suspected, a diagnosis might be established definitely by a microscopical examination of the vaginal secretion, and the presence of the bacilli thus be deter- mined. The enlarged and thickened tubes could be recognized by bimanual palpation. The swollen tube may form a tumor the size and shape of a goose-egg, or it may have an elongated sausage-like feel to the touch. In other cases it may be felt as a series of nodules strung together. In some cases the tubes may be so sur- rounded and covered by an adhesion and exudation that it is impossible to detect them. Their situation is often changed. They may be displaced into Douglas's cul-de-sac, where they are frequently fastened by adhesions. An enlargement of the uterus might suggest the infection also of that organ. Curetting the inner cavity of the uterus might yield material for a microscopical examination. The local treatment of tuberculosis of the uterus and the vagina consists principally in antiseptic douches, and in the application of iodoform to the diseased surfaces after the use of the curette or the cautery. Inasmuch as the tubes seem to be affected primarily in 576 SURGICAL PATHOLOGY AND THERAPEUTICS. the majority of cases, the recognition of tubercular salpingitis before the other organs were involved would be of importance. Laparotomy for the removal of tubes affected with tubercular dis- ease has frequently been performed with satisfactory results. Tuberculosis of the ovaries is much rarer, according to Klebs, than tuberculosis of the uterus and the tubes, and the former dis- ease does not occur simultaneously with the two last-named affec- tions. Klebs infers that it must become infected, therefore, through the circulation. Quite a number of observers have found diseased ovaries in connection with tuberculous uterine disease. Mosler found tuberculosis of the ovaries seven times in a series of forty- six cases of tuberculosis of the female genital organs. The organs are enlarged to the size of a hen's ^gg y and are filled with numer- ous nodules and cheesy masses. Some cases of tuberculosis of ovarian cysts are reported. The surface of the cyst is, in this case, studded with subperitoneal tubercles. In two cases reported the adjacent peritoneum was affected in one and the tubes in the other. Klebs reports a case of ovarian cyst with tubercles on the inner surface in which the infection seems to have proceeded from the uterus. It is not probable that this is the route usually taken, but that the ovaries are affected either primarily or simultaneously with the tubes. If the diagnosis of tuberculosis of the ovaries were made, it would be proper to remove them. In tuberculosis of the genital organs of man the bacilli, accord- ing to Cornil and Babes, are not easily found. In cheesy degenera- tion of the testicles and in epididymis it is often the case that none are obtained. Kocher, however, was able to find bacilli in the periphery of a tuberculous nodule, but not in the pus. Tuberculosis of the testicle usually begins in the epididymis, and when seen in the early stages it appears as a nodule which is hard to the touch, and in section as a grayish-red, firm, homogeneous mass that has no well-defined boundary, but shades off into the surrounding connective tissue. In this tissue are seen the round or oval or shrunken cylinders of the canals. As the disease progresses a number of these nodules form. The canals are filled with broken- down material and are distended considerably. Occasionally, when these nodules soften, there form in the adjacent tissue small abscesses which frequently break and become fistulous openings. In the testicles the disease shows itself at first as one or two large nodules which may involve the whole or a large part of the organ. These nodules soften down in the centre and form small abscesses, which also break and form fistulse. When the testicle is TUBERCULOSIS OF THE SOFT PARTS. S77 affected secondarily to the epididymis, there are found a number of small nodules in the otherwise normal tissue of the organ. When the whole testicle is involved, a section shows it to consist of the gelatinous homogeneous tissue, in which lie several yellow cheesy masses of stellate or irregular shape. According to Kocher, a microscopical examination of the tubercles in the earliest stage of their development shows within the seminal ducts a collec- tion of giant-cells and epithelioid cells supported between the two layers of the membrana propria and filling out the lumen. The tuberculosis begins, therefore, as an intracanalicular process. As the intracanalicular masses undergo cheesy degeneration the new tubercle is found in the membrana propria. In some cases the membrane seems to be the part chiefly affected, the amount of cell- formation in the ducts being comparatively slight. The neighbor- ing ducts in this case rapidly become involved. In other cases the stroma seems to be the part in which the disease is situated; but as early stages of this process are not seen, it is probable that even the stroma is not in these cases the primary seat of the disease. In many cases the testicle is no doubt the region in the genito- urinary apparatus where tuberculosis begins. The bacilli have been found in the seminal ducts and in the semen of patients affected with pulmonary tubercle in whom the testicles showed no sign of disease. The organisms are carried to the organ in this case through the blood-vessels, and are transported through the epithelium of the canals into the lumen. The localization of the disease in this organ may be produced by trauma; Simmonds demonstrated this by experiment on a rabbit. An emulsion of tubercular sputum was introduced into the peritoneal cavity of the animal, and a few days later there was produced a contusion of the left testicle. The organ swelled somewhat at first, but the swelling subsided in a short time. Two months later the rabbit was killed, and a general miliary tuberculosis was found, with a broken-down nodule of considerable size in the left testicle. Gonorrhoea is not an infrequent predisposing cause of the disease. In fifty-two cases of tuberculosis of the testicle Kocher found that in fourteen cases the patient had suffered from gonorrhoea. In Simmonds' sixty cases eleven had had gonorrhoea. The question is often discussed as to the direction the disease takes in the genito-nrinary organs. Does it ascend from the urethra or the testicle to the kidney? or does it originate in the kidney and descend through the uro-genital tract? Rokitansky and other more recent authorities are of the opinion that the dis- 37 57§ SURGICAL PATHOLOGY AND THERAPEUTICS. ease ascends from the testicle, but Virchow takes the opposite view. Tubercular disease of the urinary organs is rarely found in connection with disease of the testicle. Tuberculosis of the testicle, although it is rare as a purely primary disease, is often found with- out tuberculosis of other portions of the genito-urinary apparatus. Primary affection of the kidney, with subsequent disease of the testicle, is not so rare as it is usually supposed to be. Nevertheless, the usual mode of progression is an ascending one. That is, the disease is transmitted from the testicles to the cord, and subsequently to the prostate. From this point it may be transmitted to the bladder and the kidneys, but this is by no means frequent. An infection of the other testicle occasionally takes place. It is possible that disease of the testicle may give rise to a miliary tuberculosis, and, although this is only a possibility, it is never- theless to be taken into consideration in deciding upon the propri- ety of removing the testicle. Salleron, in a series of fifty-one cases of tuberculosis of the testicle and the epididymis, found other organs affected in only one case. Coming now to the symptoms of the disease, it will be found that it is observed principally in youth and in early manhood, but it may also be found late in life. The disease, as has already been seen, begins in the epididymis or the testicle as a painful swelling, which reaches its full growth in a few days or weeks, and it is fol- lowed in a short time by the formation of an abscess and the estab- lishment of a fistula which may remain unhealed for several years. The progress is not always rapid, and the swelling may last several months before suppuration takes place. A long interval may elapse before the other testicle is affected. The local tuberculosis may occur without any sign of disease of the lungs or of the uri- nary organs, although the prostate usually will be found involved. The vas deferens is frequently enlarged, and it may be felt as a cylindrical cord or as a chain of nodules. This enlargement may extend for a few centimetres from the epididymis or it may be fol- lowed to the ring. It is rare that an effusion takes place into the tunica vaginalis. The walls are more frequently glued together by an adhesive inflammation. The infection of the vesicula seminalis follows disease of the vas deferens. It may also follow disease of the bladder. The walls of the duct are thickened and infiltrated and its cavity is distended with cheesy pus. When in this condition the vesiculae can easily be felt per rectum : they may reach the size of a walnut. Abscesses may form and discharge both into the rectum and the TUBERCULOSIS OF THE SOFT PARIS. 579 bladder. Weichselbaum found a perforation of one of the larger veins of the pudendal plexus by a tubercular abscess of one of the seminal vesicles. The prostate is usually affected at the same time, and chiefly on the corresponding side. Abscesses may form and dis- charge through the perineum. From the prostate the disease may extend to the bladder and produce multiple ulcerations. The presence of tuberculosis is the cause of frequent and painful micturition and perhaps haematuria. An examination of the urine for the bacilli (see p. 58) will usu- ally settle the diagnosis. Tuberculosis of the bladder rarely occurs in women : according to Klebs, it is seen only in the male bladder, as the chance of a progression of the disease from the vagina or the vulva is infinitely less than from the prostate in man. Tuberculous ulcers, however, have been seen in the female bladder. Albers reports a case of small tubercular nodules near the urethra and in other parts of the bladder. The left ureter was filled with tubercle, and there was tubercular degeneration of the medullary tissue of the left kidney. Winckel, Hewitt, and Scan- zoni all report similar cases. Two of Winckel' s cases were second- ary. In one case the disease of the bladder followed that of the lung; in the other it was preceded by disease of the kidney and the ureter. The kidneys are often involved in the form of pyelitis or of cheesy nephritis. Tuberculous disease of the testicle is so often followed by ab- scess and fistula that the diagnosis is not usually difficult to estab- lish. The so-called " scrofulous testicle " presents a clinical picture sufficiently characteristic. The scrotum is swollen and reddened, or it is perforated by several fistulae, and the testicle and its adjacent structures are found thickened and enlarged. When suppuration has not yet taken place the diagnosis is more difficult. The disease can be distinguished from syphilis, as the peculiar stony hardness of the syphilitic testicle is not present. A chronic enlargement of the testicle coming on after a slight trauma or without history of injury is suggestive of tuberculosis, and this suggestion will be strengthened if there is any evidence of tubercular disease else- where. The disease runs a milder course in old people than in early life. It may be confined entirely to the testicle, and may be cured without the involvement of any other organ, but it has been seen that it frequently spreads locally and that it may be followed by miliary tuberculosis. Although it is possible for a cure to take place without operation, the function of the testicle is probably 580 SURGICAL PATHOLOGY AND THERAPEUTICS. destroyed in all cases. For these reasons the removal of a tubercu- lous testicle is strongly advocated by most surgeons. Castration is advised even when the vesiculce seminales and the prostate are involved, as it has been observed that disease of these organs as well as of the bladder has undergone speedy improvement, and finally a cure has been effected. Castration is therefore indicated in young people when there are no evidences of advanced kidney or of lung disease. In older people the chance of a cure by local treatment is much better. It has been the writer's experience that many cases, even in young people, when the course of the disease has not been too acute, do well without operation. Andrews states: • ' I have repeatedly ventured in Illinois, where tuberculosis is far less prevalent than on the sea-coast, to take the patients through the whole affection without other operation than the lancing, drainage, and cleansing of the abscesses; and the patients have ultimately done excellently well and no infection of the lungs or the prostate followed." This experience has certainly been the writer's in several cases. Salleron mentions but two deaths in the fifty-one cases already mentioned. When the local inflammation is severe, however, and there is considerable constitutional disturb- ance, an operation is advisable. Such a case occurred to the writer recently in an overworked professional man. The testicle was at first much enlarged and there was considerable effusion into the tunica vaginalis. A few months later an abscess formed and the scrotum became greatly swollen and reddened. There were great debility and an evening rise of temperature. No tuberculosis could be discovered in any other portion of the body. Removal of the testicle and a portion of the cord, which appeared to be healthy, was followed by rapid improvement, and the patient now — several years after the operation — is in excellent health. In some of the less acute types of the disease the sinuses may be curretted thor- oughly and dressed with iodoform. Careful attention to the gen- eral health and to the surroundings of the patient is of great im- portance. The old-fashioned recommendation of a long sea- voyage is often followed by excellent results. In young adults, however, when the disease comes on rapidly and an enlargement of the pros- tate and the vesiculse seminales can be felt in the rectum, castra- tion is certainly indicated. The presence of tuberculosis of the bladder is a grave compli- cation. In some cases, however, a cure may be obtained by gen- eral treatment, combined with such remedies as have a curative effect upon the vesical catarrh which accompanies the disease. TUBERCULOSIS OF THE SOFT PARTS. 581 Operative interference is hardly indicated. In the female it would be possible to reach and to cauterize the ulcers by means of vaginal cystotomy. Applications could also be made through such an opening to the diseased surface of the bladder. Supra- pubic cystotomy might enable the treatment to be carried on in the same way in man. These operations would, however, be indi- cated only in exceptional cases. Tuberculosis of the urethra, a very rare affection, is, according to Kanfmann, always part of a generalized tuberculosis. Infection takes place secondarily from the bladder or the prostate. The prostatic portion is frequently the part affected, and also, but less often, the membranous portion. Vettesen reports a case of tubercular ulcer of the meatus in a phthisical patient seventeen years of age. There had been painful micturition for some time ; an indurated ulcer occupied one side of the meatus and extended inward into the fossa navicularis ; the glands in the groin were enlarged ; there was enlargement also of the epididymis and the prostate ; bacilli were found in the secretions of the ulcer. At the autopsy there was found exten- sive urogenital tuberculosis: the right kidne}', the bladder, the prostate, and the bulbous portion of the urethra were affected. Hnglisch describes a tuberculous peri-urethritis in the deeper portions of the urethra. It may exist either inside or outside the deep layer of the superficial fascia. It begins with a discharge of a chronic character from the urethra, followed later by the forma- tion of perineal abscesses and fistulse. Some of the cases of incur- able "watering-pot perineum " are doubtless tubercular in nature. Langhans reports a case of polypoid tubercle situated in the ure- thra about one inch from the meatus. At the autopsy there were found extensive disease of both kidneys, ulceration in the bladder, and prostatic urethra. It might be mentioned here that Senn reports a case of tubercular ulcer of the dorsum penis that might easily have been mistaken for chancre, and he dwells upon the importance of remembering the possibilities of such a lesion in making a diagnosis. Tuberculosis of the kidney may occur either as a miliary tuber- culosis, as a part of a general infection, or as a nodule or tumor of considerable size. In " nephro-phthisis," as the latter form is called, there are in the renal tissue large caseons nodules which run together, and involve so large a portion of the organ that but little healthy kidney tissue can be found. Frequently the papillae are the parts first affected when the disease has invaded the pelvis of the kidney from below, the disease working its way along the 582 SURGICAL PATHOLOGY AXD THERAPEUTICS. mucous membrane of the urinary passages. But the pelvis iu other cases may become infected secondarilv. As the tissue breaks down it is discharged into the pelvis, and the ureter inav become blocked with cheesy debris. In this way pyonephrosis may occur. There may be some enlargement of the kidney during the development of the disease, but it is offset bv the shrinking oi the cavities which form in its interior. Wedee- shaped tubercular infarctions are sometimes found which sug- gest the lodgment of an infected embolus, probably from the lungs. As the disease progresses there is frequently, as in the lungs, a mixed infection of the pyogenic cocci with the bacilli, and a suppurating inflammation hastens the process of disor- ganization. When this disorganization is completed the capsule forms a thickened wall or shell, from which spring septa, the remains of the connective-tissue stroma, the capsule enclosing a cavity communicating with the pelvis of the kidney. The walls of this cavity are lined with broken-down tissue and cheesy masses and remains of the kidney structure. When there is great dis- tention from obstruction abscess may form, or rupture into the peritoneal cavity may occur. The tubercular process may originate in the kidney as the result of tubercular disease in the lungs or elsewhere, or it may be the result of an ascending tubercular infection of the £enito- urinarv tract. The latter form of origin is far more common in men than in women. Tuberculosis of the kidney occurs at all periods of life, being found in children as well as in adults, but it is commoner in men than in women. The symptoms are those of chronic pyelitis, and they are in no way characteristic of tubercular disease. An examination of the urine, however, shows the presence of bacilli, and occasionallv also minute masses of cheesy matter in addition to pus, blood, and casts. If the urine is acid, it is probable that the kidney and not the bladder is affected. Inoculation experiments might settle the diagnosis if the bacilli could not otherwise be detected. The presence of lumbar pains and perhaps of an inflammatory swelling in the region of one kidney, or possibly a tumor, would point to that or^an as the seat of the disease. Loss of strength and emacia- tion, with anaemia, together with hectic fever, would be additional evidence in favor of tubercular disease. In the exceptional cases of isolated tuberculosis of the kidney — which cases are exceedingly rare — nephrectomy has successfully been performed. If there were indications of the presence of a TUBERCULOSIS OF THE SOFT PARTS. 583 large pus-cavity in the lumbar region, an attempt might be made to open and drain and to treat the diseased surfaces with appro- priate remedies. The tubercular membrane would not, of course, be found in such a cavity, but a great deal of debris could be scraped away, and under favorable circumstances the patient might recover with a urinary fistula. This result, although it exposes the patient to the discomforts of such a fistula, leaves a larger secreting surface than would remain if one kidney had entirely been removed. 5. Tuberculosis of the Mamma. Tuberculosis of the mamma is a rare disease. Recently Roux succeeded in collecting the records of 34 cases, in 2 of which the disease occurred in males. In 2 cases both breasts were affected. The ages varied from sixteen to fifty- two years. In only 3 cases was an injury supposed to have been the cause of the disease. In 24 cases the disease was secondary to tuberculosis elsewhere. Man- dry collected 40 cases, in 21 of which there was histological proof of the tubercular nature of the disease. He found only 1 case in which the male breast was affected, which, he thinks, shows that the functional activity of the gland is important. The ages of the patients in his series ranged from seventeen to fifty-two years. Most of the cases seemed to develop shortly after confinement. In 8 cases the patients had not borne children. In 17 cases the disease was in the right breast and in 8 cases in the left breast. In 7 cases no glands were noticed; in 17 cases there were enlarged glands, and in many of these fistulae had formed. The glands appear to have been affected secondarily, and not, as Konig suggests, primarily. According to Roux, infection appears to take place through the blood-vessels or the lymphatics, or by the breaking of tubercular foci which formed in the adjacent ribs or sternum. Roux also thinks that infection may take place through the ducts, and this appears to have been the mode of entrance of the virus in one of the writer's cases. A tubercular cavity about the size of an Eng- lish walnut formed near the nipple in a young unmarried woman about twenty years of age. A microscopic examination showed the presence of bacilli. The sinus was treated by curetting and an iodoform dressing, and it healed without further infection of the gland. According to most authorities, the principal form of tuberculo- sis of this organ is a primary disseminated or confluent type of the 584 SURGICAL PATHOLOGY AND THERAPEUTICS. disease. There may also exist an isolated tubercular nodule. There is also the cold abscess in a certain limited number of cases. Ac- cording to Roux, there may be a secondary involvement of the organ due to disease in adjacent tissues. The tuberculous breast is sometimes enlarged and sometimes it is smaller than normal. It is often riddled with fistulse, and the nipple is usually retracted. Pale, flabby granulations protrude from the fistulous openings, and pressure brings out a thin pus with cheesy masses. It contains a number of irregularly-shaped swell- ings, which on section are found to be indurations of various sizes in which there are irregular cavities with prolongations running in various directions and communicating often with one another. The walls of these cavities are lined with a soft yellowish-gray mem- brane of varying thickness, and they contain cheesy debris. The surrounding tissue is much indurated, and is dotted over with miliary tubercles. When a large tubercular nodule forms in the breast, a lump is usually seen in the upper and outer quadrant extending to the axilla. The nipple is retracted and the axillary glands are enlarged. These nodules eventually break down and tuberculous fistulae form. In cold abscess the breast is more or less enlarged by a fluctuating tumor which is situated in the upper and outer quadrant and which appears to be secondary to suppurating glands. The lining membrane of such abscesses is the charac- teristic tubercular membrane. Miliary tubercles are rare in this situation. An abscess in this locality was once sent into the writer's ward as a case of malignant disease. An exploratory incision revealed its nature. Another case illustrated secondary infection of the organ. A large collection of pus had formed beneath the gland, and had already burrowed into the breast in several directions. The origin of the pus-cavity was a carious rib. It was necessary to turn up the breast by a curved incision along its lower border in order to reach the diseased bone and to check the burrowing of pus in the mammary gland. In a third case the abscess was situated in the lower hem- isphere of the breast of a girl eighteen years of age : a bacteriological exami- nation showed the presence of bacilli in the abscess-walls. The abscess was opened and healed readily under an iodoform dressing. Under the microscope are found a large number of small tuber- cles containing giant-cells in and around the tubercular nodules. Clusters of epithelioid cells are found in the interstitial tissue as well as in the acini. Many of the giant-cells appear to originate in the acini, and, according to Bender, they are of epithelial origin, as shown by Arnold to be the case in giant-cell formations in the heart and the lungs. TUBERCULOSIS OF THE SOFT PARTS. 585 Patients are not usually aware of the beginning of the disease. Small nodules are accidentally discovered that grow slowly. In fact, the axillary-gland enlargement may have been noted first. As the nodules increase in size the skin becomes involved and the nipple retracts. The disease may last a long time without special change, but finally suppuration takes place and fistnlse form. The development of a cold abscess is almost without symptoms. The disease may be mistaken for a carcinoma which has suppurated or for a submammary abscess. Exploration with the punch or experi- mental inoculation would in most cases settle the question. In more than half the cases other organs are involved, but the prog- nosis is favorable if the disease is confined to the breast. When there is extensive disease of the breast with involvement of the axillary glands, and other organs are not involved, amputa- tion may be performed with, a careful dissection of the axilla. Attempts to treat the fistulse by curetting and the application of iodine are usually followed by a relapse. This clinical experience is in accord with the histological examination, which shows that the disease is not confined to the pus-cavities and fistulse. In cold abscess curetting may be performed, as in this case the disease is localized. The same treatment may be used for milder forms of the disease when only a limited portion of the gland is involved. 6. Tuberculosis of the Lymphatic Glands. Tuberculosis of the lymphatic glands is a more common affection than any of those hitherto mentioned. In fact, it occurs both inde- pendently and in combination with all the forms that thave been described. All those types of disease formerly known as scrofulous glands are now recognized as genuine tuberculosis. In the Bleg- dams hospital in Copenhagen, out of 384 autopsies of children who died of acute infectious disease, 198 showed undoubted tubercu- losis, and in all these cases the glands were affected. The glands of different parts of the body vary greatly in their susceptibility. On the surface of the body the cervical glands are most frequently affected, next the cubital, and less frequently the axillary glands (Volkmann). The glands of the lower extremities are much less liable to disease than those of the upper extremity. Internally the bronchial glands are frequently involved, but the existence of such disease is often overlooked. In children the glands most frequently found diseased at autopsies are the cervical, the mediastinal, the mesenteric, and the retroperitoneal glands. Babes found the cervical, bronchial, and mediastinal glands affected 586 SURGICAL PATHOLOGY AND THERAPEUTICS. in more than half of all the autopsies performed at the children's hospital at Buda-Pesth during eight years. When there is a predisposition to tuberculosis, simple enlarged or inflamed glands, due to catarrhal or to cutaneous affections, remain enlarged after these inflammations have subsided. These glands increase in size, soften, and are found, on removal, to be filled with tuberculous deposits. The two principal forms in which tuberculosis appears, large tuberculous foci with cheesy degenera- tion and miliary tubercles, can both be observed in perfection in the lymphatic glands, though the former type is the one most com- monly seen. When an enlarged gland is removed and is laid open with the knife, there is found hypertrophy of the glandular tissue that shows a pale transparent and uniform surface. In the centre are one or more cheesy masses the size of a ten-cent piece. A careful inspec- tion will show some thickening of the capsule and here and there a miliary tubercle. In a more advanced stage of the disease the cheesy masses soften down, and the cavity thus formed enlarges until nearly all the newly-formed glandular tissue has melted away, and finally the softened material breaks through the capsule of the gland and makes its way to the surface. A microscopic examination reveals the presence of giant-cells and epithelioid cells around the margins of the cheesy foci. In the miliary form well-marked examples of submiliary tubercle abound. The surrounding tissue shows merely the structure of hypertrophied glandular tissue. In the earlier stages of the process the bacilli are found, often in considerable numbers, as the soil appears to be favorable for their growth, but during the stages of suppuration it may be impossible in many cases to find a single bacillus. Never- theless, the inoculation of the cheesy material into animals always reproduces the disease. The most frequent seat of tuberculous adenitis with which the surgeon has to deal is the cervical region. The most common sources of irritation of the cervical glands, particularly in the New England climate, are the prevalent chronic catarrhs of the nose or the throat. Eczema of the face or the scalp, or chronic inflam- mation about the eyes and the ears, may also be the point of departure of the disease. These inflammations are rarely tubercu- lar, but they produce hypertrophy of the gland, which furnishes a fertile soil for the bacilli. The bacilli are readily grafted upon an inflamed skin or mucous membrane, and they can be carried thence through the lymph-stream to the adjacent glands. The TUBERCULOSIS OF THE SOFT PARTS. 587 enlarged gland may, however, receive the bacilli from the circu- lating blood, the organisms having already obtained an entrance to the body elsewhere. The glands enlarge to the size of a walnut, and they can be felt as nodules lying beneath the skin, somewhat tender to the touch, but freely movable. They may remain in this condition for years, and may eventually disappear spon- taneously. More frequently they grow gradually, and, by the matting together of several glands from capsular inflammation, form tumors of considerable size. They are usually not painful, and they may remain without further change for a long period. They are not, however, absorbed. At some moment, when the patient's condition has become enfeebled, they begin to soften and to present some of the symptoms of inflammation, and they are much more tender to the touch. It is possible in such cases that a mixed infection has taken place and that true suppuration will follow. More frequently a chronic softening takes place, and fluctuation gradually makes itself apparent. At some point the skin finally becomes adherent to the tumor, changes in color to a purplish red, and finally perforation takes place, there being discharged either tubercular pus or a small amount of pus mixed with cheesy debris, and perhaps calcareous masses. Several such openings may occur, each of which communicates with a separate cluster of glands. The skin becomes undermined, and sinuous fistulae and pockets are formed which may extend even beneath the sterno-mastoid muscle. The covering to these cavities is a deep red or a purple color, and may be as thin as paper. When the skin is destroyed in this way, tuberculous ulcers form, which after healing leave the unsightlv scars so common in tuberculous or "scrofulous" subjects. The axilla is occasionally, though less frequently, the seat of tubercular adenitis. A young woman, seventeen years of age and in good general condition, presented herself at the hospital recently for the treatment of a sinus open- ing on the inner aspect of the short head of the biceps muscle. On probing, the sinus was found to communicate with a chain of glands in the axilla extending beyond the borders of the pectoralis major as far as the margin of the mammary gland. Several operations were performed on this patient : the glands were carefully dissected out, and she left the hospital improved in health. The following winter she returned, hoping to get some benefit from the tuberculin treatment. At this time the disease had not only returned in its original site in the right axilla, but it had also spread across to the opposite side. The supra- and infraclavicular glands on both sides were also involved, and her neck was riddled with tubercular sinuses. There was also SURGICAL PATHOLOGY AND THERAPEUTICS. marked cachexia. A few weeks later, marked symptoms of tubercular peri- tonitis having set in, the patient was carried home to die. The inguinal glands may occasionally also break down and simulate a venereal bubo. The scrofulous bubo, however, is, not associated with any lesion of the genitals. The origin of the glandular enlargement is generally attributed to a sprain. A gentleman consulted the writer for this affection, which he attrib- uted to a strain received while playing tennis. Volkmann reports a case of hemorrhage from the crural artery, the result of the breaking down of a mass of inguinal glands, and also a case of secondary infection of the peritoneum and pleura. The prognosis of tuberculosis of the lymphatic glands is in certain stages of the disease not unfavorable. As has been seen, there is discovered at many a post-mortem examination infected glands whose presence during life had not been suspected. The very large number of such cases leads to the supposition that at a given moment such glands may be present and may subsequently disappear: during the early stage of the glandular affection they are undoubtedly in many cases curable. When, however, the period is reached when several glands have become matted together, forming a visible tumor in the centre of which cheesy deposits have formed, the time has arrived for operative inter- ference. If operative treatment is carried out before suppuration is established, the glands can be enucleated from surrounding healthy parts. Every effort should be made to remove all frag- ments of diseased tissue. It is not sufficient to shell out a few of the most obvious nodules: all suspected structures should be dissected away, and the whole diseased tissue should be removed en masse if possible. Senn recommends division of the mastoid muscle for the removal of the deeper-seated glands, with subse- quent suture of the muscle. The disease should be regarded as one which must be treated by the surgeon's knife as rigidly as if the case were one of cancer. It is also of the utmost import- ance — and this point is almost invariably overlooked by operators — that the greatest care should be taken to avoid local infection of the exposed healthy tissues. The readiness with which the cheesy products of tuberculosis, when introduced into healthy animals, can reproduce the disease is proof of its virulent power. Carelessness in this respect doubtless explains many cases of relapse after operation. By thorough surgery the patient may not only be relieved of an annoying deformity, but may also TUBERCULOSIS OF THE SOFT PARTS. 589 escape the dangers of pulmonary or of acute miliary tubercu- losis. Many a fatal case of tuberculosis had its origin in the "scrofulous" cervical gland. When suppuration is established and a cold abscess has devel- oped, it is not sufficient to open the abscess or even to curette care- fully its lining membrane. Usually a search with the probe will detect in the deep cervical fascia an opening, on dilating which the remains of an enlarged gland will be found as the source of the suppuration. This gland should carefully be removed, and the heal- ing process will thereby greatly be accelerated. When a small gland softens and suppurates and becomes adherent to the skin, the entire diseased mass can be included between two semi-elliptical incisions, and a clean wound will be left which can be brought together with sutures. When the skin is undermined by superficial pouches or by fistulous tracts, the diseased skin should be trimmed away with scissors, and the tuberculous granulations can then be thoroughly scraped. The importance of internal treatment in these cases need hardly be dwelt upon. Much may be accomplished in the milder forms of the disease with cod-liver oil, careful diet, and suitable environ- ment. Arsenic is supposed by some writers to have a certain specific action upon these glands. Nothing definite can yet be said on this point, but, as arsenic is also a useful tonic, it is at least worth a trial in cases where there is no great amount of cachexia. Iodide of potassium and syrup of the iodide of iron are also valu- able agents in certain cases. Primary tuberculosis of the connective tissue is rare. In the great majority of cases the disease is secondary to tuberculosis of the glands, bones, or joints. The burrowing of a cold abscess infects long tracts of connective tissue and fasciae. The primary affection occurs in the panniculus adiposus in small children. A number of small nodules form beneath the skin and run together, involving later the skin itself. These nodules are substantially the gommes tuberatleuses already described. Fluctuation is ob- served finally, and pus is discharged. Volkmann describes these nodules as the furuncular form of skin and connective-tissue tuber- culosis. Occasionally the pus may burrow and form a cold abscess quite independent of bone or joint. 7. Tuberculosis of the Tendon-sheaths. Tuberculosis of the tendon-sheaths, or tendo-vaginitis tuber- culosa, may be either primary or secondary. The secondary form, 59° SURGICAL PATHOLOGY AND THERAPEUTICS. which occasionally accompanies tubercular disease of a joint, is the variety that has been recognized as tubercular. Later studies have shown, however, that the disease may occur quite independently of any joint disease, and Garre has shown that it is not so rare as has been supposed. This observer met with twenty-five cases of the dis- ease in seven thousand cases seen by him in two and a half years. This disease occurs in two forms. Thefungotis form is charac- terized by the formation of an exuberant granulation tissue, which at times assumes the characteristic gelatinous appearance and en- velops the tendon within its sheath. At other times growths occur on the inner surface of the sheath, which growths become detached, forming the so-called "rice bodies," "melon-seed bodies," or cor- pora oryzoidea, as they are variously styled. This affection, known as hygroma, was supposed to be quite distinct from tubercular dis- ease, but it is now definitely established that the greater portion of these bodies contain tubercle bacilli. Similar bodies are found in the mucous bursse, and it has been proved, of some of them at least, that they are tubercular. These same bodies are found also in joints (hydrops fibrinosus), and they develop from the fibroid degeneration of tubercular granulations. There has been a great deal of speculation about these peculiar structures from first to last. Dupuytren, for instance, thought that they were hydatids, but the careful histological studies of late observers have definitely estab- lished their true nature. Primary tuberculosis of the tendon-sheaths occurs chiefly in adult life. It is commoner between the ages of thirty and forty than at any other period. The affection seems to follow some injury or sprain, and it is seen most frequently in laboring people. The right side is more frequently affected than the left, and the flexors more frequently than the extensors. In the fungous form of the disease the sheath of the affected tendon is lined with a grayish-red, highly- vascular tissue, which forms a long cylindrical rather firm connective-tissue growth. This growth distends the sheath of the tendon, and it is sometimes firmly attached to the tendon itself, the growth having penetrated its fibre. At other times the tendons can be dissected out clean from this tissue. The cavity of the sheath is usually not entirely obliterated, and occa- sionally rice bodies may be found in it, showing the relationship of this form to the other variety of the disease. The fungous growth may extend beyond the sheath of the tendon and invade the mus- cle. This complication is sometimes seen in the peroneal tendons. When examined under the microscope the walls of the tendon- TUBERCULOSIS OF THE SOFT PARTS. 591 sheaths are found thickened by a small-cell infiltration in which are found giant-cells. The fibrous layer of the sheath gradually disappears, and it is replaced by fungoid granulations. The visceral or peritendinous layer is also often affected. The tendon in this case appears to be thickened, and its sheath is covered with a fibrinous exudation. Under the microscope there are seen on the surface tubercular products in a state of fibrinoid degeneration. Beneath these products there is a layer of highly-vascular granula- tion tissue containing giant-cells, and next the tendon there is either a loose connective tissue or the granulation tissue has pene- trated into the substance of the tendon itself (Garre). The number of tubercles varies: sometimes they are found quite numerous and arranged in rows, each one being encapsuled in a ring of connec- tive tissue. If the cavity of the sheath remains well defined, there may be seen several layers of endothelium upon it, but this is often worn away at the points of greatest friction, and there are found papillary granulations which probably are the beginning of the rice bodies. In the hygroma type the inner surface of the cyst has slight excrescences which have undergone fibrinoid degeneration. By friction these excrescences become pediculated, and they are entirely separated as rice bodies. They consist of a stratified or a structureless fibrinoid tissue which contains only a few cell- nuclei, but here and there is a giant-cell with tubercle bacilli. These bacilli are still capable of growth, and when the rice bodies are introduced into the tissue of animals tuberculosis may be pro- duced. In many cases the inoculation fails, showing that active bacilli are not always found in these bodies. The disease, thus produced, develops slowly, demonstrating that it takes a certain amount of time for the bacilli to be liberated from their somewhat dense capsule. The wall of the hygroma cyst is also found to be in a state of tubercular degeneration. Isolated tuberculous tumors are occasionally seen in the tendon-sheaths, similar to those already spoken of as occurring in the joints and in the nasal cavity. The cell-growth in these tumors is so large as to suggest in some cases sarcomatous tissue. The symptoms of the disease are quite chronic in character, and they develop very slowly, usually dating back to some injury. The swelling found at that time does not go down, but rather increases in size and becomes painful. The tumor is flat, oval, or sausage- shaped, and it is soft, elastic, and pseudo-fluctuating. In the case of hygroma the fluctuation is quite distinct. When the diseased ^^H \^~ 592 SURGICAL PATHOLOGY AXD THERAPEUTICS. tendons run beneath an annular ligament a constriction is found, giving the tumor an hour-glass appearance. The palmar bursal tumors of the hand belong to the hygroma type of the disease, and pressure above and below the annular ligament forces the rice bod- ies to and fro in a manner quite characteristic. The skin is not involved at first, but later, when suppuration occurs, it may become infiltrated, and ulcers and sinuses eventually are formed. This is more commonly the case in the fungous type. True cold abscess is rarely seen. When cicatricial contraction sets in the function of the tendon may seriously be interfered with. If the hygroma breaks externally, acute suppuration may follow, which greatly impairs the use of the hand. In some cases the joint over which "the tendons run may become involved in the disease. The tendons most frequently affected are those situated on the palmar and dorsal aspect of the wrist (Fig. 82). In the neighbor- hood of the ankle-joint is found the fungous form in the perineal sheaths, and also in the tibialis posticus and the extensor communis digitorum. Ulceration occurs here earlier than in the hand. The plantar surface of the foot is not affected. In the neigh- borhood of the knee-joint some of the tendons may be affected with this dis- ease, but here it is much less com- mon. Secondary tubercular disease of the tendon-sheaths is almost always of the fungous type. It is important to rec- ognize this complication in operations upon the joint: otherwise the diseased tissues may be overlooked. The dif- ferential diagnosis between the pri- mary and the secondary forms is often hard to settle if the joint happens to be affected. Fatty tumors are also rarely seen Fig. 82.— Tuberculosis of Tendon- in the tendon-sheaths under the name sheaths or Palmar Bursal Tumor. of lipoma arborescens. Sendler reports such a case in a girl fourteen years of age. The tumor occupied the sheaths of the extensor tendons of the hand, and when removed it appeared as a reddish-yellow lobu- TUBERCULOSIS OF THE SOFT PARTS. 593 lated mass of fatty tissue with prolongations extending to each ten- don. Three months after the operation the patient died of pulmo- nary tuberculosis. Although in these cases the presence of tubercles does not appear to have been established by the observers, it is probable that these forms closely resemble the same tumor observed in the knee-joint in which miliary tubercles are found. Moreover, in another case there was a family history of tuberculosis, and in a third the patient was suffering from cachexia. Many of the forms of primary tuberculosis of the tendon-sheaths may be treated by excision of the diseased mass. A lady sixty years of age consulted the writer for tuberculosis of the sheaths of the peroneal tendons at their point of contact with the external malleolus. The disease extended nearly to the point of their insertion and some distance above the malleolus. She had suffered in her youth from caries of the rib. The tendons were exposed by an incision about five inches in length, and a long spindle-shaped gelatinous mass was carefully dissected out, leaving both tendons clean and bright. The wound, which was complicated by sinuses, healed slowly by granulation. Perfect motion of the joint was obtained. When the elastic tourniquet is applied these operations can be performed without hemorrhage and an elaborate dissection can be made. In the palmar bursal tumor the annular ligament may be divided, if necessary, and the tendons dissected out one by one. During the healing process the tendons appear to form new sheaths for themselves in the granulation tissue, and the func- tion of the tendons usually is but slighty impaired by the ope- ration. When this condition is secondary to joint disease the operator must pay careful attention to this complication in performing resec- tion of the joint. When resection is not indicated amputation is probably the only resource if the general condition of the patient will permit of such an operation. The prognosis is favorable in primary disease of the tendon-sheath, as the fibrinoid type of tuberculosis is not likely to be followed by metastasis. Tuberculosis of muscular tissue is very rare. A muscle may, however, be affected secondarily to disease of an adjacent bone. 8. Scrofula. Scrofula is a name that was formerly given to a large propor- tion of the affections just described as tuberculous disease, and the question naturally arises whether there are any affections which should still be classed under this head. The name is derived from sus, scrofa, a sow, to indicate the peculiar fulness which the en- 38 594 SURGICAL PATHOLOGY AND THERAPEUTICS. larged lymphatic glands give to the neck. As is now known, these glands are tuberculous, but there still remains a class of inflammations that are not tuberculous in character, to which certain children are liable, and which some authors are still inclined to include under the head of scrofula. Landerer de- scribes two types of scrofulous patients — the torpid and the ere- thitic. The former is the type generally recognized in the so- called "scrofulous child." The complexion is usually of a pale blond or pasty hue; the hair is frequently red; the features are coarse, the eyes watery blue, the lashes long, the lips thick, the nostrils large, the expression dull, and the figure inclined to plumpness. There is a tendency to chronic inflammations of the eyelids or of the cornea. There is often nasal catarrh, with fissures about the lips and nostrils, and pharyngeal catarrh, with enlargement of the tonsils. Such patients are also afflicted with chronic inflammation of the ear, and are likely to have eczematous eruptions of the face and scalp. The glands of the neck are almost always enlarged. Such children have a tendency to catch cold easily, to suffer from bronchial catarrh, and they are a constant source of anxiety. In the second type the erethitic, the children are of dark com- plexion, nervous and restless. They possess the tendency to suc- cumb easily to conditions by which healthy children would not be affected. There is less tendency to enlargement of the glands, but the same susceptibility to chronic inflammatory processes exists. This seems a somewhat fanciful sketch. There is, however, this foundation for it : namely, that there exists a type of chil- dren who are subject to chronic inflammatory infections, and who, although they may not have an inherited predisposition to tuber- culosis, nevertheless are more susceptible to the virus than are those who have sound constitutions. It is possible, moreover, that many of these inflammations, and even glandular enlarge- ments, may be due to other microbes than the bacillus of tuber- culosis, and the observations and experiences of quite a number of observers appear to strengthen this opinion. Charrin and Roger studied an organism which produces a lesion similar to that produced by the bacilli of tuberculosis. They found in the liver and spleen of a guinea-pig which died in the labora- tory, not having been the subject of experiment, numerous minute granulations resembling miliary tubercles. On taking gelatin cul- tures from these they obtained at the end of forty-eight hours a whitish growth which grew for a few days without liquefying the TUBERCULOSIS OF THE SOFT PARTS. 595 gelatin. Under the microscope the organisms appeared as movable bacilli from 1 to 2 fi in length. Inoculation of animals subcutane- ously produced a local tumor containing cheesy matter and accom- panied by a swelling of the adjacent glands. At the autopsies the spleen and kidneys were found enlarged and full of miliary nodules. A large number of experiments with this organism were followed by a constant result. PfeifTer describes also a short bacillus which when introduced into mice produces enlargement of the adjacent glands and nodules in the spleen and liver, and also in the in- testine. Cornil and Babes report two cases occurring at Bucharest of acute bronchitis accompanied by the formation of miliary nodules. In the first case there was also intermittent fever. At the autopsy miliary tubercles were found around the bronchi, which tubercles, when examined, were found to contain chains and clusters of oval microbes about 0.8/i in size. Cultures in gelatin produced a foul- smelling bacillus about 0.6/i in length. In the second case, in which there was no malaria, the same organisms were observed. Malassez and Vignal as early as 1883 described under the name of tuberculosis zoogloeica a disease microscopically resembling tuberculosis. In the centre of the nodules were found large zooglcea masses of a variety of different organisms, but no bacilli of tuberculosis. Zagari obtained gelatin cultures at ordinary temperature from tubercular nodules in a guinea-pig. A fragment of this culture introduced into the subcutaneous cellular tissue of another guinea- pig reproduced the same disease and the same organisms. Each nodule under the microscope appeared to consist of a collection of small round-cells, "infiltration" cells, and leucocytes. The bor- ders of the nodule were not well defined, but the growth spread irregularly into the surrounding tissue. Other nodules showed the epithelial type and occasionally also giant-cells. Signs of hyaline degeneration were found in the nodules and also in the neighboring tissue. In the centre of each nodule was a mass of peculiar gran- ular consistency which appeared like cheesy material. By a some- what complicated method of staining it was found that these central masses contained bacilli with rounded ends, 1// long, and also oval bacteria from 0.4-0.8// long and about 0.3/i wide. In the centre were long chains and threads ; at the periphery were short bacilli and isolated micrococci. In the surrounding granulation tissue there were small groups of micro-organisms, some of which were micrococci and some diplococci, arranged in coils or straight lines — 596 SURGICAL PATHOLOGY AND THERAPEUTICS. all apparently phases in the growth of the same organism. After frequent inoculations the type changed to a finer miliary nodule. To reproduce the coarser nodules it was necessary to introduce small amounts of the culture into the intestinal canal or to subject the organism to the drying effect of the air, or to a lower temper- ature, or to a struggle with other organisms. Zagari thinks that this virus, which is evidently widely spread in nature, should be studied with reference to its occurrence in man. Some of the cases of peritonitis reported above were found not to be genuine tubercu- lar disease. It is highly probable that further study will show that the bacil- lus of tuberculosis is not the only organism capable of producing this type of chronic inflammation in man. Surgeons are, in fact, still but on the threshold of this line of investigation. XXVII. DISEASES OF BONE. i. Osteomalacia. Osteomalacia is a disease of the bones in adult life that occurs most frequently in puerperal women, but it is seen also in women who are not in the puerperal state and in men. It is characterized by a progressive softening of the bone-substance, giving rise to deformity and sometimes to fracture. The first change noticed in osteomalacia is a gradual absorption of the lime-salts from the outer v\ s * Fig. 83. — Trabecula of Bone in a case of Osteomalacia — on the left osteoclasts, and on the right osteoblasts (oc. 3, obj. D.). layers of the trabecular or those layers in direct contact with the medullary tissue. The portion of the bone thus decalcified is com- posed of fibrous or striated tissue in which are found the bone-cells: 597 59§ SURGICAL PATHOLOGY AND THERAPEUTICS. these cells, however, have changed somewhat in shape, having lost their prolongations, and some of them having entirely disappeared. The outline between the bony tissue which still remains in the centre of the trabecular and this altered tissue, which may be called "osteoid tissue," is said to be well denned. Sometimes the trabec- ular become quite irregular, presenting indentations or the so-called "Howship's lacunae." The bony trabecular become narrower and narrower, and they may disappear entirely as the disease advances, leaving the osteoid tissue, which in its turn may be absorbed by the action of the osteoclasts. In case of improvement, however, the lime-salts may be deposited again and the trabecular may assume their former condition. In well-advanced stages of the morbid process destruction and repair may be seen going on simultaneously, the osteoclasts causing absorption of the bony tissue, and the osteoblasts formation of new bone (Fig. 83). In the mean time the medullary tissue throughout the bone is undergoing a marked change. The fatty tissue of which it is mostly composed in adult life is infiltrated with round-cells, and there is also hyperarmia of the blood-vessels; which affection changes the tissue into one resembling the red marrow of infancy. This tissue appears to take on active growth and to deprive the surrounding bony trabecular of their lime-salts, and subsequently to break up and absorb the decalcified bone. The trabecular of the spongy bone are gradually absorbed, the Haversian canals become wider, and the cortical bone is soon converted into spongy bone. As the bony tissue gradually melts away there is little left but marrow and periosteum if the process continues long enough (Fig. 84). Bones in which the disease has made much progress become, therefore, soft and yielding, and they are easily twisted out of shape or are broken, and they can readily be cut through with a stout knife. The cortical layer of a long bone like the femur sometimes becomes as thin as paper, and its marrow has a red, succulent, spongy look. Numerous hemorrhages often occur in the vascular medullary tissue, and pigment is deposited. This new tissue may at any time undergo mucous degeneration, many of the cells dis- appearing and a gelatinous intercellular substance taking its place, or it may appear as a yellowish fatty tissue. In some cases the gel- atinous softening takes place to such an extent that cysts form, sometimes of considerable size. Later it may resume its medullary activity and continue the destruction of the bone, for it would seem that it is owing to this unusual activity of the medullary tissue that the bone is deprived of its salts and is absorbed. DISEASES OF BONE. S ( )9 Although osteomalacia is regarded as a degenerative process, the changes seen in the cellular structures closely resemble an in- flammatory process, so far as the formation of a granulation tissue is concerned; but there is not found other evidence of bone-inflam- Fig. 84. — Section of Femur in a case of Osteomalacia : below is the medulla rich in cells, and above, the periosteum (oc. 3, obj. A.). mation, such as the formation of new bone. One indication of a disturbance of nutrition is the chemical change seen in the bone in this disease. The presence of lactic acid in excess in the bones affected has been supposed by several writers to be the cause of the absorption of the lime-salts. At certain periods of the disease lactic acid has been observed in the urine. This acid was found to diminish greatly in the cases reported during convalescence, and to disappear entirely with cure. Lime-salts have been found to a very limited extent in the urine. A chemical examination of the bone shows marked diminution of the gluten, and there has been found in the urine an albuminous substance which has been sup- 6oo SURGICAL PATHOLOGY AND THERAPEUTICS. posed to be connected in some way with this change. The signif- icance of these chemical changes, however, has not been suf- ficiently determined to throw any light upon the origin of the disease. It has been thought possible that the disease might be of bac- terial origin, owing to the fact that it is often found in damp dwellings and it has followed sudden drenching of the clothing. Animals improperly fed and kept in damp stalls have also suffered from the disease. In a certain prison in Prague the disease ap- peared to prevail. It is, in fact, more frequent in certain localities than others, and it is observed frequently in Bavaria, Westphalia, Alsace, and along the borders of the Rhine, but in other parts of Germany it is extremely rare. It is rarely seen in England and in America. According to Busch, in 1888 only one hundred and sixty cases of this disease had been reported. Eighty-five of these cases were women in the puerperal state, and all were between twenty and forty years of age. Frequent pregnancies and long nursing, with poor opportunities to obtain proper nourishment, seem to have been the condition most favorable for the development of the disease in these cases. An analysis of these cases shows that the pelvis and the spine are the parts most frequently affected, far more so in puerperal cases than in non-puerperal women and in men. In the latter class all regions of the skeleton were affected, but in both classes of cases the disease was found less frequently in the head than elsewhere. Fehling attributes the disease to a pathological increase in the activity of the ovaries, in consequence of which there is a reflex action exerting itself upon the vaso-dilators of the blood-vessels of the bones. As the result of this there is hyperemia, under the influence of which an absorption of bony tissue takes place. This view is based upon the fact that a marked improvement of the dis- ease has followed removal of the ovaries. Fehling regards osteo- malacia, therefore, as a reflex tropho-neurosis of the osseous system proceeding from the ovaries. Winckel and others who have had experience in ovariotomy for osteomalacia do not accept this view. The sympto7ns of the disease begin usually after confinement. The patient complains of acute pain in the pelvis and in the lum- bar region, with radiating pains down the thighs and up the back. They are more severe at night, and continue throughout the prog- ress of the disease. The morbid change almost always begins in the iliac bone in puerperal cases. Pressure or movement seems to aggravate the pain, which is brought on by the weight borne upon DISEASES OF HONE. 6oi the pelvis when in the sitting posture. As the disease spreads and involves the spine and the inferior extremities, standing and walk- ing become painful. The deformity of the bones now becomes apparent. If the spine curves forward, there is lordosis; if the curve is backward, there is kyphosis, and with this malformation the ribs are often pressed in upon the spine. There may also be lateral curvature, or scoliosis. The vertebrae are compressed by pressure against one another, and the stature of the patient is in this way often materially diminished. The deformity of the pelvis consists principally in an approximation of the acetabula. The promontory of the sacrum and the symphysis pubis are brought close to each other. In the long bones fracture often occurs. The deformity of the pelvis is so great that in subsequent confinements, notwithstanding the softening of the bones, normal delivery "cannot take place, and ovariotomy or Caesarian section must be performed. In the extremities the softening of the bones permits of their being twisted about in every direction. If respiration is not interfered with, the internal organs usually perform their functions well. In severe forms of the disease there may be bronchial catarrh and diarrhoea with cachexia. In some cases there is often a spasmodic action of the muscles, and some- times convulsions. Fever is not present at first, but in the later stages a hectic fever may establish itself in case of inflammatory complications. A remission of the symptoms often occurs after recovery from a confinement, but with the return of pregnancy the disease reappears. The intellect does not seem to suffer. The section of bone shown in Figures 83 and 84 was taken from a case of spontaneous fracture of the left femur. The patient, a native of Ire- land and twenty-two years of age, was confined twenty-two months before, being delivered of a seven-months' child. Since then she had suffered from stiffness of knee and pains in the thigh of the left limb, and also in the right limb. The record of the case does not state the cause of fracture, which was at the junction of the upper and middle thirds of the femur. The bone fail- ing to unite and there being suspicion of malignant disease, the thigh was amputated. The next day a fracture of the right thigh was discovered, which united without delay, but six months later the patient was still unable to stand upon it. The prognosis of the disease appears to be extremely unfavor- able, particularly in its puerperal form. Of 87 such cases reported "by Lietzmann, 60 died, although it should be said that a majority of these cases died of complications occurring during confinement. The duration of the disease may, however, be long, varying all the way from two to ten years. The prognosis is somewhat more 602 SURGICAL PATHOLOGY AND THERAPEUTICS. favorable in non-puerperal cases. In its early stages the disease may be mistaken for rheumatism or for syphilis, owing to the peculiar osteocopic pains. With the appearance of deformities in the bones or of fracture there is usually little doubt as to the diagnosis, although it may be supposed that some of the bony displacements are caused by the presence of malignant disease. In the treatment of osteomalacia there appears to be no thera- peutic agent which seems to exert a beneficial effect upon the condition of the bones. The remedy which has most often been used — namely, the phosphate or carbonate of lime — is thought by- some to be worthless and to throw additional work upon the kidneys; but the fact remains that there is an unusual drain upon the system of these chemical substances, and an artificial supply may at least tend to restore the desired equilibrium. The employ- ment of food rich in lime-salts, such as vegetables, fish, and meat, and porter, is recommended. Careful attention to the diet is probably the most important requirement in the management of the case. Cod-liver oil (with or without phosphorus) and iron are tonics frequently recommended for this affection. They have no specific action upon the processes going on in the bone, but they serve the purpose of maintaining the patient's strength, and thus placing the system in a condition more favorable for reparative processes. Women should be warned of the dangers of a second pregnancy. Recently ovariotomy has been performed for this affection. In the early Porro operations, which were performed on women with rachitic pelves, it was found that a rapid improvement of the disease followed the operation. It occurred to Fehling, therefore, to try the effect of the removal of the ovaries. Winckel proposed that the operation should be limited to such cases where all other methods had failed and the patients had already had many children. The first operation of this kind was performed in 1887, and since that time 41 cases have been operated upon, with 5 deaths, or a mortality of 12 per cent. Of these cases, 2 died of sepsis and 1 of fatty degeneration of the heart. A marked improvement was observed very soon after the operation, but it was not always permanent. The pains in the bones, particularly in the pelvis and thighs, were greatly relieved. The ability to walk came more slowly. In the majority of the cases there was permanent cure. In the case of pregnancy Porro' s operation — or, as a substitute, Caesarian section combined with ovariotomy — may be performed. In the great majority of cases DISEASES OF BONE. 603 Potto's operation (removal of the uterus and ovaries) is the one which should undoubtedly be chosen. 2. Rickets. Rachitis, or rickets (/>«^c, a spine), is a disease of infancy and childhood characterized by a disturbance of nutrition and an irreg- ular development of bone, causing a change in its composition, texture, and form. The period of life at which this disease is most commonly seen is in the first and second years. In a series of cases compiled by Bradford and Lovett, 710 occurred in the first year, 831 in the second year, 232 in the third year, 50 in the fourth year, 27 in the fifth year, and after that period 26 cases only. It seldom begins before six months or after three years. Rickets is occasionally seen in individuals at the age of puberty, although the affection at this period is rare. It is an old theory that rickets is due to an abnormal develop- ment of acids. Heitzmann suggested that it may be due to the presence of lactic acid. This acid is supposed to be formed in the body as the result of digestive disturbances, acting as an irritant on the bone-forming tissues and causing solution and excretion of lime-salts. According to other authorities, the absence of lime is explained by its insufficient administration in food. Kassowitz called attention to the great vascularity of the medullary tissues in rachitic bones, and he sought in this condition of the bone an explanation of the disease, which he assumed was due to inflam- matory hyperaemia of the osteogenic tissues. Pommer, seeing the early and frequent disturbances in the motor system in this disease and the frequent complications of the nervous system, advanced the theory that the disease has its origin in the central nervous system. According to Monti, the cause of rickets lies in a defective nutrition of the affected children. All forms of nutriment which cause dyspepsia, and consequently makssimila- tion, or which do not contain the proper nutritive elements, bring on rachitis. The artificial feeding of children with patent foods has been thought to be a fertile source of the disease. In menage- ries, where animals live under highly artificial conditions, rickets is often seen. Any disease or condition of life which favors debility in an infant serves as a predisposing cause. Bad hygienic surround- ings, damp dwellings, crowded tenements, and poor ventilation are conditions under which the disease seems to thrive. Acute febrile 604 SURGICAL PATHOLOGY AND THERAPEUTICS. diseases, such as pneumonia, scarlet fever, and measles, are frequent forerunners of rickets. Rickets is not so distinctly an inherited disease as one resulting from an enfeebled condition of the parents engendered by constitutional affections, such as syphilis or tubercu- losis, or as the result of poverty. Rickets is common in Northern and Middle Europe, and especi- ally in England. In America the disease is neither very prevalent nor severe, and, except in negroes, Italians, and Portuguese, very great deformity is rare (Bradford). According to Stedman, it is much less common among the children of Irish parents, but negroes are, almost without exception, rachitic. The disposition in the colored race seems to be an acquired one, for it is said that native Africans seldom, if ever, show any evidence of the disease. Rickets may develop during intra-uterine life (foetal rickets), or it may begin then and develop fully after birth (congenital rickets). The principal pathological change is seen at the epiphyseal lines of long bones and beneath the periosteum. It consists apparently in an insufficient supply of lime-salts to the bone, and is character- ized by an extensive absorption of bony tissue and the formation of bone without lime-salts, or the so-called u osteoid tissue." A description of the normal ossification of long bones at the epiphyseal line serves to make clearer the peculiar changes seen in rickets. Near the line where cartilage and bone come in contact are seen the cartilage-cells beginning to increase in numbers, and as this line is approached they are arranged in columns. Arriving close to the line, these columns are found to contain cartilage-cells closely packed together and much increased in size. These changes are characteristic of active growth in the cartilage. At the line of junction with the bone it is found that the further growth of the cartilage is arrested by the deposition of a narrow layer of lime- salts. Directly below this calcified layer is the medullary tissue of the bone, with its loops of blood-vessels pushing up against the calcified zone, which it presently absorbs. The cartilage-cells lose themselves in the advancing medullary tissue, some of them probably becoming marrow-cells. As these finger-like processes of vascular tissue push their way up into the cartilage, the tra- becular of cartilage left between them are partly absorbed, and partly changed into bone through the agency of osteoblasts which form around them. The most marked divergence from this process in rickets is the absence of the calcification-line which is so constant and so charac- teristic a feature of the normal growth of bone. In severe forms DISEASES OF BONE. 605 it is wanting entirely; in moderate rickets traces of it may be found here and there. The next most important change — and one that never fails — is the increase in size of the zone of active cartilage- cell growth. The columns of crowded cartilage-cells extend over a much greater area than normally. The third important change is the formation of the most irregular and enlarged and highly- vascular medullary spaces, which grow up into the cartilage in the most tortuous shapes (Ziegler). The white line of calcification between cartilage and bone is therefore wanting; the growing cartilage forms a very broad transparent layer, and the boundary- line between cartilage and bone is most irregular. Patches of car- tilage are consequently seen still unaltered much below the upper edge of the bony tissue. The rest of the cartilage, as it is gradually enveloped by the vascular medullary tissue, changes into osteoid tissue. A zone of osteoid tissue — that is, bone which has not yet become calcified — is formed beneath the cartilage. This zone is consequently more or less soft and yielding, and it has a tendency to bend under pressure. These osteoid trabecular have no regular form or arrangement like the normal bony trabecular. Still lower down are found lime- salts deposited in the central axes of these trabecular, and in this way a layer of partially ossified substance is formed. In the peri- osteal layer of growing bone spongy bone-tissue forms, partly by the absorption of old bone and partly by the formation of osteoid tissue, so that when the disease is well advanced the surface of bones is covered with a highly vascular tissue which offers resist- ance to firm pressure, but which can easily be cut with a knife. While in this stage of the disease the condition of the bone resembles strongly that seen in osteomalacia; the difference lies in the process. The layer of bone which has no lime-salts in it is, in the case of osteomalacia, decalcified bone; in rickets it is newly- formed osteoid tissue. The bone which contains lime-salts is in osteomalacia always old bone; in rickets it is partly old and partly newly-formed bone (Ziegler). As a result of the disturbance of the process of ossification there is thickening of the ends of the bones, caused by a growth of epiphyseal cartilage. The periosteal growth of uncalcified osteophytes causes a thickening of the shafts of long bones and of the outer table of flat bones. When a cure finally takes place the bones appear unusually thick and heavy. The bones often fail to attain their full growth, owing to this disturbance at the growing point, and as a result of the yielding nature of the new tissue they 6o6 SURGICAL PATHOLOGY AND THERAPEUTICS. are unfit to perform their functions properly, and they become bent by pressure or twisted out of shape by muscular action. If the periosteum of a long bone is the principal seat of the disease, the shaft of the bone becomes curved; if, however, the disturbance is greater in the epiphyseal line, there will be a crook at the end of the bone when pressure is brought to bear upon it. In conse- quence of these changes in the skeleton the subjects of rickets become not only deformed, but are often greatly stunted in their growth (Kg- 85). The accompanying illustration (Fig. 85) is from a drawing of the skeleton of an Indian, twenty-one years of age, one of the Six Nations. His mode of locomotion was by a large wooden bowl in which he sat, and moved forward by advancing first one side of the bowl and then the other by means of his hands. The nodules or ''ad- ventitious joints" were "the result of im- perfect ossification, or, in other words, of motion before ossification was completed." The principal deformity of the head appears to consist in an enlargement of its transverse diameter, and there is a great prominence of the frontal and pa- rietal bones. The head has the appear- ance of being unusally large, but care- ful measurements seem to show that this is due partly to its shape and partly to the imperfect development of other re- gions of the body. The fontanel les remain open an unusual length of time, and the parietal and occipital bones are often soft and yielding, giving to the touch a parchment-like sensation, due to the absorption of bone at certain points, while at others it remains very porous. This con- dition is known as craniotabes. The sutures also remain broad and soft and membranous. The bones of the face appear to be impeded in their growth, and they give, therefore, to the skull an appearance of unusual size. Dentition is in consequence retarded, and the teeth show an unusual tendency Fig. 85. — Extreme Deformity of Skeleton due to Rickets, showing enlargement of the ends of the bones (Sp. 1545, Warren Museum). DISEASES OF HONE. 607 to caries. The upper incisors considerably overhang the lower. The very profound disturbance of nutrition which permeates the entire system is shown particularly in the changes found in the brain, which is often enlarged. More frequently, however, there is effusion into the ventricles, and as the result of this there is occasionally hydrocephalus as a complication of the disease. As a rule, these effusions come slowly, and they may eventually be absorbed. If they occur rapidly, they are often accompanied by convulsions, which may terminate fatally. The earliest change seen in the thorax is a slight swelling of the sternal ends of the ribs or at the line between cartilage and bone. This row of protuberances, which is very characteristic of the disease, has often been called the "rachitic rosary." These swellings are caused partly by the growth between cartilage and bone and partly by periosteal growth. Deformities of the thorax are due to the pressure of the atmosphere on the thorax-wall, and to muscular action, and to the impairment of growth of the ribs. The circumference of the chest is small, and there is a sinking in of the ribs in respiration at the point of insertion of the dia- phragm. Gradually the whole side of the chest becomes flattened. In this way the so-called "pigeon-breasted" deformity is pro- duced. The clavicles are usually bent forward in a sharp curve, and the scapulae may also be more or less distorted. The spinal column may be curved backward. Kyphosis is a very common deformity in this disease. Scoliosis and lordosis are also not unfrequently seen. The pelvis in moderately severe rickets is somewhat flattened; the sacrum sinks deeply into it, and the lower portion of the bone is bent sharply forward. The iliac bones are small and flaring. If the pelvic bones are excessively softened, the promontory of the sacrum protrudes, the region of the acetabulum is pressed inward, and the symphysis becomes prominent, the deformity somewhat resembling that seen in osteomalacia. Epiphyseal swellings are seen at the wrist- and ankle-joints, and in severe cases at the ends of the phalanges of the fingers and the toes. Where the shaft of the long bone is profoundly affected, not only deformity, but even fracture, may occur. The humerus and the femur appear to be the bones most liable to break under these circumstances. In the graver forms of the disease there is usually a prodromal stage, during which a change seems to have taken place in the child's character. It no longer seems disposed to walk, and may 608 SURGICAL PATHOLOGY AND THERAPEUTICS. not even be willing to leave its bed. Its temperament becomes irritable, and there is a great restlessness at night, with a tendency to throw off the bed-clothes. Some children have a tendency to bore their heads into their pillows, so that the scalp is often deprived of its hair. The appetite is capricious, and diarrhoea is not an infrequent accompaniment of an outbreak of the disease. There is loss of strength, and the skin becomes pale and is often bathed with perspiration, particularly about the head. A more or less well-marked febrile disturbance accompanies these symptoms, which may continue for two or three months. When the changes in the bones have developed the appearance of the child is strikingly characteristic. The patient is diminutive for its age. The head is apparently large, the face small and pinched. The expression is intelligent, and the child is preco- cious rather than backward in its mental development. The muscles are soft and flabby, but there is no actual impairment of their movements. Although there is no genuine paralysis, reflex nervous disturbances are not uncommon. There is often great hyperesthesia of the skin. Colicky pains in the abdomen are explained in this way, as are also attacks of laryngeal spasm, which is apt to accompany the hydrocephalic condition or inflammation of the air-passages. The parts of the skeleton most likely to be affected first are the bones of the wrist and the ends of the ribs. Kyphosis is also a most common deformity, the curve being most frequent at the juncture of the dorsal and lumbar regions. The articulations are in general more or less relaxed. Later the other osseous deform- ities already mentioned occur. In the lighter forms of the disease the constitutional disturbance may be very slight. Beyond a tendency to diarrhoea there may have been no disturbance whatever, and the first evidence of any disease may be the deformity in bone. In some cases the children appear to be in robust health. The disease in the bone may in this case be well marked: there may be found swelling of the ankles, the wrists, and the knees, and curved spine, narrow chest, and protuberant belly when the lower extremities are affected. The child assumes the rachitic attitude on standing. The thighs are straddled, the knees bent, the shoulders thrown back, and the belly prominent. The disease is usually very slow in its progress, and it may last one or two years. In America the prognosis is rarely grave. In the severe cases death rarely occurs as a direct consequence of the DISEASES OF 'BONE. 609 disease, but rather as a result of the enfeebled condition combined with some complication. When the deformities are well marked they may remain permanently in a certain degree. Sometimes a spontaneous straightening- of a curved limb may take place. Spon- taneous arrest of the disease mav occur at any staee. The most effective prophylactic treatment consists in the proper feeding of children. The child should be kept at the breast as long as possible during the first year of its life. If the disease comes on during the nursing period, it may be necessary to resort to bottle- feeding or to careful attention to the condition of the mother's milk. In artificial feeding the rules of sterilization of food should be adhered to strictly if it is possible to carry them out. After six months the child may be given meat-juice or raw beef in small quantities. Baths and friction of the skin have often a beneficial effect upon the circulation, and they are strongly recommended by Monti. Cod-liver oil may be given in small doses even during the first year of life. Stimulants in small doses are also well borne in the very young, and they take the place of a tonic. Iron may be given to older children. The tincture of eucalyptus globulus in doses of from 10 to 40 minims, three or four times a day, is recommended by Stedman. The compound syrup of the hypophosphites and the syrup of the lactophosphate of lime are remedies which are fre- quently given. Kassowitz, whose theory of the disease has already been referred to, recommends very small doses of phosphorus, and he regards this drug almost as a specific for the disease. He bases his view upon an experimental study of its effects upon animals. The dis- ease being due, in his opinion, to an increased vascular action of the bone-forming tissues, he finds that phosphorus produces a decrease of vascularity and prevents an absorption of bone. Small doses of phosphorus were found by him to check the softening of the bone in a comparatively short time. These views are not, however, shared by other writers who have tried this drug. Brad- ford and Lovett find the syrup of the iodide of iron the most useful of the many drugs advocated in rickets. 3. Osteoporosis. Osteoporosis, senile atrophy, and fragilitas ossium or osteo- psathyrosis ( ( g»\ these organisms in cancer 43k J /~*% of the nipple, suggests that ^^*%1 ^ e corpuscles may have XJ? .jJ become implanted between the papillae of the nipple during washing, as the coc- cidia live in water. The cultivation experiments of Balbiani in wet sand have already been alluded to. Haviland, who made a care- ful study of the geographi- cal distribution of cancer in England, found that the disease is most prevalent in marshy regions and in the wet soil of river-basins sub- ject to inundations. Wood- head points out that the conditions present in these localities are exactly those necessary for the development of psorosperms in rabbits — a disease which is most frequently met with among rabbits whose run is over marshy ground or over narrow areas where the drainage is imperfect. Observers are not unanimous, however, as to the parasitic nature of these organisms. Schutz thinks that most of the questionable intercellular structures found in carcinomata should be regarded as Fig. 89. — Cell-inclusions in Cancer of the Breast, the so-called "protozoa" (oc. 3, obj. -^ oil-im.). CARCINOMA. 643 due to leucocytes which have become imbedded in the cell. Klebs, after careful study and experiment, decides that there are no posi- tive grounds for regarding these cells as parasites. He sees in the presence of these cells within the epithelial cells evidence ap- parently of the old French theory of the action de presence, the leucocytes exerting a fructifying influence upon the cancer-cells and causing them to multiply. Many still hold to the old idea that they are degenerated epithelial cells. All attempts to cultivate these cells from cancer- growth appear to have failed, and the num- ber of cases in which cancer has been inoculated successfully into animals is exceedingly limited. Hanau succeeded in transferring a typical epithelium from a rat to two other rats. He succeeded also in transplanting an epithelioma from one part of a man to another portion of his body, and in obtaining metastatic deposits around the implanted growth. Cancer has been transferred from one locality to another in the same individual in several other cases. Wehr also successfully transferred cancer from man to dogs. Hanau does not, however, regard his experiment as proof of the infectious nature of cancer. Councilman does not consider these structures parasitic, having seen them in many other morbid processes as well as in cancer. The parasitic origin he does not think has yet been proved, and on theoretical grounds it is hardly likely to be proved. Park, how- ever, sees in these investigations sufficient to encourage the hope that surgeons are on the eve of great discoveries which will settle the question of the origin of cancer. Cancer is said to be less common in tropical than in temperate climates. Haviland, as has been seen, proved the disease most prevalent in damp and in low-lying districts in England. It is said to be less frequently seen in Turkey, in Egypt, and in the West Indies, but this is doubted by Ziemssen. Negroes are generally supposed in America to be much less afflicted with cancer than the white race. In England statistics show that there are about 30,000 patients suffering at all times from cancer. In the Tenth Census of the United States (1880) Billings states that the number of deaths during the census year was 13,068, of which 4875 were males and 8193 were females. He found also that cancer is most frequent among farmers, hotel- and restaurant-keepers, carpenters and joiners, physi- cians, clergymen, and sailors, while it is comparatively rare among printers, railroad officials, clerks, government officials, factory operatives, miners and iron- and steel-workers. An interesting map prepared by Billings shows that cancer is especially prevalent in the New England States and on the Southern Pacific coast ; that it is prevalent in New York, Pennsylvania, 644 SURGICAL PATHOLOGY AND THERAPEUTICS. and Ohio, in the interior of Michigan, and in the southern part of Wis- consin. It is least prevalent in the Mississippi Valley and in the South, and the proportions are generally lower in the coast regions than in the interior. According to Park, the mortality from cancer is larger in and about Western New York and the adjoining region than in any part of the country save a limited area in California. Shattock has recently called attention to the fact that cancer, like tubercle, may repeatedly show itself in certain houses. This author reported a series of four cases of cancer occurring within fourteen years in persons unrelated by blood who were living in a single house. Power reports the history of three housekeepers who slept in suc- cession for several years in the same bed-room. The first lived in the room for thirteen years and died of cancer of the stomach; the second after a residence of twenty years died of cancer of the liver; the third died at the end of eight years of cancer of the breast and uterus. They were all in good health at the time of their instal- ment in the position. Chapman reports a series of three successive unrelated occupants of a house who became affected with cancer of the rectum. The cancer-cells, by their peculiar form, indicate their origin from epithelium. They are large cells of varying sizes and shapes, containing one or more round or oval nuclei with large, glistening nucleoli. They retain more or less the appearance and arrange- ment of the parent cells, so that the descendants of epidermic cells have the rough edges and a tendency to the horny change, and those which grow from cylinder epithelium have a tendency to re- main cylindrical ; but this is not always so, and in consequence of the rapid growth the cells are crowded into various shapes and they assume a polymorphous type. The departure from the anatomical type is so great at times that the new growth, although still epi- thelial, might with justice be regarded as a caricature of the nor- mal cells. The stroma, which is composed of fibrous tissue, is usually more or less infiltrated with small round cells. It may be abundant or scanty. When there are few epithelial cells the stroma makes up the greater part of the tumor, and there is a dense, hard growth, but when the epithelium appears to predominate the trabecular, which separate them into different clusters, are thin and the growth is soft. If the cut surface of a soft cancer be scraped with the sharp edge of a knife, there is obtained a milky fluid, the so-called sue canckreuse, which was supposed to be a diagnostic sign of can- CARCINOM. I. 645 cer, but which is merely the fluid and the pulpy tissues that contain the cells. There is nothing specific in the appearance of these cells. Usually there are several clusters of cells adherent to one another, which are suggestive of cancer, but a positive diagnosis can be made only with the microscope, when the epithelial cells are seen lying in their alveoli. Cancer begins to grow by multiplication of the epithelial cells of the part. If the very first change seen in a cancer of the breast be studied, a proliferation of the epithelium of an acinus will be found, so that it becomes distended with the growth. The hyaline membrane of the tunica propria presently disappears, and later the outer layer. The epithelial growth now breaks through into the surrounding connective tissue and makes its way along the route of the lymphatics. The rapidity with which such a growth may take place depends largely upon the power of resistance of the sur- rounding tissues. The thin walls of a gland or a duct may yield readily, but the thick layer of the corium is much more resistant, and carcinoma in this region pursues, therefore, a much more chronic course. The route through which cancer spreads to distant parts is through the lymphatic system. In this respect it differs from sarcoma, which spreads much more frequently through the blood- vessels. The cells are pushed forward chiefly by the pressure caused by their growth. It is possible that they may progress also in virtue of active movements that have been observed in them (Carmalt). The lymphatic glands are affected early in the disease. In a case of cancer of the breast which the writer removed recently the patient was able to state the exact date of its origin, the place where the growth was formed having been examined a day or two before. The opera- tion was performed when the growth was three weeks' old, and already a nodule the size of a small pea was found in a lymphatic gland of the axilla. If such a gland be examined, at first the lymph-spaces will be found crowded with cancer-cells. The tissue of the gland is soon invaded, however, and it becomes plugged by the new growth, so that the disease is arrested for the moment at this particular point. Later the cells grow into the neighboring tissue and the process of infection continues. As the cancer spreads it becomes more vigor- ous in its growth, and during the later stages of the disease it destroys dense fascia and even bone. It progresses here by substituting its tissue for that of the organ which it invades. Occasionally it may 646 SURGICAL PATHOLOGY AND THERAPEUTICS. be carried through the blood-vessels in an embolus to a distant organ. The internal organs that are most frequently the seat of metastatic deposits are the lungs and the liver. The secondary deposits are usually nodular in character, but occasionally there may be diffuse infiltration of an organ, as if the capillary vessels had been filled with an infective mass of cancer. The secondary nodules, as a rule, show a strong resemblance in their structure to that of the original growth; even some of the degenerative changes seen in the primary growth may be repeated. Occasionally in rapidly-growing cancers the metastatic growths may depart from the original type, and in some cases the cell- growth is so active that the alveolar arrangement seems to be lost, and it is only by careful study that carcinomatous structure can be demonstrated. In such rapid forms of growth a general metasta- sis may take place, to all parts of the system probably, by multi- ple minute emboli. Such a condition is termed an acute miliary carcinosis. The constitutional disturbance caused by the disease is known as the cancerous cachexia, and it consists in rapid emaciation, anaemia, and loss of strength. The growth of cancer is supposed to produce this condition in virtue of the injurious influence which it exerts upon the organs. It also abstracts material from the system for the nutrition of the growth. Rindfleisch assumes that the normal epithelial cells aid in the elimination of certain chemical substances from the system. When, however, these cells are enclosed in spaces in the interior of the tissues, as in cancer, the substances cannot be thrown off, and at the same time the products of the degenerative processes that are going on in the growth are carried into the cir- culation, and they exert a poisonous influence upon the blood. The retrograde changes seen in cancerous growths show them- selves often quite early. Cancer-cells are prone to undergo fatty degeneration, particularly those remote from the supply of nutri- ment. In this way the central portions of a nodule break down and a central depression is seen. In cancer of the skin ulceration takes place in virtue of these changes. Many forms of cancer undergo colloid degeneration, which involves frequently not only the cells, but also the stroma. As this change frequently occurs in the beginning of the disease, it gives a character to the growth that places it among the special forms of cancer to be noticed pres- ently. Calcification is occasionally seen in cancers whose growth is feeble. As the carcinomatous tissue is an imperfectly organized one, and as the walls of the blood-vessels are softened by cell- CARCINOMA. 647 growths, frequent hemorrhages and necroses occur, and consid- erable portions of the diseased mass break down and are absorbed. The carcinomata are divided into certain groups according to differences which exist in the nature of the cells. Those cancers consisting of pavement epithelium constitute the variety to which the name epithelioma was given. This term, which was used before it was recognized that all cancers were epitheliomatous, was intended to represent a class of cancers that were less malig- nant in their type. The name is still retained, principally for this reason. " Epitheliomata " are situated upon the skin, but they may likewise be found upon the vagina and the cervix uteri and in the mouth and the oesophagus. Cylinder-cell carcinoma is composed of cells such as are found on intestinal mucous membranes. This form of cancer, which has a strong resemblance to glandular tissue, is therefore frequently called " adeno-carcinoma " or malignant adenoma. Carcinoma of the breast is characterized by the pres- ence of a more globular type of epithelium. It is, however, chiefly in those cancers where the type of epithelium is very striking in its appearance that the cell-names are given, such as pavement- and cylinder-epithelial-cell carcinomas. Cancers may be divided into several groups, according to their coarse appearances, which are due principally to the relative amount of cells and stroma of which they are composed. Thus, cancers of the breast, where they contain a large amount of epithelial cells ar- ranged in a delicate alveolar stroma, are necessarily soft and juicy; consequently, they are known as medullary cancers. Those cancers containing an abundant dense stroma, in which a few small alveoli are found, have but few cells, and they are known as scirrhous or hard cancers. Carcinoma simplex is a name given to denote an intermediate stage of density, but this term is rarely used. The medullary forms are, as may be supposed, much more malignant than the scirrhous. Colloid is a name given to those forms of cancer in which the cells have undergone colloid degeneration. This variety is found in various regions of the body, and the same type of cell does not always prevail. The colloid cancer should not be considered as a special variety, but rather as a form of degeneration. The colloid material is deposited in the cells at first in small drops which run together, and eventually the whole cell is altered. The cells break down and many of them disappear, and the alveolus becomes distended. The tissue is very transparent, and, as little 648 SURGICAL PATHOLOGY AND THERAPEUTICS. is seen but large alveoli formed by the absorption of many of the trabecular, this variety is sometimes called "alveolar cancer." There is some difference of opinion as to the origin of the colloid matter. Some think it is elaborated by the cell; others assume that it is exuded by the vessels; Miiller suggests that it is developed first in the stroma. These cancers are seen principally in the stomach, the intestine, and the peritoneum; they are found, though rarely, also in the breast. The writer has seen a typical colloid-cylinder-cell cancer growing from the nasal mucous mem- brane. The development of colloid cancer is unusually slow. This peculiarity is attributed to the change in the cells, which interferes with the rapidity of its growth. When the cells of a cancer are filled with granules of pigment there is presented a variety known as melanotic carcinoma, but this form is exceedingly rare. "Endothelioma" is a name given to certain varieties of car- cinoma by pathologists who wish to distinguish those forms that originate from endothelium from those forms which develop from epithelium. The cells of these tumors closely resemble those of epithelial cancers, and it is quite difficult to distinguish between them. They may often appear as pavement-cells or as cylinder-cells. A differential diagnosis can only be made in such cases when it is possible to determine the exact point of origin of the tumor. They are found in the skin, in the meninges, and in the serous cavities, where they are often seen as disseminated miliary nodules. This distinction is one rather of scientific than of practical interest. A practical method of division of cancers is one based upon the localities in which they grow; therefore there will be described separately cancers of the skin, of the breast, of the uterus, of the mucous membranes, etc. These groups correspond pretty ac- curately to the different types of cancer-cells which have already been described, for the cells of a cancer resemble always the epithelial cells of the region in which they first appear. 1. Carcinoma of the Skin. Cancers of the skin belong to that variety known as epithelioma or pavement-cell epithelioma. There are, however, two varieties of the disease, which may be distinguished not only by their histological, but also by their clinical, peculiarities. These varieties are, first, the superficial form, which is composed largely of a single type of small epithelial cell; and the deep-seated or CARCINOMA. 649 polymorphous type, which is composed of large pavement-cells and of small epithelial cells. The superficial form, which is a far less malignant type of cancer, is found on the face principally, and is often known as a rodent ulcer. The deep-seated form is found on the lip, the penis, the scrotum, and the back of the hand, and, although much less malignant than other forms of cancer, is more frequently followed by infection of the lymphatic glands than the superficial variety. The deep-seated form begins as a growth of cells from the epi- thelial layers of the skin, from the interpapillary space, and, ac- cording to some authorities, from the hair-follicles and the seba- ceous glands. The first change usually noticed is an enlargement of the interpapillary masses of epithelium, which masses become elongated and grow down into the connective-tissue spaces of the cutis. They branch here in various directions and become con- stricted and distorted, and finally they are found in the deeper tis- sues of the skin separated from the epithelial layers above. The connective tissues in which they are now imbedded form a vascular stroma rich in cells. The cells of these epithelial clusters have more or less the characteristic peculiarities of the epidermic cells. A careful study of their shape shows that the outer layer is com- posed of a more or less perfectly formed epithelium, resembling the layer of cells found in contact with the papillae of the skin. The cells nearer the centre are of the large pavement type, and in consequence of the rapid growth they are squeezed together and form concentric cir- cles of cells, which are flattened out and undergo horny degeneration. In this way are formed the "epithelial pearls" or "cell-nests," as they are called (Fig. go). If a fresh specimen of this form of cancer is cut open and the surface is slightly squeezed, there will be pressed out little comedo- like plugs which are composed of these epithelial nests. \m,% mm h »*« * ml 3 Fig. 90. — Cell-nests in Cancer of the Lip (oc. 3, obj. D.). 650 SURGICAL PATHOLOGY AND THERAPEUTICS. In some of these epithelial pearls is occasionally found one of the so-called " psorosperm ' ' bodies, appearing as a mass of nucleated protoplasm which has shrunk away from the sur- rounding cells, leaving a space or vacuole. There is seen in this type of cancer, growing luxuriantly, all the cells found in the normal epithelial layers of the skin. There is not only the small-cell, which is found in the deeper layers of the rete mu- cosum, but also the large pavement-cells, and even the horny cells of the epidermis. We have, then, a polymorphous type of epithelial growth. It is not always easy to see the points from which spring these masses of cancer-cells. Usually they spring from the deep layers of the rete. Many of the sections made show clusters of cells which appear to be altered and degenerated sebaceous glands. The transition changes, however, are not easy to observe, and the writer has been unable to trace such growths from the sebaceous glands, although most authorities agree that these glands are often the starting-point of the disease. It is an interesting fact that clinically there is seen considerable disturbance of the sebaceous glands in many cases of carcinoma cutis. The superficial form of cancer of the skin is, as before noted, much less malignant, and there is found here a very different type of cell-growth. The cell-masses in most cases appear to grow down from the deep layers of the rete into the cutis vera in columnar masses which anastomose freely with one another. The epithelium is small and delicate, and it reminds one strongly of that seen in the rete mucosum near the borders of the papillae or in the sheath of the hair-follicle. These columns of cells occasion- ally swell into large and irregular shapes, and there is found at cer- tain points in such clusters a larger epithelium around which there is a concentric arrangement of cells; but these epidermic balls are extremely rare. In many cases the amount of epithelium is very small for cancer, and the stroma, which is composed of dense fibrous tissue, seems to make up the greater part of the growth. In such cases there is presented a delicate anastomosing network of columnar masses of cells, such as is described by the French writers as epitheliome tubule (Fig. 91). It is claimed by Thiersch and others that this variety takes its origin from the sudoriparous glands, and by some writers it is known as adenoma of the sweat- glands. These cell-masses, whatever their shape or size, grow very slowly, and they remain for a long time confined to the upper layers of the skin. When the number of cells is very small and the stroma predominates, there is quite a dense, hard growth, and CARCINOMA. 651 the name scirrhus cutis has sometimes been applied to this condition. From what has been written it is evident that the cancer-cells spring from pre-existing epithelium: this is a fact which long 4 <». # ■•'■v **# 1 ~<£ ■y / % ;*..- Fig. 91. — Tubular Epithelioma, from a case of Rodent Ulcer (oc. 6, obj. aa.). since has fully been settled. It is learned also that as cancer grows its epithelial cells appropriate everything that comes in their path, and that bone, muscle, and nerve all seem to melt away before the active cell-growth. In some of the writer's early investigations it seemed, when one studied carefully the outer edge of a cancerous growth, that the spaces first filled with cells did not always contain epithelial cells, and that the clusters of round cells as one approached nearer the centre of the disease gradually became epithelial. This suggested that the round cells in some way had to do with the development of the cancer-cells. French writers speak of the action of the epithelium on the round cells as an "action de pre- sence" the young cells becoming in this way impregnated and endowed with epithelial properties. However these appearances may be interpreted, the fact remains that in rapidly-growing carci- noma the round cell infiltration of the surrounding tissue is 652 SURGICAL PATHOLOGY AND THERAPEUTICS. abundant and the cancer-cells present an appearance less typical of epithelium. This view is held also by Rindfleisch. Gussenbauer maintains that not only the endothelium of the capillaries, but also the muscular fibres from the media, form embryonic cells which develop into cancer-cells. Weil has also observed similar changes in striped muscular fibre (V. Ziemssen). Carcinoma of the skin occurs most frequently between the ages of fifty-five and sixty. In 948 cases collected by V. Ziemssen, 739 were men and 209 were women. The superficial form of cancer is almost invariably found on the face, and it has frequently been called " rodent ulcer." This term was used before the pathology of the disease had been recognized, and it describes one of its most striking clinical peculiarities. Cancer of the face — and it might also be said cancer of the skin in general — is apt to be accompanied by a peculiar condition of the epidermal structures known as keratosis. This affection is characterized by the formation on the face and the back of the hands of scabs or crusts, which exist for a long time before any malignant disease manifests itself. At first they appear as scales, slightly elevated above the skin surface and of somewhat darker color than the surrounding skin. The surface of the spots is sometimes shining and smooth, and is sometimes dry and covered with minute lightly-adherent scales. The spots are without sensation and attract little attention at first. Gradually they become more noticeable by increase in elevation and in depth of color, but their development is very slow, and years may pass before they attain sufficient growth to become troublesome. Eventually they present elevations, one-eighth of an inch above the general surface, consisting of dry, horn-like scales, which vary in color from the faintest yellow to the deepest black, and which may be removed with little violence by the nail, leaving exposed a superficial excoriation, either smooth or exhib- iting minute conical elevations that are enlarged sebaceous glands (White). Microscopically, there is seen a great thickening of the upper horny layer of the skin, which thickening is continued downward into the ducts of the sebaceous glands, distending them and form- ing prominent protrusions. The sebaceous gland is not changed, but it is much distended by retained secretions which become mingled with the epidermic crusts. There is more or less cell- infiltration in the surrounding corium. The appearance of the complexion is often characteristic. There is a peculiar wax-like CARCINOMA. 653 transparency of the temples and the upper part of the cheeks, and just beneath the surface of the skin can be seen the yellow sebace- ous glands. The true skin is thin and is in a state of senile atrophy. At some one spot a crust has gradually become more prominent than elsewhere: this may be upon the side of the nose or be over the malar bone or on the temple. On picking off this crust it is now seen that there is beneath it a papule with a moist and somewhat ulcerated surface. On excising this papule it will be found that a downward growth of epithelium has taken place and that the development of the cancer has already begun. Schuchardt interprets the series of changes just described as the symptoms of a chronic inflammatory process which is, he thinks, highly favorable to the development of cancer. He failed, how- ever, to find that the sebaceous glands were in any case the point of origin of the malignant growth. The superficial carcinoma begins usually after middle life, is extremely slow in its progress, and, inasmuch as it does not cause pain, and sometimes not even itching, it is neglected for many years, and it is therefore often not seen by the surgeon until it has assumed large dimensions. When observed in the early stage of development it is found that the new formation has broken down in the centre and an ulcer has formed. The ulceration is not deep, and the surface is quite flat and is surrounded by a pearl-colored rim. The shape often closely resembles that of a horn waistcoat- button. Around the edge of the ulcer the skin appears in a healthy condition. The absence of inflammation in the diseased, part is characteristic of cancer. There is no red and infiltrated skin, as is seen around tubercular or syphilitic ulcers. The pearl color of the rim is due to the presence of the epithelial cells, and it is characteristic of this form of cancer. When there is extensive breaking down of tissues and inflammatory complications the pres- ence here and there of fragments of this pearly rim, perhaps made visible by the use of a hand lens, will enable the surgeon to recog- nize the disease under its disguise. As the growth slowly advances its ulcerating character becomes more apparent: it may take years to double in size. Sometimes one portion of the rim will suddenly begin to grow out of all proportion to the other parts, and the ulcer is replaced or is masked, as it were, by a tumor. Usually, however, it continues to spread slowly, but is still as superficial as ever, and if the patient lives long enough it may cover large surfaces, involving the nose, the eyelids, the eye, and even the whole side of the face. To 654 SURGICAL PATHOLOGY AND THERAPEUTICS. Fig. 92. — Noli-Me-Tangere. this formidable condition the term noli-me-tangere has appropriately been applied (Fig. 92). In the case of the patient whose portrait is here given (Fig. 92) there was no enlargement of the lymphatic glands. The same absence of glandular involvement was observed recently in another indi- vidual, in whom there was extensive ulceration. The disease had in this case originated in the scar of a gunshot wound received during the Civil War, and had destroyed the side of the nose, the eye, the ear, and the cheek, including the corresponding half of the upper and lower lips. The slight malignity of these of cancer has been plained by the feeble reproductive power of the small epithe- lial cells, but it is more probable that there are other factors to be considered, such as the anatomical seat of the disease and, possibly, the nature of the parasite — if there be one — which caused it. Carcinoma of the face does not always ulcerate. Occasionally, and not infrequently, the growth of epidermal cells is abundant, and there is also an active development of the stroma, so that there arises a nodular or papillary form of growth. These tumors may sometimes attain considerable size, reaching the dimensions of an English walnut. Such growths, which have been described by Hutchinson as a fungating form of rodent cancer, are found on the temple or near one of the lids. When such exuberant growths break down prematurely, there is formed a deep ulcer with raised edges, and this appearance Hutchinson named " crateriform " ulcer. Such growths, though formidable in appearance, are not liable to recurrence if they are so situated that they can radically be excised. One of the most important strategic points of cancer of the face is the region over the nasal process of the superior maxilla. A carcinoma originating here or gradually working its ulcerating forms ex- CARCINOMA. 655 way toward the inner margin of the orbit may suddenly involve the lymphatic vessels leading to the base of the skull. When once the margin of the orbit has been passed the disease may be regarded as incurable. There is a period in the life-history of this disease when the benign type may suddenly be changed to a malignant type, and a superficial cancer will then be transformed into the deep-seated variety. Irritating modes of treatment often rouse a sleeping can- cer to frightful activity. The deep-seated or polymorphous-cell cancer has its type in cancer of the lip. Here also the disease has been ascribed to chronic irritation, in this case the irritant being the constant use of tobacco. Mason Warren reports 77 cases of cancer of the lower lip. It w r as ascertained that all but 7 w T ere in the habit of smoking. In many cases the fact of a habit of smoking could not be ascer- tained, but the interesting feature of this series w T as the fact that 4 were women, 3 of whom were in the habit of using a pipe. The writer remembers having seen but one case of cancer of the lip in a woman, and she was in the habit of smoking. In this case the cancer was in the upper lip. So many smoke, however, who do not have cancer that it must remain doubtful whether such a cause predisposes to cancer. According to Mason Warren, the disease is seen oftener on the left side of the lip than on the right ; it may occur on the median line. Like other forms of carcinoma of the skin, it appears after middle life, and is commoner between the ages of sixty and seventy than at any other period ; occasionally it is seen between the ages of thirty and forty, and in the latter case the disease is much more active. The point at which the disease begins is the junc- tion of the mucous membrane with the skin, and it appears either as a small papule or as a flat crust which falls off only to re-form. It soon assumes the appearance of a superficial infiltration of the vermilion border of the lip, and it has a well-marked, though shallow, circular outline. When examined under the microscope at this period the disease is found to consist in a thickening of the epidermal border of the lip. The outer papillae are thickened and elongated, and as the centre of the disease is approached the downward growth of the epithelial cells is w r ell marked. The disease, however, is still very superficial. The large epithelial cells are seen here, and the number of epithelial pearls is very great. When allowed to pursue its course the disease may involve 656 SURGICAL PATHOLOGY AXD THERAPEUTICS. a greater portion of the lip, and even attack the bone. The cen- tral portion is then ulcerated, and the ulcer is surrounded by thick and overhanging edges. The next point of attack is the sub- maxillary gland of the side on which the disease lies. This point can be felt readily by standing behind the sitting patient and pressing the tips of the fingers against the inner margin of the jaw-bone. A small bullet-like nodule rolls between the bone and the finger. In the later stages of the disease the glands of the neck become enormously enlarged, and the patient dies slowly with symptoms of marked cachexia. Metastatic nodules may be found in the internal organs, but they are not common. The prognosis of the disease is favorable if an operation is per- formed while the growth is superficial ; this is not always the case. The writer remembers a physician who applied for operation about three months after the first appearance of the disease. There was no return in the lip, but a gland under the jaw began to enlarge six months later, and the patient succumbed eighteen months after the first appearance of the disease. The question of operation upon infected submaxillar}' glands is one about which there is much difference of opinion. When small and movable the glands should undoubtedly be extirpated bv a verv free and extensive dissection of the region in which thev lie. Under these circumstances the prospect of a final cure may be looked forward to with some hope of success : it is, however, a grave complication of the disease. After operation patients frequently return in a few months very much alarmed about an induration of the cicatrix. Such cicatrices are not infrequently excised, and it is then found that there is nothing but cicatricial tissue. If let alone the induration will eventually disappear. Cancer on the back of the hand is of the same type as cancer of the lip. It is associated usually with marked keratosis senilis. Although polymorphous, the cancer grows slowly at first, and a papule covered by a crust may exist for years before the patient seeks relief. Such growths are not infrequently multiple. The danger is that the glands at the elbow may suddenly become involved. In one patient who suffered from this affection the writer removed four or five such growths, not only from the hands, but also from the face. Axillary involvement eventually took place, and after seven or eight years' duration the disease finally terminated life by metastatic deposits in the liver. The writer has also seen cancer originate upon the palmar surface of the hand In CARCINOMA. 657 a case of palmar psoriasis. This case likewise terminated fatally, notwithstanding amputation at the wrist. Cancer of the penis occurs in about 1 per cent, of all cases of cancer. It is seen most frequently between the ages of forty and seventy years. It may occur on the preputial fold, but it is oftener seen on the glans. It can be distinguished without difficulty from chancre or a syphilitic condyloma by the history of the case, as the growth is very slow. It is said to appear at first as a small vesicle or a wart on the frenum, which vesicle increases in size and develops into a papillary growth. As it enlarges the centre breaks down and leaves an ulcerated surface. It may remain localized for a long time, the tunica albuginea appearing to offer considerable resistance to the growth, but eventually it attacks the body of the organ and infiltrates the lymphatic vessels and the glands in the groin. The glandular infection is said by Kaufmann to be more frequent than is generally supposed. In 48 cases, 40 were found to have this complication. The glands in the groin are the first involved, and usually those near the point of junction of the saphenous and femoral veins. Occasionally the glands in both groins are affected. Phimosis, accompanied with more or less balanitis, is seen frequently in this disease. Demarquay found in 59 cases, 42 in which there was phimosis. The writer remembers two such cases which were cured by operation. Metastases are occasionally found in the internal organs. The disease runs its course if untreated in from one to two years. Kaufmann found the average duration of life in 38 cases to be twenty-two months. If the disease comes into the surgeon's hands early, the prognosis is favorable for minor operations. Carcinoma of the labia is of the same type as that of the penis. It appears usually on the inner surface of the labia majora, and it is first seen as a circular ulcer. It might be mistaken for a syphilitic lesion, were it not that there is an absence of inflamma- tory change and a history of slow growth. If allowed to follow its course, it may extend around the ostium vaginae and destroy the clitoris. The mons veneris may be undermined by an extensive infiltration, and the vulva is then converted into one large foul, ulcerating surface. The glandular involvement comes late. The disease is more malignant than cancer of the lip. It generally runs its course, if untreated, in about two years. Butlin, in an analysis of 31 cases operated upon, places the percentage of cures — that is, of those who have passed the three-year limit — at 16. If the dis- ease is operated upon before glandular enlargement occurs, the 42 658 SURGICAL PATHOLOGY AND THERAPEUTICS. chance of a radical cure is good. Owing to delay while trying specific or local treatment this golden moment is often lost. Cancer of the scrotum is also of the large- or polymorphous-cell type. It appears to be a disease almost exclusively confined to English chimney-sweeps; hence it has been called "chimney- sweep's cancer." It was supposed to have disappeared since the law has been enforced forbidding sweeps to ascend flues; Butlin's investigations, however, show that this is not the case. In the St. Bartholomew Hospital in the course of twenty years 39 patients were treated for cancer of the scrotum. In the Middlesex Hospital from 1867 to 1882 there were 20 cases of cancer of the scrotum under treatment. At the St. George Hospital 9 cases were treated from 1869 to 1878. The statistics of the Registrar General show that during a period of three years there w r ere 23 deaths from can- cer of the scrotum, penis, testis, or groin. A careful investigation by Butlin of the various hospitals of Europe shows that the chimney-sweeps in Continental Europe do not suffer from this form of cancer: this immunity he attributes to the protective costume worn by them and to their personal cleanli- ness. In England, although chimney-climbing has been aban- doned, no efforts were made to protect the body from the soot which falls in greater or lesser quantity upon the sweep. In the United States the disease is extremely rare. At the Boston City Hospital from 1881 to 1889 there occurred but 1 case of cancer of the scrotum. The writer remembers having seen but 1 case at the Massachusetts General Hospital, and that was thirty years ago. The disease begins as a wart. Many such warts form on the scrotum and are known as ' ' soot-warts. ' ' They may exist for years, and some sweeps are covered with such warts upon the scro- tum without suffering from cancer. In the course of time, owing probably to some special irritation, one of the warts slowly grows larger, becomes more prominent, and at the same time becomes deeply fixed, and its centre ulcerates. The cancer spreads slowly along the scrotum, being confined to the skin. Occasionally it penetrates more deeply until it reaches the tunica vaginalis, and even the testicle, which may be laid bare and in time be destroyed. Before the days of anaesthesia the disease was said often to destroy everything from the anus to the pubes, leaving a foul sore against which no treatment availed. Secondary infection of the glands of the groin may occur late in the disease. Metastatic deposits in the internal organs are not reported, probably because autopsies are rare (Butlin). CARCINOMA. 659 Tar and Paraffin Cancer of the Scrotum. — This disease was described almost simultaneously by Volkmann in Halle and Bell in Edinburgh. Ogston in 1871 had written on the local effects of crude paraffin. This disease occurs among the operatives in coal- tar and paraffin factories, who are obliged to be in contact with the products of the manufacture in a more or less liquid state. These products induce great irritation of the surfaces exposed, such as the skin of the forearms. The skin of the body is described as dry and parchment-like, somewhat resembling the irritation pro- duced by carbolic acid. The ducts of the sebaceous glands are dilated, and in the ducts are seen dark, comedo-like plugs, and acne-pustules abound. There is considerable thickening of the epidermic layer, which is raised into little prominences on the extremities as well as on the scrotum. Sometimes there is a more distinctly scaly condition. In new operatives there is con- siderable infiltration of the skin at some points, and the part is red and shining and is tender to pressure. In old cases, after the first acute irritation subsides, the epidermic thickening increases gradually. Warty growths appear, and finally at one spot car- cinoma develops. The series of changes is not unlike that seen in cancer of the lip. A histological study of the irritated skin shows a growth of the lower layers of the epidermis and of the rete mucosum. The hair-follicles are frequently distended with masses of epidermic cells, and in the deep layers of the rete are found spots of brown pigment. Near the carcinomatous nodules the dividing-line be- tween epidermis and the cutis becomes very irregular, and the interpapillary masses of cells are enlarged and irregular in shape. The skin shows also a small cell-infiltration. When the zone of the cancer is reached there are found enormous numbers of epider- mic balls and a polymorphous-cell growth into the deep layers of the cutis. It is evident that we have to do here with a chronic irritation of the skin affecting its epithelial structures for a long time, producing at first hypertrophy of some of these structures, and finally a tendency to indefinite growth, as in cancer. In the deep rugae of the scrotum the soot- or tar-products remain untouched for long periods of time, and it is here that the disease most frequently shows itself. It is possible, as Butlin suggests, that certain areas possess physiological and chemical properties, which differ from those of other areas of the integu- ment as decidedly as they do in their coarse appearance. It has been suggested by Butlin that the crude paraffin, the brown 660 SURGICAL PATHOLOGY AND THERAPEUTICS. coal-tar, and the stone-coal soot have' specifically irritating qualities which favor the development of cancer. It has also been suggested that tobacco-smoke and tobacco-juice bear the same relation to cancer of the lip that these substances do to cancer of the scrotum. Xeroderma pigmentosum is a skin disease in which cancer is a frequent complication which appears in early life. Cancer in Cicatrices. — Cancer has been associated with scars by writers ever since Alibert described keloid, which he confounded with cancer. Cancer appears long after the scar is originally ac- quired, and it is seen most frequently in individuals from forty-five to fifty years of age. Males are said to be more frequently afflicted than females. Cancer seems to develop preferably in those scars which have been subjected to long periods of irritation. Cancers are found, therefore, in cicatrices of the limbs that hamper movement; consequently they are subjected to undue tension, or they are found in the scars of ulcers or of old wounds or of fistulae. Ulcers form and heal in the cicatrices many times before cancer develops. The greater part of a lifetime may pass in this condition, and finally the disease breaks out. Reid reports a case in which the disease appeared sixty-one years after the original injury. The scars of ulcers on the lower extremity often exhibit this peculiarity. The disease in these cases is usually of a mild type. There may be present the polymorphous- as well as the small-cell type of cancer, but the growth of the cancer is almost always exceedingly slow, and there is a history not unlike that of rodent ulcer. These cases may, however, take on a more malignant action at any time. In such cases there is likely to be found involvement of the inguinal glands. In 128 cases reported by Rudolf Volkmann of cancer developing in scars of the extrem- ities only 12 cases were known to have died of cancer. In a case recently operated upon the writer found a large ulcer, with a peculiar fur-like surface, that had evidently developed from the scar of an old varicose ulcer. It had already involved the shaft of the tibia, but, as it had existed for many years and had caused no pain, it was only with the greatest difficulty that the patient was persuaded to allow amputation of the limb. It proved to be a large-cell epithelial growth. The writer has already re- ferred to a most formidable case of rodent ulcer of the face that developed from a scar. The treatment of cancer of the skin, as indeed of cancer in gen- eral, may be stated to consist in the removal not only of all appa- rent disease, but also in the excision of as broad a margin as pos- CARCINOMA. 66 1 sible of healthy tissue. In the case of cancer of the skin this treatment can be carried out more effectually than in any other portion of the body, and, inasmuch as glandular infection conies late in the disease, operation is more frequently followed by cure in this than in any other region. Rodent ulcer is perhaps the mildest type of cancer known, and in its earliest stages it can be scraped away, the base of the wound being bored with a caustic or touched lightly with the fine point of a Paquelin cautery. If the papule or ulcer is situated where it can be excised, this operation should be performed, as the wound heals speedily and leaves an almost imperceptible scar; and one should train one's self to take as much tissue as possible in order that the cure may be permanent. This is one of the hardest habits for the surgeon to acquire, as economy of tissue appears to be urgent upon exposed places. Occasionally a small nodule situated upon the side of the nose, if not radically removed, will begin to grow with frightful rapidity. Cancer of the face can per- manently be cured, even though it has returned several times after operation and has involved cartilage and bone. The writer recalls the case of a gentleman who allowed a cancer to grow on the left side of the nose until it involved the skin of that side and a portion of the skin of the right side. The disease returned three times after thorough scraping and burning with the actual cautery. Finally, the left half of the nose and the ascending process of the superior maxilla were excised, and the cavity thus left was covered by a flap taken from the forehead. The disease never returned after this operation. Beyond the use of the Paquelin cautery for exceed- ingly small growths, the writer has abandoned the use of caustics in the treatment of this affection, as the results of incomplete re- moval are occasionally most serious. Cancer of the lip should be excised by a V-shaped incision, including at least one-quarter of an inch of healthy tissue on each side. There is no danger of taking away too much, as the lip is elastic and its suppleness is entirely restored even when very large portions have been removed. Careful examination should always be made to detect infected glands, and the patient should be warned to search for the appearance of any lump under the jaw. A very free dissection of the upper cervical triangle may even then give the patient a chance for his life. Cancer of the penis, when operated upon early, is curable. The disease should be scraped away, and the base of the growth should be sliced off as one would pare a corn until healthy cavernous tis- 662 SURGICAL PATHOLOGY AND THERAPEUTICS. sue is seen. In more advanced stages amputation should be per- formed, and the groin should carefully be searched for enlarged glands. Winiwarter reports 12 amputations, of which 5 remained permanently well ; 1 died of the operation ; 6 had recurrences, 3 of which were in the stump and 3 in the glands. If the glands are removed early, there is still hope of cure, as the progress of the disease is slow. The bad reputation of this form of cancer is un- doubtedly due to many incomplete operations; the same may be said of cancer of the vulva. Time is frequently lost in determin- ing the diagnosis and in using specific remedies. The writer succeeded in prolonging life for several years by yearly operations on a case of advanced cancer of the vulva, so that at the present time there is no vulva. The meatus and ostium vaginae, much narrowed, now open in the centre of a cica- trix. A few months ago the patient was seen in good condition. The treatment of cancer of the scrotum is attended with good results if taken in the early stages. The rule of free excision holds good here. In cancer of cicatrices the disease is generally found in the centre of a large scar. If this scar is situated on an extremity, there is an excellent chance of saving the patient by an amputa- tion, as the glands in the groin are usually not infected, although they may be enlarged by inflammatory infiltration. If the scar is situated on the face or the trunk, the best that can be done is probably a thorough curetting followed by the actual cautery. In some cases it would be possible to excise the ulcer, the wound thus made being covered by Thiersch grafts. The tendency at the present time of following up the operative treatment of cancer by a subsequent course of internal medication should be encouraged. In the case of cancer of the skin the bro- mide of arsenic or Fowler's solution may be tried in doses of 2 or 3 drops three times a day for months after the operation. Patients should be asked to report every three months during the following year for inspection. 2. Carcinoma of the Breast. The breast is one of the most frequent seats of cancer. In a series of 7881 cases of cancer collected by Andrews the disease appeared in the breast 1232 times. This region comes third upon the list, following that of the uterus and the stomach. In the great majority of cases it occurs in the female breast, and in the male breast the disease is extremely rare, being seen in about 1 per CARCINOMA. 663 cent, of the cases. In a collection of 1 10 cases of cancer of the breast made by Dietrich 3 occurred in males. The number of deaths from cancer of the breast reported in the United States in 1880 was 1387. The period of life in which the disease is oftenest found is that immediately preceding the menopause. In an analysis of 1622 cases Gross found that the average age was 48.66 years. It may be said that from forty to fifty is the commonest decade in which the disease is likely to occur; it is next most frequently found in women between fifty and sixty years of age; the period from thirty to forty years comes next, and that ranging from sixty to seventy follows. There is but one case reported at the age of twenty-one, but Bryant states that he has seen cancer of the breast at an earlier age. The writer had one patient in whom the disease was first noticed when she was twenty-two years and three months old. It was a well-marked case of cancer, as shown by microscopic ex- amination, and it recurred, after operation, the following year. Although the disease appears during the period of the functional decline of the organ, it is said that 80 per cent, of the cases are found among married women, and according to Bryant it appears to occur among women who are prolific to an extreme degree. The question of heredity having already been discussed, it remains merely to add here that of 1164 cases analyzed by Gross, in only 55, or 4.72 per cent, of the cases could the disease be said to have been transmitted. Traumatism, according to some writers, has a direct influence on the development of carcinoma of the breast in about 13 per cent, of the cases. Cancer of the breast in the negro is extremely rare. The writer does not remember having seen a case. As to the locality of the disease, it may be said that it occurs about as frequently in one breast as in the other. If a line be drawn vertically and one horizontally through the nipple, the breast will be divided into quadrants. If now a circle be drawn around the areola, the breast will be divided into five anatomical areas in which cancer may be found. The disease was found by Gross to be seated more frequently in the upper than in the lower hemisphere, and more frequently in the outer than the inner hem- isphere. The most frequent locality was found to be the upper and outer quadrant, that nearest the axilla, while the region of the areola came next in order. In exceptional cases it develops in an accessory gland or lobule below the clavicle, near the sternum, or in the axilla, where it may be mistaken for disease originating in a lymphatic gland. Cancer constitutes about 80 per cent, of all tumors of the breast. The classification of cancer of the breast varies considerably in 664 SURGICAL PATHOLOGY AND THERAPEUTICS. different works. The simplest and most practical arrangement is a division of the various forms into two classes — namely, medul- lary, or soft and rapidly-growing carcinoma; and scirrhous, or the hard or less malignant type. The cells of carcinoma of the breast are of a more or less globular type of epithelium. They are very irregular in shape and vary considerably in size. They are contained in alveoli, and are grouped together in no well-defined order, but fill the alveolus usually with a solid mass of cells which are directly in contact with one another. In the meditllary form the alveoli are either large or numerous, and they vary according to the shape of the plugs of cells that accumulate in the stroma. These plugs are sometimes round or oval in shape, and at other times are long and narrow, and cancers in which one or the other form prevails have been called by Billroth "acinous" or tubular. The stroma is composed of connective-tissue fibres in which there is more or less round-cell infiltration. It is sometimes exceedingly small in amount, only a few fibres forming the trabecular which separate the different alveoli, and in such cases the cell-masses or plugs are very numerous. The larger the number of cells the softer the tissue, and the term medullary is therefore a most appropriate one to describe such a condition (Fig. 93). In the periphery of the tumor the tissue which immediately surrounds the cancerous growth is usually infiltrated extensively with small round-cells. The stro- ma is not always the same in character throughout the growth, for at certain points it may be abundant, and may form broad fibrous bands which separate the soft cellu- lar portions from one another. This is the case in tumors of medium density, which are sometimes called "carcinoma Fig. 93.— Medullary Carcinoma of the Breast simplex "—a term frequently (oc. 3, obj. D.). used in books, but rarely employed by surgeons. In the scirrhous variety the stroma is a predominant feature of the new growth, and the cell-clusters are few in number and small rare instances found to undergo \ s* . , *$£i* broad semi-transparent bands ' c - ^i^^SpSS? 5* <: " of tissue, with a few pigment- ed RCINOMA. 665 in size. The latter are found scattered at greater or lesser distances from one another, and are enclosed in elongated and spindle- shaped alveoli. They are in •or *o calcification. The fibrous stro- ?* ^ ' > " ,v \$?4 # , ma is very dense and scar-like 4 % &>r z ^*§ \ ^ ^ X at certain places, and the fibres '^jjfti^. "--a&^A^ often run together, forming ^ •« ''^jBJBfeAj*^ * " V ^V ^ granules scattered here and T&v*^ - f*^S^^ : there, but with very few cells (Fig. 94). In the extreme , -^ 2-3^ - -^* type of this form of cancer the ~~**[*j$?f' --V&V* SCOpe this form was called a Fig. 94.— Scirrhous Cancer of Breast (oc. 3. "connective-tissue cancer," as obj. D.). it was supposed that no epithe- lium existed in it. This type of scirrhus has been called "atrophying scirrhus;" the dense forms of cancer, being very slow in growth, are consequently much less malignant in cha- racter. The coarse appearances of these two forms of cancer also differ markedly from each other. The cut surface of a medullary cancer has a grayish-red color in which grayish striae are seen formed by the fibrous trabeculae which support the soft juicy masses of cells. There is no well-defined border, as the growth appears to infiltrate the surrounding tissues. By scraping lightly such a surface an abundant cancer-juice is obtained upon the blade of a knife, the juice showing under the microscope epithelial cells of most irreg- ular shapes, single or in clusters, and floating in a turbid serum. The scirrhous cancer when cut open shows a mass of scar-like tis- sue which has caught in its projecting bands of fibres portions of the lacteal ducts and of other structures pertaining to the breast, that are in a more or less advanced stage of atrophy. An unusual form of cancer of the breast is colloid cancer. It is so rare that the writer remembers having seen but two speci- mens. The appearance of a microscopical section is very striking. The alveoli are large and the stroma is thin and transparent. The alveoli appear to be distended with a transparent gelatinous mate- 666 SURGICAL PATHOLOGY AND THERAPEUTICS. rial having circular streaks in it, as if it recently had been stirred with a glass rod. There are very few cells; sometimes one or two remain adherent to the wall of the alveolus, but more frequently a cluster of cells are found near the centre undergoing degeneration. An example of the earliest change found in the epithelial struc- ture of the breast in the development of cancer is seen near the periphery of a growing carcinoma. Here is found a growth of the epithelium filling up and distending a gland acinus. The hyaline membrane of the tunica propria of the acinus presently disappears, and the cells break through the deeper layers of the tunic into the surrounding tissue, and they begin to grow in dif- ferent directions in the lymph-spaces. Let attention now be turned to the clinical history of cancer of the breast. The first symptom noticed by the patient is a hard lump in the breast. It is only accidentally found, as there has been no previous pain and no symptoms of constitutional disturbance of any kind. When a healthy woman between forty and fifty years of age presents herself with such a lump, the chances are strongly in favor of its being a malignant growth. The nodule is usually seated in the upper and outer quadrant or beneath the nipple. To the touch the nodule appears to be firm and ill-defined as to its bor- ders. In some cases the nipple is retracted, and if the axilla be explored with the tips of the fingers, there will be found one or more glands firm and matted together that slip between the fingers and the ribs. Often there is no retraction of the nipple, but in many cases a careful inspection will show that the skin overlying the tissues is depressed slightly, forming a shallow dimple. This pitting of the skin and the retraction of the nipple are due to the shrinkage which has taken place in the breast-tissues in conse- quence of the destruction that has been brought about by the diseased growth. The lump in the breast slowly grows, and finally it becomes attached to the skin, which gradually becomes destroyed, so that there is found in the centre of a reddened and infiltrated lump an ulcer which gradually increases in size. In many cases the tumor forms without pain, but as the growth progresses there may be lancinating pains. Pain is not, however, an important symptom, as many women of middle age are apt to suffer from neuralgia of the breast, particularly at or near the menstrual period. In such cases the writer has noticed a slight fulness of the breast, and even an enlargement of the axillary glands. The con- dition is readily distinguished from cancer, however, as in such cases there is no tumor to be felt. The nodulated masses felt in CARCINOMA. 667 a mamillary gland should not be mistaken for a tumor, and the best way to determine definitely the presence of a new growth is to press the breast firmly against the thorax-wall with the palmar surface of three extended fingers. The tumor develops not only forward, but also backward into the pectoral muscle and the retromammary connective tissue. Even though the muscle appears to be free, the delicate fascia is often affected. The muscle may eventually become adherent to the growth, and later it may be perforated, and the tumor then becomes fastened to the ribs. This condition is recognized by the immobility of the nodule. While growth in this direction is taking place, the surrounding skin occasionally appears also to have become affected, and numerous red nodules crop out in various directions. In this way a large area of the skin of the chest may become diseased, and there is presented the condition known by French writers as cancer en cuirctsse. Occasionally the original tumor enlarges with frightful rapidity, and often with the appear- ance of an inflammation. The skin of the breast becomes red- dened and slightly cedematous, showing a well-defined outline (Fig. 95). This redness spreads over the whole breast, which becomes hard and brawny, and the infiltration in- volves the skin of the thorax-wall beneath the axilla. Such fulminating cases are fortunately rare. As the disease prog- resses in the mammary gland the glands in the axilla become enlarged and matted together, and they fill out the cavity of the axilla with a firm nod- ulated tumor. At this time there may be observed in the supraclavicular re- gion a slight fulness which is not to be seen on the other side. This appearance shows that the axillary infection has spread beneath the clavicle. From this point the cancer-cells follow the chain of glands which accompany the internal mammary artery, or they may next infect the bron- chial glands at the root of the lungs. Fig. 95. — Brawny Infiltration of Breast in Cancer. 668 SURGICAL PATHOLOGY AND THERAPEUTICS. When the tumor is very near the sternum, Volkmann has seen the axillary glands of the opposite side also infected. It is stated by Billroth and Winiwarter that glands felt in the axilla and above the clavicle may in some cases disappear after operation. This dis- appearance can only be explained on the theory that they were inflammatory. In the case of inflamed cancers such enlarged glands might be found, but so far as the writer's experience goes such fortunate retrograde changes are not seen. The infection of the lymphatic glands in the axillary and sub- clavian regions finally becomes so extensive that the return of the venous blood and lymph is retarded, and an cedematous enlargement of the arm results, which involves the whole limb and sometimes attains enormous proportions. This symptom is then a sign of deep-seated glandular involvement, and is a contraindication to operative interference unless for the relief of pain (Fig. 96). There is, however, al- ways a tendency to degener- ation and absorption of the cancerous growth, and so far as this goes there is a tend- ency consequently to spon- taneous cure. The writer does not, however, find any such case reported in litera- ture, although Billroth men- tions a case of scirrhous cancer that had almost en- tirely disappeared, at the time of the patient's death, from metastatic deposits. Metastasis is supposed to occur through the lymphatic system in cancer, but this is probably not always the route taken by the disease. Bill- roth suggests that the nod- ules found in the lungs, the liver, and the kidneys reach those regions by embolism, a growth of cancer-cells in- vading the vein, being carried thence to the heart and through the Fig. 96. -QEdema of Arm in late stages of Cancer of Breast. CARCINOMA. 669 pulmonary system to the various organs. He doubts whether the disease can be transmitted by the lymphatics through the diaphragm to the liver and through the posterior mediastinum to the spinal column. In one case seen by the writer a line of infected lymphat- ics led along the ribs to the spinal column and thence to the liver, which was completely infiltrated with cancer. In this case there had been no return of the disease in the axilla, but one or two nodules were found in the cicatrix of the breast. The liver and lungs are most frequently the seat of metastatic deposits. The pleura may be infected by direct extension of the growth from the primary nodule through the chest-wall. These deposits may also be found in the bones and in the dura mater, and more rarely in some other internal organ. Billroth observed an appearance of the disease in the other breast several times, but the experience of most surgeons is that metastasis to the breast is an extreme rarity. It is not probable that the disease ever spreads directly from one breast to the other. The average duration of life in cancer of the breast that runs its course untreated is, according to Gross, 28.06 months. In 536 cases which were operated upon, and in which the disease returned, the average duration of life was 38.5 months. The operation appears, therefore, to have had the effect of prolonging life in those cases for ten months. Dietrich's estimates place the prolongation of life at seven months. It is usually considered that after the lapse of three years from the date of operation the patient may be regarded as permanently cured if no return has been observed, the percent- age of recurrence after that period being exceedingly small. Gross found that 11.83 P er cent - of the cases in his collection met that requirement. A combination of the statistics of Banks, Kiister, and Gross, consisting of 257 cases, shows that 19.38 per cent, were cured. The mortality of the operation amounted in this series to 12.06 per cent. In Dietrich's series of no cases there were 8 deaths, or a mortality of 7.6 per cent. His percentage of cures was 16.2. In the series of cases operated upon by him Dennis estimates the cures at 25 per cent. In 71 cases operated upon by him there was 1 death from haemophilia. His mortality was, then, 1.4 per cent, or if the haemophilia case be excluded it was o. Bull reports 75 cases with 3 deaths and 20 cures, the percentage of cures being 26.6, showing an increase over pre- vious records. Richardson found that the mortality of all cases (290) operated upon at the Massachusetts General Hospital up to the year 1877 was 7.9 per cent. The mortality of the operations 670 SURGICAL PATHOLOGY AND THERAPEUTICS. performed from 1877 to 1887 was 8.3 per cent, showing an increase due to the so-called "completed" operation. 1 The completed operation, so called, implies thorough dissection of the axilla. It has since been found necessary to dissect off the fascia of the pectoralis major muscle, and many operators have within the last year or two removed both the pectoralis major and the pectoralis minor. Notwithstanding the increasing severity of the operation, the mortality is steadily decreasing. In the writer's cases there have been* but two deaths since he began to perform the completed operation. This series includes an amputation of both breasts with dissection of the axillae, in many cases the re- moval of the two pectoral muscles and in one case the division of the clavicle. It would be fair to place the mortality of the writer's cases at 2 per cent. ; it is probably less than that. In regard to the number of cures the writer is unable to give any figures, but he found that all those cases which passed the three-year limit proved to be scirrhous cancer. The writer has in several cases dissected the supraclavicular space : this is the almost invariable practice of Halstead, who also removes both pectorals. In 50 cases Halstead has had but 6 per cent, of local recurrences. He advises the removal of breast and glands in one continuous mass to avoid wound-infection. In regard to the question of operation in the axilla, many sur- geons speak of the period previous to axillary infection. Since the writer has been in the habit of dissecting the axilla in every case of operation for cancer of the breast, he has never yet found an axilla that had not already been infected, and in one case, already referred to, the operation was performed three weeks after the disease had first made its appearance as an extremely small nodule in the upper and inner quadrant. The diagnosis of cancer of the breast often presents great diffi- culties. Although a lump in the breast of a woman between forty and fifty years of age is cancer in 80 per cent, of the cases, there is a residue in which non-malignant growths occur. The commonest form is cyst-formation due to chronic mastitis. This cyst usually develops in the upper hemisphere, and it is accompanied by the enlargement of a few glands in the axilla. These glands, however, are discrete and soft, and unlike the matted glands of cancer. The writer finds the use of the Mixter punch most valuable in such cases, and in fact in all doubtful cases of cancer. The operation when performed with cocaine injection is painless and harmless, and it secures a specimen amply sufficient for microscopic diag- CARCINOMA. 671 nosis. Chronic mastitis with fibrous thickening or tubercular abscess may be mistaken for cancer. There remains to be considered still one form of disease which is usually described as an affection of the breast, although belong- ing strictly to the class of carcinoma of the skin. Page? s disease of the nipple has been compared to an eczematous affection limited to the nipple and the areola, which affection eventually becomes malignant and may involve the whole breast. The disease is rarely seen before the age of forty. It may make its first appear- ance after a confinement or after nursing, and shows itself on or about the nipple as a crust which cannot easily be removed. Presently the skin becomes red and more or less inflamed, and the nipple gradually becomes retracted. The area of the disease con- tinues to spread, and the part becomes indurated and slightly raised above the level of the skin. The diseased surface gradually be- comes more moist and bleeds easily, and finally ulceration takes place, often becoming quite deep in the vicinity of the nipple. The disease is accompanied by itching and burning. As the carci- noma grows the ulceration becomes deeper and the induration greater, and eventually it may extend into the deeper portions of the breast. Glandular involvement is rare except in the latest stages of the disease. The histological changes observed in this disease have been studied by Paget and Porter among the earlier observers, and more recently by Thin, Darier, and Wickham. In the earlier stages the disturbance is limited, as in keratosis, chiefly to the epidermic layers. During the earliest period there are found an elevation and a thickening of the epidermis, and the cells of the rete lying between the papillae are more abundant, and project more deeply than normal into the cutis vera. The true skin is infiltrated with small round-cells in its upper layer, but the deeper layers appear to be normal. Wickham made a special study of the psorosperms in this disease, and at this stage found them numerous in the Mal- pighian layer. They appear as round or oval bodies with thick glisten- ing capsules, and they are situated in the protoplasm of the epithelial cells, pushing the nucleus to one side. When treated with alcohol the protoplasm of these bodies contracts, and leaves a space which was regarded as a vacuole in the cell. In a more advanced stage the epidermic cells are often wanting, and even the Malpighian layer is more or less destroyed, so that the papillae are covered chiefly by round-cells. The corium is now infiltrated with an inflammatory exudation. At the beginning of the cancerous stage 672 SURGICAL PATHOLOGY AND THERAPEUTICS. there is found an epithelial growth invading the corium and the various glandular structures to be found there, such as the seba- ceous and sudoriparous glands and the ducts of the mammary gland. These ducts are eventually filled with pavement-epithelial cells. As these cells grow the walls of the smaller ducts give way and the epithelial growth invades the stroma of the gland. It pre- serves the type of epithelial cancer, and in that form involvement of the axillary glands does not take place until late in the disease. During the active stage of the epithelial growth the psorosperms have been observed by Wickham forming cyst-like structures con- taining a number of oval corpuscles. The prognosis of the disease is favorable for cancer, for the pre- cancerous stage may endure for many years: after the cancerous stage has developed the breast can be removed in time to forestall involvement of the axillary glands, and a permanent cure may be the result. In the early stage the part should be treated as for eczema, but if soothing ointments fail to heal the disease, the growth can be destroyed with chloride-of-zinc paste or with solid caustic potash, or be seared with the actual cautery. The ' ' nitric-acid method ' ' described by Chiene enables one to detect with greater accuracy the presence of cancer in an amputated breast. The breast should be washed in water to remove all traces of blood; it should then be submerged in a 5 per cent, aqueous solution of nitric acid (B. P.) for about ten minutes. Wash the specimen in plenty of running water, and place in methylated spirit for two or three minutes. Epithelial structures are turned an opaque white, fibrous tissue is rendered transparent, and fat is unaltered. The cut surface should be treated in the same manner. In this way the sur- geon can determine more accurately than by the naked eye whether all dis- ease has been removed. 3. Carcinoma of the Uterus. The uterus, before all other organs, is the one most frequently affected with cancer. Schroeder reports that in an examination of 26,200 cases in his gynecological clinic, cancer of the uterus was observed in 812, or in 3 per cent, of all cases examined. In 7881 cases of cancer collected by Andrews, cancer of the uterus existed in 2308. Although affected so frequently with primary cancer, the uterus is more rarely the seat of metastatic cancer than any other organ. Cancer occurs in this organ in middle life or near the period of the menopause. From statistics of deaths in Vienna from 1862 to 1869 it is seen that deaths from cancer of the uterus occur most frequently from the thirty-sixth to the sixtieth year. CARCINOMA. 673 It may occur in early life, but it is far more rare, though usually more malignant, at that period. The figures of Williams show that heredity does not play a very important part. In 108 cases investigated, malignant disease was found to have existed in the relatives in 23 cases, or in 21.3 per cent., but in only 8 cases were the parents affected with cancer. The disease occurs most frequently in women who have borne children, particularly in those who have had large families. It is rare in the nulliparae, and when it does occur it appears chiefly in the body of the uterus. Among the diseases of the uterus that seem to favor the develop- ment of cancer may be mentioned chronic endometritis, particu- larly that variety which is accompanied by glandular hypertrophy. It seems to occur more frequently in the poor than in the rich, though negresses — who are particularly liable to uterine fibroids — are far less subject to cancer than white women. There are three principal seats of cancer of the uterus: it is found in the vaginal portion, in the cervical canal, and in the body of the uterus. Recent investigations seem to show that many of the cancers seen in the cervical canal or on the vaginal portion do not spring from the surface epithelium, but from the glandular structures in the deeper parts of the neck of the uterus, and that they appear sometimes in the cervix, and sometimes make their way out through the vaginal mucous membrane. Many of the papillary growths spring from this source (Ruge and Veit). Cancer of the neck and the cervical canal is far commoner than cancer of the body of the uterus. The cancer of the vaginal portion develops from the epithelium of this region, and is a pavement-cell epithelioma. It is of the same type as cancer of the skin. There is an abundant stroma in which the clusters of cells are imbedded. It may grow on one or both lips. It is occasionally seen developing from the surface of an old laceration, and very rarely it occurs in the interior of the uterus. The pavement-cell epithelioma, however, does not occur so frequently as was formerly supposed to be the case, for many of the cancers of this region are of the alveolar type, resembling more the adeno-carcinomata springing from glandular structures deep in the cervix. Cancer of this part of the uterus grows frequently as a papillary tumor, and it may assume considerable size, producing the so-called u cauliflower " growth. These pap- illary growths may have a broad basis or they may be attached only by a pedicle. A certain portion of these cauliflower growths are composed of pavement epithelium; others, however, have 43 674 SURGICAL PATHOLOGY AND THERAPEUTICS. cylinder epithelium, and they closely resemble the villous cancer of the bladder (Orth). Other forms of epithelioma may be flat and superficial, resembling somewhat the type known as rodeiit ulcer. The epithelial type, or cancroid, spreads outward into the vagina; it is rarely seen in the interior of the uterus or the cervix, although it may invade the cervical canal. Carcinoma of the cervical canal is more of the glandular or alveolar type, and it is developed from the glandular structures of this region. The disease may develop here without showing itself externally before it has produced a general ulceration of the cervical canal. It may, however, grow upward and involve the cavity of the uterus, or it may grow outward into the vaginal portion. Eventually the cervix is destroyed, and when the disease is found in an advanced stage of ulceration it is difficult to decide from which region the cancer originally developed. In cancer of the body of the uterus there is presented a type more distinctly glandular in character, the so-called " adeno-carci- noma" or malignant adenoma. Here the growth spreads deeply into the muscular tissue of the uterus, and many of the trabecular of the stroma contain unstriped muscular fibres (Fig. 97). The Fig. 97. — Cancer of the Uterus (oc. 3, obj. A cells in the alveoli are cylindrical, and are often arranged around a central lumen as in gland acini. Near them, however, are other alveoli, which contain solid masses of cells. These carcinomata may vary from the scirrhous to the medullary type, according to the amount of stroma they contain. By changes in the stroma there may occur a mixed form of growth, such as myxo-carci- CARCINOMA. 675 noma or sarco-carcinoma, according as the stroma changes to mucous or to sarcomatous tissue (Orth). As cancer of the cervix spreads the parts about become con- verted into one large ulcer, and the anatomical relations are lost. The cervix is destroyed, and the disease next involves the mucous membrane of the vagina, when the border of the ulcer may be raised, forming the margin of a crater. From this point the dis- ease may spread to the subserous tissue about the uterus and at the base of the broad ligaments and the parametrium. It also extends into the wall of the uterus in a horizontal line, so that the entire thickness of the wall is simultaneously affected. Occasionally there may be found an isolated nodule of cancer higher up than the apparent upper edge of the disease. Whether this has spread by lymphatic infection, or whether it is possible that multiple can- cer can form, seems to be undecided. The pathological fact, how- ever, is extremely important in its bearing upon the choice of an operation. A curious complication sometimes occurs owing to a constriction of the cervical canal: as a result of this the secretions of the uterus are retained, and the condition known as hydrometra is established. In cancer of the body of the uterus the cavity may become much enlarged by ulceration before the cervical canal has been affected. This form of the disease spreads more rapidly in the direction of the peritoneum. Ulceration may, however, occur in the cervical mucous membrane from the irritation produced by the discharges. The whole organ often becomes enlarged, not simply when the body is infiltrated with cancer, but even when the disease is limited to the cervix. As the disease advances the bladder and the rectum become involved. The bladder is the or^an first attacked, and a fistulous opening may eventually be established between the bladder and the vagina, and the ureters may likewise become involved in the growth. A fecal fistula is also one of the possible complications of the disease. Infiltration of the broad ligaments is often accompanied with severe pains. As the disease progresses even the bones of the pelvis may be attacked. When the disease reaches the peritoneum the intestines become glued to the fundus of the uterus, and during the process of ulceration the cavity of the uterus may open into a loop of intestine. The tubes and ovaries are affected only quite late in the disease. Lymphatic infection is found in the lumbar, retroperitoneal, and inguinal glands. Metastatic deposits in the large abdominal organs are seldom seen. The presence of carcinoma in the uterus is not often recognized 676 SURGICAL PATHOLOGY AND THERAPEUTICS. before it has reached the stage of ulceration. The earliest symptom is usually hemorrhage — perhaps only a slight staining, particularly after unusual exertion or after the act of coitus. It may, however, appear in the form of profuse menstruation, or it may come on after the menopause as a frequently-recurring hemorrhage. Of sixty cases examined by Gusserow, in no less than fifty was hemorrhage the first symptom. When the ulceration becomes more extensive there is often a watery discharge, which later may become sero-sanguinolent. In the papillary form of cancer the discharge may be purulent and be mixed with foul fragments of sloughing tissue. Pain is often entirely absent. The attacks of internal pain sometimes accompanying the disease indicate an extension to other organs or in the direc- tion of the peritoneum. Irritability of the bladder or of the rectum is caused by the gradual involvement of these organs in the cancerous infiltration. More rarely there may be pruritus or pain in the breast or symptoms of nausea. In advanced stages of the disease there may be symptoms of localized peritonitis. A singular lack of constitutional disturbance often continues for a long time, but later the foul discharges may occasion sepsis which, combined with uraemia, may produce typhoidal symp- toms. With the development of the cancerous cachexia comes emaciation, and the patient eventually succumbs with the symp- toms of marasmus. The duration of the disease may vary greatly. Its course is usually more rapid than that of cancer of the breast, and the patient succumbs in most cases in from six to twelve months from the appearance of the first symptoms. Many attempts have been made to determine the nature of the malady from the local appearances, but the only certain way of settling definitely the question of diagnosis is by microscopic exam- ination. For this purpose fragments scraped away are almost useless; pieces of considerable size should only be used for this purpose. Frequently, however, it is possible only to obtain scrap- ings, particularly in cases of malignant adenoma. In this case the scrapings should be rolled up while fresh into a ball and hard- ened in alcohol. Sections can then be taken from this mass for examination. If there are found in these scrapings typical gland- ular structures, perhaps with ciliated epithelium within the tunica propria, and a round- or spindle-cell stroma, the surgeon has to do probably with hyperplasia of the mucous membrane. If, however, there are found irregular alveoli filled with epithelial cells or an anastomosing network of epithelium containing possibly epithelial CARCINOMA. 677 balls and a stroma in which muscular tissue is found, the diagnosis of carcinoma may be made. The presence, on the one hand, of tubular masses of gland-like tissue, very closely packed together without any tunica propria or muscular tissue, is strongly sugges- tive of malignant disease. On the other hand, an irregular gland- ular growth, consisting of dilated acini or of acini filled with cells or papillary growth situated in a normal stroma, is not sufficiently typical of cancer to establish a diagnosis (Orth). The old operation for cancer of the uterus, consisting in local excision or cautery, was almost invariably followed by a prompt return of the disease. The modern operations show better results. High amputation of the cervix is not a dangerous operation, and it shows good results, but it is less frequently employed now that more radical methods have come into use. Baker reports sixteen, cases of high amputation with no deaths. In six the disease recurred, and in ten there was no recurrence at periods varying from two to eight years. Hofmeier performed thirty-three high amputations with only one death. The after-results are reported by him to be as good as those for total extirpation. The early statistics of abdominal and vaginal hysterectomy show a large mortality. Thus in 1885 Duncan reported 137 cases of abdominal hysterectomy, with 99 deaths, or a mortality of 72 per cent. In 276 cases of vaginal hysterectomy there were 79 deaths, or a mortality of 28 per cent. Sarah K. Post, in 1887, collected 722 American cases of vaginal hysterectomy, with a mortality of 24 per cent. Scheyron, in 1890, reported 337 vaginal hysterectomies, with a mortality of only 16.9 per cent. Of 854 cases of vaginal hys- terectomy collected by Richardson and Stone for the writer — which cases were operated upon between 1887 and 1892 — there was a mor- tality of 9.48 per cent. In 483 cases of vaginal hysterectomy col- lected from reports in which an attempt had been made to furnish results, it was found that in 53 there was no recurrence at the end of two years; in 26, no recurrence at the end of three years; in 14, no recurrence is reported at the end of four years; and in 38, no recurrence was reported at the end of five years. In 34 cases the disease recurred at the end of the first year; in 45, recurrence was reported at the end of the second year; and in 2 only was the disease known to have returned during the third year. 4. Carcinoma of the Tongue. Cancer of the tongue is invariably of the pavement-epithelium type, or epithelioma, such as has already been described in Cancer 678 SURGICAL PATHOLOGY AND THERAPEUTICS. of the Skin. The cancer springs from the epithelial layer of the mucous membrane, but never from the glandular apparatus of the tongue. The disease is much commoner in men than in women. In 122 cases reported by Billroth there were 6 in which the disease was observed in women. In 293 cases reported by Barker there were 46 females. In a collection of 991 cases 151 were women. Statis- tics show that the percentage of women as compared with men varies from 43 to 33 per cent. The writer remembers having seen the disease certainly four times in women, one of whom, at least, was addicted to the use of a pipe. It occurs most frequently between the ages of forty and sixty-five, although it is occasionally seen at a much earlier period, as the writer has operated at least once upon a man not yet thirty years of age. Cancer is found in all parts of the tongue, but more frequently in the anterior half than in the posterior half, and on the edges rather than on the median line or dorsum, though it is seen occa- sionally on the posterior portion of the tongue near the papillae circumvallatae and in the region of the frenum. Occasionally two carcinomata may be found upon the same tongue, both of them being primary growths. The writer has observed this condition in one case, both nodules developing almost simultaneously and at some distance from each other. There may also be seen secondary nodules or a diffused form of cancer in the tongue; which fact is of importance to remember in making the selection of an operation. In no region of the body does the origin of the disease appear more clearly due to previously existing irritation. The presence of carious teeth, the foul condition of the mouth, the eating of highly-spiced food, the use of alcoholic drinks, and the "rough eating" indulged in by men may account partly for the greater frequency of the disease in the male sex. All authorities agree that a very large proportion of the cases of cancer are preceded by various abnormal conditions of the surface of the tongue. These conditions are variously described as chronic glossitis, psoriasis, icthyosis, smoker's patch, leucoma, or leucokeratosis. The latter condition strongly resembles that which has already been studied in the morbid conditions of the skin preceding cancer. Leucoma may assume various forms, but the commonest form is a patch or patches of white furry membrane, which patches appear to be somewhat thicker than, and therefore slightly raised above, the surface of the surrounding membrane. The patches seen by the CARCINOMA. 679 writer were very white and in striking contrast to the red mucous membrane. They were limited to the side of the tongue, and they covered the border rather than the dorsal surface. The whole sur- face of the tongue may be affected in this way. Associated with this condition are numerous fissures and small ulcers which appear from time to time. Warts are also liable to form in the latter stage of the disease, and, according to Butlin, a wart on a leucomatous base never gets well and always becomes cancerous. These con- ditions have been called the " pre-cancerous stage," and the fre- quency with which cancer seems to follow such conditions both on the skin and in the mucous membrane appears to justify the ex- pression. According to Wallenberg, leucoma — or " leucoplakia, " as it is often called — is caused most frequently by the irritation produced by the volatile and empyreumatic oils of tobacco. It may also be caused by disturbances in the digestive tract, with which of course the tongue sympathizes. Syphilis is also supposed to be a predis- posing cause. A section made through a leucomatous patch shows a growth of the epithelium of the rete mucosum both upward and downward. According to Butlin, the papillae are obliterated, but in a section made by Gannet, a drawing of which is before the writer, the interpapillary epithelium seems to be elongated down- ward. There is a thickening also of the epidermic layer. The papillary layer is infiltrated with round-cells. Such a condition strongly resembles that seen in keratosis senilis, and it could with propriety be called "keratosis linguae." Leucoma is almost un- known in persons under twenty years of age. It appears rarely to begin in persons over sixty, and it seldom attacks women (Butlin). The writer has seen but few cases of leucoma — one in a lady on whose tongue it first appeared in youth, and remained in the shape of several large brilliant white patches until old age, when it disappeared ; in another case, a man forty-three years of age, the tongue had been troublesome from child- hood ; the mucous membrane was sensitive and easily irritated, and it was prone to inflammatory conditions, during which small ulcers appeared. At the age of thirty-four typical leucoma appeared, situated for the most part on the right side of the tongue. Three years later the patches enlarged and a warty growth formed in the centre. Three years after this the writer removed with the knife the largest patch, which was about the size of a silver half-dollar. This operation was performed in June, 1891. In October, 1891, a small epithelial growth of an apparently malignant nature appeared on the opposite side of the tongue. This growth was removed, and it was found to be typical cancer. In December a similar growth was removed from the tip of the tongue. In April, 1892, both growths having reappeared, a large portion of the left side and the tip 680 SURGICAL PATHOLOGY AND THERAPEUTICS. of the tongue was removed by a wedge-shaped incision. The disease never returned in the tongue, but six months afterward a glandular enlargement was observed under the left jaw, and the patient died two months later. The growth was found to be typical carcinoma. In the case above alluded to the writer had an opportunity of observing the earliest stages of the cancerous growth, as it was shown to him but a few weeks after it had made its appearance. It even then had an unmistakably cancerous aspect. There was a distinct infiltration of the tissues of the tongue, and the growth was surrounded by the pearly rim so characteristic of epithelial disease. When fully developed the cancerous growth usually breaks down in the centre and presents itself as an ulcer with indurated and elevated margins. Such ulceration occurs in cancers situated on the side of the tongue and subjected to friction against the edges of the teeth. It may appear also on the side of the tongue as a nodulated mass in the form of a rosette, without any tendency to ulceration. As the disease grows the fold of mucous membrane extending to the jaw becomes involved, and the tongue is bound down by the contractions that occur to the floor of the mouth. When these ulcers are situated near the base of the tongue, the anterior pillar of the palate, and eventually the tonsil and the wall of the pharynx, become involved. Less frequently the disease begins as a nodule in the substance of the tongue, which nodule slowly enlarges, and finally shows itself above the surface. More rarely still the disease appears to originate beneath the floor of the mouth, and never comes to the surface, but it is felt as a hard, indurated mass beneath the chin. The tongue is so drawn down as to be deeply indented at some one point, and speech, and even swallowing, are often materially affected. In one such case that the writer has under observation the patient is greatly distressed by a constant flow of saliva. The enlargement of the lymphatic glands occurs at varying periods during the progress of the disease. Usually the glands do not appear to be affected until several months after the first appearance of the disease in the tongue. Many cases are on record where the tongue has been removed, in which event there has been no subsequent manifestation of the disease. It is, however, not an uncommon occurrence to find a return of the disease, if such an expression may be used, in the lymphatic glands, while the tongue remains healthy. In such a case it is clear that the gland in question was already affected at CARCINOMA. 68 1 the time of the operation, but that it was too small to be felt. Kocher mentions a case in which glandular infection occurred in five weeks, and the writer has seen one where the glands were infected equally early in the disease. The writer is so strongly impressed with the danger of leaving such an infected gland that he should not be contented to operate upon a case of cancer of the tongue without exploring the glandular region. He has, however, followed one case for two years in which half of the tongue was excised through the mouth and no glands were sought for. There was at the last report no evidence of disease, but such a result is hardly sufficient to authorize a repetition of the operation in the light of the usual experience. The most frequent seat of glandular infection is the floor of the mouth and the submaxillary region. A gland may be felt in front of the sterno-mastoid muscle and at the side of the thyroid carti- lage. The glands of the neck are quite as likely to be involved as are the glands of the axilla in cancer of the breast, and the writer has no doubt that the small percentage of cures reported is due to the fact that ' ' completed operations ' ' are not so frequently performed as they should be. Occasionally there is seen an exten- sive enlargement of the submaxillary and cervical glands, with little or no primary disease of the tongue. In a case which came under the writer's observation the upper triangle of the neck was so filled with enlarged glands as to form a tumor of considerable size. The tongue presented the appearance of the so-called " fern- leaf" pattern, but there was only slight induration, and it was difficult to say exactly where the primary lesion was situated. As the disease progresses in the mouth the ulceration increases, and the interior of the mouth becomes converted into a foul crater. The pain, which at first is usually slight, becomes severe, and it radiates in the direction of the ear, and a great deal of acute pain is often experienced in the later stages of the disease. The glands of the neck become enormously enlarged, and they form a tumor filling out the side of the neck from the jaw to the clavicle. The trachea is often pressed over under the opposite ear, and the rings can be felt beneath the skin; but difficulty of breathing is rarely experienced, although it may be impossible for the patient to swallow solid food. Metastatic deposits are said to be compara- tively rare, but they may be seen in the lungs, the liver, and the kidneys. Death may occur from hemorrhage or from exhaustion. The diseases most likely to be mistaken for cancer are simple ulcers formed by the friction of the sharp edge of a displaced 682 SURGICAL PATHOLOGY AND THERAPEUTICS. tooth, syphilis, and tubercle. In the case of the simple ulcer the position of the lesion, when the tongue is in its natural position, usually indicates sufficiently clearly the origin of the affection. The removal of the tooth is promptly followed by healing of the ulcer. In syphilis there is usually an induration of the substance of the tongue rather than a new growth of tissue: the disease is said to be found more frequently upon the median line than cancer. Tuberculosis of the tongue occurs as a chronic inflamma- tory process, and it appears as an ulcer with a more or less ill- defined inflammatory infiltration of the adjacent parts, whereas cancer does not produce an inflammation of the surrounding tissues. The line between the healthy structures and the new growth is therefore usually well marked. In all uncertain cases — and they are numerous — a fragment should be removed for microscopical examination, and this removal can be effected in no better way than by the Mixter punch. Cancer of the tongue runs a comparatively acute course, the duration of life varying from six to eighteen months from the first appearance of the disease. The operations for removing the tongue vary greatly, and they may in general be classified under three heads. Formerly a large number of cases were operated upon by the ecraseur^ owing to the fear of hemorrhage, and many operators still prefer this method, but it is rapidly going out of use. Whitehead's method of remov- ing the tongue through the mouth with scissors has replaced the older operation. It consists in a rapid excision of one-half or the whole of the tongue with the scissors, care being taken to keep the mouth well open during the operation. Hemorrhage is prevented by the use of haemostatic forceps, which seize the lingual arteries either before or as they are divided. In the third group belong those operations which contemplate an incision for the purpose of expos- ing the submaxillary and cervical glands, and the removal of the tongue either through the mouth or through the incision thus made. The submental incision, which enables the operator to remove the tongue through the floor of the mouth, is a useful method in case of cancer near the frenum or in the apex of the tongue. The submaxillary incision exposes the upper triangle of the neck, and enables the operator to remove the infected glands in this region before the mouth is opened, and the tongue is drawn through the wound. This method is sometimes called " Kocher's operation," and it is frequently preceded by tracheotomy in order that the wound in the mouth may be treated antiseptically. CARCINOMA. 683 The operation preferred by the writer consists in an incision directly downward from the corner of the month to the lower edge of the jaw, and thence backward to the angle of the jaw. After the cheek is reflected the jaw is divided at a point opposite the disease. A vertical incision downward from the wound exposes the infected gland region of the neck. Through a wound thus made the whole infected area may be removed in one continuous mass. The mortality of operations upon the tongue for cancer is some- what difficult to obtain, owing to the great variety of operations and to the varying degrees of severity of the disease. The causes of death are usually bronchitis, pneumonia, or gangrene of the lung. The German expression schluck-pneumonie suggests the infective nature of the process. Death rarely occurs from hemor- rhage or from shock. In 139 cases reported by Whitehead there were 20 deaths, showing a mortality of 14. 3 per cent. Separating the cases where the tongue alone was removed from those in which the glands and the jaw were involved, it is found that in the for- mer cases the mortality was only 4.5 per cent., whereas in the more complicated operations where the glands were involved the mortality ran as high as 77 per cent., and where a portion of the jaw was also involved as high as 57 per cent. In a series of 58 cases reported by Kocher, belonging to the class of "glandular" or " completed " operations, in which the most strict antiseptic precautions were observed, the mortality was only 10.3 per cent. These results are better even than those following the use of the ecraseur. A series of 40 cases reported by Barker operated upon in this way gives a mortality of 12.5 per cent. Bill- roth's clinic gives a mortality of 10. 1 per cent, in 148 cases. This mortality is a marked diminution from that in his earlier cases, which at one time was as high as 25 per cent. The results of treatment in this disease cannot be said to be encouraging. In the series of 148 cases just alluded to there were only 10 cases that remained well at periods varying from fourteen months to eight years. On an average the patients died one year after the operation from a return of the disease. In 38 cases in which reports were obtained by Kocher it was found that the dis- ease had returned in 25. The earliest return appeared within seven months, and in one case the disease did not appear until ten years after the operation. In the 13 cases in which there was no return reported, 5 were found well at the end of seven, eight, ten, and twelve years, respectively. In Barker's series of 170 cases 684 SURGICAL PATHOLOGY AND THERAPEUTICS. there were less than five who were well three years after the ope- ration; and in Butlin's 70 cases there were but 6 cases of cure on the three-years' limit. Richardson obtained 13 answers from 20 cases operated upon at the Massachusetts General Hospital. Of these cases 11 were dead, and of the 2 living cases it is uncertain whether one of them was cancer. It will be seen that the best results thus far reported have been obtained after Kocher's operation. The very small percentage of permanent cures reported by nearly all surgeons may in part be accounted for by the imperfect nature of the method of operating employed. Few surgeons are content at the present time to remove the breast without a dissection of the axilla, but the number of those who attempt a dissection of the strategic points in the neck in cancer of the tongue is yet small. In the writer's opinion the whole neighborhood of the infected region should carefully be explored for disease, and in a majority of cases it is advisable to perform temporary section of the jaw in order to expose thoroughly the seat of the trouble. It is only by such radical measures that it can be hoped to reduce the fearful mortality of cancer of the tongue. 5. Carcinoma of the (Esophagus. Carcinoma is one of the most frequent forms of disease of the oesophagus. It belongs to the pavement-epithelium type of car- cinoma, and on microscopic examination epidermic balls are found here and there among the clusters of epithelial cells. It develops from the epithelium of the mucous membrane or from the ducts of the mucous glands. Colloid cancer of the oesophagus is said to be extremely rare. Butlin refers to a scirrhous type in which the progress of the disease is unusually slow. The disease is said to occur oftener in men than in women, although the writer has seen it in about an equal number of each sex. Of 510 cases analyzed by Newman, 108 were women and 402 were men. It is most frequent- ly found in persons over forty years of age. Mackenzie in a study of ico cases found 92 in which the patients were over the age of forty. The seat of the disease varies greatly. Rindfleisch places it in the middle third of the oesophagus, particularly at the point where the left bronchus crosses the oesophagus. Mackenzie found the disease in more than half the cases in the upper half of the oesophagus. Petri and Zenker, however, found 63.8 per cent, of the cases in the lower third. Newman states that the commonest spot in his experience is behind the cricoid cartilage. The writer CARCINOMA. 685 found it usually below the level of the cricoid cartilage or on a level with the upper edge of the sternum: in one case he saw it at the junction of the pharynx and oesophagus. The disease usually encircles the tube and causes a firm constriction. When the oesoph- agus is laid open the disease appears as an ulcer with elevated and everted edges. The width of the carcinomatous ring varies from 2 to 8 cm., but it may rarely be much more extensive. As the disease progresses the ulceration becomes more extensive, and perforation may take place into the trachea or the bronchi, the posterior mediastinum, the pleura, the pericardium, or the blood- vessels. Perforation of the trachea is a not infrequent complica- tion, and it can be recognized by the presence of a muco-purulent expectoration containing particles of food. The growth may press upon the recurrent laryngeal and pneumogastric nerves. Meta- static deposits are found in the adjacent lymphatic glands, and not infrequently in the lungs, the liver, and the kidneys. The first symptom of the disease is, in the majority of cases, difficulty in swallowing. On questioning the patient a history of loss of flesh during the previous six months may usually be ob- tained. As the disease progresses a tumor can be felt in the region of the neck or the cervical glands are perceptibly enlarged. The presence of a cough shows that the disease has begun to infringe upon or to involve the tracheal wall. The passage of a bougie w r ill usually settle the diagnosis, for strictures from any other source except from swallowing corrosive liquids are extremely rare. The treatment of cancerous strictures formerly consisted in the frequent passage of bougies, but this method is liable to be fol- lowed by perforation of the softened tissue. Symonds devised a method of oesophageal tubage which is far superior. Symonds' tubes are about 4 inches in length, and have a funnel-shaped open- ing which permits them to be introduced and left in the stricture; a ligature attached to the end of the tube emerges from the mouth and is fastened to the ear. Mixter devised an ingenious method of sounding the narrow strictures and of dilating them, and he has improved Symonds' method of introducing the tubes. These tubes can be worn for several days at a time w 7 ith great comfort. This method supersedes largely the formation of a gastric fistula. Gastrostomy, as originally performed, established a fistula through which the patient could easily be fed. The operation provided no means of preventing the escape of the contents of the stomach through the fistulous opening. The cough with which patients in the advanced stage of cancer of the oesophagus are 686 SURGICAL PATHOLOGY AND THERAPEUTICS. afflicted often favors leakage through the fistula. Several ope- rations have been devised to overcome this difficulty. Von Hacker makes the fistula through the left rectus muscle, so as to secure a sphincteric action from the tonic contraction of its fibres around the extruded portion of the stomach-wall. Witzel aims to combine a sphincter-like action of the muscles of the abdominal wall with a valvular fistula. The fistula passes through both the rectus and the transversalis muscles, whose fibres, running at right angles to each other, may be expected to contract still more efficiently than the rectus muscle alone. The second feature of this operation is the unfolding of a tube in the wall of the stomach, which is stitched over the tube so as to form an oblique canal. This method is said efficiently to overcome the tendency to leakage from the stomach. A third method, described by Meyer as the Ssabanejew-Frank method, consists in drawing out a loop or cone on the stomach- wall through the ordinary oblique incision, and passing it under a bridge of skin to a point above the border of the ribs, where it is fastened and opened. This operation has not as yet had an exten- sive trial, but Meyer, in a review of these various methods, looks upon it as the coming operation in cases of malignant oesophageal stenosis. The writer has succeeded in establishing a srastric fistula with perfect valvular action on a dog by the following operation : A fold of the anterior wall of the stomach is pinched up and stitched one and a half inches higher up on the surface of the organ. If an incision is made into the stomach just below the line of suture, a double fold of mucous membrane will be found hang- ing over the inner opening of the cut. In the stomach of Alexis St. Martin a similar fold of mucous membrane covered the internal orifice of the fistula. According to Knie, the average duration of life in thirty-five cases successfully operated upon was one hun- dred and twenty-five days. Tracheotomy may be necessary on account of oedema of the larynx or pressure upon the recurrent laryngeal nerve. CEsophagectomy was performed in 1877 by Czerny for a small growth in the oesophagus, the lower segment of which was united to the external wound. Ashurst collected twelve cases of ©esophagectomy with eight deaths. If the growth could be discovered early enough, such an operation might be con- templated with a view to a radical cure of the disease. 6. Carcinoma of the Larynx. Cancer of the larynx appears usually as a pavement-cell carci- noma; rarely an encephaloid or a scirrhous form exists in the CARCINOMA. 687 larynx. Cancers of this region are divided into intrinsic and extrinsic. Intrinsic cancer includes growths originating from the vocal cords, the ventricular bands, and the ventricles. Extrinsic cancer is situated upon the epiglottis, the ary-epiglottic folds, and the interarytenoid region. Cancer of the larynx is a disease of advanced life, 50 per cent, of the cases occurring between the ages of fifty and seventy. Males are more liable to the disease than females. The abuse of tobacco and strong alcoholic drink, prolonged residence in humid, cold climates, as well as respiration of gases or of vapors of an irri- tating nature, are predisposing causes (Morgan). Intrinsic cancer has at first the appearance of a wart-like growth taking its origin somewhere in the middle or the upper portion of the larynx, from the vocal cords, or the margin of the ventricle. Ulceration takes place at an early period, and it infiltrates the surrounding parts, involving the cartilages and eventually spreading beyond the limits of the organ. The lym- phatics are infected ultimately, but only to a limited extent Metastatic deposits are probably exceedingly rare, as death oc- curs in the majority of cases from changes produced by the local conditions. Extrinsic caiicer originates in the epiglottis or the ary-epiglottic folds or anywhere on the upper margin of the larynx. From this point it spreads to the surrounding parts, and it may involve the pharynx, the tongue, the tonsils, and the palate. The lymphatic glands are infected early in the disease. The earliest symptom of this disease is hoarseness; later there may be difficulty of breathing and of swallowing. Pain, which at first is dull, may later be of a sharp, cutting character, and it extends to the ear, cheek, and neck of the affected side. There is cough, with a more or less foul, purulent expectoration. An early diagnosis of the disease is of the greatest importance, for there may be sarcoma as well as cancer in the larynx, in addi- tion to the many benign forms of growth, and tubercular and syphi- litic ulceration may exist within the larynx. The removal of a fragment for microscopical examination should, according to New- man, not be done until it is decided to operate immediately if the growth prove to be carcinoma, as the growth often becomes more malignant after such an operation. The prognosis is unfavprable in all forms of cancer of the larynx, but it is much worse in extrinsic cancer. In intrinsic cancer the disease progresses slowly and death may not occur for several years. 688 SURGICAL PATHOLOGY AND THERAPEUTICS. Patients affected with extrinsic cancer die usually at the end of a year or eighteen months. The treatment may be palliative or be operative. Under the former heading comes tracheotomy, which often relieves many of the most distressing symptoms of this dis- ease. The principal operations are thyrotomy and unilateral or complete laryngectomy. The mortality of total extirpation of the larynx has decreased somewhat within the last ten years, but it is still quite high. In 121 cases compiled by Newman there were 41 deaths, or a mor- tality of 33.88 per cent. In 55 partial extirpations there were 16 deaths, or a mortality of 29.09 per cent. The results of operation in cases of intrinsic cancer show that after total extirpation of the larynx 16 per cent, of the cases remained well at the end of three years, and in partial extirpation the percentage of cases of intrinsic cancer remaining well after three years was 17.40. The number of operations is now exceedingly large, and many have been per- formed in America. In carefully-selected cases, such as that recently reported by Monks, where the disease was confined to the vocal cord and the patient remained well in active work eighteen months after the operation, it is reasonable to hope that a perma- nent cure may be effected. 7. Carcinoma of the Stomach. Cancer of the stomach is one of the commonest forms of carci- noma. It takes its origin from the cells of the gastric follicle, and as the disease develops it perforates the muscular layer and then spreads rapidly. The commonest variety is the cylinder-cell cancer, which may appear both as a medullary and as a scirrhous form, and colloid cancer is also occasionally seen. The disease attacks men slightly oftener than women. It is rarely seen before the age of thirty, three-fourths of all cases occurring between the ages of forty and seventy. The most frequent seat of the disease is at the pyloric orifice. Welch analyzed the reports of 1300 cases, and found the pyloric region the seat of the disease in 60.8 per cent. The growth shows a tendency to break down and ulcerate. At times this tendency is so great that only a small margin of cancer remains, as in rodent ulcer of the skin. At other times the growth is very exuberant. Metastatic deposits in the lymphatic glands and the abdominal organs are frequent accompaniments of the disease. The principal symptoms are pain in the epigastrium, with CARCINOMA. 689 symptoms of dyspepsia, vomiting, the development of a percepti- ble tumor, and emaciation. The disease may be regarded as incurable, but attempts have been made during the last decade to remove the growth by resec- tion of the pylorus. Billroth, the originator of this operation, reports 29 operations with 16 deaths. Of the 13 who survived the operation, 5 died within ten months after the operation; 2 lived over one year; 1 lived one and a half years; 1 lived two and a half years; and 1 lived five and a quarter years. Only 2 patients remained well at the time of the report, but in 1 the operation had been performed only four and a half months before, and in the other two and a half months before. The total number of cases reported at the Berlin Congress was 56, with a mortality of 48.2 per cent. Among the most recent reports are those of Czerny, who gives 12 operations with 5 deaths: 2 were living in complete health fifteen and twenty-six months after the operation. The other 5 died two, seven, ten, fifteen, and eighteen months, respectively, after the operation, with symptoms of a return of the disease. 8. Carcinoma of the Intestines. Carcinoma of the Intestines. — The most frequent seats of car- cinoma of the intestines are at the ileo-csecal valve, the descend- ing colon, and the sigmoid flexure. Cancer may, however, occa- sionally be seen in the small intestine. Of 37 cases collected by Butlin, 32 were in the large intestine and 3 in the small intestine, the seat of 2 being uncertain. In 4 cases the disease was in the ascending colon; in 3, in the transverse colon; in 7, in the descending colon; and in 9, in the sigmoid flexure. The variety usually seen is the cylinder-cell carcinoma, which may at times assume the medullary or the scirrhous type. Colloid cancer is also found in this locality. Ulceration begins early, and cicatricial contraction accompanies it, so that the disease may appear as a narrow fibrous stricture with little if any new formation. At other times considerable length of the bowel may be affected. As the disease progresses the muscular coat is perforated and the peritoneal coat becomes infiltrated. As a result of this infection,, adhesions occur to adjacent peritoneal surfaces, and the diseased gut becomes so bound down that an operation for resection or one for intestinal anastomosis is rendered exceedingly difficult: sometimes it is impossible to perform either operation. Death occurs usually as the result of chronic obstruction of the bowels. According to< Butlin, the duration of the disease is short. From the beginning 44 690 SURGICAL PATHOLOGY AND THERAPEUTICS. of the symptoms to the time of death the period varies from six to eighteen months. The disease attacks males and females about equally. It occurs generally after the age of forty years. Operative statistics collected by Weir and Butlin show a high mortality. In 37 patients reported by Butlin on whom the opera- tion was performed, 18 died shortly afterward. In only one instance among those who survived the operation was there a patient still well at the end of a year. Czerny reports 10 cases of resection for malignant growths — 4 at the caecum, 2 at the sig- moid flexure, 3 in the transverse colon, and 1 in the descending colon. In 3 cases an adjacent coil of intestine was involved; 1 was a medullary cancer, 1 was a papillary growth, and 4 were adeno-carcinomata; of the latter four, 3 were of the scirrhous type; 3 were cases of colloid cancer, and 1 case proved to be an alveolar sarcoma which appeared five years after the removal of an ovarian sarcoma. This patient remained well six years after the resection of the intestine. Of the cases, 5 recovered from the operation and 5 died. Of the five recoveries, 1 died six months afterward from local recurrence, and 4 were alive six, fifteen, nineteen months, and six years respectively after the operation. Of the patients, 6 were women and 4 were men. The men all died from the effects of the operation. The average age was forty-five years. Czerny regards the most favorable cases for operation those of the scir- rhous type, which cause stricture early and thus lead to operation. 9. Carcinoma of the Rectum. Carcinoma when found at the anus is of the pavement-cell variety, and when growing from the mucous membrane it appears as a cylinder-cell carcinoma. There are, therefore, in this locality both types of the so-called "epithelioma." The pavement-cell form, which takes its origin in the cutaneous coverings of the anus, begins as a warty or papillary growth that breaks down early and ulcerates. It is not unlike cancer of the lip in its early stages. The surrounding parts are more or less hard and infil- trated, and the edges of the ulcer are elevated and sharply defined. The growth spreads inward and involves the mucous membrane, and it invades also the external integument, involving the peri- neum or the commissure of the vagina and the labia in women. The cylinder-cell carcinoma (Fig. 98), which develops from the follicles of Iyieberkuhn, begins as a more or less exuberant growth, which soon breaks down and develops into a crateriform ulcer involving more or less of the circumference of the bowel. This CARCINOMA. 691 growth is found some little distance within the rectum, and it is often difficult for the exploring ringer to reach its upper margin. ivsiwS^&SSS? . — Cancer of the Rectum (oc. 3. obj. A.). The cells are arranged in acini, and they have a strikingly glandu- lar appearance, closely resembling that seen in cancer of the uterus (Fig. 99). It is therefore often called " adeno-carcinoma n or malig- nant adenoma. This is the common- est variety of cancer of the rectum. Cancer occurs also in the medul- lary form, but more rarely. It is exceedingly malignant, and it soon infiltrates the walls of the rectum, converting the latter into a rigid tube and gluing it to surrounding parts. Scirrhous cancer is said to occur high up near the sigmoid flex- ure or in the neighborhood of the prostate. It infiltrates the submu- cous tissues, and the mucous mem- brane over it for a time appears healthy. It grows slowly and causes annular stricture, or it is felt as a hard nodule in the wall of the rectum. Colloid cancer appears as a diffuse infiltration of the mucous membrane that spreads to the deeper parts. It is, however, a rare form of cancer in this region. Villous cancer is occasionally also seen. Fig. 99. — Cancer of the Rectum, showing cylinder-cells (oc. 3 obj. D.). 692 SURGICAL PATHOLOGY AND THERAPEUTICS. Cancer of the rectum occurs usually in middle life or in old age. There are, however, exceptions to this rule, cases having been reported in youth and even in childhood. In a collection of 107 cases, Kelsey found 50 cases in males and 57 in females. As ordinarily seen, cancer of the rectum forms a large crateri- form ulcer, with raised edges, encircling the bowel, and it is situ- ated two to three inches from the margin of the anus. As it grows it spreads chiefly to the deeper parts. As the surrounding layers become involved there is great destruction of tissue; contraction consequently takes place, and a long, narrow stricture forms, the walls of which are made up of the cancerous growth. In the female the vagina and the uterus become attached to the growth, and in the male the prostate and the bladder are invaded. The growth may extend also to the sacrum. As the walls of the adja- cent organs give way before the advance of the disease, fistulse are established and fseces may be discharged in the urine or urine may flow into the rectum. Cancer of the rectum remains for some time a localized disease. In 47 autopsies reported by Iversen there were no metastases in 21. After a certain period of time the lymphatic glands in the peri- rectal fat become enlarged, and the infection spreads along the pelvis into the abdominal glands. When the disease is situated near the anus the glands of the groin may become involved, and, according to Czerny, this form of cancer is much more likely to recur after operation. The duration of the disease is seldom more than two years, although instances have been recorded in which the symptoms have existed for as many as five or six years. Patients sometimes die, however, within a few weeks or months of the first appear- ance of the symptoms of rectal affection (Butlin). The early symptoms of the disease are often mistaken for hem- orrhoids. The breaking down of the new growth gives rise to a bloody or muco-purulent discharge which is mistaken for diar- rhoea. Later, the constriction causes apparent constipation, with intercurrent loose discharges or tape-like stools. Accompanying this condition there may be a certain amount of ill-defined, colicky pain. As the growth increases there is a sense of weight or deep- seated pain in the pelvis or the back. In the more rapid-growing forms of cancer the pain may become excruciating as the new growth forces its way into the tissues. Later the symptoms of obstruction are observed. Cachexia in the later stages of the dis- ease is very marked. Cachexia is caused partly by the disease and CARCINOMA. 693 partly by the septic absorption from the bowel and the secondary affection of other organs. The operation that was formerly employed for a radical cure of the disease was known as the u Lisfranc" operation, and it consisted in an excision of the bowel from below. Statistics compiled up to 1881 show a high mortality, varying from 31 to 58 per cent, in the hands of different surgeons. During the next ten years the im- proved methods produced a considerable reduction in the death- rate. Thorndike estimates the mortality of the operations of vari- ous kinds done during this period in a selected series as low as 16. 1 per cent. Butlin collected 100 cases, including part of both periods, with a mortality of 35 per cent. Of the 65 patients who survived the operation, all were not subsequently heard from, but 13 cases were reported alive and well for at least two years after the opera- tion. Iversen in an analysis of 247 cases of all kinds of operations found in 70 patients who survived the operation (but who died subsequently) that there was a local recurrence in 42, and in 32 cases that were still living there were 6 with local recurrence of the disease. Kraske's method was first described in 1885: it consists in a pos- terior incision with resection of the coccyx and a portion of the sacrum. There are other operations of a similar nature, but dif- fering in the amount of bone resected. This operation, although it is more severe than the earlier method, does not appear to be much more dangerous. A collection of 102 cases operated upon in this way gives a mortality of 21.5 per cent., though Thorndike' s collection of cases gives a mortality of only 14.7 per cent. It is early yet to determine the merits of the modern operation as a curative measure. Arnd, in a collection of 98 cases operated upon by various methods, reported 24 "cures" (time-limit not stated), and of these he found 15 had been operated upon by the modern method. Of 39 cases operated upon by Albert, 3 were well one year after operation, 2 were well two years after ope- ration, 1 had passed the three-year limit, and 1 was well four years after operation. The number of cures by any method is not yet known to be large. The disease is, however, in many cases exceedingly slow in its course, and if cases are carefully selected for operation it seems probable that the future will show an increased percentage of cures. 694 SURGICAL PATHOLOGY AND THERAPEUTICS. 10. Carcinoma of the Bladder. Cancer may grow from the walls of the bladder or from the prostate gland. Cancers growing from the latter organ are in no way to be distinguished clinically from those of other regions of the bladder, and they form a large proportion of the malignant growths in the vesical cavity. The precise origin of carcinoma at the neck of the bladder is indeed difficult to determine, and even those carcinomata situated more posteriorly at the base of the bladder are uncertain in their origin, as the middle lobe of the prostate may have prolongations extending some distance into the walls of the bladder, and the disease may be found to spring from these glandular bodies, as in a case reported by Marchand. The epithelium of the acini of the prostate is a short cylinder-epithelium, and in the deeper more spongy portions of the prostate it is cubical. A small- cell carci- noma with a glandular arrangement of the cells in the alveoli is strongly suggestive of prostatic origin. There are, however, forms of carcinoma that spring from the bladder-wall directly, although Klebs claims that such do not exist. Bode found that in 30 cases of cancer of the bladder 14 were in women. Orth describes the villous cancer as the commonest form. There may be a benign papilloma appearing as a villous tumor, and also a villous cancer. In the papilloma are found very long fimbriated processes composed of a connective tissue in which run blood-vessels covered by several layers of columnar cells. In the villous cancer are found similar villi, and in the base of the tumor at the point of origin of the broad villi and also in the bladder- wall are found alveoli containing cancer-cells. The villi are, how- ever, as Krister shows, merely an accidental feature of these growths, and indicate nothing as to the microscopical character of the tumor. Cancers of the bladder-wall spring from the deeper layers of the epithelium and rarely from the epithelium of the mucous glands. The commonest form of cancer of the bladder, according to Krister, is that composed of squamous and pear-shaped cells, a polymorphous type with cells resembling those of the bladder- wall. There is an abundant connective-tissue stroma which produces a scirrhous type of cancer. The medullary form is much less fre- quent. Sometimes the cells assume the pavement-epithelium form, producing pavement-cell carcinoma or epithelioma, such as is seen in the skin. In these cases well-marked epithelial nests CARCINOMA. 695 or epidermic balls may be found. Colloid cancer may also occur here. This condition may involve the whole or only a part of the growth. All these varieties appear as rounded, more or less flattened elevations in the mucous membrane. The membrane may run smoothly over the growth, or it may be infiltrated, or, finally, papillary growths may develop on the surface of the tumor. A papilloma may precede the development of a cancer for several years, and Kiister suggests that the irritation produced by the pull of the tumor upon the mucous membrane during urination may be a source of irritation which gives rise to the cancerous growth. The conditions resemble those in the skin where warty growths precede epithelioma. As the cancer grows ulceration takes place, and the villi, if present, disappear. The growth penetrates the muscular wall, which becomes thickened, and it finally reaches the peritoneum, causing the bladder to become adherent to adjacent organs, some of which may eventually become involved in the disease. There is a remarkable tendency, however, of these carcinomata to remain local; which fact Watson attributes to the lack of connection of the larger lymphatic channels with the mucous membrane. The inguinal glands may occasionally be infected. The lungs and the pleura are the most frequent seats of metastatic deposits. As the carcinoma breaks down and ulcerates, the urine may become exceedingly foul, and be mixed with blood, bacteria, and frag- ments of tissue. As a result of the irritation thus produced the kidneys become diseased, and patients affected with this disease are said to die most frequently of pyelitis. Secondary cancer of the bladder has been observed, although it is extremely rare. In a case reported by Targett the disease was found in the muscular layer. The most characteristic and commonest symptom of bladder- tumors is hsematuria. The symptoms of catarrhal inflamma- tion come later, and a microscopical examination may lead to a diagnosis of the disease. Pain is not always present, but at times the emptying of the bladder is accompanied by severe cramp. At first there is slight constitutional disturbance, but as the disease progresses there may be emaciation, and later symptoms of cachexia or of kidney complications may arise. The course of the disease in isolated cases may be extraordi- narily slow. Budor reports one case in which the patient died twenty-four years after the first symptoms, and Guyon reports a case of eighteen years' duration. 696 SURGICAL PATHOLOGY AXD THERAPEUTICS. The opera:: :ment of cancer of the bladder consists in suprapubic or perineal cystotomy, with curetting and cautery of the growth, which is of course but a palliative measure, or in an attempt to perform a radical cure. The operation devised for this purpose consists in excision of a portion of the bladder-wall or in extirpation of the bladder. Marsh mentions five cases of resection of a portion of the bladder-wall. Of these cases, two only could be said to have recovered from the effects of the operation, one living twelve months and one living four years. Marsh also adds a sixth case of his own, which was fatal. These results show a mortality of 66 per cent., and not one radical cure. Extirpation of the bladder has been performed in four cases, according to Watson, with three recoveries, but it does not appear that the operation was performed for cancer. In a collection of eight cases made by Stone, four were found to have died of the operation, giving a mortality of 50 per cent. One case, in which two-thirds of the bladder was removed, lived one month, dying of v ' asthma. " In another case, in which one-third of the bladder was removed, the wound healed in fifty-five days. Recurrence of the disease took place in six months, the patient dying at the end of a year. One patient lived four years, the disease reappearing two years after the operation. Fenwick reports nine cases of operation by twisting with forceps and cutting with scissors. In one case the disease returned in three months and the patient died. In one case the growth was removed a second time, and in another two subsequent operations were performed. Baker operated upon a woman through the vagina, cutting out the growth with scissors. Three months later the patient left the hospital in good condition. n. Carcinoma of the Kidney. The commonest form of cancer of the kidney is the medullary; scirrhous cancer is also seen, but less frequently. Colloid cancer of the kidney is rare. The disease is most frequently seen after middle life, but it is found also in very young children, and a few cases of congenital cancer of the kidney have been reported. The disease occurs twice or three times as often in men as in women. Among children the difference in sex is not so marked. Cancer occurs in the kidney in an infiltrated form or as a nod- ular growth. In the infiltrated form the kidney is somewhat enlarged, and the cortical portion is found thickened, particularly at certain points corresponding with nodular enlargements on the CARCINOMA. 697 surface. These points are not sharply-defined foci, but they are caused by a greater development of the disease there. They have a grayish medullary appearance on section. Under the microscope the cancer-cells are seen crowding the uriniferous tubules, which are very irregularly distended. The cancer-cells are distinguished from the normal epithelium by their large vesicular nucleus. At some points these cells can be seen in the cortical portions of the kidney, and it is probable that they develop from the epithelium of these portions of the organ as well as in the deeper structures. The nodular cancer, which develops as a distinct nodule often separated from the rest of the kidney by a capsule, many attain a considerable size. The remainder of the kidney in such cases is flattened out against the side of the tumor. The tubules may be seen in the diseased portion, but they are much elongated and con- stricted. The cortical portion of the kidney is often seen still partially preserved in the periphery of the tumor. These large tumors undergo many retrograde changes, such as fatty degeneration and necrosis; also cystic degeneration, and occa- sionally calcification. They are often separated into lobules by broad bands of fibrous tissue. The trabeculse which surround the alveoli are often very delicate, and they seem to consist almost solely of blood-vessels. Such growths are necessarily highly vas- cular (Orth). There is occasionally seen adeno-carcinoma of the kidney strongly resembling adenoma, and this form may assume the villous type. The lymphatic glands behind the peritoneum and in front of the spine are affected early in the disease. The results of opera- tions upon the kidney for cancer are not encouraging. In fourteen cases of nephrectomy compiled by Gross the operation was very fatal, giving a mortality of 71.42 per cent. Death was caused either by uraemia, by shock, or by peritonitis. Of the four survi- vors, two died of secondary growths at the expiration, respectively, of forty-four days and two months, and the remaining two were alive at the end, respectively, of two months and thirteen months. Gross regards the disease as one which should be excluded from the category of cases for which nephrectomy should be performed. Both Butlin and Greig Smith speak unfavorably of the operation. Fenger recently reported a case of adeno-carcinoma of the kid- ney the size of an tgg^ for which he performed lumbar nephrec- tomy successfully. The patient was alive and well two and a half years after operation. Fenger quotes a case of Israel who diagnosticated a carcinoma the size of a cherry and operated, 698 SURGICAL PATHOLOGY AND THERAPEUTICS. obtaining a radical cure; that is, according to the three-year limit. 12. Carcinoma of the Testicle. Carcinoma testis occurs in the medullary form in most cases. Scirrhous and colloid carcinomas are also occasionally seen. In no case has the disease been observed before the age of twenty. In 37 cases collected by Kocher it was found in 29 between the ages of twenty and forty. In about one-fourth of the cases the same author found that the disease followed trauma. The cancer-cells develop first in the convoluted tubes from a proliferation of the seminal cells. The tubes nearest the centre of the organ are usu- ally the first affected, the upper portion of the testicle remaining intact or being involved later in the disease. The rete is also affected secondarily. In the scirrhous form there is a large development of connective tissue, and sometimes of hyaline cartilage and bone. On section the growth appears as a smooth surface, on which are fibres run- ning in various directions without any evidence of normal tissue. Medullary carcinoma appears as a grayish nodular tumor with a slimy surface. The tumor may often be quite large, and may con- tain many foci of broken-down tissue, and it often attains a large size. In many cases of cancer of the testicle there are a large number of cysts (cysto-carcinoma). Secondary growths are often felt in the iliac fossa, and the lymphatic glands are enlarged along the spine, sometimes as high as the kidneys. The skin of the scrotum may be involved in many cases. Eventually metastatic deposits occur in the liver and lungs, and with the extension of the disease cachexia becomes marked. In consequence of the enlargement of the lymphatic glands pressure may take place upon the vena cava and the feet may become cedematous. The duration of the disease appears to be about two years. Many cases of permanent cure are reported after removal of the testis, but it is in most of the cases quite uncertain whether the disease was cancer or sarcoma. Winiwarter found in twelve cases only one in which there was no return of the disease two years and seven months after the ope- ration. Kocher reports six cases in which a reliable microscopic examination had been made. Of these patients all were alive and well at periods varying from one to ten and a half years. Of the few methods of curing cancer by medication which have been brought forward from time to time, there are none which have CARCINOMA. 699 stood the test of practice. In view of the interest which has been taken in Koch's method of treating tuberculosis, it may be worth while to notice a similar method of treating cancer that has been recently brought to notice by Adamkiewicz. He advances peculiar views as to the nature of cancer-cells, regarding them all as pro- tozoa, which, though they resemble epithelium, are not epithelial cells. Implanted into the brains of rabbits, they are found to pos- sess the power to migrate into the surrounding tissues, where some of them are destroyed and some grow and form new foci of cancer- cells. He also found that when fragments of cancer are thus implanted they produce an inflammatory reaction which does not take place when fragments of healthy tissue from the living body are substituted. If the fragments of cancer are dipped for a few minutes in a 3 per cent, solution of carbolic acid or are subjected to the action of boiling water for one or two seconds before inplan- tation, no inflammatory reaction takes place. Adamkiewicz con- cludes, therefore, that there is a toxic property in the cancer-cell, and that it is due to the action of this substance that the healthy tissues melt away before the advance of cancer. This substance he calls " cancroin," and he obtains it in solu- tion by treating minute fragments of cancer (cut up finely) with distilled water. The mass is then rubbed up in a mortar and filtered. A slightly opalescent and alkaline fluid is thus obtained. Such a fluid, if injected into rabbits subcutaneously, is found to act as a deadly poison. Adamkiewicz obtained a similar substance from the muscle and skin of fresh cadavers by a similar method of preparation, which substance was found to resemble closely neurin. The filtrate obtained from a watery extract of fresh cadaver tissue is a clear yellowish fluid of alkaline reaction and smelling like alkaline urine. Cancroin injected subcutaneously into cancerous growth sets up inflammatory reaction, and it gradually produces a disappearance of the cancer. Before injection this alkaline fluid is neutralized with citric acid. A 25 per cent, watery solution is then saturated with carbolic acid and is diluted with an equal quantity of water. This preparation is called u Concentration I. " Concentration II. is diluted to one-half the strength, and Concentration III. is diluted to one-quarter the strength, of No. I. The author begins with a subcutaneous injection of No. III. at some point not too remote from the growth. The results of these experiments are not suffi- ciently encouraging to authorize a general adoption of the method. In a personal communication from Adamkiewicz to the writer yoo SURGICAL PATHOLOGY AND THERAPEUTICS. he states that, although he has had thus far but little success with the method, he nevertheless regards it as an important advance in the treatment of cancer. The post-operative treatment of cancer is now regarded by many surgeons as a feature in the management of every case in which an operation has been performed for malignant disease. Among the drugs most frequently used for this purpose is arsenic. Wight recommends the administration of the bromide of arsenic in doses of from ^ to ^ grain after meals, and the carbonate of lime before meals in 5- to 10-grain doses in the tincture of calumba. Clemens' solution is a convenient form of administering the bromide of arsenic. It may be given in doses of 2 to 3 drops three times a day after meals. Wight advises that its use should be continued for from six to twelve months. In several cases of inoperable cancer he has found the progress of the disease delayed and considerable relief to pain. Roswell Park employs arsenic in the following combination, which contains the haloid salts of mercury, arsenic, and gold: It is administered in 10-minim doses, each of which contains -^ of a grain of bromide of arsenic, ^- of a grain of bromide of gold, and the y^-q of a grain of bichloride of mercury. The doses may be increased up to the physiological limit, and the use of the drug should be continued for months after the operation. It may also be given in inoperable cases. (See Appendix.) Pyoktanin was first recommended by Mosetig-Moorhof. In his original experiments anilin trichlorate was used, but in large doses this had a poisonous effect. Pyoktanin possesses the advantage of not being poisonous to the system. His object was to attack the nuclei of the proliferating cancer-cells, and then to arrest the growth of the tumor. The affinity which the anilin dyes have for nuclei first suggested to him that this staining process might be brought about upon the living cells, and their vitality be thus impaired. The agent is injected subcutaneously, so as to come in contact with the diseased cells. The pathogenic cells are dyed by pyoktanin in the living body. The cell-stain is not apparent at first. Mosetig accounts for the absence of coloring by the presence in the cancer-cells of a chemical substance which is able to reduce the anilin dyes in such a way that they lose their color. When the tumor has been extirpated and sections have been prepared from it for microscopical examination, exposure to the oxygen of the air brings out the blue stain. It may be used in solutions of the strength of 1 : 1000, 1 : 500, and 1 : 300. It is probable that much stronger solutions may be CARCINOMA. 701 used with safety. Mosetig-Moorhof has given as much as 6 grammes of a 1 : 300 solution without ill effects. The injection should be repeated every two or three days. The whole mass of the tumor should gradually become impregnated with the stain- ing fluid. Park has seen undoubted benefit from the use of pyoktanin, although as yet in no case a cure. He gives it in solutions of the strength of 1 : 1000 to 1 : 400. He also uses methyl-blue chemically pure internally, giving it usually in con- nection with the extracts of nux vomica and cinchona. Meyer reports one or two cases by other observers that appear to have been cured by this treatment, but in his own experience, which has been large, there has been no cure, although great improve- ment has been obtained in several cases. Mosetig-Moorhof reports a case of cancer of the gall-bladder which had been opened for gall-stone. A pencil of methyl-violet was introduced every two to four days, and 0.6 Gr. methyl-blue was given by the mouth daily. The general condition of the patient improved, the growth, a villous cancer, largely disappeared, and the incision contracted to a small fistulous opening. This surgeon reports several cases of sarcoma and carcinoma in which, although permanent cure had not been effected, there was considerable improvement in the condition of the patient. (See Appendix.) The use of Chian turpentine, Southall's solution, or Metcalf's emulsion is occasionally followed by some improvement in the ulceration which accompanies the growth of cancer. These preparations are usually given in doses of a teaspoonful three times a day, and are continued for three months. The writer has given this remedy a thorough trial, and in but one case only, a case of cancer of the tongue, did there appear to be any result whatever. In this case the ulceration in the mouth healed, but the progress of the disease continued as before. Although the therapeutic results of the treatment of cancer are most discouraging, the disease is not one in which the patient should be abandoned hopelessly to his fate. Both mental and physical relief has been obtained by the measures already mentioned: much may also be accomplished by general measures. Park recommends efforts to improve elimination in every possible way from the skin, kidneys and the alimentary canal. In cases of internal cancer the utmost care should be given to the condition of the digestive organs, and special rules should be laid down for the management of cases according to the locality in which the disease is situated. XXX. SARCOMA. The term l< sarcoma," derived from adoc (flesh), was first used to denote all kinds of fleshy growths. There was also supposed to be a resemblance between the fibre of sarcoma — particularly of certain forms — and the fibre :: muscular tissue This group of tumors is composed of the embryonic types of connective tissue, and in this respect it differs from most other tumors, which correspond in their structure to the rally-developed tissues of the body. Its embryonic nature is shown in the large numbers of cells of which it is com- posed. These cells vary greatly in their character in different varieties of sarcoma, but they are all types found in embryonic connective tissue. The round- and spindle-shaped cells are found not only in these tumors, but also in certain stages of development :: thetrh tissue. cmd tls: ;.t certrhn ;:rt::ls in the trrccess :•: rercir in a healing wound. The giant-cell is also characteristic of the embryonic structure of the medulla of bone, and it is seen both in bone and in connective tissue during that period of a morbid pro- cess when the embryonic type reasserts itself. There is this im- portant difference, however, between the cells of inflammation and repair and those of sarcoma: in that the former have but a temporary existence, whereas the latter tend to indefinite growth; it is this tendency which gives to sarcoma its malignant cha- racter. These cells tire characteristic :::t :my in their shtme. but also in their disposition in an intercellular substance, as is the case with all cells of the group of connective substances This intercellular substance may at times be very scanty and difficult t: see. and it is then composed either of delicate fibres or of granular material; at : ther times it may be more distinctly fibrous. It may also be com- posed of a transparent mucous substance, such as is found in the foetal cord. Occasionally it forms between the cells a delicate net- work which resembles the reticulum of the lymphatic glands. As the intercellular substance increases in quantity the cells diminish in number, and with this change is found a corresponding diminu- tion in the maliornancv of the growth. By adhering very strictly to these lines in deciding upon the - : SARCOMA. 703 microscopic diagnosis of sarcoma the surgeon is not likely to mis- take it for a tumor arising from a different form of tissue, such as carcinoma, wherein the epithelial cells are in direct contact with one another, being cemented together, and are enclosed in alveolar spaces by the stroma. The combined forms of sarcoma and car- cinoma mentioned by Virchow are, in the light of these dis- tinctions, no longer recognized. These growths originate from different germinal layers in the embryo, and they remain for ever after distinct. The endothelial growths in this respect come nearer to sarcoma, and they are so classified by some authors, although they have been placed among the carci- nomata. Sarcoma is usually a very vascular tumor, and in some cases the blood-vessels are developed to such a degree that the tumor actually pulsates. Microscopically, the walls of the vessel appear inti- mately connected with the new growth, and many of the walls seem to be made up almost solely of cells, being in many cases simply blood-spaces in the centre of the growth. Interesting in this connection is a growth regarded by some observers as allied to sarcoma, and described by Billroth as cylindroma, which is com- posed of columnar masses of endothelial cells in a more or less transparent matrix, and which is supposed to be formed from a growth of the endothelium of the blood-vessels, whose walls have undergone hyaline degeneration. Sarcoma seems closely associated with the blood-vessels, except that class known as lymphosarcoma, which is as intimately associated with the lymph- atics. The classification and definition which Virchow laid down for the sarcomata is substantially maintained to-day, although certain tumors that were formerly placed in this category have been dropped from the list. The tumor seen in actinomycosis was at one time supposed to be sarcomatous, until eventually its true nature was detected. It is possible that future discoveries may still further limit the number of tumors which are now regarded as sarcoma. At present little is known about the etiology of this class of tumors. Cohnheim's theory that these growths depend upon a dis- turbance in the embryonic structure from which they spring has something suggestive in it in the light of the fact that sarcoma is often seen in infancy, or that it is even congenital in the sense that it springs from moles or other growths of congenital origin. Con- genital sarcoma is comparatively rare. As a rule, sarcoma appears 704 SURGICAL PATHOLOGY AND THERAPEUTICS. first at a much more mature period of life. In ioo cases of sar- coma collected by Stort 56 were men and 40 were women. The ages of the majority of the cases ranged from forty to seventy years. It appears to be of traumatic origin, and it has been known to fol- low blows upon the testis, the mamma, and the bones, and accord- ing to Nasse trauma is more frequently the cause of sarcoma than of any other tumor. Any source of irritation may serve apparently as a cause. Sarcoma appears occasionally in scars, and it may fol- low chronic inflammatory processes. Hesse reports that the lungs of the cobalt-miners of Schneeberg are invariably affected with lymphosarcoma, although other people in the vicinity do not have the disease. Recent investigations show that the so-called " organisms of a cellular nature ' ' are found in the cells of sarcoma as well as in those of carcinoma. Pawlowsky, following a suggestion of Steinhaus, studied the cells of sar- coma, and found organisms which he regarded as sporozoa (microsporidia). These structures are seen in the protoplasm of the cells, and they contain spherical or oval spores. They react differently from the other cells to stain- ing fluids. He traces the spore into the cell, where it is surrounded by a ring of protoplasm which forms a capsule around the multiplying spores. Event- ually, the capsules burst, and the spores are set free in the intercellular sub- stance of the tumor, whence they reach other cells. The sarcoma-cells begin to grow and to multiply under the influence of the parasite. Pawlowsky thinks it probable that in the melanotic sarcomata these parasites obtain their nourishment from the constituents of the blood, and that they stand in close relations to the haemoglobin of the red blood-corpuscles. So far as his own experience goes, these organisms are less frequently seen in the cells of sarcoma than in those of carcinoma. Sarcomata may grow wherever connective tissue exists, but they are more frequently seen in the skin, the fascia, the inter- muscular connective tissue, the bones, the periosteum, the brain, the ovaries, and the testicle. The classification it is customary to adopt at present is that based chiefly upon the character of the cells of which the tumor is composed. The round-cell sarcoma is composed either of small or of large cells. The small round-cell sarcoma consists of round cells con- taining but little protoplasm, and of a globular or an oval nucleus. The intercellular substance is slight in quantity, and it is granular or is faintly fibrillated. The vessels are numerous, and they have very thin walls. This tissue closely resembles that seen in granu- lations. Such tumors are found in the skin, the testicles, and the ovaries (Ziegler). When the intercellular substance forms a retic- ulum of stellate cells anastomosing by numerous prolongations, the round cells are found in large numbers in the meshes of this SARCOMA. 70S Fig. 100. — Alveolar Sarcoma (oc r a 2 oilim.). reticulum, and there is found an arrangement such as is present in the lymphatic glands. Such a tissue is found in lympho- sarcoma. The la roc round-cell sarco- ma is composed of cells con- taining an abundant proto- plasm and of a large vesicular oval nucleus. These cells are so large that they look like epithelium, and the stroma is so slight that the cells appear to be in contact with one an- other. Running through the growth, however, are tra- becular of connective tissue, forming alveoli from the walls of which, spring the delicate fibres which run between the cells. The tissue is very vascular, containing large vessels giving off fine capillaries that penetrate the alveoli in the delicate stroma. This tumor is called " alveolar sarcoma" (Fig. 100). Such an arrange- ment of cells and stroma corresponds very closely with that found in carcinoma, and it is only by careful preparation that the differ- ence between the two kinds of growth can be detected. If a thin section taken from an alveolar sarcoma is shaken up with water in a test-tube or is brushed with a camel' s-hair pencil, many of the cells drop out and the connective-tissue stroma is made apparent. This is not a very common form of sarcoma. It is found in the cutis, the muscle, the bone, and the testicle. The spindle-cell sarcoma (Fig. 101), however, is the commonest form. It is composed of long spindle-cells, of varying size, closely packed together. The cells lie with their broad surfaces in con- tact with one another, and they are arranged in bundles running in various directions, so that in a section one sees longitudinal and cross-sections of such bundles (sarcoma fasciculatum). There is but a small amount of intercellular substance, and blood-vessels are seen in the axes of the bundles of cells. These cells are often so closely packed together that their form cannot be made out dis- tinctly, and the nuclei seem to lie very close to one another. The grain of the tumor is, however, characteristic, and on picking the cells apart or on brushing them the spindle-cells with their long prolongations are seen. These cells are not always fusiform, but 45 706 SURGICAL PATHOLOGY AND THERAPEUTICS. they may have several prolongations, giving thein quite an irreg- ular shape. This variety of sarcoma is usually a good deal firmer Fig. ioi. — Spindle-cell Sarcoma (oc. 3, obj. D.). in consistency, and is less malignant, than the round-cell sarcoma. Medullary forms occur occasionally. The prognosis of these tumors depends, however, greatly upon their locality. The giant-cell sarcoma, or myeloid sarcoma, is characterized by the presence of cells of a great variety of shapes and sizes, but more particularly of the giant- cell, and a mass of protoplasm containing a large '^ number of nuclei (Fig. 102). The nu- clei are large and S l'tt%&W^~tt'&&*$ refractive, and are Isi^*^ ~^>%A % *' usuall v massed near Fig. 102.— Giant-cell Sarcoma (oc. 3, obj. D.). the centre of the cell, and the protoplasm is composed of a thick, finely-granular mate- rial which has a yel- SARCOMA. 707 lowish or a brownish tinge. These cells are often quite numerous; at other times they are found only in certain portions of the growth. The other cells of which the tumor is composed are polymorphous. There are found spindle-, stellate, club-shaped, and round cells. The amount of intercellular substance is usually exceedingly small; con- sequently, it is a soft and pulpy tumor which often has a brownish tinge. Similar giant-cells are seen in the marrow of embryonic bone, but they are not so large. These tumors are almost always seen in the marrow of bone, but giant-cells are found also in peri- osteal sarcomata. Melanosarcoma is characterized by the presence of a dark pig- ment in the cells. Any of the forms of sarcoma may be pigmented, but melanosarcoma usually contains round or spindle-cells. The pigment-granules are found in the body of the cells, but never in the nucleus. The pigment is arranged in many cells so as to dis- tend the cells and alter their shape, the pigment-granules appearing as large, dark, globular masses, the clear nucleus being crowded into one corner of the cell. All the cells are not pigmented, and the younger portions of the tumor may have no pigment whatever. These granules are not to be mistaken for blood-pigment, which, seen in "multiple-pigment sarcoma," may have been absorbed from a blood-clot the result of hemorrhage. In such a case pigment- granules are also to be found between the cells. Virchow believes that the pigment is formed in the cells, and this view is most gen- erally accepted ; others have supposed that the pigment is formed directly from the blood. These tumors grow in the choroid coat of the eye and in the skin, especially on the foot and the hand ; they have also been seen in the lymphatic glands. Melanosarcoma is one of the most malignant varieties of tumor known, and metastatic deposits are found in the liver and in other internal organs, many of these metastases being unpigmented and presenting white nodules. Sarcoma may also be classified according to the changes observed in the intercellular substance. When there is a large amount of fibrous stroma, which occasionally occurs in spindle-cell sarcoma, it is called a "fibrosarcoma." In myxosarcoma the intercellular substance is clear and homogeneous, like that seen in myxoma ; the cells may be round, stellate, or fusiform. Such tumors are seen in the intermuscular septa and also in connection with sar- coma of bone. Gliosarcoma is a round-cell growth with an inter- cellular substance similar to that seen in the neuroglia. It is found in the central nervous system and also in the retina. It is a soft, white medullary growth, and is usually very malignant. Angio- 708 SURGICAL PATHOLOGY AND THERAPEUTICS, sarcoma has been denned as an angioma with sarcomatous growth of the vessel-wall. The sarcoma-cells form in columnar masses, apparently in the perivascular spaces, and each column of cells contains a blood-vessel in its centre. The cells have a distinctly endothelial character, which brings it close to the class of endothe- liomata. These columnar masses of cells form coils which may anastomose freely with one another. The tumor may be more or less diffuse in the membranes of the brain or the peritoneum, or it may be nodular. It may be found in the brain, the nerves, the testicle, the lymphatic glands, the breast, the skin, and the bones. The tumor is very malignant, and the metastatic deposits have the same general character. Although sarcoma seems much more isolated from the adjacent tissues than carcinoma, and it is in many cases surrounded by a sort of capsule, a histological examination shows that the cells have invaded the surrounding tissues much more deeply than the micro- scopic appearances would lead one to believe. The cells not only rapidly proliferate, usually by mitosis, but it is probable that many of them also possess the power of amoeboid movement, and in this way detached foci may be found in the neighborhood of a tumor. For these reasons sarcoma has a strong tendency to recur locally after removal. These tumors have the power also to produce metastatic deposits, which in some cases may be so small and so numerous that the term "sarcomatosis" has been devised to express this peculiar condition. Metastasis does not occur, however, until a late period in the history of the disease, and local return of sar- coma may take place several times after operation before general- ization of the grow r th occurs. The metastatic growths take place along the course of the blood- vessels rather than in the lymphatics, although in the case of sar- coma of the bones the lymphatic glands may become involved. Councilman points out the closer relation of these growths to the blood-vessels, showing that it is by no means rare to find a sarcoma growing directly into a large vein, and that it may extend in this way for a long distance as a fleshy polypus moving freely in the blood-stream. As one would suppose, metastases are most com- monly found in the lungs, and next in order of frequency come the spleen, the kidneys, and the liver. Sarcoma may undergo retrograde changes during its period of growth, the most frequent being fatty degeneration of the cells. The most cellular and actively-growing sarcomata seem to possess this tendency. The sudden diminution in size or the disappear- SARCOMA. 709 ance of sarcoma as the result of treatment by arsenic or through the action of erysipelas is in many cases to be explained in this way. M neons degeneration may also occur, and as the result of these changes cysts may develop in the tumor. Portions of the tumor often break down, owing to rupture of the softened walls of the blood-vessels ; consequently extravasations of blood are frequently seen. Sarcoma has in its early history a period during which it is far less malignant than in the later stages. During this period the tumor seems to remain stationary. The change to a more malig- nant growth may take place suddenly or gradually. The clini- cal significance of a sarcoma depends not only upon the nature of its tissue, but also upon the locality in which it is situated. The gliosarcoma, although confined to one locality, presents a condition of grave importance, owing to its relation to the cen- tral nervous system. The more rich in cells and the smaller the cells, the more rapid is the growth of the tumor. The various localities in which the disease grows will next be studied. 1. Sarcoma of Skin. Sarcoma of skin occurs quite frequently, although not nearly so often as cancer. It may occur primarily, but also as the result of metastasis. Sarcoma develops quite often from warts and moles, which for a long time after adult life has been reached remain unchanged, and eventually, as the result of irritation through fric- tion or injury, change into sarcoma. It may also develop after trauma, or it may grow from granulation tissue or from a scar. Sarcoma may be congenital, and Babes reports a case of sarcoma the size of a dollar which was removed from the foot of a new-born child. The commonest period of life to see sarcoma of the skin is from thirty-five to fifty years. The disease may develop from the superficial or the deep layers of the skin or from the subcutaneous cellular tissue. In the latter case the skin is affected secondarily, and on section one can often see the sarcoma-cells pressing their way to the surface through the columnse adiposae. According to Babes, many of the sarcomata of the skin spring from the walls of the blood-vessels and are of endothelial origin. According to Winiwarter, sarcomata grow from the connective- tissue structures, from the walls of the blood-vessels and lymphatic walls, and from the sheaths of the nerves. The forms generally seen here are the spindle-cell sarcoma, the myxosarcoma, the alveolar sarcoma, and the melanosarcoma. The small round-cell yio SURGICAL PATHOLOGY AND THERAPEUTICS. sarcoma is comparatively rare. The superficial form appears on the surface as a sarcomatous wart, which may eventually attain considerable size, retaining a nodulated or a papillary appearance. The course of the disease is slow at first. There is often a period, perhaps of several years, during which the tumor bears the reputation of being benign. Then a change comes suddenly, and it is evident that the growth is sarcomatous. Even then the growth may be slow and may extend over several years. A sarcoma sometimes develops, however, with great rapidity. The adjacent portions of the skin may become affected, and eventually metastatic deposits are found in the internal organs. Sarcoma of the subcutaneous tissue is usually more distinctly defined as to its limits, and it may attain considerable size before any metastasis takes place. The superficial papillary sarcoma contains either round-cells or spindle-cells. It may also consist of alveolar sarcoma tissue. As it develops from some old-standing wart-like structure of the skin, it assumes a fungous growth. Sarcomatous ulcers, seen not infrequently upon the lower extremities, contain usually a variety of cell-forms. Congenital sarcoma appears as a circumscribed, hard, round growth of doughy consistency and of a bluish color. It is either a spindle-cell sarcoma or a myxosarcoma, and it recurs rapidly after removal. The papillae are often greatly enlarged in the affected portion of the skin (Winiwarter). Sarcoma may be multiple, and the tumors, often found in great numbers, vary considerably in size, but they are usually small. They are either subcutaneous or they infiltrate the skin, appearing as reddish nodules. They are either round-cell or alveolar sarcomas. They may also contain spindle- cells, and they are often very vascular. Death occurs from cachexia at the end of two or three years. Melanosarcoma generally originates from a pigmented mole or it may occur in previously healthy skin. It is often found on the hands or the feet. It is not uncommon to find it springing from the sole of the foot as if it had been produced by some injury. Hutchinson describes a form of " melanotic whitlow" which ap- pears to be connected at first with disease of the toe-nail. The nail falls off, and there is found a sarcomatous growth which later assumes a most malignant character. Pigmentation may occur in all forms of sarcoma, whether round-cell, spindle-cell, or alveolar sarcoma. The tumor when first seen may not be larger than a pea, but it may finally grow to be as large as the fist. The pig- SARCOMA. 7 'ii ment-granules are found principally in the protoplasm of the cells, but they are seen also in the deep layers of the rete mucosuin, and the pigmentation may affect the hair-follicles. The walls of the blood-vessels and the capillaries contain pigment, and pigment- granules may also be found in the subcutaneous tissue. Wickham L,egg describes the case of a man fifty-four years of age in whom there was a diffuse pigmentation of the skin of the face, from which metastatic deposits eventually took place. The lymphatic glands are affected early in the disease, and all the internal organs, including the meninges, and even the brain itself, are found to contain metastatic growths. The duration of the disease seldom exceeds eighteen months to two years. Multiple-pigment sarcoma differs from the melanosarcoma in that the pigment is apparently not obtained from the same source as in melanosarcoma, but is the result of hemorrhages which cause the deposit of blood-pigment. Some of this pigment is found in the cells and some in the intercellular substance. Micro- scopically, these tumors consist of small round cells or of spindle- cells, and are very vascular. The disease begins in the corium, and it later involves the papillary layer and the subcutaneous cel- lular tissue. In the papillae are seen numerous extravasations of blood that have occurred as the result of laceration of the capillary walls. The walls of the vessels may also show evidences of cell- growth and pigmentation (Winiwarter). This variety of sarcoma does not originate in a pigmented mole, but is first seen on the palms or the backs of the hands or on the soles of the feet. Here the nodules occur in groups, perhaps on all four extremities, and they gradually spread toward the trunk. They begin at first as small bluish spots which are painless, but which often itch badly. Later, the nodules appear, which at first are quite small, but eventually they may increase to the size of a hen's &gg. The progress of the disease is very gradual, and at the end of two or three years it may have involved the trunk and have reached the face. The whole cutaneous surface is by this time covered with nodules varying from the size of a pea to that of a hen's egg^ which nodules are of a brownish or of a bluish-red color, and are more or less painful, but are rarely ulcerated. In one-fourth of the cases nodules of infiltra- tion are found on the glans penis, the prepuce, and the scrotum. There is also a characteristic elephantiasis-like thickening of the fingers and hands and of the legs and feet, so that the fingers are stiff and distorted and the patient walks and stands only with difficulty. 712 SURGICAL PATHOLOGY AXD THERAPEUTICS. The lymphatics are only moderately affected. Many of the nodules undergo retrograde changes, and after some desquamation of the epidermis over them they disappear and leave behind a dark pigmented cicatricial depression. Many undergo atrophy in the cen- tre, while the periphery remains as an indurated wall. As the disease advances the mucous membranes become affected. Dark bluish- red patches, diffuse infiltrations, or little nodules arise on the gums, the palate, or the uvula, and the tonsils become swollen. The patients begin to have fever; bloody diarrhoea and haemoptysis make their appearance; the liver and spleen become enlarged; and death is preceded by the symptoms of general marasmus. Metastatic deposits are found in the lungs, the heart, the liver, the spleen, and the intestine, particularly in the descending colon 'Kaposi). The age at which this disease occurs varies greatly, although the majority of cases have been of persons in middle life. The prognosis is most unfavorable, although an occasional recovery is recorded. An interesting feature of the disease is the spontaneous disappearance of many of the nodules. 2. Sarcoma of Boxe. The term "osteosarcoma n is commonly used to denote sarcoma of bones, but in reality it signifies simply a sarcoma which is ossi- fying or which contains bone, it being used in the same way as is fibrosarcoma. It is. therefore, a term which, in this connection, should be dropped. Sarcoma of bone may in general be divided into two kinds — according to its seat in the periosteum or in the medullary tissue of the bone. The former class is called "perios- teal sarcoma ; n the latter, " central" or "myeloid sarcoma." The latter division shows a marked difference in histological structure, for the periosteal growths are spindle-cell tumors and the medullary growths are mant-cell sarcomata. Round-cell sarcoma is seen also both in central and in peripheral growths. Some of these tumors belong to the most malignant class of all tumors, and others are so mildly malignant that they have been supposed to be benign. According to Gross's computations, the spindle-cell form is sup- posed to be 43.5 per cent, more malignant than the central giant- cell sarcoma. The giant-cell form is fortunately the commonest. Sarcomata of bone appear chiefly during the early half of life. Thus, they are seen most frequently between the ages of twenty and thirty, and they are almost as commonly met with between those of ten and twenty. Traumatism was found by Gross to be an assignable cause in fullv one-half the cases he collected. SARCOMA. 713 According to Nasse, in no other form of tumor is the statement of the patient so often made that some sort of an injury had previously been received. Surgeons are yet, however, entirely in the dark as to the origin of these tumors. The myeloid tit mors are essentially a polymorphous cell-growth, the most striking of the various cell-forms being the giant-cells, which have been referred to above. Spindle-cells and round cells are also seen. They are usually situated in the centre of the bone, but are occasionally seen in peripheral growths. One of the most frequent points of origin is the spongy tissue at the head of the tibia. They are seen also in the upper and lower jaw and in all the other long bones. In these situations they appear as soft ma- hogany-colored growths, which are very characteristic. For a long time they are surrounded by a shell of cortical bone, but eventually they break through at some point. They are not so vascular as might be expected from their succulent nature and from the inter- stitial hemorrhages to which they are so liable. They are particu- larly liable to fatty degeneration, and thus have a soft creamy or an amber color. They also undergo a mucoid softening, as a re- sult of which cysts are formed containing a straw- or a buff-colored fluid. Owing to the fact that these tumors often pulsate, they are not infrequently mistaken for aneurism. They are found with about equal frequency in men and in women, and usually be- tween the ages of twenty and thirty years. They grow more slowly than any other form of sarcoma of bone, and, as a rule, are confined to the parts in which they originate and grow; but sometimes they recur after removal, and occasionally form me- tastatic deposits in distant organs, principally the lungs. In 22 cases operated upon, Gross found that seventeen remained perma- nently well and five died of recurrence of the disease. Central spindle-cell sarcoma is the next commonest variety. The cells may be large or small, and it is found that the small cell type is much more malignant. This form of sarcoma occurs as a smooth or slightly nodulated growth, limited by a capsule which is partly bony and partly periosteal. The cut surface is usually of a grayish-white color, and the consistence is firm and elastic. The growth is not particularly vascular, and retrograde changes are uncommon. In 16 cases Gross found two in the upper epiphysis •of the tibia, five in the lower epiphysis of the femur, and two in the upper epiphysis of the humerus. The ages of the patients varied all the way from ten to sixty-eight years, the duration of life, from the beginning of the disease, averaging 37. 2 months. Metastatic 7i4 SURGICAL PATHOLOGY AND THERAPEUTICS. deposits are seen in many cases, particularly in the small-cell variety. Spontaneous fracture is met with in about one-half the cases. Pulsation is not felt frequently in this form of sarcoma. Central round-cell sarcoma is either a simple round-cell sarcoma or an alveolar sarcoma. The latter form, which is often exces- sively vascular, has been regarded by some writers as a plexiform angiosarcoma. These central round-cell sarcomata are generally globular or ovoid, and are of a smooth, even outline. They are contained in a capsule which is either membranous or osseous, and from the inner surface of the capsule bands are given off which give it a lobulated appearance. The simple round-cell sarcomata are not particularly vascular, but the alveolar form is often so rich in vessels that pulsation takes place. A pulsating central sarcoma of the shaft of a long bone is al- most always composed of round cells. Pulsation of the myeloid tumor at this point rarely occurs. Extensive hemorrhages may take place, and the seat of the disease may be converted into a large blood-cyst, the walls of which are ijl^vs composed of a thin layer of the S < v l*3Hk - original sarcomatous tissue. In A ,V such cases the so-called "sponta- neous fracture" not unfrequently occurs. These tumors also undergo fatty or myxomatous degeneration. They grow more rapidly than any other form of tumor of bone, some- times attaining a very large size. These growths not only infil- trate the medulla of the bone, but % 'fft£ , ^ r '' occasionally also invade the sur- rounding muscles and the liga- ments of the adjacent joints. En- largement of the neighboring lymphatic glands occurs occasion- ally. Gross found this enlarge- ment to exist in only three in- stances. Metastatic deposits were found by him in one-third of the cases, the lungs, pleura, liver, kid- neys, and osseous system being the various points invaded at differ- . Y ■i '• -. ^ o Fig. 103. — Periosteal Sarcoma : amputation at the hip-joint (Warren Museum, 1 517). SARCOMA. 715 ent times. In one case a large vein was found filled with the sar- comatous tissue. Of 12 cases of round-cell sarcoma observed by Gross, three ran their course without amputation. Of these cases one died in six months, one in twenty-seven months, and one in thirty-eight months. Of the 9 cases in which amputation was performed, five died of the operation, one died eleven months sub- sequently from secondary growths in the brain and skull, and three remained well, respectively, six weeks, four months, and four and a half years after amputation. Periosteal sarcomata are seated between the deeper layers of the periosteum and the bone (Fig. 103). The varieties are round-cell sarcoma, the spindle-cell sarcoma, osteoid or osteosarcoma, and chondrosarcoma. These forms of sarcoma occur more frequently in early life, the average age being estimated by Gross at twenty- two and one-seventh years. Giant-cells are occasionally seen in these tumors, but only to a limited degree. Fracture of the bone rarely occurs, and the tumors do not pulsate. Elevation of the local temperature is often marked. These tumors are not sur- rounded by a shell of bone as in the central sarcomata. The round-cell sarcomata are either of the simple round-cell type or they may belong to the class of alveolar sarcoma. They are found principally on the shafts of the long bones. They are more malignant than the central sarcomata, and their growth is usually continuous and rapid. As they grow by deposits on the periphery, the bone is usually at first not affected, although it may later become involved. They appear as more or less spindle- shaped swellings, and on the cut surface they have a radiating grain or are more or less lobulated. The skin is often involved in the growth when fully developed. These tumors may recur locally, and the lymphatic glands are more frequently affected than in the case of myeloid sarcoma. In many cases the lungs contain metastatic deposits. The average duration of life is esti- mated by Gross at eighteen months. Of 6 cases that were suc- cessfully operated upon, only one remained well without local recurrence. The spindle-cell sarcomata surround the epiphyses more fre- quently than they do the shafts of the long bones. They con- sequently assume more or less a pear shape. The spindle-cells vary greatly in size. While the outer layers may be rich in cells, the inner layers contain more or less fibrillated cartilaginous or bony intercellular substance. This growth, however, rarely in- volves the bone or the cartilage. The development of these yi6 SURGICAL PATHOLOGY AND THERAPEUTICS. tumors is, as a rule, uninterrupted and comparatively slow, but they appear to be almost invariably followed by metastatic deposits, and they recur frequently after operation. Their average duration of life is estimated by Gross at twenty months, or seventeen months less than the mean life of the central spindle-cell sarcomata. Osteoid sarcomata usually occur as long pear-shaped tumors, involving the epiphysis and a portion of the shaft of the bone. They are composed of bony or calcified tissue, and of a cell- growth which is usually of the spindle-cell variety, but many also contain round cells. The bony growth radiates from the bone in the form of bony plates or spiculae, which pursue a course perpendicular to the surface of the affected bone. The shaft is usually not involved in the disease, but at times the medullary canal may be occupied by a growth of dense bone, which may assume an ivory hardness. The outline of the shaft of the bone may still be seen on section running through the tumor. Osteoid sarcoma, or osteosarcoma, as it grows shows a tendency to extend beyond the limiting capsule and to invade the surround- ing structures. The lymphatic glands are infected in about one- fourth of the cases. Osteoid sarcomata are followed by metastatic growths in the internal organs, and are regarded by Gross as the most malignant of all forms of sarcoma of bone except the pure periosteal spindle-cell sarcoma, since 65.62 per cent, of all cases die sooner or later with metastatic deposits, whether they have been subjected to operation or not. Chondrosarcoma resembles closely the above variety in the earlier stages of its development, the nature of the cell-growth being the same in both cases. The newly-formed cartilage is found in the deepest portions of the tumor near the bone. The radiating character of the growth is also a well-marked peculiarity. Combination of the two forms not infrequently occurs, and on sec- tion some of these tumors (which frequently reach immense size) show patches of myxomatous and sarcomatous tissue, cartilage, and bone, and they present a most striking pathological and varie- gated appearance. Epulis (ini, upon, ouXov, the gum) is a name given to any growth upon the gums. The term is chiefly used, however, to denote a form of periosteal sarcoma. An epulis may contain round cells, but it is more frequently of the spindle-cell variety, and the growth is charac- terized by the presence of giant-cells, usually in large numbers. For this reason, and for the reason also that the bone is often involved, SARCOMA. 717 some writers have undertaken to describe a central as well as a perios- teal form. It is, however, periosteal in its origin, but inasmuch as the growth may spring from the periosteum of the alveolar process, the bone may become affected by the time the growth has pushed aside the tooth and made its appearance. As the tumor grows the bone becomes softened and eroded, and the whole thickness of the alveolar process, and even the medullary portion of the bone, may be- come involved. Virchow distinguishes two forms, a hard and a soft epulis. In some cases there is a large amount of fibrous tissue and very few small cells, but the giant-cells are also seen here and there between the fibres. The softer kind is quite vascular, and fre- quently a vessel breaks and hemorrhage takes place into the tissue of the growth, pigment-granules being left behind when the clot is absorbed. These granules are found both in and between the cells, and they give the tumor a brownish color (pigmented epulis). This disease is one of early life, but it may appear also in mid- dle or in old age. It is usually seen, in the early stages, between two teeth, pushing forward as a bright red lump or granulation and attached apparently to the gum, often only by a pedicle. The deeper tissues are involved, however, and the lump returns promptly after an attempt to destroy it by tying a ligature around its base, as is often done. The disease is only locally malignant, and it may return several times after operation when not enough of the sur- rounding tissue has been removed. It is necessary to extract the adjacent teeth and to remove that portion of the alveolar process to which the tumor is attached. In rare cases, when the tumor is small, an incision down to the periosteum around its base will enable the surgeon to peel off the periosteum with the growth, and in this way effect a cure. Sometimes a large portion of the bone of the lower or the upper jaw must be removed to prevent recurrence. Sarcoma of the bones of the cranium occurs as a periosteal or as a myeloid sarcoma. The periosteal form grows outward princi- pally, but it may grow inward and destroy the bone and invade the cranial cavity. The myeloid form destroys first the diploe and separates the two tables from each other, but for some time the growth remains covered by a bony capsule. Externally these tumors may become quite prominent, and eventually they break through the cutaneous coverings. Internally they push the dura before them, but they do not become so prominent in this direc- tion. Occasionally other portions of the bone are attacked and multiple tumors are formed. The periosteal tumors are either spindle-cell or small round-cell sarcomata. 7i8 SURGICAL PATHOLOGY AND THERAPEUTICS. The most frequent seat of these tumors is in the parietal bone, the temporal and frontal bones coming next in order. Tumors springing from the dura mater grow principally into the cranial cavity and compress the brain. If the tumor grows from the outer layers of the dura, the bone is first absorbed, and through the hole thus made the tumor grows out, sometimes reaching a formidable size. The tumor is usually covered with a connective-tissue cap- sule, which consists of the outer layer of the dura that separates it from the cranial bone. Sometimes the growth behaves more like an ordinary periosteal sarcoma, and it becomes intimately connected with the bone from the beginning. Sarcoma of the dura is usually a spindle-cell sarcoma. Its most frequent seat is beneath the parietal bone. It attacks principally individuals of middle or of late life. J. C. Warren describes a "fungoid tumor" growing from the dura and forming a large growth on the right temple of a young lady who applied for treatment in 1846. The tumor was cut away close to the bone, and the dura was cauterized and the wound healed. Five years later she consulted Mason Warren for a return of the growth, which was quite small. Xo operation was advised. In 1S66 she was heard from in good health. The tumor had slowly enlarged until three years previously, and it since had undergone no material change. Other cases of slow growth of these tumors are recorded : one of twenty years' , one of fifteen years' , and several of four or five years' duration. 3. Sarcoma of Kidxev. Primary sarcoma of the kidney is not common, and it is most frequently seen in infancy or in childhood, whereas cancer of the kidney at this period of life is extremely rare. Many of these growths are congenital, and are discovered at or soon after birth. Sarcoma of the kidney is generally a very soft medullary growth composed of round or spindle-cells and also of stellate cells. In some portions of the tumor may be found fibrous or myxomatous tissue. The tumors attain at times considerable size, which may exceed that of a man's head. These large tumors are filled with fatty degenerated necrotic or hemorrhagic portions and cysts. True cysts with an epithelial lining are rare. Remains of the kidney structure may be found in the peripheral portion of the tumor. The capsule is generally preserved, as are also the adrenal glands. The renal tubules and pelvis may generally also be found. The sarcoma appears to develop in the inner portion of the organ. The renal vein, and even the vena cava, may be invaded by a mass SARCOMA. 719 of sarcomatous tissue. The lymphatic glands are eventually affected, and secondary deposits may be found in the other viscera. In a large number of sarcomata of the kidney both striped and unstriped muscular fibre are found (myxosarcoma). The presence of such structures in the tumors is regarded by many pathologists as evi- dence of a disturbed embryonic formation, but Orth thinks that it is possible that these muscular growths -may develop from the muscular fibre of the urinary tract. Such tumors are usually per- fectly encapsuled, are separable without much difficulty from the surrounding tissues, and are not associated with involvement of the lymphatic glands or with secondary growths in any other part of the body. The disease is limited to one kidney. Angiosarcoma may be found in the kidney, although it is an extremely rare growth. The kidneys maybe the seat of metastatic sarcoma, and also of lymphosarcoma, nodules of which are seen also in the lymphatic glands. Gross collected in 1885 the statistics of 33 cases of nephrectomy for sarcoma of the kidney. The mor- tality of the operation was 57. 57 per cent. Of the fourteen survivors, five were known to have died of metastases at periods varying from five to eighteen months; five were alive and well at the end, re- spectively, of seventeen, twenty-two, twenty-three, and thirty-five months, and five years. Of the 33 cases, sixteen were children under seven years of age ; of these, seven survived the operation. Of these seven, one was living at the end of four mouths, and the others died of recurrence in five, six, nine, and eighteen months, respectively. In one of the cases that died secondary deposits were found in other organs. An analysis of the adult cases shows that seven of the seventeen recovered, and five were well at the end of thirty-one and a half months, on an average. From these data Gross concludes that nephrectomy for sarcoma in children should not be performed, but that in adults it is eminently justifiable, as it apparently cures 29.41 per cent, of the cases. 4. Sarcoma of Bladder. Sarcoma of the bladder is an extremely rare affection. The dis- ease is seen more often in childhood or in youth than at other periods of life. Hinterstoiser in a collection of 20 cases of sarcoma of the bladder found five in persons under twenty years of age. There were six cases, however, between the ages of fifty and sixty. The disease occurs more frequently in males than in females, thir- teen of these cases being males. Some of the tumors are round- cell sarcomata, and they bear a close resemblance to the lympho- 720 SURGICAL PATHOLOGY AND THERAPEUTICS. sarcomata; some have spindle-cells, and in some there is a mixture of the two kinds of cells. Myxosarcomata are occasionally seen, in such cases unstriped muscular cells being found mingled with the sarcoma-cells. Chondrosarcoma is seen in connection with polypoid growths (Orth). In a collection of 20 cases of tumor of the bladder by Sir Henry Thompson the writer finds one stated by him to be probably sarcoma, one which was probably myxosarcoma, and one which was probably round-cell sarcoma. Winckel reports a remark- able case of round- and spindle-cell sarcoma of the bladder in a girl three years of age. The tumor sprang from the anterior wall of the bladder, by the contraction of which it was forced into the urethra, whence it pushed its way into the vagina, distended this, and even dilated the os uteri. In 88 cases of tumor of the bladder collected by Albarran, sixty- eight were carcinoma, three were sarcoma, and seventeen were benign tumors. Secondary sarcoma is occasionally found in the bladder. Fenwick in an examination of 600 cases of tumor of the bladder found but five that were really secondary (direct extension of a tumor into the bladder not being included), and of these four were sarcoma. Cabot reports a case of tumor of the prostate and bladder seen secondary to sarcoma of the testis. 5. Sarcoma of Uterus. Sarcoma of the uterus springs from the mucous membrane or from the body of the uterus. In the latter case sarcoma-growths seem to be developed from a previously existing fibromyoma. In both forms round cells are found, but in the sarcoma of the body of the uterus may also be seen spindle-cells. Many observers have reported the presence of giant-cells. Sarcoma of the mucous membrane appears earlier in life than carcinoma, sometimes even before puberty, and comparatively often in women who have not borne children. It is situated gen- erally in the body of the uterus and rarely in the cervix. Lobu- lated or polypoid growths are usually developed, and the surface may become ulcerated. In both cases there is considerable hyper- trophy of the uterus-wall, which becomes infiltrated by the new growth. When the wall has been perforated the disease attacks the peritoneum and the intestines through the adhesions which have been made, and it even attacks the abdominal walls. Poly- poid papillary or cauliflower growths which are distinctly sarcoma- tous may occur in the cervical canal or at the os. Combinations of leiomyoma and rhabdomyoma, or tumors containing unstriped SARCOMA. 7 21 or striped muscular fibre, may be observed in these growths, and Orth reports a case in which both forms of muscular fibre were observed. The mural sarcomata or fibrosarcomata are found in the wall of the nterns, and chiefly in the body rather than in the cervix. They are combined with muscular cells, the sarcomatous cells usually being situated at the centre of the growth, as if a fibromyoma had undero-one a sarcomatous change. These tumors resemble more or less, in their coarse appearance, the uterine fibroids, and they are often found in the interior of the uterus as a polypoid tumor (Orth). In some cases these sarcomata appear not as isolated growths, but as infiltrations of the uterine wall. They are chiefly composed of round cells, and they are often soft and medullary. Some of the uterine sarcomata may attain immense size. Gusserow reports the case of a woman fifty-one years of age with a sarcoma the size of a child's head, which tumor, on being expelled from the uterine cavity, proved to be a round-cell sarcoma. Some of the sarcomata are exceedingly vascular, and they resemble angiosarcoma. Others closely resemble carcinoma, but they are probably endothelioma. Metastatic deposits are not often found, and less frequently in the diffuse forms. The retroperitoneal glands may be affected, and metastases may be found in the lungs, the liver, the pleura, and the adjacent organs, and the bladder and vagina may be affected by direct extension of the disease. As the disease progresses cachexia becomes very marked, and death usually occurs from peritonitis, pyaemia, or intestinal ob- struction. The progress of the disease is slow, many cases having been observed in which the disease existed ten years before death. Operative interference rarely effects a cure. A few doubtful cases have been reported as permanently cured. The growth, however, usually returns after operation. In 50 cases reported by Rogivue, three appear to have been cured; in thirty-two return of the disease was known to have taken place; and in all but two cases this return occurred within a year after the operation. 6. Sarcoma of Testis. Sarcoma of the testis is much commoner than carcinoma. It occurs during both childhood and middle life, and even in old age. It has been seen in a child five months old and in a patient seventy years old. It is occasionally observed to follow a blow, but more frequently it occurs without any known cause. It is an interesting fact from an etiological point of view that it is not infrequently seen in both testicles. Langhans has collected 15 46 722 SURGICAL PATHOLOGY AND THERAPEUTICS. such cases, in many of which the second testicle has been affected several months after the removal of that first diseased. Sarcoma may occur also in the testicles as a secondary disease. Histologically considered, there are two forms of sarcoma of the testicle — the spindle-cell and the round-cell sarcoma. In the spindle-cell variety the cut surface shows a firm growth of homogeneous appearance, with a few cysts in the substance of the tumor. The spindle-cells are found lying between the seminal ducts, which are often quite well preserved. The round-cell sarcoma mav be a large- or a small-cell growth, and it mav even contain giant-cells. Alveolar sarcoma is not infrequently seen. Many of the small-cell sarcomata probably belong to the lympho- sarcomata. It is this variety which is most liable to attack both testicles and which is most malignant. Cartilage, myxomatous tissue, and unstriped muscular cells are sometimes found in sarcoma of the testis. The round-cell variety is seen more often in children. Occasionally the disease assumes the form of an angiosarcoma or a plexiform sarcoma. The disease appears to take its origin, in the majority of cases, in the posterior portion of the testicle or in the epididymis and cord. Kocher observed three cases in which the disease began in the epididymis. If the testis is first involved, the growth enlarges as a nodular tumor inside the organ, which it gradually destroys. When the growth has attained considerable size the tissue of the testis is often seen spread out over the tumor in a thin layer. The epididymis retains for some time a well-defined outline on the posterior wall of the tumor. Finally the tunica albuginea be- comes involved and is merged in the sarcomatous growth, and the tunica vaginalis may follow in the same way. A hydrocele, or even a haematocele, may occasionally develop during the course of the disease. Nodular enlargement of the cord is often observed as the disease progresses. The disease begins as a painless enlargement of the testicle, which may exist for many years before a rapid growth takes place. It is quite difficult to make a diagnosis between sarcoma and carcinoma, and usually the microscope alone will settle the question. The lymphatic glands are frequently affected, and in well-developed cases a large abdominal tumor may be found, caused by the involvement of the retroperitoneal glands. Meta- static deposits may occur in the skin, in the lungs, in the liver, and in the brain, and occasionally in the abdominal organs. Sarcoma of the testicles usually runs a rapid course in children, SARCOMA. 723 but in adults the disease may last from eight or nine months to one or two years. In the great majority of the cases, according to Kocher, the disease returns after operation, either locally or in distant organs. One or two cases of undoubted permanent cures are reported in children, and numerous cases of immunity for several years are reported in adults. 7. Sarcoma of Breast. Sarcoma of the breast includes nearly all the various forms of sarcoma. Round-cell sarcoma appears usually as a medullary growth, and Billroth describes such a form in a girl nineteen years of age. In this case there were striated spindle-cells, showing the development of striped muscular fibre in the tumor. In a case of round-cell sarcoma of the breast which the writer examined microscopically the growth appeared to develop around the walls of the blood-vessels. Cases of lymphosarcoma are occasionally mentioned, and also alveolar sarcoma. The great resemblance of the alveolar type of sarcoma to carcinoma has doubtless caused it to be mistaken fre- quently for the latter disease. Billroth reports a case of alveolar sar- coma which assumed a melanotic type. In this case pigment-moles existed on the face and back before the development of the tumor, and metastatic deposits formed soon after the removal of the breast. Giant-cell sarcoma is found also in the breast, usually as an alveolar sarcoma. It is, however, a rare form of the disease. Spindle-cell sarcoma is seen in the variety known as cystosarcoma. This is the commonest form of sarcoma of the breast. As a rule, these growths, with the exception of the cystosarcoma, are unattached to the gland, but they push it aside and compress it. While the round-cell sarcomata are soft and medullary, the spindle-cell sarcomata are firm, and in places fibrous, and are dotted over with the numerous little cysts caused by a distortion of the glandular tissue of the breast. Some of these cystic tumors contain portions that are myxomatous, and cretaceous material and some bone have been found in them. The cystosarcomata often grow to enormous size. In many cases the skin over the tumor in the different forms of sarcoma becomes involved and a hernial pro- trusion of the growth takes place. The commonest seat of the disease is beneath the nipple, but when it develops at the circumference of the organ it is usually in the upper and inner quadrant. The central growths are usually cystic. Sarcoma differs markedly from carcinoma in that it is found in 724 SURGICAL PATHOLOGY AND THERAPEUTICS. early life. In 60 cases collected by Gross, eight appeared between the ages of ten and twenty years ; ten appeared between twenty and thirty years ; twenty-three appeared between thirty and forty years; and thirteen appeared between forty and fifty years. Spindle-cell sar- coma develops earlier in life than round-cell sarcoma. The giant-cell sarcoma alluded to above appeared in the forty-second year. The rate at which these tumors grow varies greatly. The small-cell tumors develop as a rule more rapidly than spindle- or giant-cell growths. During its progress the tumor remains mobile and free from attachments. If the skin is not perforated, it remains natural in color. When the tumor attains considerable size, which is the case in cystosarcoma, the subcutaneous veins may be enlarged, and may give to the growth a much more malignant appearance than it really has. The nipple is usually not retracted. The lymphatic glands are rarely affected, and the contrast in this respect between sarcoma and carcinoma is very striking. In regard to the prognosis of sarcoma of the breast, Gross, with his accustomed enterprise, collected 156 cases of the disease, the data of which throw much valuable light upon this point. The reputation of sarcoma in this situation had been that of a compara- tively benign tumor. The growth was supposed to show a decided tendency to recur after operation, but the generalization of such growths was supposed to be comparatively rare. The local infec- tion of structures adjacent to the mammary gland is indeed exceed- ingly rare, but Gross found metastasis to be much commoner than was supposed to be the case. The prognosis appears to be influ- enced materially by the age of the patient and by the size and the rate of increase of the tumor. Before the age of thirty-five, when the mammary gland is functionally most active, a small, slowly-growing sarcoma does not return; but a rapidly-increasing tumor, especially the cystic variety, is thought by Gross to be very liable to recur. After this period the danger of metastasis increases with advancing age. "A sarcoma occurring in a functionally active breast evinces a marked disposition to recur after operation, with less disposition to metastasis, while a sarcoma of the declining breast recurs less frequently, but is generalized in a greater number of instances. ' ' The round-cell sarcoma is said to be the most malignant, but the cystosarcoma recurs, according to Gross, in more than one-half of all the cases. The good reputation of this growth maintained by numerous writers is doubtless due to the close resemblance of sarcoma to fibroma of the cystic type. Notwithstanding frequent SARCOMA. 725 recurrence, the removal of the tumors as fast as they appear seems to prolong life. Erichsen in 1859 removed the breast for a cysto- sarcoma, and operated five times for the recurrent growth between that date and 1866, the patient dying, some years after the last operation, of another disease. S. D. Gross in 1857 enucleated from the left breast a small tumor which proved to be a spindle-cell sar- coma. Between that date and 1862 the patient underwent twenty- one operations. Ten years and nine months after the last opera- tion she was in perfect health. According to Gross, sarcoma has a greater tendency to metastasis, than has carcinoma ; but this statement the writer hardly believes to be correct, for it is based upon the supposition that in carcinoma, metastases are found post-mortem in only fifty per cent, of the cases. Gross estimates the average life of round-cell sarcoma at fifty-four months, of spindle-cell sarcoma at ninety months, and of giant- cell sarcoma at one hundred and eight months. It appears from an analysis of the data offered by Gross that, although sarcoma of the breast has a decidedly malignant tendency, surgical inter- vention prolongs life, and it probably results in permanent recov- ery. The patient may be considered safe from recurrence of the disease if four years have elapsed since the last operation. 8. Sarcoma of the Air-passages. Sarcoma of the tonsil is a much more common disease than has usually been supposed. In Boston alone quite a number of operations have been performed for this affection, that of Cheever by the external method being the first recorded operation of its kind. Cases have also been reported by Homans and Richardson. An unrecorded case was operated upon successfully by Porter. The writer also had one case, not reported, the patient dying about one week after the operation. Newman mentions ten cases observed by himself, and he succeeded in collecting (1892) 52 cases of sar- coma of the tonsil. Of these, nine were stated to be round-cell sarcoma and eighteen were called "lymphosarcoma." A case examined microscopically by Gray proved to be alveolar sarcoma. The disease is stated by Butlin to attack males principally, and between the ages of twenty and sixty years. As several cases of disease of both tonsils are reported, it is probable that a certain percentage of the cases belong to the family of lymphosarcoma. Cases of spindle-cell sarcoma have been reported. The slight enlargement of one of the tonsils usually causes the patient to present himself for treatment. There is nothing 726 SURGICAL PATHOLOGY AND THERAPEUTICS. in the local appearance at this time to suggest the presence of malignant disease if the description of reported cases may be trusted. Presently the tonsil begins to grow rapidly : it pro- jects toward the median line, and at the same time the anterior pillar of the fauces and the soft palate become reddened and infiltrated. By this time it will be found that there are other nodules than that of the original tumor. Growths may be ob- served below in the pharynx, and others may be felt externally in the cervical region. Glandular infection appears to occur early, and it is sometimes quite extensive. In the case upon which the writer operated a row of retropharyngeal glands on the affected side were exposed and removed. As the disease progresses swallowing and articulation become difficult, and occasional attacks of dyspnoea are observed. Meta- static deposits have been observed in the lungs, the liver, the mes- enteric glands, the intestine, and the peritoneum. Death, how- ever, probably takes place in most cases before the disease has become generalized, owing to the exhaustion of the patient's strength by local complications. These growths have been re- moved through the mouth by knife, by ecraseur, or by galvano- cautery, and through the neck by external incision. The prognosis of the early operations seems to have been most unsatisfactory, due probably to the fact that the nature of the malady had not been recognized sufficiently early to enable the surgeon to obtain a satisfactory result. Butlin mentions two cases in which there had been no return at the end of one and two years, respectively. Cheever says : "So far as I know, recurrence has taken place in all my cases in from four to six months. It has occurred usually in the glands of the neck — once on the palate. I believe I have now operated four times, always with temporary relief and good recoveries from the operation." Homans' case was reported well eighteen months after operation, and Richard- son's case was in perfect health five years after the operation. Suffocation may be produced, not only by the growth of the tumor, but also by hemorrhage, which is a common accompaniment of malignant disease of the tonsils. Sarcoma of the larynx is a comparatively rare disease. It is not often seen in childhood, but it is an affection of middle and advanced life. In 13 cases collected by Wasserman, two occurred between ten and nineteen years of age, two between twenty and thirty, and eight between forty and sixty. Most of the cases are found in males, at least three times as many males as females being SARCOMA. 727 attacked. Nearly all the varieties of sarcoma are said to be found here. Butlin mentions the spindle-cell sarcoma as the principal form, but round-cell, giant-cell, and alveolar sarcomata have been observed. Sarcoma of the larynx generally originates in the subcutaneous tissue, grows slowly, and does not attain a very large size. It most frequently originates in the interior of the larynx, and princi- pally upon the vocal cord or on the ventricular band, as irregular spheroidal masses, smooth, nodulated, mammillated, or even some- what dendritic. Thence the growth may extend outward by infil- tration, penetrating not only the membranous, but even the car- tilaginous, framework of the larynx (Cohen). It is sometimes deeply ulcerated, like cancer, and at other times it is covered with a normal or congested mucous membrane. The epiglottis may also be the seat of sarcoma. The glands are usually unaffected, and in this respect the prog- nosis of the disease is more favorable than that of carcinoma. There does not appear to be any tendency to metastasis. Death usually takes place from obstruction of the air-passage before the growth reaches a sufficient size to lead to generalization of the disease. A number of operations for excision of the larynx for sarcoma have been performed in which the patients have been reported well one and two years after the operation, and one case has been reported as well ten years after the operation. Sarcoma of the nasal passage is not a very rare disease. Bos- worth collected forty-one cases. The round-cell and alveolar forms of sarcoma seem to be the prevailing types of growth. Fibrosarcoma and myxosarcoma are seen, and also angiosarcoma and melanosar- coma. The disease occurs as a pediculated tumor attached, with about equal frequency, to the outer and the inner wall of the nasal cavity. The average age at which the disease appears is about forty years, and it is seen about equally in males and in females. The disease does not appear to show the same malignant tendencies in the nasal passage that it does in other localities. Many of the reported cases were well without recurrence several months after the operation. The single case seen by the writer was that of an old woman from whom he removed a sarcomatous polyp with the cold wire-snare. The tumor was so large that it could not be extracted without turning back the left ala nasi. She made a good recovery, and was then lost sight of. Nasopharyngeal polypi are often sarcomatous, although they 728 SURGICAL PATHOLOGY AND THERAPEUTICS. may be examples of almost pure fibroma. These growths occur most frequently in males at about the age of puberty. They grow from the base of the skull, often originating in the retromaxillary fossa, whence they send out prolongations into the nose, the pharynx, and beneath the zygoma. The sarcomatous variety of this tumor may be a spindle-cell sarcoma or a myxosarcoma. At times it is highly vascular, and cases of death from hemorrhage have not infrequently occurred during attempts at removal. A very curious feature of this growth is that it shows a marked tendency to disappear at the period when the skeleton becomes fully ossified, although it frequently recurs before that period after operation. According to Bosworth, the disease may occur also later in life. The writer has operated on several cases of sarcoma in this region in young men. In the first case the disease was limited to the nasopharynx and the tumor projected from the nostril. Frequent hemorrhages had much reduced the patient. The growth was removed with the galvano-cautery loop, and it proved to be a myxosarcoma. For two or three years after the operation fragments of tumor were removed by Dr. Hooper from the pharynx. Finally, one day, when the patient had been sent for to consider the question of an osteoplastic resection of the jaw, it was found that the growth had disap- peared. The writer saw the patient several years later and found him in per- fect health. A second patient applied with a similar growth which had sur- rounded the upper jaw and had appeared beneath the zygoma. The writer accordingly performed Langenbeck's osteoplastic resection of the jaw. Send- ing for him two or three years later, the writer found that in the mean time he had had two other operations performed — one through the jaw and one through the soft palate ; a recurrence had taken place after the last opera- tion, but the growth was then diminishing in size. The patient regarded himself as well. A third case was operated upon recently by the osteo- plastic method. Sarcoma occurs occasionally in the soft palate as a round-, alveolar-, spindle-cell sarcoma or myxosarcoma. Melanotic sar- coma has also been seen here. It usually begins on the side and extends across the palate. The neighboring tissues are rarely invaded. It occurs either early or late in life. It seems to have a tendency to remain encapsulated in many instances, and opera- tions for its removal have been successful. In 17 cases operated upon death occurred in seven; in eight cases a cure was obtained (Bosworth). Sarcoma is found also in the pharynx, where it is said to develop during middle life. Histologically, the disease does not differ essentially from the diseases above mentioned. It occurs SAfiCOMA, 729 most frequently in a pediculated form, and the prognosis after operation is quite favorable. 9. Sarcoma of the Digestive Tract. Sarcoma of the stomach is a rare occurrence. Torok mentions a case in which he performed resection. The patient was a female twenty-one years old. The tumor was quite firm and of the size of a fist. It proved to be a lymphosarcoma. A case of cystic sarcoma is mentioned among the cases for which a resection of the pylorus was performed by Billroth. Brodinsky reports a case of myosarcoma growing from the greater curvature of the stomach. The tumor weighed twelve pounds, and it lay between the layers of the omentum. Cavities were found in it varying in size from a walnut to a child's head. An ulcer the size of a hand was seen in the interior of the stomach at the point at which the tumor took its origin. The muscular layer of the stomach was much thick- ened, and a large portion of the tumor was made up of a growth of unstriped muscular fibre-cells. There were also spindle-cells. Nodules of the same character were found in the liver. This and a case of Eberth's of myosarcoma of the kidney were at the time the only reported cases of secondary myomatous growths. In Eberth's case the metastasis was in the diaphragm. Sarcoma of the intestine is exceedingly rare. Baltzer collected fourteen cases of undoubted primary sarcoma of the intestine. They were nearly all males (92.8 per cent.), and the disease oc- curred chiefly between the ages of forty and fifty years. In the majority of cases the growth was reported to be a small round-cell sarcoma. The disease appeared to develop from the mucosa or the submucosa. It seems to be a peculiarity of these growths that they do not cause intestinal obstruction. In 4 cases resection of the intestine was attempted, with death in two cases. The result of the operation in the other two cases was not reported. Spindle- cell sarcoma is reported by Leichtenstern and also by Edwards. 10. Sarcoma of Brain. Sarcoma of the brain may occur as a primary or as a secondary growth. Primary sarcoma of the brain appears either as a hard or as a soft tumor, and it is usually flat or wedge-shaped. The former variety was originally called by Virchow u fibrosarcoma, ' ' and many of the denser forms of tumors are genuine fibromata. In many cases the cells abound, particularly spindle-cells, and in some of them the intercellular substance has an almost cartilagi- 730 SURGICAL PATHOLOGY AND THERAPEUTICS. nous hardness. These types are firm, translucent, and of a gray- ish or a yellowish-white color (Knapp). The softer form may be a spindle-cell sarcoma purely or a myxosarcoma or gliosarcoma or a small round-cell sarcoma. The latter is the most malignant of the sarcomata in this region, except the melanotic form. It shows in sections a moist milky- white surface. Stellate and giant-cells are occasionally found in these growths, and many sarcomata are distinctly polymorphous in their cell-structure. Some forms are highly vascular and present appearances known as angiosarcoma. Sarcoma is sometimes easily separable from the surrounding cerebral tissue; in other cases it seems so continuous with the cerebral substance that it appears as a simple enlargement of the same. Sarcoma of the brain shows a tendency to undergo fatty degeneration which may produce an appearance strongly suggest- ive of a gumma. It appears to develop from the pial sheaths of the vessels, and it is known to occur at all periods of life. Meta- static deposits from primary sarcoma of the brain are not reported, but occasionally multiple growths occur within the brain that appear to have originated from a single nodule. Sarcoma of the pia mater may occur in that membrane as a diffused growth of endothelial origin, which growth may spread itself over a large surface, causing a thickening of the membrane which extends inward along the pial sheaths of the vessels of the brain and the cord. Ordinary types of sarcoma and myxosarcoma may, how- ever, develop from the pia mater. 10. Lymphosarcoma. Lymphosarcoma is a disease to which various names have been applied, as is usually the case in affections whose true nature is obscure and in those which are confounded with other allied affec- tions. It is known also as malignant lymphoma, psendo-lenkczmia, and Hodgkirt s disease. It may be defined as a disease character- ized by an enlargement of the lymphatic glands and by the forma- tion of lymphatic tissue in the spleen, the liver, the kidneys, the intestine, and the lungs — more rarely in other organs as a diffused infiltration of the tissues of the body — and by marked anaemia and the absence of leucocythsemia. Owing to its name, as well as to the impossibility of classifying it with any other group of tumors, it seems best to place it in the same chapter with sarcoma. It has been customary to recognize among tumors of the lym- phatic glands the enlargements due to tuberculosis, syphilis, and SARCOMA. 731 other infectious diseases; the enlargements due to leucocythsemia in which is a greatly increased number of white corpuscles in the blood; the multiple tumors of lymphosarcoma; and, finally, simple hypertrophy of the lymphatic glands due to some of the above causes to which the term lymphoma has been applied. This term, originally used when the knowledge of the etiology and classifica- tion of these various affections was much more imperfect than it is at present, must now be dropped if it is intended to apply it in any other sense than as an enlargement of a lymphatic gland, no matter what the cause, as those cases which were supposed to occupy an independent position under the name of lymphoma or lymphadenoma can now be classified under some one of the other headings. The lymphatic tumors which are so prominent a feature of lymphosarcoma are composed of the tissue of the lymphatic glands. The lymphoid cells are found supported in a delicate reticulum. According as one or the other of these structures predominates, there will be a difference in the consistency of the tumors : a hard and a soft variety have been distinguished. The soft lymphatic tumors are almost fluctuating, and they con- tain a considerable amount of fluid, which flows when the tumor is cut open. The cut surface shows a grayish- white substance equally distributed over the growth, so that there is no distinc- tion between cortical and medullary portions. The lymph-cells are enormously increased in number (Fig. 104). The harder tumors have a yellowish color and they are dryer and tougher. The capsule is much thick- ened, and there are numer- ous fibrous bands running through the tumor. These growths very rarely spread beyond their capsules, and they do not undergo cheesy degenera- tion. Suppuration is known to occur, but it is extremely rare. The disease usually begins in the cervical glands, which often Fig. 104. ■Retroperitoneal Lymphosarcoma, show- ing cells and stroma. 73* SURGICAL PATHOLOGY AND THERAPEUTICS. become enormously enlarged. One side of the neck is chiefly affected, and a large number of glands grow and form a swelling filling out the side of the neck and causing a great deformity (Fig. 105). The glands do not run together into a single mass, but they are movable upon one another, and can be shelled out separately. The writer removed in this way as many as forty glands from the Fig. 105. — Lymphosarcoma (Warren Museum, Sp. 4635). neck of a boy. The axillary, inguinal, retroperitoneal, bronchial, mediastinal, and mesenteric glands become enlarged, usually in the above order (Gowers). The spleen is enlarged in the majority of cases, and in some instances it is almost the only gland affected. The tonsils, the thymus gland, the papillae of the tongue, and the follicles of the intestinal mucous membrane are also affected. In cases described by Flexner there were very few glandular tumors, but the structure of the mucous membrane of the intestinal canal had largely been destroyed and replaced by lymphoid tissue. In one of the reported cases the mucous membrane of the duodenum was of a dead-white color: it was infiltrated uniformly with an SARCOMA. 733 opaque white material, and was marked here and there with small erosions and superficial ulcerations. Sessile and polypoid tumors are sometimes found in the stomach, and a portion of the wall of this organ may be trans- formed into a continuous infiltrated mass of the disease. Occa- sionally the medullary tissue of bones may undergo a lymphoid change, and may become like the red marrow of children, but this is not always the case. Metastases occur often in the liver and the kidneys, and also in the lungs, in which latter location they have been mistaken for tubercle. Large growths have been reported occasionally in the mediastinum. The trachea, pleura, peritoneum, heart, testicle, and ovary are also seats of the disease. In fact, there is hardly a spot in the body which may not be involved in the diseased pro- cess. The place of its origin, however, seems to be the lymphatic apparatus. The principal symptoms in the early stages of the disease are those caused by the glandular enlargements, which are chiefly in the cervical region. Usually there is no febrile disturbance, but occasionally recurrent elevations of temperature have been reported. The blood shows diminution in the number of red cor- puscles, without any increase in the number of white corpuscles, and toward the end of the disease there is marked anaemia com- bined with cedema and a tendency to hemorrhages. If the patient does not succumb to complications in the respiratory apparatus from pressure, death occurs from marasmus. The course of the disease is usually chronic, and it may sometimes last for years. Rarely the symptoms may be of the most acute type. Flexner reports the case of a girl eleven years of age who up to the day of her death had shown no symptoms of the disease. Death in this case was caused by cerebral hemorrhage. The lymphoid infiltra- tions were marked, but few glandular tumors were found. The disease appears slightly more often in men than in women. In ioo reported cases seventy-five were males and twenty-five were females. It occurs at all ages of life, although more frequently in the early half of life. Occasionally the colon bacillus and pyogenic cocci have been found in some of the enlarged glands, but the presence of these organisms is not constant, and it seems to have been acci- dental. They may account for those exacerbations of temperature which are found in certain cases. Flexner' s studies lead him to believe that in this disease there is a toxic substance capable of producing profound degenerative 734 SURGICAL PATHOLOGY AND THERAPEUTICS. changes in certain tissue-elements of the body. He observed cer- tain bodies in the lymphoid tissue that possibly may belong to the kingdom of the protozoa. They are certainly foreign to the tissues in which they are found, and are not to be regarded as altered cells or as nuclei in the usual sense. They are round, oval, or slightly irregular in shape, and consist of a rim of protoplasm which stains faintly in eosine, and each cell contains a particle that stains in hsematoxylin. The stained particles in the interior of the proto- plasm are round, oval, or crescentic. These bodies are not con- tained within other cells. They are much smaller than the tissue- cells among which they are found, and they do not exceed one- third to one-half the size of a red blood-corpuscle. They are distributed irregularlv in the diseased areas in the tissues, and an occasional organism may be seen in parts adjacent to the affected areas. They have been found in the stomach, the intestines, the liver, and the kidneys. In this connection the observations of Wagner on the peculiar disease affecting the cobalt-miners of Schneeberg are of unusual interest. All persons working in these mines for a number of years become affected with a disease of the lungs characterized by the formation of nodules, which grow slowly and often reach considerable size, metastatic deposits form- ing- in other organs. In other localities, where the same metals are mined as in Schneeberg, the disease is unknown. It has been sug- gested that the disease owed its origin perhaps to the water drunk in the mines. The probable infectious nature of lymphosarcoma has also been suggested by other authors. The only drug which has ever had any effect upon this form of sarcoma or any other form is arsenic. Fowler's solution, adminis- tered in doses reaching as high as 20 drops a day, given by the mouth and subcutaneously and as parenchymatous injections in the tumors, cured a certain number of cases of lymphosarcoma. In the case of an old man with a sarcoma of the neck the size of a small cocoanut the use of Fowler's solution produced a temporary remark- able diminution in the size of the tumor. This is the only case in which the writer has ever obtained any decided result from the use of the drug. Some few years ago Fehleisen experimented with cultures of the erysipelas coccus, inoculating cases of sarcoma and carcinoma. Several tumors were made to disappear in this way, but after one or two fatal results had been obtained by certain experimenters the method seems to have been abandoned (p. 400). This method has been revived by Sprouk of Utrecht and Coley SARCOMA. 735 of New York. Coley' s attention was drawn to this investigation after observing the cure of a case of inoperable sarcoma of the neck by an attack of erysipelas. Since 1891, Coley has been investigat- ing the antagonistic action of erysipelas cultures upon malignant growths, more particularly on sarcoma. The first series of cases were ten in number (six sarcoma, four carcinoma), and they were treated by means of repeated injections of pure living bouillon cul- tures. In but four of these cases w T as actual erysipelas produced, although cultures of marked virulence were used. In two of the cases where erysipelas did occur the tumor disappeared completely — the one three years and the other two years later — and both patients are alive and in good condition at the present time. Most of the other cases showed more or less improvement. To avoid the dangers of an attack of erysipelas, Coley experi- mented with the toxines alone, made with bouillon cultures steril- ized by subjecting them to a temperature of ioo° C. Of this fluid 1 to 3 C.c. were injected into the tumors, with the effect of pro- ducing all the symptoms of actual erysipelas; which symptoms, however, disappeared within twelve to twenty-four hours. The effect upon the tumors was similar in character, but less marked than when living cultures were used. Cultures prepared without heat grown three weeks in bouillon, then filtered through porcelain, and preserved by the addition of thymol, were next used. The great difficulty lay in the weakness of the preparation, necessitating the injection of large doses to pro- duce a marked reaction, without which no great decrease in the size of the tumors occurred. Utilizing the principle that one germ frequently has the power to increase the virulence of another when associated with it — this being especially true of the bacillus prodigiosus — the toxines of this germ were prepared in a similar manner and used in conjunc- tion with the erysipelas toxines in doses of .2 to .5 C.c. The results were satisfactory. The effect was not only to intensify greatly the reaction, but careful experiments with the toxines, singly and com- bined, in a large number of cases, confirmed the belief that the curative action of the erysipelas is likewise greatly enhanced by the prodigiosus. Coley recently reported 35 cases of inoperable malignant tnmors treated by these combined toxines: 24 of these cases were sarcoma, 8 carcinoma, 3 sarcoma or carcinoma. In 5 cases of sarcoma there is, according to him, a reasonable hope of permanent cure, and in most of the others there was marked improvement. All the cases were inoperable, and in all the diag- 73^ SURGICAL PATHOLOGY AND THERAPEUTICS. nosis was confirmed clinically and microscopically by eminent surgeons and pathologists. During the past year the proportion of the toxines has greatly been improved, and the filtration method is no longer used. Better results have been obtained by utilizing the toxines contained in the dead germs as well as the soluble products, and experiment has shown that heat- ing the cultures one hour at 58 C. is sufficient to render them sterile. Further improvement is due to Mr. B. H. Buxton, who suggested growing the two germs together in the same bouillon. (See Appendix.) The experience of many prominent surgeons with this method of treatment has not been satisfactory. There is little doubt that it is of little if any value in the treatment of carcinoma. The fact that a considerable number of cases of sarcoma have been benefited by this treatment, and that a few have been cured, renders it desirable to experiment further in this direction. XXXI. BENIGN TUMORS. The members of the group which are now about to be studied vary greatly from one another in their anatomical peculiarities, and some are quite complicated in their structure. They possess one characteristic, however, in common — in that they do not tend to recur after removal. Many of them at times show a tendency to become malignant, often after a period of prolonged quiescence, but this tendency is due to a change of anatomical structure to that resembling one of the forms of malignant tumors. i. Adenoma. An adenoma is a tumor consisting of new-formed gland-tissue. Quite a number of tumors are classified as adenomata by some authors, but they are rejected by other authors, who insist that the growth must consist of a new formation of gland-tissue only; so that there is at present much confusion as to the precise place which many tumors should occupy. Many small growths contain a glandular structure which is clearly nothing more than hyper- trophy of pre-existing gland-tissue, due, probably, to an inflamma- tory process, and they should not, therefore, be regarded as adeno- mata. Many of the cysts that form in glands present the appear- ance of a tumor, but they are simply the result of an obstruction of the gland-ducts. A classification of the pure adenomata cannot be attempted beyond the general statement that the gland-struc- ture of which they are composed consists either of acini or of tubes, as one or the other of these component parts of a gland usually predominates in the new growth. Adenoma is found in the breast, the skin, the mucous mem- branes, the kidney, and the liver. It is, in fact, quite widely distributed, although not a common form of tumor. The typical adenoma is a benign tumor, notwithstanding there are certain types of growth where the adenoma seems to merge into the carcinoma, and it has therefore been supposed that certain forms of adenoma should be regarded as malignant. These growths properly belong in the category of cancer. The criterion of a benign adenoma is 47 737 738 SURGICAL PATHOLOGY AND THERAPEUTICS. the presence of the membrana propria which separates the invest- ing epithelium from the surrounding connective tissue. Combina- tions with other forms of growth not infrequently occur, owing to development of the stroma of the gland-structure. There are obtained in this way forms known as adenoma fibrosnm, myxoma- tosum, or myxo-adenoma and fibro-adenoma, as they are called by different writers. Cysto-adenoma occurs not infrequently, par- ticularly in the breast and the ovary. Adenoma occurs both as a congenital tumor and as one developed during early life, but it may also be found occasionally during all the periods of adult life. Pure adenoma of the breast is a rare growth. Gross was able to collect but eighteen examples. He describes it as an ovoid or a nodulated tumor of hard consistence, occasionally cystic, and limited by a distinct fibrous capsule. On section the surface is milky-white in color and dotted with small orifices. It is a solitary growth, and it generally originates in the upper and inner quadrant. Its development is slow, and it does not attain a large size. When examined under the microscope it is found to be composed of ducts or of acini containing an epithelium which is usually arranged in an orderly manner, closely resembling that seen in a normal gland. The interstitial tissue of the mammary gland is often the seat of a growth that gives rise to tumors of considerable size. The gland-structure found in these tumors is always a prominent fea- ture, but many writers regard them as belonging to the fibromata or to the myxomata, according as their tissue is fibrous or mucous in character. These tumors often attain great size, and present striking peculiarities which have attracted much attention, opin- ions varying greatly as to their character. They have been called by Paget "proliferous cysts," and the terms adenocele and intra- canalicular papillary fibroma have also been applied to them. They are seen most frequently in young women from fourteen to nineteen years of age, and they first appear in the upper and outer quadrant of the breast. Being surrounded by a capsule, they are more or less movable, and they appear to be situated just beneath the skin, but after removal a deep hole is left in the mammary gland, which has been cut into in many places during the operation. Occasionally they grow to immense size. These tumors are seen in elderly women, and they have taken many years, perhaps half a lifetime, to develop. A recent writer, Schimmelbusch, called these tumors " fibro-adenoma," and this name seems to the writer BENIGN TUMORS. 739 most appropriate, for there can be no doubt that there is a consid- erable new formation of gland-tissne. The cut surface is most characteristic, showing a lobnlated growth dotted over with numer- ous small and tortnons slits. Occasionally this formation is a most complicated one, and numerous papillary growths may be turned out from cyst-like cavities. This formation is apparently due to the peculiar way in which the fibrous tissue has developed. Micro- scopically, there is found a fibrous tissue surrounding these glandu- lar cavities, which are lined with a more or less columnar-shaped epithelium (Fig. 106). It is not always possible to say beforehand Fig. 106. — Fibro-adenoma of Breast (oc. 4, obj. A.). whether the growth in question is or is not a benign one, as the interstitial tissue is occasionally sarcomatous (cystosarcoma). The writer has removed quite a number of such tumors, but has never observed a recurrence. Schimmelbusch also describes as cysto-ade?toma a diffused en- largement of the mammary glands studded with numerous small cysts containing a dark-colored fluid. Both breasts are said to be affected in the majority of cases. His description corresponds with that condition usually described as chronic mastitis with cyst-forma- tion. As the epithelial structures of the gland actively participate in the growth, as may be shown by a careful microscopical exam- 74° SURGICAL PATHOLOGY AND THERAPEUTICS. ination, the growth should be regarded essentially as glandular. These cysts sometimes assume considerable size, and a breast thus affected may thoroughly be disorganized. A microscopical exam- ination shows that there is an epithelial growth, and that the cyst- formation is caused by proliferation of the cells of the gland. The acini are increased in number — a condition resembling the changes observed during lactation. The epithelial layer is at first single, but subsequently the cells heap upon one another and dilate the acinus, and a cyst is formed by the subsequent breaking down of the cells. These tumors are found most frequently in women about forty years of age, and are benign in character. Closely allied to this condition is that known as diffused hyper- trophy of the breast. In one case, described and illustrated by Bill- roth, the coarse appearances of the growth are those of a fibro-ade- noma. The case of which the accompanying illustration is a portrait (Fig. 107) was operated upon by C. B. Porter. The following are the measurements : Right breast, largest circumference, 38 inches ; length from chest-wall to nip- ple, 17 inches ; circumference at base, 23 inches. L,eft breast, largest circum- ference, 28 inches ; length from chest-wall to nipple, 14 inches ; circumference at base, 23 inches. The skin was cedematous, thickened, and porky. Throughout both breasts were to be felt movable hardened masses the size of an orange. Microscopical examination showed the growth to be a diffused intracanaliclular fibroma. A similar case recently came under the writer's care. The breasts were nearly as large as in the above case, but as the patient was several months advanced in pregnancy, it was thought best to wait and see what influence the birth of the child might have upon the growth. After the confinement the breasts diminished to less than half the former size. Amputation has been performed in many cases with success. In the skin adenomata are found both in the sudoriparous and in the sebaceous glands. Adenoma of the sweat-glands is found in various parts of the body, but principally on the face, where it occurs as a small soft tumor of a dirty grayish-white color and with a nodular surface. On the cut section are seen coils of dilated ducts, from which degenerated epithelium can be pressed. At times these little tumors appear to have developed from pre- existing sweat-glands; at other times they seem to grow quite inde- pendently, one observer having found such a growth in the diploe of a cranial bone. It is a rare form of growth. Adenoma sebaceum appears on the face in the form of papules, BENIGN TUMORS. 741 which are usually of congenital origin. According to Crocker, the disease is often found on the persons of epileptics, and its Fig. 107. — Diffuse Hypertrophy of the Breast. true nature is frequently overlooked. This variety of adenoma forms roundish, convex papules, ranging from a pin-point in size to that of a split pea; these are often bright crimson in color, and they are not infrequently associated with small fibromata, such as are seen in the "dotage" of the skin of old people. Adenoma is found occasionally in the salivary and in the lach- rymal glands. The writer has seen a very perfectly-formed ade- noma in the parotid gland : it was about the size of a hen's egg^ and quite soft in structure, differing markedly in this respect from the ordinary parotid tumors. Small miliary multiple adenomata are also found in the liver. Adenoma of the kidney is found usually in the cortical sub- stance, and it is about the size of a bean or a cherry, and often is very much smaller. It is usually yellowish or brown in color, and 742 SURGICAL PATHOLOGY AND THERAPEUTICS. frequently contains small cysts which give it a porous appearance. Under the microscope are seen coils of tubules containing cells which are cylindrical in shape. There is occasionally seen a papil- lary variety in which the interstitial tissue forms papillary growths that project into cyst-like cavities. The epithelium is more cuboid in shape. These adenomata are often surrounded by a capsule. Many small superficial growths in the kidney that have been supposed to be lipoma are shown by Grawitz to be fragments of accessory adrenal glands situated between lobes of kidney-tissue. The new-formed cells, like the cortical cells of the adrenal gland, contain large drops of fat. These tumors are soft and are yellow- ish in color, and they appear to be separated from the adjacent kidney-tissue by a capsule. They are often highly vascular and contain clots, the result of hemorrhage, which when absorbed lead to the formation of cysts: as myxomatous degeneration often takes place in them, the whole tumor may in this way be converted into a mass of debris containing fat and cholesterin. Under the micro- scope sections of these tumors show gland-like structures lined with polygonal cells containing fat-drops. Adenoma of the testis is a comparatively rare growth. It is usually combined with the formation of cysts, and, in fact, the majority of cases of multilocular cysts of the testis are developed in adenomata. The tumor appears as an enlargement of the testi- cle. On section the new formation is found to be lobulated, and to consist of a stroma containing cysts and gland-tubes which are usually lined with a cylinder epithelium. These glandular struc- tures do not appear to be characteristic of any particular form of gland. They are more or less dilated and tortuous canals of vary- ing shapes and sizes. Occasionally they are filled with masses of epithelial cells heaped upon one another, giving the appearance of the epidermic clusters seen in epithelioma. The cysts do not appear as completely-closed cavities, but they communicate more or less freely with the glandular structure of the tumor. Adenoma of the testis appears to spring from the seminal ducts by growths of the epithelium and the subjacent stroma. All cysts of the testicle do not appear, however, to be of glandular origin in this sense. Some of them seem to be the result of hemorrhage or seem to develop from dilated lymphatics, while others take their origin in embryonic remains in the testicle. When multiloc- ular cysts have fully developed, they may, by the pressure which they exert, destroy the original growth from which they sprang, and evidence of their origin is thus lost. Some of the cysts con- BENIGN TUMORS. 743 tain a mucous fluid with gland-cells, and others have atheromatous contents containing particles of calcareous matter and pavement epithelium. There is found also cartilage in adenoma of the tes- ticle. According to Langhans, cartilage forms in the fibrous stroma of the tumor. Striped muscular fibre has also been ob- served. These tumors are most frequently found between the ages of twenty and forty years. They are non-malignant, and they do not return after castration, but, inasmuch as cancer is sometimes found in combination with adenoma, removal of the testicle should always be advised. Cyst of the epididymis is known as spermatocele, a condition often mistaken for hydrocele. The sac, which is usually quite large, contains a milky fluid in which are found spermatozoa. It is not developed from any glandular new-formation, but it is a a pure retention-cyst. It is a curious fact that while, in the male, cysts are found more frequently in the epididymis than in the tes- ticle, in the female cysts are more frequent in the ovary, while parovarian cysts are less common. Spermatocele occurs most fre- quently in the later years of life. Mucous polypi may contain well-marked adenomatous struc- tures. Such glandular polypi are found in the nose, in the large intestine, and, most frequently, in the rectum. One of the most perfect types of adenoma which the writer ever examined was an adenomatous polyp removed from the rectum of a young man. 2. Goitre. The names goitre, struma, and bronchocele are applied indis- criminately to all tumors of the thyroid gland, of which tumors, however, there are several distinct varieties, among them being true adenoma, which therefore deserves a place here. Wolfler gives the following classification of thyroid tumors: i. Hypertrophy of the thyroid gland, which is a comparatively rare disease. It may occur either at birth or at the period of puberty or of pregnancy, and it consists in a uniform increase in the normal glandular tissue, so that there are no nodules to be felt in any part of the gland. It is soft to the feel, and when vascular is compressible. 2. Foetal adenoma, which is a formation of gland-tissue from the remains of foetal structures in the gland. It may exist either as a single circumscribed nodule, usually firm and movable, or in numerous nodules varying in size from that of a cherry to that of an apple. It develops in both sexes at the period of puberty. 744 SURGICAL PATHOLOGY AND THERAPEUTICS. ., Fig. 108. — Adenoma of Thyroid Gland. 3. Gelatinous or interacinous adenoma, which consists in an enlargement of the acini by an accumulation of colloid ma- terial, and an increase in size of the interacinous tissue by a growth of round-cells (Fig 108). This form appears usually in the later periods of life, and it develops rapidly at the time of pregnancy or the change of life. At first there is a uniform en- largement of the gland, but later the different portions grow unequally and the gland pre- sents great irregularity in shape. It is this form in which cysts are frequently found (Fig. 109). Wolfler prefers to recognize clinically as a special variety those tumors which are highly vascular, although this condition may accompany any of the above forms. With the increase of vascularity there is frequent- ly a visible pulsation, and a perceptible bruit is heard through the stethoscope. The tumor may preserve the form of the gland and have a crescentic or horse-shoe shape, or it may be circular, surrounding completely the trachea. The latter form is seen in congenital goitre, and it occasionally causes death of the new-born child by asphyxia. One lobe may enlarge and assume various shapes, or the tumor may consist of a single cyst, which in old people occa- sionally reaches enormous Fig. 109.— Cystic Goitre. size. ■v*t BENIGN TUMORS. 745 Goitre may develop ill unusual and unexpected situations in the throat, the neck, and the thorax. This mode of development is due to the displacement of portions of thyroid-gland tissue during fcetal life, and such lobes are known as accessory glands. According to His, the middle lobe of the gland is developed in a tract which is directly continuous with the foramen caecum of the base of the tongue, and this tract is still frequently marked in the adult by the so-called "processus pyramidalis," a continuation of the middle lobe to the hyoid bone. It is here also that the glandulae supra- and epi- hyoideae are found. Such accessory glands may also be found in the vicinity of the aorta, at the base of the tongue and behind the pharynx, and in the larynx and trachea. Fig. i 10. — Accessory Thyroid Gland at the Base of the Tongue. Fig. hi. — Section of Accessory Thyroid Tumor. A tumor at the base of the tongue (Figs, no, in, 112) was removed by the writer from a woman fifty-two j^ears of age. She first noticed a lump in her throat thirty-two years before, since when it slowly and steadily increased in size, and at the time of operation it was about the size of a hen's egg. It consisted of thyroid-gland tissue. No return was reported two years after the operation. Mucous cysts are sometimes found in connection with the glandula suprahyoidea. They are lined with ciliated or pavement epithelium. Retrosternal tumors form as the result of a down- ward growth of thyroid tissue from the isthmus. Goitre occurs both in man and in animals, and it appears to be independent of race. It may be either sporadic, endemic, or epi- demic. Endemically, it is found in certain mountainous districts, 746 SURGICAL PATHOLOGY AND THERAPEUTICS. particularly on the continent of Europe. Epidemically, it breaks out in schools and in garrisons. It occurs much more frequently Fig. 112. — Thyreoglossal Tract (after His): 71, tongue; U. y, under jaw; 77iorac. y thoracic cavity; PP., epiglottis; H.B., hyoid bone; F.c, foramen caecum; T.L., tractus lingualis; Th. Th., thyroid gland; Tky?)i., thymus gland; Pa., arytenoid fold. in women than in men, and pregnancy seems to be a not infrequent cause. Whether the micro-organisms found by Klebs and Bischer in water are in reality a cause of the disease in certain cases is not yet clear. Acute infective diseases are not without their influence in the development of thyroid tumors, as they have been observed to form after malarial fever, diphtheria, and scarlet fever. Thyroid tumors usually grow extremely slowly, but occasionally an acute form is observed; this is particularly true of the vascular type. Goitre may prove fatal, owing to the effect of its growth upon the trachea, the cartilage of which undergoes degenerative changes. In this way it becomes softened, and is easily compressed or twisted on its axis by the movements of the head, as a result of which sudden death may take place. Cysts may be treated, if small, by injection of tincture of iodine. Many cases of adenoma have been treated successfully by electrol- ysis. If the tumor is excised, a fragment of gland tissue about the size of an English walnut should be allowed to remain, other- wise myxcedema may develop. Closely allied to myxcedema, which may also occur idiopathically, is cretinism. Cretinism is characterized by idiocy and imperfect development of the bones,. BENIGN TUMORS. 747 particularly marked in the skull. Cases of myxcedema have suc- cessfully been treated with thyroid juice. The parenchymatous, but not the cystic, forms of goitre sometimes diminish rapidly in size under the use of preparations of sheep's thyroid. Five grains a day of the dried gland, or about one-third of one lobe, is a suit- able dose to begin with. Some patients can take a much larger quantity with benefit, but, on the other hand, a remarkable sus- ceptibility to the toxic effects is occasionally present. It is important to say a word about the relation between ordi- nary goitre and that form characterized by the signs and symptoms of the so-called "Graves's disease" or "exophthalmic goitre," though the subject is so complex that only the broad outlines can be indicated. It is, in the first place, noteworthy that ordinary goitre is apt to be attended with nervous symptoms, of which tachycardia, or a tendency to palpitation, is the chief. It is a matter of great doubt what is the relation in which goitre and nervous symptoms stand to each other. Wette thinks that local nerve-irritation plays an important part, but he rather inclines to a theory which has been advanced of late (Mcebius and others) that an increased or perverted thyroid secretion, acting as a poison, has to do a good deal with the production of the symptoms of typical Graves's disease. If the matter is looked at from another side, it will be found that Graves's disease is strongly associated with other neuropathic conditions, and that it occurs under conditions of nervous excite- ment. Some writers (Greenfield; Maude) believe that even when Graves's disease arises through nervous excitation thyroid-poison- ing forms an important, if not a necessary, factor. This theory is not yet substantiated or even made highly probable, and the more conservative view is that the enlargement of the thyroid is on the same plane with the other symptoms in the first instance, but that it may become secondarily a source of mechanical irritation or of poisoning, or both. Thyroidectomy has been performed more than fifty times within the past few years, mainly by German surgeons, for the relief of Graves's disease. The eventual results, on the whole, are very encouraging, but severe symptoms are apt to show themselves during the first days after operation, occasionally leading to death. It is probable that the extreme irritability of the nervous centres of these patients makes thyroidectomy a more serious operation than in cases of ordinary goitre. Putnam suggested that these symptoms may be due in part to poisoning with a thyroid secre- 748 SURGICAL PATHOLOGY AND THERAPEUTICS. tion squeezed out during the operation and the healing of the wound. The writer has operated upon two cases of exophthalmic goitre. In the first the temperature rose to 106 the first evening, and the pulse to 204. On removing the dressing a small quantity of thy- roid juice was found upon it. The wound healed by first intention, and the patient was benefited by the operation. In the second case no bad symptoms followed the operation at first, but on the fourth day the temperature, which had been normal, suddenly rose, the pulse became extremely rapid and weak, and the patient died in a few hours. All the cases of glandular and cystic goitre which the writer has operated upon have recovered without bad symptoms, although occasionally an acceleration of the pulse has been noticed for a few days. 3. Cystoma. Cysts of the ovary were formerly supposed to be developed from a Graafian vesicle by distention of such a cavity with fluid. Such dropsical effusion may occur to a limited extent partly as the result of inflammatory conditions. Small cysts may develop also in the corpus luteum. True cystoma is, however, epithelial in origin, and in many cases it begins as an adenoma. It is devel- oped from an ingrowth of epithelium into the stroma of the ovary, very much in the same way that the Graafian vesicle is formed. There are two principal varieties of ovarian cysts: the simple cystoma or cysto-adenoma, and the papillary cystoma. In the wall of the simple cystoma are numerous follicular depressions lined with cylinder or ciliated epithelium, and near them are small cysts lined with similar epithelium. By this ingrowth of epithe- lium into the wall of the cyst new cysts may be developed and the tumor may become multilocular. Parts of the tumor may dis- tinctly be adenomatous instead of cystic. Such growths are occa- sionally found in the walls of large cysts or in the septum between two cysts. The papillary cystoma is characterized by the presence of a warty or papillary growth into the interior of the cyst. These growths show the greatest difference in their development. The wall of the cyst may be covered with numerous small warty tumors, or the cyst may be filled with a cauliflower mass. In rare cases the outer surface of the cyst is covered with a similar growth. There may also be an ingrowth of the epithelium into the stroma and glandular structures, thus producing a combination of ade- noma with papilloma. The epithelium of the papillary cystoma BENIGN TUMORS. 749 is usually ciliated epithelium. Occasionally a limited metastasis is found, the peritoneum being studded with papillary growths. It has been suggested that these papillary growths may develop from the parovarium, as they are often found within the broad ligament, but it is probable that in the majority of cases they originate in the same way as the simple or glandular cystoma. The material contained in the cysts may vary greatly in color and in consistence. It is usually of a mucous character, but it may be gelatinous. It appears to be developed from the cells that line the wall of the cyst, and it is either a product of their secretion or it may be the result of degenerative changes in the cells. The cells may undergo not only colloid degeneration, but also fatty degen- eration and necrosis. Necrosis of the cyst-wall may take place, and sometimes suppuration may occur. Calcareous degenera- tion of the cyst-wall is also observed. It is probable that cys- toma of the ovary is not of fcetal origin, but that the epithelial growths from which they are developed may begin at any period of life. Ovarian cysts are for the most part benign, but, as has been seen, the papillary form may be accompanied by peritoneal growths. The papillary growths in the cyst may break through and appear as cauliflower excrescences on the surface, and in this way there may be a gradual metamorphosis into a carcinoma. Cysts of the broad ligament are not of new formation, but they are caused by an accumulation of secretion in the gland-tubes of the parovarium. They develop probably from the remains of the Wolffian bodies. The ovary at times also contains cysts, which are either in part or are wholly made up of dermoid structures. These cysts may contain only dermal structures, or a great variety of tissues may be found in them, such as bone, teeth, cartilage, muscle, or mucous membrane, glands, nerves, etc. Tumors of the latter class are called "teratoma." The commonest forms are the dermoid cysts and the simpler forms of teratoma. They are usually found on one side, but they may occur simultaneously in both ovaries. They are usually smaller than the adeno-cystoma, growing not larger than an apple at first, but they may occasionally reach the size of a man's fist or head. Several varieties can be recognized, according to the more or less complicated nature of their construction. The epidermoid cyst has a wall of connective tissue lined with epidermis, but it possesses no other attribute of the skin. The contents in this case 750 SURGICAL PATHOLOGY AND THERAPEUTICS. are, distinctly, epidermic scales, which may be rolled up in firm masses or are more or less soft or soapy in appearance (Orth). The commoner form is the dermoid cyst. In this form of cyst the wall is made up of skin containing small and ill-defined papillae, but rich in hair-follicles and sebaceous glands. Even the erector Fig. 113. — Dermoid Cyst of Ovary, showing hair, tooth, and adipose tissue. pili muscle and the sudoriparous gland are often found. The hair is partly free and partly rolled up into thick balls, or it is still attached to the walls. A large mass of sebaceous material is also found in these cysts (Fig. 113). The simpler forms of teratoma are dermoid cysts containing bone and teeth. The bone appears as a series of plates in the wall of the cyst, giving to the touch the feel of an infant's head. The teeth, which are not always well formed, are arranged without order. The complicated teratoma may contain, in addition to the above-mentioned structures, cartilage and glands, such as mucous and salivary glands, mucous membrane with cylinder or ciliated epithelium, smooth and striped muscular fibre, nerves and cerebral substances, portions of eyes, fingers with nails, mammas, etc. It is probable that these more complicated forms of cystic growth have the same origin as the cysto-adenoma of the ovary, and they result from the activity of the germinal cells (Orth). The growth of dermoid cysts is slow, and they are generally first observed at the period of puberty, although not infrequently found in young children. Combinations of dermoid cyst with adeno-cystoma are occasionally observed, Thomson reports a case of dermoid cyst of the bladder containing hair, which cyst he re- BENIGN TUMORS. 751 moved. It was a pedunculated growth, and it was undoubtedly vesical, and not expelled from some ovarian source through the urinary passages, as sometimes occurs. Dermoid cysts are found also in regions of the body quite remote from the ovary. The so-called "orbital wens" are true inclusion of skin of a congenital origin, as are also some of the cysts in the neck. Many of the cysts in the latter region are due to imperfect closure of the branchial clefts, and they have been called by Senn "branchial cysts." This author recognizes — 1, mucous cysts; 2, atheromatous cysts; 3,- serous cysts; and 4, hae- matocysts. Many of the so-called u ranula cysts" about the base of the tongue belong to the class of mucous cysts. The atheromatous cysts are. situated near the hyoid bone, and they appear as tumors bulging out from beneath the lower jaw. They do not contain hair or sebaceous material, but they are filled with an atheroma- tous substance containing cholesterin crystals. The cyst is of the epidermoid type. The serous cysts correspond to what is usually known as hydro- cele of the neck. These cysts are single or are multilocular, with a thin membranous wall lined with pavement epithelium. They are found anywhere in the neck, within the area of the branchial clefts, between the lower jaw and the clavicle. These branchial cysts are often found in children, but are not infrequently seen in adults also. The haematocysts are of the same nature, the blood mingling with the serous contents from minute hemorrhages from the cyst-walls. 4. Papilloma. Many writers place this form of growth among the fibromata, but certain forms — particularly those seen on mucous membranes — have so marked an epithelial character that it would be incorrect to recognize the stroma as the characteristic feature of the disease. This type of the papilloma is found in the papillae of the skin and the mucous membrane. It consists of a papilla containing a vas- cular connective tissue, and is covered with epithelial cells. The connective- tissue portion of the growth may consist of a single stem or of a trunk with numerous branches. The tissue consists ordinarily of nbrillated connective tissue, and it is not infrequently infiltrated with small round cells. The vascular sup- ply varies greatly, but in certain forms, such as the villous growth from mucous membranes, it may be very abundant. The epithe- 752 SURGICAL PATHOLOGY AXD THERAPEUTICS. Hum covers each villus separately, but occasionally there may be an epithelial covering extending over several villi. There are two forms of papilloma, the hard and the soft. The hard form occurs on the skin and the mucous membranes. The ordinary wart consists of hypertrophy of several papillae with their epithelial coverings. It need not, therefore, strictly speaking, be called a papilloma, as there is no new formation of papillae, but it is usually classed with these growths. The venereal wart (condy- loma acuminatum) is, however, an example of a true papillomatous growth. The hard form of papilloma is found in the mucous mem- branes upon the lips, in the mouth, the uvula, the nasal cavity, in the larynx, the urethra, the vagina, the labia, the cervix uteri, and the bladder. It has a firm, well-developed stroma, and it is covered with layers of pavement epithelium. The soft papilloma is cha- racterized bv the formation of long, delicate, single or branched villi, the surface of which is covered with a cylinder or pavement epithelium of one or more layers in thickness. This cylinder may cover several villi, and may give to the surface of the growth a smoother appearance than is seen in the more typical velvety villous tumors. These growths may spring from one stem or they may be multiple, covering a large surface of mucous membrane. They are very vascular, and the capillaries have ampulla-like dila- tations, which account for the extensive and repeated hemorrhages that are liable to occur. The soft, villous papillomata are found in the bladder, in the stomach and intestine, particularly in the colon and duodenum (Birch-Hirschfeld), and also in the uterus. Some writers distinguish those papillomata found on the membranes of the brain from the other forms, as they are here covered with endothelium. The Pacchionian bodies are the types of this variety; they are found in the parietal region and also at the base of the brain. Springing from the dura, they may grow into the venous sinuses (Klebs). Papillomata growing on the skin and the mucous membranes may be congenital or be acquired. They appear to be the result in the latter case of chronic irritations, as catarrhal affections. Papilloma may occur at any period of life. Watson, in a col- lection of 89 cases, found 59 in males and 30 in females. In the male, 21 cases occurred between the ages of sixty and seventy, and 35 between the ages of thirty and sixty. In the female, 17 occurred between thirty and forty, and 12 after fort}'. Papilloma may be multiple or single, sessile or pediculated. Thompson describes the hard variety as fibro-papilloma, and the soft form as fimbriated BENIGN TUMORS. 753 papilloma. He reports several cases of fibro-papillomata removed from the bladder through the median incision in the male and through the urethra in the female, all of which cases made a good recovery with permanent cure. The tendency of papilloma of the bladder to bleed is one of its most marked clinical features. Papil- loma of the bladder may be combined with carcinoma, in which case characteristic epithelial cells are found in the base of the tumor in the bladder-wall. Papillomata of the larynx occur more frequently than all other forms of benign tumors of this region. They are situated in the large majority of instances on the vocal cords, usually in the anterior portion of the larynx. In rarer cases they are found upon the ventricular bands, the ary-epiglottic folds, and the epiglottis (Bosworth). As a rule, they confine themselves to the supraglottic portion of the larynx in adult life, although in children they occasionally extend below the cords. They are usually sessile in character, though occasionally pedunculated. They may occur singly or in groups, and they vary in size from a millet-seed to a growth more or less completely filling the supraglottic laryngeal cavity. They become a growth of great clinical importance, owing to the obstruction which they offer to the air-passages. Papilloma of the soft palate and the uvula may occasionally grow to consider- able size, but it does not, as a rule, give rise to serious symptoms. Newman describes a papilloma of the oesophagus situated on the anterior wall immediately behind the cricoid cartilage, which papilloma caused during life considerable obstruction to swal- lowing. 5. Fibroma. Fibrous tissue occurs in nearly all tumors, and in some it forms a very considerable portion of the growth, as in the tumors already described. It occurs as a mixed form with other growths, as in myxoma, sarcoma, neuroma, etc. Fibroma occurs in two principal forms, which correspond in character with the two varieties of con- nective tissue found in the body — namely, the hard and the soft or areolar fibroma (Birch-Hirschfeld). The hard fibroma consists of bundles of fibres closely packed together, interspersed with numerous connective-tissue corpuscles. The relation in the number of cells to the intercellular substance is characteristic of this tumor (Fig. 114). When the cells begin to ex- ceed in number the intercellular substance, there are presented con- ditions approaching those found in sarcoma. A fibroma is usually a 48 754 SURGICAL PATHOLOGY AND THERAPEUTICS. well-defined nodular growth, showing a tough tissue when cut open, and containing very few blood-vessels, and is situated principally in trie subcutaneous cellular tissue, in the connective tissue of the skin, of the muscles, periosteum, nerve-sheaths, and serous membranes. Fig. 114. — Fibroma. Fibrous tumors occur in the interstitial tissue of organs, such as the kidney, the female breast, and in the liver, the spleen, and the ovaries. Many of the polypoid growths found on mucous membranes must be regarded as fibromata. One of the commonest seats of fibroma is the skin. The warty growths, although largely composed of fibrous tissue, are usually classified with the papillomata. A variet}^ which has lately excited much attention is seen in the multiple fibromata of the skin. They occur sometimes in enormous numbers, covering nearly the whole surface of the body, and associated with them are often pendulous tumors of considerable size. Such growths in the skin were called "fibroma molluscum " by Virchow, but V. Recklinghausen called attention to the fact that these growths take their origin from the fibrous sheaths of the nerves and the various channels, such as the sweat-ducts and the hair-follicles. In his opinion, many of these tumors should be regarded as neurofibromata. He found the papil- lary layer of the skin quite unaffected. In many of the cases of multiple fibroma reported it was found that tumors connected with the nerve-trunks also existed. Such was the condition found in a case reported by Payne, who, however, observed no actual connec- BENIGN TUMORS. 755 tion between the fibromata of the skin and nerve-fibres. Payne explains the coexistence of nerve-fibres and skin fibroids on the supposition that, inasmuch as both the epidermis and the nervous system arise from the epiblast, these two structures have a deep- lying connection which makes them homologous parts. Keloid {yj t h' h a claw), which is a fibroma of the cutis vera, may develop spontaneously or in a scar. Two varieties are recognized — the true and the false keloid. There is, however, a tendency among writers at the present time to disregard this distinction. True keloid has always been considered as a spontaneous new for- mation in the corium independent of pre-existing wound. It is now supposed that true keloid may take its departure from some minute scar which has escaped notice. The typical true keloid is situated over the sternum, and it appears as a raised elongated growth, frequently with claw-like prolongations at either end. Its surface is smooth and shiny, and the color red like that of a hypertrophied scar. It grows to a cer- tain point, reaching the length of about two inches, and then re- mains stationary. There is no tendency to ulceration. It is an extremely rare disease, and the writer has seen but two examples. According to Hebra, it is found once in two thousand cases of skin disease. It is not painful, but it gives rise to an itching, prickling sensation. It rarely disappears, and if excised it returns promptly. False keloid, which is a growth similar in color and consistency to true keloid, develops from a scar, no matter in what part of the body. It varies greatly in size, and it may be of any shape. A favorite seat is the lobe of the ear after puncture, and it is also found frequently on the chest-wall. It occasionally springs from acne-pustules, and in this case it is multiple. Keloid is said to be found rarely on the mucous membrane. Verneuil reports a case of keloid of the conjunctiva. Ziemssen reports the case of an individual who had one hundred and five keloids. True keloid appears to be a disease of adult life, but false keloid may appear at any age. There seems to be a keloid disposition in certain families and individuals, and the peculiarity of the African race in this respect is well recognized. False keloid grows to a certain point, remains stationary for many years, and finally flat- tens somewhat and becomes paler. In negroes, although it attains unusually large size, it is said eventually to disappear entirely. Hutchinson observed in a negro an extensive keloid growing in the cicatrix following a burn. After the keloid developed numer- ous small scars, which had existed before, began also to indurate. 756 SURGICAL PATHOLOGY AND THERAPEUTICS. This occurrence suggested to Hutchinson the probability that in some way the keloid patch had shed into the blood infective mate- rial which had the power of developing only scar-tissue. Fig. 115. — True Keloid (longitudinal section). Microscopically, the tumor, both in true and in false keloid, is found to be composed of bundles of fibres running horizontally some little distance beneath the surface of the corium and arranged parallel with the long axis of the tumor. In true keloid the pa- pillae with their normal covering of epidermis are seen above the growth (Fig. 115), whereas in false keloid only scar-tissue exists over the tumor. In true keloid, however, when there is consider- able pressure from growth the papillae are flattened out. The fibrous growth so characteristic of keloid can be traced to the walls of the blood-vessels in the vicinity. It is probable that the fibrous tissue develops from the outer walls of the blood-vessels, as the writer has been able to observe a round-cell growth and also fusi- form cells in the adventitia. As bundles of fibres in this way form around the arteries, the tissue of the corium is gradually com- pressed by them, and the different bundles thus uniting form the keloid. The origin of these tumors from the walls of blood-vessels sug- gests the possibility of the existence of muscular tissue at some pe- riod in the development of these growths, and it is not improbable that some forms of keloid may be classed with the fibromyomata. BENIGN TUMORS. 757 One case is reported of a spontaneous growth in the face having returned, after excision, in the scar and in the points of suture, and being subsequently cured by hypodermic in- jections of ergot. Pendulous tumors occur in the skin, and they some- times attain a large size. Some of them may develop from scars; others are spontaneous growths which lie in overlapping folds. Closely allied to this group of tumors is dermatolysis, but this term should be applied Strictly to a loose Fig. n 6.— Nasopharyngeal Fibroma (Sp. 1247-2, War- fold of skill containing 110 ren Museum). fibrous tissue. The enormous growths of elephantiasis depend upon the forma- tion of a fibrous tissue similar to that seen in fibroma. It is, how- ever, a diffuse growth, with an etiology peculiarly its own, and it is not now classed with this form of tumor. Some forms of fibroma arise from the tissue of the periosteum. A striking example of this form of tumor is the nasopharyngeal polyp, which is often a pure fibroma springing from the base of the skull. When composed of fibrous tissue the polyp is a perfectly benign tumor, and it does not recur after removal. The accom- panying illustration (Fig. 116) shows such a growth which had involved the nasal passage and the pharynx and had grown out- ward beneath the zygoma. A lobe had also penetrated the antrum and perforated the hard palate. It was therefore so intimately connected with the superior maxilla that it was decided to excise that bone. The patient, who was a boy aged fourteen, has re- mained well for several years since the operation. Fibrous polyps are found also growing from the walls of the large intestine, taking their origin from the connective tissue of the submucosa. They are found occasionally also in the rectum. Another form of tumor which is occasionally fibrous is the intra- canalicular papillary growth in the breast, in which case the inter- stitial tissue of the tumor is purely fibrous. Its association with sarcoma and myxoma is mentioned elsewhere. The soft fibroma contains loose areolar connective tissue, the 75 8 SURGICAL PATHOLOGY AND THERAPEUTICS. spaces of which are filled with serous fluid, which gives the ap- pearance of cedematous tissue. Occasionally large cyst-like spaces are found in them. It may be found in the skin, in the subcuta- neous connective tissue, in the intermuscular tissue and the peri- osteum, and, according to Birch-Hirschfeld, even in bone. A familiar type of this soft fibroma is the mucous polyp, which, in many cases, is purely fibrous. It has sometimes been called the "cedematous fibroid." Many of the cases of molluscum verum of the skin belong in this class. A fibroma has a very slow growth. It may remain for a long time without any change whatever, and then suddenly take on a rapid growth. In such cases there is probably a transformation into sarcoma. Fibroma occurs in both sexes and in various races, and it may begin in early life. It often undergoes calcification and sometimes fatty metamorphosis. 6. Myxoma. Myxoma (/i^«, mucus) is a tumor composed of tissue which finds its type in mucous tissue. It corresponds to the fibrocellular tumor of Paget. This tissue is found in abundance in embryonic life, and it is the structure from which adipose tissue is subse- quently formed. It is seen also in the foetal cord. In the adult it is found in the vitreous humor, and it is observed also as a degen- erative change in adipose tissue and in the medulla of bones of old people. Myxoma is closely allied, therefore, to lipoma, and indeed combinations of both structures in the same tumors are not infre- quently seen. Tumors of this nature which grow from adipose tissue should therefore be considered fairly homologous. There is also a semi-homologous type in the myxomas arising from the perineurium, the neuroglia being closely allied also to the mucous tissue. Histologically, mucous tissue is found in two forms. In one the cells are round and are imbedded in a transparent intercellu- lar substance. In the other form the cells are long and spindle- shaped, or are stellate with long prolongations which anastomose with one another. The substance of which the matrix of the tumor is composed is mucin, which coagulates on the addition of alcohol, foiming a thread-like or membranous deposit. There is a network thus formed somewhat like that seen in fibrin (Fig. 117). Myxoma may occur alone or in combination with other tissues. A pure myxoma with very few cells in it, consisting principally of BENIGN TUMORS. 759 transparent intercellular substance, is known as a hyaline myxoma. If there is a considerable amount of fibrous tissue in the intercel- lular substance, it is known as myxoma fibrosum. A very cellular type is called "myxoma inedullare." Myxoma may also be combined with cartilage and adipose tissue, and at times may be 4 • # £2, t 43/?-: K % IB % % 9 vSg) V 1 * m Fig. 117. — Myxoma (oc. 4, ^ oil-im.). very vascular. The term myxosarcoma is used when in sarcoma the intercellular substance is of a transparent character and contains mucin. Myxoma occurs most frequently w 7 here there are deposits of fat or of loose connective tissue, as in the thigh, the back, the hand, and the cheeks, or at the angle of the jaw, or in the breast, the labium, or the scrotum. It is observed also in the placenta, and it is interesting to know that myxoma may occasionally develop in later life from the navel, as if it had formed from foetal remains of the cord. Myxoma may occur in combination with enchondroma in large tumors of the bone, taking its origin apparently from the tissue of the medulla. Myxoma occasionally attains considerable size, and it has then a w T ell-marked lobulated structure. The writer removed one, about the size of a cocoa-nut, from the popliteal space. This tumor is occasionally found growing on the spinal arachnoid and in the ventricles of the brain, and even in the 760 SURGICAL PATHOLOGY AND THERAPEUTICS. cerebral substance. The pure forms are, however, rare here. The tumor more frequently found is a myxoglioma or a myxosarcoma (Knapp). The intracanalicular papillary tumor of the breast is often myxomatous. A not infrequent seat of myxoma is in the nerves, where it grows from the perineurium and presses the nerve-fibres apart, and develops as a spindle-shaped or a cylindrical tumor. On the mucous membranes these tumors appear in the guise of polyps, particularly in the nose. Similar polyps have been found also in the uterine cavity. Myxoma is essentially a benign tumor, although it often assumes importance, owing to its size, to the readiness with which it breaks down, and to the difficulty of re- moving it thoroughly in inaccessible regions. Many of the myx- omata of nerves are, however, undoubtedly malignant. Virchow reported several such examples, and metastases are reported as fol- lowing the development of myxoma in the labium. The possibil- ity that myxoma may be combined with sarcoma and carcinoma should always be kept in mind. 7. Lipoma. A lipoma is a tumor consisting of adipose tissue. It is a soft or a moderately firm lobulated tumor, and in its structure closely resembles the subcutaneous adipose tissue, consisting of lobules of fatty issue separated by fibrous septa of greater or lesser thickness. More rarely it occurs as a smooth globular mass. Its circumfer- ence is sharply limited by a capsule which is more or less loosely attached to the surrounding parts, so that it can readily be enu- cleated. The true lipoma must be distinguished from diffuse accumula- tions of fat in different parts of the body in the same way that fibroma is distinguished from elephantiasis. Such are the diffuse formations of adipose tissue in the mammary glands and in the abdominal walls in cases of obesity, the accumulation of fat around the kidney, or the polypoid growths on the joints (lipoma arbor- escens). Masses of fatty tissue occur on the fingers and toes in consequence of disease of the spinal cord, and great development of the adipose tissue occurs congenitally in the extremities in cases of gigantism. There are, however, certain diffuse forms of lipoma which deserve the name of tumors and which should be classified as such. Microscopically, lipoma is seen to be made up of adipose tissue containing fat-cells similar to those seen in the subcutaneous tissue, BENIGN TUMORS. 761 but somewhat larger. It is usually developed from adipose tissue, but it also grows where 110 fat is found normally, as in the sub- mucous layer of the intestine. When there is a large amount of fibrous tissue in the new growth the tumor is much firmer, and it is known as fibrolipoma. Another variety is known as myxolipoma where there is a combination of the two allied tissues. In some cases the blood-vessels are very numerous, and a form of erectile tissue may be developed. Birch-Hirschfeld describes such forms of cavernous lipoma in the subcutaneous tissue of the arms of old persons. Combinations may occur also with sarcoma and car- cinoma. The typical circumscribed lipoma is found in the subcutaneous cellular tissue, and it appears as a lobulated soft tumor lying beneath the skin. It is more or less movable, and the lobulated shape may readily be determined by picking up the margin of the tumor between the thumb and finger. It grows slowly, but sometimes reaches enormous size, and then assumes the shape of a pendulous tumor (Fig. 118). The skin on such tumors is coarse and hyper- trophied, and sometimes is cedematous. When these huge growths are allowed to remain unop- erated, the most depend- ent portion of the skin eventually breaks down, and there forms a deep, well-defined ulcer, which extends through the skin, but which does not in- volve the tumor. Hemor- rhage often occurs under these circumstances, and the patient is finally driv- Fig. 118. — Lipoma of Thigh : on the left, skin ulcerated. en to seek surgical relief. The diffuse Upo7na occurs in the neck, and it gives to the patient a peculiar and grotesque appearance (Fig. 119). It was first de- scribed by Brodie, and later by McCormack, Hutchinson, and others. It is called u fat-neck " {Fetthals) by Madelung. The growth begins usually as a tumor situated over the mastoid pro- cess and behind the ears. It may exist on one or both sides of the neck. Finally, it covers the back of the neck, being divided into symmetrical halves by a depression on the median line. It is 762 SURGICAL PATHOLOGY AND THERAPEUTICS. sharply defined above at the superior curved line of the occipital bone, and it eventually grows around the neck, forming large folds at the side and the appearance of a" double chin ' ' in front. In one of Madelung's cases a large lobe extended downward over the clavicle. The tumor-growth spreads downward and below the muscular fibres in some cases, and even between the larynx and the pharynx. Diffuse lipoma appears usually in in- dividuals between thirty-five and forty- five years of age, and chiefly in men. Many of the patients are addicted to the use of alcohol, but in no case is general obesity described. The single case seen by the writer corresponded very accurately with the descriptions and portraits given by other writers. The patient was a middle-aged man ^^m an d a heavy drinker. The tumor was removed at several operations, and, owing to the fact that there was no well-defined boundary to the growth, the dissection was difficult. In no case has there been any return of the growth after removal. Other forms of diffuse lipoma occur congenitally. The writer has on several occasions removed such diffused accumulations of fat from the cheeks of infants and young children. The situation of circumscribed lipomata has been carefully studied by Grosch, who finds that they are most frequently situ- ated on the neck and the shoulders and on the posterior surface of the trunk and the nates, consequently on those portions of the skin where the sudoriparous and sebaceous glands are most sparingly distributed. It is supposed that these glands rely largely upon the adipose tissue for the production of the excretion, and con- sequently unusual accumulations of adipose tissue are less likely to occur where they are found in large numbers. Multiple lipo- mata are also confined to the same localities, and they are often distributed symmetrically. Lipoma is rarely found on the head, but when so found it occurs more frequently on the face, particu- larly the forehead, than on the scalp. The palm of the hand and Fig. 19. — Diffuse Lipoma of the Neck and Abdomen. BENIGN TUMORS. 763 the sole of the foot are localities where it is seen less frequently than in any other part of the extremities. Lipoma is found also in the serous membranes and in the sub- mucous tissues of the mucous membranes. Enormous myxolipo- mata are often developed in the retroperitoneal space. Lipoma of the tongue has recently been observed by Rosenstirn. Lipoma is more frequently found in women than in men, and makes its appearance usually after middle life. Multiple lipomata are occa- sionally developed during childhood. Lipoma is a benign tumor, and it never returns after extirpation. It rarely disappears spon- taneously, even though the patient becomes greatly emaciated. 8. Glioma. Gliomata are tumors that develop from the neuroglia or retic- ular substance which supports the fibres and cells of the central nervous system. Examined under the microscope, they are found to contain a network of extremely fine glistening fibres in which numerous oval nuclei are supported at some little distance from one another. A careful examination of these nuclei shows that they belong to cells which anastomose with one another by numer- ous delicate prolongations. These cells closely resemble the normal cells of the neuroglia, but they are usually larger, and some con- tain several nuclei. It is from the cells of the neuroglia that these growths develop, and not from the nerve-cells (Ziegler). The num- ber of cells in a glioma vary greatly. At times the cells predomi- nate, at other times the fibrous network. The vessels are occasion- ally very numerous. Glioma forms in the brain a tumor that is not easily distin- guished from the surrounding cerebral substance, with which it appears to be more or less continuous. Its presence is recognized chiefly by a swelling and by a diffusion of color. In the cord the glioma appears to form around the central canal, and it often spreads out over considerable portions of the spinal cord. It is usually of a bright-gray color, and is somewhat transparent, or it is a grayish-white or grayish-red, and even of a deep-red color when highly vascular. Gliomata are divided into hard, soft, and vascular forms. The hard form, or fibrog Ho >ma, which is found in the ependyma of the ventricles, is composed principally of a delicate fibrillated inter- cellular substance, and it is often associated with hydrocephalus. It may also occur elsewhere in the brain, and it is sometimes of almost cartilaginous hardness. It rarely attains great size. The 764 SURGICAL PATHOLOGY AND THERAPEUTICS. soft glioma has a bluish-white color, such as is seen in hyaline cartilage, and it is sometimes hard to distinguish in alcoholic preparations from the surrounding cerebral substance, as it usu- ally has no well-defined outline. It often grows to the size of a child's head, being usually found in the white substance of the anterior and posterior lobes of the brain. It contains generally numerous large cells. The small-cell glioma is more vascular, and is particularly liable to hemorrhage. The gliomata may also undergo fatty degeneration and softening. Glioma is found in the retina in children. It contains both round and stellate cells. Eventually it may break through the sclerotic, and metastases may form in the orbital fat, in the diploe of the bones, and in the brain. In some cases metastatic deposits have been described in the liver, the kidneys, and the ovaries, but it is probable that these tumors belong in the group of sarcomata rather than to the gliomata. Neuroglioma ganglionare is a growth composed of neuroglia, of ganglion-cells, and of nerve-fibres, and it may be diffused or be circumscribed. A portion of the tumor undergoes a myxomatous change occasionally, and these growths are then known as myxo- glioma. In other cases there may be a combination with sarcoma (gliosarcoma). Glioma is rarely found in the cerebellum. When extensive degenerative changes occur in glioma it is often difficult to recognize the new formation, which is not suited to surgical interference, owing to its ill-defined outline. The subject of syringomyelia, that has been so much discussed of late in neurological literature, deserves consideration in connection with the general subject of glioma. The prevalent view is that in such cases, owing to a lack of developmental differentiation, there is a growth of quasi-embryonic tissue of the spinal cord specially involving the neighborhood of the posterior commissure and the posterior gray horns. Sometimes, also, there is an imperfect closure of the posterior cleft. Eventually, this gliomatous tissue is liable to break down, giving rise to the formation of cavities which are generally lined with pieces of membrane. This con- dition is commonly met with in the cervical portion of the cord, but occasionally is met with in other parts as well. It is some- times associated with spina bifida and sometimes with hydro- cephalus. The clinical symptoms which are most characteristic are a loss of the sense of pain and of temperature in certain well-defined areas, associated with a relative preservation of the sense of touch. BENIGN TUMORS. 765 There is also a high degree of muscular atrophy, which usually occupies a smaller area than the sensory disorders. The disease is progressive and is not amenable to surgical treatment. 9. Chondroma. Enchondroma, or chondroma, is a tumor which consists of cartilage. It occurs principally where cartilage is found nor- mally — that is, on the bones and in the cartilage of the respira- tory organs — but it mav also be found where there is no car- tila°:e. Virchow divided the chondromata into two forms: those which grow from cartilage, or the ecchondromata, and those which grow independently of cartilage, or the enchondromata. The former class is, however, a small one, the great majority of cartilaginous tumors belonoduor to the class of enchondromata. Enchondroma varies greatly in size. It may appear as a small round tumor or as a large lobulated growth (Fig. 120). It consists of either hyaline cartilage or of fibro-cartilage. The tumor may be in a state of mucous softening or be partially ossified. It may also be composed of osteoid tissue, such as is found in the ossify- ing callus between the bone and the periosteum, and it is then known as osteoid chondroma (Virchow). The tumor consists not only of cartilage, but also of connective tissue, which, however, is usually small in quantity. It separates the cartilage into numerous lobules. At times the fibrous tissue may preponderate to such an extent that very little cartilage is seen. The cells vary greatly in size, in form, and in numbers in different tumors and even in the same tumor. At times they are so numerous as to crowd against one another and leave little inter- cellular substance. They may be exceedingly few in number in other growths. They are often quite large, and contain one or more nuclei and a well-marked capsule. In other cases the capsule is wanting (Fig. 121). In some forms the cells are stellate with anastomosing prolongations: in these tumors the tissue is usually soft, and it has the appearance of myxoma. The intercellular substance is either hyaline or fibrous. Chondroma may be com- bined w T ith sarcoma. Cartilaginous tumors may undergo a mucous softening so far as the intercellular substance is concerned, and the cells in this case undergo fatty degeneration: these changes lead to the forma- tion of cysts. These tumors may also undergo calcification or ossification. At times chondroma may be highly vascular. Chon- 766 SURGICAL PATHOLOGY AND THERAPEUTICS. droma occurs most frequently during youth, at a time when the Fig. 120. — Enchondroma of the Tibia, just below knee-joint (female; duration five years). -■•;;-.: v,--*,^ :••: v.- X *t *'- Fig. 121. — Hyaline Enchondroma (oc. 3, obj. D., and oc. 3, obj. A. ; hematoxylin staining). bones are developing: there is probably some connection between the formation of these tumors and irregularities in the development BENIGN TUMORS. 767 of bones. According to Birch-Hirschfeld, trauma appears to exert a decided influence upon the origin of this form of tumor. En- chondroma is often found on the long bones, and particularly upon the phalanges of the hand or upon the metatarsal bones (Fig. 122). It is observed 011 the larger long bones, on the scapula, on the bones of the cranium, on the jaws, and on the ribs. It is found also in the testicle, the parotid gland, the mammary and submaxillary glands, and the lungs. Virchow has given the name of ecchondrosis to those cartilag- inous tumors that grow directly from cartilage. Small cartilag- inous tumors are found in the thyroid cartilage and in the rings of the trachea, and also in the epiphyseal lines and in articular cartilage. They are found also on the costal cartilages, on the synchondroses, and on the intervertebral cartilages. Those that grow from the articular cartilage are often separated from their Fig Enchondroma of the Thumb. Fig. 123.— Mixed Cartilaginous Tumor of the Parotid Gland. base and wander about within the joint. These tumors are known as "loose cartilages" or "joint mice." They may spring also 768 SURGICAL PATHOLOGY AND THERAPEUTICS. from the synovial membrane or from the periosteum. They give rise to considerable irritation and effusion in the joint, but they may eventually become anchored in some pouch of the articular capsule. If a spontaneous cure does not occur in this way and they continue to give trouble, they should be excised. One of the most frequent of the fibro-cartilaginous tumors is the u mixed cartilaginous " tumor of Paget, which grows in the in- terstitial tissues of the parotid gland. In these tumors are seen numerous cylindrical masses of epithelial cells which are of gland- ular origin. These tumors are of slow growth and are nodular, and they can easily be separated from the tissue of the parotid gland. If allowed to grow, they may eventually attain an enor- mous size (Fig. 123). The hyaline enchondroma is also of slow growth, but it may at times assume immense propor- tions, as shown in the scapula of the patient whose portrait is here given (Fig. 124). The osteoid chondroma has a fibrous appearance. It develops from the periosteum, and it may form a spindle-shaped growth of considerable size in the long bones. These tumors are often sarcomatous, and Billroth pre- fers to classify them with the periosteal sarcomata. Chondroma is a benign growth, but in the rapidly-grow- ing forms the cell-growth is abundant, and the transition from chondroma to sarcoma not Fig. 124-Hyaline Enchondroma of the Scapula, infrequently occurs in portions of the tumor. Metastatic deposits of chondroma are to be distinguished from multiple chondromata, which are occasionally seen. Schuh re- ports the case of a girl, twelve years of age, who had such tumors on all the bones except those of the head and the spine. Chon- dromata show a tendency to break into the blood-vessels and the lymphatics, and portions of the growth are transmitted by em- bolism to distant organs, particularly the lungs. BENIGN TUMORS. 7 6 9 10. Osteoma. Osteoma signifies a tumor composed of bony tissue. There are, however, several forms of bony growth which should not be re- garded as tumors. Such are the osteophytes, which form as the result of an inflammation of the periosteum; the diffuse enlarge- ments of bones, such as have already been studied; and the ossi- fication of tendons and muscles. An osteoma may grow upon the surface of the bone, and it is then called an "exostosis;" or it may grow in the interior of the bone as a firm bony nodule, and it is called an " enostosis. " It may also grow quite independently of bone, and it is this variety which Virchow regards as heterologous. Osteomata are placed in two different classes, according to the character of the bony substance of which they are composed. There are the hard or eburnated osteoma and the spongy osteoma. The most characteristic variety of osteoma dicrum is the ivory exostosis which occurs in the bones of the skull and the face (Fig. 125). It consists of a thick osseous tissue which is arranged in the form of concentric parallel lamellae: in the lamellae the bone-corpuscles are so arranged that their prolongations are directed to- Fig. 125.— Ivory Exostosis of the Orbit. ward the periphery of the tumor. The vessels are exceedingly few in number. The surface of the tumor is nodular and is covered by a thin layer of periosteum. There are also dense forms of osteoma that resemble more closely the structure of cortical bone. The ivory exostosis is found most frequently in the frontal bone, and it encroaches upon both the cavities of the cranium and the orbit, compressing the brain and protruding over both eyes (Paget). These tumors grow in the diploe or sinuses as isolated or as nar- rowly-attached masses. The size and situation of these growths make their removal often impossible, although in the simpler kinds operations have been performed with success. Their slight attach- ment is not infrequently destroyed, and necrosis follows and the tumors may be discharged spontaneously. Hutchinson describes such a growth lying loose in the orbit, which growth after its re- moval left a cavity nearly the size of the fist, over the upper and 49 77° SURGICAL PATHOLOGY AND THERAPEUTICS. Fig. 126. — Osteoma of the Lower Jaw. inner cavities of which the brain could be felt pulsating. The Warren Museum possesses the frontal bone of a patient from whom a portion of such a tumor was removed. The odontoma also consists of a dense ivory structure, and it may spring from the tooth or from the alveolar process. It is often associated with an ir- regularly-developed tooth. Hard os- seous tumors have also been found on the lower jaw (Fig. 126). Osteoma spongiostim contains in its interior more or less well-marked medullary tissue and spongy bone. These tumors are found growing from the epiphyseal lines of long bones, and are usually covered with a thin layer of cartilage. They are attached to the bone by a more or less well-defined pedicle. Some- times they are partially covered by a bursa filled with fluid, which gives them the appearance of being much larger than they really are. The writer has removed such tumors also from the scapula, and they may be found on other flat bones. Another form of spongy osteoma is the so-called ''subun- gual exostosis," which, according to Birch-Hirschfeld, is a perios- teal growth. It is found not infrequently growing beneath the nail of the great toe. This growth also has frequently a cartilag- inous surface. All these spongy osteomata grow to a certain size and then cease growing. With the exception of the last named they give little trouble. Occasionally, however, they reach an unusual size, and cases are reported in which the tumor grew to be as large as a man's head. Osteoma of bone develops either from the connective tissue of the periosteum or from cartilage or from the medullary tissue. Osteoma is also found entirely independent of bone. Such growths have been observed in the brain : they are supposed to develop from the neuroglia, and they have been regarded as an ossifying encephalitis (Birch-Hirschfeld). They also spring from the me- ninges. Bony tumors are found in the eye and in the lungs, and miliary bony tumors are also seen, though rarely, in the skin. Multiple osteomata are seen not only upon the bones of the skull and other flat bones, but also upon the long bones. In regard to the etiology of osteoma, it is supposed by many BENIGN TUMORS. 771 that there is an hereditary predisposition, particularly in cases of multiple osteoma. These tumors appear occasionally after injuries. Syphilis and gout are also supposed at times to exert an influence favorable to the development of bony growths. The prognosis of osteoma is favorable, as it is strictly a benign tumor. 11. Neuroma. "Neuroma" is a term originally applied to a tumor supposed to consist of nerve-tissue. Many of these tumors prove on micro- scopical examination to be composed of nerve-tissue to a limited extent only, the bulk of the growth consisting of fibrous tissue. A new formation of nerve-tissue does, however, occur. The term neuroma fibrillare is used to indicate growths of nerve-fibres. Neuroma cellulare is a tumor consisting of new-formed ganglion- cells. When the tumor is composed of fibres which contain no myelin, it is spoken of as a "neuroma amyelinicum." When the fibres contain myelin, the growth is called "neuroma mye- lenicum." Neuroma cellulare is an exceedingly rare growth. One case is reported as existing in the ala of the nose of a man thirty-one years of age. It is more frequently found in the brain, usually in the lateral ventricle. A growth of ganglion-cells may be found in a teratoma of the ovary or the testicle, and also in congenital sacral tumors. Neuroma myelinicum occurs either as a circumscribed round or lobulated nodule, as a spindle-shaped tumor, or as a diffuse thick- ening of a nerve arranged in knots or in loops. It consists of a mass of firm, grayish-white tissue, composed of interlacing bun- dles of fibres, between which is a moderate amount of loose con- nective tissue poorly supplied with blood-vessels. A microscopic examination shows the myelin-fibres, which are stained black by hyperosmic acid. The amyelinic neuroma is a yellowish or a whitish -gray tumor of considerable firmness, having somewhat the appearance on section of a fibroma. Under the microscope the nerve-fibres with their nuclei can be made out by picking them gently apart (Wini- warter). Neuroma may occur either singly or as a multiple tumor, and it is accompanied by an increase in the connective tissue of the nerve, particularly of the outer (and less frequently of the inner) layers of the endoneurium, so that the bundles of nerve-fibres at the seat of the tumor are surrounded by a loose growth of connec- 772 SURGICAL PATHOLOGY AND THERAPEUTICS. tive tissue. The perineurium may also be involved in this growth, but the epineurium is rarely affected. Such a tumor is therefore, strictly speaking, a neurofibroma. Multiple neuromata may be found existing at several points in a nerve-trunk, or they may be situated in the various branches of a nerve, or they may be indiscriminately distributed throughout the body. A single neuroma is more likely to be painful than the multiple form. The nervous disturbance depends, however, upon the attachment of the tumor to the nerve. If it is so situated that the nerve-fibres are compressed, whether the tumor be central or be peripheral there is more likely to be pain than when the fibres are spread out tape-like over the tumor. Multiple neuromata may be seen as a string of nodules following the course of a nerve- trunk, or as nodular growths spread out beneath the skin in various directions. They are usually movable. If adherent to the surrounding structures, there is a possibility that the growth may be sarcomatous — a combination that not infrequently occurs. Many neuromata are congenital or they appear during the early years of life. They are not infrequently found in persons of defective mental development. Heredity appears to exert an important influence, as multiple neuroma is often seen in various members of a family. Acquired neuromata appear between the ages of twenty and forty years. The so-called "malignant neuroma'''' is usually neurosarcoma or neuromyxoma. There is in these growths a new formation of nerve-fibre, but their principal feature is the malignant element, and these tumors may be the origin of metastatic deposits. The neuroma amyelinicum may suddenly change its benign nature and become converted into a malignant growth. Plexiform neuroma consists of a convolution of numerous bundles of fibres which have nodular swellings at various points, and which are intertwined in a tangled mass. They are held together by a loose connective tissue that lies in a fold of skin, which is hypertrophied and pigmented and covered with a thick, coarse hair. The tumor is congenital, and it is usually situated on the scalp, on the neck, or on the cheek. There is a thickening also of the connective-tissue structures of the skin, particularly those surrounding the vessels and the hair-follicles, such as has already been described in the case of multiple fibromata. The growth is regarded by many as a local congenital elephantiasis of the nerves. The neuroma found in the ends of divided nerves is the form of tumor with which the surgeon is most familiar. Such BENIGN TUMORS. 773 growths occur both in the peripheral and in the central end of a nerve which has been divided in continuity, and are often observed by the surgeon who lays bare the nerve for the purpose of uniting the severed ends. But the commonest form is that found in amputation- stumps, and it is the cause often of intense neur- algic pain (Fig. 127). It is evident that these growths are the result of an abortive attempt at repair of the injured nerve, and there is found here virtually the same process going on which has already been described in the section devoted to the repair of nerve-fibres. There is a growth of the nerve-cylinders, which are imbedded in a mass of fibrous tissue forming around the end of the nerve. Such tumors appear to form in the nerves of the stump of an amputated arm more fre- quently than elsewhere. The excision of a portion of the affected nerve- trunk usually results in a cure of the neuralgia. Occasionally the pain returns. Winiwarter in- vented an ingenious operation to meet the dif- ficulties presenting in an obstinate case. On one occasion he divided the brachial plexus above the clavicle and united the central stumps of the nerves in pairs, so that the peripheral portion should completely be isolated. This operation was successful. A form of tumor which is generally supposed to be a neuroma is the so-called u painful subcittaneous tumor" described by Paget. It is usually found in the extremities, especially the lower. Very rarely it occurs on the trunk and the face. It is seen more fre- quently in women than in men. It consists of a small tumor situ- ated just beneath the skin. Occasionally amyelinic nerve-fibres are found in it, but it may consist also of a loose or a dense con- nective tissue or of fibro-cartilage. Some of these little tumors proved to be leiomyoma and others angioma, and still others adenoma of the sweat-glands. Their structure is therefore not cha- racteristic of any particular variety of tumor, and the pain is prob- ably due to the involvement of some sensitive nerve-fibre in the growth. Fig. ma from an Am- putation-s tump (Sp. 1 154, War- ren Museum). 774 SURGICAL PATHOLOGY AND THERAPEUTICS. 12. Myoma. Tumors composed of muscular fibre are divided into two classes. To the first class belongs the leiomyma, or a tumor made up of un- striped muscular fibre; to the second belongs rhabdomyoma, a much rarer form, which is composed of cells closely resembling striped muscular fibre. Virchow named these two forms "myoma lsevi- cellulare ' ' and * ' myoma striocellulare, ' ' respectively. Leiomyoma is found most frequently in the uterus, and occasion- ally also in the muscular layer of the intestine and the urinary organs. It is also seen, though rarely, in the ovary; it is likewise found in rare instances in the skin and in the subcutaneous cellu- lar tissue. The muscular cells are arranged in bundles which run in straight or in wavy masses more or less parallel with one another. Many bundles, however, are found running at right angles or more or less obliquely to the others. Between these bundles there exists a more or less vascular connective tissue. When properly stained the long staff-shaped nuclei are brought out quite distinctly, and the cells are then seen to exist in great numbers (Fig. 128). The Fig. 128. — Myoma of the Uterus. cells may be isolated by picking them apart in the fresh state, by allowing them to remain for twenty-four hours in a 20 per cent, so- lution of nitric acid, or by placing them for twenty or thirty min- utes in potash. In the small and succulent myomata of the uterus BENIGN TUMORS. 775 the tissue is made up almost entirely of muscular fibre. In the large tumors a considerable portion of the substance of the growth consists of a firm, dense fibrous tissue. These tumors are called " fibroinyomata. " In some cases the connective-tissue growth is soft and areolar, and such tumors are much less dense. Myoma is not usually a vascular tumor, but in some cases the development of blood-vessels is quite marked. In other specimens larger lymph- spaces are found between the bundles of fibres,, and at times there are seen cysts of considerable size, due to a dilatation of these spaces. Nerves are occasionally also seen in these growths. The fibrous portions of these tumors appear as a glistening white, almost ten- dinous, tissue; the muscular portion, as a reddish-white or a gray structure. The growth of these tumors in the uterus is exceedingly slow, but they may eventually assume a greater size than that of any other known tumor. They may be single or multiple. They may grow on the outer wall of the uterus, and in that case they project into the peritoneal cavity. Such tumors are known as subserous myomata. When the growth originates in the middle layers of the uterine wall the tumor is called an "interstitial myoma." Those growths projecting into the cavity of the uterus are known as " sub- mucous myomata." All these forms may occur in the cervix as well as in the body of the uterus. Uterine myoma frequently undergoes considerable changes in volume, increasing materially in size at the period of menstruation. Many of the changes are produced by the increased flow of blood or by a dilatation of the lymph-spaces. A marked decrease in its size may be produced by contraction of the muscular fibre, partic- ularly when it is subjected to the long-continued action of ergot. Uterine myomata may undergo softening. This change occurs in large growths, and it is due to disturbance of circulation. Fatty degeneration and cysts are seen under such conditions. Calcification occurs in old myomata, particularly in those attached by a narrow pedicle. The change takes place in the connective tissue, the muscular fibres undergoing at the same time fatty degeneration. In some cases osteoid tissue is found, and some of these tumors have a bone-like hardness. Many cases of leiomyoma have been reported growing in the stomach and in the intestinal canal. It is only in exceedingly rare instances that they attain a large size. The growth is found in the ovary, and it may produce a large solid ovarian tumor. Such a tumor was recently removed by the writer from a woman about yy6 SURGICAL PATHOLOGY AND THERAPEUTICS. forty-five years of age, and it had a large amount of unstriped mus- cular fibre. It was about the size of a child's head and weighed eight and a half pounds. Many of the cases of enlarged prostate are due to a new forma- tion of muscular fibre. In some cases there is general hypertrophy of all the constituent parts of the gland ; in other cases the glandu- lar structures appear to form the greater part of the growth. The principal seat of the muscular growth is in the upper and posterior portions of the gland in the condition known as hypertrophy of the middle lobe (Birch-Hirschfeld). Myoma of the skin is always composed of unstriped muscular fibres. The development of the new muscular cells takes place either from the muscular walls of the blood-vessels, from the erec- tores pilorum, or from those muscular structures seen in the sub- cutaneous tissue in the scrotum, the labia, the nipples, or the face. Pure myoma of the skin or of the subcutaneous tissue may either be solitary or be multiple, and it usually grows to the size of a cherry. It is moderately soft, and it appears on section as a red- dish-white tissue resembling either a sarcoma or a fibroma accord- ing to its density. It may be found in the scrotum, the labia, or the nipple, or in almost any region of the body. When situated in the skin it appears as a yellowish-red or a dark-red tumor. It is found more frequently in young people, and is probably in most cases congenital. Many of the cases of true keloid are undoubtedly partly muscular in structure; hence they should be regarded as fibromyomata. Combinations of myoma with sarcoma rarely occur. In angioma the walls of the blood-vessels or the vascular spaces are composed of muscular fibre, which frequently constitutes the prin- cipal portion of the tumor. Such a tumor should, therefore, be called " angiomyoma." Diffuse forms of myoma are seen in those cases of hypertrophy of the skin of the scrotum partaking of the character of elephantiasis. Rhabdomyoma, or a tumor consisting of striped muscular fibre, is a rare growth as an independent tumor. It is found more fre- quently in combination with sarcoma. Bands of spindle-cells with striae are then seen. A pure rhabdomyoma contains bands of these cells that are marked more or less clearly with striations. In addi- tion to long spindle-shaped fibres there are seen round or club- shaped cells with or without prolongations (Ziegler). Rhabdo- myoma is found in the testicle, in the heart, and in the muscular system. Myosarcoma is found in the kidney and in the testicle. It BENIGN TUMORS. 777 has been observed also in the stroma of an ovarian cyst and in cer- tain forms of teratoma. 13. Angioma. The name angioma is given to tumors the main portion of which is composed of new-formed blood-vessels. There are two princi- pal varieties of angioma — the plexiform angioma or naevus and the cavernous angioma. In the former there is presented a tumor composed of vessels which have preserved their character. In the latter there are no distinct vessels, but there is a spongy tissue composed of a stroma containing spaces lined with endothelium and resembling the erectile tissue. Plexiform angioma, teleangiectasis, or naevus is of two kinds. The superficial forms of naevus, or "mother's marks," appear either as bright-red or claret-colored marks upon the skin or as slightly raised portions of the skin also stained a deep red. In the former the skin appears to be unaltered as to texture. These dis- col orations appear to be due to an enlargement of the capillary vessels in the papillae from which spring other vessels. The out- line of these spots is either well defined or there are a number of minute prolongations running in varying directions. Minute blemishes of this kind, which are not uncommon on the nose or the cheeks of young children, are popularly known as "spider cancers ' ' (naevus aranaeus), and the larger spots are known as "port-wine marks." Occasionally the skin appears to be hypertrophied and coarse- grained, which is due to hypertrophy of the papillae. These spots appear at or soon after birth, and they may increase considerably in size, but usually they do not materially change. In the cavern- ous form the vascular structure is more developed. Here one finds coils of capillary vessels or arterioles which are grouped together in lobules, and which have apparently taken their origin in the subcutaneous adipose tissue, and gradually worked their way up through the channels of the skin to the surface, where they make their appearance soon after birth. They are raised somewhat above the surface of the skin, and have a bright-red color, with a slightly irregular border. The part beneath the skin is much more extensive than that which appears upon the surface. When pressed upon firmly the vessels are emptied of their blood and the tumor disappears, but it is soon again filled by faintly-pulsating waves. In some of these growths the muscular cells are very numerous, 77 8 SURGICAL PATHOLOGY AND THERAPEUTICS. and the vessels are then usually narrow. These growths are known as "angiomyomata." Sometimes the walls of the vessels are very thin, and they here and there present varicosities. Such conditions are found in angioma of the brain and in a telangiec- tatic condition of certain tumors. Plexiform angiomata, or naevi, are found principally upon the head, the neck, and the chest. They are rarely found on the mucous membrane or on the serous surfaces of the liver, the spleen, or the kidney. They are often multiple. The more vascular forms of nsevus sometimes become very for- midable growths, and they are difficult to arrest in their progress, covering as they do large surfaces and ultimately causing death from hemor- rhage (Fig. 129). Fortunately, this class is rare, and the little tumors if excised do not re- turn. The smallest naevi may be cured by puncture with a hot needle or with the fine point of a Paquelin cautery. The port-wine marks, which are usually too extensive for excision, are not affect- ed by any other treatment. They do not, however, tend to grow beyond a certain point. The cavernous an- gioma is composed of tissue like that of the corpora cavernosa. It is probable that the pure form of this disease develops from the venous capillaries by a process of budding of solid masses of protoplasm, which subsequently became hollowed out and con- verted into cavernous tissue. It is supposed that in some cases the growth develops from the capillaries of the part, which become dilated and fused together. In other cases it is possible that com- munication takes place between previously-formed spaces (lymph- spaces) and the veins. The stroma consists of a connective-tissue trabecular, which surround spaces whose walls are lined with en- dothelium, and in which spaces the blood is largely venous (Fig. 130). It is only in rare cases that these tumors communicate with Fig. 129. — Angioma of the Lip and the Neck. BENIGN TUMORS. 779 a large arterial branch. Nerves are sometimes found in these tumors, and the muscular cells are often seen in large numbers. The tumor appears as a raised and lobulated mass occupying the skin or the subcutaneous tissue, with a more or less well-defined outline. The color is either that of the skin or of a deep-blue shade. When connected with the arterial system the color is a bright red. Naevi are found not only on the surface of the body, but more rarely also in the muscles, the glands, and the bones. Their com- hi Fig. no, -Cavernous Angioma. monest seat in the internal organs is the liver, but they are seen also in some instances in the uterus, in the intestine, and in the bladder. The cavernous angioma is rarely congenital, but it appears rather late in life in the internal organs, and during the first half of life it appears in the skin and the subcutaneous tissue. Many of these tumors are exquisitely sensitive. They grow slowly, but they may become quite formidable and dangerous, owing to their size and to their liability to hemorrhage. The accompanying drawing shows such a growth upon the scalp of a young man (Fig. 131). It was removed by an almost bloodless operation with the Paquelin knife. There were in the neighborhood several smaller wart-like angiomata, which, as they 780 SURGICAL PATHOLOGY AND THERAPEUTICS. Fig. 131. — Angioma of the Scalp. had not increased in size, were not treated. In cases where the growth is too deep for excision the cautery may be used or a deep ligature may be made to encircle the mass. Angioma venosum, or varix, is a tumor composed of dilated veins, such as are seen in hemor- rhoidal tumors. They are found also in the face and the neck and in the scrotum and the labia. Some of these tumors are simply dilated veins; others are probably formed by a new development of venous blood-vessels, particularly those in the face and the neck. Aneurisma racemosum, or cir- soid aneurism, resembles the va- rix closely, but it is composed of dilated arteries instead of veins (varix arterialis). This dilatation is found in arteries of medium size, and principally upon the head, on the upper extremity, and on the back. Most of these tumors are composed of arteries of new formation, and are therefore genu- ine tumors. The growth of new arteries occurs very much in the same way that new vessels form in the healing of wounds. These growths are sometimes most formidable affairs. Such a case occurred in the hospital service of trie late Dr. G. H. Gay. The tumor, which covered the median portion of the scalp, had a prolonga- tion that divided on the bridge of the nose and ran obliquely across each cheek. Near the vertex the mass appeared to consist of one or two large chambers, and radiating from the main body of the tumor were large arteries occupying the seat of the temporal, occipital, and facial vessels. The writer was called to the hospital to see the patient, and he found him with an abdominal tourniquet applied to a rupture on the top of the tumor. On removing this compress a perfect geyser of blood spurted up to the height of a foot into the air. This discharge emptied the sac, which was seized and ligatured. The writer ligatured several of the large arteries. A few weeks later Dr. Gay transfixed the growth with long needles and over them passed figure-of-8 ligatures. The mass sloughed away and left a healthy granulating surface which healed. About fifteen years later the writer removed an epi- thelioma from the nose of this patient, on whom there was hardly a trace of the old scar. A tumor of precisely the same description is given in Ziegler's BENIGN TUMORS. 781 Pathological Anatomy. In the case reported the vessels seem to have fused together, forming in the tumor several large chambers. 14. Lymphangioma. Lymphangioma is a tumor which bears the same relation to the lymphatics that angioma does to the blood-vessels. It consists of a connective-tissue network the meshes of which contain lymph- spaces lined with an endothelium. In addition to the connective- tissue stroma there exists often fibrous tissue and adipose tissue, and occasionally numerous blood-vessels. The following de- scribed three varieties are recognized: The lymphangioma sim- plex, or teleangiectasia lymphatica, which consists of a congeries of dilated lymphatic vessels that are in part a new formation and in part a dilatation of pre-existing vessels : according to Wegner, this variety is due to an obstruction in the lymphatic circulation, and it is analogous to the venous varix; the lymphangioma caver- nosum, which consists of a stroma that surrounds cavities formed by the fusion of pre-existing and new-formed lymphatic vessels and of lymph-spaces filled with lymph (Winiwarter); the lymph- angioma cystoides, which consists of a cyst, simple or compound, filled with lymph, supposed to be formed by the fusion of the lymph-spaces of a cavernous lymphangioma. Lymphangioma is a rare form of tumor. It is frequently con- genital, but it may also be an acquired growth. It is found in the skin and the subcutaneous tissue, and also in the tongue, the gums, and the lips, as well as in the scrotum and the labium. The writer has seen a well-marked cavernous angioma in the skin of the back of an adult and in the axilla of a child. The simple lymphangioma is often accompanied by an oedema and thickening of the skin, which condition has been called "elephantiasis" or "pachydermia lymphangiectatica." Such conditions are found in the scrotum, the penis, the prepuce, the clitoris, the labia majora, etc. It is found also in the tongue in macroglossia, and on the conjunctiva. It often forms a part of the congenital diffuse hypertrophies of the lips and the cheeks. According to Virchow, in tropical countries lymphangiectasia may occur in bunches of lymph-glands. This form of lymphangioma may be circumscribed or be diffuse. Occasionally perforation may- take place at some point, and a lymph -fistula is developed from which a clear serum exudes drop by drop. The cavernous lymphangioma consists of a number of large 782 SURGICAL PATHOLOGY AND THERAPEUTICS. Fig. 132. — Lymphangioma. lymph-spaces communicating more or less perfectly with one another and containing a clear or a milky fluid. It appears as a soft, more or less fluctuating tumor on the face, the trunk, or the extremities, and it is easily mistaken for a lipoma or an angioma, and even after op- eration it is often difficult to decide as to the exact nature of the growth. The accom- panying drawing is a por- trait of the cavernous type (Fig. 132). One of the lobes was aspirated and the child died of septicaemia. Cystic lymphangioma, which is usually found in the neck, is one form of hydrocele of the neck. It should, however, be re- membered that a certain number of these cases of hydrocele are branchial cysts, as has already been seen. The cyst is lined with endothelium, and it may contain either a clear or a bloody fluid. Some of these cysts run in between the muscles. Winiwarter reports such a complicated cyst associated with mic- roglossia. These cysts are situated in the upper part of the neck, and they may send prolongations as far as the mediastinum. In one case which came under the writer's care there was a swelling beneath the angle of the jaw, on opening which swelling a large quantity of clear serum escaped. The ramifications of the cyst were so extensive that it was impossible to follow them. The patient was an adult. Most of these cases of hydrocele, however, are con- genital, but they grow slowly. Congenital cystic lymphangioma is also found between the skin and the sacrum. The operative treatment of these tumors at the present time is not nearly so dangerous a proceeding as formerly, but the direct communication with the lymphatic system renders such cases liable to general septic infection if strict asepsis is not observed. In the cases of hypertrophy wedge-shaped masses should be excised to relieve the deformity. Many of the well-defined forms of lymphangioma can be extirpated: when this is not possible free BENIGN TUMORS. 783 incision should be made, and the cavities should be stuffed with an aseptic or iodoform gauze. 15. PSAMMOMA. Psammoma is a growth usually found on the membranes of the brain, and it contains calcareous concretions. Particles of sand are found in the pineal gland, on the choroid plexus, in the Pac- chionian bodies, and in small bodies on the dura mater. Tumors containing sand are found occasionally also in the lymphatic glands, the thymus gland, and on the capsule of the testicle. They may also be found in sarcomatous and in carcinomatous growths. The particles of sand are scattered over the tumor, and they are found lying either in a connective-tissue stroma which has under- gone a hyaline degeneration, or are surrounded by concentric layers of cells, which, according to many observers, are endothelial in character. The origin of these concretions, according to Birch- Hirschfeld and others, is due to a retrograde change in a growth of bud-like sprouts from the walls of the blood-vessels. The only specimen examined by the writer was a tumor the size of a pigeon's egg which was removed from the dura mater. It was white and had a fibrous appearance. Microscopically, it consisted of numerous concretions surrounded by cells apparently of an endothelial nature. There were numerous fibrous septa which supported this rich cell-structure. The fibrous forms of psammoma are benign growths, but k is well to remember that these concre- tions may also be found in malignant tumors. APPENDIX I. SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. IT is the purpose in this section to consider the methods which have been developed whereby the surgeon is enabled, by the exam- ination of the blood and the various excretions and secretions of the body and the other methods of precision, to have the most exact data possible in order for him to arrive at his diagnosis and prognosis. It is not intended to speak in detail of the methods to be employed in making the examinations, but to consider so far as possible only those processes which will probably throw light upon surgical conditions. The mass of literature upon the various lab- oratory methods and the routine experiments carried on in hos- pitals are most perplexing to the practitioner ; yet from this large amount of material some certain results have been obtained, and it is desired to set forth these so far as possible, leaving the problem- atical questions entirely aside. These latter may or may not find a place among the permanent aids to diagnosis ; but until they do, thev deserve no place in a text-book devoted to facts. The student who wishes to do his own laboratory work is referred for the details of the methods which are here mentioned to Mallory and Wright's Pathological Technique or to Simon's Clinical Diagnosis ; and he is assured that patience and persever- ance will make him sufficiently proficient in making practically all of the important tests which will yield valuable clinical evi- dence for the establishment of accurate diagnosis and prognosis. It is part of every surgeon's duty, in so far as he is called upon to be a diagnostician, as well as an operator, to know what labora- tory methods can be expected to yield him positive results, and to be able to call upon his assistant or an expert to make the report upon the point to be elucidated. He should not send a specimen of blood or urine, or any secretion or excretion, simply on the chance that it may yield some knowledge, but must have a clear idea of the point upon which he wants negative or confirmatory information. No attempt is here made to consider symptoms which, though closely connected with the subject under consideration, really belong to the clinical history of the case. As an example of what is meant, would be the fact that in hemorrhage coming from the bladder, if micturition is painless, it is strongly indicative of tumor of the bladder ; or if from the kidney and intermittent, it strongly points to a new growth. These are clinical observa- tions which are important in the case, but have nothing to do with 50 785 786 SURGICAL PATHOLOGY AND THERAPEUTICS. laboratory observations for the determination of the seat of the hemorrhage. Blood-examination as an Aid to Surgical Diagnosis. — Although a great deal has been written of late years about the examination of the blood, but very little of it is applicable as an assistance to surgical diagnosis. Practically no surgical diseases present pathognomonic blood-conditions ; but in spite of this a good deal of light may be obtained which will be of great value in arriving at a correct diagnosis. As regards anemia : Many people are by no means absolutely deficient in hemoglobin, though they may be very pale. People may also have a very exaggerated idea of the amount of blood they have lost in hemorrhages from the bowels, stomach, uterus, nose, or elsewhere. In cases where there is doubt as to the patient's or friends' statements, the estimation of the hemoglobin will usually determine whether or not there is profound anemia resulting from these conditions. By far the greatest amount of information about surgical condi- tions is to be derived from the white blood-count showing absence or presence of a leukocytosis, and its amount if present. The normal number of white blood-corpuscles, or leukocytes, is about 6000 to 7500 to the cubic millimeter. This is increased in all inflammatory conditions produced by the ordinary pyogenic cocci. The value of such a fact is at once clear, for inflammatory condi- tions are by far the most frequent with which the general surgeon has to deal. Next of importance for the surgeon to remember is that uncomplicated typhoid fever, tuberculosis, and malaria give rise to practically no increase in the number of leukocytes; hence in all those obscure cases where one of these diseases rather than an inflammatory condition could explain an obscure clinical his- tory, the probability would be made all the stronger by finding a practically normal leukocytosis. In the cases of both typhoid fever and malaria this probability can be made certainty by further blood-examination if in the former case the agglutination-reaction is demonstrated, or the presence of the. Plasmodium malarics in the latter. Intestinal obstruction, whether or not of malignant character, usually shows leukocytosis, which is especially apt to be marked in cases of cancerous obstruction. Therefore the blood-count can- not be resorted to in order to give differentiation between intestinal obstruction and intestinal paralysis, resulting from peritonitis, whether general or local. Further, in regard to the acute inflam- matory processes in the abdomen in very light cases, as, for exam- ple, catarrhal appendicitis and salpingitis, the leukocytosis is often small, while the same is true in the severe cases of fulminating appendicitis. So no one should make the mistake, in a case of appendicitis where symptoms all point to severe trouble, that the absence of all leukocytosis or the presence of only a small increase in the white count at all does away with the diagnosis established by the clinical symptoms ; it rather strengthens the diagnosis and may make the prognosis more unfavorable. SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. 787 In cases where a diagnosis has been made of an inflammatory condition or of suppuration, bnt where it seems doubtful whether operative interference is necessary, repeated white blood-counts are of the greatest assistance, an increase in the number of leukocytes denoting an extension of the process and a diminution showing favorable progress toward absorption. Sudden increase in leuko- cytosis is often the first sign of pocketing of pus in or about a wound. This sometimes occurs even before a corresponding rise in the temperature ; or in other cases it will show that the rise of temperature which has been observed is due to extension of the inflammatory or suppurative process, and not to other general con- ditions which might explain the appearance of fever. Where a surgeon is removed from the facilities for making suit- able microscopic examinations, not having the necessary apparatus for making blood-counts and examination of fresh blood, it is well to remember that often a good many points may be obtained by an expert examination of the dried specimen of the blood. One who has done a great deal of blood- work is able from such a prepara- tion to give a very fair estimate of the amount of hemoglobin from the color of the corpuscles, and of the degree of leukocytosis from the proportion of whites that appear in the field. The presence of malarial parasites can also be determined ; while the variety of the leukocytic cells present will give more or less indication, as the case may be, of the actual condition of the patient. The cover-slips for such an examination should be carefully spread and sent by mail to the nearest expert on the blood. Although as much cannot be hoped for as from repeated examina- tions by an assistant at the bedside, yet such examination may help in the diagnosis of some doubtful and perplexing case. When such a specimen is sent it is especially important, as it is also desirable in all cases, to give the examiner as clear an idea as is possible of what is expected. For example, do the red corpuscles show marked loss of hemoglobin? Are there malarial parasites present ? Is there an apparent leukocytosis ? A differential count is not desired unless it should seem necessary. As has been stated in the first part of this section, the surgeon should know what he wants looked for and ask for it. Then, should anything of diagnostic value accidentally appear, the exam- iner is bound to add it in his report. In cases of doubtful cancer of the stomach the presence or absence of the so-called digestive leukocytosis will give a hint as to the functional activity of the stomach ; but as this activity is checked by so many non-malignant conditions it is at best but a hint. Of the chemical constituents of the blood but one deserves special notice from the standpoint of the surgeon. Sugar is a normal constituent of the blood. In certain conditions it is much increased above the normal ; chief of these is carcinoma. Tuber- culosis and syphilis, though showing an increase, are so far below the amount found in cancer that usually they do not cause confu- sion. It seems that this increase in the sugar in the blood proba- 788 SURGICAL PATHOLOGY AND THERAPEUTICS. bly appears early and is not augmented by advancing cachexia. Should one wish for such an examination of the blood for the presence of excess of sugar, half an ounce of blood should be col- lected and be put in four or five ounces of strong alcohol. The time of taking the blood should be marked upon the label, and the mixture should be sent to the analyst so as to arrive within two or three hours from the time it was drawn. Bacteriological Examinations. — The varieties of bacteria found in the various inflammatory processes are often of great aid in both prognosis and diagnosis, and often determine questions arising as to the extent of an operation. The methods are simple by which this information is obtained ; and even where no direct knowledge is gained it is well for each surgeon, as far as possi- ble, to collect such statistics as he can in order that at some time a comparison with other similar work may lead to an advance in our clinical information. A very small outfit is needed to enable one to do all the necessary proceedings : cover-glasses on which smear-preparations can be made, a few test-tubes plugged with cotton and sterilized, and a few brass or copper wires on one end of which a little cotton has been rolled. These sterilized cotton swabs are used to collect pus or other fluids to be examined (see page 160). For obtaining joint, pleural, or pericardial fluid an ordinary hollow needle or small trocar, suitable for the occasion, and an ordinary glass syringe, having a short piece of rubber tubing which serves as a connection with the needle, are all the equipment necessary. This combination is easily sterilized by boiling. The size of the syringe can be graduated to the wants of the individual case ; if, however, one wishes to use a more elabor- ate form of syringe, he will find plenty in the market from which to select. For purposes of study of pathological bacteria by means of cult- ures, blood-serum is the easiest and best medium to employ, and except in very rare instances none other is needed. A few drops of the fluid withdrawn by the needle are put upon the sur- face of the blood-serum or the swab which has been dipped in the pus is drawn over the surface. In most instances the bacteria are so infrequent in the pathological material which it is desired to study, that discrete colonies are formed on the surface of the serum ; and further it is to be remembered that unless the cavity has had a chance of infection from without it is rare to find more than two or three varieties of bacteria. Great care should be taken in secur- ing pus, blood, or serum for cultivation that no corrosive subli- mate, carbolic acid, or other antiseptic comes in contact with it, as very minute quantities check bacterial growth even when they do not destroy it. In some instances where the bacteria are very infrequent animal inoculation has to be employed in order to get a correct diagnosis. This is especially so in cases of tuberculosis, where it may be practically impossible to find the bacilli of tuberculosis and their slow growth makes the culture-method of no value. The guinea- pig is by far the most useful animal for inoculation-purposes. It SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. 789 is always well to use two, so as to have control and provide for pos- sible accidents. Joints. — In the case of effusions into the joints, much may be learned by the use of the needle. Cover-glass preparations will probably tell whether the condition is due to some of the pus-cocci — usually the streptococcus, the Staphylococcus pyogenes aureus, or the gonococcus. Although all may appear within the leuko- cytes, and the streptococcus and gonococcus look very much alike, yet the Gram stain will serve to differentiate them. Should, how- ever, there be no pyogenic cocci found either on the cover-slip or in the cultures, and no bacilli of tuberculosis, it would be well to have recourse to animals to make sure of the presence of tuber- culosis. Should gonococci be suspected, it must be remembered that they require special media for their growth ; but usually they can be found in the cover-glass preparations. The meaning which the presence of the various forms of bac- teria carries to the surgeon may be interpreted in general as fol- lows : Streptococci and staphylococci usually lead to suppurative conditions with destructive processes ; the gonococcus seldom pro- duces more than a serous effusion into the joint and mild inflam- matory reactions. The presence of bacilli of tuberculosis practi- cally always means trouble starting in the bone and from there invading the joint. These considerations, modified as they may be by the clinical picture, determine the action of the surgeon in the individual case he has under consideration. Pleura. — Where there is reason to suspect an effusion in the chest, the needle will show almost always the organism causing the inflammatory process. If the fluid is clear, the pneumococcus is the most common form of bacteria found ; but the bacillus of tuberculosis may also be found in such a fluid. If the culture- tubes planted from the fluid show no growth at the end of sixteen to twenty-four hours, and if the bacilli are not found by means of the appropriate staining-methods, resort must be had to animal inocu- lations. When pus is present in the pleural effusion the tempera- ture and general reaction are usually less with the pneumococcus than with the more virulent staphylococcus or streptococcus, and there is more chance of getting resolution than if these latter organisms are present. Where a large number of organisms are found, communication must have been established with the lung or w r ith an abscess penetrating from without or from below into the pleura. The colon-bacillus points especially to a sub-dia- phragmatic origin of the pus. In all cases the variety of the bacteria found is of prognostic rather than of diagnostic value ; but it is possible to have apparently desperate cases where the presence of pneumococci would decide whether or not to attempt to operate. In addition to what has already been said in regard to the bacteria commonly found in abscess-formation, other bacteria may be found in pure culture or combined with the usual forms. Thus pure culture of the typhoid bacillus has been noted in cholecystitis, and the Bacillus coli communis is common in abscesses about the 79° SURGICAL PATHOLOGY AND THERAPEUTICS. bowels. In liver-abscesses the Amoebae coli may be found, or the hooklets of the hydatid, and at times the yellow calcareous granules of the actinomycetes, which of themselves are sufficient to give an accurate diagnosis of the condition which previously may have been most puzzling. Where anthrax is suspected, the serum from blisters about the wound will often show the bacilli. In pus from an anthrax infection of the neck it is often hard to demonstrate the large bacilli ; but culture or inoculation of a mouse will settle the matter in from twelve to twenty-four hours. UriJte. — The bacteria found in urine containing pus are either bacteria of decomposition, as found in many cases of cystitis, or pyogenic organisms and bacilli of tuberculosis. If pyogenic bacteria have been introduced through the urethra and found their way into the kidney, other bacteria will usually be found with them. In making a diagnosis of tuberculosis of the genito-urinary tract the possibility of mistaking the smegma bacilli for the bacilli of tuberculosis must be borne in mind, and the specimen washed in strong alcohol after passing through the sulphuric acid, instead of through the usual 60 per cent, alcohol. In cases of doubt as to which kidney has been infected the urine should be collected in the manner described in the portion of this section devoted to urine; and if the bacilli cannot be detected by the usual method of examination, some of the urine, with the sediment thrown down by the centrifugal machine, should be injected into a guinea-pig. It goes without saying, that all such urine must be collected with the greatest precautions to insure it from contamination. Urinary Conditions which are of Valne in Surgical Diagnosis and Prognosis. — In every operative case, as practi- cally in all cases, there should be a routine examination of urine to eliminate the possibility of renal degeneration entering in to com- plicate the existing surgical conditions. The presence or absence of a nephritis has its value in the determination of the desirability of an operation and its influence upon the prognosis of the case, all of which are to be found set forth at length in the books upon renal diseases. The urinary conditions, however, which it is pro- posed to study are those where, in the absence of so-called nephritis, whether acute or chronic, a single condition or chain of conditions may give assistance to the surgeon. First of all, we shall consider the amount of urine, which is of slight importance in diagnosis. In America the daily excretion seems to be less than in Europe. Whether this is because the dryness of our climate in summer and the similar condition of our furnace- and steam-heated houses in the winter cause greater activity of the sweat-glands, or whether it is due to other causes, has not been determined. Nevertheless the fact seems to be sure that a healthy man excretes about 1200 c.c. of urine daily, and a woman somewhat less. This amount is often much diminished in those confined by any reason to their room or their bed, and the same conditions affect the solid constituents of the urine. SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. 791 Where the kidneys are particularly sluggish the shock of an oper- ation may be sufficient to produce suppression of urine. In such cases there seems to be a decidedly unanimous opinion that suppres- sion of urine is much less liable to follow operative measures if the urinary excretion can be increased to normal or even to more than the normal amount ; and surgeons feel much safer in operating under such conditions, even though the total amount of solids may have increased but slightly or not at all. The color of the urine will give diagnostic suggestions when it is smoky or dark, suggesting, as it may, the presence of blood-pig- ment or carbolic-acid poisoning ; bile, when the color is greenish or brown. The latter may be present without a corresponding jaun- dice of the skin, and give a hint, otherwise not obtainable, of biliary obstruction. It is well to remember, in this connection, that cer- tain drugs, as carbolic acid and salol, give peculiar color to the urine. In such cases the urine may be dark green or even black. Rhubarb and senna produce shades of brown, and santonin a yellow or greenish tint. Hence a few questions may prevent one being put on the wrong track when attempting to make a diagnosis from the color of the urine. If the coloring-matter in the urine proves to be derived from blood, the case assumes much greater surgical importance. First of all, the distinction is to be made between free blood and blood-coloring matter; between hematuria and hemoglobinuria. Hemoglobinuria, excepting in the case of bums, has little surgical significance; and here it may indicate much greater severity than would be supposed from the external appearances. Hematuria, on the other hand, is of special surgical significance, and demands careful consideration whenever it is found. The blood in the urine may come from any portion of the urinary tract. Bright blood appearing at the first part of micturition, while the urine voided during the latter part is partially or wholly clear, points to the urethra as the seat of the lesion. If, on the other hand, the act of micturition is closed by a few drops of bright blood, the seat of the hemorrhage is probably near the neck of the bladder. The principal vesical conditions giving rise to hematuria are acute cystitis, traumatism, calculus, ulcers, new growths (whether malignant or benign), parasites, and rupture of varicose veins. In case the hemorrhage is profuse, there will be blood-clots. The blood-corpuscles are not usually equally distributed through the urine, and for the most part they are of normal appearance or somewhat crenated. On allowing the urine to stand, the corpuscles tend to sink to the bottom of the glass, leaving the urine above nearly clear, and, if there is no nephritic complication, almost devoid of albumin. Should, however, there be marked alkaline cystitis present, the blood-corpuscles will be found to have lost their hemoglobin and characteristic shape, appearing simply as colorless spheres. That the blood comes from the bladder, may be made certain in doubtful cases by washing out the bladder and then catheterizing again in a short time, when the condition of the blood-corpuscles 792 SURGICAL PATHOLOGY AND THERAPEUTICS. will show whether they come from the upper urinary tract or vesi- cal wall. It is very difficult to decide whether or not the seat of hem- orrhage is in the ureters. The worm-like clots supposed to be indicative of hemorrhage from the ureter may come as well from a hemorrhagic clot extending downward from the pelvis of the kidney. Hematuria arising from the kidney may be due to calculus, new growths, tuberculous ulceration, and trauma, in addition to a number of strictly medical conditions, which must be eliminated. Primary or concurrent renal disease is usually to be determined by the presence of urinary casts, especially if there are blood-cor- puscles adherent to them. At times it may be necessary to make a quantitative estimate of the amount of iron and of albumin pres- ent in a given urine, in order to decide whether there is albumi- nuria greater than that due to the presence of blood in the urine. The same methods to be detailed later in connection with renal pyuria are applicable to determine whether the hemorrhage origi- nates in the right or the left kidney, or comes equally from both. Carefully considered clinical history will often give a definite answer to many of the questions suggested, by finding the symptom of hematuria, and make the subsequent examinations simply con- firmatory. The further study of the sediment may also throw light upon the cause of the hematuria. In some instances shreds of new growth are found ; which should at once settle doubtful cases. The presence of a large crystalline deposit in the sediment would be a finger-mark as to the possibility and make-up of a renal or vesical calculus ; and although it may be unimportant to know what the exact form of salt is which makes up the bulk of the calculus, yet the presence of such a deposit may turn the scale in deciding to operate or not to operate where there is doubt whether the case is one of stone or tuberculosis. Pyuria, or pus in the urine, is distinctly a surgical condition. The pus, like the blood, may come from any portion of the urinary tract. The presence of a drop of pus at the meatus, following pressure along the urethra, indicates a urethritis. That the urethra alone is involved, may be determined by passing the urine into two, or, better, into three glasses, and allowing it to stand. If the pus comes from the urethra, only the first glass or the first two will be cloudy and contain pus in the sediment, while the last glass will contain practically normal acid urine. Should, however, the blad- der be the seat of a cystitis, the last glass will contain as much, if not more, pus than the first. When a cystitis has been present for some time, there is usu- ally an alkaline, foul-smelling urine. Should the urine contain considerable pus, and yet remain acid in reaction, tuberculosis is to be distinctly thought of as the cause, provided this is not contra- indicated by the presence of crystalline deposits, as calcic oxalate and uric acid. In case of marked cystitis, the pus settles as a stringy, sticky, adherent mass at the bottom of the glass. The SC/EXTIF/C AIDS TO SURGICAL DIAGNOSIS. 793 most common causes of cystitis is retention of urine from an enlarged prostate. Here the age and symptoms give the probable diagnosis. The next most common cause, if not of equal fre- quency, will be the introduction of foreign bodies into the bladder (catheters, calculi) or ulcerations (whether tuberculous or from new growths). Sudden increase, followed by a slight or marked de- crease, in the amount of pus probably means that a pus-cavity has opened into the urinary tract and is draining freely. The origin of the abscess must be determined by the clinical symptoms. Further, it must be remembered that in most cases sudden disap- pearance of pus from the urine of a patient who has a supposed pyelitis does not mean that the condition has cleared up, but rather the reverse, bein^ a si^n that the ureter has in some way become POO plugged, and that symptoms from retained pus may be expected within a short time. To determine definitely in doubtful cases whether the pus comes from the bladder or from the kidney or ureter, it is well to catheterize and note the amount of pus in the urine. Then wash out the bladder with a solution of boric acid, continuing the process until the wash-water returns perfectly clear. The patient should be again catheterized at the end of an hour, and the urine so withdrawn compared with that first taken from the bladder. If both urines are of the same or nearly the same cloudiness and thickness, it is probable that there is pyelitis rather than cystitis. Should the question arise whether one or both kidneys are involved, the urine must be collected as it flows from the ureters. This is done by catheterization of the ureters — a most difficult process for one who has not had much practice — or by the instrument of Harris, which appears to answer every* purpose and can be used by anyone at all skilled in the use of instruments. Anesthesia will often greatly facilitate the process. This instrument gives important information where the extirpation of one kidney is con- sidered, showing, as it does, the condition of each kidney. It has happened that the surgeon has removed the only kidney that the patient possessed; but it would seem that in future such an accident should not be allowed to occur. The urethra and the bladder may be examined by the endoscope. Especially is this true of the female bladder, where the larger sized endoscopes make it fairly easy to get an idea of the condition of the mucous mem- brane of the bladder and urethra. Care and judgment must always be exercised to make sure that the instrumentation employed will yield results which shall be commensurate with the personal dis- comfort of the patient and the local irritation of the canals. Chlorides in the urine are said to be markedly diminished in all cases of carcinoma ventriculi. Probably this phenomenon does not occur until later in the disease than would make it of value in diagnosis in early cases when operation for cure might be considered. Nevertheless, it is well to consider the amount of chlorides as confirmatory evidence in cases of suspected cancer of the stomach, remembering that there may be marked diminution also in cases of dilatation of the stomach with hypersecretion of the gastric juices. 794 SURGICAL PATHOLOGY AND THERAPEUTICS. Urea is much diminished in certain liver diseases, and among them carcinoma. Where the separate secretion of the two ureters has been secured, it may prove of value to know which kidney is functionally the better, as found by the quantitative estimation of the urea in each specimen. It may be demonstrated by this means that, though one kidney shows greater activity of the destructive process, the other in reality is less valuable as an excreting organ. Indican in normal conditions is produced in the large intestine; and diseases of the large intestine alone are never associated with increase in indican. If indican is produced in excess of the normal amount in the large intestine, it is due to the action of putrefactive bacteria, either developing in the intestine under favor- able conditions or when the indol-producing bacteria cause an albu- minous putrefaction in certain conditions, as gangrene of the lung, putrid bronchitis, etc. The greatest amount of indican in the urine is found in intestinal obstruction, especially if located in the ileum. This may be a diagnostic hint of the greatest importance, since the amount of indican in such a condition is greater than it would be in local or general peritonitis or in the stomachic condi- tions associated with diminished and absent hydrochloric acid secre- tion, in which cases the amount of indican is also increased. Sulphates are of two groups — preformed and conjugate. The latter are markedly increased in obstructive jaundice, returning to normal when the bile-passages are again opened to the intestine. In cases of non-obstructive jaundice the total sulphates is dimin- ished. These facts may prove of value in getting all possible data for the expediency of an operation in an obscure case of jaundice. Spinal Puncture. — Possibly none of the expedients by which accurate diagnosis is sought for yields such uniformly positive results as does spinal puncture. The amount of the fluid, in the first place, with the addition of leukocytes and blood-corpuscles, shows whether one has to do with an inflammatory or a hemor- rhagic process. The bacteria found in the cells or fluid, or developing when this fluid has been planted upon blood-serum, give the cause of the meningitis. Should tuberculosis appear probable, animal injec- tions have to be resorted to in many cases, in order to demonstrate the bacilli. The presence of blood, leukocytes, or bacteria, as the case may be, is so constant in morbid conditions, that where one gets a negative observation in case of spinal puncture and does not find these elements, it is of much greater value than the usual negative bacterial or microscopical examination. The latter usually means simply not found, but in spinal puncture it means that these diag- nostic elements are not present. No case of accident has been reported from spinal puncture, and in many instances favorable therapeutic results follow withdrawal of the fluid ; hence no one should hesitate to use spinal puncture wherever it seems probable that any information may be obtained as to existing meningeal conditions. SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. 795 Feces. — The microscopic examination of the feces offers but little aid to surgical diagnosis. Pus in quantities sufficient to be seen with the naked eye indicates an active inflammatory process or the presence of an abscess discharging into the rectum. Small amounts seen only on microscopic examination show but little, as any ulceration or inflammatory process will produce some pus ; and therefore, more than confirming the opinion that one has to do with some intestinal or peri-intestinal condition causing ulceration, nothing can be determined. The search for and finding the A?ncebcz colt in the feces in cases where there are symptoms of abscess in or about the liver would be of positive value in diagnosis, giving a definite causal element for the evolution of an hepatic abscess. The presence of other intestinal parasites, or their eggs, in the stools in rare cases may suggest an explanation of otherwise obscure symptoms. Search for the bacilli of tuberculosis in intestinal conditions may give positive results and -prove of great satisfaction. Here it is well to dilute the feces with water, shake them vigorously, and allow them to stand. The portion for examination is taken from the layer just above the deposit of solid materials at the bottom of the jar. Cellular elements, represented by fragments of tissue from an ulcerated surface, do not establish a diagnosis, as there is no way by which cancer-cells can be differentiated from ordinary prolifera- tion-cells coming from any ulceration-process. Blood-corpuscles are never found in the stools, even when the fecal matter is bright red, unless the seat of the lesion is below the ileocecal valve. Practically the only exception to this is where severe hemorrhage occurs accompanied by diarrhoea, as in typhoid fever, where large blood-clots are passed so rapidly that decomposition of the corpuscles does not have a chance to take place. Where small amounts of blood occur, this fact will help to localize the lesion. Microscopical Examination of Pieces of Tissue Suspected of being of Malignant Growth. — The diagnostic and prognostic importance of the examination of tissue suspected of being malig- nant is perfectly clear to all. All tumors upon the surface of the body can be investigated before operation, by securing a piece of the tissue and submitting it to a competent pathologist for exam- ination. In many cases it is possible to have a pathologist present at an operation, and to get from him exact data in regard to the extent of involvement of surrounding tissues, especially neighboring lymph-glands, and so determine the extent to which it is neces- sary to operate. The presence of the pathologist is of great value to the surgeon, who can thus devote his whole attention to the technique of the operation, going ahead in his dissection as long as the pathologist tells him it is necessary. In cases where pieces of tissue are to be obtained for diagnosis, a number of considerations must be complied with to enable the 796 SURGICAL PATHOLOGY AND THERAPEUTICS. pathologist to make a satisfactory report on the question submitted to him. First and most important is that the piece of tissue taken from the suspected growth should be large enough to show clearly the cellular structure. Care especially should be taken, in securing pieces from an ulcerated surface, not to take the hypertrophied tissue alone. In all such conditions, both malignant and benign, the microscopic appearances are too nearly alike to permit of any sure differentiations. A thin piece extending deeply into the healthy tissues is what is desired, rather than a broad superficial portion. In all cases it is necessary to include in the specimen a portion of the normal tissue ; and this must be done even if it involves the necessity of putting in a catgut suture to check the immediate hemorrhage and close the gap. With the complete local anaesthesia to be obtained by the infiltration of cocaine, there is almost no part of the surface of the body that is not accessible for such preliminary examination. In the case of hyperplastic endometritis, where it is frequently desired to determine the character of the scraping from the uterine cavity, it is necessary to observe the same general principles just laid down. The curetting should be carried deeply enough, so that there shall be some portion of the uterine tissue in the scrap- ings. These should be washed in water to remove all the blood- clot, and then the tissue should be rolled into a ball for con- venience in handling and cutting. If there is no doubt that the tissue will reach the pathologist within twenty-four hours and in good condition, it is well to send the specimen wrapped in a damp cloth or piece of gauze, and this packet enclosed in oiled silk or waxed paper. In cases where the specimen might become dried or not reach the laboratory till after this period of time, a small bottle should be filled with alcohol (about 95 per cent), and a small bit of absorbent cotton placed in the bottom of the bottle, and into this alcohol the rolled-up mass of scrapings should be dropped. There should be a label upon the bottle, giving the date, the address, and, not less important, the portion of the body from which the specimen has been taken. Nothing is more provoking to a pathologist than to be asked to examine something with no hint as to what is wanted. In many cases he can tell what is expected ; but this is from long experience ; and time will be saved if it is plainly stated whence the specimen was obtained and what is suggested by the clinical conditions. The same is true of material sent for bacterial examination. Always state where the material comes from, and what forms of bacteria you specially want it examined for, as the methods of examination differ greatly for different organisms. Should, for any reason, it be necessary to keep the specimen for several days before getting it to a pathologist, it is well to change the alcohol each day ; do not be afraid to use a good deal of alcohol. Rontgen Rays in Surgery.— The application of skiagraphy to surgery is necessarily limited, and must remain so, because we are SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. 797 dealing with that which casts a shadow according to the density of the part or object and the impervionsness of the same to the A'-rav. By means of skiagraphy we can determine with almost absolute accuracy the presence of foreign bodies in any part of the body, provided, of course, that the foreign body be opaque to the X-ray. In order to do this accurately, it is necessary to take at least two plates at different angles, as one plate alone may be very misleading. The surgeon may thus be guided as to what opera- tion is best or whether operation is advisable. It is not always necessary to take skiagraphs of foreign bodies, as their presence or Fig. 133. — Fracture of the neck of the femur. absence can oftentimes be demonstrated with the fluoroscope, when by marking on the skin the exact location can be found. Some of the more difficult objects to locate are glass splinters, rubber drainage-tubes, and aluminum splinters. The value of skiagraphy in determining the presence of foreign bodies in the eye is very great, and special apparatus and technique have reached such perfection that it can be done with great accuracy. The next important branch of surgery to which skiagraphy is applied is that of fractures. To have at hand the means by which an accurate diagnosis can be made in doubtful cases or in cases SURGICAL PATHOLOGY AND THERAPEUTICS. where swelling of surrounding tissue is so great that palpation is impossible, is certainly of great value ; and in skiagraphy we have that means. Its application to fractures of the skull is as yet of no value ; and, of course, great difficulty is experienced in fractures of the scapula, sternum, and pelvis. In fractures about the shoulders and hips, owing to difficulty in getting a lateral view, the extent of fracture or displacement often cannot be accurately ascertained (Fig. 133). The above applies equally to dislocations (Fig. 134). The skiagraph is of value not only in confirming the diagnosis of fractures, but also to a limited extent in treatment, as after fracture is reduced the skiagraph will demonstrate the degree Fig. 134. — Dislocated patella. of reduction. The surgeon can thus see whether it is advisable to attempt further correction ; and also as to the advisability of refracture in cases with much deformity. Skiagraphy is also of value in fractures about the joints, in exostoses, bony tumors, and necrosis. The extent of diseased areas can in many cases be dem- onstrated ; also ununited fractures, epiphyseal separations, and congenital dislocations. Spinal caries can also be detected. As yet, comparatively little has been accomplished in detecting renal calculi. Much work has been done, of a very encouraging nature ; but much more must be done in order to convince the surgeon that calculi are present or absent from evidence furnished by the skiagraph alone. Some observers maintain that a positive SCIENTIFIC AIDS TO SURGICAL DIAGNOSIS. 799 diagnosis can be made by this means as to the presence or absence of calculi, no matter what the composition of the stone may be. This lacks confirmation, and certainly seems very doubtful. If true, it shows a wonderful advancement in technique as well as in apparatus, and certainly will be of vast value. Renal calculi have been located by skiagraphy and removed by operation ; but so far only those composed of oxalate or phosphate of lime (see Fig. 135). Fig. :35. — 1, drainage-tube; 2, 3, 4, 5, renal calculi composed of oxalate of lime (case of A. T. Cabot). Uric-acid calculi cast so slight a shadow — barely more than that of the surrounding tissue — that it seems impossible to locate stones of this type by means of the X-ray. Organic matter casts so slight a shadow that it is very doubtful as to the possibility of demonstrat- ing the presence of either uric-acid calculi or gall-stones. The disadvantages of the X-ray in its application to foreign bodies are practically nil, but in regard to fractures there are many. We must bear in mind that a skiagraph is a shadow- picture, and that necessarily in some parts of the body a skiagraph will always show more or less distortion. There is some distortion under the best conditions, and it is a simple matter to exaggerate any deformity or displacement that may exist. This is of consid- erable importance, as already the skiagraph has been accepted as evidence in court. If the skiagraph is to be admitted as evidence, positive proof should be furnished that certain conditions giving correct results have been complied with. Even then the advisa- bility of such evidence is questionable, for in many cases complete reduction of a fracture is impossible, and in many such cases the 800 SURGICAL PATHOLOGY AND THERAPEUTICS. skiagraph is somewhat startling to the layman's eye, yet function- ally the results may be almost perfect. The manipulations of the surgeon may occasionally reveal what the skiagraph fails to do. In such cases a fracture may sometimes be demonstrated by the skiagraph if the surgeon use some force to separate or rotate the fragments. Skiagraphy must, therefore, not be considered an absolute method of diagnosis in fracture, but simply an aid in this branch of surgery. The so-called X-ray dermatitis is produced by long exposure at short range. This complication does not occur when the apparatus is placed at a distance of twelve to thirteen inches from the surface of the body. In 4500 cases of exposure at the Massachusetts General Hospital, ranging from one minute to two hours, no dermatitis occurred. During the period covered by these observa- tions eight cases of dermatitis have been observed, all of which were caused by near exposure. The peculiar form of apparatus employed did not seem to be a factor in the production of the inflammation, as in no two cases was the same form employed. II. SURGICAL BACTERIOLOGY OF THE 5KIN. The surface of the human body is the natural habitat of many different forms of bacteria. The essential conditions for bacterial growth — warmth, moisture, and nutrient material — are all present ; and in spite of a certain amount of germicidal power which has been found in certain cases to be present in the skin (Binaghi) abundant culture-growths can be obtained from the skin of every individual. Some parts of the body, as the axillae and the sub- ungual spaces, afford more favoring conditions for growth than other more exposed parts, and there seems to be also a variation to a certain degree between one individual and another. The con- stant presence of bacteria, however, upon the surface of the human body has led to much study in connection with wound-treatment and aseptic surgery. The pathogenic bacteria most commonly found upon the sur- face of the body are as follows : Staphylococcus pyogenes aureus, albus, and citreus (Passet) ; Staphylococcus epidermidis albus (Welch), Staphylococcus viridis flavescens (Babes), Staphylococcus cereus albus (Tavel), Staphylococcus cereus flavus (Passet), Staphy- lococcus gilvus (Robb), Micrococcus tetragenus, Streptococcus, Bacillus pyocyaneus (Gottstein), Bacillus proteus (Binaghi), Bacil- lus coli communis (Binaghi). In addition to these forms, almost any of the other bacteria which are pathogenic to man may be found under certain conditions, although so rarely as safely to be disregarded in connection with wound-infection. The bacterium most commonly met with in skin bacteriology SURGICAL BACTERIOLOGY OF THE SKIN. 801 is without doubt the Staphylococcus albus ; and a form of this organism has been described by Welch as being a constant inhabi- tant of the follicles and the deeper layers of epithelial cells of the human skin. That this organism differs essentially from the Staphylococcus pyogenes albus is not definitely decided ; but the probability exists that the form described by Welch is rather an attenuated form, and that under such favoring conditions as are afforded by the presence of drainage-tubes or necrotic tissue in a wound, the pus-producing function may be acquired. The Pyogenes aureus and the streptococci also vary in viru- lence, although not reaching such a degree of attenuation as the albus. As a rule, they always produce pus. Many instances are cited, however, where, although aureus was present in wound-secre- tion or upon stitches, healing proceeded uninterruptedly by first intention. The Bacillus pyocyaneus is another germ which appears fre- quently in septic wounds, giving the characteristic blue or green color to the pus ; and it is interesting to note that this is one of several bacteria which especially endure drying and can be trans- ported for long distances in currents of air (Neisser). The characteristic peculiarities of these several forms of bac- teria will be found elsewhere (under the section on Surgical Bac- teria), and no further discussion of them is necessary in this con- nection. The constant endeavor in surgery has been to obtain perfect wound-healing. The greatest contribution to this end was un- doubtedly the work of Lister, and his use of carbolic acid marked the beginning of modern surgery. Since that time, however, one germ after another has been found to be capable of setting up sup- puration in a wound, and we have come to look upon perfect wound-healing as demanding absolute asepsis — the total absence of bacteria. Healing by first intention, however, does not in the least imply a total absence of bacteria : it implies rather that there is present in the wound only such a quantity of bacteria as can be overcome by the natural germicidal power of the tissues and the wound-secretions. This germicidal action of fresh wounds is found to be most powerful in the first twenty-four to forty-eight hours, and it is found to differ in individuals, and probably in the same individual at different times (Schloffer). Furthermore, the conditions which favor bacterial growth, such as necrotic tissue, "dead " spaces, and foreign bodies, as pointed out by Welch, vary in different wounds ; and it is readily understood that with so many varying conditions the desired first intention may fail in any given case and the reason be difficult to find. The surgeon, how- ever, who realizes the dangers of all these conditions, and so acts in any given case as to avoid as many as possible of the conditions favoring wouud-infection, will obtain the best results. Avoidance of Wound-infection. — Absolute and continuous sterility of the field of operation, both superficially and in the deeper layers of the epidermis, seems with our present methods to be unattainable. The number of germs, however, and their 51 802 SURGICAL PATHOLOGY AND THERAPEUTICS. vitality can be markedly diminished by several procedures, both mechanical and chemical. Mechanical. — (a) Scrubbing with a clean brush and soap and water. This removes gross macroscopic dirt ; masses of fat in which germs are imbedded and protected from the antiseptic solu- tions we wish to use later ; the actual germicidal power of soap solutions is too weak to be worthy of attention. (b) Shaving. — Removing the hair and also the outer scales of the epidermal layer. Chemical. — (a) Cleansing. — Here again soap and water must be considered, by reason of the solvent action on fats ; this action, however, being inferior to that of alcohol or turpentine. Alcohol combines, with the cleansing action, a certain antiseptic power also, and seems to prepare the way for the better action later of the antiseptic solution. It mixes readily with water, and as such is to be preferred to ether. Turpentine is irritating and inferior to alcohol. Alcohol is best used in 80 to 90 per cent, concentra- tion. (b) Disinfection. — The number of drugs which have been found to have a germicidal action upon bacteria are so numerous that a detailed account of the value of each is beyond the scope of this section. In a general way, however, the drugs used in surgery fall into one or another of the following classes : 1. Mercurials : bichloride, iodide, oxycyanate. 2. Carbolic acid group : carbolic acid, sulpho-naphthol, lysol. 3. Gases : chlorine, formaldehyde. ^4. Silver and its salts : lactate, citrate, nitrate. 5. Other drugs : permanganate of potassium, oxalic acid, per- oxide of hydrogen, iodoform, boric acid, etc. Corrosive sublimate, or bichloride of mercury, is the antiseptic agent most frequently used in surgery, and may be regarded as the type of the mercurial antiseptic. It is effective in killing germs when it can be brought into close contact with them in a strength of 1 : 20,000. In actual practice, however, much greater concen- tration is necessary, as the bacteria lie imbedded in fat and dirt, and are not readily accessible to the germicide on the surface of the body. When used in wounds corrosive sublimate has two disad- vantages — first, that the body-tissues enter into chemical combina- tion with the mercury and form an insoluble and inert albuminate; and secondly, as shown by Halsted, that the use of even very weak solutions produces a necrosis of the superficial layers of the tissue with which they come in contact. The first of these disadvantages may be overcome by the addition of common salt or of ammonium chloride to the solution, whereby the albuminate is less readily precipitated; but for the necrosis there is no help. Carbolic acid is the original antiseptic introduced by Lister. It is germicidal in a strength of 1 : 100. Its chief advantage is its ability to penetrate greasy substances, and its chief disadvantage its irritative properties, both local and remote. It is readily absorbed, and produces toxic symptoms, chiefly in the kidneys. To this group belong lysol, kresol, and sulpho-naphtol, both less SURGICAL BACTERIOLOGY OF THE SKIN. 803 potent and less irritating- than carbolic acid. Lysol is used by Mikulicz in 1 per cent, solution. Sulpho-naphtol may be used in 2 per cent, solution. The gases, formaldehyde and chlorine, have been used only recently for disinfection of wounds, although long known to be powerful disinfectants. They are very effective germicides, but unpleasant and undesirable on account of their irritating fumes. Formaldehyde is now used as formalin (a 40 per cent, solution of the gas in water). Formalin, 1 part to 100 of water, is used on the surface of the body, and gives a sterile operation-field in 80 to 90 per cent, of the cases. This is as much as can be claimed for any method of skin-sterilization. Applications of this strength must not be allowed to remain over twenty-four to thirty-six hours in contact with the skin, as a hardening of the skin will follow, and delayed union or even necrosis result. Weaker solutions are used for irrigation and dressings, but cause considerable pain. Glutol (formalin-gelatin) is also used for dressings, and has marked anti- septic properties. Nascent chlorine is used, as suggested by Weir, in preparation of the skin of the patient and of the surgeon's hands. A tablespoonful of chlorinated lime and the same amount of washing-soda are placed in the palm of one hand, and enough sterile water added to form a creamy paste ; this paste is rubbed into the skin for about five minutes and is then washed off with sterile water. A large percentage of sterile results is claimed for this method, but the fumes of the nascent chlorine are very irritat- ing and decidedly disagreeable. The salts of silver are used to a much greater extent as anti- septics abroad than in America. The expense and the need of freshly prepared solutions at frequent intervals have worked against their adoption in this country. The citrate (itrol) and the lactate (actol) are effective germicides in 1 : 1000 solution, and are to be preferred to argonin and argentamin (Blumberg) and to the com- mon silver nitrate. Permanganate of potassium and oxalic acid used in sequence, as recommended by Schatz, and later by Kelly, are effective in satur- ated solution, but are very, irritating. The use of peroxide of hydrogen to complete the oxalic decolorization diminishes the annoyance to a certain extent without loss of effect, but the irrita- tion caused to the surgeon's hands by this method, when used as freely as a busy hospital-service demands, is a serious disadvantage. Salicylic and boric acids, styrone, iodoform, and other drugs have a certain amount of antiseptic power, but cannot be relied upon to kill the bacteria in any concentration which it is possible to use. They rather retard the growth of bacteria, and are of more value in wound-treatment than in obtaining sterile surfaces. This retarding of the growth of bacteria has been studied by Welch, who finds that even corrosive sublimate may have only a temporary germicidal action, and that a certain number of the germs may be resuscitated, as it were, by the application of chemi- cals, like ammonium sulphide, which precipitate the mercury and allow the bacteria to come to life again. This suggests a union 804 SURGICAL PATHOLOGY AND THERAPEUTICS. of the mercurial salt with the germ-envelope, or some such chemical reaction, which inhibits growth so long as the combina- tion exists, but does not totally destroy the living organism. Absolute asepsis in surgery is a goal toward which every one must strive, but which few can attain. This is not hard to believe, when we consider the number of factors which enter into the ques- tion. First, the skin in which the wound is to be made contains countless germs, many of which if inoculated in sufficient quantity may produce suppuration. Secondly, the hands of the surgeon are of necessity subject to repeated contaminations and are extremely difficult to render absolutely sterile. Thirdly, the air of the operating-room is a source of infection which cannot with perfect safety be disregarded. Inanimate objects, which can be subjected to dry heat or steam, or which are not injured by the application of concentrated solutions of certain germicidal power, can be made absolutely free from living bacteria, and all that then remains to do is to keep them sterile. Instruments can be boiled, silk and gauze can be steamed; but the living tissues of the patient and the hands of the surgeon can obviously be treated with neither steam nor heat. Even the stronger and more certain germicides are useless for this purpose, because of their caustic and irritating effects upon all living tissues; and the sterilization of the patient's skin and the surgeon's hands is thus the greatest problem at the present time in surgical technique. We have seen, however, that absolute asepsis is not needed for the best results .in surgery. Primary union can be obtained with a certain number of bacteria in the wound; and the surgeon must therefore rely upon the patient's tissues to dispose of the few germs which, in spite of his best efforts, will occasionally reach the wound during the operation. The methods adopted by those whose statistics show the best results must, therefore, be taken as the standard of surgical procedure, and for this reason a short resume of several methods of technique may here be given : Operation-field. — i. Alcohol and Corrosive Method. — (a) Shave ; (b) Scrub with potash soap and soft hot water for five minutes ; (c) Alcohol, 90 per cent. ; scrub for three minutes ; (d) Corrosive sub- limate, 1 : 1000, for eight minutes. 2. Nascent Chlorine Method. — (a) Shave ; (b) Scrub with soap and water for five minutes; (V) Washing-soda, jounce; chlorinated lime, y 2 ounce, mixed and diluted to a creamy consistency with water, and rubbed into the skin for three minutes; (a) Wash with sterile water. 3. Permanganate and Oxalic Method. — (a) Shave; (b) Scrub with soap and water for five minutes, rinse off; (c) Saturated solu- tion of permanganate of potassium for two minutes; (d) Hot satu- rated solution of oxalic acid till stain is nearly gone; (e) Peroxide of hydrogen to complete decolorization ; (f) Corrosive sublimate, 1 : 1000, for two minutes. These three standard methods may be modified in many ways and to suit the taste of the surgeon or the peculiarities of the indi- vidual case. A poultice of green soap (one teaspoonful to the pint SURGICAL BACTERIOLOGY OF THE SKIN. 805 of water) may be applied after shaving the part, and be allowed to remain for from four to twelve hours before the antiseptic solutions are applied. A minimum number of bacteria, however, may be expected to survive in the deeper skin-layers in a certain percent- age of cases after every one of these preparations. 4. Formalin. — (a) Shave ; (b) Scrub with soap and water for five minutes ; rinse off; (c) 1 per cent, formalin solution, by poul- tice, for twelve to thirty-six hours (frequently changed) ; (d) Alco- hol, 90 per cent., for one minute ; (e) Corrosive sublimate, 1 : 1000, for two minutes. By this method the formaldehyde-gas penetrates the follicles and deeper layers of the skin, and, as reported by Landerer, gives a sterile operation-field in 80 to 90 per cent, of cases, or primary union in 100 per cent. (Brewer). Care must be taken that the formalin solution be not in contact with the skin for more than twenty-four to thirty-six hours, as a hardening of the tissues and delayed union may result. Surgeon's Hands. — Any of the above methods of skin-disinfec- tion, except formalin, may be used for the sterilization of the sur- geon's hands, and large numbers of culture-tests are reported to prove the efficacy of each method. As a fact, however, surgeons have felt so little confidence that absolute safety could be obtained by these methods in every case, that various methods for covering the hands have been advocated, and the operating-glove has obtained a place in the surgeon's list of apparatus. Halsted introduced rubber gloves in 1889, first for his assist- ants, and later for himself. The rubber glove is impervious until torn or punctured, and can be boiled and sterilized to a certainty. For such operations as do not require the utmost delicacy of manipulation, the rubber glove gives admirable security against infection from the surgeon's hands. Mikulicz sought to obviate the annoyance of the rubber glove by substituting common white-cotton gloves, which were sterilized by steam; and this procedure has been widely adopted. When wet with blood, cotton gloves are readily pervious to bacteria, how- ever; so that, to be other than a source of danger, they must be fre- quently changed during the operation, and the hands prepared as carefully as when operating without gloves. Paraffined gloves and leather gloves have been used; but they offer no especial advan- tages over rubber and cotton gloves. Doderlein found that the hand remained sterile inside the rubber glove; and argues from this that the germs found so uniformly on the operator's hand at the close of the operation come rather from the air and the imper- fectly sterilized skin of the patient than from the sweat-glands of the operator's hands. Whatever the source of the infection, it seems certain that the glove is a powerful agent in securing union by first intention and in protecting the hand of the operator from infection, and, as such, is a valuable addition to surgical tech- nique. Infection of wounds from the air was thought by Lister to be of frequent occurrence; and it was to prevent this infection that 8o6 SURGICAL PATHOLOGY AND THERAPEUTICS. the carbolic spray was designed. Later, however, when more emphasis was laid upon the hands and patient's skin, as carriers of infecting germs, less weight was put upon air-infection ; it is only comparatively recently, from the investigations of Flugge, Neisser, and others, that we have been taught that the air itself, and the fine droplets of moisture which are present in the surrounding air when laughing, talking, or sneezing occur, may carry a consid- erable number of pus-producing organisms and deposit them upon the wound. Mikulicz and others wear masks of fine gauze while operating, to avoid this manner of infection. The mask is in itself so irksome an appliance that we may feel at liberty to disre- gard this additional precaution in the greater number of cases, while improving our technique in other directions ; provided always that the surgeon recognizes the danger of talking or cough- ing, and avoids them as much as possible. Gauze and linen for sponges, dressings, gowns, tozvels, etc. can be sterilized by steam under pressure or in the Arnold sterilizer ; best of all, perhaps, by the fractional method of half an hour on three successive days. By this method the spores which are not killed at the first heating grow into adult forms in the interim, and are killed at the second and third sterilizations. Copper canisters, or even cotton-cloth wrappers, will protect for at least four weeks dressings sterilized in this way. Instrume?tts may be sterilized by boiling ten minutes in water to which have been added a few teaspoonfuls of sodium carbonate, or by exposing to formaldehyde- vapor from ten to fifteen minutes. The latter method is recommended for fine instruments, as in oph- thalmology, because it does not injure the cutting-edges ; but, for simplicity, boiling is much to be preferred, and little injury to the instruments will result if the addition of the soda be rigidly ad- hered to. In addition to protecting the instruments from rust, the soda increases the efficacy of the sterilization, as shown by Schim- melbusch, by its solvent action upon the gross dirt and the pro- tective envelopes of the germs. Sutures and ligatures have probably caused as much discussion in surgery as any other factors entering into wound-treatment; and undoubtedly more unjust accusations have been brought against them, whether silk or catgut, than they deserve. As a fact, any ligature-material can be rendered aseptic before it is placed in a wound ; and where the material is thought to have been septic, from failure of primary union, in many cases the cause is to be sought rather in an infection of the material by the surgeon or by the patient's skin at the time of operation. In this connec- tion, catgut is far more liable to produce trouble than silk, because of the fact that catgut is in itself a favorable medium for the growth of bacteria, while silk is not. Add to this the fact that a catgut strand needs to be two or three times as great in diameter as a silk one of the same strength, and it is obvious that the larger foreign body is the one more liable to favor infection. With absolutely sterile hands and operation-field, catgut is as little liable to produce suppuration as silk ; catgut may be sterilized by TREATMENT OF WOUNDS. 807 any one of several methods, that by boiling in cumol, as modified by Clark and Miller of Baltimore, being perhaps the best. 1 Silk and silkworm-gut can, of course, be boiled or steamed, and are therefore to be relied upon. A recent modification of suture-material has been introduced abroad, and is perhaps a return to earlier principles in that the antiseptic rather than the aseptic suture is coming to the front again. This is due to the general realization of the fact that the deep layers of the epidermis cannot be rendered aseptic in every case with any one of our present methods of preparation, and to the desire on the surgeon's part to prevent the growth of those germs which he is at present unable to kill. For this purpose iodoform, alcoholic and silver preparations of silk have been de- vised ; but, owing to the retarding action of all antiseptics upon cell-growth and wound-healing, there is much to be said in opposi- tion to them as well as in their favor. Catgut is to be preferred to silk where suppuration is inevitable. Silkworm-gut is the best material for skin-sutures, its greatest advantage beins: due to the fact that it is non-absorbent and readilv sterilized. The manner of sterilization is unimportant, as any one of the recognized methods will give sterile results if properly carried out. Absolute asepsis, then, is an ideal; and, however much desired, cannot be obtained in every wound with our present methods of procedure. Fortunately, however, this absolute degree is not essential for perfect wound-healing, and many series of cases are now reported in which healing by first intention occurred in 100 per cent, of the cases. The greatest obstacles to continuous asepsis are the skin of the patient and that of the surgeon's hands. The procedures, however, described above have already succeeded, in the hands of certain surgeons, in producing perfect results ; and a pains- taking adjustment of these precautions in every individual case should never fail to reduce the number of bacteria to a quan- tity so small as to be easily conquered by the natural resistance of the patient. TREATMENT OF WOUNDS. The end and aim of all wound-treatment are to obtain perfect healing — a rapid union of the surfaces in apposition with as little 1 The Kr5nig method of catgut sterilization, as modified by Clark and Miller of Johns Hopkins University, is as follows : 1. The gut is cut in suitable lengths, and several pieces are wound into figure-of-eight shape, of a size to fit into an ordinary test-tube. 2. These pieces are placed on cotton in a jar and gradually raised to 8o° C, at which temperature they remain for one hour, to drive off all water. 3. The catgut is then placed in cumol at ioo° C, in a vessel surrounded by a sand- bath, care being taken that the catgut does not touch the sides or bottom, but rests upon wire gauze or cotton. The temperature is then gradually raised to 165 C, and kept there for one hour. 4. The cumol is poured off. and the heat of the sand-bath allowed to dry the catgut. 5. The dried catgut is picked up with sterile forceps and placed in test-tubes which have been previously plugged with cotton and sterilized, and in this way is kept until used. 808 SURGICAL PATHOLOGY AND THERAPEUTICS. systemic disturbance as possible. The measures at our command are practically those which have been discussed in the section upon Skin Bacteriology, and their application alone requires modification to suit the individual case. In a wound of any sort, whether made by the surgeon's knife, under practically aseptic conditions, or by an accidental injury, under conditions not at all aseptic, certain principles of treatment, if faithfully carried out, will be found to contribute much toward a union by first intention. i. The wound must be made clean of foreign matter, both gross dirt and microscopic germs. 2. Necrotic or strangulated tissues, of uncertain vitality, must be removed. 3. The wound must be dry, and hemorrhage must be effectu- ally controlled. 4. Where copious oozing is inevitable, or where doubt exists as to the cleanliness of the wound, provision must be made for the escape of fluids. 5. The cut surfaces must be brought together under as little tension and with as few stitches as possible. 6. A proper covering must be provided to absorb discharges and protect the wound from contamination. 7. The wound must be placed and kept in a position such that tension is relieved and motion restricted as much as possible. These principles of wound-treatment may be observed in widely different methods and with many different agents, according to the resources and taste of the surgeon and the needs of the individual case ; but the principles remain the same, and are not with safety to be disregarded. Cleanliness. — Wounds made by the surgeon under aseptic condi- tions may need no cleansing whatever at the close of the operation: after any prolonged operation, however, a flushing of the wound with warm sterile salt-solution (NaCl 3J to water Oj) will carry off certain of the germs which have entered the wound in the course of the operation, and will in no way retard the healing process. Wiping the cut edges of the skin with stronger antiseptics, as 2 per cent, peroxide of hydrogen or formalin, is recommended by some surgeons, in order to destroy such germs in the deeper layers as may have escaped the preliminary preparation, and threaten the failure of first intention by stitch-abscess. Wounds made under non-aseptic conditions, however, require much more painstaking cleansing, and the time spent in these procedures may often determine the question of life or death to the patient. Not the wound alone, but the skin of the surrounding parts, must be made as nearly aseptic as possible, unless the de- lay is directly contraindicated by such a condition of hemorrhage or shock as to threaten life. The hair of the surrounding skin must be shaved, and the skin surface scrubbed with soap and water, and then with 90 per cent, alcohol. Where greasy sub- stances, as oil or wheel-grease, are present near the wound, as upon the hands of an engineer or mechanic, a 1:10 solution of liquor TREA TMENT OF WOUNDS. 809 sodce chloratae may be used with very good effect. After these preliminary steps the wound must be thoroughly laid open, so that all parts exposed to outside contamination during the injury may be subjected to the irrigating fluids. For the irrigation of accidental wounds, corrosive sublimate (1: 10,000), carbolic acid (j4 per cent.), or formalin (1:300) may be used ; all of these solutions will delay healing to a certain extent, and are to be followed by salt-solution or boiled-water irrigation to remove the antiseptic. While irriga- tion is being carried out the wound must be thoroughly explored with forceps or director, and any gross foreign bodies, like bits of cloth or gravel, are to be removed. Irrigation of from five to ten minutes will generally be sufficient to insure clean healing in acci- dent cases when performed within an hour or two of the injury. Necrotic Tissue. — Tissues which have undergone such a degree of bruising or so great a loss of blood-supply as to give no prom- ise of surviving the injury, must be sacrificed in the interests of the patient. Sepsis is greatly favored by the presence of necrotic tissue, and only with absolutely certain asepsis can doubtful tissues be allowed to remain in the wound. Bruising of tissues is not confined to accidental wounds, but occurs in many operations where it might be avoided by the surgeon by a more rigid adher- ence to the proper principles of wound-treatment. The cuts of the knife should be made clean and straight. Blunt instruments and fingers should be used as little as is compatible with safety, and two cuts should never be made where one would have been sufficient. Buried stitches should be tied only tight enough to serve the purpose of approximation of the parts; and it should be remembered that the swelling which follows every operation will tighten a loose stitch, and perhaps cause a strangulation-necrosis in a tight one. In the choice between absorbable material and silk for ligatures and sutures, much must be left to the personal taste and experience of the operator. Silk is known to be absorbed in the course of time; but where germs are present in sufficient quan- tities to set up suppuration this absorption does not occur in time to prevent the opening of the wound and the discharge of the ligature. On the other hand, silk is a less favorable culture-medium for bacteria, and a smaller strand will give the necessary strength. Silk may be sterilized easily at the time of operation, while animal sutures require more elaborate preparation. The length of time during which an animal suture may be depended upon varies within wide limits. Cases are reported, on the one hand, where catgut ties gave way and allowed fatal hemorrhage from the uterine artery on the eighth day; and, on the other, chromicized catgut sutures have been removed intact from a hernia-wound four years after the operation. The use of animal sutures in the service of some of the sur- geons of the Massachusetts General Hospital is as follows : 1. In cases of undoubted sepsis catgut is used for deep stitches and ligatures, except where large arteries require ligature. 2. In cases of undoubted asepsis silk is used throughout. 3. In skin-sutures silkworm-gut is used almost exclusively, either interrupted or continuous or subcutaneous. 810 SURGICAL PATHOLOGY AND THERAPEUTICS. 4. For sutures in mucous membranes, as the mouth or the vagina, catgut is used to avoid the necessity of removal. Dryness of Wounds. — Fluids collected in a wound force the sur- faces apart and delay or prevent healing in proportion to the amount of fluid present in any given case. The secretion of a clean wound has been found to possess a certain germicidal power for the first twenty-four to forty-eight hours ; but this power is not sufficient to protect the individual from the inoculation of any large number of bacteria, and after forty-eight hours the wound- secretion becomes a most favorable culture-medium for bacterial growth. For these reasons, oozing of blood, as well as more active hemorrhage, must be controlled by pressure of dry gauze sponges, preceded if necessary by a douching with salt-solution at 118 F. Active hemorrhage must be controlled, of course, by pressure- forceps; but care must be used to pick up only the bleeding point itself, and to save the surrounding tissues as much as possible from laceration. Blood-vessels which are not occluded by the temporary use of pressure-forceps will need ligature; but in each case the finest strand of ligature-material must be used which will bear the strain, in order that the amount of foreign material left in the wound may be reduced as much as possible. The application of pressure after closure of the wound contributes also to the pre- vention of hemorrhage and serous oozing. When copious oozing of blood or serum is unavoidable, as in wounds of large extent and in parts that are especially vascular, or where, as in thyroidectomy, pressure cannot be safely applied, some form of drainage is indicated to allow the escape of fluids. The materials used for drainage are tubes of glass or rubber, strands of gauze and wicking, and solid material like silkworm-gut. The tubes are rarely needed in clean cases; a small piece of gauze, folded in such a way as to prevent the ravelled edges remaining in the wound, or a bit of wicking will be sufficient to carry off the excess of fluid into the outer dressing. In many cases this wick may be removed at the end of twenty-four hours, and the skin closed at the point of exit by a " provisional " suture placed at the time of opera- tion, but left untied at the time w r ith this end in view. In this manner the advantages of drainage may be obtained without the sacrifice of primary healing. Where doubt exists with regard to the cleanliness of a wound, or when a wound opens an abscess-cavity or is undoubtedly septic, drainage becomes a matter of more than temporary expediency, and drainage-material must be adopted suitable to the amount and character of the discharge. Here tubes of glass or rubber are of decided advantage, and a system of double tubing which will allow of frequent flushing out with some antiseptic fluid is often much to be recommended. Rubber tubing, after a thorough washing in soap and water, may be sterilized by boiling for ten minutes, and kept for use in a 5 per cent, carbolic acid solution. Glass tubes can be boiled with the instruments, and are particularly valuable for deep abdominal drainage in that they are not collapsible. When used in this way, however, the glass tube should be sur- TREATMENT OF WOUNDS. 811 rounded by several layers of gauze, to prevent erosion of the intes- tines. An efficient adjunct to the use of drainage-tubes in abdominal cases is a small glass syringe and a rubber catheter, with which the nurse can at frequent intervals suck out the fluids which collect in the lower portion of the tube. Closing the Wound. — All the cut surfaces in a wound must be brought together in such a way as to leave as small a space for the collection of wound-secretion as is possible. This end is best attained by a well-directed application of pressure in the final dressing, but can be materially aided in certain cases by the careful placing and gentle tieing of a few buried sutures. The skin-surfaces must be approximated, and many methods of suture are to be recommended — interrupted sutures, continuous, and subcutaneous. The special point to be emphasized, however, is this: That the part of the wound which is most doubtful in the matter of asepsis is the deeper layer of epidermal cells, and for this reason the suture, like the double-header (where two needles are threaded upon one piece) which is passed from within out, is always to be preferred to that which is passed from without in; and the subcutaneous stitch, which does not enter the epidermis at all, is a greater safeguard even than the "double-header." Whichever method of suture is adopted, only as many stitches should be placed as are essential to approximation; and none must be tied so tightly as to endanger the vitality of the tissue either by tension or by strangulation. Dressings. — The materials used for surgical dressings have been simplified in the last few years to such a degree that in clean wounds, at any rate, dry sterile gauze is almost universally pre- ferred. The dressing is intended to protect the wound and to absorb the discharges. Dry gauze is sufficient for both purposes; but when soaked through with blood and serum must be immediately re- placed by fresh sterile gauze, to avoid the contamination that will result from the ready migration of the bacteria from the outside through the serum-soaked meshes to the wound. Septic wounds with a large amount of discharge require frequent renewals of the dressing, to prevent decomposition of the discharges ; and for this end the antiseptic poultice is devised. Weak hot solutions of corrosive sublimate (i : 8000) or sulpho-naphtol (,5J to Oij) are pre- pared every four hours; and a gauze pad wrung out in this solution is applied, and covered with paper or oiled silk, to prevent evapora- tion. In septic conditions of the arm or foot, a bath of the same proportions may be substituted for the poultice, and the part remain immersed for one hour in every four, with beneficial effect. An- other variation of this use of antiseptic solutions is the constant- drip apparatus, by which a continuous stream of one of these weaker solutions is made to flow over or through a wound for hours at a time. Immobility. — Rest is one of the greatest factors in repair, and a proper restriction of the motions of the part affected is one of the greatest desiderata in wound-treatment. The limb must be placed in a comfortable position, so as to relax the tissues to the utmost; and it must be kept in this position by splints and bandages until 8l2 SURGICAL PATHOLOGY AND THERAPEUTICS. healing is so far progressed as to preclude the possibility of sudden muscular action pulling the surfaces apart. With the painstaking observance of these principles, the surgeon has done all in the way of operative procedure that can be done to promote the healing of a wound, and the actual process of repair may thereafter be safely entrusted to Nature. III. BACTERIOLOGY OF THE MOUTH AND PHARYNX, EYE, EAR, AND NOSE. THE MOUTH AND PHARYNX. The mouth and pharynx possess conditions which are admir- ably adapted to the development of micro-organisms — namely, warmth, moisture, and an abundance of nutrient material. The exposed situation of these cavities favors the continual introduc- tion of bacteria in air, food, and a variety of foreign substances. While most of the species occurring are saprophytic, yet a few pathogenic ones may usually be found in healthy individuals, and under certain circumstances may multiply to a considerable extent without producing any discoverable local or general disturbance. Bacterial invasion of the tissues of the mouth and pharynx is largely restricted by the following agencies : i. The character of the mucous membrane ; 2. The action of ingested food and secreted fluids ; 3. Phagocytosis. 1. The mucous membrane is of the pavement-form, in most places compact and well nourished by an abundant blood-supply. Epithelial regeneration and desquamation are rapid and contin- uous. In the mucous membrane covering the tonsils and lymph- oid structures of the pharynx, however, a looser texture exists, with actual deficiencies and channels communicating with the efferent lymph-vessels. Such places, although protected to a cer- tain extent by the active phagocytosis there present, nevertheless constitute frequent entrance-points of bacterial infection. 2. The ingestion of food and fluids flushes the mouth and throat periodically and removes large numbers of micro-organisms. With regard to the action of saliva, recent investigations have shown that, while it does not markedly influence the vegetative activities of most bacteria, it distinctly lessens the virulence of pathogenic forms. This diminution in virulence exists, however, only so long as the micro-organisms are in contact with the saliva, and may be restored by cultivating them upon other culture-media. 3. Phagocytosis in the mouth probably does not play a conspic- uous part in controlling the activities of micro-organisms. In the crypts of the tonsils, however, the polynuclear leukocytes are an important barrier against infection, and compensate more or less completely for the loose epithelium and imperfect drainage there present. BACTERIOLOGY OF THE MOUTH AND PHARYNX. 813 From the surgical standpoint, the occurrence of pathogenic bacteria in the mouth and pharynx offers two important subjects for consideration : First, the possible transportation of such germs to vulnerable parts of the body during operative procedures; sec- ond, the effect of their presence upon wounds of the oral and pha- ryngeal tissues. With regard to the first possibility, the inhalation of bacteria from the mouth immediately suggests itself as the cause of pneu- monia following etherization. It has been shown that during forcible inspiration particles of mucus or saliva may be drawn into the bronchi and bronchioles, whence they are driven, by the air- pressure during the succeeding act of coughing, into the alveoli. In this manner, pathogenic bacteria may be carried, suspended in particles of fluid, into the lung-tissue. This mode of origin ap- pears more probable than that the pneumonia is caused by the inhalation of pathogenic germs from the surrounding air, inas- much as the latter contains an insignificant number in comparison with those present in the mouth. It thus would seem to be of practical importance to sterilize, as far as possible, the mouths of patients previous to etherization (see below for formulas). The Surgical Preparation of the Mouth for Operation. — While the use of antiseptic washes has been shown to destroy bac- teria in the saliva or on the exposed surface of the mucous mem- brane, it is not likely to affect germs situated in the cavities of carious teeth, unless a mechanical cleansing be also performed. The routine followed at the Massachusetts General Hospital, sug- gested by W. F. Whitney, is to be recommended as calculated to minimize the danger from inhalation-pneumonia : Several days before the operation the patient's teeth are examined by a dentist and thoroughly cleansed. Any cavities present are filled. Me- chanical cleansing and sterilizing are continued by rinsing the mouth and brushing the teeth, especially about the roots, several times a day with an antiseptic solution. The pharynx and tonsils are sprayed at the same time with the antiseptic. As shown in the section on the Bacteriology of the Nose, sterilization of the nasal passages is superfluous, with the exception of the vestibule, which contains great numbers of bacteria, and will tolerate vigorous anti- septic measures without injury. It is well to adopt this prepara- tion in all cases in which anaesthesia is to be produced, and espe- cially in all cases of operations upon the mouth or the abdomen, in order to avoid the dangers of a septic pneumonia. Notwithstanding the abundance of micro-organisms in the mouth and pharynx, wounds and injuries of these parts ordi- narily heal with rapidity, a result due to the great vascularity of the tissues and to the continual flushing and free drainage. Asepsis is practically impossible to secure, and the entrance of new organisms into the mouth and pharynx cannot be prevented. Strong antiseptic solutions, especially salts of mercury, inhibit the normal processes of regeneration in wounded tissues, and may even cause a breaking down of previously healthy structures in the vicinity. 814 SURGICAL PATHOLOGY AND THERAPEUTICS. The subject of mouth-sterilization has been most fully investi- gated by Miller, who has shown that many of the agents ordinarily relied upon for this purpose are of little or no value. Among the preparations which show but slight power to disinfect the mouth are potassium chlorate, borax, and carbolic acid. The value of these and similar remedies probably lies chiefly in the mechan- ical acts of flushing and cleansing during their use. Of the anti- septics which may be used daily without injury to the teeth, sac- charine and benzoic acid were shown to be the most efficient. The following formulae are recommended : R. Acid, benzoic, 3. Tinct. eucalypt., 15. Alcohol., 100. 01. menth. pip., 0.75. — M. Sig. — To half a wineglassful of water add enough of the solution to produce distinct clouding. Hold in the mouth for one minute. The antiseptic strength of the mixture is increased by the addi- tion of 0.8 gram of corrosive sublimate, although this is not to be recommended for daily use. R. Saccharini, 2.5 Acid, benzoic, 3. Tinct. ratanh., 15. Alcohol, absol., 100. 01. menth. pip., 0.5. 01. cinnam., 0.5. — M. Sig. — Dilute with ten parts of water, or, better, ten parts of a 4 per cent, solution of hydrogen peroxide, and hold in the mouth for one minute. These preparations have been shown to exert a powerful bac- tericidal effect without apparent injury to the teeth or the soft tissues. It should, however, be emphasized that their use is not indicated in clean wounds with good drainage, as epithelial regen- eration is likely to be more retarded than if a simple cleansing wash were employed. Formalin is a powerful disinfectant, about equal in germicidal action to corrosive sublimate. Its irritating effect renders it unsuit- able for use upon mucous membranes, except in solutions of y 2 per cent, or less. In combination with various neutral salts and essential oils, it enters into the composition of several recent proprietary solutions, and is probably the chief factor in the antiseptic efficacy of such preparations. Pathogenic Bacteria of the Mouth. — Streptococcus Pyo- genes. — This organism is found in catarrhal and ulcerative stomatitis, in parenchymatous inflammations, especially of the tongue, in acute inflammation of the lingual and faucial tonsils, and in most suppurative processes. It is generally associated with other pyogenic bacteria, especially forms of staphylococci. BACTERIOLOGY OF THE MOUTH AND PHARYNX. 815 Staphylococcus Pyogenes Albus, and the varieties Aureus and Citrcus. — These organisms are the etiological factors in many acute inflammations of the mouth and pharynx, such as aphthous stomatitis, acute lingual and faucial tonsillitis, and in most suppu- rative processes, occurring either alone or in association with the Streptococcus pyogenes. Klebs-Loffler bacillus gives rise occasionally in the mouth to a fibrinous inflammation, which may either be isolated or occur in association with diphtheria of the fauces. Pneiunococcus of Frdnkel. — This organism occurs normally in the mouth and on the surface of the tonsil. It gives rise rarely to a tonsillitis characterized by sudden onset, the presence of a false membrane, and termination of fever by crisis. Bacillus of Friedlander. — This bacillus has been found in cases of tonsillitis running a subacute or chronic course, and has been held by some observers to be the etiological factor. Bacillus of Tuberculosis. — This bacillus may invade the tissues of the mouth and pharynx, either primarily or secondarily, in the course of pulmonary tuberculosis. The lesions may be miliary in character at the beginning, forming later superficial ulcerations; or they may take the form of nodular swellings. The lupous form is generally an extension from lesions of the adjacent skin. Bacillus of Lepj'osy. — This bacillus at times produces lesions of the mouth during the course of the general disease. Bacillus of Glanders. — This organism frequently invades the tissues of the mouth and pharynx in persons suffering from the general affection. The lesions of the mucous membrane are analogous to those on the skin, occurring as circumscribed infil- trations and losses of substance. Bacillus of Typhoid Fever. — This bacillus has been found in the mouths of patients suffering from the general disease, and is supposed to be the cause of the superficial ulcerations sometimes found on the anterior pillars of the fauces. Among other micro-organisms, may be mentioned the ray-fungus (the cause of actinomycosis) and Saccharomyces albicans (the cause of thrush). Caries of the teeth is due to the action of several acid-forming species of bacteria, and not to a single specific organism. The acids are excreted by the bacteria in situ on the surface of the teeth. According to J. L. Williams, at least two-thirds of the dental decay now prevalent may be prevented by the faithful use of germicides. For this purpose, the milder form of the two anti- septic mouth-washes previously given (page 814) may be used with regularity daily. The Antiseptics of Tooth-filling. — Complete sterilization of a cavity requires, as shown by Miller's experiments, a consider- ably longer time than has ordinarily been supposed. In many cases it is advisable to allow the antiseptic to remain in the cavity for half an hour, or even for twenty-four hours. This is best done by applying the antiseptic on a small pledget of cotton, and closing the cavity with soft cement or other protective material. After 816 SURGICAL PATHOLOGY AND THERAPEUTICS. removal of the antiseptic, and immediately before introducing the filling, a current of hot air is to be blown into the cavity. This has been shown to diminish very considerably the chance of any germs persisting in the walls of the cavity. Of the various antiseptics used to sterilize cavities, carbolic acid is most generally employed. Styrone, trikresol, and lysol are also efficient disinfectants. These are all used pure. Where a bleach- ing of the tooth is desired in addition to a powerful germicidal action, pyrozone in ethereal solution is to be considered a most useful preparation. The weaker solutions are to be used only where all caries has been removed, as their penetrating powers cannot be relied upon. Proper cutting and polishing of the enamel-margins of cavities, and the absolute sealing of them, are matters of as great importance as sterilization, since upon them depends the prevention of subse- quent penetration of micro-organisms. Diagnosis of Acute Infectious Inflammations of the Throat. — In acute exudations of the upper air-passages the neces- sity for accuracy in diagnosis has been emphasized by the intro- duction of serum-therapy. Whether the inflammatory phenomena are excited by pyogenic bacteria or by diphtheria-bacilli is a matter of the gravest import to prognosis and treatment. In a large percentage of cases such a knowledge can be attained by applying the bacteriological test. Within the space of twenty-four hours cultures from the affected mucous membranes suffice to establish the diagnosis with a precision unattainable by clinical methods. Where culture-tubes of serum are not procurable, or are so seldom employed as to be likely to dry out, the culture may be conveni- ently taken on the sterilized swab shown in Fig. 81, and thus transmitted to the bacteriological laboratory for inoculation. In taking a culture from the throat, care should be taken to press and twist the cotton of the swab rather firmly against the affected surface, as diphtheria-bacilli are frequently more deeply situated in the false membrane than are pus-cocci, and consequently are more likely to escape removal. For practical purposes, at the present time we have to consider, in a doubtful case of pharyngitis or tonsillitis, only the diphtheria-bacillus, the Streptococcus pyogenes, and the Staphylococcus albus and aureus as the possible causative factors. In a very few cases the pneumococcus was found to be the cause of an exudative tonsillitis, while occasionally Friedlander's bacillus and the Micrococcus tetragenus were apparently the infecting agents. Such conditions deserve further investigation. THE EYE. The normal conjunctiva contains always large numbers of micro-organisms. While most of these are being constantly drained away by the tears, a certain number persist in the sac, owing to their deep situation under the epithelium, or in the ducts of the glands. They are, furthermore, especially abundant in the lid-borders and the roots of the lashes. A germicidal action has BACTERIOLOGY OF THE EYE. 817 been attributed to the tears; but this property, if present, is exercised only against certain bacteria, not toward all. Bacteria are not, as a rule, found in the secretion of perfectly normal glands (Gifford). Owing to the fact that many bacteria are so deeply seated, it is impossible to sterilize the conjunctiva completely, even over limited areas; while it is even more difficult to remove the germs from the lid-borders and the roots of the lashes. In preparing for opera- tions and in the treatment of wounds, antiseptics should be avoided, as they are likely to injure the delicate structures, especially the cornea, as well as to inhibit the processes of repair. Douches of normal salt-solution and mechanical cleansing before operations are, however, eminently desirable. Observance of the following details is recommended: The face and lids are washed with soap and warm water prior to the operation. The conjunctival sacs and surfaces are washed with sterilized normal salt-solution. A moderately firm wiping of the lids and lashes has been shown to diminish very considerably the number of bacteria present in these situations. During the operation everything that touches the eye is to be aseptic, but no antiseptics are allowed to come into contact with it. After the operation the eye is gently douched with salt-solu- tion. The dressing consists of moist linen and one or two layers of absorbent cotton, kept in position by horizontal and vertical plaster strips. The aim before, during, and after the operation is to keep the conjunctiva as nearly as possible in its normal condition and free from irritation. Sterilization of the more delicate instruments must be performed with great care, to avoid injuring their edges. The edge of the instrument should first be examined with a magnifying-glass, to see that it is in proper condition; then the instrument is wrapped in cotton and placed in the boiling soda-solution. From this it is placed in absolute alcohol until ready to use, when the blade is freed from the alcohol by dipping into sterilized water. Sterilization of small instruments by the vapor of formaldehyde is now generally practised, and is most conveniently done in one of the special sterilizers now for sale. A classification of conjunctivitis, depending upon the demon- strated presence of certain microbes, has been proposed ; but any such attempt can only lead to error in the present state of our knowledge, since there may be cultivated from the discharge certain germs which have no influence in causing the disease ; thus, one dare not say, in the absence of membrane upon the con- junctiva, that diphtheria is present merely because one has suc- ceeded in demonstrating the diphtheria-bacillus in the exudation. Nor must it be forgotten that two infections may be present at one time, as when we infect a patient suffering from trachoma with gonorrhceal ophthalmia (Morax and R. Petit). At least ten species of bacteria have been isolated from the normal conjunctiva. Although most of them are not ordinarily pathogenic, they may become harmful if the tissues in which they exist become bruised or irritated (Randolph).. 52 818 SURGICAL PATHOLOGY AND THERAPEUTICS. The pathogenic micro-organisms which occur also under condi- tions of health are the Staphylococcus pyogenes albus and aureus, and the xerosis bacillus. Staphylococcus Pyogenes Albus and Aureus. — These occur nor- mally in greatest abundance along the lid-borders and in the roots of the lashes. Pathologically, they are found in many inflamma- tions, such as blepharitis, phlyctenular conjunctivitis, in ulcera- tions of the cornea that are not typically serpiginous, in suppu- rative conditions; and in association with other specific inflamma- tions, such as diphtheritic and gonorrhoeal conjunctivitis. Xerosis Bacillus. — This micro-organism resembles closely the bacillus of diphtheria; but it is not virulent for animals. It occurs normally in the conjunctiva; and is also found in inflammations, especially in association with the Koch-Weeks bacillus. The following bacteria are not found normally in the eye, and their presence is usually attended by pathological alterations in the tissues : Koch-Weeks Bacillus. — This bacillus resembles closely the bacil- lus of mouse-septicaemia; and measures i to 2 mm. in length, and 0.25 mm. in thickness. It is found in the conjunctival sac as the etiological factor in acute contagious conjunctivitis. Diplobacillus of Morax and Axenfeld. — This occurs in the form of a diplobacillus, each member of which measures 2 to 3 mm. in length, and 1 to 0.5 mm. in breadth. Chains of these diplobacilli are not infrequent with no apparent sign of division. It is decol- orized by Gram's method. It causes a subacute or chronic con- junctivitis, running a course of from six weeks to six months. Pneumococcus of Frdnkel. — This organism may give rise to an acute contagious inflammation of the conjunctiva, closely resem- bling, clinically, the conjunctivitis produced by the Koch-Weeks bacillus. It is one of the etiological factors in typical serpiginous ulceration of the cornea, where it may at times be found in almost pure culture. It is also one of the causes of panophthalmitis. Kyle found that in Matanzas, during the Spanish War, the great majority of cases of conjunctivitis that occurred were due to this organism. Streptococcus Pyogejzes. — This organism is found in many sup- purative inflammations and in certain forms of corneal ulceration. It may also give rise to membranous conjunctivitis. Gonococcus of Neisser. — This organism is an etiological factor in gonorrhoeal conjunctivitis and in severe cases of conjunctivitis neonatorum. Klebs-Lbffler Bacillus. — This bacillus is the cause of diph- theritic conjunctivitis. It develops on the conjunctiva, however, only when the mucous membrane is in a condition to receive it, such as might be brought about by an antecedent simple con- junctivitis or general depressing illness. Bacillus of Tuberculosis. — This bacillus produces characteristic tuberculous lesions in the ocular coats. Bacillus of Leprosy. — This organism, at times, invades the eye, and gives rise to characteristic nodules. BACTERIOLOGY OF THE EAR. 819 Other micro-organisms have been cultivated from infectious diseases of the eye, such as trachoma ; but their etiological rela- tionship has not yet been demonstrated. THE EAR. The external ear forms, so far as its bacteriological relations are concerned, simply a portion of the cutaneous covering of the body, and does not require special consideration. The most frequent bacterial affection is furunculosis of the external meatus, caused by staphylococci, generally the Staphylococcus pyogenes aureus. Invasion of the middle ear by bacteria occurs most frequently from the nasopharynx through the Eustachian tube. The latter is lined with ciliated epithelium, the motion of which is directed from the tympanum toward the pharynx, thus constituting, under normal conditions, an effective barrier against the entrance of micro-organisms. When, through accident (such as too forcible blowing of the nose) or through disease of the tubal epithelium, germs enter the middle ear, they may remain there without harm and lose their virulence, or they may be thrown out again. If external influences (as chill or trauma) depress the vitality of the mucous membrane of the tympanum through impairment of its nutrition, then favorable conditions for the growth and develop- ment of micro-organisms appear to be provided, and a reactive inflammation results. Less frequent avenues of infection of the middle ear are through the blood-vessels in endocarditis and in general septic conditions, through the dural process in the petrosquamosal suture, and through the drum-membrane if the latter be wounded or perfo- rated. Sterilization of the external meatus and drum-membrane, prior to opening the tympanic cavity, should be done by gentle irriga- tion with a warm solution of mercuric chloride of the strength of 1 : 5000; followed by instillation of alcohol, which is then removed by pledgets of sterilized absorbent cotton. In irrigation of the exposed middle ear, the same practice should be followed as in the case of other delicate mucous membranes — namely, to cleanse without irritation. In the absence of second- ary infection, sterilized normal salt-solution fulfils all requirements. Where a moderate degree of antiseptic action is desirable, mercuric chloride in 1 : 5000 solution or saturated boric-acid solution may be used. In chronic suppurations, with accumulation of foul pus, peroxide of hydrogen is very useful, and may be injected, a few drops at a time, through a slender glass pipette into the middle ear. This not onlyiexerts a germicidal action directly, but also disintegrates the masses of epithelium and cheesy pus, so that their subsequent removal is greatly facilitated. These instillations may be repeated several times at each sitting until no more effer- vescence takes place. Antiseptic powders find their place in chronic infections of the middle ear, where a prolonged mild germicidal action is desired. 820 SURGICAL PATHOLOGY AND THERAPEUTICS. Among these may be mentioned boric acid, europhen, aristol, nosophen, and iodoform. Alcohol is an excellent antiseptic, and is well tolerated in most chronic middle-ear suppurations, especially if exuberant gran- ulations are present. At the beginning, it should not be used stronger than 70 per cent. ; but later this may be increased to 95 per cent. Solutions of nitrate of silver are often very useful in suppura- tive conditions, especially when the mucous membrane is relaxed and flabby, both from its antiseptic action and from its power of constricting the blood-vessels. It may be injected into the middle ear in strengths of from o. 5 per cent, to 1 per cent. The sterilization of instruments should be performed according to general surgical principles. In the case of hard-rubber catheters and other instruments, which cannot be boiled, the formaldehyde sterilizer may be used to advantage. Acute infectious inflammations of the middle ear are most commonly due to the pneumococcus of Frankel and the Strepto- coccus pyogenes, less frequently to the Staphylococcus pyogenes albus and aureus. Occasionally the bacillus of Friedlander, Pfeiffer's bacillus of influenza, and the Bacillus pyocyaneus are causative factors. The clinical phenomena excited by these micro- organisms vary chiefly as regards their severity, the complications of greatest gravity occurring in infections with the bacillus of Friedlander and the Streptococcus pyogenes. The latter organism is the principal one found in inflammation of the internal ear. At the beginning of the inflammation, previous to perforation of the drum-membrane, there is generally but one species of micro- organism present. After perforation, secondary inoculation of the tympanic cavity with pyogenic and saprophytic germs often occurs, which crowd out the original species. Infections of the middle ear occurring in scarlet fever, diph- theria, typhoid fever, measles, and mumps show the presence of pus-cocci, generally the Streptococcus pyogenes. In tuberculosis of the lungs and other organs an involvement of the middle ear may occur, characterized by chronic suppuration and caries of the bony structure. THE NOSE. The number of bacteria entering the nose with the inspired current of air varies naturally within wide limits. In ordinary city-air the number reaches several thousand per hour. Where the nasal vestibule is provided with vibrissas, these serve to retain a large proportion of the micro-organisms. As may be shown experimentally, the incoming stream of air, with its suspended dust and bacteria, after passing the vibrissas, is deflected by the constricting band of the vestibule against the septum at about the middle of its cartilaginous portion. From this point the cur- rent is again turned upward and outward, against the anterior end of the middle turbinate. The bacteria which still remain BACTERIOLOGY OF THE NOSE. 821 suspended in the air are almost wholly filtered out in their subse- quent passage through the nasal chambers and the nasopharynx, with the result that nasally inspired air is normally free from micro- organisms when it reaches the larynx and trachea. Although bacteria are thus constantly being deposited in great numbers upon the nasal mucous membranes, under ordinary condi- tions they not only fail to develop there, but they are removed with great rapidity. Cultures of known bacteria spread experimentally upon the nasal mucosa, begin to disappear within a few minutes, and after two hours cannot be recovered. The agencies which contribute to this disposal of bacteria are: 1. The action of the ciliated epithelium. 2. The drainage downward of fluid from the upper portions of the nasal chambers. 3. The composition of the nasal mucus, which is unfavorable for the growth of micro- organisms, although destructive to only a few pathogenic ones — i. e. anthrax-bacilli. Polynuclear neutrophilic leukocytes are found in considerable numbers upon the nasal mucous membrane, but the extent of their phagocytic action is probably limited. Where, however, the lymphoid tissue of the nasopharynx is present in considerable amount, as in children, phagocytosis is a conspicuous factor in disposing of micro-organisms. In view of the efficiency of these natural agencies which repel bacterial invasion, it is evident that artificial sterilization of the nasal mucous membrane is superfluous. Furthermore, chemical substances capable of destroying bacteria are likely also to affect unfavorably the delicate tissues within the nose, by inhibiting the customary rapidity of epithelial regeneration, or by checking ciliary action, or by altering the character of the nasal secretions. Sterilization of the skin and hairs of the vestibule previous to intranasal operations is, on the other hand, eminently desirable, in order to destroy, so far as possible, the immense numbers of bacteria situated in this region, which might otherwise be carried into the nose upon the fingers and upon instruments. While it is doubtless impossible to sterilize the skin of the vestibule com- pletely — for instance, at the roots of the hairs — yet, as shown by experience in other localities, as in the conjunctiva, removal of the greater portion of the bacteria may contribute materially to the success of operations. The hairs and the skin should first be freed mechanically from germs, as far as possible, by firm wiping, after which a pledget of absorbent cotton wet with corrosive-sublimate (1 : 1000) solution, but not dripping, should be left for several minutes in the vestibule. The after-treatment of wounds within the nose consists essen- tially in filtering out the germs of the inspired air, in keeping the nasal discharges moist, and in aiding free drainage. These results are best secured by the following measures: After the operation, if hemorrhage has ceased, an antiseptic powder — nosophen or aristol — is dusted upon the cut surface, and a loose pledget of cotton placed in the nostril. After a few hours the wound is covered by a false membrane, composed of fibrin and leukocytes, beneath which granulations form and epithelial regeneration takes place. This is 822 SURGICAL PATHOLOGY AND THERAPEUTICS. the normal method of healing, and it is only necessary to see that no irritating bacterial process takes place beneath the false mem- brane. Mucus is apt to dry over the surface of the exudate, preventing free drainage. Such crusts should be softened by spraying with some bland alkaline watery fluid, and removed with nasal forceps. Antiseptic solutions should be avoided after opera- tions within the nose, with the exception of peroxide of hydro- gen, which is useful at times for its power of disintegrating and softening the discharges, thereby aiding in free drainage. Pathogenic Bacteria of the Nose. — Streptococcus Pyogenes and Staphylococcus Pyogenes Aureus and Aldus. — These micro- organisms may occur either singly or in association, in acute and chronic catarrhal processes, in suppurations such as septal abscess, and as a complication with other specific inflammations, especially diphtheria. Klebs-L&ffler Bacillus, or the Bacillus Diphtherias . — This organism at times produces an inflammation of the nasal mucous membrane, either isolated or in connection with faucial diphtheria. Other infections of the nose, generally of a chronic character, occur from inoculation with the tubercle-bacillus, the bacillus of glanders, the leprosy-bacillus, and the bacillus of rhinoscleroma. In atrophic rhinitis many organisms occur in the nose, without, however, playing any other role than that of saprophytes. IV. BACTERIOLOGY OF THE GENITOURINARY SYSTEM. An understanding of the bacteria that are present normally or in disease in some portion of the genito-urinary tract is essential; for without such knowledge the etiology is obscure, the diagnosis incomplete, the prognosis valueless, and not only may the treat- ment be inappropriate, but serious delay may follow. In general, without the presence of bacteria the genito-urinary system is free from inflammatory disorders; but their presence alone is not usually sufficient to cause disturbance. They act as the exciting cause; and they are able to multiply and do harm only in some region made less resistant and unable to withstand their pyogenic action by some predisposing cause, whether it be a direct trauma or a purely nutritive disturbance. For the reason that the bladder serves as a common reservoir for the urine, and communicates more or less directly, especially in the male, with all the genito-urinary organs, it is most convenient and satisfactory to study the effect of the presence of germs from this center. As a result of laboratory research and clinical obser- vation, certain principles would seem to be established : r. Like the cutaneous surface of the body, the external genitals are the habitat, even in health, of micro-organisms, but in far greater profusion. This will include the vulva and vagina in the female, the prepuce in the male, and the urethra in both sexes as BACTERIOLOGY OF THE GENITOURINARY SYSTEM. 823 far as the constrictor urethral muscle. 2. Normal urine is sterile ; therefore, in health, the urinary tract above this u cut-off" muscle is free from bacteria. 3. Ligature of the urethra in health does not give rise to cystitis, but is followed by nutritive disturbances in the bladder-wall, thereby rendering this organ a locus minoris resistentue. 4. Pure cultures injected into a healthy bladder are soon voided with the urine, and do no harm ; the proteus Hauser, however, is an exception to this general statement, for reasons to be described later. 5. Pure cultures of pyogenic bacteria injected into a bladder whose vitality or power of resistance has been suf- ficiently diminished will give rise to a cystitis. Retention from any cause is a powerful factor in lowering such vitality. 6. In health, ligature of a ureter is followed in due time by renal atrophy without suppuration, and usually unattended with serious disturb- ance. 7. It is doubtful whether a healthy kidney will allow the passage of bacteria from the circulation into the urine ; but if dis- eased, bacteria unquestionably pass through the tissue into the urine. 8. As in the bladder, suppuration in the kidney demands suitable conditions in addition to the presence of micro-organ- isms. Predisposing Conditions ; Role Played by Bacteria in the Causation of Cystitis. — Cystitis is an inflammatory process of varying severity in the bladder-wall, and is characterized by the presence of pus-corpuscles in addition to other cell-elements. Furthermore, no cystitis can arise without the presence of bacteria, which, in turn, demand a suitably prepared soil. A healthy mucous membrane does not offer a favorable nidus, and it is not unusual to observe a urine swarming with bacteria (notably Bacterium coli commune), and yet the bladder-wall remain intact and resist bac- terial invasion. Such a condition is known as " bacteriuria." The factors tending to lower the resistance of the bladder-wall are numerous. The age and general health of the patient are important considerations, for young and vigorous subjects possess correspondingly healthy and tonic bladder-walls, active in repair- ing injury, and able to void the urine without any residuum ; bacteria are rapidly expelled, even if accidentally introduced; and the nutrition of the part is sufficient to overcome the effect of ordi- nary trauma. In the aged, the bladder-walls are atonic and dis- tended, and often unable completely to void the urine. An en- larged prostate gland not uncommonly gives rise to retention, which is one of the most powerful factors in lowering the resist- ance of the wall to infection, so commonly introduced with the catheter. Such cases are particularly susceptible to infection, which not infrequently may extend to the kidney. Strictures of the urethra, with obstruction, act in a similar manner. Acute retention from any cause, and pressure on the bladder by pelvic tumors, also impair its nutrition. Trauma, whether it result from instrumentation or follow the constant irritation due to the pres- ence of foreign bodies, particularly calculi, is a potent factor in this connection. Chemical irritants (drugs and local applications), hyperacidity, alkalinity, venous stasis, and arterial congestion 824 SURGICAL PATHOLOGY AND THERAPEUTICS. from chilling of the skin may interfere with the resisting power of the bladder-wall. Bacterial Invasion. — The presence of bacteria in the bladder is not sufficient cause to produce a cystitis (proteus Hauser ex- cepted), unless some nutritive disturbance has preceded their advent, or unless they remain long enough for such change to take place ; but nevertheless, their presence is an absolute necessity. When once the soil is predisposed, the resulting inflammations will vary according to the kind of infection, the number of micro- organisms, and the absence of mixed infection, as well as the con- dition of the bladder-wall and the urine. Cystitis is a suppurative process, hence the invading bacteria must be pyogenic ; and it would seem that the power to decom- pose urea possessed by many varieties is not sufficient per se to give rise to such an inflammatory process. These two powers, however, may be combined in a single variety of micro-organism. The varieties possessing only the power to decompose urea are commonly voided before they cause trouble, for fresh acid urine is constantly being excreted by the kidneys in sufficient quantity to overcome the alkaline tendency of the urine in the bladder, which is voided from time to time. If, on the other hand, retention should take place, then these micro-organisms multiply rapidly ; the urine becomes alkaline, thereby favoring the action of any pyogenic bacteria that may already be present or be introduced in the effort to relieve the retention. Bacteria which are purely pyogenic multiply in the urine, and under favorable conditions penetrate the bladder-wall and cause suppuration : and only bacteria with this characteristic, which may or may not be combined with the power to decompose urea, are able to cause a cystitis. Suppurative processes in the urinary tract, therefore, demand two conditions — the proper condition of the soil and the presence of pyogenic bacteria. Reaction of the Urine. — Given a cystitis consequent on the invasion of purely pyogenic bacteria, the urine will remain acid throughout its course. Some of these bacteria have a feeble power of decomposing urea ; but even then the urine ordinarily remains acid. Such forms of acid cystitis are the commoner, and also include the more serious types (Bacterium coli commune, tuber- cle-bacillus, Streptococcus pyogenes). If the invading bacteria are feeble decomposers of urea, the periodical evacuation of the bladder and the constant flow of acid urine from the kidneys are sufficient to maintain an acid urine ; but sudden retention of urine is sufficient to render it alkaline, and even ammoniacal, and thereby the pyogenic property is often en- hanced. For the above reason, simple decomposers of urea may be present for a long time without overcoming the normal acidity of the urine. An acid cystitis, therefore, may persist as such or become alkaline under the circumstances just cited; but, furthermore, it may become alkaline: (a) if the micro-organism decomposing urea is active (proteus Hauser, Staphylococcus ureae liquefaciens); (b) if BACTERIOLOGY OF THE GENITO-URINARY SYSTEM. 825 the relation between the soil and the virulence of the micro- organism is altered (^alcoholism, excesses, violent exercise); or (c) if a purelv pyogenic variety becomes secondarily infected with decom- posers of urea. Drugs may influence the reaction of urine. It is not unusual for an alkaline cystitis to become acid on the removal of some of these causes — dilating strictures, use of catheter to prevent residual urine, rest, diet, local irrigations, and internal medication. Nevertheless, many a cystitis tends to persist when once thoroughly established. Ammoniacal decomposition is generally due to a mixed infection, and is of secondary importance; but of itself it is not a direct cause of cystitis, although such a condition enhances the activity of many pyogenic bacteria. Bacteria in the Vicinity of the Meatus Urinarius and in the Male Urethra. — Much confusion exists at present among authorities, both in regard to the varieties of micro-organisms associated with the genito-urinary organs in health and disease, and also in regard to the role they play. This confusion is readily understood when we consider the large number which frequent the external genitals in health, as well as the additional varieties associated with disease. Several varieties are usually present in every case, and it is a difficult task to isolate and cultivate them. Furthermore, polymorphism adds to the difficulty of isolation and identification. As has been stated, the external genitals as far as the constrictor urethral muscle are the habitat in health of many varieties of bacteria; but above this muscle the genito-urinary tract is sterile. Some of these bacteria are pathogenic; but the great majority, so far as known, do not give rise to trouble. Even the varieties which may give rise to a fatal cystitis or pyelonephritis may remain in the urethra for an indefinite period without causing trouble. The difficulty of rendering the urethra aseptic and the danger conse- quent on introducing instruments into the bladder will be con- sidered later. At least twenty varieties of micro-organisms have been obtained from the external genitals by different observers; but later research may show many of these to be one and the same variety. Many of them have the power to decompose urea, but comparatively few are pathogenic. There are many reasons for believing that the majority of these varieties may complicate cases of cystitis in which there has been much instrumentation, and that they play a decidedly secondary role, for examination of cases of cystitis fre- quently shows a pure culture of some pyogenic variety. The commoner bacteria found in the flora of the external genitals and urethra are merely enumerated in this connection; but the important ones will be considered in detail in connection with the flora of cystitis. Flora of Urethra and about the Meatus Urinarius and Vulva. — Bacterium coli commune; Coccobacillus liquefaciens urethrse; Bacillus urethrae non-liquefaciens; Leptothrix urethrae; Diplococcus candidus urethrae; Pseudogonococcus; Gonococcus of Neisser; Staphylococcus ureae liquefaciens; Streptococcus pyo- 826 SURGICAL PATHOLOGY AND THERAPEUTICS. genes; Streptococcus liquefaciens urethrae; Sarcina urethrae; smegma-bacillus; tubercle-bacillus; Bacillus typhosus; Staphy- lococcus pyogenes aureus and albus; Streptobacillus anthracoides. The question of the kind of infection giving rise to the various ulcers and inflammatory processes of the external genitals will not be considered in this section. Bacteria of Cystitis. — The bacteria giving rise to or compli- cating cases of cystitis are as follows: Bacterium coli commune; Streptococcus pyogenes; uro-bacillus liquefaciens septicus (proteus Hauser); bacillus of tuberculosis; Bacillus typhosus; Diplococcus urese liquefaciens; Staphylococcus urese liquefaciens; Streptobacil- lus anthracoides; gonococcus of Neisser; Staphylococcus pyogenes aureus and albus; diplobacillus (Friedlander) ; Bacillus lactis aero- genes. In all probability, suppurative processes in the genito-urinary system can be attributed to the presence of one or more of the bacteria enumerated above; but not infrequently a cystitis is found to give only a pure culture. The most important of these micro- organisms will be considered in some detail. Bacterium Coli Commune. — This bacterium has been studied under a multitude of names; and it would seem to be without question the commonest cause of cystitis. Its presence is constant in the normal intestinal canal, and its virulence is increased in disease of that tract. In health it is commonly found on the external genitals. In cases of obstinate constipation it may enter the circu- lation, and then the urine via the kidneys; or it may pass directly through the rectal and bladder walls; but usually it reaches the bladder by extension up the urethra, with or without the aid of instruments. It is polymorphous; hence one cause of confusion in identification. It may multiply in the urine of a healthy bladder and give rise to no trouble ( lt bacteriuria "). Its virulence is very variable; it is pyogenic, probably decomposes urea very slightly, and may give rise to septicaemia. Unless mixed with decom- posers of urea or after prolonged retention in rare instances, it gives rise only to an acid cystitis. A pure culture is common. Its pathogenic property is enhanced in an alkaline medium. It may ascend to the kidneys and give rise to a suppurative pyelonephritis ("surgical kidney"). Streptococcus Pyogenes. — Not such a common source of infec- tion as the preceding, but its presence is more serious. It is pyogenic, does not decompose urea, and hence in pure culture will give rise only to an acid cystitis. It commonly causes septicaemia; it penetrates the bladder-walls, causing lymphangitis, phlebitis, and even gangrene. Its presence should suggest greater care in the use of instruments and caution in considering the advisability of operation. Pyelonephritis is to be guarded against. Strepto- coccus pyogenes is the commonest germ of puerperal septicaemia. Urobacillus Liquefaciens Septicus {Proteus Hauser). — Polymor- phous, and characterized by the great energy and rapidity with which it decomposes urea. It is pyogenic, and has the power to cause a violent ammoniacal cystitis by first decomposing the urea, BACTERIOLOGY OF THE GENITO-URINARY SYSTEM. 827 and thus predisposing the mucous membrane of the bladder to its own pyogenic action. It is prone to cause pyelonephritis. It is often a serious complication. Bacillus of Tuberculosis. — Not an unusual source of genito- urinary infection. Pyogenic; does not decompose urea; therefore gives rise to an acid cystitis when found in pure culture, which sometimes occurs; but more commonly it is associated with other micro-organisms, particularly the Bacterium coli commune and the Staphylococcus aureus. It does not grow on ordinary culture- media; therefore its identity must be verified by inoculation-experi- ments. In staining-properties it resembles the smegma-bacillus; but it differs in form, size, and grouping. Its occurrence in the genito-urinary tract may be primary or secondary. It is commonly secondary to foci in the lungs, first attacking the pyramids and pelves of the kidney, and later the bladder-walls about the orifices of the ureters. In primary cases the epididymis, kidneys, and Fallopian tubes are the commoner seats of origin. Tuberculous cystitis is insidious, runs a chronic progressive course, and frequently yields to no method of treat- ment. The urine remains acid, unless invaded by the more active decomposers of urea, and the lesions are located about the trigonum and the ureteral orifices. The bladder may contain bacilli of renal origin for a long period without any evidence of cystitis. Infection commonly extends to the prostate and the seminal vesicles, but less often to the kidneys than vice versa. Tuberculous cystitis is often the first warning given of the presence of tuberculosis which may have existed for a long period in the kidneys. The above characteristics apply to the chronic variety, and not to the acute miliary type, which is twice as common, but rapidly fatal without giving rise to ulcerative lesions. The prognosis of genito-urinary tuberculosis is very grave, and medicinal and sur- gical treatment offers but little encouragement in the great major- ity of cases. Like tuberculosis elsewhere, it is more amenable to hygienic and climatic treatment; but when primary in the epidid- ymis and Fallopian tubes surgical measures offer the greatest encouragement. Bacillus Typhosus. — Found in the urine in at least 25 per cent. of the cases of typhoid fever during convalescence. Not rarely associated with a moderate degree of nephritis, and occasionally a cystitis ; it is pyogenic, does not decompose urea, and is usually in pure culture; therefore gives rise to an acid cystitis. The presence of these bacilli in the urine is a dangerous source of infection to the community. Diplococcus Urecz Liquefaciens (Mel choir). — Rapidly decom- poses urea ; probably not pyogenic. Staphylococcus Urecz Liquefacieus. — Decomposes urea ; but slightly pyogenic ; always associated with a purulent ammoniacal urine. Streptobacillus Anthraco'ides (Melchoir). — Decomposes urea slowly ; non-pyogenic ; associated with an alkaline urine, but never in pure culture. 828 SURGICAL PATHOLOGY AND THERAPEUTICS. Gonococcus (Neisser). — The micro-organism of specific urethritis (gonorrhoea), necessarily a mixed infection in the urethra, com- monly so in the bladder, but occasionally found in pure culture in cystitis. Pyogenic, but probably does not decompose urea. This is the commonest cause of suppuration in the female, and fre- quently causes purulent salpingitis and local peritonitis. Staphylococcus Pyogenes Aureus and Albus. — The common pus- producers. Usually associated with mixed infection in the blad- der, which tends to remain superficial and comparatively mild. They decompose urea, and they frequent the urethra in health. The aureus is the commoner, and is to be looked for as complicat- ing suppurative processes about the female genitals, and also in "surgical kidney." Diplobacillus of Friedlander. — Common in diverse suppurative lesions following pneumonia, and occasionally present in the urine even in pure culture. Bacillus Lactis Aerogenes. — Occasionally present, and gives rise to gas-production within the bladder. This may be the same germ found in puerperal emphysematous gangrene. Routes of Invasion of the Genito -urinary System by Micro -organisms. — In general, bacteria reach this tract by one or more of the following routes : i. Direct extension along the normal passages, favored or not by instrumentation. 2. Direct extension through tissues (lymph-channels or direct contact). 3. Hematogenic. External Genitals and Urethra. — As already mentioned, these localities are normally the abode of many pathogenic and non-pathogenic bacteria, and they are furthermore peculiarly ex- posed to invasion from external sources as well as to infection con- tained in urine. The likelihood of the involvement of these parts will depend upon their integrity and power of resistance on the one hand, and the virulence of the invading organism on the other. Bladder. — Inasmuch as the bladder-walls and urine are nor- mally sterile, infection must be conveyed from some external source; but whether such infection will cause a cystitis or not has been sufficiently considered. Urethral Origin. — In the female, infection often reaches the bladder spontaneously ; but in the male this happens less fre- quently. The constrictor urethrse muscle must be passed and the sterile posterior urethra reached, which is in one sense a part of the bladder, for its walls are directly continuous, with no barrier of separation. The introduction of instruments, even though sterile at the' outset, is the usual mode of infection. The instru- ment travels through a normally infected urethra, which is not generally irrigated before such introduction ; but, furthermore, the ordinary means of rendering the urethra aseptic are almost useless, and it is even questionable whether this passage can be made sterile with much degree of certainty. Probably bacteria are car- ried into the bladder with nearly every instrument; and a cystitis would be common if it depended solely on the presence of an BACTERIOLOGY OF THE GENITO-URINARY SYSTEM. 829 exciting cause. However, other factors must coexist with such introduction, as demonstrated by clinical experience. The passage of instruments for urethral complications where the bladder is generally healthy and tonic does not give rise to a cystitis ; but where instrumentation is necessary for the relief of retention, the detection of calculi, cystoscopy, etc., where the integrity of the bladder-wall is involved — here a cystitis frequently follows where previously there was no evidence of such. The causes leading to the use of instruments in the bladder have already damaged the bladder-walls, and demand extreme precaution on the part of the surgeon. Extension from the Kidney. — In many of the infectious diseases bacteria are eliminated by the kidney, and thus reach the bladder, as shown particularly in typhoid fever, pneumonia, and erysipelas. This circumstance, however, does not usually give rise to a cys- titis. Tuberculous cystitis, however, commonly extends from a tuberculous pyelonephritis. Extension from Neighboring Organs. — In the female, inflam- matory disorders of the pelvic viscera may give rise to cystitis, and the route of infection is probably through the lymphatics. In the male there is evidence to show that the colon-bacillus may pass directly through the walls of the rectum and bladder into the urine. Occasionally abscesses may open directly into the bladder. Hematogenic sources of cystitis are possible, but not very prob- able. On account of the direct communication of the bladder and the posterior urethra (which are a single cavity from a bacteriological point of view) with other organs of the genito-urinary tract, a cys- titis or a posterior urethritis is most often the source of infection, resulting in acute prostatitis, vesiculitis, and epididymitis. Under favorable circumstances, certain varieties of infection are prone to extend from the bladder to the kidney without involving the ureter. Inflammation of the ureter is unusual, except at its extremities in tubercular processes, and along its course during the passage of calculi. Kidney. — The hematogenic sources of inflammatory processes in the kidney are common, consequent on the direct invasion of the micro-organism, and perhaps aggravated by their toxic products. It is open to question whether micro-organisms can pass through a perfectly healthy kidney; but when its nutrition is disturbed they pass readily from the blood into the urine. The nephritis accompanying the infectious diseases offers many examples: erysipelas, pneumonia, typhoid fever, streptococcus- and staphylcoccus-infection, and probably scarlet fever and diphtheria. Tubercle-bacilli reach the kidney through the blood generally from foci elsewhere. Under certain circumstances a cystitis may be a dangerous source of infection. In chronic cases of cystitis in elderly subjects, particularly when associated with prostatic or urethral obstruction or complicated by 830 SURGICAL PATHOLOGY AND THERAPEUTICS. calculi, inflammation is prone to extend to the kidneys. Retention of urine, with consequent dilatation of bladder, ureters, and pelvis of the kidney, is a dangerous complication, and demands the greatest care with instruments and the strictest asepsis. A suppu- rative pyelonephritis may result, known as '* surgical kidney," which is not only serious to life, but it is also probable that the kidney never ceases to produce pus when once thoroughly infected. One kidney may become infected from below, and the other secondarily through the blood. Direct extension to the kidneys from neighboring organs is rare. Perinephritis is generally secondary to inflammation in the kidney. Prophylaxis and Treatment. — For the most part, only such questions will be considered as pertain to the bacteriology of the subject. Preparation of the Field of Operation. — If we" are unable to remove micro-organisms from the field of operation, then there must always remain a certain degree of danger accompanying the use of instruments. The question of asepsis is determined by bacteriological examinations; and these show that the ordinary routine of preparation of the external genitals is far from what could be desired. Furthermore, it is questionable whether we can sterilize these parts with any degree of certainty by any known methods, particularly without resulting in injury which may per se predispose the parts to later infection. Most of the antiseptics that are found to be reliable on cutaneous surfaces are too irritating when used profusely and in sufficient concentration on mucous membranes. Vicinity of Meatus Urinarius, Urethra, Bladder. — For the passage of instruments, the penis, including the glans and pre- puce, should be washed carefully with green soap and warm water, and then rinsed with sterile water. Then wash the same with a solution of corrosive sublimate, 1 : 3000, and rinse with sterile water or a saturated boric-acid solution (boric acid, so commonly used, is practically valueless as a germicide). Protect the parts with sterile towels. If possible, the patient should always urinate just previous to the above preparation; and it is probably wise to defer the passage of an instrument into the urethra until the latter has been flushed by the stream of urine, provided that such delay is possible and is not contraindicated. From the fact that the urethra is always the habitat of micro- organisms, it would seem that we ought to strive to disinfect it; but the usual antiseptic solutions are too irritating, so that harm rather than good is apt to follow. The best results are obtained from prolonged copious irrigations with a saturated boric-acid solution, the action of which is mechanical rather than antiseptic; but the great obstacle to this is the fact that it is tedious and is not practicable in a large clinic. Urethral irrigation, however, should be made use of in selected cases in which extreme caution is demanded. The bladder will need no preparation unless it is already the seat of inflammation. Previous to operation on this organ, it is JL 1 CTERIOL OG Y OF THE GENITO- URINAR Y SYS TEM. 83 1 well to irrigate its walls with boric-acid solution or Thiersch solu- tion (ac. salicylates, 3ss; ac. borici, siiiss; warm water, Oij), the latter being valuable in removing the mucus. It is impossible to remove the micro-organisms imbedded in the bladder-wall. As a prophylactic after the passage of instruments through a morbid urethra into a healthy bladder, a solution of argentum nitratis, 1 : 1000, may be injected into the bladder and allowed to remain about five minutes; then this is to be withdrawn and the bladder rinsed with boric-acid solution. Scrupulous cleanliness, should be exercised in relieving acute and chronic retention, and the volume of urine gradually reduced, as is customary in chronic cases. In all manipulations the greatest care should be used to avoid trauma. Unnecessary instrumentation is harmful. It is obvious that the hands of the operator should be clean. Enough has been said to show that certain cases are more susceptible to infection than others; nevertheless, this should be no excuse for careless- ness in detail in any case. Vulva and Vagina. — The vagina is the first of a series of pas- sages of communication between the exterior and the peritoneal cavity which nature carefully and successfully guards against the entrance of pathogenic bacteria unless certain conditions are over- come. These safeguards in the vagina are principally contact and integrity of its walls throughout, secretion of an acid mucus, and the presence of bacteria which may inhibit the action of noxious germs. For obvious reasons, our present methods cannot be relied upon to render these parts strictly aseptic, and the use of powerful antiseptics is contraindicated. Preparation of Vagina and Vnlva. — All hair should be shaven and the parts, including abdomen, buttocks, and thighs, most thoroughly washed with green soap and warm water, for this is probably the most important step in the preparation. All folds should be carefully cleansed, and the fingers and speculum used to expose thoroughly all parts of the vagina. Instead of a hard bristle brush for this delicate membrane, pledgets of cotton on forceps can be used somewhat vigorously, in order to remove mechanically all loose particles. Rinse with sterile water. The cutaneous surfaces are now to be prepared in the usual manner with potassium permanganate, etc. ; but this is probably too harsh for the vagina. After the soap and water have been washed out, a warm corrosive-sublimate douche (1 : 2000) should be given, followed by one of sterile water or creolin. If the uterus is already infected, preliminary curetting and local treatment may be neces- sary. Rectum and Anal Canal. — On account of the proximity of these parts to the female genitals, it is often well to render them as aseptic as practicable. As a preliminary step, the bowels should be thoroughly evacuated by cathartics, and then the rectum pro- fusely irrigated with high suds-enemata, followed by cleansing enemata of boric acid, Thiersch solution, or sterile water. The folds leading to the anal canal should be carefully separated and 832 SURGICAL PATHOLOGY AND THERAPEUTICS. washed with green soap and water, using pledgets of cotton, followed by the usual cutaneous disinfectants about the anus. Preparation of Instruments. — Metallic instruments and soft- rubber catheters should be boiled or steamed. Woven instruments should be used as little as possible, on account of the difficulty in making them sterile ; but sometimes they are invaluable. They should be carefully washed with soap and water, both before and after use, and, in addition, they may be immersed in a solution of corrosive sublimate, 1 : 1000, and then thoroughly rinsed in sterile water. It is repeated here that care in avoiding trauma is a matter of the greatest importance. Metallic instruments should be warm when introduced, unless the patient is under the influence of an anaesthetic. Lubricaiits. — Sterile glycerine should be used in cases in which local applications are to be made, on account of its solubility. Sterile olive oil or liquid vaseline will serve the purpose in other instances. IyOCal Applications. — L,ocal applications may be of value either for their destructive action on micro-organisms or for some specific action on the mucous membrane. The list of local remedies for the various genito-urinary diseases in innumerable ; some of these drugs are of real germicidal value, others serve to decrease the amount of pus-formation, and some are only astringents. As a general rule, local applications are contraindicated in the early stage of acute inflammation of the mucous membranes; but meanwhile diluents and carminatives may be administered inter- nally. As the acute inflammation subsides, then local applications may be made use of, particularly for germicidal purposes; and for still later stages astringents will be more serviceable. There is but little danger attending the use of vaginal douches, which should be given warm and in copious amounts while the patient is recumbent, with the hips elevated. A fountain-syringe will be found most useful. Injections into the male urethra in cases of gonorrhoea should be administered only after the patient has urinated. Abortive injections in acute gonorrhoea are rarely efficacious after the gono- coccus has penetrated the mucous membrane and the exudate is purulent. As the acute symptoms subside the local injections may be used: first, with the idea of destroying as many bacteria as pos- sible, and, later on in the course of the infection, in order to serve as an astringent. A blunt-pointed syringe should be used, so as not to enter the urethra and injure the mucous membrane; and the force of the injection should be moderate, but at the same time sufficient to dilate the canal and obliterate all folds. The great danger in the use of injections in the male urethra is the liability of spreading the infection to deeper parts, and thus causing such complications as folliculitis and posterior urethritis. Injections intended for the posterior urethra (prostatic portion) are administered by means of a soft-rubber catheter or a metallic syringe. In certain cases, concentrated solutions of silver nitrate BACTERIOLOGY OF THE GENITO-URINARY SYSTEM. 833 (1 per cent, to 5 per cent.) in very small amounts may be useful; but they demand precision and care. Copious irrigations with very mild germicides or astringents are often of greater service; and are applied to the whole length of the urethra, first irrigating the anterior and then the posterior urethra from behind forward as the catheter is slowly withdrawn, pausing for a moment at the constrictor muscle, so that the stream will flow both toward the bladder and out the external meatus. Posterior irrigations demand great care, for they are frequently the cause of extending the inflammation to the prostate gland, seminal vesicles, epididymis, and bladder. The onset of these complications demands the immediate cessation of all local treat- ment. Acute cystitis calls for general treatment by means of diluents and sedatives. Chronic cystitis is usually benefited by local irriga- tion — depending, however, on the variety of the infection, for tuberculous cystitis is apt to be aggravated thereby. For germi- cidal purposes the silver-nitrate solutions (1 : 3000 to 1 : 1000) give the best results ; but, nevertheless, the boric-acid solutions are fre- quently very effective in diminishing the amount of pus. In cer- tain chronic cases daily irrigations are necessary for the comfort of the patient, and these can often be performed by the patient himself. The most important drugs for local applications are as follows : Argentum Nitratis. — Silver nitrate would seem to be the sov- ereign local remedy as a germicide for the genito-urinary tract; and the inorganic salt would seem to be preferable to its various organic derivatives. Its prophylactic value against cystitis has been sug- gested. Its action is marked on all the pathogenic bacteria, in- cluding the gonococci, except the bacillus of tuberculosis, where its use has been of practically little avail. It should be used in solutions varying from 1 : 3000 to 1 : 500, according to circum- stances. Potassium Permanganate. — Solutions of 1 : 2000 to 1 : 1000 are frequently of great value. Corrosive Sublimate. — A powerful germicide, which must be used with care on the mucous membranes of the urethra and bladder, where a strength of 1 : 10,000 should not be exceeded. It should be washed out with sterile water or boric acid, in order to prevent absorption into the system. Boric acid does not possess germicidal properties of any value; but it is a very valuable aseptic wash which does not injure the mucous membranes, and has in a certain measure an antiseptic action in the suppurative processes to which they are subject. It is a very valuable drug for local use in the bladder, and should be prepared as a warm saturated solution (4 per cent.). Thiersch Solution is of value on account of its power of remov- ing mucus and the germicidal property of salicylic acid (its formula is given on page 831). Salt-solution is always to be obtained and is easily prepared. It is a good solvent for mucus, and therefore it is efficient in cleansing 53 834 SURGICAL PATHOLOGY AND THERAPEUTICS. the bladder- walls. Its strength should vary from that of the normal solution (0.6 per cent.) to about 12 per cent. Formaldehyde may prove to be a germicide of local value, but it is still in its trial stage. Internal Medication. — There are numerous drugs which act as astringents when eliminated by the kidneys; but laboratory experi- ments show that none is actively germicidal — except, perhaps, urotropine — in cases of the typhoid bacillus. Nevertheless, internal medication is of inestimable value for the inflammatory disorders of the urinary system. Balsams. — Sandal-oil and copaiba are invaluable in cases of gonorrhceal infection, and sometimes in other varieties of infection. The oleum santali is best administered in 10-minim capsules, giving one or two after each meal. Copaiba is more commonly administered in conjunction with other drugs, particularly sandal- oil, cubebs, and salol, combined in one capsule. Both drugs not uncommonly interfere with digestion, and copaiba may prove to be too strong an irritant to the kidneys, and may give rise to an extensive erythema, which often alarms the patient. Boric acid is eliminated as such by the kidneys, and decreases the suppuration in chronic cystitis; it is administered in 10-grain doses in a tumbler of water three times a day. Salol is one of the most useful of all the internal remedies for suppurative processes in the urinary system. It is best adminis- tered in pill or tablet form, giving 5 to 10 grains three times daily, after meals. Sodium benzoate, in 20-grain doses with plenty of water, may be administered with benefit. Urotropine is a new drug which seems to have a specific action in destroying the Bacillus typhosus, and favorable results are reported in other varieties of infection; but it is too early to draw definite conclusions. It is administered in water in 20- to 30-grain divided doses in twenty-four hours. It has been shown that local irrigations with large quantities of sterile or mildly antiseptic solutious are of great value on account of their mechanical action. The same principle is made use of internally by drinking large quantities of water, particularly for suppurative processes in the kidney. V. BACTERIOLOGY OF PERITONITIS. Peritonitis, localized or general, is always caused by bacterial invasion. It may be suspected that there are cases of peritonitis, the causative organisms of which cannot be isolated by our present culture-methods; and there is no question that some peritoneal infections are so virulent that death results so promptly that none of the usual signs of peritonitis is evident post-mortem. All the forms of pyogenic cocci have been found in the exuda- BACTERIOLOGY OF PERITONITIS. 835 tion of peritonitis. The streptococcus is the organism most to be dreaded, although under certain conditions the colon bacillus may be possessed of equal primary virulence. The Staphylococcus albus is least virulent; and this organism, as also the citreus and the aureus, is often found in association with colon bacilli or strepto- cocci. At times the aureus may cause a very virulent peritonitis. The colon bacillus and its kindred, the Bacillus lactis aerogenes and the Bacillus fcetidus (for these two are admitted to be practically identical with the colon-bacillus), are not as yet entirely beyond dispute as causative agents of peritonitis. It may be that the colon bacillus is the vigorous, highly resist- ant organism that overgrows the causative germs, the absorption of which is already causing toxaemia. In general peritonitis from perforation of a typhoid ulcer the typhoid bacillus has never been found; but in most of the cases colon bacilli have predominated, in others pyogenic cocci. Klein found typhoid bacilli in the pus of a localized peritonitis after typhoid. Korte found typhoid bacilli in a case of general peritonitis originating from a suppurating mesen- teric gland in the course of typhoid fever, but not from intestinal perforation. This is of certain significance as supporting the theory that in peritonitis from intestinal perforation the causative germs may be overgrown by the other bacteria of the intestinal canal. Recent observers, however, are united in deciding that in many cases the colon bacillus is possessed of great primary viru- lence. Elting and Calvert, in a study of perforative peritonitis in dogs, found that the intense hemorrhagic peritonitis present in all cases gave definite bacteriological results in 20 cases out of 22. In 18 cases members of the colon-group were found, 4 times alone, and 14 times in association; streptococci once alone, and 7 times in association. Staphylococcus albus was found in 5 cases, but never alone; Staphylococcus aureus once alone, and 3 times in com- bination. In these cases cultures were made in from six to twenty hours after perforation, and the colon-bacillus was the predominant organism. Orlowski of St. Petersburg has furnished the most recent work on this bacillus. He isolated n varieties, and found the most virulent to be what he calls the "ground type," farthest from the typhoid bacillus in its characteristics. He found a constant rela- tion between the virulence of these varieties, experimentally, and their power of milk-coagulation. Injections of the sterilized toxins always caused prostration and diarrhoea — not always death. Injections of living cultures, as well as the sterile toxins, into the peritoneal cavities of dogs or guinea-pigs always caused peritonitis. The pneumococcus can cause peritonitis. This infection may occur without the association of pneumonia. It is undoubtedly a rare infection, but may be extremely virulent. Morisse collected 8 cases in which it was the only organism found. Rosthorn, in 1895, reported 3 cases. Hartman and Morax report 2 cases. Reymond, in 1895, collected 6 cases. Flexner reported 2 cases, 836 SURGICAL PATHOLOGY AND THERAPEUTICS. both fatal. Cases have been reported by Barbacci, Frankel, Sevestre, Netter, Gaillard, Wright and Stokes, and others. The Bacillus pyocyaneus is not infrequently found in association with other bacteria. It may increase the virulence of a mixed infection from intestinal perforation. Gonococci alone can cause peritonitis. There is, however, dif- ference of opinion on this point. McCosh reported a case of so- called gonorrhceal peritonitis in the male in which the cause was rupture of a periprostatic abscess. In this article he collected 8 additional cases of gonorrhceal peritonitis from literature. In these cases there are no bacteriological examinations reported, and we must infer that the peritonitis was due to mixed infection with pyogenic organisms. Von Winckel speaks of gonorrhceal perito- nitis, but does not report any cases of peritoneal infection with gonococci. Cushing has reported 2 cases of diffuse peritonitis in which the gonococcus was the only organism found. The Bacillus aerogenes capsulatus has been found in a few cases of perforative peritonitis. It is not pyogenic alone, but in the presence of pyogenic organisms may be the main cause of death. A very rare form of peritonitis is caused by infection by the Bacillus proteus vulgaris. Only 1 case has been found — that reported by Flexner of Johns Hopkins University. This is the putrefactive organism found post-mortem in great numbers; but under normal conditions it is not pathogenic to man. This case was most carefully studied by Flexner, and he seems to prove beyond reasonable doubt that the infection was primary, and not a post-mortem invasion. Infection with any of the enumerated organisms will cause peritonitis of varying intensity and character, either local or gen- eral. The anatomico-pathological varieties have been best classi- fied by Pawlosky : 1. An extremely toxic variety, the "mycotica," in which death may occur before reactive inflammation takes place on the peritoneal surfaces. In some cases the peritoneum may be covered with a slimy fluid containing a few blood-corpuscles, small flakes of fibrin, and many bacteria. There is no doubt that cases of such virulent infection occur that death results in a few hours, with all the symptoms of shock. 2. An infection of great virulence is also manifest in the hem- orrhagic form, characterized by hemorrhagic extravasations and ecchymoses on the peritoneal surfaces of varying extent (with the intestinal coils markedly injected and distended), by a thin, brown- ish fluid exudation in which are pus-corpuscles and masses of bac- teria and fibrin, and by fibrin-flakes on the peritoneum. This is the common form met with in intestinal perforation. 3. Fibrinopurulent and seropurulent peritonitis, characterized by a thin, seropurulent exudation with flakes of fibrin floating through it, and masses of fibrin on the peritoneal surfaces. This form is the first stage (according to Pawlowsky) of purulent perito- nitis. The seropurulent fluid is made up chiefly of pus-corpuscles and bacteria. BACTERIOLOGY OF PERITONITIS. 837 4. Purulent peritonitis — a form characterized by au abundant purulent exudation of varying consistence. These forms must run together to a great extent ; no sharp division is possible. The kind of peritonitis met with will depend upon the kind of infection, its amount and virulence, and upon the intraperitoneal and systemic conditions in each case. The less serious forms of peritonitis are the nbrinopurulent and the purulent ; the most virulent, the hemorrhagic forms. The purulent forms are of longer duration, and may be caused by less virulent organisms or by smaller amounts of infection. Streptococci, colon-bacilli, and pneumococci are the organisms usually causing the rapidly fatal and hemorrhagic forms ; but they may, under certain conditions of virulence, amount, or tissue- resistance, cause the less fulminating and slower forms. Con- versely, while under usual conditions staphylococci may be expected to cause the less fulminating variety, they may, and especially the aureus, under changed conditions, cause the rapidly fatal types. Under abnormal conditions, bacteria possessed of little or no pathogenic power may cause a rapidly fatal peritonitis. In any condition where the fluids of the body depart from normal, where the vital resistance of the tissues is lessened and the peritoneum damaged, an infection usually of lesser amount may cause the gravest clinical picture. Such conditions are especially chronic renal or hepatic disease, with or without ascites. Perforation of the intestine is the commonest cause of the rapidly fatal hemorrhagic forms of peritonitis ; yet in intestinal perforation any form of peritonitis may be found. The serofibrinous, nbrinopurulent, and purulent forms are dif- ferent stages of a milder infection. In these forms operation is most favorable, for the fatal issue from toxaemia is delayed. In some of these cases the fluid exudation will be found sterile at the time of the operation. This does not mean that the process was an aseptic one from the start. The life of bacteria in the fluid exudation is frequently self-limited, and active organisms have been found in the fibrin-masses on the parietal peritoneum when cultures from the fluid exudation gave no growth. The fact that no culture-growth can be obtained is no proof that the individual may not have received previously enough sepsis to cause death. Sterile cultures are favorable prognostically, but they do not alter the fact that bacterial infection existed ; neither do they influence methods of operation. A knowledge of the histology of the normal peritoneum, and how fluids and solid particles are taken into the lymph- and blood- systems, is of the utmost importance to the abdominal surgeon; and a clear understanding of the changed conditions in a general or local peritoneal infection is of great moment in the surgical treat- ment of peritonitis. Muscatello, in 1895, reviewed all preceding study of the normal peritoneum and its absorptive channels, and his work has been of 838 SURGICAL PATHOLOGY AND THERAPEUTICS. extreme service to abdominal surgeons. All careful investigators are agreed upon the following points : 1. The absorption of fluids by the peritoneum is enormous. In an hour it will take up from 3 to 8 per cent, of the body-weight ; but under the influence of toxic or irritant substances an equal transudation into the peritoneal cavity may take place. 2. Over the centrum tendinosum of the diaphragm, between the connective-tissue fibers in the diaphragmatic peritoneum, open spaces are situated, measuring from 4 to 16 millimeters ( T 3 g- to f inch) in diameter, and grouped in collections of fifty to sixty. These lymph-spaces exist nowhere else in the peritoneum; and through them the greatest absorption of both fluids and solid par- ticles takes place. Fluids may pass through the endothelium in many places, but the solid particles are absorbed only by these lymph-spaces in the diaphragm. 3. Minute solid particles are carried from the peritoneal cavity through the diaphragm into the mediastinal lymph-vessels and glands, and thence into the blood-circulation, by which they are distributed to the abdominal organs, to appear later in the collect- ing lymph-glands of these organs. Larger sterile solid bodies are partly absorbed, and the remainder encapsulated. 4. The leukocytes are largely the bearers of foreign bodies from the peritoneal cavity into the mediastinal lymph-glands. 5. There is normally a force or current in the peritoneal cavity which carries fluids and foreign particles from the pelvis toward the diaphragm, regardless of the posture of the animal (though gravity may favor or retard the current greatly). Muscatello used carmine granules suspended in solution, in his experiments; and his work proves that bacteria and all solid par- ticles gain entrance to the system only through the lymph-chan- nels of the diaphragm and the mediastinal glands. This absorp- tion by the normal peritoneum is nature's safeguard against peri- tonitis. Colonies of bacteria are foreign particles that are absorbed by these lymph-spaces, just as the carmine particles in Muscatello' s experiments ; but the absorption of bacteria has definite limits, as will be seen. It is well known that certain amounts of bacteria will be taken care of by the peritoneum without peritonitis, if the peritoneum is normal structurally when the infection is introduced. The ability to remove bacteria and their products depends upon the kind and amount of infection, upon the systemic condition of the individual, upon the integrity of the peritoneum, upon the unobstructed con- dition of the diaphragmatic openings, and upon the presence or absence of culture-media in the peritoneal cavity. The experimental work of Wagner, Grawitz, Pawlowsky and Reichel, Orth, Waterhouse, and Halsted, from 1876 to 1892, is practically harmonious in these conclusions, and is of great in- terest. The early experiments dealt exclusively with less virulent germs — ^the staphylococcus group, especially the aureus. In 1895, Cobbett and Melsome performed some interesting and valuable intraperitoneal experiments with streptococci. BACTERIOLOGY OF PERITONITIS. 839 Washburn, in 1895, experimented with the pneumococcus. One of his important points is, that death may result from toxaemia after intraperitoneal injections, and yet but slight signs of perito- nitis be present. Askanazy, in 1897, experimented on the introduction of the con- tents of the intestinal canal, and Orlowski on the injections of colon-bacilli, as has been noted. A study of the work of these men is very interesting, but the conclusions of all can be thus briefly stated : 1. Normally the peritoneum can dispose of bacteria in varying amounts, depending on the virulence of the organism, without producing peritonitis; and the less the absorption from the peri- toneal cavity the greater the danger of infection. 2. Death may result from general septicaemia, and not peri- tonitis, where large quantities of bacteria or bacteria of special virulence are taken up by the lymph-channels. 3. Irritant material or trauma which destroys or injures the peritoneal surface, even in limited area, prepares a place for lodg- ment of germs which may be the starting-point of peritonitis. 4. Stagnation of degenerated fluid in dead spaces favors the growth of organisms, and the presence of infected blood-clots is especially liable to cause a virulent peritonitis. 5. Injury to the abdominal viscera^ as strangulation of an intes- tine, constriction and ligature of larger areas of tissues in the presence of pyogenic organisms, will almost certainly be followed by peritonitis. It has therefore been proved that the normal peritoneum, when unhampered by artificial conditions (as blood-clots, irritants, and trauma), can certainly dispose of certain amounts of pyogenic infection; but in direct opposition is the abnormal condition of the peritoneum in general septic peritonitis or in severe local peritonitis. In general peritonitis or severe local inflammatory conditions of the peritoneum the lymph-channels of the diaphragm are com- pletely choked by masses of bacteria, free and enclosed in leukocytes; these, by their mechanical obstruction, and also by setting up inflammation in surrounding tissues, effectually prevent absorption. Pawlowsky has shown that this obstructed condition of the lymph-channels always occurs, and has illustrated it very beautifully in a series of plates. Just as in Muscatello's experi- ments the absorbing channels of the peritoneum were filled with carmine granules, so in Pawlowsky's they were choked with bacteria and debris. This obstructed condition of these all-impor- tant absorbing channels occurs very early. Clark of Johns Hopkins University, accepting the facts of absorption and disposal of small amounts of infection by the normal peritoneum, reasoned that the slight infection occurring in the course of abdominal operations, such as contamination with pus or blood or septic fluids, would be taken care of by the absorp- tive channels of the peritoneum better than by intraperitoneal drainage. He maintained that drainage was used far too often, and that the normal peritoneum could take care of moderate con- 840 SURGICAL PATHOLOGY AND THERAPEUTICS. tamination, if given favorable conditions, without drainage. The method advised by him for operations in which there had been septic contamination of a previously normal peritoneum, or where raw and oozing surfaces were to be left, was to wash out the abdominal cavity thoroughly with gallons of hot salt-soluton, leave in the peritoneal cavity 500 to 1000 c.c. , close the abdominal wound without drainage, and place the patient for twenty-four hours in a position with the pelvis elevated. By this technique he washed out most of the infection, and by filling the abdomen with salt-solution and elevating the foot of the bed he followed the known facts of Muscatello's experiments — namely, that there are currents in the intraperitoneal cavity carrying particles to the lymph-spaces in the diaphragm, which currents are best favored by gravity. This method Clark called "postural drainage." It is distinctly stated by Clark, and also by Finney, that this method must not be used in general peritonitis, but that in such conditions free drainage is demanded. All experimental evidence proves that in a very few hours the absorbing channels of the diaphragm are clogged with debris and bacteria. The keynote of the treatment of general septic peritonitis must be the relief of the peritoneum and these obstructed lymph- channels; and this can be done only by removal of the septic exudation and subsequent drainage. There can be no doubt that in many cases of localized peri- tonitis the integrity of the peritoneum is so damaged that it would not be safe to abandon drainage. The absorbing channels have become so clogged that any fresh infection during an operation on localized peritonitis could not reasonably be disposed of by them. A statistical study of the operative treatment of peritonitis is almost worthless, because of the confusion in the reported cases between general and localized peritonitis, because of the lack of evidence in regard to the kind of peritonitis found, and the absence of bacteriological reports. Early in the present decade some remarkable percentages of recovery were published by numerous surgeons. Stuehlen reported 78 cases, with 50 recoveries; and surgical literature from 1890 to 1892 abounds in equally glowing statistics. These reports were misleading in that the operations were mainly done upon localized pus-collections in the course of appendicitis. Such percentages of recovery from general peri- tonitis are yet beyond possibility. There are infections so virulent and so rapid that the profound toxaemia, even at the outset of the disease, must always forbid operative interference. Acute puerperal sepsis with peritonitis frequently presents a con- dition in which the entire system has received a fatal amount of poison. Operation for the peritonitis will not remove the main source of infection, and the operation which includes removal of the uterus, tubes, and ovaries can seldom be wise. There are cases of peritonitis of puerperal origin, not so acute, which offer a favor- able chance of recovery by operation. Such cases as von Winckel BACTERIOLOGY OF PERITONITIS. 841 reports as successful operations for puerperal peritonitis are chronic cases, operated on weeks after the primary infection. The treatment by injections of antistreptococcic serum is as yet experimental and inconclusive. Wallick concluded that its use had not modified the mortality. Peritonitis associated with acute septic inflammation of the gall-bladder has been thus far uniformly fatal when operated upon. The infection is usually streptococci or colon-bacilli, and is of extreme virulence. Abbe has suggested that albumin in the urine of peritonitis cases is a contraindication to operation. There is no way of veri- fying this statement, because of the incomplete case reports. Cases of peritonitis occurring in the course of advanced renal and hepatic diseases — the cases of " terminal peritonitis" — cannot be regarded as suitable for operative treatment. Operations for typhoid perforation and for perforation of gastric or duodenal ulcers may be more accurately studied and the per- centages of recovery reasonably estimated. But a statistical study of the vast numbers of operations for general peritonitis from all other causes can give only one or two valuable points. The factors entering into each case are various, and differ with every indi- vidual; the virulence of the infection and the resisting powers of the patient cannot be estimated by statistics. The operation is dealing with a septic infection of varying virulence, which will cause death from toxaemia, and will be more successful as under- taken early in the infection. Operative methods must remove as much of the products of infection as possible; this can be done only by washing out and wiping the peritoneal cavity. The fact that one or two cases have recovered without drainage is no reason for deciding against it. Within five years opinions as to washing out and drainage have varied, but at the present time there is no uncertainty. Von Winckel, in his recent monograph on peritonitis, shows how those at one time denying the value of irrigation and drainage have been converted. Finney, in 1897, reported 5 consecutive successful cases — 1 in the course of a mild typhoid, and 4 caused by perforating appendi- citis. Cultures are reported in 2 cases; in 1 the infection was colon-bacilli and a doubtful coccus; the other was colon-bacilli and staphylococci. McCosh, in June, 1897, reported all his cases, and with special care 8 cases operated on in the year 1896. From 1888 to 1895 he had operated on 43 cases, with 37 deaths — a mortality of 86 per cent. Of the 8 cases operated on in 1896, all but 2 seemed in des- perate condition, but operation was considered the only possible chance for recovery. Of these 8 cases, 1 died as the immediate result of the operation, 1 died five weeks later of lung complica- tions, and 6 recovered. Bacteriological studies were made in 4 cases ; in 2 streptococci were found, in 2 colon-bacilli. Six cases were caused by gangrenous appendicitis, 1 by a septic uterus, and 1 by a perforating gastric ulcer. 842 SURGICAL PATHOLOGY AND THERAPEUTICS. The methods of operating adopted by Korte, Finney, and McCosh differ but slightly, and illustrate the best technique to be employed. All use very free incision, median or lateral, fully exposing the peritoneal cavity, and in some cases make an addi- tional cut in the right or left flank for further exposure and drain- age. All remove the intestines from the abdominal cavity if the patient is not absolutely moribund, keeping them warm with hot towels and hot salt-solution irrigation, and cleansing them and the peritoneal cavity as thoroughly as possible by very free irrigation and by gentle wiping with gauze pads. Finney pays special atten- tion to wiping off the flakes of fibrin from the intestines and wiping out the abdominal cavity, and especially the pelvis. McCosh does this, but lays stress on irrigation. If the distention of the intestinal coils is too great to permit replacing them in the abdominal cavity, multiple aspiration or incision of them is done, with subsequent suture. Salt-solution at a temperature of 112 to 114 F. is the irrigating fluid used. All use drainage : Korte, gauze, or rubber tubes and gauze ; McCosh, gauze or strips of silk ; Finney, gauze. McCosh injects an ounce of Epsom salt into the ileum with a large aspirating-needle, clos- ing the puncture with a Lembert stitch before replacing. Few cases are so desperate as not to permit these extensive procedures. These details of operation are proved wise by experiment and investigation. The fibrin-flakes on the peritoneum may contain bacteria. Irrigation will not remove these masses, but gauze wiping will. In certain forms of peritonitis this fibrin clings so firmly to the bowel that considerable force must be used to remove it. These are likely to be fatal cases. Irrigation will carry off much of the exudation. Reichel has shown that the irrigating fluid will not return sterile, but that it will return clear. Calvert and Kiting' s experiments proved that constant irrigation of the intestinal coils with hot salt-solution will rapidly reduce congestion and distention. The use of chemicals, such as peroxide of hydrogen and corro- sive sublimate, which is advocated by certain surgeons, is shown plainly to be wrong by Thompson and by Walthard. From their experimental work it is certain that even weak solutions of corro- sive sublimate may of themselves cause peritonitis, and that sterile water is often irritating, but normal salt-solution is not. VI. BACTERIOLOGY OF THE GALL-BLADDER. The bacteriology of the gall-bladder relates essentially not to the organ itself, but to the bile for which it acts as a reservoir ; for pathological changes in the walls of the gall-bladder due to bac- teria, though they may in rare instances be primary, are, as a rule, secondary to the invasion of the bile by micro-organisms. The BACTERIOLOGY OF THE GALL-BLADDER. 843 bile is not, therefore, as was formerly supposed, antagonistic to the growth of bacteria; but, on the contrary, allows the great majority of pathogenic organisms to flourish vigorously. The two chief channels of entrance by which bacteria reach the bile are the portal vein and the bile-ducts. Rarely the mode of ingress may be by the hepatic artery or the lymph-channels, but the importance of these two avenues for infection is comparatively small. Experimentally, organisms introduced into the portal vein or even the general circulation appear very soon in the bile ; and a similar process of elimination undoubtedly takes place in the human subject when a general septicaemia occurs, or when, by reason of pathological change in the intestinal mucous membrane, micro-organisms gain access to the portal vein. The ascending infection through the bile-ducts is determined largely by the character of the organisms in the duodenum and by the patency of the bile-ducts. The healthy duodenum is said to harbor colon-bacilli, staphylo- cocci, and streptococci ; abnormally, typhoid bacilli and pneumo- cocci ; but under normal conditions the bacteria do not leave the intestine, and the bile remains sterile. If, however, there be any obstruction to the flow of bile (calculi, malignant disease), or if the amount of bile be much decreased, as is said to be the case in acute infectious processes, conditions favorable to bacterial inva- sion are produced. The organism most often encountered in the bile is the Bacillus coli communis ; less often, the typhoid bacillus, bacillus of Fried- lander, streptococcus, Staphylococcus aureus and albus, and pneu- mococcus. The writer made bacteriological investigations in a series of 27 cases in which the gall-bladder was opened because of the presence of gall-stones or of inflammation from other causes, and a variety of the colon-bacillus was found 5 times ; the typhoid bacillus, 3 times ; Bacillus mucosus capsulatus, once ; pneumococ- cus, once ; and an unidentified diplococcus, once. In the other 16 cases cultures were negative. The invasion of the gall-bladder by the typhoid bacillus is a subject of great interest, and its importance has been emphasized by a number of investigators during the last ten years. The observations of Chiari showed that in typhoid fever the bile is very commonly infected by the specific germ of the disease. Out of 22 cases in which the bile was examined at autopsy, 19 showed the presence of typhoid bacilli. In 13 out of 19 positive cases the walls of the gall-bladder showed distinct evidence of inflammation. The inflammation was, to be sure, in most cases slight, affecting only the mucous membrane. In 1 case, however, all the coats of the organ were affected. Moreover, other observers have seen the pathological process go on to perforation and peritonitis. The 3 cases of typhoidal cholecystitis referred to above by the writer were of especial interest, because at the time of operation the nature of the affection was entirely unsuspected, and might have remained undetected had not the attending surgeon made 844 SURGICAL PATHOLOGY AND THERAPEUTICS. cultures as a matter of routine. Furthermore, 2 of the 3 cases (as yet unpublished) must be regarded as primary rather than secondary typhoidal infections of the gall-bladder, to which latter group, of course, the great majority of these cases belong. In both instances the patients were operated on for impacted calculi. In Case I. the operation, at which many gall-stones were removed, was followed by typical typhoid fever, with relapse. In Case II. no stone was found, but the gall-bladder showed marked thickening and was bound up in old adhesions. The patient insisted, how- ever, that he had never been ill in his life until within two weeks. In both cases the blood showed well-marked typhoid reaction (Widal). In the light of this experience, it seems probable to the writer that a considerable number of these typhoidal infec- tions of the gall-bladder escape observation because many surgeons fail to follow up their cases bacteriologically. Another case was especially remarkable because of the specific blood-changes that were shown in it. The infecting organism in this instance was a bacillus having points of resemblance to both the typhoid bacillus and the Bacillus coli communis — a so-called paracolon bacillus. In this case the blood showed a well-marked specific reaction (Widal) with its own infecting or- ganism, but upon the typhoid and colon bacillus it had no effect whatever. Another fact of importance is that bacteria, having invaded the bile, may persist in it for great lengths of time. Von Dungern records a most remarkable case illustrating this point. The patient had been seized with biliary colic five years subsequent to an attack of typhoid fever. Symptoms of gall-stones recurred from time to time, but it was not considered necessary to operate until fourteen and a half years after the typhoid fever. At the operation, how- ever, together with many calculi, was found a pure culture of the typhoid bacillus. Moreover, this persistence of the typhoid organism in the bile should be borne strongly in mind in all cases in which at autopsy a previous typhoid fever is suspected, for it has been the experi- ence at the Pathological Laboratory of the Massachusetts General Hospital, not only that the bile was infected in practically every case, but also that the gall-bladder might be the only organ to show the specific organism. The relation of bacteria to the formation of gall-stones has been during the last decade the subject of much investigation, especially by French observers. In a considerable proportion of cases the gall-stones have been associated with bacteria, notably the Bacil- lus coli communis and the typhoid bacillus. Moreover, micro- organisms have been demonstrated in the center of certain biliary calculi. Thus, Gilbert and Fournier examined bacteriologically gall-stones from 27 different cases. The results were as follows: In 19 cases cover-glass examination and cultures were negative. These stones were all old. In 7 cases cover-glass examination and cultures showed Bacillus coli communis. Of these stones, 6 were of recent formation; 1 was old. In 1 case culture was neg- BACTERIOLOGY OF THE GALL-BLADDER. 845 ative, whereas cover-glass examination showed bacillary forms very imperfectly stained. The writer has investigated gall-stones in 10 cases, but has been able to demonstrate bacteria — Bacillus mncosns capsnlatns — in a single case only. In this instance the same organism was culti- vated from the bile. The stone examined was large, hard, stratified, apparently of considerable age, and its surface was, as far as could be seen, unbroken. It does not, therefore, seem prob- able that the bacilli soaked into the stone from the surrounding bile, though this mode of inoculation must always be considered as possible, especially in the softer stones of recent formation. The temptation to declare a causal relation between the bacteria and the stones is great. This relation is, however, far from estab- lished, though theoretically it has much in its favor. Thus it is argued that cholesterin and pigment are held in solution by the alkaline salts of the biliary acids. If now, for any reason (stagna- tion with absorption of water), the amount of cholesterin becomes excessive or the reaction of the bile becomes acid (acid-production of colon and typhoid bacilli), the conditions for the precipitation of biliary pigments and cholesterin are realized, and formation of cal- culi is determined. Furthermore, in the typhoid infection of the gall-bladder it was noted by dishing and the writer that the bacilli were often arranged in large clumps; and these collections of bacteria were frequently associated with considerable masses of pigment and debris. There was therefore suggested the possibility that these aggregations of bacilli and pigment would serve as excellent nuclei for the formation of calculi. The typhoid organisms might in this case act in two ways: First, to cause an acid reaction in the bile, with consequent precipitation of cholesterin and pigment; secondly, to serve as nuclei upon which the stones should form. As already stated, the subject has been a favorite one with French observers, and a great many investigations have been made, especially by Gilbert and his associates, Fournier, Dominici, and Claude. In experiments upon rabbits, Gilbert succeeded in producing a calculus as large as a grain of wheat by injecting into the gall- bladder three drops of a typhoid culture which had been heated for ten minutes to 50 C. Mignot introduced his bacteria upon pledgets of cotton. After a number of days the cotton was removed. The bacteria, then left to themselves, produced in one-third of the cases regularly stratified cholesterin calculi. The writer, working on the "clump" theory of origin for biliary calculi, injected into the gall-bladder of a rabbit typhoid bacilli which had been agglutinated by the addition of typhoid serum. In this case, after four months a brown calculus, the size of half a pea, v/as found. In its clinical aspect this relation between typhoid fever and gall-stones has been the subject of especial study by Dufourt, who records 19 cases in which enteric fever was followed by distinct 846 SURGICAL PATHOLOGY AND THERAPEUTICS. symptoms of cholelithiasis. Previous to the typhoid there had been nothing to suggest the presence of calculi in the gall-bladder. In 12 cases the symptoms appeared within six months of the typhoid attack; in the other cases the interval was much longer, and a connection between the two pathological conditions was more difficult to trace. Dufourt acknowledges that the gall-stones may have been present without causing symptoms previous to the typhoid fever, but he does not consider this probable. The evidence seems, therefore, quite strong that bacteria do have an important part in the formation of gall-stones; but much more extended investigation is needed before well-defined con- clusions can be drawn. VII. SERO=THERAPY IN TETANUS, TUBERCULOSIS, AND SYPHILIS. Tetanus. — The fact that sero-therapy in diphtheria has more than justified its early promise as a life-saving treatment has given grounds for hope that the antitoxin of other diseases, notably streptococcus-infection and tetanus, might also be brought under control by the antitoxins produced by the growth of the organisms themselves, and of recent years great activity has been shown in the endeavor to elaborate and apply in both experimental and clinical work the antitoxin treatment to tetanus and streptococcus- infection ; but in both these diseases the difficulties met with in the endeavor successfully to put in practice the antitoxin treatment have been much greater than was the case in diphtheria. In the case of tetanus the chief difficulty has consisted in the fact that during the incubation of the disease, and even before the first symptoms have developed, in animals at least, so large an amount of toxin has been absorbed, and perhaps fixed, in the system that the most concentrated antitoxic serums which it has so far been found possible to produce have been found to be too weak to neu- tralize them. In order to save the life of a horse inoculated with tetanus- toxin, it is found necessary to inject the antitoxin before the symp- toms have appeared. This fact does not hold true in man, as in the human subject tetanus is a vastly more variable disease, and less uniformly fatal, than in horses. As is well known, the mor- tality in human tetanus varies with the acuteness of the case, especially as manifested by the time of onset of the symptoms. Rapidly progressing cases, in which the symptoms appear early, give a mortality of 90 per cent, and upward. In the class of cases in which the symptoms appear later aud progress slowly the mor- tality has been estimated at only about 40 per cent. The difficulty in securing an effective antitoxic serum for use in human tetanus is greatly enhanced by the fact that the acute and virulent cases, which have the highest mortality and in which the SERO-THERAPY IN TETANUS, ETC. 847 need for a suitable antitoxic serum is greatest, are the very cases in which the disease most nearly approaches the type seen in horses — when, by the time the symptoms have appeared, so large an amount of toxin has been absorbed into the system that the strength of the antitoxic serum has been too slight to cope with it effectively. There has been no evidence so far published that the antitoxin treatment has lessened the mortality of the very acute cases. Carefully compiled statistics of 167 cases of tetanus treated by antitoxin up to June, 1898, 1 gave a mortality of about 40 per cent, for all cases treated by the subcutaneous injection of antitoxin, as against a roughly estimated mortality, for all cases of the disease under previous methods of treatment, of 60 per cent. These statistics are open to criticism, owing to the not infrequent failure to record unsuccessful cases, and the fact that in many of the cases that were treated by antitoxic serum the dosage was so small and the strength of the serum so various that it becomes extremely difficult to decide in any case that recovered whether the recov- ery was due to the serum or not. The amelioration of symptoms that so definitely follows the administration of antitoxin in diph- theria does not occur in tetanus. Of all the experimental workers who have engaged in the prep- aration of antitoxic serum, Behring alone has produced a dried serum of considerable condensation and of an antitoxic strength of 100 units to the gram of the dry powder (the unit is the amount of antitoxin that will neutralize 1,000,000 minimum fatal doses for a 250-gram guinea-pig). The strongest liquid serum which Behring has put on the market contained 5 units to the cubic centimeter. The serum produced by the Massachusetts State Board of Health contains 1 unit to the cubic centimeter, and it is probable that the majority of the antitoxic serums on the market do not exceed this in strength. As a result of experimental and clinical work, Behring has con- cluded that in the human adult no less than 500 units must be administered at one dose in order to prove effective against the tetanus-toxin. With a serum of 1 unit to the cubic centimeter it would therefore be necessary to administer 800 c.c. at a single dose in order to have any reasonable probability of affecting favor- ably the course of the disease. In the vast majority of the reported cures the dose has been from 10 to 40 c.c. of the serum, so that it seems hardly reasonable to suppose that the course of the disease has been favorably or unfavorably influenced thereby. 2 In order to secure the immediate action of the antitoxin in the largest possible quantities upon the nerve-centers of the body, it is advisable to administer the serum by intravenous infusion. This is especially true of trie serums of which a large amount must be 1 Lund, Boston Med. and Surg. Jour., Aug. 18, 1898. 2 A recent test by Theobald Smith of the tetanus-serum furnished in sealed tubes by Tavel of Zurich, of which the dose advised is 10 to 20 c.c, showed that it was at least 10 per cent, weaker in antitoxic strength than that furnished by the Massachusetts State Board of Health. It must therefore contain less than I unit of antitoxin per cubic centi- meter, and the dose advised must be utterly inadequate. 848 SURGICAL PATHOLOGY AND THERAPEUTICS. employed, owing to the slowness and difficulty of administering large quantities of fluid hypodermically. The serum should be warmed to a temperature of 101 or 102 ° F., and, of course, all antiseptic precautions should be taken. The serum, when ob- tained from the manufacturers, is put up aseptically in sealed receptacles. It should be kept on ice in a dark place. With a view of obtaining immediate action upon the nerve- centers, by which experimental work has shown that the tetanus toxin is fixed, and into combination w r ith which it enters, the intracerebral injection of from 4 to 6 c.c. of the serum has been practised during the past years. Roux and Borel found that the intracerebral injection of anti- toxin was effective in guinea-pigs, and more so than the subcu- taneous injections. In the human subject, in December, 1898, the intracerebral injection had been practised in 12 reported cases, of which 5 died. As was to be expected, the fatal results occurred in the more acute type of cases. One unreported acute case is known to the writer, in which death followed intracerebral injection. In case this operation is practised, it is advisable to administer the serum intravenously as well, in order, if possible, to neutralize any toxin which may already be circulating in the blood. About 3 c.c. of antitoxin are injected into the center of the frontal lobes, slowly, in order not to injure the brain-tissue. A small trephine-opening must be made on either side. Owing to the small number of cases reported, the value of this procedure remains in doubt. Recent experience with intracerebral injections of the serum have failed to establish its value. It is difficult, for the same reason, to form an estimate of the value of the antitoxin treatment as a whole, owing to the varying gravity of the disease and the small number of cases that fall within the experience of any single observer. There is good rea- son for hope, however, that with the amount of activity that is being shown by laboratory workers in endeavoring to produce antitoxic serum of greater strength, and by clinicians to perfect methods of administration, the treatment may in the not distant future become an efficient aid in lessening the mortality of tetanus. The Antistreptococcic Serum. — In 1895, Marmorek, using the horse and the ass for immunization against streptococcus-infec- tion, produced a serum which, if injected into rabbits sufficiently early after a fatal dose of the streptococcus toxin, would protect the animal against the latter. The amount of serum which it was necessary to employ, however, increased rapidly with the time after the toxin was given, and in the case of 10 times the fatal dose of a very virulent culture it was found that no amount of antitoxic serum, if injected more than six hours after the original injection, would protect the animal. In the case of less virulent cultures the infection might be checked twenty-four to thirty hours after the injection. Koch and Petruschky have shown, however, that the virulence SERO-THERAPY IN TETANUS, ETC. 849 of a streptococcus culture for animals was no index of its activity for the human subject, and found that no effect was produced on man with several cultures which were highly virulent for rabbits. Petruschky also found that neither Marmorek's nor Aronson's serum sensibly modified the course of an erysipelas produced in the human subject by inoculation with a culture from human erysipelas. In puerperal fever, according to Cotton, 1 the serum had been employed in 107 cases, with 34 deaths — a mortality of 31.7 per cent. In erysipelas Marmorek reports 413 cases, with a mortality of 3.87 per cent., as against a mortality of 5. 12 per cent, in previous cases treated in the same service. In regard to other general infections — pyaemia, endocarditis, osteomyelitis, etc. — too few cases have been reported to enable any conclusion to be drawn. In attempting to estimate the value of the serum, we are con- fronted by the fact that we are dealing with isolated cases seen by different observers, and with a disease which runs no definite and typical course. In Marmorek's series of erysipelas, the only large series treated by a single observer, the reduction in the mortality was very small, and within the limits of variation in the mortality of the untreated disease. An improvement in the subjective symptoms immediately following the administration of the serum occurred in a certain number of cases, but was not by any means constant. Cotton 2 concludes that although the serum is not, broadly speaking, effective against streptococcus-infections, a certain degree of passive protection is certainly present in the laboratory-experi- ments, and something of the sort is possible in man. He advises further trial of the serum as a symptomatic and adjuvant to other treatment, if nothing more. In no case should it be employed to the exclusion of stimulation and other methods of treatment, as advised by Marmorek, but only in conjunction with them. It should be employed in doses of from 10 to 25 c.c. ; and care should be taken to select a serum the preparation of which is known to have been conscientious. Surgical Tuberculosis. — It is chiefly in the field of pulmonary tuberculosis that the serum treatment has been employed. The serums employed have been obtained from horses subjected to treatment by injections of tuberculin or the new tuberculin T. R. of Koch. The results have been in the early cases favorable, and in the advanced cases with mixed infection the treatment has naturally done no good. The fact that the early cases have so often done well under the climatic and general hygienic treatment with which the serum treatment has been naturally conjoined renders it impossible to form an estimate of the value of the latter. In surgical tuberculosis such good results are attained by immobilization combined with hygienic treatment, ablation of the foci by operations, etc., that the reasons for the employment of the serum treatment in the early cases — the only ones in which it could render any promise of being effective — have not demonstrated 1 Boston Med. and Surg. Jour., Feb. 2, 1899. 2 Loc. cit. 54 850 SURGICAL PATHOLOGY AND THERAPEUTICS. themselves sufficiently to lead to its general employment. The chronicity of the disease and the length of time during which the treatment would have to be continued have militated against its trial. The infectious granulomata, such as syphilis and tuberculosis, are so manifestly different in their nature from the acute infectious diseases in which antitoxins have proved of value that the success- ful application of the antitoxin treatment is in them fraught with additional difficulties, and the extension of the principle of immunity to them is a matter of doubt. Syphilis. — Acting on the theory that immunity from syphilis is present in those who have previously passed through the dis- ease, numerous attempts have been made in the treatment of this disease with the serum of animals, the serum of syphilitic patients, the serum of animals previously treated with mercury, etc. No definite results have so far been reported. INDEX OF NAMES. Abbot, 202 Abemethy, 633 Adamkiewicz, 699 Adams, Z. B., 572 Albarran, 720 Albers, 579 Albert, 442, 693 Alibert, 660 Allingham, 561 Amidon, 444 Anagnostakis, 785 Andrews, 580, 662, 672 Arnd, 693 Arning, 65 Ashhurst, 392, 686 Askanazy, 839 Assaky, 243 Aufrecht, 444 Babes, 25, 45, 470, 472, 474, 482, 485, 486, 559, 574, 576, 5»5» 595, 709 Baker, 677, 696 Balbiani, 640, 642 Ballance, 220, 254, 379 Baltzer, 729 Banks, 669 Barbacci, 836 Barbieri, 385 Barker, 678, 683 Bartacci, 49 Baumgarten, 25, 38, 45, 56, 61,62,74,75,77,107,143, 145, 146, 33%, 360, 373, 383, 384, 486, 507, 508, 612 Beach, 243, 794 Becker, 43 Behring, 153, 450, 847 Belfield, 469 Bell, Hamilton, 404 Bell, John, 295 Bell, Joseph, 659 Bender, 584 Bennett, 357 Berard, 487 Berger, 288 Bergmann, 24, 336, 787, 799 Bernard, Claude, 79, 82, 114, 116, 290, 305 Bernhardt, 442 Besnier, 558 Besser, 338, 359 Betoli, 436 Bichat, 289, 633, 634 Bigelow, 385 Billings, 643 Billroth, 135, 140, 144, 277, 282, 289, 290, 314, 326, 3 2 9, 334, 3 6 7, 372, 374, 3 8 4, 435, 5*4, 5 2 3, 539, 545, 548, 550- 55i, 664, 668, 669, 678, 683, 689, 703, 723, 729, 740, 7 6 8 Binaghi, 800 Biondi, 143 Birch- Hirschfeld, 752, 753, 758,761,767,770,776,783 Birdsall, 460 Bischer, 746 Blodgett, 464 Blum, 278, 281 Blumberg, 803 Bockhart, 139 Bode, 694 Boll, 636 Bollinger* 76, 469, 475, 487, 491, 509, 510, 515 Bonome, 70, 145, 146, 360, 493 Booker, 49 Bordoni, 65, 70 Borel, 848 Borner, 125 Bostrom, 470, 474, 475 Bosworth, 728, 753 Bouchard, 47 Bourgeois, 480 Bowen, 562 Boyle, Robert, 17 Bradford, 523, 536, 539, 540, 554, 603, 604, 609 Braidwood, 369, 376 Brandenburg, 515 Brewer, 805 Brieger, 24, 55, 436 Bristowe, 288, 377, 424 Brock, 558 I Brodie, 533, 761 Brodinsky, 729 Brouardel, 456 1 Brown, 563 Brown-Sequard, 84, 282, 305, 444, 46o Brugmanns, 418 Brunner, 441, 442 Bruns, 249, 250, 626, 747 Brunton, L., 292 Bryant, 663 Buchner, 20, 41, 73 Bucq, 563 Budor, 695 Bull, 669 Bumm, 51, 52, 139 Busch, 600, 619 Busch, W., 401 Butlin, 657, 658, 659, 679, 684, 689, 690, 692, 693. 697, 725, 727 Buxton, 736 Cabot, 720 Cabot, R. C, 100 Cabot, S., 385 Cagniard-Latour, 17 Calmette, 502, 503 Calvert, 835, 842 Carmalt, 645 Cattani, 451, 804 Cayla, 575 Cenkowski, 74 Chamberlain, 69 Chandler, 412, 413 Chapman, 644 Charrin, 594 Chassaignac, 211 Chauveau, 69, 341 Cheever, 212, 286, 297, 298, 725, 726 Cheyne, 137, 141, 142, 144, 148, 149, 150, 151, 338, 341, 506, 507, 510, 518, 519, 520, 530, 535, 537 Chiari, 843 Chiene, 672 Chomel, 402 Christmas, 141 Clark, 807, 839, 840 Clark, Le Gros, 292 Clarke, Lockhart, 444 Claude, 845 Cleveland, 419, 420, 432 Cobbett, 838 Cohen, 727 Cohn, 22 Cohnheim, 56, 92, 94, 95, ioi, 102, 103, 104, 106, 113, 116, 118, 135, 218, 309, 504, 635, 636, 703 851 852 INDEX OF NAMES. Coley, 401, 734, 735, 806 Colin, 570 Colles, 445 Cooper, Sir Astley, 277, 282, 291 Cornet, 61, 509 Cornil, 25, 104, 149, 402, 508, 5io, 559, 574, 576, 595 Cotton, 849 Councilman, 53, 140, 574,639, 643, 708 Courmont, 1 94 Coze, 336 Crocker, 741 Cruveilhier, 356, 375 Curling, 439 Curtis, 457, 460, 461, 464 Cushing, 836 Czerny, 686, 689, 690, 692 Dana, 459 Darier, 641, 642, 671 Davaine, 17, 18, 71, 336, 477 Davidson, 100 De Bary, 19, 140 Decroix, 486 Delapine, 640 Delpech, 409 Dernarquay, 657 Dennis, 669 Desportes, 439 Dexter, 381 Dietrich, 663, 669 Disse, 67 Dbderlein, 805 Doleris, 358, 455, 458 Dominici, 845 Dufourt, 845, 846 Duhring, 276 Duncan, 337, 344, 677 Dupuytren, 439, 590 Duret, 297 Dussaussoy, 409, 418 Ebermaier, 196 Eberth, 729 Edwards, 220, 254, 729 Eiselberg, 144, 338 Elting, 842 Englisch, 581 Erichsen, 725 Ernst, H. C, 48, 61, 136, 143, 456 Ernst, Paul, 48 Escherich, 48 Esmarch, 561 Etiolles, Leroy d', 636 Eulenburg, 280 Eve, 66 Ewart, 499 Eyles, 276 Falk, 279 Farr, 17 Fayrer, 495, 497, 499, 500 Fehleisen, 382, 734 Fehling, 600, 602 Felix, 421 Feltz, 336 Fenger, 697 Fenwick, 696, 720 Feoktistow, 497, 502 Ffolliott, 325 Filene, 296 Finney, 840, 841 Fischer, 278, 279, 280, 281, 288, 289, 296, 418, 613, 6i5 Fitz, 462, 463 Fleischmann, 634 Flemming, 104, 219 Flexner, 732, 733, 835 Fliigge, 69 Fol, 455 Foote, 270 Forcade, 612 Fournier, 844, 845 Frankel, 25, 37, 40, 47, 49, 61, 198, 486, 508, 836 Frothingham, 55 Gaillard, 836 Gamaleia, 459 Gamgee, 378 Gannet, 679 Gardner, 579 Garre, 42, 138, 172,420, 590, 591 Gartner, 150 Gaskell, 306 Gaspard, 335, 349, 357 Gay, Geo. H., 780 Gay, Geo. W., 289, 291, 293 Gay-Lussac, 17 Gensmer, 132 Gibney, 614 Gifford, 817 Gilbert, 844, 845 Glax, 96 Godwin, 70 Goldsmith, 411, 432 Goltz, 82, 84, 85, 279, 280, 281, 289 Gosselin, 392, 402 Gottstein, 800 Gowers, 461, 462, 463, 467, 732 Graefe, 123 Gram, 43, 46, 48, 49, 5°, 5 2 , 64, 66, 67, 68, 72, 77, 135, 270 Grawitz, 105, 106, 140, 220, 221, 742, 838 Gray, 460, 725 Greenfield, 747 Grinelle, 444 Grivet, 400 Gronin, 477 Groningen, 85, 280, 281, 282, 283, 285, 287, 288, 289, 291, 292, 300 Grosch, 762 Gross, S. D., 278, 280, 287, 292, 725 Gross, S. W., 663, 669, 697, 713, 714, 715, 716, 719, 724, 725, 738 Gruber, 613 Gubler, 641 Guerin, 378 Gueterbock, 442 Gussenbauer, 288, 339, 342, 346, 35°> 363, 369, 377, 652 Gusserow, 676, 721 Guthrie, 277 Guyon, 695 Hacker, von, 686 Haidenhain, 261, 264 Haight, 86 Hall, 381 Halsted, 150, 572, 788, 802, 805, 838 Hamilton, 271 Hammic, 67 Hanau, 643 Hankin, 153 Hansen, 64 Hare, 296 Harrington, 340 Hartman, 835 Haviland, 642, 643 Hebra, 755 Hegar, 575 Heine, 416, 420, 421, 426 Heitzmann, 603 Hesse, 704 Heuppe, 40 Heuter, 122, 140, 348, 359, 367, 388, 399, 406, 433 Hewitt, 579 Hinterstoiser, 719 Hippocrates, 356, 447, 785 Hirt, 617 His, 745 Hochenegg, 473, 475 Hodge, 285 Hoffa, 324, 325, 326, 327, 348 Hofmeier, 677 Hofmeister, 370 Holmes, Bayard, 492 Holmes, O. W., 386 Holmes, T., 212 Homans, 725, 726 Homes, E., 500 Hooper, 728 Horner, 500 Horsley, 324, 350, 379 Howell, 238, 239, 240 Huber, 149, 238, 239, 240 Hunter, 92, 1 15, 117, 288, 356 INDEX OF NAMES. 353 Hutchinson, S5, 305, 376, 617, 654, 755. 756, 761, 769 [AKOWSKI, 4S Israel, 76, 469, 485, 697 Iversen, 692 Taboulay, 194 Jack, 379 Jeffries, 49, 790 Jensen, 470 Jewell, 444, 448 Johne, 470 Jones, Joseph, 41 1, 412, 413, 414, 418, 420, 427, 428, 431 Jordan, 277, 294 Kalming, 492 Kaposi, 712 Karlinski, 478 Kassowitz, 603, 609 Kaufrnann, 581, 657 Keen, 85, 87, 124, 410, 411, 420,431 Kelley, 803 Kelsey, 692 Kitasato, 54, 55, 153, 45° Klebs, 67, 576, 579, 610, 643, 694, 746, 752 Klein, 835 Klemm, 442 Knapp, 136, 730, 760 Knecht, 448 Knie, 686 Koch, 18, 31, 32, 34, 42, 48, 56, 59, 61, 67, 70, 71, 74, 296, 337, 338, 356, 383, 415, 478, 479, 493, 5°5, 515, 558, 699, 848 Koch, W., 70 Kocher, 149, 194, 210, 576, 577, 681, 682, 683, 684, 698, 722, 723 Koenig, 524, 528, 545 Kolesnikoff, 462 Kolliker, 238, 242, 244 Konetschke, 325 Konig, 583 Koplik, 196, 205 Koionyi, 479, 484, 487, 491 Korte/835, 842 Koster, 533 Kraske, 195, 693 Krause, 515, 516, 522, 525, 533, 538, 540, 546, 548, 556 Krebs, 242 Kubasoff, 637 Kiister, 669, 694, 695 Kyle, 818 Lacerda, 502 Laennec, 504 Landerer, 96, 1 13, 243, 514, 594, 800 Langenbeck, 469, 636 Langenbuch, 284 Langhans, 581, 721, 743 Lannelongue, 211, 464 Larrey, 435, 439, 444, 445 Lathrop, 61 1 Latta, 277 Laveran, 444 Lawrence, 511 Leber, 141 Lebert, 469, 634, 636 Leeuwenhoek, 17 Legg, W., 463, 711 Leichtenstern, 729 Leloir, 561 Letievant, 243 Lewisson, 284 Leyden, 283 Liborius, 69 Liebig, 17 Lietzmann, 601 Lilienfeld, 311, 312 Lingard, 66, 70, 270 Lister, 122, 139, 215, 333, 801, 805 Litten, 332 Lobker, 243 Lobstein, 633 Loffler, 61,485 Lombard, 84 Lovett, 523, 603, 609 Lucan, 498 Lustgarten, 65, 66 MacAllister, 306 Macewen, 379 Mackenzie, 684 Maclagan, 310 Macleod. 410, 420, 428 Madelung, 761 Maissonneuve, 394 Makin, 202 Malassez, 595 Malphigi, 612 Mandry, 583 Mann, 411 Mansell-Moullin, 278, 280, 282, 286, 291, 297 Maragliano, 369 Marchand, 694 Marchant, 212 Markoe, 618 Marmorek, 848 Marsh, 696 Martineau, 67 Maschka, 290 Maude, 747 McCormack, 761 McCosh, 836,841 McKenzie, 614 McPhedran, 614 Mears, 618, 619 Melcher, 65 Melchoir, 827 Menzel, 627 Merillat, 414 Metschnikoff, 40, 106, 107, 153, 384, 642 Metsome, 838 Meyer, 282, 686, 701 Michaud, 444 Middledorff, 510 Mignot, 845 Mikulicz, 548, 803, 805 Millat, 612 Miller, 807, 814 Mills, 272 Mitchell, Weir, 84, 85, 86, 87, 124, 275, 282, 284, 286, 292, 435, 497, 5o° Mixter, 379, 476, 685 Moebius, 747 Moller, 29 Monks, 688 Monnier, 179 Monti, 603, 609 Morax, 817, 835 Morehouse, 85, 86, 124 Morgagni, 356 Morgan, 687 Morland, 385 Morrow, 562, 563 Mosetig-Moorhof, 700, 701, 790 Mosler, 576 Mueller, 502 Muller, 648 Miiller, J., 634 Muller, W., 516, 555 Mumford, 299 Murphy, 469, 475 Murray, 611 Muscatello, 837, 838 Nageli, 20 Nancrede, 132 Nasse, 238, 704, 713 Nauwerck, 235, 236 Neelsen, 339 Neisser, 50, 64, 801 Nelaton, 208, 614 Netter, 836 Neudorfer, 277 Neumann, 237, 239, 240 Newman, 684, 687, 688, 725, .753 Nicaise, 452 Nicolaier, 54 Nocard, 59, 486 Norton, 124 Obersteiner, 242 Ogata, 483 Ogston, 43, 135, 136, 144, 146, 194, 333, 337, 342, 358 Oilier, 196, 212, 213 Ollivier, 418, 419, 420 Ore, 448 854 INDEX OF NAMES. Orlowski, 835, 839 Orth, 259, 674, 675, 677, 694, 697, 7*9, 720, 721, 75o, 838 Ortmann, 65 Osier, 98, 361, 365, 376, 569, 57o Ostroumoff, 82 Ott, 305 Packard, 87, 430, 432 Page, 293 Paget, 124, 179, 298, 324, 326, 613, 671, 738, 758, 768, 769, 773 Paltauf, 562 Panum, 336 Paracelsus, 356 Pare, A., 356 Park, Roswell, 195, 196, 267, 643, 644, 700, 701 Partsch, 471, 472, 475 Pasca, 456 Passet, 45, 48, 143, 800 Pasteur, 17, 18, 22, 23,30, 39, 40, 67, 71, 74, 140, 194, 336, 357, 35 8 , 455, 4&4» 465, 467, 468, 478 Pawlosky, 836 Pawlowski, 839 Pawlowsky, 359, 704, 838 Payne, J. F., 571, 754, 755 Pearson, 492 Pelot, 412 Perron cito, 469 Peterson, 212 Petit, 356 Petit, R., 817 Petrone, 140 Petruschky, 848 Pfeiffer, 595 Pick, 404, 405 Piorry, 335, 356 Pirogoff, 277, 288, 390, 394, 405, 424 Pithia, 425, 426 Podwyssozki, 641 Poland, 439 Pommer, 603 Poncet, 434, 439, 440, 443, 447, 448, 449, 630 Ponfick, 76, 469 Porter, 671, 725, 740 Post, Abner, 574 Post, Sarah E., 677 Potter, 617 Pouteau, 409, 430 Power, 644 Preusse, 492 Prudden, 509 Putnam, 461, 615, 747 Raimbert, 480 Randolph, 817 Ranke, 70 Ranvier, 104, 238, 240, 246, 444 Rayer, 71 Raynaud, 274, 275, 395, 397, 398, 400 Recklinghausen, von, 87, 93, 97, 101, 103, 116,118,241, 257, 271, 754 Redard, 297 Reichel, Z^, 842 Reichert, 497 Reid, 660 Remak, 638 Reyher, 627 Reymond, 835 Ribbert, 143, 149, 360 Richardson, Anna G., 677 Richardson, M. H., 49, 669, 684, 725 Riedel, 528 Riedinger, 526 Riehl, 562 Rindfleisch, 646, 652, 684 Rivolta, 455, 469 Robb, 800 Roberts, 287 Robin, 469 Rochard, 420, 430, 431 Roger, 594 Rogivue, 721 Rokitansky, 357, 577, 634 Rose, 435, 442 Rosenbach, 43, 46, 53, 56, 69, 136, 143, 194, 338, 358, 359, 3%3, 417, 420, 421, 425, 442 Rosenblath, 75, 482 Rosenstirn, 763 Rosenthal, 309 Roser, 208, 537 Roux, 59, 69, 211, 451, 583, 848 Ruge, 673 Russell, 641 Salleron, 578, 580 Samuel, 256, 270 Sanderson, Burdon, 96, 103, 113, 119, 120, 122, 357 Savory, 277, 281, 283, 366, 377, 378 Sayre, 541, 547 Scanzoni, 579 Schatz, 803 Schede, 215, 280 Scheuerlen, 639 Scheyron, 677 Schieffendecker, 242 Schimmelbusch, 139, 270, 738, 739 Schloffer, 801 Schneider, 279 Schroeder, 672 Schuchardt, 653 Schuh, 363, 768 Schutz, 61, 485, 642, 804 Schwann, 17 Scott, 640 Selmi, 24 Sendler, 592 Senn, 70, 216, 254, 553, 555, 556, 581, 588, 751 Senner, 173 Sevestre, 836 Shakespeare, 56, 103, 106 Shattock, 644 Shattuck, 456, 464 Simmonds, 577 Simon, John, 115 Simmourin, 449 Simpson, Sir Jas., 365 Sims, Marion, 347 Sjobring, 641 Siting, 835 Smith, Greig, 697 Smith (Theobald), 847 Smith, Thomas, 324, 326 Sokoloff, 623 Soltmann, 470 Sonnenburg, 279 Spallanzani, 17 Sprouk, 734, 806 Ssabenejew, Frank, 686 Stantly, 208 Stedman, 604, 609 Steinhaus, 48, 139, 142, 143, 144, 640, 704 Sternberg, 25, 31, 355 Stilly 386, 387,393,399,402, 404, 405 Stokes, 836 Stone, 61, 144, 340, 677, 696 Stort, 704 Strassburger, 104 Straus, 482, 491, 787 Strieker, 80, 83, 84, 86, 103, 105, 108 Stromeyer, 292, 434 Stuchlen, 840 Sudan, 276 Suzor, 454 Sylvius, 297 Symonds, 685 Taguchi, 67 Targett, 695 Taylor, 547, 614, 615 Thieberge, 614 Thiersch, 189, 224, 636, 650 Thin, 671 Thoinot, 18 Thorn a, 641 Thompson, 842 Thompson, Sir Henry, 720, 752 Thomson, 419, 423, 427, 750 Thornbury, 412 Thorndike, 693 Tillmans, 381, 382, 383, 385, 394, 397, 401, 405 Tizzoni, 451, 46S, 616 Torek, 729 Trau be, 30S, 309 Travel, 800 Travels, 277, 286, 296, 435 Tricomi, 70 Trousseau, 39S, 402, 446 Tscherning, 510 Uffreduzzi, 70 Ullmann, 195, 197, 207, 210 Van Arsdale, 205, 212 Van I Jure 11, 119, 122 Van Harlingen, 560 Vanlair, 243 Vaughn, 339, 342 Veit, 673 Velpeau, 356, 403 Vernet, 123 Verneuil, 436, 444, 482, 639, .755 \ etiesen, 581 Viering. 234 Vignal, 595 Villemin, 56, 504 Vincent, 289 Virchow, 97, 101, 1 18, 126, 218, 357, 485, 578, 612, 613, 633, 634, 635, 636, 637, 640, 703, 707, 717, 729, 754, 760, 765, 767, 769,874,881 Vogt, 243 Volkmann, 166, 205, 208, INDEX OF NAMES. 212, 390, 392, 400, 514, 516, 520, 531, 532, 536, 539, 543, 566, 567, 5*5, 588, 589, 630, 659, 060, 668 Vollert, 630 Von Hacker, 686 Von Winckel, 836, 840 Vulpian, 79 Wagner, 734, 838 Wall, 497 Wallenberg, 679 Waller, 86, 238 Wallick, 841 Walthard, 842 Walton, 309 Warren, J. C, 634, 718 Warren, M., 655, 718 Washburn, 839 Wasserman, 726 Waterhouse, 838 Watson, 695, 696, 752 Weber, 314 Weber, C. O., 116 Weber, O. 421 Wegner, 617, 781 Wehr, 643 Weichselbaum, 579, 622 Weigert, 106, 257 Weil, 652 Weir, 690 Welch, 138, 143, 571, 688, 800, 801, 803 Wells, Spencer, 572 855 Wette, 747 White, J. C, 406, 641, 652 Whitaker, 483 Whitehead, 682, 683 Wickham, 641, 671, 672, 71 1 Wiggleworth, 139 Wight, 790 Williams, 94, 673 Williams, J. L., 815 Winckel, 573, 579, 600, 602, 720 Winiwarter, 187, 662, 668, 698, 709, 710, 711, 771, 773,781, 782 Witzel, 686 Wolff, 637 Wolfler, 743, 744 Wood. 40, 305 Wood, H. C, 313 Woodhead, 642 Wright, 836 Wyssokowitsch, 42, 360 Yandell,437, 441, 443, 447, 448, 450 Yarrow, 495, 497 Zagari, 595, 596 Zahn, 122, 361 Zeigler, 104, 106, 156, 218, 219, 605, 610, 612, 616, 624, 704, 763, 776, 780 Zeisler, 561, 562 Zenker, 683 Ziemssen, 643, 652, 755 INDEX Abscess, 156, 157 atheromatous, 259 callosities of the hand the starting-points of, 1 71 drainage in, 165 fluctuation in, 158 formation, 147 lung, experimental, 145 psoas, 525 retropharyngeal, 525 shirt-stud, 168 tubercular, membrane of, 520 wall of, 157 Abscess-formation, bacteria of, 789 in osteomyelitis, 198 Abscesses, cold, 519 treatment, 548 mammary, 165 metastatic, 362 of heart, 376 of kidneys, 376 miliary, in pyaemia, 363 palmar, course of pus bur- rowing in, 171 Absorption in bone-tuberculo- sis, 522 callus, 249 Acetabulum wandering, 536 Acid, carbolic, in asepsis, 789 causing fever, 323 in erysipelas, 406 in gangrene, 275 in treatment of boils, 174 nitric, in hospital gangrene, 431 method for detection of cancer, 672 Acromegaly, 615 relation of thymus gland to, 615 Actinomyces, 76 cultures, 470 staining, 77, 809 Actinomycosis, 469 history, 469 prognosis, 475 symptoms, 471 treatment, 475 Actinomycosis, appearances of, post-mortem, 471 in cattle, 476 Actinomycosis, deposits in, metastatic, 473 expectorations in, 474 infection through the intes- tinal tract, 474 through the respiratory tract, 474 lungs in, condition of, 474 in man, 471 of mouth, 472 progress of the disease, 472 of skin, 475 transmission, 470 Active hyperemia (see Hy- pe?-cemia). Actol, 803 Adenitis, tubercular treatment, 588 of neck, tuberculous, 586 Adeno-carcinoma of kidney, 697 of rectum, 691 of uterus, 674 Adenoma, 737 of breast, 738 classification of, 738 cysto-, of breast, 739 fibro-, of breast, 738 of kidney, 741 sebaceum, 740 of sweat-glands, 650, 740 of testis, 742 Aerophobia, 458 Agar-agar, 34 Air and sepsis, 786 Air, bacteria in the, 786 embolism, 296 Air-passages, sarcoma of, 725 Alcohol in septicaemia, 354 Ammonaemia, 346 Amputation in gangrene, 263, 433 in osteomyelitis, 21 1 Amputation- stumps, neuroma of, 773 Amyloid degeneration, 329 Anaesthesia in rabies, 454 Anal canal, sterilization of, 830 Aneurism, cirsoid, 780 Aneurisma racemosum, 780 Angioma, 777 cavernous, 779 venosum, 780 Angio-myoma, 776 -neurology, 79 -sarcoma, 708, 719 of kidney, 719 Animal-inoculation in bacteri- ological examinations, 788 Animals, rabies in, 453 Ankylosis, 625 cartilage, destruction in, 625, 626 experimental, 627 in joint-tuberculosis, 534 Anthrax, 477, 484 convulsions, tetanic, 481 diagnosis, 481 epidemics, 477 incubation, 479 infection, method of, 478 prognosis, 482 treatment, 483 Anthrax, appearances of, in man, 480 pathological, 481 post-mortem, 482 bacillus, 70 in catgut, 798 distribution of, in man, 482 pyocyaneus, action of, 483 spores, 72, 477 Antiseptics, 784, 801 of tooth-filling, 815 Antistreptococcus serum, 848 Arsenic, bromide of, in can- cer, 700 Arteries, healing of, 250 ligature of, 251, 254, 255 callus after, 251 organization of thrombus after, 252 role of thrombus after, 254 nutrient, in osteomyelitis, 197 Arthrectomy, 554 Arthritis, chronic dry, 623 deformans, 620 eburnation of bone in, 622 treatment, 624 osteomyelitis followed by acute suppurative, 205 Arthropathy, spinal, 624 857 INDEX. Arthrotomy, 553 Ascites, hypersemia following tapping for, 87 Aseptic fever (see Fever). Asphyxia, local, 272, 274 Atrophy, bone, in joint-tuber- culosis, 534 neuro-paralytic, 6 II senile, 609 Auto-clave, t>Z -transfusion, 299 Bacilli, anthrax, in man, 482 in submiliary tubercle, 506 of tetanus in garden soil, 436 of tuberculosis, demonstra- tion of, 56, 505 staining sputa for the, 57 | of typhoid, a cause of osteo- myelitis, 196 Bacillus anthracis, elimination . of ' 75 coli communis, 48 distinguished from ba- cillus typhosus, 49 infection, 73 lactis aerogenes, 828 mallei, 61 mucosus capsulans, 845 passage through the pla- centa. 75 pyocyaneus, 47, 801 action upon anthrax, 483 pyogenes fcetidus, 48 spores, 72, 477 typhosus in cystitis, 827 vaccination against, 74 Bacillus, anthrax, cultures of, methods of obtaining, 55 growth, 59 Bacillus of cancer, 639 of glanders, 61 in mouth, 815 of leprosy, 64 of malignant oedema, 67, 163 of pseudo-oedema, 69 of syphilis, 65 of tetanus, 54, 435 where found, 436 of tuberculosis, 56 in cystitis, 827 of xerosis, 818 staining methods, 57 Koch's demonstration of, 5°5 Lustgarten's, 66 Ziehl*s, 57 Bacteria, 18 action in disease, 37 in the living body, 38 aerobic, 23 anearobic, 23 in the blood, 144, 359 Bacteria, capsule, 19 cell-structure, 19 chromogenic, 19 classification, 18 color-producing, 19 culture-media, 33 solid, 31 culture, plate, 36 stab, 35 destruction of, by leuco- cytes, 106 dilution of, 36 dose, 137 elimination of, from the system, 144 examination methods, 25 facultative, 23 in aseptic fever, 323 in suppurative fever, 329 fever without, 315 forms, 19 in gangrene, 266, 267 in garden soil, 69 gas-formation, 24 growth favored by state of the blood, 150 favored by strong anti- septics, 150 history of, 17 in the body, 143 infection, toxic, 39 can inflammation exist with- out ? 122 causing inflammation, 121 in infective inflammation, l 35 inflammation due to, 139 toxic products, 138 types of, 135, 136 immunity, 39, 152 inoculation, protective, 39 kidneys as eliminators of, 144 light on, influence of, 23 morphology of, 18 motility, 19 method of study, 26 movements of, 19 multiplication of, 22 in noma, 270 numbers of, necessary to cause suppuration, 137 in osteomyelitis, 194 of cystitis, 826 of eye, 818 of male urethra, 824 of meatus urinarius, 824 of mouth, 814 oxygen on, influence of, 23 pathogenic, 42 Koch's laws on, 42 peptonizing action of, a cause of suppuration, 155 pigment-formation, 24 Bacteria, preparation, hanging- drop, 26 products of, chemical, 23, .138 pus without, 140 in pyaemia, 359 pyogenic, 143 in man, 138 relation to aniline dyes, 18 removal of fat from speci- men containing, 29 reproduction, 20 respiratory organs in elimin- ation of, 145 saprogenic, 22 saprophytic, 22 in scrofula, 594 in septicaemia, 337, 338 specimen, preparation of, 28 spore-formation, 20 staining, 29 staining, double, 27 color-picture, 25 methods, 26 structure-picture, 25 sterilization, dry heat, 31 steam, 31 in suppuration, 137, 155 frequency, 139 in temperature, 22 in text-books, 25 tissue containing, prepara- tion of a, 30 Bacteria, micrococcus pyog- enes tenuis, 46 tetragenus, 48 staphylococcus albus, 45 cereus, 45 citreus, 45 erysipelatis, 53 flavus, 45 pyogenes aureus, 43 viridis flavescens, 45 streptococcus erysipelatis,53 pyogenes, 46 Bacteria : bacillus anthracis, 70 coli communis, 48 foetidus, 48 of malignant oedema, 67 mallei, 61 pseudo-oedema, 69 tuberculosis, 56 Bacteriological examinations, 788 Bacteriology of ear, 819 of eye, 816 of gall-bladder, 842 of genito-urinary system, 822 of mouth, 812 of nose, 820 of peritonitis, 834 of skin, 800 INDEX. 859 Bacterium coli commune in cystitis, 826 Bacterraria, S2$, 826 Balsam, xylol, 29 Bath, cold, reaction from, 304 in treatment of inflamma- tion, 133 vapor, in tetanus, 450 Bed -sore, 271 Benign tumors (see Tumors). Bichloride of mercury, 802 Big-jaw, 469 Black tongue, 397 Bladder, bacterial invasion of, 823 cancer of, 694 villous, 694 disinfection of, 830 distended, catheterization of, in hyperemia, 87 extirpation of, 696 papilloma, 752 routes of infection by bac- teria, 828 sarcoma of, 719 sterilization of, 830 tuberculosis of, in women, 579 Blood, buffy coat of, 100 circulating, toxic products in, 138 coagulation of, 100 color of, in inflammation, 96,97 corpuscles of, third, 98 in fever, 312 bacterial growth favored by the state of, 1 50 in lymphoma, 733 pus in, 363 in pyaemia, 363 in pyaemia, 371 slowing of, 89 sugar of, 787 Blood-clot, absorption of, fever caused by, 100, 321 in after-treatment of osteo- myelitis, 215 organization, 231 in tendon repair, 233 Blood-corpuscle, third, 98 Blood-corpuscles, white, dia- pedesis, 93 increase of, in inflamma- tion, 99 Blood-examination, 786 dry, 787 Blood-flow, increased, in ac- tive hypersemia, 80 Bloodletting, 133 Blood-pigment in ulcer, 184 Blood-plaques, 99 in pyaemia, 361 Blood-serum as a culture-me- dium, 788 Blood-serum, bactericidal ac- tion, 41 in tetanus, 451 in therapy, 153 therapy in rabies, 803 Blood-vessels in inflammation, 92 action of, 92 dilatation of, 95 escape of fluids from, 108 small budding growth from, 229 Body exposed to cold, 303 to constant heat, 303 temperature, inequalities in, 302 Boil, core of a, 172 Boiling instruments for sterili- zation, 795 Boils, treatment of, carbolic acid in, 174 prophylactic, 174 sulphide of calcium in, 175 Bone atrophy in joint-tubercu- losis, 534 neuro-paralytic, 61 1 senile, 609 callus, 245, 246 intermediate, 245 ossification of, 247 chemical changes in, in osteomalacia, 599 chips in after-treatment of osteomyelitis, 216 diseases of, 597 eburnation of, 208 in arthritis deformans,62i fistula after osteomyelitis, 214 fracture of, callus after, 245 changes following histo- logical, 246 healing of, 244 hyperplasia of, 61 2 internal callus, 245 lime -salts of, absorbed in osteomalacia, 597 marrow, changes in, patho- logical, 616 necrosed, solvent action of pus on, 200 spontaneous fracture from, 200 non-union, 250 osteoblasts, 246 repair, 245 absorption of callus, 249 hyaline cartilage in, 249 reproduction, 246 sarcoma of, 712 central round-cell, 714 central spindle-cell of, 713 spontaneous fracture in, 7H Bone, sequestra of, in osteo- myelitis, 199 tissue, destruction of, in hip- joint disease, 536 tuberculosis (see Tubercu- losis). tumors, myeloid, 713 typhoid, 193 Bones affected in osteoporosis, 610 in ostitis deformans, 613 in rickets, 608 chemical changes in, in ostitis deformans, 599 of cranium in sarcoma, 717 flat, in osteomyelitis, 203 medullary tissue of, in os- teomalacia, 598 in pyaemia, 377 Boric acid, 803, 834 Bottles, hot-water, burns from, 272 Brain, nerve-tissue repair in, 242 in pyaemia, 376 sarcoma of, 729 Breast, adenoma of, 738 cancer of, 662 colloid, 665 heredity in, 663 medullary, 664 metastasis in, 667 pain in, 666 scirrhous, 664 traumatism in, 663 cysto-adenoma of, 739 fibro-adenoma of, 738 hypertrophy of, 740 pigeon, 607 sarcoma of, 723 malignancy, 724 Breath in pyaemia, odor of, . 369 Bromide of arsenic in cancer, 700 Bromine in hospital gangrene, 432 Brownian movement, 19 Budding growth from small blood-vessels, 229 of muscle-fibres, 237 Buffy coat of blood, 100 Burns from hot-water bottles, 271 shock from, 290 Cachexia, cancerous, 646 Calabar bean in tetanus, 448 Calcium, sulphide of, 175 Callus absorption, 249 after fracture of bone, 245 ligature of an artery, 251 bone, 245, 246 intermediate, 245 ossification of, 247 86o INDEX. Canals, plasma, in capillary development, 230 Cancer, 638 bacillus of, 639 cells, 644 as protozoa, 640 chimney-sweeps', 658 in cicatrix, 660 coccidium in, 640 detection of, nitric-acid method for, 672 diagnosis of, extent of, 672 distribution, 643 en cuirasse, 667 etiology of, 639 extension through lymphat- ics, 645 infiltration in, round-cell, 651 ; lymphatic system in, 645 medication in, 698 melanotic, 648 origin of, epithelial, 638 pearls in, epithelial, 649 protozoa in, 640 scirrhous, 647, 664 spider, 777 stricture of rectum from, 692 treatment, therapeutic, 701 bromide of arsenic in, 700 Chian turpentine in, 701 pyoktanin in, 700 Cancer of bladder, villous, 694 of breast, 662 classification, 663 colloid, 665 diagnosis, 670 duration of life of, 669 heredity, 663 history of, clinical, 666 locality, 663 medullary. 664 metastasis in, 668 operation, mortality after, 669 Paget's disease of the nipple, 671 pain in, 666 scirrhous, 664 traumatism in, 663 of face, 652 seat, 654 superficial, 653 ulcerations in, 654 of hand, 656 metastasis in, 656 of intestines, 689 of kidney, 696 of labia, 657 t of larynx, 686 of lip, metastasis in, 656 smoking a cause, 655 treatment, 661 Cancer of oesophagus, 684 treatment, 685 of penis, 657 treatment, 661 of rectum, 690 Kraske's operation, 693 relieved by erysipelas,398 of scrotum, 658 tar and paraffin in, 659 of skin, 652 deep-seated, 649 superficial, 650 treatment, 660 of stomach, 688 of testicle, 698 of tongue, 677 beginning of, 680 diagnosis, 682 leucoma an early stage of, 679 metastasis, 680 operations for, 682 of uterus, 672 body, 674 cervical canal, 674 diagnosis, 670 hemorrhage early symp- tom of, 676 heredity in, 673 hydrometra in, 675 metastasis, 675 pregnancy a cause of, 673 treatment, 677 vaginal portion, 673 Cancroin, 699 Cancrum oris, 270 Capillaries, distention of, in inflammation, 92 Carbolic acid (see Acid). as an antiseptic, 802 Carbuncle, appearances, cause of crater-like, 1 77 columnar adiposse in 176 condition, gangrenous, 181 constitutional diseases pre- disposing to, 175 diabetes predisposing to, . 75 excision, total, 181 fascia limiting extent of, 177 hair-follicles in, 176 inflammation of deeper tis- sues, 177 of lip, 179 meningitis from, 180 necrosis in, coagulation, 179 peculiarities,anatomical, 1 76 size, 179 swelling, features of, 177 symptoms, constitutional, 179 thrombosis of facial vein in, 180 treatment, 180 radical. 181 Carcinoma, 638 classification, 647 in the granulations of osteo- myelitis, 208 of skin, 648 Carcinosis, acute miliary, 646 Caries, 523 of the ribs, 525 Caries sicca, 531 in shoulder-joint tubercu- losis, 538 Cartilage in ankylosis, destruc- tion of, 625 cells in rickets, 605 epiphyseal, in osteomyelitis, 196, 199, 201 hyaline, in bone-repair, 249 in the joint, 767 in tuberculosis, ulceration of, 531 Castration in tuberculosis of testicle, 580 Catgut, sterilization of, 806 Cattle, actinomycosis in, 476 Cell-division, indirect, 218 Cell-infiltration, inflammation dependent on the amount of irritation, 108 Cell-proliferation, ioi, 218 Cells, amoeboid movement of, 101 cancer, 644 as protozoa, 643 cartilage, in rickets, 605 of cord in shock, 285 embryonal, 220 epithelioid, in granulation tissue, 229 in tuberculosis, 506 formative, 220 giant-, sarcoma, 706 muscular, proliferation in repair of muscle, 236 plasma, 220 slumbering, in tendon re- pair, 234 spindle-, in granulation tis- sue, 227 tissue-, proliferation of, in inflammation, 104 wandering, 93, 101 in inflammation, 101 Cephalalgia in hydrophobia, 458 Chemical sterilization of the skin, 802 Chemotaxis, 152 negative, 153 positive, 153 Chilblains mistaken for sym- metrical gangrene, 273 Children, surgical scarlet fever frequent in, 324 scrofulous, 594 INDEX. 86 1 Chill, 307 of fever, 307 Chills in pyaemia, 366 Chloral in tetanus, 44S Chlorides in urine, 793 Chlorine as a disinfectant, 803 Chloroform balsam, 29 in tetanus, 449 Chlorophyll, 22 Chondroma, 765 osteoid, 765, 768 of parotid gland, 768 Chondrosarcoma, 716 Cicatrices, cancer developing in, 660 Cicatrix, arterial, after ligature, 253 tendon, 234 Cilia, 19 Circulation in inflammation, 92 Circumcision, rite of, trans- mission of tuberculosis in, 510 Cirrhosis, 127 Civil War, hospital gangrene in, 410 Cleanliness in wound-treat- ment, 808 Clefts, branchial, 751 " Clump-theory," 845 Coagulation, blood, 1 00 of fibrous exudation, 113 Coagulation-necrosis, 257 in carbuncle, 179 after infective thrombi, 147, 148 after suppuration, 156 Cocci, erysipelas, action on sarcoma of, 735 pyogenic, experimental in- oculation in man, 139 in osteomyelitis, 194 Coccidium in cancer, 640 Cold, action of, 91 catching, 122, 303 reaction from, 304 Cold bath, reaction from, 304 in treatment of inflam- mation, 133 Collapse, 277 Color of blood in inflamma- tion, 97 of an inflamed part, ill Color picture, 25 Columnae adiposae in car- buncle, 176 Complexion in keratosis, 652 Condenser, Abbe, 25 Connective tissue, cancer, 665 formation, 221 Convulsions, tetanic, in an- ! thrax, 481 Cornea, leucocytes in, 102 structure, 102 Corpuscle, blood- (see Blood- corpuscles). Corpuscles, corneal, 102 white, migration of, 93 Corrosive sublimate, 802 as a genito-urinary germi- cide, 833 Cotton gloves, 805 Cover-glass preparations, 26 Cranio-sclerosis, 612 Craniotabes, 606 Cranium, bones of, sarcoma, 717 Cretinism, 746 Crimean War, hospital gan- grene in, 410 Croton oil producing suppura- tion, 140 Culture media, 31 Culture, plate, 36 Curetting vein of sinus in pyaemia, 379 Cushing, 845 Cylindroma, 703 Cystitis, bacteria of, 826 reaction of urine in, 824 role of bacteria in, 823 Cysto-adenoma of the breast, 739 Cystoma, 748 Cysts, dermoid, of the ovary, .749 ovarian, 748 of parovarium, 749 Daughter-star, karyokine- sis, 219 Death-rate of hydrophobia, 467 Deaths from snakes in India, 495 Debility favoring rickets, 603 Decomposition, 22 Decubitus, ulcerating, in hip disease, 536 Deformities in ostitis de- formans, 601 following rickets, 606 Deglutition in hydrophobia, 457. Dermatolysis, 757 Dermoids, ovarian, 749 Diabetes predisposing to car- buncle, 175 Diapedesis of white blood- corpuscles, 93 Diarrhoea in septicaemia, 347 Diphtheria, relation of hospital gangrene to, 420 Diplobacillus of Friedlander, 828 of Morax and Axenfeld, 818 Diplococci, 21 Diplococcus ureae liquefaciens, 827 Disease, bacterial action in, 37 germ theory of, 17 Graves's, 747 hip-joint, 514, 535, 536 Hodgkin's, 730 Paget's, of the nipple, 671 psorosperms in, 672 Pott's, 513, 523,524 wool-sorters', 76, 479 zymotic, 17 Diseases of bone, 597 constitutional, predisposing to carbuncle, 175 infectious, cause of ulcer, 182 produced by bacterial prod- ucts, 37 Disinfectants, in septicaemia, 354, 802 J Disinfection of surgeon's hands, 805 Dislocation resulting from osteomyelitis, 208 spontaneous, 533 Distention, capillary, 92 j Drainage in abscesses, 166 postural, 840 1 Dressings for wounds, 811 sterilization of, 806 Dry blood, examination of, 787 Dryness of wounds, 810 I Dumb rabies, 453, 455 Dyes, aniline, 26 acid, 27 bacterial relation to, 18 basic, 27 Ear, bacteriology of, 819 sterilization of, 819 Earthy- worm dissemination of anthrax spores, theory of, 478 Eburnation, 517 of bone, 208 in arthritis deformans, 622 Ecchymosis, punctiform, no Elbow-joint tuberculosis, 539 1 Emaciation in suppurative fever, 328 Embolism, 262 air, 298 fat, 204, 296 Emulsion, Krause's, in treat- ment of fistula, 191 Enchondroma, 765 hyaline, 768 Endarteritis deformans, 259 arterial repair, compensa- tory, 255 obliterative, 258 Endocarditis, 347 in osteomyelitis, 204 from experimental pyaemia, 360 862 INDEX. Endocarditis in pyaemia, 360 ulcerating, 363, 365, 372 Endothelioma, 648 Enemata in shock, 299 Epidemic goitre, 746 Epidemics, erysipelas, 381 of furunculosis, 173 of hospital gangrene, atmo- spheric conditions af- fecting, 420 of glanders, 493 of tetanus, 437 Epiphyseal cartilage in osteo- myelitis, 199, 201 separation, 201 Epithelioma, 647 Epulis, 716 Ergotism, 271 Eruption in septicaemia, 347 Erysipelas, 381-408 prognosis, 402 symptoms, 388 cerebral, 440 following, 392 treatment, 403 carbolic acid in, 406 iron in, use of, 404 of wound in, 407 Erysipelas, action, curative, 390 cancer of rectum relieved b y> 398 on malignant growths, 734 cause of constitutional dis- turbance, 384, 391 cocci, action on sarcoma of, 435 a complication in hospital gangrene, 427 condition of the skin in, pathological, 398 conditions predisposing to, atmospheric, 387 contagiousness of, 385 disturbance, gastric, 400 duration of, 390 of epidermis, 381 facial, 394 lachrymal ducts a start- ing-point, 395 ( meningitis following, 396 puerperal fever and, 386 habitual, 390 hemorrhage in, 399 inflammation of skin in, 388 inflammations, malignant, 393 influence, curative, 400 inoculation experiments, 382 of mucous membranes, 397 neonatorum, 388, 396 oedema of glottis in, 398 patient, isolation of, 408 Erysipelas, phagocytosis, 107 phlegmonous, 392 relapse, 408 spread of, tendency, 389 streptococci in, 399 entrance, point of, 386 seat of, 384 streptococcus of, 382 and pyogenes streptococcus, identity of, 383 synovitis following, 392 following vaccination, 385 vesicles in, 389 virus, ^82 wound, condition of, 390 Erythema, toxic, 324 Erythromelalgia, 87, 275 Euphoria, 348 Exanthemata, metastatic in- flammation of joints in, 543 Excision, treatment of tendon- sheath tuberculosis by, 593 Exostosis, 769 ivory, 769 submanual, 770 Expectorations in actinomyco- sis, 474 Exudation, 109 cause of, explanation, 113 in inflammation, 94 inflammatory, uses of, 1 13 Eye, bacteriology of, 816 Face, cancer of (see Cancer). erysipelas of the, 394 tuberculosis of, 528 Fainting, 296 Fallopian tubes a source of tubercular peritonitis, 569 tuberculosis of, 573 Farcy, 485-494 Farcy-buds, 491 Fascia limiting extent of car- buncle, 177 Fat-embolism, 204, 296 Fat in staining bacteria, the removal of, 29 in pus of osteomyelitis, 204 Fatigue, meaning of, 283 Fat-neck, 761 Feces, examination of, 795 Felon, 167 cutaneous form, 168 incision in case of, 170 character of pain diagnostic as to form, 169 periosteal form, 169 reaching to the tendon- sheath, 169 treatment, 170 Fermentation, 23 Fermentation, theory of Pas- teur, 23 Fever, absorption of blood- clot causing, 100, 321 antiseptics causing, 323 aseptic, 319 bacteria in, 323 chemicals causing, 323 temperature, 320 tension from suture caus- ing, 3 2 3 blood-changes in, 312 from carbolic acid, 323 causes of, 314 the chill of, 307 defervescence, 308 defined, 315 due to diminished heat- elimination, 308 increased heat - produc- tion, 309 fastigium, 308 heat-production in, causes of, 311 hectic, in tuberculosis, 519 iodoform causing, 323 nerve-action, 313 neurotic theory of, 314 puerperal, and erysipelas, 386 scarlet, surgical, 323, 324 toxic erythema, 324 origin in surgical cases, 323, 326 secondary, 327 splenic, 477 stage of invasion, 308 suppurative, 327 amyloid degeneration, 932_ bacteria in, 329 emaciation in, 328 leucocytes in, 329 operations in, 330 temperature in, 328 treatment, 330 symptoms of, 307 traumatic, cleaning of the wound, 318 gangrene, 265 temperature, 317 urea, excretion, 312 urethral, 124, 331 nerve-action in, ^t, without bacteria, 315 Fevers, surgical, 316-333 Fibrin formation in inflamma- tion, 108 Fibro-adenoma of the breast, 738 -glioma, 763 -lipoma, 761 -myoma, 775 Fibro-blasts, 220, 224 Fibroma, 753 INDEX. 863 Fibroma molluscum, 754 multiple, 754 nasopharyngeal, 759 papillary, intracanalicular, 738 of skin, multiple, 754 soft, 757 Field of operation, sterilization of, 804 Fistula in ano, 567 Fistula, bone, after osteomye- litis, 214 defined, 190 treatment, 191 Krause's emulsion in, 191 Fontanelles in rickets, 606 Foreign bodies, location of, by x-rays, 797 Formaldehyde, 803 Formalin, 803, 814 as a disinfectant, 805 Formalin-gelatin, 803 Fracture of bone, callus after, 245 histological changes fol- lowing, 246 spontaneous, 207 from bone-necrosis, 200 in bone sarcoma, 714 Fractures, x-rays in, 797 Fragilitas ossium, 610 Frog's tongue, passive hyper- semia, study of, 89 Frost-bite a cause of gan- grene, 268 treatment of, 269 Furuncle, 172 Furunculosis, 1 74 epidemics of, 173 Gall-bladder, bacteriology of, 842 typhoid invasion of, 843 Gall-stones, relation of bac- teria to, 844 Ganglia, perivascular, in ac- tive hypersemia, 82 paralysis of, 87 Gangrene, 256-276 ainhum terminating in, 275 amputation in, 263, 433 bacteria in, 266, 267 bed-sore, 271 carbolic, 275 causes of, 256 arterial changes, 258 arterial injury, 265 extravasation of urine, 270 mechanical action, 256 putrefactive changes, 266 vaso-motor disturbance, 274 demarcation in, line of, 260 diabetic, 264 Gangrene, diphtheritic form of, 421 emphysema, 267 tibial artery, 262 ergotism, 271 foudroyante, 267, 394 frost-bite a cause of, 268 fulminating, 267 hospital, 409-433 amputation in, 433 at Andersonville, 411 atmospheric conditions affecting epidemics of, 420 in the Civil War, 410 contagiousness, 418 in the Crimean War, 410 diagnosis, 429 discharge in, 425 erysipelas a complication, 427 forms of, 420-422 hemorrhage in, 425 incubation of, period, 420 joints as affected by, 426 micro-organisms in, 415 mortality, 430 non-infection of wounds in same person, 419 post-mortem appearances, 429 prognosis, 430 pulpy, 424 relation to diphtheria, 420 study of, microscopic, 416 synonyms, 409 temperature in, 426 treatment, 430 bromine in, 432 carbolic acid in, 433 nitric acid in, 431 ulcerating, 423, 424 infection in, bacterial, 266, 267 intoxication in, septic, 428 moist, 260 mummification, 260 neuropathic, 256 noma, 270 senile, 260 symmetrical, 272 chilblains mistaken for, 273 symptoms of, 262 traumatic, 265 ulceration in, phagedenic, 424 Garden soil, bacilli of tetanus in, 436 Gastrostomy, 685 Gelatin, 34 Generation, spontaneous, 17 Genitals, routes of infection by bacteria, 828 Genito-urinary system, bacte- riology of, 822 tuberculosis, 573 Germ-theory of disease, 17 Gentian-violet, 27 Giant-cell formation, 219 Giant-cells as phagocytes, 107 in sarcoma, 706 in tuberculosis, 59, 505 Gigantism, 615 Gland, parotid, chondroma of, 768 thymus, relation of, to acro- megaly, 615 Gland-ducts, sudoriparous, the entrance-gates of infec- tion, 172 Glanders, 485-494 acute, 487 bacillus of, 61 changes in, pathological, 489 epidemics, 493 laws concerning, 493 infection, method of, 486 in man, 487 mucous membrane in, 488 nodules in, 490 prognosis, 491 transmission in utero, 486 Glands, lymphatic, prognosis of tuberculosis of, 588 mesenteric, tuberculosis of, 570 scrofulous, 585 Glioma, 763 Gliosarcoma, 707 Glottis, oedema of, in erysipe- las, 398 Gloves, operating, 805 Glutol, 803 Goitre, 743 epidemic, 746 exophthalmic, 747 Gonococcus, 50 in cystitis, 828 diagnosis of, 52 in endocarditic and meta- static inflammation, 52 growth, 51 Gonorrhoea a factor in spread of tuberculosis, 575 Goose-flesh, 303 Gram's method, 27 Granulation, healing by, 225 tissue, 157, 226, 228 Granulations, carcinoma in the, osteomyelitis, 208 Graves's disease, 747 Grawitz, slumbering-cell the- ory, 105 Greeks, sepsis and asepsis of, 785 864 INDEX. Hair-follicles in carbuncle, 176 Hand, callosities, the starting- points of abscess, 171 cancer of, 656 metastasis in, 656 Head tetanus, 441 mortality of, 442 Healing by first intention, 222 by granulation, 225 by second intention, 225 by third intention, 232 Heart, abscesses of, metastatic, in pyaemia, 376 Heat-equilibrium, 302 Heat, metabolism a source of, 3°4 as a symptom of inflamma- tion, 115 in the treatment of inflam- mation, 133 Heat-production from glandu- lar activity, 304 in fever, causes, 311 in health, 304 in inflamed part, 115 through the nerves, 305 Hematuria, 791 Hemorrhage in erysipelas, 399 in hospital gangrene, 425 causing shock, 289 symptoms of, 286, 296 an early symptom of cancer of the uterus, 676 Heredity in cancer of breast, 663 of uterus, 673 of tuberculosis, 508 Herpes due to trophic nerves, 123 Hip disease, decubitus in, ul- cerating, 536 Hip-joint disease, 514, 535, 536 . destruction of bone tissue, .536 . Hodgkin's disease, 730 Hospital gangrene (see Gan- grene). table for patients in shock, 298 Hot water as stimulant of the constrictor nerves, 88 bottles, burns from, 272 Hydrocele of neck, 751 Hydrometra in cancer of ute- rus, 675 Hydrophobia, 453-468 cephalalgia in, 458 changes in nervous system, 462 death-rate of, 467 deglutition in, 457 etiology, 455 fear of, 460 Hydrophobia, incubation pe- riod, 455, 456 inoculation in, protective, 465 medulla, changes in, 463 melancholia, 456 nerve-centres as affected in, 462 paralytic, 459 paroxysm, 460 post-mortem, appearances, . 455 saliva, increased secretion of, 458 sexual excitement in, 459 spasm circulatoire, 458 statistics of Pasteur Insti- tute, 468 swallowing in, difficulty of, 457 temperature in, 459 treatment, 464 intensive method, 466 prophylactic, 464 protective, by digested cords, 468 virus, modification of, 464 virulence of, increased, 465 Hydrops articuli, 543 Hygroma, 590, 591 Hyperaemia, active, 79 blood-flow in, increased, 80 caused by reflex action, 84 changes in, 80 changes due to vaso-mo- tor system, 81 collateral innervation, 83 paralysis of vasoconstric- tors, 82 perivascular ganglia, 82 and inflammation, combina- tion, of, 98 catheterization of distended bladder, 87 following tapping for ascites, 87 use of Esmarch bandage, . 8 7 . of irritation, 85 of paralysis, 85 passive, 88 Hyperaemia, frog's tongue, study of, in, 89 unilateral, cause of, 85 Hyperesthesia in pyaemia, 370 Hyperplasia of bone, 612 increased length of, 615 Hyperpyrexia, 311 Hypertrophy of breast, 740 Hysterectomy, 677 ICHORRH^EMIA, 357 Icterus in septicaemia, 347 Immobility in wound treat- ment, 811 Immunity, 39, 152 phagocyte, theory of, 40, 107 to tetanus, 451 Incisions, medical, 165 in case of felon, 170 multiple, in diffuse inflam- mation, 166 Indican in urine, 794 Infarctions in bone-tuberculo- sis, 518 Infection, 73 bacterial, in gangrene, 266, 267 entrance-gates of, sudoripa- rous gland-ducts the, 172 genito-urinary, in septicae- mia, 343 of glanders, method of, 486 intravascular, in pyaemia, 364 of tuberculosis, 51 1 mixed, 47 in osteomyelitis, 195 in pyaemia, route of, 36 1 septic, 39, 338 through uninjured skin, 42, 138 toxic, bacteria in, 39 in tuberculosis, 61 through the skin, 510 Inflammation, action, chemi- cal, a cause, 1 21 age as a factor, 125 asthenic, 126 attraction theory of, 96, 1 18 bacteria in, can it exist without, 122 cause of, 121 blood-vessels in, 92 catarrhal, 128 causes of, 121 cell-infiltration dependent on an amount of irrita- tion, 108 changes in vessel-wall, 95 circulation in, 92 color of the part, II I cornea, experiments on, 102 croupous, 128 a damage, 120 defined, 120 diffuse, multiple incisions in, 166 dilatation of blood-vessels, 95 diphtheritic, 1 28 distention of capillaries in, 92 disturbance of, a process of nutrition, 119 INDEX. 865 Inflammation, escape of fluids from blood-vessels, 108 excitor, 96 experiment with thermome- ter in, Hunter, 1 15 exudation in, 94 causing swelling, III favoring bacterial develop- ment, 149 fibrin formation in, 108 formation of stomata in ves- sel-walls, 113 function of leucocytes in, 106 heat as a symptom of, 1 15 in the treatment of, 133 hemorrhagic, 129 hepatization, 112 idiopathic, 125 impairment of function in, 117 infective, 135 due to bacteria, 135, 139 thrombus formation, 147 toxic, products of bac- teria in, 138 interstitial, 127 joint, in pyaemia, 377 leeching affected area in, 132 leucocytes, 100 nerves in, action of, 123 non-infective, 126 oedema, collateral, 112 phlegmonous, 162 resolution a termination of 129 rubor, symptom of, no serous, 127 of skin in erysipelas, 388 sloughs in, 162 treatment, 164 sthenic, 126 swelling a symptom, in symptoms, cardinal, no temperature, local increase of, 116 termination of, 129 tissue-cells in, proliferation of, 104 tissues in, action of, 1 01 elasticity, 96 treatment of, 130 cold in, 133 tumor, a symptom of, ill wandering cells in, 101 white blood-corpuscles, in- crease of, 99 Inflammations, erysipelas, ma- lignant, 393 . of joints, metastatic, 543 toxic, 121 Infusion of salt solution, 299 Injuries, railway, shock from, 293 55 Injury a cause of osteomyeli- tis, 197 Inoculation experiments, ery- sipelas, 382 in hydrophobia, 465 of pyogenic cocci in man, experimental, 139 of the skin, tubercular, 563 protective, bacterial, 39 Inoculations in hydrophobia, preparation of cords for protective, 465 Instruments, sterilization of, 806 Intercellular capillary devel- opment, 229 Intestine, sarcoma of, 729 Intestines, cancer of, 689 Intoxication, septic, 337 in hospital gangrene, 428 Iodoform, 354, 803 in surgical asepsis, 790 causing fever, 323 in joint-tuberculosis, 548 use of, in surgery, 790 Iron, chloride of, in erysipe- las, 404 Itrol, 803 Ivory exostosis, 769 Jaws, hysterical contraction of, simulating tetanus, 445 Joint, cartilage in, 767 elbow-, tuberculosis, 539 hip-, disease of, 535 Joint - affection in pyaemia, 371 Joint-inflammation in pyaemia, 377 Joint-mice, 767 Joint-tuberculosis, 529 ankylosis following, 534 true, 534 arthrectomy, 554 arthropathia 529 arthrotomy, 553 atrophy of bone, 534 caries sicca, 531 changes in soft parts, 532 disturbances, febrile, 541 diagnosis, 542 in elbow-joint, 539 extension in, 547 fixation, knee-joint, 536 muscular, 549 growth of osteophytes, 533 heat in, 541 hip-disease, 535 mortality, 545 osteopathic, 529 pain in, 540 primary synovial form, 531 prognosis, 544 resection, 552, 556 Joint-tuberculosis, results of, 542 shoulder-joint, 538 spasms, muscular, 533 synovitis, obliterating, 529 treatment, constitutional, 545 iodoform in, 548 plaster-of-Paris in, 546 tumor albus, 537 Joints, adventitious, in rick- ets, 606 as affected by hospital gan- grene, 428 bacteriological examination of, 789 changes in, degeneration of the spinal cord a cause, 624 in exanthemata, metastatic inflammations of, 543 most usually attacked in bone-tuberculosis, 518 in pyaemia, 377 tuberculosis of, 529-557 Karyokinesis, 104, 218 daughter-stars, 219 metakinesis, 219 mother-stars, 219 Karyomitosis, 219 Keloid in negroes, 755 Keratosis, 652 complexion in, 652 linguae, 679 Kidney, in adeno-carcinoma, '697 adenoma of, 741 angiosarcoma of, 719 cancer of, 696 myosarcoma of, 776 routes of infection by bac- teria, 829 sarcoma of, 718 surgical, 332 Kidneys, abscesses of, meta- static, 736 as eliminators of bacteria, 144 in pyaemia, 376 tuberculosis of, 581 Knee, resection of, 556 water on the, 544 Knee-joint, tuberculosis of, 536 Kresol, 802 Labia, cancer of, 657 Lactation, suppressed shock, 294 Laparotomy in tubercular per- itonitis, 572 Larynx, cancer of, 686 concussion of, 290 shock from 290 866 INDEX. Larynx, papilloma of, 753 sarcoma of, 726 Leeching affected area in in- flammation, 132 Leiomyoma of stomach, 775 Leontiasis ossium, 612 Leprosy, bacillus of, 64 Leucocytes, appropriation of foreign bodies, 103 bacteria destroyed by, 106 in cornea, 102 in fever, suppurative, 329 forms of, 104 function of, in inflammation, 106 increase of, 786 inflammation, 100 mononuclear, 104 polynucleated, 104 in septicaemia, 347 Leucocytosis, 100, 786 Leucoma an early stage of cancer of the tongue, 678 Leukaemia, inflammatory, in osteomyelitis, 198 pseudo-, 730 Ligature, arterial, cicatrix af- ter, 253 of arteries, 251-255 double, 254 in gangrene, line of de- marcation, 260 role of thrombus after, 254 of an artery, organization of thrombus after, 252 Ligatures, sterilization of, 806 Lime-salts of bone absorbed in osteomalacia, 597 in rickets, deficient, 604 Lip, cancer of, 655, 661 metastasis in, 656 smoking a cause, 655 carbuncle of, 179 thrombosis of facial vein in, 180 Lipoma arborescens, 592, 623 diffuse, 761 fibro-, 761 Lipomata, multiple, 762 Liquor puris, 159 Lock-jaw, 438 Lumpy-jaw, 469 Lung, abscess of, experimen- tal, 145 contagion of tuberculosis through the, 509 Lungs, condition of, in actino- mycosis, 474 conditions in osteomyelitis, inflammatory, 204 starting-points in septicae - mia, 342 Lupus, 558 development of, 560 Lupus, hypertrophicus, 560 maculosus, 559 of mucous membrane, 565 ulcerating form of, 559 of vulva, 574 Lymphangioma, 781 cavernous, 781 cystic, 782 Lymphangitis, 331 Lymphatic system in cancer, 645 Lymphatics, cancer extension through, 645 in septicaemia, 347 tuberculosis of, 585 microscopic appearances, 586 Lymphoma, 731 blood in, 733 malignant, 730 protozoa in, 734 Lymphosarcoma, 730 Lysol, 803 Lyssa falsa seu nevrosa, 450 Macrophagocytes, 107 Mai perforans, 185 Malignant tissue, microscop- ical examination of, 795 Mamma (see Breast). abscesses of, 165 tuberculosis of, 583 description, 584 diagnosis, 585 microscopic appearances, 584 Marrow, bone, pathological changes in, 616 red, after spleen extirpation, 616 Mastitis, chronic, 739 Meatus urinarius, disinfection of, 830 Mechanical sterilization of skin, 802 Medulla, regeneration of, in osteomyelitis, 201 Melancholia in hydrophobia, 456 Melanosarcoma, 707, 710 Meningitis from carbuncle, 179 following facial erysipelas, 400 Metabolism a source of heat, 304 Metakinesis in karyokinesis, 219 Metastases in cancer of breast, 667 of hand, 656 of lip, 656 of rectum, 692 of tongue, 680 Metastases in cancer of uterus, 675 Micrococcus pyogenes tenuis, 46 tetragenus, 48 Micro-organisms after entering the body, 143 in hospital gangrene, 415 Microphagocyte, 107 Middle-ear suppuration, curet- ting the sinuses in, 379 Migration of white corpuscles, 93 Milk, tuberculosis in, 509 Mitosis, process, 219 in suppuration, 155 Mortality of head-tetanus, 442 in hospital gangrene, 430 in joint-tuberculosis, 545 of snake-bite in India, 495 of tetanus, 447 Mortification, 256 Mother-marks, 777 Mother-stars, karyokinesis, 218 Mouth, bacteriology of, 812 pathogenic bacteria of, 814 preparation of, for operation, 813 Mucous membrane in glanders, 488 lupus of, 565 tuberculosis of, 565 Mucous membranes, erysipelas of, 397 Mummification, 260 Muscle-fibers, budding of, 237 Muscle repair, 235, 236 sarcoblasts in, 235, 236 rupture in tetanus, 439 Muscles as heat-producers, 305 tuberculosis of, 593 Mycosis, 338 toxic, 339 Myelin sheath in nerve-repair, 239, 240 Myoma, 774 fibro-, 775 of ovary, 775 of prostate, 776 of uterus, 775 Myosarcoma of kidney, 776 of testis, 776 Myxoglioma, 764 Myxolipoma, 761 Myxoma, 758 hyaline, 759 Myxosarcoma, 707, 759 Nasal passages, sarcoma of, 727 Neck, adenitis of, tuberculous, 586 hydrocele of, 751 INDEX. 867 Nock, shock from blows in the, 290 Necrosis, 256 bone, spontaneous fracture from, 200 coagulation-, streptococci, 148 suppuration, 146 in osteomyelitis, 199 result of suppuration, 199 total, 199 phosphorus, 617 carious teeth a cause of, 617 match-making, cause of, 617 symptoms, 618 treatment, 619 a sequel of osteomyelitis, 207. (SzzCoagulalion.) Necrotic tissue, treatment of, 809 Negroes, keloid in, 755 Nephro-phthisis, 581 Nerve-action in fever, 313 in urethral fever, 332 Nerve-cells in repair, 241 Nerve-centres as affected in hydrophobia, 462 in shock, 284 Nerve-changes in tetanus, 444 Nerve-degeneration after sec- tion, 236 Nerve-exhaustion in shock, 28 3. Nerve-grafting, 243 Nerve-injury a cause of teta- nus, 435 causing shock, 286 Nerve-irritation in shock, 281, 283 Nerve-operations, plastic, 243 Nerve - paralysis, facial, in head-tetanus, 442 Nerve-repair, time of regener- ative changes, 239 myelin sheath in, 239, 240 vicarious sensibility, 238 Nerve-section, neuromata after, 241 prognosis, 241 symptoms, clinical, 241 Nerve-suture, 242 Nerve-tissue of brain, repair, 242 from pre-existing tissue, 238 Nerves, action of, in inflam- mation, 123 constrictor, hot water as stimulant of the, 88 heat-production through the, 305 trophic, herpes due to, 123 vaso-constrictor, 82 Nerves, vaso-dilator, 82 Neurasthenia following shock, 293 Neuroglioma, 764 Neuroma, 771 of amputation-stumps, 773 amyelinic, 771 malignant, 772 multiple, 772 plexiform, 772 Neuromata after nerve section, 241 Neuro-paralysis, 277 Nipple, disease of, Paget's, 671 Noli-me-tangere, 654 Noma, 270 bacteria in, 270 Nose, bacteriology of, 820 sterilization of, 821 Nucleus, 219 disappearance after death, 257 Nutrition, process of, inflam- mation a disturbance of, 119 Odontoma, 770 Odor of breath in pyaemia, 369 Odors, foul, cause of septicae- mia, 343 OZdema, collateral, 88 inflammation in, 112 of glottis in erysipelas, 398 malignant, bacillus of, 67 clinical examples, 163 pseudo-, bacillus of, 69 CEsophagectomy, 686 GEsophagus, cancer of, 684, 685 stricture of, 685 Omentum, tuberculosis of, 570 Operation, Porro's, in ostitis deformans. 602 Operations for cancer, 682, 693 I Ossification of bone-callus, 247 Osteoblasts, bone, 246 l Osteoclasts, 598 J Osteoid chondroma, 765, 768 sarcoma, 716 Osteoma, 769 spongiosum, 770 ' Osteomalacia, 597 chemical changes in bone in. 599 lime-salts of bone absorbed in . 597. medullary tissue of bones in, 598 puerperal state influencing, 600 Osteomyelitis, diagnosis, 206 etiology, 194 Osteomyelitis, prognosis, 208 treatment, 209 Osteomyelitis, 193 abscess- formation, 198 amputation in, 211 anatomical seat, 196 situation of, 196 bacteria in, 194 blood-clot in after-treatment of, 215 bone-chips in, 216 in after-treatment of, 216 bone fistula after, 214 carcinoma in the granula- tions, 208 cartilage, epiphyseal, in, 199, 201 causes of, predisposing, 197 cavity after removal of ne- crosed bone, 201 compact bone not affected, 197 dislocation resulting from, 208 eburnation, 208 endocarditis in, 204 epiphyseal line the seat of, 196 variety, 203 experimental, 194 fat in pus of, 204 flat bones, 203 followed by acute suppura- tive arthritis, 205 formation of new bone, 200 grave type, 206 infection, entrance of, 195 inflammatory conditions in, 204 leucaemia in, 198 injury a cause of, 197 involvement of the joint, 199 multiplex, 202 necrosis in, 199 the result of suppuration in, 199 a sequel of, 207 total, 199 nutrient artery in, 197 operation for, time of, 211 operations in, 210 pus in, 198 pyogenic cocci in, 194 regeneration of the medulla, 201 resection in, 212 separation of sequestrum, 213 septicaemia and pyaemia in, 202 sequelae, 207 sequestra of bone in, 199 staphylococci in, 194 staphylococcus pyogenes aureus, 194, 195 868 INDEX. Osteomyelitis, a starting-point for septicaemia, 342 symptoms, 193, 203 trephining in, 211 typhoid bacillus in, 196 a cause of, 196 Osteophytes, growth of, in joint-tuberculosis, 533 Osteoporosis, 609 bones affected, 610 lacunar absorption in, 610 symptoms, 61 1 tuberculosis, 570 Osteosarcoma, 712 Ostitis deformans, 613 bones affected, 614 changes in bone, chemi- cal, 599 in medullary tissue, 598 deformities in, 601 influence of puerperal state, 600 operation in, Porro's, 602 prognosis, 601 symptoms, 600 treatment, 602 tropho - neurosis, reflex, 600 tubercular, 516 Ovaries, tuberculosis of, 576 Ovary, cysts of, 748 dermoid, 749 myoma of, 775 Oxalic acid, 803 Ozcena, tuberculous, 566 Pacchionian bodies, 752 Paget's disease, psorosperms in, 672 Pain in cancer of breast, 666 in joint-tuberculosis, 540 rheumatic-like, in shoulder- joint tuberculosis, 538 Palate, soft, sarcoma of, 728 Papilloma, 751 of larynx, 753 villous, of bladder, 752 Paralysis, facial nerve, in head-tetanus, 442 of perivascular ganglia, 87 hyperaemia of, 86 neuro-, 277 reflex vaso-motor, in shock, 279 Parovariuum cysts, 749 Paroxysm, hydrophobia, 460 Pasteur, fermentation theory of, 23 treatment of rabies, 464 Pasteur Institute, statistics, 468, 469 " Peccant humor," 1 13 Penis, cancer of, 657, 661 Peptone in pus, 159 in pyaemic urine, 370 Peptones, protective treatment of rabies with cords treated with, 468 Periostitis, 628 acute, 629 albuminosa, 630 non-suppurative, chronic, 630 treatment, 631 tubercular, 569 Peritoneum, first mentioned in poetry, 498 Peritonitis, bacteriology of, 834 fibrinopurulent, 836 hemorrhagic, 836 mycotica, 836 purulent, 837 seropuiulent, 836 tubercular, 569, 570 Fallopian tubes a source of, 569 laparotomy in, 572 Permanganate of potassium, 803 Petri dish, 36 Phagocyte theory of immunity, 40 of Metschnikoff, 40 Phagocytes, giant-cells as, 107 macro-, 107 Phagocytosis, 41 an explanation of immunity, 107 erysipelas, 107 Pharynx, bacteriology of, 812 sarcoma of, 728 Phlogosin, 141 Phosphorus in rickets, 609 Pigeon breast, 607 Placenta, passage of bacillus through the, 75 Plasma canals in capillar}' de- velopment, 230 cells, 220 Plaster of Paris in treatment of joint-tuberculosis, 546 Plate culture, 36 Plethora, 79 Pleura, bacteriological exam- ination of, 789 Pleurosthotonos, 441 Pneumonia caused experi- mentally by infection of aureus, 145 in pyaemia, 375 Polyp, naso-pharyngeal, 727, 757 Port-wine marks, 777 Post-mortem appearances in actinomycosis, 471 in anthrax, 481 in hospital gangrene, 429 of hydrophobia, 462 Post-mortem appearances in pyaemia, 375 in rabies, 455 in septicaemia, 349 in tetanus, 443 Postural drainage, 840 Potatoes as nutrient media, 33 Pott's disease, 513, 523 tuberculosis, 524 Poultice, antiseptic, 165 Poultices, action of, 133 Pregnancy a cause of cancer of uterus, 673 Prostate, myoma of, 776 Prostration without reaction, 277 Proteid, bacterial, 152 defensive, 153 protective, 153 Proteus Hauser, 826 Protoplasm, bacterial, 18 Protozoa in cancer, 640 cancer-cells as, 699 in lymphoma, 734 Proud' flesh, 187 Psammoma, 783 Pseudarthrosis, 250 Pseudo-leukaemia, 730 -tuberculosis, 595 Psoas abscesses, 525 Psorosperms, 641 in Paget's disease, 672 Ptomaines a cause of septicae- mia, 342 Pus, action on necrosed bone, solvent, 200 in blood, 363 in pyaemia, 363 blue, 160 burrowing of, in palmar abscesses, course of, 171 calomel, 142 laudable, 160 in osteomyelitis, 198 fat in, 204 peptone in, 159 red, 160 sterile, 140 tubercular, 160 without bacteria, 140 Pustule, 172 malignant, 479 Pyaemia, 356 diagnosis, 378 prognosis, 378 symptoms, 366 treatment, 378 Pyaemia, abscesses in, meta- static, 362, 376 miliary, 363 bacteria of, 359 blood in, 371 blood-plaques in, 361 bones in, 377 INDEX. 869 Pyaemia, brain in, 376 breath in, odor of, 369 chills in, 306 chronic, 374 curetting vein of sinus in, 379 endocarditis, 360 in ulcerating, 365, 372 experimental, 358, 359 heart in, 376 history of, 356 hyperesthesia, 370 infection, intravascular, 364 route of, 361 inflammation of connective tissue in, 377 influenced by age and sex, 366 by seasons, 365 joint-affection in, 371 joint-inflammation in, 377 kidneys in, 376 in osteomyelitis, 202 pneumonia in, 375 post-mortem appearances, 375 puerperal, 373 pus in the blood in, 363 in the thoracic duct in, 3 6 4 spontaneous, 364 temperature in, 367 thrombosis in, 361 thrombo-phlebitis in, 361 urine in, 370 wounds predisposing to puerperal septicaemia, 343 Pyocyaneus, 47 Pyogenes aureus, 801 Pyoktanin in cancer, 700 Pyuria, 792 Rabies, 453 dumb, 453, 455 furious, 453. (See Hydro- phobia.) Ray-fungus, 469 Rectum, adeno-carcinoma of, 691 cancer of, 690 Kraske's operation, 693 sterilization of, 831 stricture of, from cancer, 692 tuberculosis of, 568 Renal calculi, jr-rays in, 798 Repair, arterial, compensatory endarteritis, 255 of arteries, 250 bone, 245, 249 hyaline cartilage in, 249 of brain nerve-tissue, 242 first intention, 223 vascular loops in, 233 Repair in granulation tissue, vascular loops in, 228 muscle, 235, 236 sarcoblasts in, 235, 236 nerve-cells in, 241 nerve, myelin sheath in, 239, 240 time of regenerative changes, 239 vicarious sensibility, 238 the scar, 224 second intention, 225 tendon, 232 blood-clot in, 233 slumbering cells in, 234 third intention, 232 of tissue-cells, process, 104 vascular, 229 Resection in joint-tuberculosis, 552, 556 of knee, 556 in osteomyelitis, 212 Respiratory centre, action in hydrophobic paroxysm, 4 6 . 1 organs in elimination of bac- teria, 145 Ribs, caries of the, 525 tuberculosis of, 526 Rice-bodies, 590 Rickets, 603 appearances of, microscopic, 605 bones most affected in, 608 cartilage-cells in, 605 change in disposition, 608 changes in, pathological, 604 craniotabes, 606 debility favoring, 603 deformities following, 606 distribution, 604 fcetal, 604 fontanelles in, 606 joints in, adventitious, 606 lime-salts in, deficient, 604 phosphorus in, 609 prognosis, 608 thickening of ends of bones, 605 treatment, 609 Risus sardonicus, 439 Rontgen rays in surgical diag- nosis, 796 Rosary, rachitic, 607 Rubber gloves, 805 Rubor, symptom of inflamma- tion, no Rupture, muscle, in tetanus, 439 Sacroiliac synchondrosis, tuberculosis of, 528 Salicylic acid, 803 Salol, 834 Salt-solution as a genito-urin- ary germicide, 833 infusion of, 299 Sapraemia, 337 symptoms, 343 Sarcoblasts in muscle-repair, 235. 236 Sarcoma, 702 action of erysipelas cocci on, 735 alveolar, 705 of bones of cranium, 717 changes in, retrograde, 708 chondro-, 716 Cohnheim's theory regard- ing, 7°3 etiology, 703 giant-cells, 706 metastatic, 708 organisms in, 704 osteo-, 712 osteoid, 716 periosteal, 544, 715 pigment, multiple, 71 1 pigmented, 707 prognosis, 724 round-cell, large, 705 spindle-cell, central, 713 treated by streptococcus of erysipelas, 734 of the air-passages, 725 of bladder, 719 of bone, 712 central round-cell, 714 spindle-cell of, 713 spontaneous fracture in, 714 of brain, 729 of breast, 723 malignancy, 724 of intestine, 729 of kidney, 718 of larynx, 726 of nasal passages, 727 of pharynx, 728 of soft palate, 728 of stomach, 729 of testis, 721 of tonsil, 725 of uterus, 720 osteoid, 716 pigment, multiple, 71 1 Sardonic grin, 439 Scarlet fever (see Fever). surgical, liability of chil- dren to, 324 Scar-tetanus, 435 Schluck-pneumonia, 123 Scirrhus cutis, 651 Scrofula, bacteria in, 594 bone disease in relation to tuberculosis, 515 Scrofuloderma, 561 Scrotum, cancer of, 658 tar and paraffin in, 659 870 INDEX. Sea-voyage in tuberculosis, 580 Section, nerve, degeneration after, 238 neuromata after, 241 prognosis, 241 Sepsis and asepsis of the Greeks, 785 Septicaemia, diagnosis, 353 symptoms, 343 treatment, 353 alcohol in, 354 Septicaemia, a bacterial dis- ease, 336 bacteria in, 337 cause of foul odor, a, 343 ptomaines a, 342 trauma a predisposing, 341 diarrhoea in, 347 disinfectants in, 354 entrance of poison, 341 eruption in, scarlet, 347 euphoria in, 348 genito-urinary infection, 343 icterus in, 347 leucocytes in, 347 lungs starting-points of, 342 lymphatics in, 347 in osteomyelitis, 202 osteomyelitis a starting- point for, 342 post-mortem appearances, 349 puerperal, 343 spontaneous, 352 temperature in, 346 Sequestra of bone in osteomy- elitis, 199 Sequestrum, separation of, in osteomyelitis, 213 in tarsus, 522 Sero-therapy of syphilis, 850 of tetanus, 846 of tuberculosis, 849 Shock, 277 diagnosis, 295 prognosis, 297 symptoms, 296 treatment, 297 enemata in, 299 Shock, age influencing, 293 from blows in the neck, 290 from burns, 290 causes of, 288 cells of cord in, 285 from concussion of larynx, 290 hemorrhage causing, 286 hospitals, table for patients in, 298 auto-infusion, 299 insidious, 287 irritation in pneumogastric, 281 Shock, local, 288 mental emotion a cause of, 292 condition in, 294 nature of, 279 nerve-centres in, 284 nerve-exhaustion in, 283 nerve-injury causing, 286 nerve-irritation in, degrees of, 283 mechanical, 283 pneumogastric, 281 neurasthenia following, 293 over-stimulation of nerves, 283 pain in, 291 clinical picture, 278 from railway injuries, 293 reflex vaso-motor paralysis, 279 semilunar ganglion, 289 stimulants in, 299 suppressed lactation, 294 temperature in, 294 torpid form, 286 varieties, 286 vaso-motor theory of, 280 vomiting in, 294 Shoulder-joint, tuberculosis of, 538 caries sicca in, 538 Silver nitrate in genitourinary germicide, 8^3 Sinuses, curetting the, in mid- dle-ear suppuration, 379 Skiagraphy in surgical diag- nosis, 796 Skin, actinomycosis of, 475 cancer of, 652, 660 deep-seated, 649 superficial, 650 carcinoma of, 648 condition of, pathological, in erysipelas, 398 fibroma of, multiple, 754 infection of tuberculosis through the, 510 inflammation of, in erysipe- las, 388 inoculation, tubercular, 561 pigmentation, 90 sterilization of, 801 surgical bacteriology of, 800 Skin-grafting, 189 Skin-tuberculosis, 558 treatment, 563 Slough, 128 Sloughs in phlegmonous in- flammation, 162 Slumbering-cell theory, Gra- witz, 105, 220 Smoking, a cause of lip can- cer, 655 Snake-bite, 495, 503 Snake-bite, antitoxic serum in, 503 changes following, patho- logical, 499 mechanism of, 497 mortality of, in India, 495 stimulants in, 501 symptoms, 498 treatment, 500 strychnia in, 502 venom of, action, 497 Snakes, death from, in India, 495 venom, secretion of, 496 Spasm, muscular, in joint- tuberculosis, 533 Spasmotoxin, 55 Spasms in tetanus, 438, 437 Spermatocele, 743 Spina ventosa, 521 Spinal-cord degeneration a cause of changes in joints, 624 Spinal puncture, 794 Spirilla, 21 Sponges, sterilization of, 806 Spore-formation, bacteria, 20 -staining, Moller, 29 Spores, bacillus, anthrax, 72 anthrax, theory of dissemi- nation by earth-worms, 478 Sporulation, 21 Sputa, staining for the bacilli of tuberculosis, 57 Staining, bacteria, methods, 26 removal of haemoglobin and fat in, 29 spores, 29 sputa for the bacilli of tu- berculosis, 57 Staphylococci, 21 in osteomyelitis, 194 Staphylococcus, action of, pep- tonizing, 146 albus or skin, 801 cereus albus, 26, 45 flavus, 26, 45 epidermidis albus, 790 pyogenes albus, 45 aureus, 43 in osteomyelitis, 194, 195 citreus, 45 in cystitis, 828 viridis flavescens, 45 Sterilization, 31 dry heat, 32 of ear, 819 fractional, 31 of mouth, 813 of nose, 821 of rectum, 831 of skin, 801 steam, 32 INDEX. 8 7 I Sterilization of urethra; 830 of vagina, 831 of vulva, 831 Sterilizer, Arnold, 32 Sternum, tuberculosis of, 527 Stimulants in shock, 299 in snake-bite, 501 Stomach, cancer of, 688 leiomyoma of, 775 sarcoma of, 729 Streptobacrlus anthracoides, S27 Streptococci, 21 action of, in suppuration, 146 on the tissues, 146 in coagulation-necrosis, 148 in erysipelas, 382, 383, 384, 399 point of entrance in, 382, 386 seat of, 384 in treatment of sarcoma, 734 erysipelatis, 53 pyogenes, 46 Streptococcus pyogenes in cystitis, 826 Stricture of oesophagus, 685 of rectum from cancer, 692 Structure picture, 25 Struma, 743 Strychnia-poisoning simulating tetanus, 445 in snake-bite, 502 Styrone, 803 Sugar of the blood, 787 Sulphates in urine, 794 Sulpho-naphtol, 803 Suppuration, 129, 135, 155— 161 action of streptococcus, 146 bacteria in, frequency, 139 number of, necessary to cause, 137 peptonizing action of, a cause of, 155 coagulation - necrosis, 146, 148 croton oil producing, 140 defined, 141 etiology, 151 conclusion, 159 favored by season of the year, 150 fluctuation, 158 foreign bodies cannot pro- duce, 143 locality as favoring, 151 middle-ear, curetting the sinuses in, 379 mitosis in, 155 necrosis the result of, in osteomyelitis, 199 symptoms in constitutional, 158 Surgeons' hands, disinfection of, 805 Surgical bacteriology of skin, 800 diagnosis, bacteriological ex- amination in, 788 blood-examination in, 786 examination of feces, 795 Rontgen rays in, 796 scientific aids to, 785 spinal puncture in, 794 urinary conditions in, 790 kidney, 826 Suture, tension from, causing aseptic fever, 323 nerve, 242 Sutures, sterilization of, 806 Sweat-glands, adenoma of, 650, 740 Sweating in defervescence, 31 1 Swelling in inflamed organs, causes, 112 a symptom of inflammation, ill Syncope, 296 Synovitis following erysipelas, 392 obliterative, in joint-tuber- culosis, 529 Syphilis bacillus, 65, 66 Lustgarten, 66 sero-therapy of, 850 Syringomyelia, 764 Tabes mesenterica, 570 Tar and paraffin in cancer of scrotum, 659 Teeth, carious, a cause of p hos phor us - necrosis, 617 Temperature, bacteria in, 22 body, inequalities in, 302 regulation, 302 constant, by chemical changes resulting from nerve-action, 307 local increase of, in inflam- mation, 1 16 Temperature in aseptic fever, 320 in suppurative fever, 328 in traumatic fever, 317 in hospital gangrene, 426 in hydrophobia, 459 in pyaemia, 367 in saprsemia, 345 in septicaemia, 346 in shock, 294 in tetanus, 440 Tendon cicntrix, 234 healing of, 232 repair, 232 blood-clot in, 233 slumbering cells in, 234 union of, after section, 235 Tendon-sheaths infected from a felon, 169 tuberculosis of, 589-593 Teratoma, 749 Testicle, cancer of, 698 tuberculosis of, 576 castration in, 580 relation of trauma to, 577 symptoms, 578 Testis, adenoma of, 742 myosarcoma, 776 sarcoma of, 721 Tetani, bacillus of, 53, 435 Tetanin, 55, 436 Tetanoloxin, 55 Tetanus, 434-452 diagnosis, 444 prognosis, 447 sero-therapy in, 846 symptoms, 438 treatment, 448, 804 antiseptic, 449 blood-serum in, 451 Calabar bean in, 448 chloral in, 448 chloroform in, 449 vapor bath in, 450 Tetanus, acute, 437 age in relation to, 437 antitoxine, 451, 804 bacilli in garden soil, 436 bacillus, when found, 436 caused by eating infected flesh, 436 cephalic, 442 chronic, 441 epidemics of, 437 frequency of, in the tropics, 434 head, 441, 442 facial-nerve paralysis in, 442 hydrophobicus, 441 hysterical contraction of jaws simulating, 445 immunity to, 451 mortality of, 447 muscle rupture in, 439 muscles in, masseter, 438 nerve-changes in, 444 nerve-injury a cause of, 435. . nerve-origin, 434 post-mortem changes in, 443 scar-, 435 spasm in, tonic, 438 spasms in, 439 strychnia-poisoning simulat- ing, 445 temperature in, 440 wounds in, character of, 443. following punctured wounds, 436 872 INDEX. Tetany, 446 Therapy, blood-serum in, 153 Thiersch skin-grafting, 189 solution, 831 Throat, acute infectious in- flammation of, diagno- sis of, 816 tuberculosis of, 565 Thrombi, infective, 147 coagulation-necrosis after, 147, 148 Thrombo-phlebitis, 147 in pyaemia, 361 Thrombosis, infective, appear- ance of tissue after, 148 in pyaemia, 361, 375 of facial vein in carbuncle of lips, 180 Thrombus formation in infec- tive inflammation, 147 organization of, after ligature of an artery, 252 role of, after ligature of arte- ries, 254 Thymus gland (see Gland). Thyroid, accessory, 745 extract, treatment with, 747 Tissue, appearance of, after infective inflammation, 148 abscess, wall of, 157 bone, destruction of, in hip- joint disease, 536 cicatricial, contraction, 226 connective, 220, 665 inflammation of, in pyae- mia, 375, 376 granulation, 157, 226 epithelioid cells in, 229 intercellular substance in, 229 spindle-cells in, 227 vascular loops in, 228 medullary, of bones in osteo- malacia, 598 changes in, in ostitis de- formans, 598 nerve, repair in brain, 242 from pre-existing tissue, 238 new, capillary development in, 229 repair in granulation, vascu- lar loops in, 228 Tissue-cells, proliferation of, in inflammation, 104 repair of, process, 104 Tissue-metamorphosis, theory, 103 Tissues, action of streptococ- cus on the, 146 bacterial development in, mechanical conditions favoring, 149 Tissues, hardening of, patho- logical, 30, 807 inflamed, fibrin formed in, 108 fluids in, 108 in inflammation, action of, 101 elasticity of, 96 Tongue, black, 397 cancer of (see Cancer) . of the frog, changes caused by ligature, 94, 97 tuberculosis of, 566 warts a pre-cancerous stage in the, 679 wooden-, 476 Tonsil, sarcoma of, 725 Tooth-filling, antiseptics of, 815 Torpor, traumatic, 277 Toxalbumin, 152 Trauma a cause of inflamma- tion, 121 predisposing cause of septi- caemia, 341 relation of, to tuberculosis of testicle, 577 tumors from, 636 Traumatism in cancer of breast, 663 Treatment of wounds, 807 Trephining in osteomyelitis, 211 Tropho-neurosis, reflex, in os- titis deformans, 600 Tubercle, anatomical, 510, 562 submillary, bacilli in, 506 Tuberculin T. R., 849 Tuberculosis, 504-528 abscesses, cold, 519 absorption of small nodules, 518 bacilli in, 505 staining sputa for the, 57 bacillus of, 56 Koch's demonstration of, 505 Ziehl's method of stain- ing for, 57 cartilage in, ulceration of, 531 cheesy degeneration in, 507 connective-tissue, 589 contagion through the lung, 509 contagiousness of, 504 cutis vera, 560 degeneration in tubercle, 507 direction of disease in gen- ito-urinary tract, 577 entrance of virus, mode, 508 Tuberculosis, epithelioid cells in, 506 , exanthemata, a predisposing cause, 511 experimental, 515 fistula in ano, 567 frequency of, 512 giant-cells in, 59, 505 gonorrhoea a factor in spread of. 575 hectic fever, 519 hereditary, 508 hydrops articuli, 531 infection in, 61 genital tract aided by gonorrhoea, 575 genito-urinary tract, 573 intravascular, 51 1 through the skin, 510 inoculability of, 504 in joints, 514, 529 miliary, following opera- tions, 534 in milk, 509 often multiple, 512 papillomatosa cutis, 563 Pott's disease, 524 pseudo-, 595 psoas abscess, 525 rice-bodies, 590 sea-voyage in, 580 secondary, 510 sero-therapy of, 849 spread of, from bone to joint, 530 transmission of, in the rite of circumcision, 510 urethritis, 574 verrucosa cutis, 562 vertebral column common- est seat of, 523 vesicula seminalis, 578 zooglceica, 595 Tuberculosis of bladder in women, 579 of bone, 513 absorption of diseased portion, 522 cheesy sequestra, 517 diagnosis, 521 infarctions in, 518 joints most usually at- tacked, 535 lesion, seat of, 521 secondary changes, 517 of elbow -joint, 539 of face, 528 of Fallopian tubes, 573 genito-urinary, 573-583 of mesenteric glands, 570 joint-, 529-557 ankylosis following, 534 bone-atrophy in, 534 extension of, 547 pain in, 540 INDEX. 873 Tuberculosis, joint-, resection in, 552 treatment of, iodoform in, 548 plaster of Paris in, 546 of kidneys, 581 of knee-joint, 536 of lymphatic glands, prog- nosis, 588 of lymphatics, 585-589 of mamma, 583, 584 of membrane, 519 of abscess, 520 of mucous membrane, 565 of muscles, 593 of omentum, 750 of ovaries, 576 of rectum, 568 of ribs, 526 of sacro-iliac synchondrosis, 528 of shoulder-joint, caries sic- ca in, 538 of skin, 558 treatment, 563 of sternum, 527 of tendon-sheaths, 589 symptoms, 591 treatment, 593 of testicle, 576, 580 relation of trauma to, 577 symptoms, 578 of throat, 565 of tongue, 566 of urethra, 581 of uterus, 573 of vagina, 574 of vulva, 574 Tumor albus, 537 inflammation a symptom of, ill Tumors, 633 benign, 737 bone, myeloid, 713 classification, 637 embryonic theory of origin, 635 heredity, 636 heterologous, 634 homologous, 634 from trauma, 636 Turpentine, Chian, in cancer, 701 Typhoid, bone, 193 Tyrotoxicon, 342 Ulcer, 182 blood-pigment in, 184 callous, 187 caused by infectious disease, 182 characteristics of, anatomi- cal, 182 defined, 182 Ulcer, erethistic, 186 fungous, 187 inflammatory, 184 mal-perforant, 185 phagedenic, 188 from pressure, 185 rodent, 649-655 malignancy of, 654 treatment, 661 treatment of, 188 varicose, 184 Ulceration of cartilage in tu- berculosis, 531 endocarditis in, 363, 365, 372 Ulcerations, tuberculous, 563 Ulcers, phagedenic, 188 strapping, 189 torpid, 187. (See Ulcer.) Urea, excretion of, 312 in urine, 794 Urethra, disinfection of, 830 male, bacteria of, 824, 825 tuberculosis of, 581 Urinary casts, 792 conditions in surgical diag- nosis, 790 Urine, amount of, 790 bacteriological examination of, 790 color of, 791 extravasation of, cause of gangrene, 270 in pyaemia, 370 Urobacillus liquefaciens septi- cus, 826 Urotropine, 834 Uterus, cancer of (see Cancer). diagnosis, 676 hemorrhage, an early symptom of, 676 heredity in, 673 hydrometra in, 675 myoma of, 775 pregnancy a cause of, 673 sarcoma of, 720 tuberculosis of, 573 Vaccination against bacillus anthracis, 74 erysipelas following, 385 Vagina, sterilization of, 831 tuberculosis of, 574 Vapor-bath in tetanus, 450 Vascular loops in granulation tissue, 228 Vaso-constrictor nerves, 82 Vaso-motor centre, 81 disturbance cause of sym- metrical gangrene, 274 theory of shock, 280 Venom secretion of snakes, 496 Vertebral column, commonest seat of tuberculosis, 523 Vesicles in erysipelas, 389 Vesicula seminalis, tuberculo- sis of, 578 Vessel-wall in inflammation, changes in, 95 Vessel-walls, molecular changes in, causes of inflammatory phenom- ena, 118 stomata in, formation of, in inflammation, 113 Virus, erysipelas, 382 hydrophobia, increased vir- ulence, 465 modification of, 464 tuberculosis, mode of en- trance, 508 Vomiting in shock, 294 Vulva, bacteria of, 825 lupus of, 575 sterilization of, 831 tuberculosis of, 574 Wall of abscess tissue, 157 Wart, venereal, 752 Warts a pre-cancerous stage in the tongue, 679 Water in the knee, 544 Wens, orbital, 751 White blood-count, 786 Whitlow, melanotic, 710 Women, tuberculosis of blad- der in, 579 Wooden-tongue, 476 Wool-sorters' disease, 76, 479 Wound, closing of, 81 1 erysipelas, condition of, 390 treatment, 407 flaps, coaptation of, 222 Wound-healing, 221 -infection, avoidance of, 801 -treatment, immobility in, 811 Wounds, dissecting-room, 350 dressings for, 81 1 dryness of, 810 non-infection of, in same person in hospital gan- grene, 419 punctured, followed by teta- nus, 436 treatment of, 807 X-RAY DERMATITIS, 8oO X-rays in diagnosing fracture, 797 renal calculi, 798 in locating foreign bodies, 797 Xeroderma pigmentosum, 660 Xerosis bacillus, 818 Xylol balsam, 29 Ziehl's solution, 27 Zymotic disease, 17 CATALOGUE OF THE MEDICAL PUBLICATIONS OF W* B. SAUNDERS, No. 925 WALNUT STREET, PHILADELPHIA, Arranged Alphabetically and Classified under Subjects* THE books advertised in this Catalogue as being sold by subscription are usually to be obtained from travelling solicitors, but they will be sent direct from the office of pub- lication (charges of shipment prepaid) upon receipt of the prices given. All the other books advertised are commonly for sale by booksellers in all parts of the United States; but books will be sent to any address, carnage prepaid, on receipt of the published price. Money may be sent at the risk of the publisher in either of the following ways : A post- office money order, an express money order, a bank check, and in a registered letter. Money sent in any other way is at the risk of the sender. See pages 30, 31, for a List of Contents classified according to subjects. LATEST PUBLICATIONS. International Text-Book of Surgery* See page 32. American Text-Book of Surgery — Third (Revised) Edition. See page 5. 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Cloth, $7.00 net; Sheep or Half Morocco, $8.00 net. Sold by Subscriptio?i. Illustrated Catalogue of the " American Text-Books*' sent free upon application. 4 Medical Publications of W. B. Saunders. AN AMERICAN TEXT=BOOK OF GENITOURINARY AND SKIN DISEASES. By 47 Eminent Specialists and Teachers. Edited by L. Bolton Bangs, M. D., Professor of Genito- Urinary Surgery, University and Bellevue Hospital Medical College, New York ; and W. A. Hard- away, M. D., Professor of Diseases of the Skin, Missouri Medical College. Imperial octavo volume of 1229 pages, with 300 engravings and 20 full-page colored plates. Cloth, $7.00 net; Sheep or Half Morocco, $8.00 net. Sold by Subscription. " This volume is one of the best yet issued of the publisher's series of ' American Text- Books.' The list of contributors represents an extraordinary array of talent and extended experience. The book will easily take the place in comprehensiveness and value of the half dozen or more costly works on these subjects which have heretofore been necessary to a well-equipped library." — New York Polyclinic. AN AMERICAN TEXT=BOOK OF GYNECOLOGY, MEDICAL AND SURGICAL. Second Edition, Revised. By 10 of the Leading Gynecologists of America. Edited by J. M. Baldy, M. D., Professor of Gynecology in the Philadelphia Polyclinic, etc. Handsome imperial octavo volume of 718 pages, with 341 illus- trations in the text, and 38 colored and half-tone plates. Cloth, $6.00 net ; Sheep or Half Morocco, $7.00 net. Sold by Subscription. " It is practical from beginning to end. Its descriptions of conditions, its recommen- dations for treatment, and above all the necessary technique of different operations, are clearly and admirably presented. . . . It is well up to the most advanced views of the day, and embodies all the essential points of advanced American gynecology. It is destined to make and hold a place in gynecological literature which will be peculiarly its own."— Medical Record, New York. AN AMERICAN TEXT=BOOK OF LEGAL MEDICINE AND TOXI- COLOGY. Edited by Frederick Peterson, M. D. , Clinical Professor of Mental Diseases in the Woman's Medical College, New York; Chief of Clinic, Nervous Department, College of Physicians and Surgeons, New York ; and Walter S. Haines, M.D., Professor of Chemistry, Pharmacy, and Toxicology in Rush Medical College, Chicago. In Preparation. AN AMERICAN TEXT=BOOK OF OBSTETRICS. By 15 Eminent American Obstetricians. Edited by Richard C. Nor- ris, M.D.; Art Editor, Robert L. Dickinson, M.D. One handsome imperial octavo volume of 1014 pages, with nearly 900 beautiful colored and half-tone illustrations. Cloth, $7.00 net; Sheep or Half Morocco, $8.00 net. Sold by Subscription. " Permit me to say that your American Text-Book of Obstetrics is the most magnificent medical work that I have ever seen. I congratulate you and thank you for this superb work, which alone is sufficient to place you first in the ranks of medical publishers. " — ALEXANDER J. C. Skene, Professor of Gynecology in the Long Island College Hospital, Brooklyn, N. Y. " This is the most sumptuously illustrated work on midwifery that has yet appeared. In the number, the excellence, and the beauty of production of the illustrations it far surpasses every other book upon the subject. This feature alone makes it a work which no medical library should omit to purchase." — British Medical Journal. "As an authority, as a book of reference, as a ' working book ' for the student or prac- titioner, we commend it because we believe there is no better." — American Journal of the Medical Sciences. Illustrated Catalogue of the "American Text-Books " sent free upon application* Medical Publications of W. B. Saunders. 5 AN AMERICAN TEXT=BOOK OF PATHOLOGY. Edited by John Guiteras, M.D., Professor of General Pathology and of Morbid Anatomy in the University of Pennsylvania ; and David Riesman, M.D. , Demonstrator of Pathological Histology in the University of Pennsylvania. In Prepciratio?i. AN AMERICAN TEXT-BOOK OF PHYSIOLOGY. By i o of the Leading Physiologists of America. Edited by William H. Howell, Ph.D., M.D., Professor of Physiology in the Johns Hop- kins University, Baltimore, Md. One handsome imperial octavo volume of 1052 pages. Illustrated. Cloth, $6.00 net j Sheep or Half Morocco, $7.00 net. Sold by Subscription. " We can commend it most heartily, not only to all students of physiology, but to every physician and pathologist, as a valuable and comprehensive work of reference, written by men who are of eminent authority in their own special subjects." — London Lancet. " To the practitioner of medicine and to the advanced student this volume constitutes, we believe, the best exposition of the present status of the science of physiology in the English language." — American Journal of the Medical Sciences. AN AMERICAN TEXT=BOOK OF SURGERY. Third Edition. By 11 Eminent Professors of Surgery. Edited by William W. Keen, M.D., LL.D., and J. William White, M.D., Ph.D. Handsome im- perial octavo volume of 1230 pages, with 496 wood-cuts in the text, and 37 colored and half-tone plates. Thoroughly revised and enlarged, with a section devoted to " The Use of the Rontgen Rays in Surgery." Cloth, S7.00 net; Sheep or Half Morocco, $8.00 net. «' Personally, I should not mind it being called THE Text-Book (instead of A Text- Book) , for I know of no single volume which contains so readable and complete an account of the science and art of Surgery as this does." — Edmund Owen, F.R.C.S., Member of the Board of Examiners of the Royal College of Surgeons, England. " If this text-book is a fair reflex of the present position of American surgery, we must admit it is of a very high order of merit, and that English surgeons will have to look very carefully to their laurels if they are to preserve a position in the van of surgical practice." — London Lancet. AN AMERICAN TEXT=BOOK OF THE THEORY AND PRACTICE OF MEDICINE. By 12 Distinguished American Practitioners. Edited by William Pepper, M.D., LL.D., Professor of the Theory and Practice of Medi- cine and of Clinical Medicine in the University of Pennsylvania. Two handsome imperial octavo volumes of about 1000 pages each. Illus- trated. Prices per volume : Cloth, $5.00 net ; Sheep or Half Morocco, $6.00 net. Sold by Subscription. " I am quite sure it will commend itself both to practitioners and students of medicine, and become one of our most popular text-books." — Alfred Loomis, M.D., LL.D., Pro- fessor of Pathology and Practice of Medicine, University of the City of New York. " We reviewed the first volume of this work, and said : * It is undoubtedly one of the best text-books on the practice of medicine which we possess.' A consideration of the second and last volume leads us to modify that verdict and to say that the completed work is in our opinion the best of its kind it has ever been our fortune to see. " — New York Medical Journal. Illustrated Catalogue of the "American Text-Books " sent free upon application. 6 Medical Publications of W. B. Saunders. AN AMERICAN YEAR-BOOK OF MEDICINE AND SURGERY. A Yearly Digest of Scientific Progress and Authoritative Opinion in all branches of Medicine and Surgery, drawn from journals, monographs, and text-books of the leading American and Foreign authors and investigators. Collected and arranged, with critical editorial com- ments, by eminent American specialists and teachers, under the general editorial charge of George M. Gould, M.D. One handsome imperial octavo volume of about 1200 pages. Uniform in style, size, and general make-up with the "American Text-Book" Series. Cloth, $6.50 net; Half Morocco, $7.50 net. Sold by Subscription. " It is difficult to know which to admire most — the research and industry of the distin- guished band of experts whom Dr. Gould has enlisted in the service of the Year-Book, or the wealth and abundance of the contributions to every department of science that have been deemed worthy of analysis. . . . It is much more than a mere compilation of abstracts, for, as each section is entrusted to experienced and able contributors, the reader has the advantage of certain critical commentaries and expositions . . . proceeding from writers fully qualified to perform these tasks. . . . It is emphatically a book which should find a place in every medical library, and is in several respects more useful than the famous 'Jahrbucher' of Germany." — London Lancet. THE AMERICAN POCKET MEDICAL DICTIONARY. [See Dor land'' 's Pocket Dictionary, page 10.] ANDERS' PRACTICE OF MEDICINE. Third Revised Edition. A Text-Book of the Practice of Medicine. By James M. Anders, M.D., Ph.D., LL.D., Professor of the Practice of Medicine and of Clinical Medicine, Medico-Chirurgical College, Philadelphia. In one handsome octavo volume of 1292 pages, fully illustrated. Cloth, $5.50 net; Sheep or Half Morocco, $6.50 net. *' It is an excellent book, — concise, comprehensive, thorough, and up to date. It is a. credit to you ; but, more than that, it is a credit to the profession of Philadelphia — to us." James C. Wilson, Professor of the Practice of Medicine and Clinical Medicine, Jefferson Medical College, Philadelphia. ASHTON'S OBSTETRICS. Fourth Edition, Revised. Essentials of Obstetrics. By W. Easterly Ashton, M.D., Pro- fessor of Gynecology in the Medico-Chirurgical College, Philadelphia. Crown octavo, 252 pages; 75 illustrations. Cloth, $1. 00 ; interleaved for notes, $1.25. [See Saunders' Question- Compends, page 21.] " Embodies the whole subject in a nut-shell. We cordially recommend it to our read- ers." — Chicago Medical Times. BALL'S BACTERIOLOGY. Third Edition, Revised. Essentials of Bacteriology ; a Concise and Systematic Introduction to the Study of Micro-organisms. By M. V. Ball, M.D., Bacteriol- ogist to St. Agnes' Hospital, Philadelphia, etc. Crown octavo, 218 pages; 82 illustrations, some in colors, and 5 plates. Cloth, $1.00; interleaved for notes, $1.25. [See Saunders' Question- Compends, page 21.] " The student or practitioner can readily obtain a knowledge of the subject from a perusal of this book. The illustrations are clear and satisfactory." — Medical Record, New York. Medical Publications of W. B. Saunders. 1 BASTIN'S BOTANY. Laboratory Exercises in Botany. By Edson S. Bastin, M.A., late Professor of Materia Medica and Botany, Philadelphia College of Pharmacy. Octavo volume of 536 pages, with 87 plates. Cloth, $2.50. "It is unquestionably the best text-book on the subject that has yet appeared. The work is eminently a practical one. We regard the issuance of this book as an important event in the history of pharmaceutical teaching in this country, and predict for it an unquali- fied success." — Alumni Report to the Philadelphia College of Pharmacy. "There is no work like it in the pharmaceutical or botanical literature of this country, and we predict for it a wide circulation." — American Journal of Pharmacy. BECK'S SURGICAL ASEPSIS. A Manual of Surgical Asepsis. By Carl Beck, M.D«, Surgeon to St. Mark's Hospital and the New York German Poliklinik, etc. 306 pages; 65 text-illustrations, and 12 full-page plates. Cloth, $1.25 net. " An excellent exposition of the ' very latest' in the treatment of wounds as practised by leading German and American surgeons." — Birmingham (Eng.) Medical Review. "This little volume can be recommended to any who are desirous of learning the details of asepsis in surgery, for it will serve as a trustworthy guide." — London Lancet. BOISLINIERE'S OBSTETRIC ACCIDENTS, EMERGENCIES, AND OPERATIONS. Obstetric Accidents, Emergencies, and Operations. By L. Ch. Boisliniere, M.D., late Emeritus Professor of Obstetrics, St. Louis Medical College. 381 pages, handsomely illustrated. Cloth, $2.00 net. " It is clearly and concisely written, and is evidently the work of a teacher and practi- tioner of large experience." — British Medical Journal. " A manual so useful to the student or the general practitioner has not been brought to our notice in a long time. The field embraced in the title is covered in a terse, interesting way." — Yale Medical Journal. BROCKWAY'S MEDICAL PHYSICS. Second Edition, Revised. Essentials of Medical Physics. By Fred J. Brockway, M.D., Assistant Demonstrator of Anatomy in the College of Physicians and Surgeons, New York. Crown octavo, 330 pages; 155 fine illustrations. Cloth, $1.00 net ; interleaved for notes, $1.25 net. [See Saunders* Question- Comp ends, page 21.] " The student who is well versed in these pages will certainly prove qualified to com- prehend with ease and pleasure the great majority of questions involving physical principles likely to be met with in his medical studies." — American Practitioner and News. "We know of no manual that affords the medical student a better or more concise exposition of physics, and the book may be commended as a most satisfactory presentation of those essentials that are requisite in a course in medicine." — New York Medical Journal. " It contains all that one need know on the subject, is well written, and is copiously illustrated." — Medical Record, New York. BURR ON NERVOUS DISEASES. A Manual of Nervous Diseases. By Charles W. Burr, M.D., Clinical Professor of Nervous Diseases, Medico-Chirurgical College, Philadelphia ; Pathologist to the Orthopedic Hospital and Infirmary for Nervous Diseases; Visiting Physician to St. Joseph's Hospital, etc. Jn Preparation. 8 Medical Publications of W. B. Saunders. BUTLER'S MATERIA MEDICA, THERAPEUTICS, AND PHAR- MACOLOGY. Third Edition, Revised. A Text=Book of Materia Medica, Therapeutics, and Pharma- cology. By George F. Butler, Ph.G., M.D., Professor of Materia Medica and of Clinical Medicine in the College of Physicians and Surgeons, Chicago; Professor of Materia Medica and Therapeutics, Northwestern University, Woman's Medical School, etc. Octavo, 874 pages, illustrated. Cloth, $4.00 net; Sheep, $5.00 net. " Taken as a whole, the book may fairly be considered as one of the most satisfactory of any single-volume works on materia medica in the market," — Journal of the American Medical Association. CERNA ON THE NEWER REMEDIES. Second Edition, Revised. Notes on the Newer Remedies, their Therapeutic Applications and Modes of Administration. By David Cerna, M.D., Ph.D., formerly Demonstrator of and Lecturer on Experimental Therapeutics in the University of Pennsylvania ; Demonstrator of Physiology in the Medical Department of the University of Texas. Rewritten and greatly enlarged. Post-octavo, 253 pages. Cloth, $1.25. " The appearance of this new edition of Dr. Cerna's very valuable work shows that it is properly appreciated. The book ought to be in the possession of every practising physi- cian." — New York Medical Journal. CHAPIN ON INSANITY. A Compendium of Insanity. By John B. Chapin, M.D., LL.D., Physician-in-Chief, Pennsylvania Hospital for the Insane ; late Physi- cian-Superintendent of the Willard State Hospital, New York ; Hon- orary Member of the Medico-Psychological Society of Great Britain, of the Society of Mental Medicine of Belgium. i2mo, 234 pages, illustrated. Cloth, $1.25 net. " The practical parts of Dr. Chapin's book are what constitute its distinctive merit. We desire especially to call attention to the fact that on the subject of therapeutics of insanity the work is exceedingly valuable. It is not a made book, but a genuine condensed thesis, which has all the value of ripe opinion and all the charm of a vigorous and natural style." — Philadelphia Medical Journal. CHAPMAN'S MEDICAL JURISPRUDENCE AND TOXICOLOGY. Second Edition, Revised. Medical Jurisprudence and Toxicology. By Henry C. Chapman, M.D., Professor of Institutes of Medicine and Medical Jurisprudence in the Jefferson Medical College of Philadelphia. 254 pages, with 55 illustrations and 3 full-page plates in colors. Cloth, $1.50 net. "The best book of its class for the undergraduate that we know of." — New York Medical Times. CHURCH AND PETERSON'S NERVOUS AND MENTAL DISEASES. Nervous and Mental Diseases. By Archibald Church, M. D., Professor of Mental Diseases and Medical Jurisprudence in the North- western University Medical School, Chicago ; and Frederick Peter- son, M. D., Clinical Professor of Mental Diseases, Woman's Medical College, N. Y.; Chief of Clinic, Nervous Dept., College of Physi- cians and Surgeons, N. Y. Handsome octavo volume of 843 pages, profusely illustrated. Cloth, $5.00 net j Half Morocco, $6.00 net. Medical Publications of W. B. Saunders. 9 CLARKSON'S HISTOLOGY. A Text=Book of Histology, Descriptive and Practical. By Arthur Clarkson, M.B., CM. Edin., formerly Demonstrator of Physiology in the Owen's College, Manchester; late Demonstrator of Physiology in Yorkshire College, Leeds. Large octavo, 554 pages; 22 engravings in the text, and 174 beautifully colored original illustra- tions. Cloth, strongly bound, $4.00 net. " The work must be considered a valuable addition to the list of available text- books, and is to be highly recommended." — New York Medical Journal. " This is one of the best works for students we have ever noticed. We predict that the book will attain a well-deserved popularity among our students." — Chicago Medical Recorder. CLIMATOLOGY. Transactions of the Eighth Annual Meeting of the American Climatological Association, held in Washington, September 22-25, 1 89 1. Forming a handsome octavo volume of 276 pages, uniform with remainder of series. (A limited quantity only.) Cloth, $1.50. COHEN AND ESHNER'S DIAGNOSIS. Essentials of Diagnosis. By Solomon Solis-Cohen, M.D., Pro- fessor of Clinical Medicine and Applied Therapeutics in the Philadel- phia Polyclinic ; and Augustus A. Eshner, M.D., Professor of Clinical Medicine in the Philadelphia Polyclinic. Post-octavo, 382 pages; 55 illustrations. Cloth, $1.50 net. [See Saunders' Question- Compends, page 21.] " We can heartily commend the book to all those who contemplate purchasing a 'com- pend.' It is modern and complete, and will give more satisfaction than many other works which are perhaps too prolix as well as behind the times." — Medical Review, St. Louis. CORWIN'S PHYSICAL DIAGNOSIS. Third Edition, Revised. Essentials of Physical Diagnosis of the Thorax. By Arthur M. Corwjx, A.M., M.D., Demonstrator of Physical Diagnosis in Rush Medical College, Chicago ; Attending Physician to Central Free Dis- pensary, Department of Rhinology, Laryngology, and Diseases of the Chest, Chicago. 219 pages, illustrated. Cloth, flexible covers, $1.25 net. "It is excellent. The student who shall use it as his guide to the careful study of physical exploration upon normal and abnormal subjects can scarcely fail to acquire a good working knowledge of the subject." — Philadelphia Polyclinic. "A most excellent little work. It brightens the memory of the differential diagnostic signs, and it arranges orderly and in sequence the various objective phenomena to logical solution of a careful diagnosis. " — Journal of Nervous and Mental Diseases. CRAGIN'S GYNAECOLOGY. Fourth Edition, Revised. Essentials of Gynaecology. By Edwin B. Cragix, M. D., Lecturer, in Obstetrics, College of Physicians and Surgeons, New York. Crown octavo, 200 pages; 62 illustrations. Cloth, $1.00 ; interleaved for notes, $1.25- [See Saunders' Question- Compends, page 21.] "A handy volume, and a distinct improvement on students' compends in general. No author who was not himself a practical gynecologist could have consulted the student's needs so thoroughly as Dr. Cragin has done." — Medical Record, Nevtf York. 10 Medical Publications of W. B. Saunders. CROOKSHANK'S BACTERIOLOGY. Fourth Edition, Revised. A Text=Book of Bacteriology. By Edgar M. Crookshank, M.B., Professor of Comparative Pathology and Bacteriology, King's College, London. Octavo volume of 700 pages, with 273 engravings and 22 original colored plates. Cloth, $6.50 net; Half Morocco, $7.50 net. " To the student who wishes to obtain a good resume of what has been done in bacteri- ology, or who wishes an accurate account of the various methods of research, the book may be recommended with confidence that he will find there what he requires." — London Lancet. Da COSTA'S SURGERY. Second Ed., Revised and Greatly Enlarged. Modern Surgery, General and Operative. By John Chalmers DaCosta, M.D., Clinical Professor of Surgery, Jefferson Medical College, Philadelphia ; Surgeon to the Philadelphia Hospital, etc. Handsome octavo volume of 900 pages, profusely illustrated. Cloth, $4.00 net; Half Morocco, $5.00 net. "We know of no small work on surgery in the English language which so well fulfils the requirements of the modern student." — Medico-Chirurgical Journal, Bristol, England. DE SCHWEINITZ ON DISEASES OF THE EYE. Third Edition, Revised. Diseases of the Eye. A Handbook of Ophthalmic Practice. By G. E. de Schweinitz, M.D., Professor of Ophthalmology in the Jefferson Medical College, Philadelphia, etc. Handsome royal octavo volume of 696 pages, with 256 fine illustrations and 2 chromo-litho- graphic plates. Cloth, $4.00 net ; Sheep or Half Morocco, $5.00 net. " A clearly written, comprehensive manual. One which we can commend to students as a reliable text-book, written with an evident knowledge of the wants of those entering upon the study of this special branch of medical science." — British Medical Journal. " A work that will meet the requirements not only of the specialist, but of the general practitioner in a rare degree. I am satisfied that unusual success awaits it." — William Pepper, M.D., Professor of the Theory and Practice of Medicine and Clinical Medicine, University of Pennsylvania. DORLAND'S DICTIONARY. Second Edition, Revised. The American Pocket Medical Dictionary. Containing the Pro- nunciation and Definition of all the principal words and phrases, and a large number of useful tables. Edited by W. A. Newman Dorland, M. D., Assistant Demonstrator of Obstetrics, University of Pennsylvania; Fellow of the American Academy of Medicine. 518 pages ; handsomely bound in full leather, limp, with gilt edges and patent index. Price, $1.00 net; with thumb index, $1.25 net. DORLAND'S OBSTETRICS. A Manual of Obstetrics. By W. A. Newman Dorland, M.D., Assistant Demonstrator of Obstetrics, University of Pennsylvania; Instructor in Gynecology in the Philadelphia Polyclinic. 760 pages; 163 illustrations in the text, and 6 full-page plates. Cloth, $2.50 net. " By far the best book on this subject that has ever come to our notice." — American Medical Review. " It has rarely been our duty to review a book which has given us more pleasure in its perusal and more satisfaction in its criticism. It is a veritable encyclopedia of knowledge, a gold mine of practical, concise thoughts." — American Medico-Surgical Bulletin. Medical Publications of W. B. Saunders, 11 FROTHINGHAM'S GUIDE FOR THE BACTERIOLOGIST. Laboratory Guide for the Bacteriologist. By Langdon Froth- INGHAM, M.I). Y.. Assistant in Bacteriology and Veterinary Science, Sheffield Scientific School, Vale University. Illustrated. Cloth, 75 cts. "It is a convenient and useful little work, and will more than repay the outlay neces- sary for its purchase in the saving of time which would otherwise be consumed in looking up the various points of technique so clearly and concisely laid down in its pages." — Ameri- can Medico- Surgical Bulletin. GARRIGUES' DISEASES OF WOMEN. Second Edition, Revised. Diseases of Women. By Henry J. Garrigues, A.M., M.D., Pro- fessor of Gynecology in the New York School of Clinical Medicine ; Gynecologist to St. Mark's Hospital and to the German Dispensary, New York City, etc. Handsome octavo volume of 728 pages, illus- trated by 335 engravings and colored plates. Cloth, $4.00 net; Sheep or Half Morocco, $5.00 net. " One of the best text-books for students and practitioners which has been published in the English language ; it is condensed, clear, and comprehensive. The profound learning and great clinical experience of the distinguished author find expression in this book in a most attractive and instructive form. Young practitioners to whom experienced consultants may not be available will find in this book invaluable counsel and help." — Thad. A. Reamy, M.D., LL.D., Professor of Clinical Gynecology, Medical College of Ohio. GLEASON'S DISEASES OF THE EAR. Second Edition, Revised. Essentials of Diseases of the Ear. By E. B. Gleason, S.B., M.D., Clinical Professor of Otology, Medico-Chirurgical College, Philadelphia ; Surgeon-in-Charge of the Nose, Throat, and Ear Depart- ment of the Northern Dispensary, Philadelphia. 208 pages, with 114 illustrations. Cloth, $1.00 ; interleaved for notes, $1.25. [See Saunders'' Question- Comp ends, page 21.] " It is just the book to put into the hands of a student, and cannot fail to give him a useful introduction to ear-affections ; while the style of question and answer which is adopted throughout the book is, we believe, the best method of impressing facts permanently on the mind. " — Liverpool Medico- Chirurgical Journal. GOULD AND PYLE'S CURIOSITIES OF MEDICINE. Anomalies and Curiosities of Medicine. By George M. Gould, M.D., and Walter L. Pyle, M.D. An encyclopedic collection of rare and extraordinary cases and of the most striking instances of abnormality in all branches of Medicine and Surgery, derived from an exhaustive research of medical literature from its origin to the present day, abstracted, classified, annotated, and indexed. Handsome im- perial octavo volume of 968 pages, with 295 engravings in the text, and 12 full-page plates. Cloth, $6.00 net; Half Morocco, $7.00 net. Sold by Subscription. " One of the most valuable contributions ever made to medical literature. It is, so far as we know, absolutely unique, and every page is as fascinating as a novel. Not alone for the medical profession has this volume value: it will serve as a book of reference for all who are interested in general scientific, sociologic, or medico-legal topics." — Brooklyn Medical Journal. "This is certainly a most remarkable and interesting volume. It stands alone among medical literature, an anomaly on anomalies, in that there is nothing like it elsewhere in medical literature. It is a book full of revelations from its first to its last page, and cannot but interest and sometimes almost horrify its readers." — American Medico- Surgical Bulletin. 12 Medical Publications of W. B. Saunders. GRAFSTROM'S MECHANOTHERAPY. A Text=Book of Mechanotherapy (Massage and Medical Gym= nasties). By Axel V. Grafstrom, B. Sc, M. D., late Lieutenant in the Royal Swedish Army ; late House Physician City Hospital, Black- well's Island, New York. i2mo, 139 pages, illustrated. Cloth, $1.00 net. GRIFFITH ON THE BABY. Second Edition, Revised. The Care of the Baby. By J. P. Crozer Griffith, M.D., Clini- cal Professor of Diseases of Children, University of Pennsylvania ; Physician to the Children's Hospital, Philadelphia, etc. 121110, 404 pages, with 67 illustrations in the text, and 5 plates. Cloth, $1.50. " The best book for the use of the young mother with which we are acquainted. . . . There are very few general practitioners who could not read the book through with advan- tage. ' ' — Archives of Pediatrics. "The whole book is characterized by rare good sense, and is evidently written by a master hand. It can be read with benefit not only by mothers but by medical students and by any practitioners who have not had large opportunities for observing children." — Avieri- can Journal of Obstetrics. GRIFFITH'S WEIGHT CHART. Infant's Weight Chart. Designed by J. P. Crozer Griffith, M.D., Clinical Professor of Diseases of Children in the University of Penn- sylvania, etc. 25 charts in each pad. Per pad, 50 cents net. A convenient blank for keeping a record of the child's weight during the first two years of life. Printed on each chart is a curve representing the average weight of a healthy infant, so that any deviation from the normal can readily be detected. GROSS, SAMUEL D., AUTOBIOGRAPHY OF. Autobiography of Samuel D. Gross, M.D., Emeritus Professor of Surgery in the Jefferson Medical College, Philadelphia, with Remi- niscences of His Times and Contemporaries. Edited by his Sons, Samuel W. Gross, M.D., LL.D., late Professor of Principles of Sur- gery and of Clinical Surgery in the Jefferson Medical College, and A. Haller Gross, A.M., of the Philadelphia Bar. Preceded by a Memoir of Dr. Gross, by the late Austin Flint, M.D., LL.D. In two handsome volumes, each containing over 400 pages, demy octavo, extra cloth, gilt tops, with fine Frontispiece engraved on steel. Price per volume, $2.50 net. " Dr. Gross was perhaps the most eminent exponent of medical science that America has yet produced. His Autobiography, related as it is with a fulness and completeness seldom to be found in such works, is an interesting and valuable book. He comments on many things, especially, of course, on medical men and medical practice, in a very interest- ing way." — The Spectator, London, England. HAMPTON'S NURSING. Second Edition, Revised and Enlarged. Nursing : Its Principles and Practice. By Isabel Adams Hamp- ton, Graduate of the New York Training School for Nurses attached to Bellevue Hospital ; late Superintendent of Nurses and Principal of the Training School for Nurses, Johns Hopkins Hospital, Baltimore, Md. 12 mo, 512 pages, illustrated. Cloth, $2.00 net. " Seldom have we perused a book upon the subject that has given us so much pleasure as the one before us. We would strongly urge upon the members of our own profession the need of a book like this, for it will enable each of us to become a training school in him- self." — Ontario Medical Journal. Medical Publications of W. B. Saunders. 13 HARE'S PHYSIOLOGY. Fourth Edition, Revised. Essentials of Physiology. By H. A. Hare, M.D., Professor of Therapeutics and Materia Medica in the Jefferson Medical College of Philadelphia. Crown octavo, 239 pages. Cloth, $1.00 net; inter- leaved lor notes, $1.25 net. [See Saunders' Question- Compends, page 21.] " The best condensation of physiological knowledge we have yet seen." — Medical Record, New York. HART'S DIET IN SICKNESS AND IN HEALTH. Diet in Sickness and in Health. By Mrs. Ernest Hart, formerly Student of the Faculty of Medicine of Paris and of the London School of Medicine for Women ; with an Introduction by Sir Hendry Thompson, F.R.C.S., M.D., London. 220 pages. Cloth, $1.50. " We recommend it cordially to the attention of all practitioners ; both to them and to their patients it may be of the greatest service." — New York Medical Journal. HAYNES' ANATOMY. A Manual of Anatomy. By Irving S. Haynes, M.D., Adjunct Professor of Anatomy and Demonstrator of Anatomy, Medical Depart- ment of the New York University, etc. 680 pages, illustrated with 42 diagrams in the text, and 134 full-page half-tone illustrations from original photographs of the author's dissections. Cloth, $2.50 net. " This book is the work of a practical instructor — one who knows by experience the requirements of the average student, and is able to meet these requirements in a very satis- factory way. The book is one that can be commended." — Medical Record, New York. HEISLER'S EMBRYOLOGY. A Text=Book of Embryology. By John C. Heisler, M.D., Pro- fessor of Anatomy in the Medico- Chirurgical College, Philadelphia. Oc- tavo volume of 405 pages, handsomely illustrated. Cloth, $2.50 net. HIRST'S OBSTETRICS. A Text=Book of Obstetrics. By Barton Cooke Hirst, M. D., Professor of Obstetrics in the University of Pennsylvania. Handsome octavo volume of 848 pages, with 618 illustrations, and 7 colored plates. Cloth, $5.00 net; Sheep or Half Morocco, $6.00 net. "The illustrations are numerous and are works of art, many of them appearing for the first time. The arrangement of the subject-matter, the foot-notes, and index are beyond criticism. As a true model of what a modern text-book on obstetrics should be, we feel justified in affirming that Dr. Hirst's book is without a rival." — New York Medical Record. HYDE AND MONTGOMERY ON SYPHILIS AND THE VENEREAL DISEASES. Syphilis and the Venereal Diseases. By James Nevins Hyde, M.D., Professor of Skin and Venereal Diseases, and Frank H. Mont- gomery, M.D., Lecturer on Dermatology and Genito-Urinary Diseases in Rush Medical College, Chicago, 111. 618 pages, profusely illustrated. Cloth, $2.50 net. " We can commend this manual to the student as a help to him in his study of venereal diseases. ' ' — Liverpool Medico- Chirurgical Journal. "The best student's manual which has appeared on the subject." — St. Louis Medical and Surgical Journal. 14 Medical Publications of W. B. Saunders. JACKSON AND GLEASON'S DISEASES OF THE EYE, NOSE, AND THROAT. Second Edition, Revised. Essentials of Refraction and Diseases of the Eye. By Edward Jackson, A.M., M.D., Professor of Diseases of the Eye in the Phila- delphia Polyclinic and College for Graduates in Medicine ; and — Essentials of Diseases of the Nose and Throat. By E. Bald- win Gleason, M.D., Surgeon-in-Charge of the Nose, Throat, and Ear Department of the Northern Dispensary of Philadelphia. Two volumes in one. Crown octavo, 290 pages; 124 illustrations. Cloth, $1.00; interleaved for notes, $1.25. [See Saunders'' Question- Compends, page 21.] " Of great value to the beginner in these branches. The authors are both capable men, and know what a student most needs." — Medical Record, New York. KEATING'S DICTIONARY. Second Edition, Revised. A New Pronouncing Dictionary of Medicine, with Phonetic Pronunciation, Accentuation, Etymology, etc. By John M. Keating, M.D., LL.D., Fellow of the College of Physicians of Phila- delphia ; Vice-President of the American Pediatric Society ; Editor "Cyclopaedia of the Diseases of Children," etc.; and Henry Hamilton, Author of '-'A New Translation of Virgil's ^Eneid into English Rhyme," etc.; with the collaboration of J. Chalmers Da- Costa, M.D., and Frederick A. Packard, M.D. With an Appendix containing Tables of Bacilli, Micrococci, Leucoma'ines, Ptomaines; Drugs and Materials used in Antiseptic Surgery ; Poisons and their Antidotes ; Weights and Measures ; Thermometric Scales ; New Official and Unofficial Drugs, etc. One volume of over 800 pages. Prices, with Denison's Patent Ready-Reference Index: Cloth, $5.00 net; Sheep or Half Morocco, $6.00 net; Half Russia, $6.50 net. Without Patent Index: Cloth, $4.00 net; Sheep or Half Morocco, $5.00 net. " I am much pleased with Keating's Dictionary, and shall take pleasure in recommend- ing it to my classes." — Henry M. Lyman, M.D., Professor of the Principles and Practict of Medicine, Rush Medical College, Chicago, III. " I am convinced that it will be a very valuable adjunct to my study-table, convenient in size and sufficiently full for ordinary use." — C. A. LlNDSLEY, M.D., Professor of the Theory and Practice of Medicine, Medical Dept. Yale University. KEATING'S LIFE INSURANCE. How to Examine for Life Insurance. By John M. Keating, M. D., Fellow of the College of Physicians of Philadelphia; Vice- President of the American Pediatric Society; Ex- President of the Association of Life Insurance Medical Directors. Royal octavo, 211 pages ; with two large half-tone illustrations, and a plate prepared by Dr. McClellan from special dissections ; also, numerous other illustra- tions. Cloth, $2.00 net. " This is by far the most useful book which has yet appeared on insurance examination, a subject of growing interest and importance. Not the least valuable portion of the volume is Part II., which consists of instructions issued to their examining physicians by twenty-four representative companies of this country. If for these alone, the book should be at the right hand of every physician interested in this special branch of medical science." — The Medical News. Medical Publications of W. B. Saunders. 15 KEEN ON THE SURGERY OF TYPHOID FEVER. The Surgical Complications and Sequels of Typhoid Fever. By Wm. W. Keen, M.D., LL.D., Professor of the Principles of Sur- gery and of Clinical Surgery, Jefferson Medical College, Philadelphia; Corresponding Member of the Societe de Chirurgie, Paris; Honorary Member of the Societe Beige de Chirurgie, etc. Octavo volume of 3S6 pages, illustrated. Cloth, $3.00 net. " This is probably the first and only work in the English language that gives the reader a clear view of what typhoid fever really is, and what it does and can do to the human organism. This book should be in the possession of every medical man in America." — icon Medico-Surgical Bulletin. KEEN'S OPERATION BLANK. Second Edition, Revised Form. An Operation Blank, with Lists of Instruments, etc. Required in Various Operations. Prepared by W. W. Keen, M.D., LL.D., Professor of the Principles of Surgery in Jefferson Medical College, Philadelphia. Price per pad, containing blanks for fifty operations, 50 cents net. KYLE ON THE NOSE AND THROAT. Diseases of the Nose and Throat. By D. Braden Kyle, M.D., Clinical Professor of Laryngology and Rhinology, Jefferson Medical College, Philadelphia ; Consulting Laryngologist, Rhinologist, and Otologist, St. Agnes' Hospital. Handsome octavo volume of about 630 pages, with over 150 illustrations and 6 lithographic plates. Price, Cloth, $4.00 net; Half Morocco, $5.00 net. LAINE'S TEMPERATURE CHART. Temperature Chart. Prepared by D. T. Laine, M.D. Size 8 x 13^ inches. A conveniently arranged Chart for recording Temperature, with columns for daily amounts of Urinary and Fecal Excretions, Food, Remarks, etc. On the back of each chart is given in full the method of Brand in the treatment of Typhoid Fever. Price, per pad of 25 charts, 50 cents net. " To the busy practitioner this chart will be found of great value in fever cases, and especially for cases of typhoid." — Indian Lancet, Calcutta. LOCKWOOD'S PRACTICE OF MEDICINE. A Manual of the Practice of Medicine. By George Roe Lock- wood, M.D., Professor of Practice in the Woman's Medical College of the New York Infirmary, etc. 935 pages, with 75 illustrations in the text, and 22 full-page plates. Cloth, $2.50 net. " Gives in a most concise manner the points essential to treatment usually enumerated in the most elaborate works." — Massachusetts Medical Journal. LONGS SYLLABUS OF GYNECOLOGY. A Syllabus of Gynecology, arranged in Conformity with " An American Text=Book of Gynecology." By J. W. Long, M.D., Professor of Diseases of Women and Children, Medical College of Virginia, etc. Cloth, interleaved, $1.00 net. " The book is certainly an admirable resume of what every gynecological student and practitioner should know, and will prove of value not only to those who have the ' American Text-Book of Gynecology,' but to others as well." — Brooklyn Medical Journal. 16 Medical Publications of W. B. Saunders. MACDONALD'S SURGICAL DIAGNOSIS AND TREATMENT. Surgical Diagnosis and Treatment. By J. W. Macdonald, M.D. Edin., F.R. C.S., Edin., Professor of the Practice of Surgery and of Clinical Surgery in Hamline University ; Visiting Surgeon to St. Barnabas' Hospital, Minneapolis, etc. Handsome octavo volume of 800 pages, profusely illustrated. Cloth, $5.00 net; Half Morocco, $6.00 net. " A thorough and complete work on surgical diagnosis and treatment, free from pad- ding, full of valuable material, and in accord with the surgical teaching of the day." — The Medical News, New York. "The work is brimful of just the kind of practical information that is useful alike to students and practitioners. It is a pleasure to commend the bock because of its intrinsic valuo to the medical practitioner." — Cincinnati Lancet- Clinic , MALLORY AND WRIGHTS PATHOLOGICAL TECHNIQUE. Pathological Technique. A Practical Manual for Laboratory Work in Pathology, Bacteriology, and Morbid Anatomy, with chapters on Post-Mortem Technique and the Performance of Autopsies. By Frank B. Mallory, A.M., M.D., Assistant Professor of Pathology, Harvarn University Medical School, Boston; and James H. Wright, A.M., M.D., Instructor in Pathology, Harvard University Medical School, Boston. Octavo volume of 396 pages, handsomely illustrated. Cloth, $2.50 net. " I have been looking forward to the publication of this book, and I am glad to say that I find it to be a most useful laboratory and post-mortem guide, full of practical information, and well up to date." — Willi AM H. WELCH, Professor of Pathology, Johns Hopkins Uni- versity, Baltimore, Md. MARTIN'S MINOR SURGERY, BANDAGING, AND VENEREAL DISEASES. Second Edition, Revised. Essentials of Minor Surgery, Bandaging, and Venereal Diseases. By Edward Martin, A.M., M.D., Clinical Professor of Genito-Urinary Diseases, University of Pennsylvania, etc. Crown octavo, 166 pages, with 78 illustrations. Cloth, $1.00; interleaved for notes, $1.25. [See Saunders' Question- Compends, page 21.] "A very practical and systematic study of the subjects, and shows the author's famil- iarity with the needs of students." — Therapeutic Gazette. MARTIN'S SURGERY. Sixth Edition, Revised. Essentials of Surgery. Containing also Venereal Diseases, Surgi- cal Landmarks, Minor and Operative Surgery, and a complete de- scription, with illustrations, of the Handkerchief and Roller Bandages. By Edward Martin, A.M., M.D., Clinical Professor of Genito- Urinary Diseases, University of Pennsylvania, etc. Crown octavo, 338 pages, illustrated. With an Appendix containing full directions for the preparation of the materials used in Antiseptic Surgery, etc. Cloth, $1.00;' interleaved for notes, $1.25. [See Saunders'' Question- Co?npends , page 21.] " Contains all necessary essentials of modern surgery in a comparatively small space. Its style is interesting, and its illustrations are admirable." — Medical and Surgical Reporter* Medical Publications of W. B. Saunders. 17 McFARLAND'S PATHOGENIC BACTERIA. Second Edition, Re- vised and Greatly Enlarged. Text=Book upon the Pathogenic Bacteria. By Joseph McFar- land, M. D., Professor of Pathology and Bacteriology in the Medico- Chirurgical College of Philadelphia, etc. Octavo volume of 497 pages, finely illustrated. Cloth, $2.50 net. " Dr. McFarland has treated the subject in a systematic manner, and has succeeded in presenting in a concise and readable form the essentials of bacteriology up to date. Alto- gether, the book is a satisfactory one, and I shall- take pleasure in recommending it to the students of Trinity College." — H. B. Anderson, M.D. , Professor of Pathology and Bac- teriology, Trinity Medical College, Toronto. MEIGS ON FEEDING IN INFANCY. Feeding in Early Infancy. By Arthur V. Meigs, M.D. Bound in limp cloth, flush edges, 25 cents net. "This pamphlet is worth many times over its price to the physician. The author's experiments and conclusions are original, and have been the means of doing much good."— Medical Bulletin. MOORE'S ORTHOPEDIC SURGERY. A Manual of Orthopedic Surgery. By James E. Moore, M.D., Professor of Orthopedics and Adjunct Professor of Clinical Surgery, University of Minnesota, College of Medicine and Surgery. Octavo volume of 356 pages, handsomely illustrated. Cloth, $2.50 net. "A most attractive work. The illustrations and the care with which the book is adapted to the wants of the general practitioner and the student are worthy of great praise." — Chicago Medical Recorder. " A very demonstrative work, every illustration of which conveys a lesson. The work is a most excellent and commendable one, which we can certainly endorse with pleasure." — St. Louis Medical and Surgical Journal. MORRIS'S MATERIA MEDICA AND THERAPEUTICS. Fifth Edition, Revised. Essentials of Materia Medica, Therapeutics, and Prescription" Writing. By Henry Morris, M.D., late Demonstrator of Thera- peutics, Jefferson Medical College, Philadelphia; Fellow of the College of Physicians, Philadelphia, etc. Crown octavo, 288 pages. Cloth, #1.00; interleaved for notes, $1.25. [See Saunders'' Question- Compends, page 21.] " This work, already excellent in the old edition, has been largely improved by revi- sion. " — American Practitioner and News. MORRIS, WOLFF, AND POWELL'S PRACTICE OF MEDICINE. Third Edition, Revised. Essentials of the Practice of Medicine. By Henry Morris, M.D., late Demonstrator of Therapeutics, Jefferson Medical College, Phila- delphia ; with an Appendix on the Clinical and Microscopic Examina- tion of Urine, by Lawrence Wolff, M.D., Demonstrator of Chemistry, Jefferson Medical College, Philadelphia. Enlarged by some 300 essen- tial formulae collected and arranged by William M. Powell, M.D. Post-octavo, 488 pages. Cloth, $2.00. [See Saunders' Question- Compends, page 21.] " The teaching is sound, the presentation graphic ; matter full as can be desired, and style attractive." — American Practitioner and News. 2 18 Medical Publications of W. B. Saunders. MORTEN'S NURSES DICTIONARY. Nurse's Dictionary of Medical Terms and Nursing Treat- ment. Containing Definitions of the Principal Medical and Nursing Terms and Abbreviations ; of the Instruments, Drugs, Diseases, Acci- dents, Treatments, Operations, Foods, Appliances, etc. encountered in the ward or in the sick-room. By Honnor Morten, author of "How to Become a Nurse," etc. i6mo, 140 pages. Cloth, $1.00. " A handy, compact little volume, containing a large amount of general information, all of which is arranged in dictionary or encyclopedic form, thus facilitating quick reference. It is certainly of value to those for whose use it is published." — Chicago Clinical Review. NANCREDE'S ANATOMY. Sixth Edition, Thoroughly Revised. Essentials of Anatomy, including the Anatomy of the Viscera. By Charles B. Nancrede, M.D., LL.D., Professor of Surgery and of Clinical Surgery in the University of Michigan, Ann Arbor. Crown octavo, 420 pages; 151 illustrations. Based upon Gray's Anatomy. Cloth, $1.00 net; interleaved for notes, $1.25 net. [See Saunders'' Question- Compends, page 21.] "For self-quizzing and keeping fresh in mind the knowledge of anatomy gained at school, it would not be easy to speak of it in terms too favorable."— A merican Practitioner. NANCREDE'S ANATOMY AND DISSECTION. Fourth Edition. Essentials of Anatomy and Manual of Practical Dissection. By Charles B. Nancrede, M.D., LL.D., Professor of Surgery and of Clinical Surgery, University of Michigan, Ann Arbor. Post-octavo ; 500 pages, with full-page lithographic plates in colors, and nearly 200 illustrations. Extra Cloth (or Oilcloth for dissection-room), $2.00 net. " It may in many respects be considered an epitome of Gray's popular work on general anatomy, at the same time having some distinguishing characteristics of its own to commend it. The plates are of more than ordinary excellence, and are of especial value to students in their work in the dissecting room." — Journal of the American Medical Association. NORRIS'S SYLLABUS OF OBSTETRICS. Third Edition, Revised. Syllabus of Obstetrical Lectures in the Medical Department of the University of Pennsylvania. By Richard C. Norris, A.M., M.D., Demonstrator of Obstetrics, University of Pennsylvania. Crown octavo, 222 pages. Cloth, interleaved for notes, $2.00 net. " This work is so far superior to others on the same subject that we take pleasure in calling attention briefly to its excellent features. It covers the subject thoroughly, and will prove invaluable both to the student and the practitioner." — Medical Record, New York. PENROSE'S DISEASES OF WOMEN. Second Edition, Revised. A Text=Book of Diseases of Women. By Charles B. Penrose, M.D., Ph.D., Professor of Gynecology in the University of Pennsyl- vania ; Surgeon to the Gynecean Hospital, Philadelphia. Octavo volume of 529 pages, handsomely illustrated. Cloth, $3.50 net. " I shall value very highly the copy of Penrose's 'Diseases of Women' received. I have already recommended it to my class as THE BEST book." — Howard A. Kelly, Professor of Gynecology and Obstetrics, Johns Hopkins University , Baltimore, Md. " The book is to be commended without reserve, not only to the student but to the general practitioner who wishes to have the latest and best modes of treatment explained with absolute clearness." — Therapeutic Gazette. Medical Publications of W. B. Saunders. 19 POWELL'S DISEASES OF CHILDREN. Second Edition. Essentials of Diseases of Children. By William M. Powell, M.D., Attending Physician to the Mercer House for Invalid Women at Atlantic City, N. J. ; late Physician to the Clinic for the Diseases of Children in the Hospital of the University of Pennsylvania. Crown octavo, 222 pages. Cloth, 51.00; interleaved for notes, $1.25. [See Saunders'' Questio?i-Compends, page 21.] "Contains the gist of all the best works in the department to which it relates."— American Practitioner ami News. PRINGLE'S SKIN DISEASES AND SYPHILITIC AFFECTIONS. Pictorial Atlas of Skin Diseases and Syphilitic Affections (American Edition). Translation from the French. Edited by J. J. Pringle, M.B,, F.R.C.P., Assistant Physician to the Middlesex Hospital, London. Photo-lithochromes from the famous models in the Museum of the Saint-Louis Hospital, Paris, with explanatory wood- cuts and text. In 12 Parts. Price per Part, $3.00. Complete in one volume, Half Morocco binding, $40.00 net. " I strongly recommend this Atlas. The plates are exceedingly well executed, and will be of great value to all studying dermatology." — Stephen Mackenzie, M.D. " The introduction of explanatory wood-cuts in the text is a novel and most important feature which greatly furthers the easier understanding of the excellent plates, than which nothing, we venture to say, has been seen better in point of correctness, beauty, and general merit." — New York Medical Journal. PRYOR— PELVIC INFLAMMATIONS. The Treatment of Pelvic Inflammations through the Vagina. By W. R. Pryor, M.D., s Professor of Gynecology in New York Poly- clinic, nmo, 248 pages, handsomely illustrated. Cloth, $2.00 net. " This subject, which has recently been so thoroughly canvassed in high gynecological circles, is made available in this volume to the general practitioner and student. Nothing is too minute for mention and nothing is taken for granted ; consequently the book is of the utmost value. The illustrations and the technique are beyond criticism." — Chicago Medical Recorder. PYE'S BANDAGING. Elementary Bandaging and Surgical Dressing. With Direc- tions concerning the Immediate Treatment of Cases of Emergency. For the use of Dressers and Nurses. By Walter Pye, F.R.C.S., late Surgeon to St. Mary's Hospital, London. Small i2mo, with over 80 illustrations. Cloth, flexible covers, 75 cents net. "The directions are clear and the illustrations are good." — London Lancet. "The author writes well, the diagrams are clear, and the book itself is small and port- able, although the paper and type are good." — British Medical Journal. RAYMOND'S PHYSIOLOGY. A Manual of Physiolugy. By Joseph H. Raymond, A.M., M.D., Professor of Physiology and Hygiene and Lecturer on Gynecology in the Long Island College Hospital; Director of Physiology in the Hoagland Laboratory, etc. 382 pages, with 102 illustrations in the text, and 4 full-page colored plates. Cloth, $1.25 net. " Extremely well gotten up, and the illustrations have been selected with care. The text is fully abreast with modern physiology. "—British Medical Journal. Saunders* Q Arranged in Question and Answer Form. \JI2iO 1 LkJ±\ qpHE MOST COMPLETE AND BEST ^OI^TTPThNTT^C illustrated series of V^vJlVJJrlllN DO COMPENDS EVER ISSUED. Now the Standard Authorities in Medical Literature with Students and Practitioners in every City of the United States and Canada* ^ OVER 175,000 COPIES SOLD* ^ THE REASON WHY* They are the advance guard of "Student's Helps" — that do help. They are the leaders in their special line, well and authoritatively written by able men, who, as teachers in the large colleges, know exactly what is wanted by a student preparing for his examinations. The judgment exercised in the selection of authors is fully demonstrated by their professional standing. Chosen from the ranks of Demonstrators, Quiz-masters, and Assistants, most of them have become Professors and Lecturers in their respective colleges. Each book is of convenient size (5x7 inches) , containing on an average 250 pages, profusely illustrated, and elegantly printed in clear, readable type, on fine paper. The entire series, numbering twenty-three volumes, has been kept thoroughly revised and enlarged when necessary, many of the books being in their fifth and sixth editions. TO SUM UP* Although there are numerous other Quizzes, Manuals, Aids, etc. in the market, none of them approach the "Blue Series of Question Compends;" and the claim is made for the following points of excellence : 1. Professional distinction and reputation of authors. 2. Conciseness, clearness, and soundness of treatment. 3. Quality of illustrations, paper, printing, and binding. Any cf these Compends will be mailed on receipt of price (see next page for List). Oaunders' Question-Compend Series, Price, Cloth, $1.00 per copy, except when otherwise noted. "Where the work of preparing students' manuals is to end we cannot say, but the Saunders Series, in our opinion, bears off the palm at present."— New York Medical Record. 1. ESSENTIALS OF PHYSIOLOGY. By H. A. Hare, M.D. Fourth edition, revised and enlarged. ($1.00 net.) 2. ESSENTIALS OF SURGERY. By Edward Martin, M.D. Sixth edition, revised, with an Appendix on Antiseptic Surgery. 3. ESSENTIALS OF ANATOMY. By Chari.es B. Nancrede, M.D. Sixth edition, thoroughly revised and enlarged. ($i.oo net.) 4. ESSENTIALS OF MEDICAL CHEMISTRY, ORGANIC AND INORGANIC. By Lawrence Wolff, M.D. Fifth edition, revised. ($i.oo net.) 5. ESSENTIALS OF OBSTETRICS. By W. Easterly Ashton, M.D. Fourth edition, revised and enlarged. 6. ESSENTIALS OF PATHOLOGY AND MORBID ANATOMY. By C. E. Armand Semple, M.D. 7. ESSENTIALS OF MATERIA MEDICA, THERAPEUTICS, AND PRE- SCRIPTION=WRITING. By Henry Morris, M.D. Fifth edition, revised. 8. 9. ESSENTIALS OF PRACTICE OF MEDICINE. By Henry Morris, M.D. An Appendix on Urine Examination. By Lawrence Wolff, M.D. Third edition, enlarged by some 300 Essential Formulae, selected from eminent authorities, by Wm. M. Powell, M.D. (Double number, $2.00.) 10. ESSENTIALS OF GYNAECOLOGY. By Edwin B. Cragin, M.D. Fourth edition, revised. 11. ESSENTIALS OF DISEASES OF THE SKIN. By Henry W. Stelwagon, M.D. Fourth edition, revised and enlarged. ($1.00 net.) 12. ESSENTIALS OF MINOR SURGERY, BANDAGiNG, AND VENEREAL DISEASES. By Edward Martin, M.D. Second ed., revised and enlarged. 13. ESSENTIALS OF LEGAL MEDICINE, TOXICOLOGY, AND HYGIENE. By C. E. Armand Semple, M.D. 14. ESSENTIALS OF DISEASES OF THE EYE, NOSE, AND THROAT. By Edward Jackson, M.D., and E. B. Gleason, M.D. Second ed., revised. 15. ESSENTIALS OF DISEASES OF CHILDREN. By William M. Powell, M.D. Second edition. 16. ESSENTIALS OF EXAMINATION OF URINE. By Lawrence Wolff, M.D. Colored "Vogel Scale." (75 cents.) 17. ESSENTIALS OF DIAGNOSIS. By S. Solis Cohen, M.D., and A. A. Eshner, M.D. ($1.50 net.) 18. ESSENTIALS OF PRACTICE OF PHARMACY. By Lucius E. Sayre. Second edition, revised and enlarged. 20. ESSENTIALS OF BACTERIOLOGY. By M. V. Ball, M.D. Third edition, revised. 21. ESSENTIALS OF NERVOUS DISEASES AND INSANITY. By John C. Shaw, M.D. Third edition, revised. 22. ESSENTIALS OF MEDICAL PHYSICS. By Fred J. Brockway, M.D. Second edition, revised. ($1.00 net.) 23. ESSENTIALS OF MEDICAL ELECTRICITY. By David D. Stewart, M.D., and Edward S. Lawrance, M.D. 24. ESSENTIALS OF DISEASES OF THE EAR. By E. B. Gleason, M.D. Second edition, revised and greatly enlarged. Pamphlet containing specimen pages, etc. sent free upon application. Saunders' , e , tor Students New Series and of Manua |« Practitioners, ^T'HAT there exists a need for thoroughly reliable hand-books on the leading branches of Medicine and Surgery is a fact amply demonstrated by the favor with which the SAUNDERS NEW SERIES OF MANUALS have been received by medical students and practitioners and by the Medical Press, These manuals are not merely condensations from present literature, but are ably written by well-known authors and practitioners, most of them being teachers in representative American colleges. Each volume is concisely and authoritatively written and exhaustive in detail, without being encumbered with the introduction of "cases," which so largely expand the ordinary text-book. These manuals will therefore form an admirable collection of advanced lectures, useful alike to the medical student and the practitioner: to the latter, too busy to search through page after page of elaborate treatises for what he wants to know, they will prove of inestimable value ; to the former they will afford safe guides to the essential points of study. The SAUNDERS NEW SERIES OF MANUALS are conceded to be superior to any similar books now on the market. No other manuals afford so much infor- mation in such a concise and available form. A liberal expenditure has enabled the publisher to render the mechanical portion of the work worthy of the high literary standard attained by these books. Any of these Manuals will be mailed on receipt of price (see next page for List). Saunders' New Series of Manuals* VOLUMES PUBLISHED. PHYSIOLOGY. By JOSEPH Howard Raymond, A.M., M.D., Professor of Physiology and Hygiene and Lecturer on Gynecology in the Long Island College Hospital; Director of Physiology in the Hoagland Laboratory, etc. Illustrated. Cloth, $1.25 net. SURGERY, General and Operative. Py John Chalmers DaCosta, M.D., Clini- cal Professor of Surgery, Jefferson Medical College, Philadelphia; Surgeon to the Philadelphia Hospital, etc. Second edition, thoroughly revised and greatly enlarged. Octavo, 911 pages, profusely illustrated. Cloth, $4.00 net ; Half Morocco, $5.00 net. DOSE=BOOK AND MANUAL OF PRESCRIPTION=WRITING. By E Q. Thornton, M.D., Demonstrator of Therapeutics, Jefferson Medical College, Phila- delphia. Illustrated. Cloth, Si. 25 net. SURGICAL ASEPSIS. By Carl Beck, M.D., Surgeon to St. Mark's Hospital and to the New York German Poliklinik, etc. Illustrated. Cloth, $1.25 net. MEDICAL JURISPRUDENCE. By Henry C. Chapman, M.D. Professor of Insti- tutes of Medicine and Medical Jurisprudence in the Jefferson Medical College of Phila- delphia. Illustrated. Cloth, Si. 50 net. SYPHILIS AND THE VENEREAL DISEASES. By James Nevins Hyde, M.D., Professor of Skin and Venereal Diseases, and Frank H. Montgomery, M.D., Lecturer on Dermatology and Genito-Urinary Diseases in Rush Medical College, Chicago. Profusely illustrated. Cloth, $2.50 net. PRACTICE OF MEDICINE. By George Roe Lockwood, M.D., Professor of Practice in the Woman's Medical College of the New York Infirmary ; Instructor in Physical Diagnosis in the Medical Department of Columbia College, etc. Illustrated. Cloth, $2.50 net. MANUAL OF ANATOMY. By Irving S. Haynes, M.D., Adjunct Professor of Anatomy and Demonstrator of Anatomy, Medical Department of the New York University, etc. Beautifully illustrated. Cloth, $2.50 net. MANUAL OF OBSTETRICS. By W. A. Newman Dorland, M.D., Assistant Demonstrator of Obstetrics, University of Pennsylvania ; Chief of Gynecological Dis- pensary, Pennsylvania Hospital, etc. Profusely illustrated. Cloth, $2.50 net. DISEASES OF WOMEN. By J. Bland Sutton, F. R. C. S., Assistant Surgeon to Middlesex Hospital and Surgeon to Chelsea Hospital, London; and Arthur E. Giles, M. D., B. Sc. Lond., F.R.C.S. Edin., Assistant Surgeon to Chelsea Hospital, London. Handsomely illustrated. Cloth, £2.50 net. VOLUMES IN PREPARATION. NERVOUS DISEASES. By Charles W. Burr, M.D., Clinical Professor of Nervous Diseases, Medico-Chirurgical College, Philadelphia ; Pathologist to the Orthopaedic Hospital and Infirmary for Nervous Diseases ; Visiting Physician to the St. Joseph Hospital, etc. *** There will be published in the same series, at short intervals, carefully-prepared works on various subjects by prominent specialists. Pamphlet containing specimen pages, etc. sent free upon application. 24 Medical Publications of W. B. Saunders. SAUNDBY'S RENAL AND URINARY DISEASES. Lectures on Renal and Urinary Diseases. By Robert Saundby, M.D. Edin., Fellow of the Royal College of Physicians, London, and of the Royal Medico-Chirurgical Society ; Physician to the General Hospital ; Consulting Physician to the Eye Hospitai and to the Hos- pital for Diseases of Women; Professor of Medicine in Mason College, Birmingham, etc. Octavo volume of 434 pages, with numerous illus- trations and 4 colored plates. Cloth, $2.50 net. " The volume makes a favorable impression at once. The style is clear and succinct. We cannot find any part of the subject in which the views expressed are not carefully thought out and fortified by evidence drawn from the most recent sources. The book may be cordially recommended." — British Medical Journal. 5AUNDERS' MEDICAL HAND=ATLA5E5. This series of books consists of authorized translations into English of the world-famous Lehmann Medicinische Handatlanten. Each volume contains from 50 to 100 colored lithographic plates, besides numerous illustrations in the text. There is a full description of each- plate, and each book contains a condensed but adequate outline of the subject to which it is devoted. For full description of this series, with list of volumes and prices, see page 2. " Lehmann Medicinische Handatlanten belong to that class of books that are too good to be appropriated by any one nation." — "Journal of Eye, Ear, and Throat Diseases. " The appearance of these works marks a new era in illustrated English medical works." — The Canadian Practitioner. SAUNDERS' POCKET MEDICAL FORMULARY. Fifth Edition, Revised. By William M. Powell, M.D., Attending Physician to the Mercer House for Invalid Women at Atlantic City, N. J. Containing 1800 formulae selected from the best-known authorities. With an Appen- dix containing Posological Table, Formulae and Doses for Hypo- dermic Medication, Poisons and their Antidotes, Diameters of the Female Pelvis and Fcetal Head, Obstetrical Table, Diet List for Various Diseases, Materials and Drugs used in Antiseptic Surgery, Treatment of Asphyxia from Drowning, Surgical Remembrancer, Tables of Incompatibles, Eruptive Fevers, Weights and Measures, etc. Hand- somely bound in flexible morocco, with side index, wallet, and flap, I1.75 net. "This little book, that can be conveniently carried in the pocket, contains an immense amount of material. It is very useful, and, as the name of the author of each prescription is given, is unusually reliable." — Medical Record, New York. SAYRE'S PHARMACY. Second Edition, Revised. Essentials of the Practice of Pharmacy. By Lucius E. Sayre, M.D., Professor of Pharmacy and Materia Medica in the University of Kansas. Crown octavo, 200 pages. Cloth, $1.00; interleaved for notes, $1.25. [See Saunders'' Question- Compends, page 21.] " The topics are treated in a simple, practical manner, and the work forms a very useful student's manual." — Boston Medical and Surgical Journal. Medical Publications of W. B. Saunders. 25 SEMPLE'S LEGAL MEDICINE, TOXICOLOGY, AND HYGIENE. Essentials of Legal Medicine, Toxicology, and Hygiene. By C. E. Armand Semple, B. A., M. B. Cantab., M. R. C. P. Lond., Physician to the Northeastern Hospital for Children, Hackney, etc. Crown octavo, 212 pages; 130 illustrations. Cloth, $1. 00; interleaved for notes, ^1.25. [See Saunders Question- Co?npends, page 21.] " No general practitioner or student can afford to be without this valuable work. The subjects are dealt with by a masterly hand." — London Hospital Gazette. SEMPLE'S PATHOLOGY AND MORBID ANATOMY. Essentials of Pathology and Morbid Anatomy. By C. E. Armand Semple, B.A., M.B. Cantab., M.R.C.P. Lond., Physician to the Northeastern Hospital for Children, Hackney, etc. Crown octavo, 174 pages; illustrated. Cloth, $1.00; interleaved for notes, $1.25. [See Saunders' Question- Conipends, page 21.] " Should take its place among the standard volumes on the bookshelf of both student and practitioner." — London Hospital Gazette. SENN'S GENITOURINARY TUBERCULOSIS. Tuberculosis of the Genito=Urinary Organs, Male and Female. By Nicholas Senn, M.D., Ph.D., LL.D., Professor of the Practice of Surgery and of Clinical Surgery, Rush Medical College, Chicago. Handsome octavo volume of 320 pages, illustrated. Cloth, $3.00 net. " An important book upon an important subject, and written by a man of mature judg- ment and wide experience. The author has given us an instructive book upon one of the most important subjects of the day." — Clinical Reporter. " A work which adds another to the many obligations the profession owes the talented author." — Chicago Medical Recorder. SENN'S SYLLABUS OF SURGERY. A Syllabus of Lectures on the Practice of Surgery, arranged in conformity with " An American Text=Book of Surgery. " By Nicholas Senn, M.D., Ph.D., Professor of the Practice of Surgery and of Clinical Surgery in Rush Medical College, Chicago. Cloth, $2.00. " This syllabus will be found of service by the teacher as well as the student, the work being superbly done. There is no praise too high for it. No surgeon should be without it." — New York Medical Times. SENN'S TUMORS. Pathology and Surgical Treatment of Tumors. By N. Senn, M.D., Ph.D., LL.D., Professor of Surgery and of Clinical Surgery, Rush Medical College ; Professor of Surgery, Chicago Polyclinic ; Attending Surgeon to Presbyterian Hospital ; Surgeon-in-Chief, St. Joseph's Hospital, Chicago. Octavo volume of 710 pages, with 515 engravings, including full-page colored plates. New and Revised Edi- tion in Preparation. " The most exhaustive of any recent book in English on this subject. It is well illus- trated, and will doubtless remain as the principal monograph on the subject in our language for some years. The book is handsomely illustrated and printed, and the author has given a notable and lasting contribution to surgery." — Journal of the American Medical Association. 26 Medical Publications of W. B. Saunders. SHAW'S NERVOUS DISEASES AND INSANITY. Third Edition, Revised. Essentials of Nervous Diseases and Insanity. By John C. Shaw, M.D., Clinical Professor of Diseases of the Mind and Nervous System, Long Island College Hospital Medical School ; Consulting Neurologist to St. Catherine's Hospital and to the Long Island College Hospital. Crown octavo, 186 pages; 48 original illustrations. Cloth, #1.00 ; interleaved for notes, $1.25. [See Saunders' Question- Compends, page 21.] "Clearly and intelligently written. ; ' — Boston Medical and Surgical Journal. "There. is a mass of valuable material crowded into this small compass." — American Medico- Surgical Bulletin. STARR'S DIETS FOR INFANTS AND CHILDREN. Diets for Infants and Children in Health and in Disease. By Louis Starr, M.D., Editor of "An American Text-Book of the Diseases of Children." 230 blanks (pocket-book size), perforated and neatly bound in flexible morocco. $1.25 net. The first series of blanks are prepared for the first seven months of infant life ; each blank indicates the ingredients, but not the quantities, of the food, the latter directions being left for the physician. After the seventh month, modifications being less necessary, the diet lists are printed in full. Formulae for the preparation of diluents and foods are appended. STELW AGON'S DISEASES OF THE SKIN. Fourth Ed., Revised. Essentials of Diseases of the Skin. By Henry W. Stelwagon, M.D., Clinical Professor of Dermatology in the Jefferson Medical College, Philadelphia ; Dermatologist to the Philadelphia Hospital ; Physician to the Skin Department of the Howard Hospital, etc. Crown octavo, 276 pages; 88 illustrations. Cloth, $1. 00 net; inter- leaved for notes, $1.25 net. [See Saunders'' Question- Compends, page 21.] " The best student's manual on skin diseases we have yet seen." — Times and Register. STENGEL'S PATHOLOGY. Second Edition. A Text=Book of Pathology. By Alfred Stengel, M.D., Professor of Clinical Medicine in the University of Pennsylvania ; Physician to the Philadelphia Hospital ; Physician to the Children's Hospital, etc. Handsome octavo volume of 848 pages, with nearly 400 illustrations, many of them in colors. Cloth, $4.00 net; Half Morocco, $5.00 net. STEVENS' MATERIA MEDICA AND THERAPEUTICS. Second Edition, Revised. A Manual of Materia Medica and Therapeutics. By A. A. Stevens, A.M., M.D., Lecturer on Terminology and Instructor in Physical Diagnosis in the University of Pennsylvania; Professor of Pathology in the Woman's Medical College of Pennsylvania. Post- octavo, 445 pages. Flexible leather, $2.25. "The author has faithfully presented modern therapeutics in a comprehensive work, and, while intended particularly for the use of students, it will be found a reliable guide and sufficiently comprehensive for the physician in practice." — University Medical Magazine. Medical Publications of W. B. Saunders. 27 STEVENS' PRACTICE OF MEDICINE. Fifth Edition, Revised. A Manual of the Practice of Medicine. By A. A. Stevens, A. M., M. D., Lecturer on Terminology and Instructor in Physical Diagnosis in the University of Pennsylvania; Professor of Pathology in the Woman's Medical College of Pennsylvania. Specially intended for students preparing for graduation and hospital examinations. Post- octavo, 519 pages; illustrated. Flexible leather, $2.00 net. " The frequency with which new editions of this manual are demanded bespeaks its popularity. It is an excellent condensation of the essentials of medical practice for the student, and maybe found also an excellent reminder for the busy physician." — Buffalo Medical Journal '. STEWART'S PHYSIOLOGY. Third Edition, Revised. A Manual of Physiology, with Practical Exercises. For Students and Practitioners. By G. N. Stewart, M.A., M.D., D.Sc, lately Examiner in Physiology, University of Aberdeen, and of the New Museums, Cambridge University ; Professor of Physiology in the Western Reserve University, Cleveland, Ohio. Octavo volume of 848 pages ; 300 illustrations in the text, and 5 colored plates. Cloth, $3.75 net. " It will make its way by sheer force of merit, and amply deserves to do so. It is one of the very best English tekt-books on the subject." — London Lancet. "Of the many text-books of physiology published, we do not know of one that so nearly comes up to the ideal as does Prof. Stewart's volume."- — British Medical Journal. STEWART AND LAWRANCE'S MEDICAL ELECTRICITY. Essentials of Medical Electricity. By D. D. Stewart, M.D., Demonstrator of Diseases of the Nervous System and Chief of the Neurological Clinic in the Jefferson Medical College; and E. S. Lawrance, M.D., Chief of the Electrical Clinic and Assistant Demon- strator of Diseases of the Nervous System in the Jefferson Medical College, etc. Crown octavo, 158 pages; 65 illustrations. Cloth, $1.00; interleaved for notes, $1.25. [See Saunders' Question- Comp ends, page 21.] " Throughout the whole brief space at their command the authors show a discriminating knowledge of their subject." — Medical News. STONEY'S NURSING. Second Edition, Revised. Practical Points in Nursing. For Nurses in Private Practice, By Emily A. M. Stoney, Graduate of the Training-School for Nurses, Lawrence, Mass.; late Superintendent of the Training-School for Nurses, Carney Hospital, South Boston, Mass. 456 pages, illustrated with 73 engravings in the text, and 8 colored and half-tone plates. Cloth, $1.75 net. "There are few books intended for non-professional readers which can be so cordially endorsed by a medical journal as can this one." — Therapeutic Gazette. " This is a well-written, eminently practical volume, which covers the entire range of private nursing as distinguished from hospital nursing, and instructs the nurse how best to meet the various emergencies which may arise, and how to prepare everything ordinarily needed in the illness of her patient." — American Journal of Obstetrics and Diseases of Women and Children. " It is a work that the physician can place in the hands of his private nurses with the assurance of benefit." — Ohio Medical Journal. 28 Medical Publications of W. B. Saunders. STONEY'S MATERIA MEDICA FOR NURSES. Materia Medica for Nurses. By Emily A. M. Stoney, Graduate of the Training-School for Nurses, Lawrence, Mass. ; late Superintendent of the Training-School for Nurses, Carney Hospital, South Boston, Mass. Handsome octavo volume of 306 pages. Cloth, $1.50 net. The present book differs from other similar works in several features, all of which are intended to render it more practical and generally useful. The general plan of the contents follows the lines laid down in training-schools for nurses, but the book contains much use- ful matter not usually included in works of this character, such as Poison-emergencies, Ready Dose-list, Weights and Measures, etc., as well as a Glossary, defining all the terms used in Materia Medica, and describing all the latest drugs and remedies, which have been generally neglected by other books of the kind. SUTTON AND GILES' DISEASES OF WOMEN. Diseases of Women. By J. Bland Sutton, F.R.C.S., Assistant Surgeon to Middlesex Hospital, and Surgeon to Chelsea Hospital, London; and Arthur E. Giles, M.D., B.Sc. Lond. , F.R.C.S. Edin., Assistant Surgeon to Chelsea Hospital, London. 436 pages, hand- somely illustrated. Cloth, $2.50 net. "The text has been carefully prepared. Nothing essential has been omitted, and its teachings are those recommended by the leading authorities of the day." — Journal of the American Aledical Association. THOMAS'S DIET LISTS AND SICK=ROOM DIETARY. Diet Lists and Sick=Room Dietary. By Jerome B. Thomas, M.D., Visiting Physician to the Home for Friendless Women and Children and to the Newsboys' Home ; Assistant Visiting Physician to the Kings County Hospital. Cloth, $1.50. Send for sample sheet. THORNTON'S DOSE=BOOK AND PRESCRIPTION=WRITING. Dose=Book and Manual of Prescription=Writing. By E. Q. Thornton, M.D., Demonstrator of Therapeutics, Jefferson Medical College, Philadelphia. 334 pages, illustrated. Cloth, $1.25 net. "Full of practical suggestions; will take its place in the front rank of works of this sort." — Medical Record, New York. VAN VALZAH AND NISBET'S DISEASES OF THE STOMACH. Diseases of the Stomach. By William W. Van Valzah, M.D., Professor of General Medicine and Diseases of the Digestive System and the Blood, New York Polyclinic; and J. Douglas Nisbet, M.D., Adjunct Professor of General Medicine and Diseases of the Digestive System and the Blood, New York Polyclinic. Octavo volume of 674 pages, illustrated. Cloth, $3.50 net. " Its chief claim lies in its clearness and general adaptability to the practical needs of the general practitioner or student. In these relations it is probably the best of the recent special works on diseases of the stomach." — Chicago Clinical Review. VECKI'S SEXUAL IMPOTENCE. The Pathology and Treatment of Sexual Impotence. By Victor G. Vecki, M.D. From the second German edition, revised and en- larged. Demi-octavo, about 300 pages. Cloth, $2.00 net. The subject of impotence has seldom been treated in this country in the truly scientific spirit that it deserves. Dr. Vecki's work has long been favorably known, and the German book has received the highest consideration. This edition is more than a mere translation, for, although based on the German edition, it has been entirely rewritten in English. Medical Publications of W. B. Saunders. 29 VIERORDT'S MEDICAL DIAGNOSIS. Fourth Edition, Revised. Medical Diagnosis. By Dr. Oswald Vierordt, Professor of Medi- cine at the University of Heidelberg. Translated, with additions, from the fifth enlarged German edition, with the author's permission, by Francis H. Stuart, A. M., M. D. Handsome royal octavo volume of 603 pages; 194 fine wood-cuts in text, many of them in colors. Cloth. 54.00 net; Sheep or Half Morocco, $5.00 net. " A treasury of practical information which will be found of daily use to every busy practitioner who will consult it." — C. A. LlNDSLEY, M.D., Professor of the Theory and Practice of Medicine \ Yale University. " Rarely is a book published with which a reviewer can find so little fault as with the volume before us. Each particular item in the consideration of an organ or apparatus, which is necessary to determine a diagnosis of any disease of that organ, is mentioned ; nothing seems forgotten. The chapters on diseases of the circulatory and digestive apparatus and nervous system are especially full and valuable. The reviewer would repeat that the book is one of the best — probably the best — which has fallen into his hands." — University Medical Magazine. WARREN'S SURGICAL PATHOLOGY AND THERAPEUTICS. Surgical Pathology and Therapeutics. By John Collins Warren, M.D., LL.D., Professor of Surgery, Medical Department Harvard University; Surgeon to the Massachusetts General Hospital, etc. Handsome octavo volume of 832 pages; 136 relief and lithographic illustrations, 33 of which are printed in colors, and all of which were drawn by William J. Kaula from original specimens. Revised and Enlarged Edition in Preparation. "There is the work of Dr. "Warren, which I think is the most creditable book on Surgical Pathology, and the most beautiful medical illustration of the bookmaker's art, that has ever been issued from the American press." — Dr. Roswell Park, in the Harvard Graduate Magazine. " The handsomest specimen of bookmaking that has ever been issued from the American medical press." — American Journal of the Medical Sciences. " A most striking and very excellent feature of this book is its illustrations. Without exception, from the point of accuracy and artistic merit, they are the best ever seen in a work of this kind. Many of those representing microscopic pictures are so perfect in their coloring and detail as almost to give the beholder the impression that he is looking down the barrel of a microscope at a well-mounted section." — Annals of Surgery. WOLFF ON EXAMINATION OF URINE. Essentials of Examination of Urine. By Lawrence Wolff, M.D., Demonstrator of Chemistry, Jefferson Medical College, Philadelphia, etc. Colored (Vogel) urine scale and numerous illustrations. Crown octavo. Cloth, 75 cents. [See Saunders 1 Question- Compends, page 21.] " A very good work of its kind — very well suited to its purpose." — Times and Register. WOLFF'S MEDICAL CHEMISTRY. Fifth Edition, Revised. Essentials of Medical Chemistry, Organic and Inorganic. Containing also Questions on Medical Physics, Chemical Physiology, Analytical Processes, Urinalysis, and Toxicology. By Lawrence Wolff, M.D., Demonstrator of Chemistry, Jefferson Medical College, Philadelphia, etc. Crown octavo, 222 pages. Cloth, $1.00 net; inter- leaved for notes, $1.25 net. [See Saunders' Question- Compends, page 21.] "The scope of this work is certainly equal to that of the best course of lectures on Medical Chemistry." — Pharmaceutical Era. CLASSIFIED LIST 3V\££ Medical Publications '*\ W. B, SAUNDERS, 925 Walnut Street, Philadelphia, ANATOMY, EMBRYOLOGY, HISTOLOGY. Clarkson — A Text-Book of Histology, 9 Haynes — A Manual of Anatomy, ... 13 Heisler — A Text- Book of Embryology, 1 3 Nancrede — Essentials of Anatomy, . . 18 Nancrede — Essentials of Anatomy and Manual of Practical Dissection, ... 18 Semple — Essentials of Pathology and Morbid Anatomy, 25 BACTERIOLOGY. Ball — Essentials of Bacteriology, ... 6 Crookshank — A Text- Book of Bacteri- ology, 10 Frothingham — Laboratory Guide, . . II Mallory and Wright — Pathological Technique, 16 McFarland — Pathogenic Bacteria, . . 17 CHARTS, DIET=LISTS, ETC. Griffith— Infant's Weight Chart, ... 12 Hart — Diet in Sickness and in Health, . 13 Keen — Operation Blank, 15 Laine — Temperature Chart, 15 Meigs — Feeding in Early Infancy, . . 17 Starr — Diets for Infants and Children, . 26 Thomas — Diet-Lists and Sick-Room Dietary, • 28 CHEMISTRY AND PHYSICS. Brockway — Essentials of Medical Phys- ics, 7 Wolff — Essentials of Medical Chemistry, 29 CHILDREN. An American Text-Book of Diseases of Children, . 3 Griffith — Care of the Baby, 12 Griffith — Infant's Weight Chart, ... 12 Meigs — Feeding in Early Infancy, . . 17 Powell — Essentials of Dis. of Children, 19 Starr — Diets for Infants and Children, . 26 DIAGNOSIS. Cohen and Eshner— Essentials of Di- agnosis, . 9 Corwin — Physical Diagnosis, .... 9 Macdonald — Surgical Diagnosis and Treatment, 16 Vierordt — Medical Diagnosis, .... 29 DICTIONARIES. Dorland — Pocket Dictionary, . . . . 10 Keating — Pronouncing Dictionary, . . 14 Morten — Nurse's Dictionary, .... 18 EYE, EAR, NOSE, AND THROAT. An American Text- Book of Diseases of the Eye, Ear, Nose, and Throat, . 3 De Schweinitz — Diseases of the Eye, . 10 Gleason — Essentials of Dis. of the Ear, 11 Jackson— Manual of Diseases of Eye, . 32 Jackson and Gleason — Essentials of Diseases of the Eye, Nose, and Throat, 14 Kyle — Diseases of the Nose and Throat, 15 GENITOURINARY. An American Text-Book of Genito- urinary and Skin Diseases, 4 Hyde and Montgomery — Syphilis and the Venereal Diseases, ....... 13 Martin — Essentials of Minor Surgery, Bandaging, and Venereal Diseases, . 16 Saundby — Renal and Urinary Diseases, 24 Senn — Genito-Urinary Tuberculosis, . 25 Vecki — Sexual Impotence, 28 GYNECOLOGY. American Text- Book of Gynecology, 4 Cragin — Essentials of Gynecology, Garrigues — Diseases of Women, . Long — Syllabus of Gynecology, . Penrose — Diseases of Women, . . Pryor — Pelvic Inflammations, 9 II 15 18 32 Sutton and Giles — Diseases of Women, 28 MATERIA MEDICA, PHARMACOL- OGY, AND THERAPEUTICS. An American Text-Book of Applied Therapeutics, . , 3 Butler — Text-Book of Materia Medica, Therapeutics and Pharmacology, ... 8 Cerna — Notes on the Newer Remedies, 8 Griffin — Materia Med. and Therapeutics, 12 Morris — Essentials of Materia Medica and Therapeutics, 17 Saunders' Pocket Medical Formulary, 24 Sayre — Essentials of Pharmacy, ... 24 Stevens — Essentials of Materia Medica and Therapeutics, 26 Stoney — Materia Medica for Nurses, . . 28 Thornton — Dose- Book and Manual of Prescription-Writing, 28 MEDICAL JURISPRUDENCE AND TOXICOLOGY. Chapman — Medical Jurisprudence and Toxicology, .... .... 8 Semple — Essentials of Legal Medicine, Toxicology, and Hygiene, 25 LIBRARY OF CONGRESS # i iiiiiiiiiiiiiiiii ^^■0^73250852 . I WBm M ^■^ ^^H