THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES 3 (> A TEXT-BOOK PATHOLOGICAL ANATOMY PATHOGENESIS. A TEXT-BOOK OF PATHOLOGICAlTANATOMY AND PATHOGENESIS BY ERNST ZIEGLER PROFESSOR OF PATHOLOGICAL ANATOMY IN THE UNIVERSITY OF TUBINGEN TRANSLATED AND EDITED FOR ENGLISH STUDENTS DONALD MACALISTER M.A. M.B. MEMBER OF THE ROYAL COLLEGE OF PHYSICIANS; FELLOW AND MEDICAL LECTURER OF ST JOHN'S COLLEGE, CAMBRIDGE. PART I GENERAL PATHOLOGICAL ANATOMY fconton : MACMILLAN AND CO. 1883 ^ -J& Fia. 54. SECTION FROM A MELANOTIC ALVEOLAR SABCOMA OP THE SKIN. (Haematoxylin staining : x 300) a uninuclear, a^ multinuclear epithelial-like tumour-cells ft pigment-cells t Strom's enclosing blood-vessels and pigment 220 TUMOURS. [SECT. vi. glandular type. The cellular elements, even when they seem to resemble epithelial cells, are dispersed uniformly throughout the intercellular substance, as in the connective tissues. There are however exceptions to this in special cases. There are sarco- mata which have a structure resembling that of gland-tissue, or of epithelial new growths. This appearance of structure is due in part to the epithelial look of the cells, but chiefly to their aggre- gated arrangement in groups separated by fibrous septa. Such tumours are described as alveolar sarcomata. Fig. 54 repre- sents a section from an alveolar sarcoma of the skin. The cells a exactly resemble epithelial cells : they are grouped into masses, and sharply distinguished from the fibrous framework (e) in which they are embedded. This latter contains the blood- vessels, or rather the framework is chiefly made up of a network of blood-vessels ; but no vessels enter the cell-groups. This is another point of structure in common with the epithelial growths. Tumours of this kind occur chiefly in the skin, but they are also met with in the bones, lymphatic glands, and pia mater. In the case of the skin they originate in warts and pigment-spots, which generally contain such groups or nests of cells (Arts. 156 and 398). The way in which the alveolar structure is developed can often be clearly made out, especially in tumours of the central nervous system. The normal intervascular tissue is transformed into masses of sarcoma-cells, while septa are formed between the cell- masses by the fibrous tissues lying along the course of the vessels. Jn other cases it looks as if a plexus of pre-existing or new-formed vessels took on as it were an investment of cells, and this grew thicker and thicker till at length the intervascular spaces were entirely filled up. Accordingly we find this form of growth described as plexiform angiosarcoma. It has also been described, and not infrequently, as endothelioma. On this view the cell- nests arise by proliferation from endothelial cells. This certainly happens when masses of cells are formed from the endothelial covering of the subarachnoid mesh work and pia mater: the masses afterwards group themselves into ' nests '. Sometimes the proliferous endothelial cells of the pia mater are aggregated into small spherical nodules of a peculiar lustrous appearance. The tumour into which the membrane is transformed then contains small shining pearly bodies, made up of laminated layers of squa- mous or tabular cells. Such tumours have been called cholestea- tomata or pearly tumours. The expression 'plexiform angiosarcoma' is due to WALDEYER (Virch. Arch. vol. 55). The vessels of the brain, lymphatic glands, serous membranes, and testis possess what is called a perithelium : that is, the adventitia is invested with endothelial cells. Proliferation begins in the cells of this perithelium, and the vessel is thus invested with a stratified covering. See KOLACZEK, Deutsche Zeitsch. f. Chir. ix; MAURER, Virch. Arch. vol. 77; NEUMANN, Arch, d. Heilk. 1872; KLEBS, Prager Vierteljahrsschr. 1876. CHAP. XXVI.] MESOBLASTIC TUMOURS. CYLINDROMA. 221 It is still a matter of dispute whether the cholesteatomata are really endotheliomata of the pia mater (EPPINGER, Prager Vierteljahrsschr. 1875). They may possibly belong rather to the dermoid tumours (Art. 178). Similar growths are met with in the middle ear (WENDT, Arch. d. HeilJc. 14, 1873; LUCAE, Arch.f. Ohrenheilk. (New Series) 1, 1874). Some regard them as tumours, others (with WENDT) as inflammatory products. 162. Sarcomata which contain deposits of pigment are de- scribed as melanosarcomata (Fig. 54). The pigment is black or brown, and lies partly in the tumour-cells, partly in the fibrous matrix and vessel-walls. It occurs chiefly in the form of amorphous granules ; but there are generally a number of diffusely stained cells as well. Melanosarcomata are malignant. When the pigmentation is not extreme the tumour has on section a brownish grey look, or it may only show patches of brown or black. In more marked cases the section is uniformly black. Very often the secondary growths are more intensely pig- mented than the primary tumour, and this is also the case in growths that have recurred after resection. Tumours of this kind develope in tissues like the eye and pia mater, which normally contain pigment-cells, or in pigmented pathological formations. The black pigment-spots (melanomata) of the skin are of this latter' class : it has already been mentioned that they contain peculiar clusters or nests of cells (Fig. 54). We do not know in what way the pigment is formed (Art. 67). It is not to be confounded with the brown pigment derived from extravasated blood. Patches stained with this blood-pigment are sometimes found here and there in a sarcomatous growth, but the true melanotic pigment is something quite distinct. Fsammomata, like melanosarcomata, are growths which arise in certain definite tissues, and but rarely anywhere else. They are sarcomatous, fibrous, or myxomatous tumours originating in the brain and its membranes, more particularly in the choroid plexus and pineal gland, and containing a multitude of chalky concretions. These have the same structure as the grains of the normal brain- sand (acervulus cerebri). They are made up of concentric calcareous strata, and form spherical or dendritic aggregations. They may be so abundant as to give the tumour a stony feel. We may here just mention the variety of sarcoma called chloroma. It is a cellular tumour, whose section has a light green or dirty brownish green tint. The colour soon fades on exposure to the air. Nothing is known of the nature of the colouring-matter. Chloromata occur chiefly in the periosteum of the skull. See HUBER, Arch. d. Heilk. 1878. 163. Some very peculiar forms of tumour are produced when sarcomatous tissue undergoes partial hyaline or mucoid degenera- tion; or when sarcomatous and myxomatous formations combine. They are generally included under the term cylindroma, though this may also be applied to tumours of another species in which epithelial cells are involved (Art. 173 Fig. 72). The ordinary soft cellular sarcomata have now and then a more 222 TUMOURS. [SECT. vi. translucent appearance than usual, and yield on section a turbid slimy juice. These have already begun to undergo mucoid change, as may be recognised by the swollen ap- pearance of the cells, and the for- mation of drops of liquid within them. When the tissue has been hardened the change is not so easily made out. The cells then seem shrunken (Fig. 55 6), and separated from the stroma (a) by a clear zone. Sometimes a few distended and transparent nuclei are observed, their protoplasm having become mucoid and so vanished. This mucoid change may at times extend throughout the entire sub- stance of the tumour ; or it may be confined to scattered patches, sepa- rated by unchanged cells. Isolated hyaline spherules are occasionally noticed among the cells. Such par- tially degenerate sarcomata we may describe as myxomatodes. The tumours in which sarcomatous and mucous tissue are found combined have on section either a hyaline or an opaque dirty white appearance. The mucous tissue is partly composed of a net- work of ramified and anastomosing cells (Fig. 56 a), in addition FIG. 55. SARCOMA MYXOMATODES. (Haematoxylin staining : x 400) stroma sarcoma-cells separated from the stroma by a clear zone (in part due to hardening in chromic acid and alcohol) swollen nucleus which has lost its protoplasm FIG. 56. SECTION OF MYXOSABCOMA (CYLINDBOMA). (Carmine staining: x250) a mucous tissue b strings and clumps of cells c fibrous tissue CHAP. XXVI.] MESOBLASTIC TUMOURS. CYLINDROMA. 223 to a mucoid basis-substance. Within this tissue lie also branching clumps and strings (6) made up of closely compacted cells. These strings are very irregular in form and anastomose in all directions ; they give the tumour a very peculiar texture. Its general structure justifies the name of myxosarcoma, which has been applied to it. It forms, as has been said, a subdivision of the class of cylin- dromata. It is not clear, from a histological point of view, in what way the clumps and strings of cells are formed. They seem to have no relation to the ramifications of the vessels, for these are seen to be unchanged, and run through parts where the fibrous tissue has undergone no degeneration. A third variety of cylindromatous tumour, also somewhat trans- lucent and in part gelatinous, is characterised by the hyaline degeneration which affects the walls of its vessels and the tissue around them. If one of these vessels be isolated, it is seen to be invested with a more or less abundant deposit of hyaline substance (Fig. 57 a). To this sheath are attached similar hyaline appen- dages not traversed by vessels. Outside the hyaline sheaths, alternating with them in fact, are nests and strings of cells which here and there seem fastened or anchored to the hyaline masses (Fig. 57 6). The strings of cells have much the same look as FIG. 57. BLOOD-VESSELS WITH HYALINE SHEATH AND APPENDAGES FBOM A CYLINDBOMA. (From SA TTLERS ' Cylindrome ' 1874 : x 200) a small vessel & patch of epithelial-like cells on one of the hyaline appendages those shown in Fig. 56, and we infer that the tumour in question is allied to the myxosarcomata just described. The homogeneous appendages are the result of hyaline degeneration of the vessel- walls, or of the neighbouring tumour-cells ; and this hyaline degeneration is either identical or connected with mucoid degeneration. The 224 TUMOURS. [SECT. vi. fact that actual mucous tissue (like that in Fig. 56) is occasionally found mingled with the hyaline masses tells in favour of this view. This form of cylindroma may therefore be regarded as a peculiar variety of myxosarcoma, in which the mucoid change is chiefly confined to the vessels, and in which the formation of new vessels is an essential feature. To emphasise the important part played by the vessels in this neoplasm, we might call it angiosarcoma myxomatodes. Such growths have been found principally in the lacrimal glands, salivary glands, and in the brain. They occur however elsewhere, as in the lip, placenta, adipose tissue, &c. Cylindroma is a term due to BILLKOTH (Untersuch. iiber die Entwick. d. Blutgefasse 1856). Such tumours, characterised by gelatinous masses and reticula, have since then been very variously interpreted. KOSTER described them as cancroids (Virch. Arch. vol. 40); SATTLER (Ueb. d. sogen. Cylindrome, Berlin 1874) as alveolar sarcomata, in which the cell-masses derived by proliferation from the adventitia had been transformed into hyaline cylinders ; EWETZKY (Virch. Arch. vol. 69) as plexiform angiosarcomata with hyaline degeneration of the fibrous stroma, or of the adventitia of the vessels. R. MAIER ( Virch. Arch. vol. 14, and Lehrb. d. allg. path. Anat.) found cylindro- mata in the placenta and dura mater: he regarded the presence of an abundance of hyaline mucous tissue persisting for a long period unchanged as characteristic of the tumour. This tissue may develope out of cells or out of intercellular substance, fibrous tissue, cartilage, or tunica adventitia. Various tumours have been described as cylindromata which certainly do not all belong to the same species. A number of them belong to the sarcomata. Within this group we may, as we have said, distinguish two main forms ; first, the combined sarcoma and myxoma, and secondly, the sarcoma with hyaline or mucoid degeneration extending to the cells, but chiefly affecting the sheaths of the vessels. Between these two, however, many transitional forms are found. I. Mixed tumours of the connective-tissue group. 164. We have already referred to various tumours in which combinations of different tissues present themselves. In one sense no tumour can be said to consist of a single kind of tissue only. In a new growth of any size we must always have new vessels, for instance. And tumours whose characteristic element is not fibrous tissue such as chondromata, osteomata, sarcomata, myo- mata, and myxomata always contain a very considerable quantity of fibrous tissue as an accessory. We do not speak of such cases as examples of mixed tumours, because the accessory tissue is as it were put out of sight by the characteristic element : it is entirely subordinate. But if the second tissue comes into the foreground and affects the texture of the growth in a perceptible way, we must indicate this in our terminology. This is done by applying to the name of one neoplastic tissue the name of the other as a qualifying term ; or by simply combining the two names into a compound word. Thus, as in gli'omata and fibromata, the blood-vessels may be remarkable by their abundance, size, and dilatations ; we then speak of the growth CHAP. XXVI.] MESOBLASTIC TUMOUES. OSTEOID CHONDROMA. 225 as a glioma (or fibroma) telangiectodes or cavernosum. A morbid combination of adipose tissue with mucous tissue is called lipoma myxomatodes or lipomyxoma ; a combination of cartilage and sar- coma chondrosarcoma ; and so on. It is not rare for three or more kinds of neoplastic tissue to be found within the same tumour. A growth which starts in fascia or intermuscular fibrous tissue may consist, for example, of fibrous, sarcomatous, mucous, and adipose tissue ; there may even be vascular changes here and there which give it a telangiectatic character. Such a combination is not very surprising. The neoplastic proliferation may itself result in the development of several diverse tissues or, what is more common,, the tissues of the connective group become transformed the one into the other. We shewed, for example, in Arts. 90 92, that cartilage readily passes into mucous tissue, which is also frequently produced from fibrous or adipose tissues. Sarcomatous tissue may easily be the result of proliferation of the cartilage of a chondroma, or the fibrous tissue of a fibroma; and conversely, sarcomatous tissue may equally well be transformed partially into osseous tissue. Tumours originating in bone are very apt to show a tendency to bone-formation. There are two forms especially in which this often occurs namely, osteoid chondroma, a combination of cartilage and bony tissue ; and osteosarcoma, a combination of sarcoma and bony tissue. 165. Osteoid chondroma (or osteochondroma) chiefly affects the larger long bones. If no sarcomatous proliferation has modi- fied it, it usually forms a hard tumour seated on the bone or embracing it. It often reaches an enormous size ; and cannot be cut with the knife, unless a patch of unaltered cartilage be hit upon. When sawn through, the cut surface has the look of dense white continuous bone : on closer examination this is seen to be interspersed with streaks and islands of more translucent cartilage. Fig. 58 shows well the general texture of the growth and its matrix, and its relation to the bone. The section represented is taken from a tumour of the humerus. The tumour was very firm and bony, and surrounded the bone so as to double its diameter. It was found on dividing the bone longitudinally that the medullary spaces were filled with firm tumour-tissue of the same structure as the periosteal growth. The original bone was only recognisable in the region of its cortical layer. Fig. 58 represents a section taken at right angles to the axis of the bone, and including the periosteal growth, the cortical layer, and a part of the altered cancellous tissue. We find instead of periosteum a mass of cartilaginous tissue (g) interspersed thickly with bony trabeculae (h). These run generally at right angles to the surface of the original bone, but anastomose freely. Small lacunae and canals are seen throughout the cartilage ; they contain a few blood-vessels and a small amount of fibrous M. 15 226 TUMOURS. [SECT. vi. tissue. The cortical layer (a) is still distinguished by the concentric stratification of the lamellae. Many of its Haversian FIG. 58. SECTION FROM AN OSTEOID CHONDROMA OF THE HUMEKUS. (Magnified by means of a simple lens: double-staining with haematoxylin and carmine) cortical layer medullary spaces or cancelli periostea! growth i normal Haversian canals Haversian canals distended with cartilage, which at / contains a core of new bone cartilage developed from perios- teum, which at h contains bony trabeculae cartilage developed from medullary tissue, which at k contains bony trabeculae original trabeculae m remnants of medullary tissue canals are dilated and filled up (except for a small lumen in which the blood-vessel runs) with masses of cartilage. These masses sometimes contain trabecular cores of new-formed bone (/). In- stead of the marrow, which should fill the interior of the bone (b), we find vascularised cartilage also containing numbers of trabeculae. The genesis and primary seat of the growth may thus be made out at once from this preparation. Cartilaginous proliferation has been set up in the periosteum and in the medullary tissue, and the product has subsequently been partially transformed into bone. Osteosarcoma has an exactly analogous appearance. The difference is merely that sarcomatous tissue fills the spaces between CHAP. XXVI.] MESOBLASTIC TUMOURS. OSTEOSARCOMA. 227 the trabeculae instead of cartilage. The trabeculae are at the same time more delicate and less numerous. The seat of the tumour (as is the case too with osteoid chondroma) is often confined to the periosteum. The bone is then more or less eroded. Beferences : MULLER, Mutter's Arch. 1843 ; VIRCHOW, Die kr. Oeschwiilste i ; RINDFLEISCH, Path. Hist. II ; WILKS and MOXON, Path. anat. London 1875 ; PAGET, Surg. Path. Lect. 33. A summary of cases and some beautiful drawings of sarcomatous tumours connected with bone will be found in BUTLIN'S Sarcoma and Carcinoma London 1882. 152 CHAPTER XXVII. EPITHELIAL TUMOURS. 166. The tumours we have hitherto treated of have been de- veloped out of tissues belonging to the connective-tissue group ; in other words, out of tissues derived from the mesoblast. The tumours we have now to deal with contain in addition epithelial elements, that is to say, structures derived from the epiblast and hypoblast. These epithelial elements are in fact the structures which give its special character to the class. The tumours of the class are therefore very fitly comprehended under the one title of epithelial neoplasms. All of them consist of epithelial cells on the one hand, and of vascular connective tissue on the other. The latter tissue goes to form the framework or stroma in which the epithelial elements are embedded. The type or plan of their construction is that of the simple gland, and they maintain the resemblance throughout many of the phases of their development. They thus call to mind in many ways the various glands of the body ; though the degree of resemblance differs much in the different forms. Some of them are built exactly on the plan of some particular gland : the new-formed tissue corresponds to a definite glandular type. Tumours of this kind we call adenomata. Another group never reach this perfection of structure. They exhibit as it were only the first stage of the gland-making process. Epithelium and fibrous tissue interpenetrate each other in an inchoate way. The process is never carried higher, but the crude formation is repeated 'and reproduced indefinitely. By multiplica- tion of the epithelial cells we have produced nests and clusters and strings of cells, and these are imbedded in connective tissue whose elements are likewise multiplying. The result is a neoplasm consisting of a fibrous network or framework, in the meshes of which are lodged a multitude of variously-shaped epithelial cells. But there is no orderly arrangement of these epithelial cells. In the adenomata they tend to clothe the walls of the alveoli in a regular way, leaving open a central lumen as in the acinus of a CHAP. XXVII.] EPITHELIAL TUMOURS. ADENOMA. 229 gland. In the tumours now considered the cells remain in com- pact irregular masses. Epithelial tumours of this kind, in which the glandular type is most imperfectly followed, are described as carcinomata or true cancers. Adenoma and carcinoma are generally malignant. They tend to invade the surrounding tissues ; and, by the channels of the lymph or of the blood, are apt to affect distant regions and produce metastases. But the degree of malignancy varies greatly ; it depends not only on the histological structure of the growth, but to an even greater extent on its locality. The definition we have given of adenoma and carcinoma is based partly on their histology, partly on their mode of genesis. From the morbid anatomist's point of view this is the only correct mode of definition. Tumours containing none but mesoblastic cells may and do correspond in their general structure with others, in which undoubted epithelial cells form the characteristic element ; and for this reason a merely anatomical method of diagnosis would be insufficient. If carcinoma be defined as an alveolar tumour composed of a fibrous network containing nested cells, it is impossible to separate between carcinoma and alveolar sarcoma. It is owing to this purely anatomical mode of definition that we have had controversies as to whether carcinoma really depends upon epithelial proliferation, and whether cancers may not have their origin in fibrous structures. Such controversies become irrelevant if we base the distinction on histogenetic grounds. A tumour is to be called carcinomatous only when the epithelial elements take an active part (as above described) in its formation. A connective-tissue tumour which has ostensibly the same structure, but whose mode of genesis is entirely different, is to be distinguished as an alveolar sarcoma. a. Adenoma. 167. Adenoma is a tumour constructed after the type of a secreting gland. The definition might at first sight tempt us to term every glandular enlargement, in which the elements are abnor- mally multiplied, an adenoma. This would however be incorrect. Adenoma is a true neoplasm, characterised physiologically by its impotence to produce the normal gland-secretion, and anatomically by its want of relation to the tissue in which it is seated. A gland enlarged by over-growth, or over-work, or chronic inflammation, cannot be described as an adenoma. It is a hyperplasia : and if it be the true gland-tissue and not merely the fibrous framework which is excessively developed, the physiological activity of the gland is thereupon increased. We must regard in the same way the tumour-like growths which occasionally develope in mucous membranes, chiefly as a result of chronic inflammation. They are mere localised proliferations, rising above the general surface as nodular, polypous, or papillary outgrowths. The fibrous tissue is the first to increase, and this leads to some increase of the epithelium, chiefly because the local submucous swelling involves an increase of the mucous surface. If any glands are present (as in the intestine or uterus), they also undergo change. If their ducts become blocked, they may become 230 TUMOURS. [SECT. vi. FIG. 59. PAPILLARY GROWTHS INSIDE A CYST. (From a gastric polypus : liaematoxylin staining: x 300) a gland-tubules with cylindrical epi- thelium b stroma infiltrated with cells c papillary growths into a cyst, covered with mucoid epithelium distended with secretion, and form larger or smaller cysts. Other glands may enlarge by increase of their stroma ; and lastly there may be in some an active growth and increase of the specific gland- tissue. It is easy to demonstrate that such new-formations of fibrous and glandular tissue do take place. The most suitable ob- jects for examination are per- haps the papillary or villous growths which form on the inner surface of glands undergoing cystic degeneration (Fig. 59 c). These are sometimes so abun- dant that the cyst seems quite filled up with the new tissue. Such an overgrowth of the mucous membrane, in which the local glands are simultaneously enlarged, is best described as a glandular hyperplasia. 168. True adenoma is generally distinguishable from glandular hyperplasia by obvious characteristics. Its consistence, colour, and structure all mark it off plainly from the surrounding tissue. Adenomata are usually knot-like growths arising within the substance of glands, or in glandular epithelial or epidermic tissues. In the first case it is generally a part only of the gland that is transformed into tumour-tissue. In the mucous membranes and skin the tumour is likewise circumscribed. When an entire organ like the ovary is included in the growth, it is easy to make out by the alteration in the structure that it is an adenoma, and not the result of simple hypertrophy. Adenomata are often pale soft and marrowy : in other cases they are dense and coarse. Microscopic examination will obviate any doubt, which mere inspection may leave, as to the nature of a questionable adenoma. The structure of the neoplasm is always different from that of the affected tissue. It always corresponds with the type of some normal tissue ; but this is not the type of the matrix in which it lies. Adenoma of the intestine may be made up of ramified and convoluted tubules not of Lieberkiihnian crypts. Adenoma of the liver may be made up of tubular glands instead of lobules. Ade- noma of the mamma is at once distinguished from the normal gland-tissue by the mode in which the epithelial cells are repro- duced and arranged, and by the structure of the neoplastic acini. The difference between normal and neoplastic gland-tissue is perhaps most marked of all in the case of the ovary. Ovarian CHAP. XXVII.] EPITHELIAL TUMOURS. ADENOMA. 231 adenoma is apt to grow to an enormous size, and very often imperils the life of the patient afflicted with it. It usually takes the form of a multilocular cystoma or cystaderioma, as it is called ; and is made up of a multitude of small and large cysts. These contain a ropy, clear or turbid, and variously tinted liquid. Their inner surface resembles that of smooth mucous membrane. The walls are chiefly of a fibrous texture : but here and there occur masses of tissue with a soft marrow-like section and white or pink in colour, which resemble parenchymatous gland-substance. These masses exemplify the early stages of the tumour's development : they consist of a fibro-cellular stroma, containing glandular tubules lined with tall cylindrical epithelium (Fig. 60). Some of the FIG. 60. SECTION FBOM A PAPILLIFEROUS CYSTADENOMA. (Haematoxylin staining: x 40) tubules are dilated. This dilatation is the first step towards the formation of a cyst ; it is the result of an accumulation of secretion. When small cysts are thus formed, the fibrous tissue round them often proceeds to grow into the cavity in the form of papillary protuberances (Fig. 60). These papillary growths, which often develope in vast numbers, give to this variety its specific name of papilliferous cystadenoma. 169. All adenomata have not the same grave significance, whether we regard the affected organ or the system generally. Ovarian adenoma destroys the organ and jeopardises life by its size ; but it forms no metastases and does not invade neighbouring structures. Adenoma of a sweat-gland or sebaceous gland remains as a local tumour, never reaching any great size. But the case is different with the adenomata of the alimentary canal, namely those of the stomach, large or small intestine, and rectum. Each of these tends to invade and destroy the surrounding parts, and to form 232 TUMOURS. [SECT. vi. metastases. They are as malignant as the malignant carcinomata. In order to indicate this fact in their distinctive name, they have been called destructive adenomata, or adenocarcinomata. Their malignancy is manifested even in their local behaviour. Fig. 61 FIG. 61. SECTION THROUGH THE ADVANCING MARGIN OF A DESTRUCTIVE ADENOMA OF THE STOMACH. (Haematoxylin staining: x 25) a mucosa e neoplasm which starting from the mucosa b submucosa has invaded the other layers. Small-celled c muscularis infiltration here and there accompanies the d serosa formation of the neoplastic tubules. represents a section through the advancing margin of a small destructive adenoma of the stomach ; it is remarkable for the great size of its glandular tubules and of the epithelial cells which line them. The figure (Fig. 61) shows that the neoplastic tubules are first developed in the mucosa, the normal constituents of the mucous membrane simultaneously disappearing. Starting thence the neoplasm invades the submucosa (b). It intrudes itself along the intermuscular septa between the muscle-bundles of the muscularis (c) : and finally extends along the serous layer (d). Here and there through the fibrous tissue may be seen heaps of small cells : this indicates that proliferation is going on in this tissue likewise. This invasion of the neighbouring tissues is the first step towards the formation of metastases. Clearly the lymph-spaces of CHAP. XXVII.] EPITHELIAL TUMOURS. CARCINOMA. 233 the tissue are certain to be encountered by the advancing growth, and when this happens the path of infective transport stands open. Destructive adenoma is a soft marrowy tumour, taking the form either of a papillary or fungous outgrowth, or more commonly of a level and extensive thickening of the mucous membrane. The new tissue frequently breaks down and ulcerates. The ulcers have a soft infiltrated base and raised rampart-like edges, or the surrounding tissue is beset with nodular growths. b. Carcinoma. 170. If we define carcinoma as a growth characterised by epithelial multiplication (Art. 166), and not agreeing with any normal glandular type, we must at the same time lay stress on the fact that this epithelial multiplication is no merely accessory or sub- ordinate feature. It is the essential and distinguishing character of the neoplasm. Simple non-typical multiplications of epithelium are by no means uncommon; but they are not necessarily to be interpreted as carcino- matous. Subepidermic granulomatous tumours of the skin (Art. 132 Fig. 37) will often exhibit in their superficial layers clusters and rolls and strings of epithelial cells altogether diverse from any normal mode of grouping ; and the same may be observed in skin- wounds which are in process of repair by epidermic growth and multiplication. So too in glands altered by inflammation, and in fibrous tumours occurring in glands, the glandular epithelium may begin to multiply and lead to the formation of epithelial masses that are altogether non-typical or atypical in appearance. Formations of this kind are not to be classed with the carcinomata. They lack the power of growing indefinitely and of infiltrating the surrounding tissues. They are incapable of raising themselves to the rank of the independent tumour, that is nourished like a parasite at the expense of the organism, and invades the tissues to their destruction. They can only extend where a free surface is open to them, due either to antecedent inflammation or to the formation of a true tumour. In wounds or subepithelial granula- tions, these proliferous growths have no more significance than the covering of an abraded surface with new epithelium. The epithe- lium forms only in places where the underlying tissue is so arranged as to leave free surfaces or open fissures, and the process amounts, in a word, merely to the ' skinning-over ' of internal surfaces. The mode in which true carcinoma developes and extends is quite different. The epithelial new-formation is not limited to free or bared surfaces ; it actively invades the contiguous con- nective tissues. Thus we may have a cutaneous cancer or epithe- lioma, which consists essentially of cellular prolongations of the interpapillary promontories of the Malpighian layer, penetrating 234 TUMOURS. [SECT. vi. and ramifying in the fibrous tissue of the corium (Fig. 62 /). These prolongations go on growing and multiplying, and ultimately FIG.- 62. SECTION FROM A CUTANEOUS CANCER OR EPITHELIOMA. (Aniline-brown staining : x 20) a epidermis / cancerous ingrowths from the epi- /; corium dermis c subcutaneous areolar tissue g deep- set cancerous cell-groups (I sebaceous gland h proliferating fibrous tissue e hair-follicle i (above) cell-nest or epidermic globe i (below) sweat-gland infiltrate the corium over a more or less extensive area, taking the form of detached strings and nests of cells (g). In this case then, we may regard the carcinoma as an epithelial infiltration of the corium starting in the superficial epidermis. The share taken by the corium itself is not always the same. At first we are generally unable to detect in it any histological change whatsoever. The fibrous stroma in which the epithelial cells are lodged is furnished by the unaltered corium alone. In other cases, and in later stages (Fig. 62 A), a perceptible amount of cell-multiplication and occasion- ally of vascularisation takes place. It almost looks as if the fibrous tissue were endeavouring, by compensatory growth on its own part, to counteract the invasion of its borders by the epithelium. In tumours formed in the way we have described, the intruded masses of epithelial cells are spoken of as cancerous cell-nests, and the separate cells as cancer-cells. The fibrous framework in which they lie, made up partly of pre-existing and partly of new- formed fibrous tissue, is called the cancerous .stroma. 171. The development of cancer in glands is essentially similar to that which starts in squamous epithelium or epidermis. Thus CHAP. XXVII.] EPITHELIAL TUMOURS. CARCINOMA. 235 in the glands of the uterus, we have cancer commencing with active growth and multiplication of the cylindrical epithelial cells. The single layer of cylindrical cells is transformed into a series of stratified or disorderly masses of epithelium (Fig. 63) piled upon FIG. 63. SECTION FROM A CANCER OF THE UTERINE GLANDS. (Haematoxylin staining: x 250) a stroma b cancerous ingrowths or loculi c isolated cancer-cells each other. The size of the gland (6) is thus considerably increased, and soon its typical structure is overlaid and lost by the substitution of great cell-masses and cancerous cell-nests or loculi. The cells retain their cylindrical form only at the borders of these groups. This represents the first stage. In the second, the surrounding tissue is invaded and infiltrated by cancerous cell-nests. A section from the advancing margin of a mammary cancer (Fig. 64) shows at one view the various steps of the process; a low magnification is all that is necessary. The first stages in the formation of the mammary cancer are essentially the same as those observed in uterine cancer, though the peculiarities of the matrix bring about certain minor variations. The primary aberra- tion is an excessive multiplication of the glandular epithelium. This is followed by general epithelial infiltration. The small and scattered acini of the mamma are replaced by cancerous cell-nests of various form and size (e), imbedded in a scanty stroma. Starting 236 TUMOURS. [SECT. vi. from these as primary foci, the infiltration of the connective tissues (gf) extends far and wide, beyond the region of the gland- tissue itself. The fibrous bundles are thrust asunder by the multiplying cells, which link themselves into fusiform or rounded masses, or into long ramifying strings and bands. Spreading upwards these invade the corium ; single cell-nests may even be found immediately underlying the epidermis ( T , and others in this country, have put forward like theories : they are accustomed to speak of a ' spermatic ' influence exerted by the transported germs upon the tissue-elements of their new seat (Trans. Path. Soc. 1874). ZIEGLER is unable to find any satisfactory evidence for such a view. He made numerous investigations bearing on the question, and tinder his guidance FRONISTA examined a multitude of secondary growths in various organs ; but no certain grounds for the theory were ever discovered. Active changes in the fixed cells were often very beautifully shown; but wherever it was possible to trace the fate of these cells it was found that they merely went to form the type of tissue which they would reproduce in normal circumstances. The osteoblasts of the periosteum and marrow form bone or fibrous tissue; endothelial cells likewise produce only connective tissue. It is not however to be inferred that these investigations absolutely and certainly exclude the possibility of a cancerous transformation of the products of connective-tissue proliferation. When a tissue has undergone extensive proliferous changes, nothing certain can be made out from it regarding the origin or the fate of individual cells. The cancerous embolus acts like a foreign body. Round it are set up inflammatory infiltration of leucocytes on the one hand, and multiplication of the fixed cells on the other. Both processes result in fibrous hyperplasia, which in many cases goes to form a new stroma for the growing nodule. The same processes are thus repeated here as occur in the fibrous structures of the primary focus. It is therefore well to hold by the doctrine of REMAK and GOODSIR at least until it is certainly disproved that as the descendants of the different embryonic layers are never transformed into each other in normal circumstances, so also under pathological conditions no such metaplasia can occur. Even the transformation of one epithelial formation into another suggested by some (RISDFLEISCH, Path. Histology Art. 531; PERLS, Virch. Arch. vol. 56 ; &c.) has not been established. When carcinomata of the liver are examined the liver-cells are seen to dwindle and perish, but not to change to cancer-cells. Even in cases where mammary cancer penetrates the corium and reaches the epithelial layers of the skin, it is always possible to distinguish clearly between the cancer-cells and the true cutaneous epithelium. CHAP. XXVII.] EPITHELIAL TUMOURS. CARCINOMA. 247 175. Carcinoma is very prone to undergo retrogressive change. In the juice scraped from the cut surface of a cancer we may nearly always find cells which are fatty or disintegrating. This is especially the case in soft quickly-growing tumours. If the fatty change is extensive the affected spots look white and opaque, and by and by break down into a creamy pulp. The disintegrated cells may also become condensed into cheesy masses. More commonly, however, we find that a part of the cells become absorbed. In tumours lying beneath the surface of an organ or raised above its general level, a central depression or dimple may thus be formed. The tumour is then said to be umbilicated. In cancers with a dense stroma, in which the disappearance of the cells is accompanied by hyperplasia of the fibrous elements, we may find the original growth replaced by a dense coarse deposit of fibrous tissue containing few if any cancerous cell-nests. This transformation is specially frequent in the case of mammary and gastric scirrhus. Mucoid degeneration has already been discussed (Art. 173). Amyloid degeneration of the stroma has frequently been observed. The necrotic disintegration of cancerous growths, and the consequent formation of cancerous ulcers, deserve special mention. Tumours of great size may in this way be wholly destroyed. In intestinal cancer, for example, it is no rare thing to find after a certain time nothing but an ulceration, replacing the original tumour, and bearing hardly any resemblance to it. If the ulcerative process is not far advanced, the remains of the tumour may be recognised as nodules or papillary excrescences rising from the base or border of the ulcer. In later stages the base may be smooth and clean, consisting simply of firm fibrous tissue ; while the edges rise like ramparts, or are beset with papillary or nodular growths. Now and then these may disappear in like manner, and the ulcer appears as a non-cancerous sore with an indurated base. Even on section it may not always be possible with the unaided eye to decide whether the tissue still contains cell-nests or not. We must in such cases have recourse to the microscope. Cutaneous or epitheliornatous cancers, like those of mucous membrane, may also ulcerate ; and so too may cancers of the mamma or other subcutaneous glands. The surface of these breaks down, and great putrid or foetid ulcers are the result. The seat of an ulcer is always the seat of a more or less intense inflammatory infiltration. Sometimes this results in vigorous granulative proliferation, the granulations rising above the surface as fungous excrescences. They are distinguished from ordinary granulations by the cell -nests they contain. From this granulation- tissue ordinary cicatricial tissue may be elaborated. A sort of local healing and recovery may thus result from the destruction of the tumour, and the formation of granulative and cicatricial tissue. The growth may seem to have altogether disappeared. But this 248 TUMOUKS. [SECT. vi. healing is only local and relative, and it does not last. Microscopic examination shows that the cancerous invasion of the deeper structures still persists. The formation of secondary growths, even after the surface ulceration is scarred over, testifies to the fact that the malignancy of the process is not removed with the removal of the primary growth. 176. Adenoma and carcinoma may be combined with other jieoplastic formations ; that is to say, the stroma may be composed of other than fibrous tissue. In the first place it must be remem- bered that as cancer invades successive tissues, the most various structures may in turn be utilised to form its stroma. Thus when a uterine cancer reaches the muscular coats of the organ, we find that the stroma of the tumour contains smooth muscular fibres. When secondary nodules form in the liver, we often see liver-cells, atrophied no doubt but still recognisable, in the trabeculae of the stroma. The new-formed tissues which actually originate in the stroma are to be distinguished from such pre-existing formations. In the former case we may find that not only fibrous tissue but even cartilage or sarcomatous tissue has been developed. Such neoplasms are described as complex or mixed tumours. They are most common in the testis and parotid gland. They resemble the simple carcinomata in their general relations. CHAPTER XXVIII. AETIOLOGY OF TUMOURS. 177. Our knowledge of the aetiology of tumours is still very defective. What we have to say on the subject is, generally speaking, largely hypothetical. We might at first be inclined to regard a tumour as the result of a local overgrowth of tissue, and to look for the conditions of its development among those which determine ordinary hyperplasia. But facts soon appear which tend to show that the processes are not parallel. There is, first, the histological diversity of the tumour (Art. 136) from the matrix in which it grows. Secondly, there is the associated impairment or extinction of the physiological function of the matrix-tissue. These facts do not suggest a mere over-active growth in situ. The anatomical facts are thus against our regarding tumours as localised hyperplasias. It follows that we cannot expect to discover the efficient causes of tumour-growth among the factors which give rise to such hyperplasias. Nor can we fairly compare the tumours with the inflammatory new-formations. Tumours may indeed contain foci which are infiltrated with leucocytes. But these are of secondary signifi- cance. The entire process of neoplastic histogenesis shows that it is something quite different from the formative processes which originate in inflammation. We thus exclude at once the possibility of attributing the growth of a tumour to a traumatic lesion, at least in any immediate or direct way. Clinical experience bears this out; for if now and then we have tumours developed in a substratum of tissue which has been injured and has undergone inflammatory change, it is on the whole a rare occurrence, and does not prove that such injury would of itself suffice to set up tumour-formation in previously healthy tissue. This being the case, we are perforce constrained to admit that other factors must be sought, if we are to explain the genesis of tumours. 250 TUMOURS. [SECT. vi. If we did not know that tumours may develope at the most various periods of life nay, that many forms are wont to appear only in advanced age, it might perhaps suggest itself to look for their aetiological factors in the embryo to regard them in fact as local malformations. But the peculiar modes of occurrence referred to, and the observation that tumours originate in tissues which before looked perfectly normal, would scarcely make us regard such an embryonic theory as very probable beforehand. COHNHEIM has very recently propounded an embryonic hypo- thesis of another kind. We are not to refer the actual development of the tumour itself to the embryonic period, but are to attribute its appearance in later life to the persistence of germinal embryonic tissues in the otherwise mature organism (COHNHEIM, Ally. Path. i). A tumour takes its rise in what we might call a belated rudiment a focus of formative embryonic tissue, which has not been utilised in elaborating the normal tissue of the part and so has lingered on unchanged. COHNHEIM therefore defines a tumour as an atypical new-formation starting in a latent embryonic rudiment. The tumour-germs, consisting as they do of embryonic cells, -may be very small and so elude observation. It is even conceivable, he thinks, that the germinal cells may be quite un- recognisable among the ordinary physiological elements of the part. They may linger on for a long time inactive. It is only when they are favoured by the external conditions such as the supply of nutriment, and their relation to the surrounding tissues that they begin to multiply and to form a tumour. In this way it becomes possible that a traumatic lesion may set up the active change. In most cases however the awakening impulse is beyond our power to discover. We cannot deny that COHNHEIM'S hypothesis would explain satisfactorily many of the peculiarities of tumours. Those growths, for example, whose structure reminds us so strongly of earlier developmental stages of particular tissues, would be acquitted of their (at present) unaccountable heterology. It also tells in favour of the theory that a class of tumours does actually exist, of which we can say with certainty that they date their origin from the embryonic stage. At the same time we may well question whether our knowledge of the subject justifies us in attributing an embryonic origin to all tumours, or whether we should accept the theory only with considerable limitations. COHNHEIM bases his view mainly on the arguments that many tumours have been shown to be hereditary; that many exist at birth or at least develope in infancy; that they show a preference for sites where in earlier developmental stages some complication of structure occurred, e.g. for the places where diverse epithelial formations pass one into the other (lips, anus, stomach, cervix uteri), or for parts where the entire process of development is highly complex (genital apparatus). Finally, he holds that the atypical structure of tumours generally is in favour of his account of them. It must be granted that these arguments speak strongly for the hypothesis. CHAP. XXVIII.] AETIOLOGY OF TUMOURS. TERATOMA. 251 They at least make it highly probable for certain classes of tumours. But they do not suffice to prove its applicability to all. The view that tumours arise in consequence of injury, especially of frequently repeated irritation, is very widely accepted (ViRcnow, Die krank- haften Geschwulste; KRONLEIN, Lang. Arch. f. klin. Chir. xxi; KOCHER, Art. Krankheiten des Hodens, Handb. d. spec. Chir. v. Pitha u. Billroth; BOGEHOLD, Virch. Arch. vol. 88). COHNHEIM has justly objected to this view that the number of cases of tumours in which antecedent injury has been demonstrated does not reach more than 14 per cent, of the whole number, and is by some given as 7 per cent (BoLL, Das Princip des Wachsthums Berlin 1876 ; S. WOLFF, Zur Entstehung von Geschwiilsten nach traum. Einwirk. In. Diss. Berlin 1874; Vox WINIWARTER, Beitrage z. Statistik d. Carcinome Stuttgart 1878). From this we may infer that an injury may perhaps give rise to a tumour; but that neither injury nor inflammation is at all a necessary antecedent. 178. We are acquainted with a considerable number of forms of congenital tumour, whose origin can be referred with more or less certainty to the embryonic period. Of these it is however to be remarked that their structure and composition are only in part analogous to those of the post-embryonic growths hitherto discussed. Many of them possess a structure entirely peculiar to themselves, so that they cannot be classed with any of the preceding tumours. They are therefore regarded by all authorities as special and peculiar formations, and are distinguished as teratomata. Teratomata or teratoid tumours (Art. 13) are congenital growths, which are remarkable for the heterogeneity of their constituent elements. They may be large even at birth, or they may grow from small beginnings to a large size after birth. They may contain fibrous tissue, cartilage, bone, muscle, skin, hair, nerves, gland-tissue, and simple cellular or embryonic tissue. At times they may have the look of complex histioid tumours; but the combinations they present are usually much more various and heterogeneous than in any ordinary histioid growth. We even meet in them with structures which recall the appearance of some normal organ the differences lying chiefly in the rudimentary nature of the outward shape or configuration, and the abnormal site. Sometimes the various tissues are grouped into something like orderly disposition, giving one the impression of a more or less organised foetus. Teratomata, when externally visible, are usually placed at parts of the trunk corresponding to those at which double monstrosities cohere. These are chiefly the lower end of the spine, the head, and the neck. Internal teratomata are usually connected with the genital apparatus. Such teratomata are some of them true double monstrosities. One foetus has been surrounded and enclosed by another, and so has become stunted and ill-developed (Art. 13). The remainder are due to some misdevelopment of the tissues within a single foetus. 252 TUMOURS. [SECT. vi. Dermoid cysts form a special class of teratomata. They are cysts whose inner surface has the same structure as the normal skin ; but they occur in places where no skin is ever found normally. Their commonest seat is in the generative organs, especially in the ovary. More rarely they are found in other parts, such as the peritoneum, neck, and around the orbit. The smallest examples form little cysts which, as in the ovary, are distinguishable from their contents. The contents are usually greasy, semi-solid, yellowish- white, and interspersed with hairs. The wall is thicker, firmer, and whiter, than that of the Graafian follicles. Under the microscope it is seen to be composed of a corium and epidermis : it may even contain hair-follicles and sebaceous glands, or more rarely sweat-glands. Now and then an adipose layer, like the subcutaneous fat, is found beneath the corium. In rare cases, flat or irregular fragments of bone or cartilage and even teeth are found beneath the cutaneous layer. The teeth may also be found free within the cyst. Very rarely the cyst-wall contains muscular or nervous tissue. The larger dermoids, i. e. those reaching from the size of a walnut to that of the fist, are sharply marked off from the surrounding tissues by a fibrous capsule. They enclose large quantities of oily or greasy detritus, interspersed with fair or reddish hairs. Dermoids are found in young individuals as well as old. Some are found even in the new-born. They grow very slowly. Judging by the special character of their lining membrane, these formations would seem to be derived from the same rudimentary elements as the external skin. They are probably due to aberrant germinal cutaneous cells from the epiblast, which have somehow wandered to an abnormal site, and there have at a later stage begun to develope after their kind. References on the subject of teratomata and dermoid cysts : Art. 13 ; KOHLRAUSCH, Mailer's Arch. 1843 ; LEBERT, Gaz. me'd. de Paris 1852 ; REMAK, Deutsche Klinik 16, 1856 ; HESCHL, Prager Viertelj. 1860 ; LUCRE, Handb. d, Chir. v. Pitha u. Billroth n ; HAFPTER, Arch. d. Heilk: xvi, 1875 ; PANUM, Virch. Arch. voL 72 ; KLEBS, Handb. d. path. Anat. ; DANZEL and MARTINI, Arch. f. klin. Chir. xvn ; WALDEYER, Arch. f. Gynak. i ; WILSON Fox, Journ. of Anat. 1865 ; GORDON, Jfed. chir. Trans, xni ; PAGET, Sura. Path. Lect. 23. 179. Besides the teratomata there are other tumours more nearly allied in structure to the ordinary forms, which are either congenital or appear so soon after birth that their origin may with more or less certainty be referred to the embryonic period. The best-known examples are the congenital angiomata and pig- ment-spots (beauty-spots, moles) in the skin. The former have already been discussed (Arts. 148 150). Of the latter we have merely to say that they appear as brown or black slightly raised patches in the skin, and are composed of tissue exactly resembling alveolar sarcoma (Fig. 54) covered over with epidermis. CHAP. XXVIII.] AETIOLOGY OF TUMOURS. 253 We may likewise mention in this connexion certain cutaneous fibromata ; enchondromata of the skull, spinal column, and fingers ; myxomata of the jaws ; renal adenomata and cancers ; and cystic adenomata seated on the sacrum and communicating with the central canal of the spinal cord. The number of really congenital tumours observed is by no means great. Cases of tumours appearing in the earlier years of infancy and referable to embryonic conditions are more numerous. Of this kind are the sarcomata of infancy ; especially the form of myosarcoma of the kidney referred to in Art. 153. It is not impossible that some of the ovarian adenomata may date back to the embryonic period. If we consider carefully the scanty details we possess of congenital tumours, taken in conjunction with the familiar facts of post-embryonic tumour-formation, we must admit that the support which COHNHEIM'S theory derives from this side of the subject is not very great. It must not however be forgotten that this theory requires the existence not of congenital tumours but only of congenital rudi- ments of tumours. As to these latter our knowledge is unfortu- nately very small. It is almost entirely confined to the pigmentary and vascular naevi we have mentioned. They may be regarded, and with equal justice, either as germinal rudiments of tumours, or as developed growths. The former view is justified by the fact that in later life it is not uncommon for these structures to develope into true malignant tumours. Tumour-germs in bone were discovered some years ago by VIRCHOW (Berlin, acad. Monatsbericht 1875). He showed that islands of cartilage, which remain untransformed in the general ossifying process, may in later life become the starting points for the formation of chondromata. Nothing certain is known of embryonic epithelial germs, such as may subsequently develope into tumours. Their existence may be surmised in the case of early epithelial tumours of the ovary, kidney, or intestine ; but it has not been demonstrated. The frequently observed accessory glands occurring in connexion with the pancreas, mamma, thyroid, &c. are not to be regarded as mere germinal rudiments, inasmuch as they contain fully developed gland-tissue. From what we have said, then, it will be seen that the histolo- gical evidence for the existence of embryonic germinal tissue in the fully developed organism is very slender. ZIEGLER describes a tumour of some interest which he found in the small intestine seated in the submucosa; it was as large as a pea, and was made up of minute cysts. It should probably be regarded as a local misformation, rather than a deposit of germinal tissue. Its cysts contained papillary excrescences covered with columnar epithelium; and small gland-tubules were found in the cyst-walls. It is conceivable that, from a misformation of this kind, a true tumour might at some time or other begin to develope. References on congenital tumours: VIRCHOW, Die krank. 254 TUMOURS. [SECT. vi. DUZAN, Du cancer chez las enfants Paris 1876; AHLFELD, Arch. f. Gyndk. xvi ; ROHRER, Das primare Nierencarcinom Zurich 1874 ; MAAS, Berl. klin. Woch. 47, 1880; C. VOGT, Ueber angeb. Lipome In. Diss. Berlin 1876; CHIARI, Jahrb. d. Kinderheilk. xiv ; WEIGERT, Virch. Arch. vol. 67 (reual adenoma). Many authorities are of opinion that COHNHEIM'S theory is strongly borne out by the experiments of ZAHN (Sur le sort des tissus emplante's dans I'or- gamsme, International Med. Congress, Geneva 1873) and LEOPOLD (Virch. Arch. vol. 85). They took bits of cartilage from a living foetal rabbit, and transplanted them into the peritoneal cavity and anterior chamber of the eye of an adult rabbit. The cartilage continued to grow, while pieces of cartilage taken from animals after birth were merely absorbed. This scarcely seems sufficient ground for COHXHEIM'S generalisation. The faculty of growing after transplantation is not manifested by all foetal tissues : many or most of them are dissolved and absorbed by the disintegrating action of the fixed and migratory cells of the new matrix (LEOPOLD, Arch. f. Gyncik. xvin). These experiments only show that foetal cartilage has the power of persisting and even of growing for a time in spite of defective nutrition, and the absorbent action of the cells of the other tissues. 180. The inadequacy of the evidence for the existence of germinal embryonic rudiments in the adult tissues makes it appear a somewhat bold step to ascribe an embryonic origin to all tumours whatsoever. The observed and recorded cases do not justify us in saying more than that some tumours arise in rudimental structures, which were histologically distinguishable from the normal tissues before the tumour began to grow. And even in saying so much we must not interpret the term embryonic too literally. Embry- onic formations are such as possess a structure resembling that of undeveloped tissue an indefinite structure preceding the defini- tive or specialised structure. Tissues that are merely misdeveloped, pieces of tissue (such as epithelium or gland-tissue) displaced from their proper seat and transplanted elsewhere, as in the case of accessory glands and dermoid cysts, are not what we understand by embryonic tissues. The class of tumours referable to embryonic rudiments will be somewhat enlarged, if we enlarge the signification of the term em- bryonic so as to include under it all tissues in process of active and energetic growth. So long as an organ continues to grow, so long are multitudes of new cells formed in it. These formative cells may be called embryonic, inasmuch as they continue to multiply actively and so are nearer akin to the cells of the embryo than to those of mature tissue. In this way osteoblasts and osteoclasts and the prolifera- ting cartilage of growing bone, the cells of the enlarging uterus in pregnancy, the tissue of the mamma preparing for lactation, all might be described as embryonic. If the hypothesis be thus extended, a whole series of tumours will certainly be comprehended under it. When, for instance, a tumour developes in the mamma or uterus in connexion with parturition, or a sarcoma or enchon- droma forms in bone, periosteum, or marrow during ossification, it is not difficult to believe that the same cells which are building up the normal tissue may also give rise to the tumour. CHAP. XXVIII.] AETIOLOGY OF TUMOURS. 255 But if we extend the meaning of the term embryonic so as to include all this, where are we to stop ? Growth, i. e. restoration and replacement of what is being used up, continues throughout life. Surface epithelium is cast off and is regenerated ; glandular epithelium is used up and replaced; even bone, though it seems so stationary, is exposed to changes at all stages of life it is being resorbed by the osteoclasts and built up again by the osteoblasts. If all post-embryonic processes of growth are to be styled embry- onic, we cannot refuse to give the same title to all the processes of new cell-formation that occur during life. If this be granted, em- bryonic tissue becomes exactly the same as that which VIRCHOW called proliferous tissue, i.e. tissue capable of proliferation. We gain nothing by the mere substitution of one name for another : in the present case we lose something, for we are no longer able to distinguish in expression between embryonic and post-embryonic formation. For this reason it is better to confine the term em- bryonic to tissues which actually originate in the embryonic period. The fact that we really know nothing of the persistence of true embryonic tissue or in other words, that it has not been histologically demonstrated is ackno \vledged by COHNHEIM. He seeks to explain the fact by supposing that the 'embryonic foci are very small and hard to distinguish; or even that the germinal cells may be mingled with the normal elements and so not distinguishable at all. It is not easy to imagine how embryonic cellular germs can possibly remain unchanged in the midst of mature tissue. COHX- HEIM and MAAS ( Virch. Arch. vol. 70) have shown that living tissue, such as periosteum, when introduced into another tissue like the lung, may continue to grow for a time ; but afterwards it is absorbed and destroyed by the tissue in which it lies. An embryonic germ seems to have but three courses open to it. It may remain embryonic : in this case it is as it were alien to the tissue in which it lies, and will be absorbed like an organic foreign substance. It may assimilate itself physiologically as well as anatomically with the surrounding tissue, taking part in its physiological function and working with it : in this case it loses its embryonic character. Or thirdly, it may develope into an independent formation, interpolated as it were into the general system : in this case it forms what we call a congenital tumour (naevus, adenoma, sarcoma). HASSE has attempted to give COHNHEIM'S hypothesis a morphological basis (Die Beziehungen der Morphologie zur Heilkunde Leipzig 1880). The morphologist distinguishes two kinds of substances within the organism : one kind undergoes a series of transformations, the other provides for the formation of new tissue. The latter he describes as 'embryonic substance'. It is represented by cells which have undergone little or no transformation, and are the more apt to multiply the less their original character and structure has been modified the nearer they stand to the formative cells of the embryo. From these cells only can new tissue be formed. Tumours are especially likely to be developed at spots where these 'embryonic cells' are abundant and unmodified. BASSE'S distinction between proliferous and non-proliferous tissue-elements is perfectly just (Arts. 84 89) : and any one may if he chooses call the former embryonic (as do French writers especially). In this case however the antithesis, on which COHJJHEIM lays so much stress, between the cells of the embryo and the proliferous elements of the organism after birth, simply ceases to exist. 256 TUMOURS. [SECT. vi. 181. It is plain from the above that we do not think the hypothesis tenable which refers all tumours whatsoever to pre- existing embryonic germs. Anatomical investigation forces us rather to the conclusion that tumours may arise in tissues that are in very different states embryonic, growing, mature, or retro- gressive. What is then the efficient cause of the formation of a tumour ? It is as yet impossible to give any precise answer to this question. It is highly probable that the causation of the various classes of tumours is not subject to one law only, but to several. The entire behaviour, anatomical and biological, of tumours justifies us in regarding them as formations more or less emanci- pated from the matrix- tissue. It is true they draw their nutriment from the organism, and cannot continue to grow without its support. In other respects, however, they behave like independent growths isolated from the rest of the organism. It is in this independence or quasi-isolation that the aetiological difficulty really lies. How does the neoplasm thus assume properties dis- tinct from those of its surroundings ? We believe that the phenomenon is ultimately due to some change affecting individual elements of a tissue, whereby they are rendered dissimilar to their neighbours. The change is manifested especially in this that the normal checks to the indefinite growth of the proliferous cells (Arts. 78 83) are inoperative or inadequate ; either because the formative and productive energy is increased, or because the restraining influence of the surrounding structures is diminished, or from both causes together. In the case of tumours appearing in the organism during the stage of development, it is most natural to suppose that the originating cause lies in an increased local growth due to intrinsic conditions : or, it may be, in a disturbance and diversion of the developmental process from its normal course. What the ultimate factors determining these deviations may be we know as little as we do the causes of gigantic overgrowth or local dwarfing of a limb or organ. When the anatomical and physiological relations of the affected tissue are altered to a certain extent by this local change, it would seem as if the tissue had no longer the power to maintain the normal direction in which its development should proceed. The altered relations (such as misplacement, &c.) seem to involve the withdrawal of the limiting and directing influence exerted on the growing tissue by its environing structures. The result is the development of a tissue of abnormal type, a local misformation in the histological as well as the anatomical sense. The tumours whose genesis is probably of this kind are chiefly the connective- tissue growths of childhood. Among epithelial tumours we may also perhaps include the few observed cases of renal and intestinal cancer, and of ovarian adenoma, in infants. It is thus not impossible that tumours of the developmental CHAP. XXVIII.] AETIOLOGY OF TUMOURS. 257 period may arise from causes similar to those which give rise to local malformations in the stricter sense of the term. Arrest of the process by which osteoblastic cells are transformed into bone might thus, for example, give rise to an abnormal formation of tissue such as cartilage, in other words, to enchondroma; or by encouraging an over-abundant cellular growth, to sarcoma. Tumours arising in a mature tissue are to be explained only by supposing some antecedent alteration over a more or less extensive region of the tissue. This alteration must be of such a kind as to favour the emancipation of the subsequent neoplasm from its matrix-tissue, without at the same time diminishing the neoplasm's own productive power. This last indeed must rather be increased. In this way we may perhaps explain the operation of a traumatic lesion in inducing the growth of a tumour. In special circum- stances it is conceivable that such a lesion may fulfil both the essential conditions we have named. In the case of the connective-tissue growths of later life, it would seem as if increased cell-activity were always a necessary condition for their development. This must presumably always be a condition of tumour-formation in tissues whose cells are replaced but slowly or not at all. The primary impulse which excites the cells to active growth may be derived from some change either in the cells themselves, or in the intercellular basis-substance. With regard to epithelial tumours, anatomical investigation shows that increased cell-production is not an indispensable pre- requisite. In the carcinomata of later life, for instance, it would appear that the origin of the neoplastic growth is to be looked for, not so much in any increased activity on the part of the cells, as in a change of mutual relation between the several constituents of the tissue. THIERSCH has pointed out that in old age this latter effect may be due to certain retrogressive changes which then make their appearance. In the corium, for instance, such changes lead to a loosening of its texture, and so modify the relations of the epithelial cells to the fibrous tissue. This modifica- tion may make itself felt in one of two directions. In the first place, the epithelium, always in process of decay and replacement, may in the course of its physiological growth and multiplication penetrate to regions which are normally devoid of epithelium. Loosening and displacement affecting the fibrous basis of an organ may give rise to something like fissures or spaces with free surfaces, and into these the contiguous epithelium may readily penetrate and grow. The first sproutings or outgrowths of glandular or lining epithelium may conceivably take place in this manner. We might fairly expect that the fibrous structures would as it were rise up against the intruder, and attempt to eliminate it as a foreign substance. This may well happen in many cases, and then the further advance of the process will be checked. In other cases it does not happen, probably because the invaded tissue is no longer in M. 17 258 TUMOURS. [SECT. vi. its normal or healthy state. We have indeed evidence of vascular alteration, infiltration of leucocytes, and even of new-formation of vessels and fibrous tissue ; but this, the normal eliminating process, is feeble and sluggish, and is inadequate to deal with the intrusive epithelium. The vascular changes and the increased afflux of nutriment tend rather to react favourably upon the epithelium, and to foster its reproduction. It becomes gradually more and more active and so the foundation of a carcinoma is laid. It seems not improbable that the process of neoplastic develop- ment does in fact occasionally pursue this general course. In other instances, it may well be that the fibrous basis-substance has a certain intrinsic predisposition favouring the formation of cancer, while the primary impulse which brings this into play is afforded only by some increase of formative activity on the part of the epithelial cells. The instructive discussion on the nature of cancer reported in the Trans. Path. Soc. 1874 should be consulted in this connexion. For an exposition of the constitutional theory, which makes cancer a specific blood-disease, see PAGET, Surg. Path. Lects. 34, 35. See also PAGET and MOORE, Holmes's Syst. of Surg. vol. I ; WILKS, Guy's Hosp. Rep. 1872. SECTION VII. PARASITES. 172 CHAPTER XXIX. GENERAL CONSIDERATIONS. 182. A parasite is a living organism inhabiting another living organism, and deriving its nutriment either from the tissues or from the food-supply of its host. The parasites inhabiting man are some of them animal, and some of them vegetable. If they inhabit the superficial parts of the skin or mucous membrane they are called ectozoa (or epizoa), if animal, and epiphytes, if vege- table : if they inhabit the deeper structures they are entozoa and entophytes, respectively. The parasitic animals occurring in man belong to the classes of Arthropoda, Scolecida (embracing the Platyelminthes and Nematoidea), and Protozoa. The vegetable parasites are all of them Fungi, and belong to the subdivisions Schizomycetes (bacteria), Blastomycetes (yeasts), and Hyphomycetes (moulds). The various parasites are of very various importance. Many of them produce no perceptible injury to the tissue in which they lie. Others produce very serious local changes, but have no power to extend their influence to remote tissues. Others invade the system, so to speak, and migrating in various directions produce multiple local affections. Many are conveyed throughout the body by the blood or lymph, in which case serious general affections and fre- quently death itself are the result. The great majority of parasites, and especially the vegetable parasites, increase and multiply within the body, often to an enormous extent. Others, chiefly the animal forms, pass only a part of their existence within the body. The local changes they produce are generally confined to the mechanical compression and destruction of tissue, and to the setting up of inflammation. They affect the system as a whole by abstracting nutriment and oxygen from it, and by giving rise to multitudes of centres of disturbance ; while many of them generate actual poisons. The Schizomycetes or Bacteria play the most important part of all. It is they of all the parasites that have most power of exciting general or systemic affections. The Blastomycetes and Hyphomycetes, fungi akin to the yeast-fungus and mould-fungus respectively, exert a merely local influence. The animal parasites become dangerous in virtue of their size or multitude, or by penetrating into vital organs. Parasitism is an extremely common mode of life throughout the organised world. Innumerable plants and animals are parasitic either for a season or for the whole course of their life. Accordingly there are few living organisms that are not inhabited by parasites. A plant or animal which merely inhabits the body of an organism is not necessarily a parasite. The term is only applicable to organisms nourished at the expense of their host. CHAPTER XXX. THE SCHIZOMYCETES OR BACTERIA. Morphology, Development, and Classification. 183. The Schizomycetes or Schistomycetes, frequently included under the general term Bacteria, belong to the Protophytes the smallest and simplest of all plants. Many of them are so small that they approach the limit of visibility, even when the highest powers of the microscope are used. When they occur in animal tissues they are to be distinguished only with great difficulty, and by special methods. Special reagents or staining processes must be employed ; sometimes certainty is only reached by experimental' cultivation of the products of disintegration of the tissue in question. -That they do occur in animal tissues is now established beyond all doubt. Their growth and multiplication have been experimentally demonstrated. The Bacteria are all of them unicellular organisms devoid of chlorophyll : they are often however aggregated into larger or smaller colonies. COHN has classified them according to their form into Sphaerobacteria (globular cells), Microbacteria (minute rod-like cells, Bacteria proper), Desmobacteria (larger rod-like or filiform cells, Filobacteria), and Spirobacteria (twisted or spiral cells). Movements are noticed in the three latter forms ; their protoplasm is therefore contractile. Neither potash, ammonia, nor dilute acids destroy them, so it is probable that they possess a bounding membrane. Bacteria grow longitudinally: new cells are formed by transverse subdivision. These remain in connexion with each other, or become detached. VON NENCKI'S researches (Journ.f. prakt. Chem. I879,Beitrdge zur Biologie der Spaltpilze 1880) go to show that the bacteria are composed of a peculiar albuminoid body which he has called mycoprotein. They contain only the minutest quantities of bodies resembling cellulose. The above classification of the Bacteria is taken from COHN (Beitrdge zur Biologie, der Pflanzen vol. I ; Q. Journ. M. S. 1873, 77, 79), and his work has been mainly followed in the next four paragraphs. He makes the following CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 263 remarks on the general question of classification : " I have come to the con- clusion that the Bacteria are as capable of exact specific classification as other plants. They lie at the limit of microscopic visibility. In the minuter forms it is therefore impossible to make out either structure or organisation. The size and shape of the cells, and the mode in which they are combined into colonies, are then the only differentiae : of these however it is not always easy to say whether they indicate original specific distinctions, or whether they depend on external conditions and lie within the limits of variability of one and the same species. Size is the easiest feature on which distinctions may be based, though even this is by no means easy to determine in the minuter forms. Differences in the mode of reproduction are only discoverable in the higher forms, such as the Bacilli. The genera of Bacteria have not the same significance as those of the higher plants. They are based chiefly on the characters of the vegetative cell-forms, not on the reproductive features. Every form distinguished by prominent or obvious characters is provisionally furnished with a generic name : smaller deviations serve to designate the species. It is thus not at all impossible that some of such species and genera may really represent different developmental stages of one and the same fungus." Since this utterance of COHN'S a great number of researches have been made into the growth and multiplication of the Bacteria. KOCH especially has devoted himself to the subject (Mittheil. a. d. kaiserl. Oesund- hdtsamte Berlin 1881). After long-continued experiments on cultivation, in which bacteria were bred in nutritive gelatine ('the dry process') he has reached the conclusion that each species of bacteria possesses character- istic and easily recognisable peculiarities in respect of structure, form, size, anct mode of growth of its colonies on the gelatine. The Schizomycetes have been very variously named by different authors. PASTEUR speaks of them as ve"ge"taux cryptogames ou microscopiqv.es, animal- cules, champignons, infusoires, torulacdes, bacte'ries, vibrioniens, monades, mycoderma. In Germany the terms Monaden, Vibrionen, Mikrozyma and (by KLEBS) Mikrospora and Monadine have been used. BILLROTH introduced the term Coccobacteria. In England we have corresponding terms, with others like monads, zymes, mio'ozymes (SANDERSON), microphytes, &c. 184. The Sphaerobacteria are the smallest of all bacteria. Under the microscope they appear as bright round or ovoid spherules of scarcely measurable size. Two genera are distin- guished : Micrococcus (Fig. 74, i) and Sarcina (Fig. 74, 15). The spherules known as micrococci exhibit no perceptible organisation, but it is highly probable that they are differentiated into cell-membrane and cell-contents. They are found in liquids and in tissues either isolated, or arranged like strings of beads or ' chaplets ' (Fig. 74, 16), or grouped in colonies (zoogloea, Fig. 74, 2). On examination it is found that in these colonies or zoogloea the separate spherules are united by a gelatinous intercellular substance. COHN affirms that this is nothing but the swollen and thickened cell-membrane. VON NENCKI affirms that it consists of mycoprotein. With regard to their growth and increase, it is made out that the individual cells first elongate and then subdivide transversely. If the subdivided cells remain conjoined the result is a diplococcus (BILLROTH). If the process of subdivision goes on, the new cells remaining attached and in line, chains or chaplets are produced. If large numbers of spherules remain after subdivision within the 264 PARASITES. [SECT. vir. swollen and continually enlarging membrane, the result is a mass of zoogloea. The genus Micrococcus includes several species. These are distinguished partly by their morphological and partly by their physiological characters. In the first place the micrococci are of various sizes. When cultivated on a proper soil they form colonies of various types. Many of them as they multiply produce yellow, red, blue, green, or brown colouring matters. Lastly, the effects pro- duced in the soil or liquid in which they grow are various; nor do they all flourish on the same kind of nutriment. It is still doubt- ful whether the micrococci are motile. The oscillatory movements observed in them are probably to be regarded as Brownian or pedetic movements. KLEBS believes that the zoogloea are con- tractile. The genus Sarcina is very clearly marked. The globular cells divide crosswise, and the daughter-cells usually remain combined in tetrads (Fig. 74, 15). Various species have been distinguished according to the size of the cells. BILLROTH and KLEBS assert that micrococci may grow into rodleta or bacilli. It is not to be denied that some bacterial spherules become transformed into rods (Art. 185), but COHN is probably right in maintaining that Micrococcus is a definite genus of constant form. ZIEGLER has cultivated Micrococcus luteus, a bacterium which developes on boiled eggs exposed to the air and forms yellow zoogloea ; and though the experiments fully made to that end, he coul micrococci. Experiments on parasitic micrococci seem equally to indicate were carefully made to that end, he could never obtain bacilli, but always that there is a genus of bacteria which forms globular cells only. It is not yet certain whether or not the micrococci produce spores. KOCH thinks it unlikely. See also EWART, Proc. Roy. Soc. xxvu. 185. The Microbacteria are classed together as a single genus Bacterium. The principal species are Bacterium termo (Fig. 74, 3), and Bacterium lineola (Fig. 74, 5). The first appears in the form of minute cylindrical rods, 0*5 to 1'5 micromm. in length, and appearing bright or dark according to the mode of illumination. Sometimes they remain at rest, sometimes move about more or less actively. From their manner of subdivision they are often found coupled in pairs; they do not usually form chains or chaplets ; but are often grouped as zoogloea (Fig. 74, 4), which are remarkable for the great abundance of the gelatinous intercellular substance. B. termo is very generally found in putre- fying matters. B. lineola resembles B. termo, but it is larger in every way. It is found in water, in infusions, on potatoes, &c. The cells, which are from 3'8 to 5 micromm. in length, contain a clear bright substance interspersed with fine granules. In other respects the bacterium resembles B. termo; it swims about actively, moving forwards and backwards in curves, rotating, or oscillating. At times it remains motionless. It forms continuous pellicles on the surface of liquids containing it. When micrococci or microbacteria have exhausted the nutri- CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 265 ment contained in the liquid in which they live, they fall to the bottom as a powdery precipitate. i$fa Mt, I '"I 9VA/M 6 & Q & " \$gi& ^4"l I 3 FIG. 74. VAKIOUS FORMS OF BACTERIA (x 500 in each case) 1, Micrococcus septicus ; a separate, b in chaplets. 2, Micrococcus diphtheriticus forming a ^oogloea-mass. 3, Bacterium termo. 4, Zoogloea of B. termo. 5, Bac- terium lin$ola-. 6, Bacillus subtilis. 7, Bacillus anthracis, with red blood-cells. 8, Flagellate bacillus from the mouth. 9, Bacillus leprae (ARMAUER HANSEN). 10, Bacillus with terminal and medial spores, from a putrefying liquid. 11, Bacillus malariae (KLEBS), with spores. 12, Vibrio serpens (COHN). 13, Spirochaeta Ober- meyeri ('spirillum' of relapsing fever). 14, Spirillum volutans (COHN). 15, Sarcina ventriculi. As has been indicated in Art. 184, BILLROTH, HALLIER, and KLEBS maintain that the microbacteria represent merely a developmental stage in the life-history of the micrococci. BILLROTH (Unters. iiber Coccobacteria septica Berlin 1874) believes that all bacteria belong to a single species of plants, the members of which are composed partly of round and partly of rod-like segments varying greatly in size. The round segments are the cocci, the rod-like segments bacteria. Each form may pass into the other on occasion ; though they so far breed truly that for some generations cocci produce only cocci, and bacteria only bacteria. According to size we may distinguish them as micrococci, mesococci, and megacocci, and microbacteria, mesobacteria, and megabacteria. Megacocci may break up into micrococci. The plant which passes through all these stages BILLROTH calls Coccobacterium septicum. In the process of multiplication it developes a gelatinous envelope or gliacoccus. When this occurs at the surface of a liquid so that a pellicle is formed, he calls it petalococcus or petalobacterium. Masses of cocci enclosed in a cylindrical sheath of gliacoccus are called ascococci (VAN TIEGHEM, Bull. Soc. Botanique 1880). Coupled spherules are diplococci ; chains or chaplets of spherules, streptococci : and in like manner he describes diplobacteria, and streptobacteria. RAY LANKESTER (Q. Journ. M. 8. 1873) also inferred from certain experiments of his that CORN'S forms are not really distinct. HABERKORN (Sot. Centralb. 10, 1882) maintains that COHN'S four divisions merely represent diverse species of a single genus. BILLROTH'S view of the specific unity of all the bacterial forms has been discredited by later researches (cf. TIEGEL, Virch. Arch. vol. 60 ; LISTER, Trails. Roy. Soc. Edin. 1875). KLEBS (Arch. f. exp. Path, iv) divides the globular and rod-like bacteria into Microsporina and Monadina. He defines the Microsporina as small micrococci which in the resting state form well-defined and compacted balls ; the several spherules being regularly deposited in layers and surrounded 266 PARASITES. [SECT. vn. by only a small quantity of gelatinous matter.. The peripheral spherules grow into minute motile bacteria, which tend to move away from the mass, and thus further the diffusion of the organisms through the nutrient liquid. The highest stage of their development is reached in the formation of a matted tuft of unbranched filaments. The monadina form loose balls, from which motile monads or vibrios break away. These grow into rodlets which are relatively short and broad ; and these again subdivide ; they probably increase also by conjugation. They then pass into a resting state, and lie quietly alongside each other. Lastly they break up into spherules ; it is rare for them to form tufts or clusters. They require oxygen, and thrive better on albumen than on gelatine. It is not yet certainly known whether Bacterium termo produces spores or not. It has been described as possessing flagella by DALLIXGER and DRYSDALE (Month. Mic. Journ. xiv), and by KOCH (Beitrilge zur Biol. 1877). 186. The Desmobacteria (or Filobacteria) are cylindrical rodlets of varying length ; some of them are thick, and some slender and delicate. COHX describes a straight form which he calls Bacillus, and a wavy or curved form which he calls Vibrio. Bacillus increases by transverse subdivision, and frequently forms a long string (Fig. 74, 6) commonly referred to as a leptothrix (HALLIER). It is not always easy to make out that the string is made up of distinct rodlets. In other cases bacilli form swarms. Many bacilli pass through both a resting state and a swarming state. Many are provided with a flagellum or cilium, which acts as an organ of locomotion (Fig. 74, 8). The best representatives of this genus at present known are B. subtilis (Fig. 74, 6), B. anthracis (Fig. 74, 7), B. tuberculosis (Fig. 80), and B. leprae (Fig. 74, 9). The various specific forms are distinguished by their general size, and by the relation of their length to their breadth. Some of them are cut off square at the ends, others are rounded off or pointed. Even more marked differences than these become apparent when the various forms are cultivated in nutrient liquids. ' Cultures ' of this kind have been made by COHN, KOCH, KLEBS, BREFELD, PRAZMOWSKI, LISTER, NAEGELI, BUCHXER, KLEIN, and many others, and we have thus come to know some- thing of the life-history of many of the varieties. COHN bred the B. subtilis in hay-infusions ; KOCH the B. anthracis found in the blood and tissues of animals suffering from splenic fever ; and also the B. tuberculosis (Art, 206). The life-histories of the different species differ in many details ; but they usually agree in their main features. Features which thus constantly recur are the longitudinal growth of the rodlets, their transverse subdivision and abstriction, and the formation of spores or gonidia. The life-history of B. anthracis is briefly as follows. If the anthrax-bacillus be observed under proper conditions, it is found in a short time to grow lengthwise to a very considerable size (Fig. 75 6). Within twenty-four hours a string or filament is formed (Fig. 75 c), which may be ten or twenty times as long as the original rodlet. In ten or fifteen hours more the clear contents of the filament become granular. Then appear at CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 267 regular distances small darker bodies, which grow in a few hours into larger highly refracting spores (Fig. 75 d). The FIG. 75. DEVELOPMENT OF BACILLUS AXTHRACis. (FromKOcu: x400) a bacilli from the blood d for twenty-four hours ; spores are j dead bacilli b bacilli cultivated for three hours, c for ten hours, forming and the filaments are breaking up e germination of spores filaments afterwards break up, and the spores are set free. In favourable circumstances these spores may germinate and develope into bacilli exactly like those originally taken from the blood. According to KOCH, each spore consists of a bright body surrounded by an envelope of clear protoplasm. As the spore germinates the latter grows into a rodlet (Fig. 75 e). The researches of KLEIX, BREFELD, PRAZMOWSKI, EWART, and others do not corroborate this account. They make out that the spore consists of protoplasm enclosed in a membrane. The rudimentary bacillus is developed not from the peripheral layer of the spore, but from its protoplasmic centre. In addition to this mode of increase by spore-formation observed in cultivated bacilli, the rodlets multiply by transverse subdivision. This is especially the case in the blood of living animals. As we have said, all bacilli have the power of forming spores. It is not however essential to the process that long filaments should be formed. Many bacilli produce spores without having undergone any marked increase in their length. The number of spores in each rodlet varies from one to three. They may occupy either a terminal or a medial position (Fig. 74, 10 and 11). Anthrax -bacilli cultivated on gelatine are never motile (KocH): they always form flakes or tufts made up of long wavy tress-like or twined filaments. The bacilli of hay-infusion grow out into long filaments in very young colonies only. When they become 268 PARASITES. [SECT. vu. more mature and cause the gelatine to liquefy, they are seen in active movement at the centre of the colony, while round its periphery they stand in regular array all perpendicular to the surface and penetrating the firmer gelatine. The colony then looks as if it were surrounded by an aureole of rays. Other bacilli form colonies looking like tufted roots of trees: others again spread out in one plane and form mosaic designs. COHN'S and KOCH'S researches are published in the Beitrage zur Biologie d. Pftanzen voL n, and Mittheil. a. d. kais. Gesundheitsamte Berlin 1881 : BREFELD'S are in the Botan. Zeitung 1878, and in Botan. Unters. uber Schimmelpttze 1881 : KLEIN'S, SANDERSON'S, and Ew ART'S, in the Quart. Journ, Micros. Science 1878. PRAZMOWSKI asserts (Unters. uber d. Entwick. einiger Bacterien Leipzig 1880) that the germination of the spores of B. subtilis follows a different course to that of B. anthracis. The mature spore is oval, highly refracting, sharply defined, and surrounded by a transparent zone. On germination the spore becomes pale, and loses its lustre and its sharp contour. At each pole a kind of shading appears, the spore meanwhile beginning to move in a tremulous manner. After a time the contents escape laterally in the form of a minute cylindrical shoot, which grows into a rodlet ; and this latter then proceeds to subdivide. PRAZMOWSKI has also made out the life-history of the so-called Clostridium butyricum (PASTEUR'S vibrion butyrique, VAX TIEGHEM'S Bacillus amylobacter). It forms rodlets 9 10 micromm. long, which are seen alternately at rest and in moving swarms. Before fructification they increase in thickness and become more fusiform or pear-shaped. On germination the spore swells and begins to jerk about. The membrane at one end is absorbed, the germinal cylinder escapes, and as it grows proceeds to subdivide as before. KERN describes a bacillus under the name of Dispora Caucasica (Biolog. Centralb. 5, vol. n) much resembling B. anthracis ; it is however distinguished from the latter by its always exhibiting terminal spores at each end of the rodlets. When cultivated in milk this bacillus sets up a peculiar fermenta- tion, which produces an agreeable drink much used in the Caucasus. BREFELD distinguishes an external spore-membrane or exosporium which is thrown off in germination, and an internal or endosporium which becomes the envelope of the germinal cylinder. With regard to the term leptothrix it is to be noted that all filaments or strings so named do not necessarily represent developmental stages of a bacillus. The filaments formed by algae, for example, are also spoken of as leptotriches. 187. The Spirobacteria are divided into two genera Spirochaeta (Fig. 74, 13) with long flexible close- wound spirals ; and Spirillum (Fig. 74, 14) with short stiff open spirals. For the pathologist, Spirochaeta Obermeyeri (is) and Spirochaeta denticola are the most important species of the first genus. The former (often referred to simply as ' spirillum ') is constantly found in the blood of patients suffering from relapsing fever, during the paroxysms. The latter is found in the mouth and nose of persons who may be quite healthy or suffering from nasal catarrh. The length of the former is twice or thrice the diameter of a red blood-cell. It moves with extraordinary agility through the blood, and is there- fore hard to see unless it be somehow fastened down or restrained. No structure has been made out in it. CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 269 No details are known of the life-history of Spirochaeta. It plainly increases very rapidly within the body. It probably produces resting-spores. The largest of all bacteria, Spirillum volutans, belongs to the Spirilla (Fig. 74, 14). Apart from its size it is distinguished by its granular protoplasm and its pair of flagella. It sometimes moves about actively, sometimes lies quiescent. It is occasionally found in drinking-water. Two smaller forms, Spirillum tenue and Spirillum undula, also belong to this genus (Art. 207). Biology of the Bacteria. 188. Conditions of life. All bacteria require to be supplied with certain definite nutritive substances if they are to develope normally. The requisite substances are partly inorganic, and partly organic (carbohydrates and albuminoids). The inorganic components are derived from salts containing sulphur, phosphorus, magnesium, and potassium. The requisite carbon and nitrogen are mainly derived from animal and vegetable matters. But bacteria have also the power of assimilating nitrogen from ammonia, urea, or even nitre, provided only the other mineral substances needed are also present, and in addition some appro- priate organic carbon-compound, such as sugar. These nutritive substances must be presented to the bacteria associated with a certain amount of water. None of the bacteria can develope without water, though many of them may be without it for a time and still continue to live. This is especially the case with bacterial spores. If the water contains no proper nutriment, or if the nutriment is already used up, the bacteria cease to develope, and after a time die outright. But here, as when water is lacking altogether, it is possible for the bacteria to maintain life for a time. The spores are still more tenacious of life, and can hold out almost indefinitely. Free oxygen is absolutely necessary to the development of many of the bacteria : others can do without it if they are otherwise favourably placed, and in circumstances where they can set up fermentation. The former kind, e.g. Bacillus anthracis and B. malariae (KLEBS), have been called by PASTEUR aercbious fungi. The latter, of which Bacterium termo and Clostridium butyricum are the best- known examples, are anaerobious. Pure oxygen is said to kill bacteria outright. NAGELI gives minuter details of the conditions of life of the various bacteria (Die niederen Pilze Munich 1877, and Untersuch. iiber die nied. Pilze 1882). PASTEUR, JOUBERT and CHAMBERLAND have papers in the Gaz. mdd. de Paris 1876 on the relations of bacteria to oxygen. PRAZMOWSKI asserts that so far as concerns Clostridium, oxygen is not merely unnecessary but positively harmful. B. anthracis on the other hand dies if deprived of oxygen, breaking up into rounded fragments. PASTEUR again affirms that the bacillus which gives rise to the ' Pasteurian ' septicaemia in rabbits, dies if exposed to the air. According to KOCH (Mittheil. a. d. k. Gesundheitsamte Berlin 1881), the anthrax- bacillus perishes if it is allowed to become dry ; 270 PARASITES. [SECT. vn. while the spores may be preserved for years in the. dry state. They may even be kept moist for a time without losing their power to germinate or to produce the specific infection. 189. The temperature of the nutrient medium has great influence upon the development of bacteria. If the temperature be lowered, the effect is generally to slow and to weaken the vital processes, and ultimately to put an end to them altogether. As the temperature is raised on the other hand, these processes become more and more active until a certain maximum is reached : carried beyond this point they rapidly and suddenly cease, in most instances not to revive again. The maximum temperature which can be borne by fungi varies in the different species ; a few are capable of growth at 70 to 74 C (VAN TIEGHEM). The develop- ment of all kinds is stayed at a temperature of 5C. They become stiff and immobile, but are not absolutely killed even by very extreme degrees of cold. The rigor frigoris sets in at different temperatures in different species ; in the case of B. termo at 5 C, of B. anthracis at 15 C. For B. anthracis the temperature most favourable to development is 30 40 C; at 42 C develop- ment ceases. B. termo developes best between 30 C and 35 C. All bacteria and all bacterial germs are killed by boiling-hot water or steam, after exposure for a certain time. The spores are much more resistent than the bacteria. In dry air both may endure much higher temperatures. Spores, for instance, are not destroyed at a temperature of 140(J until after three hours' exposure. B. termo perishes at 65C, if the temperature be kept up for a considerable time. Eesearches on the effect of temperature on the bacteria and their spores have been made chiefly by EIDAM (Cohn's Beitrage z. Biologie d. Pflanzen vol. n), KOCH, WOLFFHUGEL, GAFFKY, and LOFFLER (Mitth. a. d. k. Gesund- heitsamte Berlin 1881), VAN TIEGHEM (Butt. Soc. But. 1881). The following are the chief results arrived at. Bacterium termo passes into rigor frigoris at 5, into rigor caloris at 40. At 45 the ordinary putrid decomposition of albuminoids ceases to go on (ElDAM). Bacillus anthracis multiplies the more slowly as the temperature is lower, within certain limits. Between 30 and 40 growth and spore-formation are completed in twenty-four hours. At 25 this time is increased to thirty-five or forty hours. At 23 the spore-formation occupies forty-eight or fifty hours : at 20 seventy-two hours: at 18 it takes five days, at 16 seven days. Below 15 growth and spore-formation cease (Kocn). Spores are still formed at a temperature of 42. See also SANDERSON and EWART, Q. Journ. Mic. Sci. 1878. Bacteria without spores when exposed to hot air cannot endure a temperature much over 100 for so long as an hour and a half. The spores of bacilli are only destroyed after three hours' exposure to a temperature of 140. In the case of objects exposed to heat with a view to disinfection, it is note- worthy that the temperature penetrates very slowly. Objects of moderate size such as bundles of clothing, pillows, &c. are not completely disinfected even when exposed for three or four hours to a temperature of 140 (WOLFFHUGEL). Anthrax-bacilli perish when exposed to boiling water for two hours ; when exposed to steam in a closed space ten minutes suffices. On the other hand the peculiar bacillus found in garden-soil is not destroyed CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 271 by this exposure. Superheated steam at 105 kills all bacterial germs. A jet of steam is more powerful than steam in a closed chamber. It will kill all kinds of germs in ten to fifteen minutes, and it readily penetrates the articles to be disinfected (Kocn, GAFFKT, LOFFLER). When using boiling water for disinfecting purposes, care must be taken that the heat is kept up long enough, i.e. until all the parts are warmed up to 100. The effect of temperature in modifying the virulence of pathogenous bacteria will be referred to later on. 190. Another factor of importance in regard to bacterial de- velopment is the presence of foreign or non-nutritive substances in the nutrient liquid. Many substances (like corrosive sublimate, bromine, iodine, and some acids) have a very powerful effect even in small quantity. They put an end to growth and fermentive action, or kill the organisms outright. Other substances have no injurious effect unless present in considerable quantity. The fermentive action of the fungi leads to the formation in the nutrient liquid of substances which, when they reach a certain degree of concentration, may ultimately put a stop to the growth and multiplication of the fungi themselves. In alcoholic or lactic fermentation, for instance, the gradually accumulating alcohol or lactic acid ultimately brings the fermentive process to a standstill. If nutritive matters be present in excess (or if, in other words, the supply of water be inadequate), the growth and multiplication of the iungi ceases in like manner. This is the reason why conserves of fruit made with sugar do not ferment, why con- densed milk does not turn sour, and why dried or salted meat does not putrefy. By withdrawing water, or by adding substances which dissolve in the organic liquids, we are able to increase the proportion of solids to liquids in organic substances such as provisions, and so preserve them from decomposition by fungi. The quantity of water necessary for the development of fungi like bacteria and the yeast-plant is greater than in the case of the mould-fungi. HORWATH'S and REINKE'S researches (Pflugers Arch, xvu, xxin) show that constant agitation of the liquid hinders the development of bacteria, and may even check their multiplication altogether. A further factor of importance in bacterial development is the presence of lower orders of fungi in the nutrient liquid. As higher plants often encroach on and interfere with each other, so it is possible for bacteria, yeast-plants, and moulds to interfere and compete with each other for nutriment (NAEGELl). A bacterium, which is thriving and multiplying in a given liquid, may be checked and ultimately killed merely by introducing another fungus which is still more at home in the liquid. Thus if we introduce into a nutrient liquid containing sugar the germs of a number of fungi of different classes, the bacteria alone will multiply and set up lactic fermentation. If a half per cent, of tartaric acid be now added, the yeast-fungi alone will -proceed to multiply, and 272 PARASITES. [SECT. vn. alcoholic fermentation will begin. Add now from four to five per cent, of tartaric acid, and mouldy growths appear. The tartaric acid does not kill the other fungi; it merely favours one more than the others. Thus it is that in grape-must it is only the yeast-fungi which flourish, though other germs are certainly present. Only when the sugar is all used up have the bacteria a chance to multiply, and then they set up acetous fermentation. Mould-fungi may then develope in the presence of the vinegar, and they consume the acetic acid. Lastly, when this is done, the bacteria reappear and set up putrefaction. Even among the Bacteria themselves a like mutual interference and struggle for existence is observed. Micrococci may be thrust aside by microbacteria. Bacilli may be killed by Bacterium termo, when the supply of oxygen is insufficient for both. It is also a point of importance, when there are various kinds of fungus-germs present, to know which kind is most abundant. If the soil be equally well adapted for two or more forms, the form represented by the majority of germs will have the advantage. KOCH and WOLFFHUGEL have made very careful investigations into the action of various substances on the life and multiplication of bacteria. (Mittheilungen &c. 1881). The subject has also been treated by BUCHHOLTZ (Arch. f. exp. Path, iv), SCHOTTE and GARTNER (Deutsche Viertelj. f. off. Gesuiwl. xii 1880), NAGELI (Die niederen Pilze Munich 1877 and 1882), ROBERTS (Phil. Tram. 1874), HAMLET (Journ. Chem. Soc. 1881), and many others. 1'he following results of investigation are worthy of note. Corrosive sublimate has the most powerful effect on bacteria : an aqueous solution of 1 : 20,000 kills the spores of bacilli in ten minutes. A solution of 1 : 5,000 is thus a certain disinfectant, even when the time of exposure is very short. Mercuric sulphate is somewhat less active. KOCH finds that an aqueous sublimate-solution of 1 : 300,000 puts a stop to the germination of bacterial spores. Sulphurous acid does not take a high place as a disinfectant. Bacteria clinging to dry objects are killed by twenty to thirty minutes' exposure to an atmosphere containing 1 vol. per cent, of sulphurous acid. Spores of B. subtilis and B. anthracis are still capable of development after ninety-six hours' exposure to an atmosphere containing 5 to 6 vols. per cent, of sulphurous acid. Even when moist they are very hard to kill with it. It is thus an altogether untrustworthy disinfectant, and all the more because it has little power of penetrating compact masses or bundles (WOLFFHUGEL, BUCHHOLTZ, SCHOTTE and GARTNER, KOCH, BUCHNER). Carbolic acid in 5 per cent, solution will kill the spores of the anthrax- bacillus in twenty-four hours. A 3 per cent, solution will not do so in the same time. The bacilli however are killed in a few minutes even by a 1 per cent, solution. A solution of 1 : 400 checks the development of bacterial spores. Vapour of carbolic acid at ordinary temperatures is without effect ; at 55 C it kills spores in two or three hours (KocH, loc. cit. ; DE LA CROIX, Arch. f. exp. Path. xin). Chloride of zinc in 5 per cent, solution has no effect on anthrax-spores even when they have lain in it for a month (Kocn). Iodine, bromine, and chlorine are far more active than sulphurous acid. Bacilli cease to grow in presence of iodine in the proportion of 1 : 5,000, and of bromine of 1 : 1,500. Steam from bromine-water kills spores in twenty-four hours, from chlorine-water in two days. Iodine-water and chlorine-water kill spores in one day, a 5 per cent, solution of chloride of lime in ten days. Benzoic acid, sodium beuzoate, potassium chlorate, and quinine have little CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 273 effect ou spores. The following substances even in dilute solution have a restraining influence on bacterial development allylic alcohol ; oils of mustard, peppermint, turpentine, and cloves ; thymol ; chromic, picric, hydrochloric, and salicylic acids ; quinine. The effect is perceptible in solutions of 1 : 300,000 for oil of peppermint, of 1 : 800 for quinine, of 1 : 75,000 for oil of turpentine. All disinfecting agents should be used in aqueous solution. In alcohol or oil they are either inactive or enfeebled. Bacillus-spores still retain their power to germinate after lying for months in absolute alcohol. In water and in glycerine they may lie for weeks undestroyed. Bacteria become less able to resist heat in presence of small quantities of acid. They are made more resistent by alkalies. For the effect of light on their development see ENGELMANN, Rev. internal. Sci. biol. 1882. 191. Influence on the nutrient liquid. In the first place the bacteria, as they grow and multiply, withdraw from the nutrient liquid the elements they require for building up their cells. These elements are chiefly nitrogen, carbon, hydrogen, and oxygen, as also the mineral constituents mentioned in Art. 188. In the next place they set up marked chemical changes in the nutrient liquid. It is bacteria which superinduce putrid decomposition in albuminoid bodies; they transform sugar into lactic acid (as in soured milk) ; lactic acid into butyric acid (as when sourkrout ferments, or butter becomes rancid) ; sugar into a gum-like slime (as in ' slimy ' or ' long ' wine) ; and alcohol into acetic add. Large quantities of material may in this way be very rapidly transformed. When albuminoids undergo putrid decomposition, we have formed peptones and similar bodies ; a certain putrid principle or poison (PANUM), and bodies resembling ferments; sepsin (BERGMANN and SCHMIEDEBERG) ; nitrogenous bases, like leucin and tyrosin; amines like methylamine, ethylamine, propylamine; fatty acids, like formic acid, acetic acid, propionic acid, butyric acid, valerianic acid, palmitic and stearic acids, lactic acid, succinic acid, &c. ; aromatic matters, indol, phenol, cressol, pyrocatechin, hydroquiuone, hydroparacuminic acid, and paroxyphenylacetic acid (VON NENCKI, SALKOWSKI, BRIEGER); and lastly sulphuretted hydrogen, ammonia, carbonic anhydride, and water. These pro- ducts are the result partly of hydration, partly of reduction, and partly of oxidation. The immediate cause of the process is unknown. NAEGELI (Die niederen Pilze 1877), PASTEUR, LISTER, and others regard the decomposition as the direct result of the vegetation of the bacteria. Decomposition and fungus are inseparable : the one ceases when the other is removed. Processes of this nature, set up by bacteria, are best distinguished as fermentations. Considered with respect to their property of setting up fermen- tation, bacteria are often described as 'formed' or 'organised' ferments. Bacteria have also the power of setting free certain substances which have a decomposing action like themselves, but are capable of separation from them, and are known as ' unor- M. 18 274 PARASITES. [SECT. vii. ganised' ferments. Such unorganised ferments can, for instance, change lactose into fermentable sugar, transform starch and cellulose into grape sugar, and render soluble coagulated albumen and other insoluble albuminoids. In consequence of such changes milk may undergo alcoholic fermentation, wood may become soft and rotten, damp bread turn sour, and insoluble albuminous matters be transformed into a putrid ammoniacal slime. Under the influence of bacteria are also developed certain bitter, acrid, and nauseous products of whose composition nothing is known (as when milk turns bitter). Now and again colouring matters are produced by them, red, yellow, green, blue, and violet. So bread may become covered with a blood-red film of Micrococcus prodigiosus ('bleeding' bread). Bandages and pus in wounds become blue from the presence of Micrococcus cyaneus. Boiled eggs exposed to moist air are often quickly covered over with a yellow film of Micrococcus luteus. The hypotheses proposed to explain fermentation, especially the alcoholic fermentation, have been very various. Some of them attempt to connect the process intimately with the vital activity of the cells which give rise to it ; others seek to separate them. LIEBIG describes the process as a molecular motion transmitted by matter (the unformed ferment) already in a state of chemical motion (i.e. in the act of decomposing) to other matters composed of elements in loose combination. HOPPE-SEYLER and TRAUBE (Pfliiger's Arch, xii, 1875, and Physioloaisc/ie Chemie) imagine that the cells secrete certain unformed ferments, which produce decomposition by mere contact (or catalytically), without themselves taking part in the chemical changes they set up. PASTEUR (Annal. de Chimie et de Phys. 58, 64 ; Comptes Rendus, 45, 46, 47, 56, 80 ; Studies on Fermentation London 1879 ; DUCLAUX'S Ferments et Maladies Paris 1882) regards fermentation as immediately dependent on the activity of the living cells. Fermentation begins only when the supply of free oxygen to the cells is restricted. They then begin to abstract oxygen from the compounds contained in the nutrient liquid, and so disturb their molecular equilibrium. NAGELI'S physical (or molecular) theory (Abhand. d. bayr. Akad. math.- physic. Cl. xin p. 76, 1879) supposes that the natural motions of the molecules and atoms of the various constituents of the living cell-protoplasm are transmitted mechanically to the fermenting matter. The protoplasmic constituents remain chemically unchanged, but the molecular equilibrium of the fermenting matter is disturbed, and disintegration results. NAGELI'S theory emphasises strongly the dependence of the fermentive process on the life of the cells, and is thus in harmony with our general view that all vital processes are ultimately cellular. The power of exciting fermentive decomposition in nutrient liquids is very probably possessed not merely by bacteria and yeast-cells but also by the cells of higher organisms, as of man. VOIT (Physiologie des Stoffwech- sels Leipzig 1881) refers the disintegration of the soluble albumen circulating through the system to fermentive action of the tissue-cells. PASTEUR has shown that in proper conditions fruits and leaves may exhibit fermentive properties. The chemical changes occurring in the putrid decomposition of the albuminoids have been studied by NENCKI, SALKOWSKI, BRIEGER, and HILLER. See HILLER, Die Lehre von der Faulniss Berlin 1879 ; NENCKI, Zersetzung der Gelatine und des Eiweisses bei der Faulniss mit Pancreas CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 275 Berne 1874, and articles in the Journ. fur prakt. Chemie, Joum. fur physiol. Chemie, and Bericht. d. deutsch. chemisch. Gesell. 1876 82 ; SALKOWSKI, articles in the Bericht. d. d. chem. Ges. and Zeitsch. f. physiol. Chem. of the last year or two ; BRIEGER, Zeitsch. f. physiol. Chem. n, in, iv, and Zeitsch. f. klin. Ned. in; GAUTIER and ETARD, Comptes Eendus 1882. The quantity of oxygen present has an important influence on the products formed in bacterial decomposition. PASTEUR asserts that fungi which grow in presence of oxygen set up chiefly oxidative changes. Those which can multiply in the absence of oxygen give rise to non-oxidative decompositions. HOPPE-SEYLER (Ueb. d. Einfluss des Samrstoffes auf Giihrungen Strasburg 1881) supports this view by his observation that when oxygen is abundantly supplied to the yeast-plant the disintegration of sugar into alcohol and carbonic anhydride is retarded, and volatile acid bodies are produced in abundance. If bacteria in an albuminous liquid be well supplied with oxygen, products like indol, hydroparacuminic acid, and sulphuretted hydrogen (which are largely formed when oxygen is wanting), entirely disappear. The oxygen oxidises them as they are produced ; the primary products of the fermentation at once undergo further change. On pigment-producing bacteria see COHX and SCHROETER, Beitrdge z. Biol. d. Pflanzen vol. I. 192. Fermentation and putrefaction can only take place in the presence of the corresponding fungi, and the amount of decomposition produced depends on the quantity of fungi present. It does net however follow that each kind of decomposition is due to a single specific fungus, nor that one fungus may not give rise to more than one kind of decomposition. We cannot as yet define Avith certainty the kinds of decomposition which correspond to each species of fungus. We know however that ordinary putrid decomposition occurs under the action of Bacterium termo ; while COHX asserts that micrococci do not give rise to putrid change, but to changes of another kind. The butyric fermentation is said to be chiefly due to the presence of Clostridium butyricum. Anthrax- bacilli generate ammonia in the nutrient liquid. In most putrefying substances we find bacteria of several species. NAEGELI affirms that it is possible by cultivation so to alter the properties of a bacterium that it no longer has the power to produce the changes originally associated with it; while it assumes the power of calling forth fermentations of a different kind. Thus the bacterium which produces the lactic acid fermentation may, he says, be cultivated in saccharated extract of meat in such a way that at first it produces in milk an ammoniacal decomposition only ; and it does not resume its power of generating lactic acid until after several generations. If this be so we may perhaps infer that within certain limits the physiological properties of a bacterium may be transmuted : or at least that, by change of condition, one or other of several potential functions may be called into activity. The facts have not however been sufficiently confirmed. We have said that fermentation and putrefaction are always due to fungi ; but we do not thereby deny that other kinds of decomposition may affect organic substances in which fungi play no part. Such changes do in fact occur. They usually take the form of slow oxidation or combustion, in 182 276 PARASITES. [SECT. vn. which carbonic anhydride, water, and (in nitrogenous substances) ammonia, are formed. Such slow changes are set up when organic matters are in contact with water and atmospheric air. They also of course occur in the living organism. In dead organic matters the process corresponds in part to what is called ' dry rotting ' or ' mouldering '. BRIEGER (Zeitsch. f. klin. MedC\\i) thinks that the various aromatic products of the putrefaction of albumen are equally well obtained whether it is set up by the addition of sewer-mud or of pancreas. The essential factors are the duration of the putrefactive process, the temperature, and the amount of oxygen present. The albuminoids undergo the same changes in the intestine as they do in artificial putrefaction brought about outside the body. The same series of changes are also set up in putrid pleurisy and bronchitis, and in pulmonary gangrene. 193. Bacteria without and within the body. If the facts already cited be duly considered, it will appear very probable a priori that the diffusion of the bacteria is enormously wide. Matters on which they can grow and thrive are found almost everywhere. We might especially expect to find them wherever dead organic substances occur, either in solution or at least associated with a certain amount of water. This expectation is fully confirmed by experience. Bacteria are found in all waters whether flowing or stagnant, in all liquids that can ferment or putrefy, and in all vegetable and animal tissues that are sufficiently moist. KOCH'S researches have shown that the surface soil or mould is extraordinarily rich in bacterial germs. It is surprising to learn that these are chiefly the germs of bacilli ; but micrococci are also found. In soils soaked with midden-runnings the micrococci are more numerous than the bacilli. If the soil become very dry, the micrococci disappear while the bacilli persist. This is due to the fact that the resting-spores of bacilli are very tenacious of life. The micro-organisms present diminish rapidly as we go deeper. At the depth of a metre they seem entirely absent. Spring- water coming from a depth contains hardly any. But we have by no means exhausted the field of their dis- tribution. When liquids containing fungi are violently shaken or broken into spray, the fungi pass into the air. This happens also when such a liquid dries up, or when a solid nutritive substance is broken up or disintegrates. If in the latter cases no substances are present which agglutinate the bacteria into a compact mass, they may pass into the air in immense numbers. Owing to their extreme smallness and lightness (NAEGELI estimates the weight of small moist bacteria at one ten thousand millionth (1CT 10 ) of a milligramme) they are carried about by the faintest breath of air. In this way they must of course very often reach and rest on bodies which can offer them no nutriment. But they must also often fall on a fit soil, and then proceed to grow and multiply afresh. Circum- stances in general are in fact so favourable to the bacteria that we find them or their germs almost everywhere ; but chiefly where the presence of organic matters, moisture, and warmth go to favour their multiplication. CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 277 NAGELI (Die niederen Pilze Munich 1877) asserts that fungi can only pass into the air when their nutrient liquids dry up. SOYKA (Munch, acad. Sitzungsber., math.-phys. Cl. 1871) has shown that bacteria may be swept out of liquids that contain them by gentle air-currents. BUCHNER (Ueb. d. Beding. d. Ueberganges von Pilzen in d. Luft u. iib. d. Einathmung derselben, Zur Aetiol. d. Infectionskrankh. Munich 1881) disputes SOYKA'S conclusions. He maintains that even strong currents of air are insufficient to sweep bacteria from a liquid : and that even in the case of dried-up masses containing fungi, the fungi are not set free unless the surface is actually broken. ZIEGLER agrees rather with BUCHNER'S view. NAGELI further thinks that very slight upward air-currents are enough to prevent floating bacteria from settling down. The condensed watery vapour that surrounds them tends to maintain their buoyancy. Friction also retards their fall. See SOYKA, Ueb. Canalgase als Verbreiter epidem. Krankh. and Ueb. Richtung und Stdrke d. Luftzuges in Sielen, Deutsche Viertelj. f. offent Oesundh. xiv, 1882 ; and Ueb. d. Natur und d. Verbreitung d. Infec- tionserreger, Zur Aetiol. d. Infectionskrankh. Munich 1881 ; NAGELI, Untersuch. iib. nied. Pilze. Munich 1882. WERNICH (Cohn's Beit. z. Biol. d. Pflanzen m) has shown that air-currents may sweep off bacteria from moist fungus-masses adhering to the surface of solid bodies. Researches on the bacteria and bacterial germs found in the air have been published by COHN (loc. cit.), MIQUEL (Des bacte'ries atmospheriqiies, Gaz. me'd. de Paris 30, 1880), WERNICH ( Virch. Arch. vol. 79), TYNDALL (Floating-matter of the air London 1881) ; CUNNINGHAM (Microscopic exam, of air Calcutta 1874) gives an excellent summary of previous observa- tions. On bacteria and their germs in the soil, see KOCH (loc. cit.), and CECI (Arch. f. e%p. Path. xv). 194. Consideration of the wide-spread occurrence of the bacteria and their peculiar vital properties will already have raised the question whether these micro-organisms may not have the power of exciting more or less grave disturbances in the human system, provided they obtain an entrance into it. We have seen that almost all fluids contain bacteria or their germs, unless they are actually poisonous or are 'sterilised' by appropriate means, such as by boiling. Micro-organisms are also frequently found in solid organic matters. In view of this it would seem that we cannot avoid swallowing numbers of bacteria with our food. Moreover we frequently eat articles which are in a state of partial putridity or fermentation (such as cheese and milk) : in this state they of course contain numerous bacteria. The alimentary tract must thus be reached by enormous multitudes of bacteria together with the products of decomposition which they set up. This is however by no means the only way in which we come into intimate relation with these organisms. The air always contains a greater or lesser number of them. In breathing we draw them into the lungs, and they settle in the bronchi or alveoli. Lastly, all parts exposed to the air come into contact with bacteria, the unwounded skin as well as the wounded or abraded skin. What becomes of all these organisms ? The greater number undoubtedly pass out of the body again. It is hardly possible that 278 PARASITES. [SECT. vn. any can penetrate into the deeper tissues through the uninjured skin. Those which settle on the mucous membranes are certainly for the most part not absorbed, but are thrown off after a longer or shorter time. This is however not always the case. Experience shows that, in special circumstances, bacterial invasion of the system may actually start from the mucous membrane. What is the exception in the case of mucous membranes is the rule in the case of matters inhaled into the lungs. Experiment shows that fine corpuscular or particulate matters are very quickly taken up by the lymphatic capillaries of the lungs, and are so carried into the lymphatic glands, or it may be into the blood. Wounded surfaces are in like manner quick to absorb such corpus- cular bodies. Resuming what we have said, we may put it generally that bacteria of various forms may reach not only the surfaces of the body which are directly accessible from without, but also at times the deeper structures, if circumstances favour their penetration. The question whether bacteria occur in the healthy body seems easily answered from such general considerations, though it is one which has been much disputed. Bacteria are perpetually entering the body with the food we eat and the air we breathe. They must therefore be at times found in the tissues, especially in places where access is direct. The fact that they are not easy to demonstrate is readily explained. It must be only a small number that can multiply in the tissues they have penetrated ; the majority must quickly perish. See NENCKI, Journ. f. prakt. Chemie 1879 ; WEISSGERBER and PERLS, Arch. f. exp. Path, vi ; KOSENBACH, Deutsche Zeitsch. f. Chir. xm ; LEUBE, Zeiisch. f. klin. Med. in ; STERNBERG, Stud. Biol. Lab. Baltimore 1881; LISTER, Trans. Boy. Soc. Edin. 1875. LEUBE, LISTER, ROBERTS, and others have been unable to find living bacteria in healthy urine. This would indicate that the greater part of the bacteria which penetrate into the body are destroyed. 195. If the bacteria were inert corpuscular elements incapable of multiplication, we should have little more to say concerning their significance to the human organism. We should merely have to point out that they are in part taken into the body at certain points, are carried about hither or thither within it, are deposited here or there as innocuous substances, and sooner or later are destroyed or cast out again through the liver, kidney, or other secreting organ. As a fact this is what really happens with regard to some of the bacteria. Even when they pass through the bronchial glands from the lungs into the blood, they have no more significance than any other like minute foreign matters, such as occasionally circulate in the blood without causing disturbance. These are simply deposited and destroyed, or excreted. Thus the Micrococcus luteus may be introduced in considerable quantity beneath the skin of a rabbit, without inducing any serious affection either of the tissue or of the system generally. The bacteria which are thus innocuous may easily be indicated from previous considera- tions. They are such as cannot find within the human body the conditions favourable to their development. CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 279 This is unfortunately not the case with all bacteria. There are some which find their appropriate soil in the perfectly healthy organism, and in it they grow and multiply. Others are unable to settle in a perfectly healthy body ; they can only develope when the physico-chemical constitution of the tissues is morbidly altered so as to correspond with their requirements. The forms of bacteria that have the power of gravely affecting the system, whether it be healthy or diseased, are described as pathogenous bacteria. It is manifest from the above that the determination of the vital properties and conditions of the different bacteria is a matter of the greatest importance. This knowledge would enable us to combat earlier the development of bacterial disease, and the injury it produces. It would further give us the necessary hints for preventing its invasion ; for we should know where to seek the bacteria and how to destroy them or render them harmless. Our knowledge in this respect is unfortunately still defective. There are but few species of bacteria whose life-history we know with any exactness of detail. 196. The factors which determine the invasion and the course of development of bacteria within the human body are two. On the one hand the bacteria must be endowed with certain vital properties of a special kind : on the other hand there must be a predisposition on the part of the system. Our present knowledge does not yet allow us to specify accurately the properties which an infective bacterium must possess. We can only say in general that it must find within the body and in proper combination all the conditions necessary for its growth and multiplication. Thus the temperature of the body must be such as favours its development ; it must be able to abstract fit nutriment from the tissues in which it settles; it must nowhere encounter substances which check or injure it. Investigations into the bacterial affections have shown that very slight chemical changes in the constitution of a tissue are often enough to determine whether a given bacterium can develope in the tissue or not. In other words the significance of this factor of predisposition is greater than it may have appeared at first sight. Now and then of course the predisposition is due to very obvious alterations in the tissues. For instance, we find that many cases of bacterial invasion depend on the formation of a local necrosis or wound, in which the fungus can settle and develope. In other cases some grave, disturbance of the circulation may lead to a failure of resistance on the part of the tissue. These instances are however matched by others in which the anatomical basis of the predisposition is beyond our power to discover. We know, for example, absolutely no reason why of two individuals exposed to the infection of measles, scarlatina, small-pox, typhus, or tuber- culosis the one should be taken with the disease and the other left. The factors which decide the matter in such cases are plainly 280 PARASITES. [SECT. vn. such as at present escape our notice, either from their apparent slightness, or because they are not such as our tests can discover. Yet they doubtless consist in very real and very special differences in the condition of the tissues. Many of the bacteria can only come to development within the human body on rare occasions, as their usual habitat is without it. Others only meet with fit conditions for their existence and growth within the body, and do not multiply at all without it. The respective parts played by the inherent properties of the bacterium and the predisposition of the tissues to invasion have been illustrated by many observations both clinical and experimental. If a mass of bacteria of different forms be introduced into an animal's body, some of the forms develope and lead to certain tissue-changes, others perish inert. If a similar mass be injected into an animal of a different kind, the bacteria which develope are not the same as in the first instance. KOCH (Aetiologie der Wundinfectionskrankheiten Leipzig 1878, Traumatic Infective Diseases London 1880) has shown that there is a fungus which brings certain death to one species of mouse, while it is entirely inactive when introduced into another species of mouse. Mice are highly susceptible to the infection of anthrax; rats enjoy an almost perfect immunity. The poison of 'rabbit- septicaemia ' kills rabbits and mice with unfailing certainty ; guinea-pigs and rats are unaffected by it; sparrows and pigeons again are highly susceptible. The spirillum of human relapsing fever will develope only in monkeys among the lower animals. Animals of the same species but differing in age have different degrees of susceptibility. Young dogs are easily infected with anthrax, old ones are not (Kocn). We cannot at all tell on what circumstances immunity of this kind can possibly rest. Similar examples are easily obtained (Arts. 204, 206). The majority of the infective disorders are in fact limited each to a few species of animals or to a single one. Differences also exist in respect of the diffusion of the bacteria through the body. The fungus, which in one kind of animal brings about a fatal general disease, may in others produce a merely local and non-fatal dis- turbance. Even the point of entrance of the bacteria into the body has its importance. A rabbit inoculated with bacteria in the back of the neck may die, while inoculation of the ear is followed by a simple local affection. ROSSBACH has quite recently announced (Centralb. f. med. Wiss. 5, 1882) that injection of papayotin into the vessels is followed by a rapid development of micrococci in the blood, so that in two hours the blood in the heart is found to be swarming with them. If this observation be confirmed, it would seem to show that the composition of the blood is so altered by the unorganised vegetable ferment that germs can proceed to develope in it which before were unable to do so. In other words, that the action of a chemical substance has called forth a special predisposition. ROSENBERGER (Centralb. f. med. Wiss. 4 and 41, 1882) observed a like result after the injection of sterilised septic blood. The animals died of septicaemia, bacteria being developed. If the injected liquid were really sterilised, we can only interpret the observation as showing that the septic matter so altered the blood and liquids of the animals as to make them predisposed for the development of micro-organisms. The experiments do not however seem quite free from objection. In 1869 SEMXER com- municated similar results, which he obtained with the use of sepsin prepared from yeast ( Viertelj. f. wiss. Veterin. xxxii). BOSER maintains that the most essential condition for the settlement of bacteria in the body is their adaptation to the quantum of mineral salts present in the blood and tissues. This can hardly be a sufficient condition. CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 281 197. The healthy organism is always beset with a multitude of non-pathogenous bacteria. They occupy the natural cavities accessible from without, and especially the alimentary canal. They feed on the substances lying in their neighbourhood, whether brought into the body or secreted by the tissues. In so doing they set up chemical changes in these substances. While the organs are acting normally, these fungi work no mischief to the tissues in which they lie, or to the system generally. The products of decomposition set up by such non- specific micro-organisms are either harmless, or are conveyed out of the body before they begin to be active. Settlements of this kind may however become of importance, if the bacteria proceed to develope to any unusual extent. This happens when the contents of the natural cavities in question remain unchanged for any great length of time, or when (as in catarrh) the normal secretion undergoes some alteration. The products of bacterial fermentation may then accumulate to an excessive amount, and products may also be formed which do not normally occur. Thus when the contents of the stomach are not passed on, and become as it were stagnant, an abnormally acid fermentation may be set up. If the chyme is retained over-long in the* small intestine, the aromatic products of albuminoid putrefaction will gather in excessive quantity. So too we may have decomposition in the stagnating secretions of the bronchi, prepuce, &c. All these changes react harmfully on the tissues and may set up inflammation, not unfrequently ending in suppuration and necrosis. Moreover the system in general may suffer by absorption into the blood of the soluble products of decomposition. The latter contingency is not to be lightly regarded. Though we may partake with impunity of many fermenting or decaying substances as food, we must not think that all the products generated by the non-pathogenous fungi are equally harmless. Highly poisonous substances are formed in many of the bacterial decompositions. One of the most speedily fatal of diseases, septicaemia, is due to poisoning of the system with the products of bacterial putrefaction, or sepsis. Cadaveric poison, the poison of decaying fish, sausage, cheese, mussels, &c. are very probably the chemical products of special forms of putrefaction. We unfortu- nately know but little, in some cases we know nothing, of the substances which have this poisonous character. BERGMANN and SCHMIEDEBERG have, it is true, prepared their so-called 'sepsin' and PANUM his ' putrid poison,' from decaying substances ; but we do not know the composition of these bodies, and they are certainly not the only poisons of the kind. Putrid or septic poison may be absorbed by wounds as well as by mucous surfaces. Septicaemia, which has just been cited as an instance of septic poisoning, is generally due to wound-infection. 282 PARASITES. [SECT. vn. It is due to the absorption of products of bacterial decomposition formed in a wound contaminated by bacteria (Art. 204). This is especially apt to happen when necrosed tissue exists in the wound, for this affords the bacteria a suitable soil for their development. The poisonous action of putrid matters is fully discussed by HILLER in Die Lehre von der Faulniss Berlin 1879. He gives full references to the literature of the subject. HILLER lays special stress on the fact that in the septic process it is not simply the bacteria themselves that do mischief, it is the products of their action which act so as profoundly to alter or even to destroy outright the tissues exposed to them. If the infection become generalised, it is almost always due to intoxication of the system with unorganised chemical substances. PANUM'S paper just alluded to is in Virch. Arch. vol. 60 ; BERGMANN'S is a work called Das putride Gift und die putride Intoxication Dorpat 1866. WOLFF (Virch. Arch. vol. 81) has lately taken up the question. On the absorption of putrid matters by the alimentary canal see SALKOWSKI Centralb. f. med. Wiss. 46, 1876, and Berichte d. chem. "Oesells. x, 1877 ; NENCKI and BRIEGER, ibidem ; BRIEGER, Zeitsch. f. phys. Chem. n, Zeitsch. f. klin. Med. ill ; BOLLINGER, Ueber Fleischvergiftung, intestinale Sepsis, und Abdominal-typhus, Zur Aetiol. d. Infection. Munich 1881. It is possible that harmless colonies of bacteria may become dangerous if they are removed from their normal seat to other regions. Thus the saliva, when it contains bacteria, may excite violent inflammation if it reaches the bronchi or alveoli of the lungs. 198. Pathogenous bacteria have the power of settling, not merely in the ingesta and secretions or in dead tissue, but also in living tissue. This happens chiefly in the mucous membranes and in the lungs. The uninjured skin is protected against invasion by the horny epidermis. Many of the bacteria can settle in perfectly healthy mucous membranes. In the case of others we must imagine that they do not find a proper soil for their development, unless the mucous membrane is injured or altered. Of course injury or alteration of this kind may serve to make the outer skin, or any other accessible tissue, the starting-point of a bacterial invasion (wound-infection). All that is necessary is that a bacterium should reach a spot that affords the conditions for its development. If this occur, it multiplies and forms colonies or swarms. These may, according to the species of the fungus and the nature of its soil, remain in aggregation forming heaps or masses, or may spread through the tissues. Such a settlement is never without effect on the affected tissues. The bacteria may force their way into the substance of the constituent elements, and especially into the tissue-cells, which are sometimes found to be crammed with bacteria. The effect of the invasion is not always at once apparent, even under the microscope. The cells attacked by the fungi often appear quite uninjured : in other instances they are seen to be altered. The epithelial cells swell up (Fig. 76 c) and liquefy, or degenerate into flaky homogeneous lumps, or turbid denucleated masses. Often they break down into granular detritus. The CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 283 nucleus is broken up, or swells and disappears (Fig. 76 c). The fibrous elements of the connective tissue degenerate like the epithelial cells. The ground-substance alters at the same time. It becomes turbid, loses its structure, and ultimately dissolves. FIG. 78. SECTION CONTAINING COLONIES OF MICBOCOCCI FROM THE VOCAL COBD OF A CHILD. ( X 200) a epithelium d layer of micrococci b connective tissue of the mucous e inflammatory small-celled infiltration membrane of the degenerated epithelium and c swollen degenerated and denude- of the fibrous structures ated epithelial cells In general terms we may say that local settlements of bacteria will sooner or later bring about degeneration and necrosis of the affected tissue. When this may occur, and how widely it may spread, are circumstances depending on the nature of the bacteria and of the tissue. The processes we have considered are not without their influence on the circulation. The direct action of the bacteria, and the influence of the chemical changes they set up, tell at length on the vessel-walls within the affected region. The result is to disturb the circulation in various ways, chiefly in the way of inflammatory exudation and haemorrhage. In some instances the circulation is stopped altogether, and the preservation of the affected tissue is then impossible. The inflammatory process set up by bacterial action (Fig. 76 e) may be of very different intensity and extent in different cases. It may be slight and transient, or it may be severe and issue in suppuration and necrosis. Not unfrequently a more or less perfect granulation-tissue is formed as a result of the inflammation, as in tuberculosis. The extravasated cells often take up the bacteria into their substance. 284 PARASITES. [SECT. vii. 199. The inflammation excited by the presence of bacteria often results in a great aggregation of living cells in the tissue affected. These may so act as to repel the continued advance of the fungi, which straightway perish, and the affection issues in healing and cicatrisation. The fixed tissue-cells of the region may likewise act so as to check the development of the bacteria, and may further suffice to make up any loss of tissue by their regenerative activity. If this does not happen the bacterial invasion continues to advance. The bacteria spread first into the surrounding tissues, passing along the natural lines of division. Then they break into the lymphatics, and often into the blood-vessels also. If they can live in lymph or blood they go on multiplying ; if not they perish. Many bacteria, like the micrococcus of erysipelas, flourish best in the lymphatics. Others, like the anthrax-bacillus, are more at home in the blood. The extent to which the bacteria can spread within the lymphatic system is subject to no general rule. Many of them make a halt at the first gland they come to. Others pass beyond, and finally reach the blood-vessels by way of the thoracic duct. Their path is generally marked by degenerative and necrotic changes, and by the inflammatory reaction they excite. The degree and amount of these changes are determined partly by the nature of the bacteria, partly by their number. They reach the blood either through the lymphatics or directly. In the latter case the walls of the veins in the invaded region are penetrated by the fungi, or they pass into the veins from the capillaries. Once in the current they are carried on by it to remote parts. Many of them perish in the blood, others again increase and multiply. Of the last some (anthrax-bacillus) thrive best in blood that is flowing; others (tubercle-bacillus, pyaemic micrococcus) prefer blood that is at rest, that is to say, they only Fig. 77. Fig. 78. FIG. 77. MICROCOCCUS SEPTICUS IN HEPATIC CAPILLARIES : NECROSIS OF THE LIVER-CELLS. ( X 350) FlG. 78. BACILLUS ASTHRACIS: LIVER-CELLS UNAFFECTED. ( X 350) CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 285 grow when they have come to a standstill in some venule or capillary. It depends on the properties of the fungus, which of these events takes place; just as do the changes it calls forth in the course of its multiplication. - Fig. 79. FIG. 79. HEPATIC ABSCESS : FIRST STAGE. (Bismark-brown staining : x 40) e aggregation of small round-cells in a a normal lobules b necrosed lobules c capillaries filled with micrococci d small-celled infiltration of the peri- portal tissue vein, into which opens an intra- lobular venule crammed with micro- cocci The tissue-changes are the slightest in the case of bacteria which circulate and multiply in the blood (Fig. 78). Bacteria which settle in the smaller vessels give rise on the other hand to degenerations, necroses (Fig. 77 and Fig. 79 e), inflammations (Fig. 79 d e), and haemorrhages. The spot where a lodgement takes place is mostly matter of chance ; but it is to be noted that a bacterium may not be able to 286 PARASITES. [SECT. vn. settle in every spot indifferently. One part of the vascular system may be more favourable to it than another. Many bacteria remain and multiply within the vessels. Others escape from them, and when the surrounding tissue is suitable they may multiply in it, and set up changes resembling those produced at the point of first invasion (as in tuberculosis). References: FRISCH, Exp. Studien iiber d. Verbreitung der Fdulnissorganis- men in d. Geweben Erlangen 1874; KOCH, Traumatic Infective Diseases (Syd. Soc.) London 1880 ; PERLS, Lehrb. d. allg. Path. n. We should mention with regard to the spread of bacterial infection within the system, that the mode of invasion and the number of the fungi present are points of importance. If mice or guinea-pigs be inoculated beneath the skin with a few oedema-bacilli, the resulting affection is merely local. If the bacilli be numerous the animals die of a general disorder. The bacilli of anthrax and those of 'rabbit-septicaemia' may be injected in small quantity into the ear of a rabbit without causing its death. In the quantity ordinarily used in inoculative experiments they are always fatal. 200. The facts just given (Arts. 198, 199) regarding the spread of bacterial infection within the system are derived from observations on pyaemia, erysipelas, anthrax, and tuberculosis. The greater number of the diseases now referred by many to the action of bacteria (such as typhoid, relapsing fever, diphtheria, the exanthe- mata, croupous pneumonia, acute atrophy of the liver, cholera, etc.) are as yet too little known to enable us to give the corresponding details for them. We do not exactly know how the poison finds entrance, where it is multiplied, and in what manner it spreads. We only know that in these affections we find at certain times in the blood or tissues definite bacterial forms ; and we believe that they are the exciting cause of the disease. If this belief be correct, we must admit that many kinds of bacteria have the power to penetrate into the blood and other juices without leaving any traces at the point of entrance. This supposition is confirmed by the fact that in anthrax we are often unable to detect the point of entrance of the bacilli. In the case of these diseases we must likewise assume, as in the case of the others, that the bacteria find access through the mucous membranes or lungs, or through open wounds if any exist. Once the bacteria have entered the body they multiply in the blood or in some tissue, spread through the system, and call forth the special changes characterising the several diseases. It is worthy of remark that each poison has a corre- sponding special group of tissues, in which its mischievous effects are invariably and especially apparent. The anatomical changes produced in these diseases as in the others are of the nature partly of degeneration and necrosis, partly of inflammation or haemorrhage. Proliferous changes in the tissues may also ensue as secondary to the former. 201. We are not yet in a position to formulate a theory of bacterial action that will apply to all cases. The researches of CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 287 the last year or two have however enabled us to form some picture at least of the way in which bacteria affect the several tissues and the system in general. The pathogenous bacteria are parasites which draw their nourishment from man's body. They withdraw this nourishment only from the tissues among which they are growing and multi- plying. The effect of this withdrawal is in general not very grave. It can only become dangerous to life, when the bacteria multiply within the circulating blood and withdraw from it the indispen- sable oxygen it contains. The withdrawal of nutriment is not however the only result ; it is seldom even the most important. Investigations show that the vital activity of the bacteria of necessity sets up extensive chemical change in their own nutrient materials. These changes are partly due to their direct action (Art. 191), partly to the action of the unorganised ferments which they form. Lastly, in the course of these changes matters are produced which act as poisons upon the system. This effect of the bacteria on their nutrient fluids, and the production of poisonous matters, have much more to do with the genesis of the symptoms in most of the microparasitic affections, than has the mere with- drawal of nutriment. The influence of such factors is manifested in disturbances of the functional, formative, and nutritive activities of the organism. These activities are the expression of the cell-life of the tissues ; hence the statement that bacteria disturb the vital actions of the tissue-cells. In Art. 81 we compared the life-history of the tissue- cells with that of the bacteria. We may not inopportunely refer to the comparison once more in this place. The nutritive activity of the tissue-cells is not confined to the replacement of used material by the absorption and assimilation of new material. Like the bacteria the tissue-cells act catalytically on their surroundings, partly by fermentive action (Art. 191), partly by the formation of unorganised ferments. Many cells have in addition the power of setting up synthetic processes. When bacteria proceed to multiply within a tissue, a double influence is brought to bear on the common nutrient medium ; the bacteria enter into conflict with the tissue-cells. We do not of course know in what exact way this conflict is carried on. But we may believe that the bacteria do not communicate to the organic compounds contained in the juices the same kinds of chemical motion as the tissue-cells. They will not therefore give rise to the same chemical changes as the latter. More or less serious disturb- ance of 'the normal metabolism of the tissues must ensue. This is the first effect, but not the only one. Different kinds of fermentation cannot go on in presence of each other for any length of time. One is more and more repressed, and at length suppressed, as the other advances. This cannot of course happen without simultaneous injury to the corresponding ferment. Thus 288 PARASITES. [SECT. vn. the prolonged presence of bacteria results in the suppression not alone of the nutritive activity, but also of the other functions of the tissue-cells ; and at length their life itself is enfeebled or extinguished. The products of the decomposition set up by the bacteria, the unorganised ferments and other poisons, also give rise to changes in the tissue-cells. It is possible that in many cases they only tend to modify the nutritive activity, i.e. the metabolism of the cells ; but the other functions are doubtless often affected likewise. These modifications of the normal cell-life in their totality are manifested as disturbances of the functions of the organism, and we speak of them as symptoms of disease. The mode in which the several symptoms are produced we cannot here stop to discuss. All we need say is that a disturbance of cellular activity is always at the bottom of a morbid symptom : mere alteration in an organic fluid is not enough to give rise to symptoms. Thus the origin of fever cannot be explained otherwise than by assuming the existence of some cellular disturbance. The chief factor in producing the elevation of temperature may be a change in the fermentive action of the cells, or it may be a dis- turbance of the functions of the central nervous system. That is a question which is open to discussion ; but it does not touch the question of the cellular nature of the febrile process. Inflammation itself is only to be explained by cellular change. In bacterial affections, inflammation appears as a specially benefi- cent process. By it a number of living cells are thrown out at the seat of danger, and they are the readiest instruments for checking the harmful influence of the fungi. The issue of a bacterial affection is either the death of the patient, or the death and elimination of the bacteria. In the former case the bacteria interfere with the functions of cells so numerous or so essential to life, that life becomes impossible. In the latter case the tissue-cells gain the upper hand in the struggle for nourishment and existence, and the bacteria are at length deprived of the conditions essential to their continued life. Observations on the infective diseases of man and on experi- mentally-produced bacterial diseases in animals have shown that a disease of the kind successfully withstood leaves the tissues in a peculiarly unsusceptible condition. This condition may endure for months or years, and it ensures an immunity almost or quite complete against a fresh invasion of the same or kindred bacteria. We do not know whether this singular effect is due to a modifica- tion in the chemical constitution of the tissues, or to a change in the vital activity of the cells. References: VOIT, Physiologic des Stofwecksels Leipzig 1881 ; NAGELI, Die niederen Pilze Munich 1877, and 1882 ; BUCHNEK, Die Ndgeli'sche Tkeorie der Infectionskrankheiten Leipzig 1878 ; KLEBS, Article Ansteckende Krankheiten, Realencylopadie der gesammten Heilkunde von Eulenburg, CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 289 and Cettular-Pathologie und Infectionskrankheiteri, Tageblatt der Natur- forscherversammlung in Kassel 1878 ; VIRCHOW, Krankheitswesen und Krank- heitsursachen, Virch. Arch. vol. 79 ; HILLER, Die Lehre von der Faulniss Berlin 1879 ; WERNICH, Die Entwickelung der organisirten Krankheitsgi/te Berlin 1880; KOCH, Untersuchungen iiber Wundinfectionskrankheiten Leipzig 1878, Traumatic Infective Diseases London 1880 ; WOLFF, Zur Bacterienlehre bet accidentellen Wundkranklieiten, Virch. Arch. vol. 81 ; TOUSSAINT, Comptes Rendus nos. 2 and 5, vol. 91 ; CHAUVEAU, ibidem, no. 16 ; DUCLAUX, Ferments et Maladies Paris 1882 ; BRIEGER, Einige Beziehunge-n der Faulnissproducte zu Krankheiten, Zeitsch. f. klin. Med. in ; BUCHNER, Ueber d. Wirkung d. Spaltpilze im lebend. Korper, Zur Aetiol. d. Infectionskr. Munich 1881 ; CHEYNE, Antiseptic Surgery London 1882 ; Discussion, Trans. International Med. Congr. vol. I, 1881. Of late years many experimenters have sought to furnish an experimental basis for the doctrine that individuals who have passed through an infective disorder are 'protected' against the same or a kindred disorder (as in the case of vaccinia and variola). They have attempted to make out that this holds for bacterial disease artificially communicated to animals. PASTEUR was the first to make communications on this head (Gaz. med. de Paris no. 18, 1880). TOUSSAINT refers the so-called fowl-cholera to the action of a certain micrococcus. Fowls die when inoculated with the bacteria culti- vated in chicken-broth. If the poison be attenuated by letting it stay in the culture-liquid exposed to the air for eight or ten months, it is no longer fatal on inoculation : but the fowls become by one or more inoculations ' protected ' against the unattenuated poison. PASTEUR further discovered that the ac- tivity Qf the anthrax-bacillus may be diminished by cultivation at a tempera- ture NEISSER have lately succeeded in CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 207 demonstrating the presence of a bacillus (B. leprae) in the nodes and tubercles of leprosy. The constancy with which it occurs in leprous patches would indicate that it is the exciting cause of the disease (Art. 131). KLEBS and TOMMASI-CRUDELI have likewise found a bacil- lus (B. malariae ) in cases of malarious or intermittent fever, and have experimentally investigated its properties. They assert that it is to be met with in the soil and air of malarious districts, and can be demonstrated in the blood of affected patients. The significance of the bacillus has not however been fully made out. In cases of typhoid fever KLEBS and EBERTH have discovered a bacillus lodging in recent infiltrations of the mesenteric and intestinal glands. KOCH and FRIEDLAENDER have verified the discovery, but the life-history of the bacillus is as yet unknown. KOCH has recently made comprehensive researches into the aetiology of tuberculosis. He finds that bacilli (B. tuberculosis) are constantly present, not merely in tubercles, but in various diffuse inflammatory infiltrations and granulomatous growths, and in the sputa of phthisical patients (Fig. 80). He is also able to FlG. 80. BACILLUS TUBERCULOSIS IN PHTHISICAL SPUTUM. (Stained by GIBBE&S method with magenta and methylene-blue : the pus-cells appear blue, the bacilli crimson : x 800 circa) cultivate the bacilli in gelatine impregnated with blood-serum, and to produce tuberculosis with striking success by inoculation with the cultivated bacilli (Art. 127). It is probable that the bacillus is unable to develope outside the animal body ; and that it forms spores within the body of its host (Art. 127). (1) Anthrax (splenic fever, malignant pustule, c/iarbon). TheBacttlut anthrads was first discovered by POLLENDER in 1849 (Casper's Yiertelj. vm, 1855). and BRAUELL (Virch. Arch. vol. 11, 1857). DAVAINE was the first to recognise it as the specific virus of splenic fever (Comptes Rendus vols. 57 (1863) and 77 (1873) ; Archiv. ffe'n. Feb. 1868). Since then many 298 PARASITES. [SECT. vn. investigators have examined the question of the significance of the bacillus (see BOLLINGER, Splenic Fever, Ziemssen's Cyclopaedia vol. .m). KOCH has made the most careful researches on the subject (Beitriige z. Biol. d. Pftanzen von Cohn n, p. 277, and Mitth. a. d. k. Gesund/i. Berlin 1881), and his experiments have thrown much light on the biology of the bacillus. TOUSSAINT also has lately published some elaborate researches (Recherches expe'rimentalcs sur la maladie charbonneuse Paris 1879). SPEAR and GREENFIELD have investi- gated anthrax in man as it occurs in the form of ' \Voolsorters' disease ' ( Med. Off. Report to Local Gov. Board for 1880). The life-history of the anthrax-bacillus has already been given in Art. 186. It can only develope at a temperature over 18C and in presence of a free supply of oxygen. Hence no spores are found in the bodies of animals buried more than a metre deep. Spores may however very readily be produced, if in burying the animal its blood or secretions (such as urine) be allowed to contaminate the superficial soil : in summer the temperature there may rise above 18 C (KocH). PASTEUR (Bulletin de Vacad. de m4d. 28, 1880) thought that earthworms might carry spores from buried beasts to the surface, and eject them with their excreta. But KOCH regards this hypothesis as unlikely and unnecessary to explain the spread of the disease. The contamination of the surface-layers in the process of burial is enough. KOCH'S experiments show that the transmission of the spores through the bodies of worms does not play the important part assigned it by PASTEUR, but they do not exclude it altogether. Other experiments prove that the bacillus may be cultivated on potatoes, in alkaline or neutral hay or pea-straw infusions, on crushed oats or barley, on turnip-juice, maize, beans, lentils, and many varieties of dead vegetable matter, if only sufficient water be provided. It is therefore probable that they may normally grow and develope outside the body of an animal. This takes place most readily in marshy spots and river-banks (Kocn). Spores are formed in summer, and persist through the winter. Inundations then carry the germs into the pasture-lands. If KOCH'S views are correct, the invasion of the animal body by the bacillus is as it were an accidental incursion of an ectogenous organism. PASTEUR has shown that birds enjoy no immunity against anthrax. (2) ' Symptomatic ' anthrax (Rauschbrand], This disease is probably due to a bacillus found in the affected animals. It is shorter and thicker than the anthrax-bacillus, forms local aggregations in the tissues, and is accompanied by the development of gas. See KOCH (loc. cit.\ and ARLOING, CORNEVIN, and THOMAS on i Charbon symptomati. Nat. Board of Health (V. S.} 1881. (7) Leprosy. Bacillus leprae was found in all the leprous nodules they examined by ARMAUER HANSEN (Virch. Arch. vol. 79 and Q. Journ. Micro. Sci. 1880) and NEISSER (Breslauer arzt. Zeitsch. 1879 and Virch. Arch. vol. 84). The bacilli are rather longer than the semi-diameter of a red blood-cell : they lie partly within and partly without the cells of the leprous nodules. NEISSER cultivated them in blood-serum and extract of meat, and observed them develope into filaments. They form spherical spores which are seated at 300 PARASITES. [SECT, vii: the ends of the rodlets, or form bright vacuoles in the middle of them. They spread through the system bv way of the lymphatics, not of the blood-vessels. They are surrounded by a gelatinous envelope and at times seem to be motile. CORXIL and SCCHARD (Annales "de Derinat. 1881) have confirmed the statements of the first observers. (8) Typhoid fever. KLEBS (Arch. f. exp. Path, xn, xm) and EBERTH (Virch. Arch. vol. 81) have found bacilli in the diseased patches of the intestine, and in the mesenteric glands, in cases of typhoid fever. KOCH has confirmed the state- ment (Mitth. a. d. k. Gesundh. 1881). In the sloughs from the intestinal ulcers long and short bacilli have been seen, in the lymphatic glands only the short ones. The latter are found also in the vessels of various organs;, especially the spleen, kidneys, and liver. They are probably the exciting cause of the disease. MARAGLIANO has found similar bacilli in the blood of living typhoid patients (Cent. f. med. Wiss. 41, 1882). The above results seem at first sight to disagree with those of FISCHB and EPPINGER (Beitrage z. path. Anat. n Prague 1880), LETZERICH (Arch. f. exp. Path, ix), and TIZZQNI (Studj di pat. sperim. sulla gen. d. tifo abdom. Milan 1880). These observers detected micrococci. It is possible that micrococci may settle in the typhoid ulcers by way of a secondary invasion. (9) Tuberculosis. KOCH'S Bacillus tuberculosis, mentioned already in Art. 127, grows in gelatine impregnated with blood-serum between the temperatures of 30 and 40 C, but not beyond these limits. It cannot therefore complete its develop- ment outside the body, at least in temperate climates. In most cases tuberculosis starts in the lungs, which become infected from the inspired air. The chief agent in contaminating the air is the sputum (Fig. 80) of phthisical patients which invariably contains the specific bacillus, either with or without spores. The infective power of the sputum is not destroyed by drying. It is highly probable that the spores are likewise unaffected thereby. The tubercle-bacilli grow very slowly and therefore do not readily succeed in making a settlement on the surface of mucous membranes. Healthy tissues are besides at all times difficult to infect. The settlement is favoured by wounds, loss of epithelium, stagnating secretions, &c. The tuberculosis of domestic animals and the 'pearly-disease' of cattle are due to the same bacillus as the human disease (Kocn, Berl. Jclin. Woch. 15, 1882). The bacilli grow well in sterilised ox-serum, but they develope and multiply very slowly. The colonies of fungi are only visible to the naked eye after ten days' growth : they then appear as dry whitish scales. These are made up of delicate rodlets. Each patch attains in three to four weeks the size of a poppy-seed, and then ceases to grow further until transplanted to a fresh substratum. This is owing to the fact that the bacilli have no power of locomotion, and so cannot spread over the nutrient gelatine. 207. Of Spirobacteria two forms are known to occur in man. The one, apparently quite innocuous, is the Spirochaeta denticola : it inhabits the mucous membrane of the mouth and nose. The other, the Spirochaeta (or Spirillum) Obermeyeri is found in the blood of patients suffering from relapsing fever, during the attacks. It is almost beyond doubt that the disease is caused by its invasion and multiplication within the blood. Quite lately the disease has been transmitted to monkeys by inoculation with the spirillum. Nothing certain is known of the habitat of the spirillum outside the body, _ It is easily detected by the microscope in the blood by CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 301 reason of its lively movements : these sometimes cause the red blood-cells to be driven and pushed about in the field of view. The spirillum of relapsing fever was discovered by OBERMErER in 1873 (Centralb. f. med. Wiss. 10, 1873" and Berl. Iclin. "Wocli. 33/1873). Since then it has often been examined and described. See WEIGERT, Deutsche med. Woch. 1876 ; HETDENREICH, Der Parasit des Riiclcfalhtyphus Berlin 1877 ; MOCZUTKOWSKY, Arch. f. klin. Med. xxrv ; GEDDES and EWART, Proc. Roy. Soc. xxvii. The successful inoculation of the monkey was performed by CARTER (Deutsche med. Woch. 16, 1879, Lancet 1, 1880, and Spirillum Fever London 1882). 208. If we accept for a moment the hypothesis that all or most infective diseases (other than those due to animal parasites) are caused by the development of bacteria in some tissue or fluid of the body, we are met at once by the question whether in that qase each specific form of disease has a corresponding specific bacterium, From a clinical standpoint this question must be answered in the affirmative. The most marked feature of the infective diseases is just this, that they run a typical and special course. Even though this may in individual cases be. modified by various influences, it is in general so characteristic, so patho- gnomonic, that the disease can often be diagnosed by its course aloae. We should therefore have no hesitation in inferring from the specific course of the disease that the virus which excites it is also specific. Histological examination of the tissues of patients affected, with bacterial disease has shown that in some cases (relapsing fever, anthrax, tuberculosis, leprosy) well-marked forms of fungi are always detected : and further that these forms of fungi, or at least forms belonging to one or other of their developmental stages, are the only ones constantly found. In other cases such histological distinction has not yet been possible. The micrococci occurring in various infective diseases do not as yet afford us characters sufficiently well-marked to form a basis for distinguishing them into species. It must not however be assumed that these various micrococci are identical, and that it is merely the accidental association with them of this or that poison which makes them seem to have different properties. If the micrococcus that is found be in fact the exciting cause of the disease, we must admit that it must be endowed ab initio with distinct properties. From the pathological point of view as well as from the clinical, we must regard it as belonging to a distinct species. As we pointed out in Art. 183, we are compelled to classify the bacteria into species on other grounds than those that apply to the higher plants. Our classification is based as yet on their morphological and physiological peculiarities. In the case of the micrococci we are confined almost entirely to the latter. We are compelled to set up physiological species. Thus as the chroma- togenous micrococci are classified according to the colour they S02 PARASITES. [SECT. vn. produce, so the infective micrococci are classified into species according to their pathogenous properties. KOCH has shown that in the case of many bacterial affections it is possible to discover in the fungi well-marked morphological differences corresponding to the physiological differences (Traumatic Infective Diseases 1880). STRUCK'S papers also contain many valuable contributions of this nature. See Arts. 204207 for further references. . 209. Each specific microparasitic disease presupposes a specific exciting cause, that is, a bacterium with special physiological properties. In affirming this proposition we do not imply that the specific bacterium constitutes a distinct species in the biological sense. This is a question which cannot be answered by the physician : it belongs to the biologist. He will have to make out whether the properties attributed to the bacterium are constant, and whether these properties are the only ones possessed by the corresponding biological species. On these points observers differ widely. KOCH from his culture-experiments has come to the conclusion that the patho- genous bacteria, like the non-pathogenous, do not alter in their properties. If bacteria be cultivated for several generations, the same developmental forms continually recur, and their physio- logical properties remain in every respect the same. Even when the nutrient medium is altered from time to time no recognisable differences are produced. KOCH does not dispute that mutability of species is possible among bacteria, but he holds that no adequate evidence has yet been brought to prove it. This view has now many adherents, especially among clinical observers. Some go even further and assert that mutability of species is impossible. The most important opponents of KOCH on this point are NAEGELI, DAVAINE, BUCHNER, and WERNICH. NAEGELI thinks that both the morphological and the physiological characters of the bacteria are mutable. A given bacillus does not invariably produce bacilli of the same structure, and does not always pass through the same developmental stages. A bacterium which under given conditions gives rise to a definite kind of fermentation may lose this property when cultivated under different conditions (Art. 192). Thus the same fungus can set up butyric acid fermentation or lactic acid fermentation according to circumstances. NAEGELI regards the various species of bacteria above described not as biological species, but as vegetative forms of a few as yet undetermined species. References: NAGELI, Die niederen Pihe Munich 1877 and 1882; BUCHNER, Die Nagdfsche Theorie Leipzig 1878 ; BIRCH-HIRSCHFELD, Schmidts Jahrbucher 1875; WERNICH, Die accommodative ZiicMung der Infectionsstoffe, Kosmos 4, 1880; Die Entwickdung der organisirten Krankheitsgifte Berlin 1880; Des- infectionslehre 1880 ; PASTEUR, De V attenuation des virus et de Isur retour d la CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 303 virulence, Comptss Rendus vol. 92; KLEBS, Arch. f. exp. Path, xm; BUCHNER, Exp. Erzeug. d. Milzbrandbacillen aus Heubacillen Munich 1880, Miinchener Acad. d. Wits. Jan. -12, 1882, and NAGELI'S Uiitersuch. iib. n. Pilze Munich 1882; URLICHS, Arch. f. klin. Chir. xxiv; KOCH, Traumatic Inf. Dis. 1880, Mitth. a. d. L Gesundh. Berlin 1881; GAFFKY, ibidem; FOKKER,' Virch. Arch. vol. 88 ; WOLFF, Virch. Arch. vol. 81 ; SEMMER, Virch. Arch. vol. 83 ; DAVAINE, Acad. de md. Paris 1872; GREENFIELD, Proc. Roy. Soc. Edin. 1880, Journ. Roy. Agric. Soc. 1880 ; KLEIN, Rep. Med. Off. Loc. Oov. Board 1881 ; MIQCEL, Bull. Soc. Botan. 1881. WOLFF maintains that micrococci and short bacilli change into each other, and seeks to support this by showing that transitional forms exist. What he takes for transitional forms may very easily however be nothing more than germinating spores, or even rodlets viewed obliquely. His statement that he obtained bacilli from a rabbit into whose peritoneal cavity he had injected micrococci is explicable by supposing the injected matter to be impure. WERNICH also asserts that the various forms may be interchanged, and speaks of the circumstance as evidence' of " unstable morphological equilibrium." He gives no other evidence in support of his idea. With regard to KLEBS and BILLROTH, and their views in this connexion, see Art. 185. 210. The defective state of our knowledge makes it for the present impossible to give a definite answer to the question of the mutability of the bacteria. It would however appear from the researches of NAEGELI arid others that we are not absolutely justified in regarding all the various forms as representing distinct biological specites. The idea of a species must be based on characters that are constant, not on those which may alter with the surroundings. The researches of KOCH and his pupils do not prove that the properties of the bacteria examined by them are perfectly constant. They only show that the morphological and physiological qualities possessed by a bacterium at a given time are retained by it with some tenacity, even when a certain amount of variation takes place in its environment. On the other hand the researches of NAEGELI, BUCHNER, WERNICH, and others seem to afford evidence that this constancy is not shown under all conditions : that changes of the nutrient medium may have some effect on the form and size of the cells, on their mode of multiplication, and on their physiologi- cal or fermentive properties. Changes of this kind and extent do not however indicate that one species is transformed into another. We must rather conclude that one or other of the properties possessed by a biological species of bacterium may be brought into prominence by proper modifications of the external conditions. The mutability manifested by a given bacterium will thus have definite limits. The bacterium cannot in any period of time within the extent of our observation acquire properties different from any of those possessed by the species to which it belongs. As to the extent of the cycle of varieties through which any one of the known bacteria may pass, we know indeed but little. It is possible that the properties of many of them admit of only the slightest variations from those with which we are acquainted. It is moreover probable that many of the varieties known to us constitute true biological species. 304 PARASITES. [SECT. vn. 211. If we accept the hypothesis that different vital proper- ties of the bacteria may be brought out by different external conditions, we have next to enquire whether the pathogenous bacteria may not be peculiar varieties of non-pathogenous forms. It is conceivable that in certain circumstances a bacterial virus might be developed from an innociious bacterium, and might ultimately be transformed back to the innocuous form again. This view has been maintained by several authors (NAEGELI, BUCHNER, WERNICH) and has been supported by various experi- mental results. They have chiefly relied on the observation that many bacterial poisons appear to become more virulent by trans- mission from animal to animal (e. g. that of Davaine's septicaemia), in other words, that by continual inoculation the parasite learns to accommodate itself more and more completely to the conditions in which it is placed. The opponents of the theory of mutability diminish the force of this argument by showing that the increase of virulence corresponds with an increase in the ' purity ' (or freedom from admixture with other bacteria) with which the fungus is cultivated. If a mass of mixed bacteria be inJ3cted into an animal, there will be at first several forms which develope simultaneously, and it is only after the virus has been trans- mitted through the living body twice or thrice that one form gets the upper hand, and developes to the exclusion of the others. The theory of mutability, and especially that of the transforma- tion of non-pathogenous into pathogenous forms, receives stronger support from an experiment of BUCHNER'S in which he seemed to show that anthrax-bacilli can be bred from hay-bacilli (B. subtilis) and conversely. KOCH, GAFFKY, and KLEIN dispute the validity of the experiment, but BUCHNER stands by it and claims to have confirmed it by fresh results of a like kind. The weight of evidence is for the present against him. At present we are unable to draw any certain conclusion regarding the relation of non-pathogenous to pathogenous bac- teria. Clinical experience would indicate that the activity of the infective virus may vary within certain limits. And we must apparently admit that the infective bacteria have not always possessed their noxious qualities, but have acquired them somehow in the course of ages. But this is not enough to convince us that harmless bacteria can acquire infective properties rapidly, that is to say in the course of comparatively few generations. They appear rather to hold by their properties with a certain tenacity. We may therefore provisionally conclude that the transformation of innocuous into noxious bacteria can occur but rarely and under special conditions. In other words, the pathogenous bacteria, even if they do not represent biological species, are wont to maintain the pathogenous form for long periods of time. DAVAINE, COZE, and FELTZ experimented on the septic poison obtained from putrefying blood. They at first asserted that its virulence increased CHAP. XXX.] THE SCHIZOMYCETES OR BACTERIA. 305 with extraordinary rapidity, so that in the twenty-fifth generation one-trillionth of the amount of matter originally used in the inoculation was all that was necessary to produce the same infective results. DAVAIXE became afterwards convinced that the virus attained its full power in the second or third genera- tion. KOCH confirmed this, and explained it by showing that the original matter used in the inoculation was impure, i. e. contained other bacteria, and that the repeated inoculations gradually eliminated the admixture. GAFFKY'S experiments brought out the same result. ROSEXBERGER (Centralb. f. med. Wiss. 4, 1882) has lately found that the gradual increase of virulence is more protracted in the case of the Bacillus oedematis. WERSICH finds that the potency of the Micrococcus prodigiosus (that is, its faculty of multiplying and producing red colouring-matter) can be in- creased by modifying the mode of cultivation. GAFFKY regards this fact as likewise due to the elimination of impurities. BUCHXER first announced in 1880 that hay-bacilli could be transformed into anthrax-bacilli. If hay-bacilli are injected into the blood of animals they do not give rise to anthrax. If however they are bred for several generations in meat-extract and then in the arterial blood of a rabbit, they acquire noxious qualities and give rise to anthrax in mice after two to nine days' incubation. Conversely, if anthrax-bacilli are properly cultivated they can be transformed into bacilli whose properties are identical with those of hay-bacilli. KOCH (loc. cit.} disputes the correctness of BTTCHXER'S observations, and suggests that he has been experimenting with the oedema-bacillus (Art. 206 (3) ) instead of the Bacillus anthracis. According to KOCH the anthrax-bacillus and the" hay-bacillus do not resemble each other. Hay-bacilli are rounded at the end* and possess cilia or flagella: anthrax-bacilh' are as it were cut off square. BUCHNER'S cultures were impure, they contained germs of other bacilli and these by degrees suppressed the original forms. While the hay- bacillus was supposed to be breeding in the blood the oedema-bacillus, or some other of similar action, was developed ; in the converse process the so-called anthrax- bacilli were gradually suppressed by others. In a later memoir (Akad. d. Wiss. Munich 1882) BUCHNER maintains his position and mentions fresh experiments bearing on it. In his view COHN'S Bacillus subtilis includes several varieties ; namely (1) hay-bacilli, (2) PAS- TEUR'S butyric- acid ferment, (3) FITZ'S bacterium (Ber. deutsch. chem. Gesellsch. ix, 1878) which converts glycerine into ethylic alcohol, (4) anthrax-bacilli. This fungus, which he regards as constituting a biological species, he calls Bacterium subtile. The properties of the variety which produces anthrax may be retained or withdrawn at pleasure by proper modes of cultivation. In the process of transformation transitional varieties appear representing inter- mediate stages between anthrax-bacilli and hay-bacilli. The middle forms only produce anthrax when injected in very large quantities. The process of transformation may be completed by cultivation in an alkaline solution of egg- yolk for twenty-four to forty-eight hours. The transformed bacillus (hay- bacillus) is distinguished by its energetic fermentive activity, and causes albumen to coagulate. It is inert when injected into the blood. NAGELI, in his recent book entitled Untersuchungen iiber niedere Pilze (Munich 1882), takes up the same position as BUCHNER with regard to the muta- bility of the bacteria. He believes that one and the same species may assume different forms according to the nutriment it is supplied with. These forms may exhibit different physiological and even morphological characters. The pathogenous bacteria are ' nutrimental ' modifications of non-pathogenous species. KLEIN in an important report just published (Rep. Med. Off. to the Loc. Gov. Board for 1881) communicates the results of a series of researches under- taken to test BUCHNER'S hypothesis. He points out the probable sources of error in BUCHNER'S work, and concludes that the anthrax-bacillus retains its full power to produce specific disease so long as it retains any power at all. References : see under Arts. 209 and 219. M. 20 CHAPTER XXXI. HYPHOMYCETES AND BLASTOMYCETES (MOULDS AND YEASTS). 212. Mould-fungi and yeast-fungi, with their congeners, belong like the bacteria to the achlorophyllous Thallophytes. They appear to have no nearer affinity than this to the bacteria, and they have no phylogenetic relation to them. The mould-fungi and the yeast-fungi are however more nearly akin to each other, for it is probable that the yeast-fungi are the primitive forms from which the higher fungi have developed (BREFELD). Moulds and yeasts, like bacteria, can only draw their nutriment from organic carbon-compounds. These they mostly find in dead organic matters, and they are therefore classed as Saprophytes. Some of them however are able to abstract nutriment from living tissues, and are therefore to be reckoned as Parasites. Both forms are met with in connexion Avith the human body. The mould-fungi or Hyphomycetes are well known outside the body. They form the familiar flocculent covering or pellicle seen on decaying organic substances, and variously known as mould, mildew, mother, &c. They belong to several distinct genera and even to distinct sub-classes of the Thallophytes. The yeast-fungi or Blastomycetes are also familiar organisms. They set up alcoholic fermentation, and form the yeasty scum which appears on the surface of alcoholic liquors. The systematic classification of the Thallophytes has in the last year or two undergone considerable modification. The earlier classification, based on certain obvious characters of form and habit, was into Algae, Lichenes, and Fungi. This subdivision has been modified since the discovery of the reproductive organs, and in many cases of the entire life-history, of the various forms. No sharp line divides the algae from the fungi. Many families of so-called algae and fungi are really correlated, inasmuch as they agree in the characters of reproduction and 'alternation'. The lichens have been regarded as ascomycetous fungi which are parasitic on particular algae, the gonidia. The absence of chlorophyll, and the variety of external forms (polymorphism) which occurs, are secondary characters ; the latter especially being influenced by parasitism (SACHS, Text-book of Botany Oxford 1882 ; BREFELD, Botanische Untersuchungen uber SchimmelpUze Leipzig 1874 77). CHAP. XXXI.] HYPHOMTCETES OR MOULDS. 307 BREFELD'S classification is (1) PAy 113> FuLL . GEOWN smaller vesicles (brood-capsules). The wall TAENIA ECHINOCOCCUS. of these is likewise two-fold ; but the cuticular (From LEUCK ART: x 12) layer is within and the parenchymatous layer without. On these brood-capsules develope numbers of heads or scolices (Fig. 114). According to LEUCKART they are formed out of sacculated out- growths from the external wall of the capsules (see the left side of Fig. 114). When the rudimentary head has become fully developed into a scolex (sometimes even sooner), it is retracted within the cyst which it thereby invaginates (Fig. 114). What was before the FIG. 114. BROOD-CAPSULES OP ECHINOCOCCUS IN CONNEXION WITH THE PAKENCHYMATOUS LATER OF THE CYST. (From LEUCKART: some of the capsules are closed, some have been bur*t open in making the preparation : x 50 circa) internal or cuticular surface of the head now becomes the outer surface. The original outer surfaces, which are parenchymatous, come now into contact and adhere to each other. The head is then 342 PARASITES. [SECT. vn. about 0'3 mm. long, and has a rostellum with tiny blunt booklets, four sucking-discs, a water- vascular system, and numerous calcareous granules in its parenchyma. The fore-part of the body is often invaginated within the hind-part. In many cases these echinococcus-cysts remain single. The only change they undergo is that they grow larger as fresh capsules and scolices are formed, so that they at length reach the size of a big orange, or of the closed fist. The surrounding tissues form, by condensation and thickening, a pseudo-cyst round the cuticular membrane. The cavity of the cyst is filled with clear liquid which is not coagulable by heat or acid. The brood-capsules are always seated on the inner surface, unless they are shaken loose mechanically. They appear as small white points lying in the transparent parenchyma. Occasionally the cyst may remain al- together sterile. 246. In many cases 'daughter-cysts' are formed. They de- velope in the thickness of the cuticle independently of the proper parenchymatous layer. Between two lamellae of the cuticle is formed an aggregation of granules which becomes surrounded with a secondary cuticle. This forms the starting-point of a new series of layers. As the layers multiply the inner cavity increases in size and its contents at length become clear and liquid. As the daughter-cyst grows it forces out the wall of the parent cyst like a hernial sac, until it at length gives way and sets the daughter- cyst free. Escaping thus into the tissues round the parent cyst it receives from them an external fibrous envelope, and proceeds to develope brood-capsules in the same way as the primary cyst derived from the six-hooked embryo. An echinococcus which is thus reproduced exogenously is called Echinococcus granulosus or scokcipariens (KUCHENMEISTER). It is also described as E. veterinorum, as it often occurs in domestic animals. A second compound echinococcus is the E. hydatidosus. It is characterised by the formation of internal daughter-cysts. NAUNYN (Dorpat. med. Zeitsch. 1870) asserts, and LEUCKART agrees with him, that the scolices and brood-capsules may undergo a cystic transformation, and so become daughter-cysts. NAUNYN goes on to say that these endogenous daughter- cysts may migrate from the parent cyst and so produce the E. granulosus ; but this LEUCKART disputes. The internal daughter-cysts sometimes develope daughters of their own or ' granddaughter-cysts.' Each of the cystic forms of which mention has been made may reach to a very considerable 247. The third form, or Echinococcus multilocularis, only forms small cysts, from the size of a millet-seed to that of a pea. They are always present in very large numbers. CHAP. XXXII.] TAENIA. 343 The E. multilocularis appears as a hard tumour seated in the liver. It is built up of a multitude of alveoli separated by dense scar-like fibrous tissue. The contents are transparent and jelly-like or semi-fluid. The alveoli are spherical or irregular in form. Here and there the tissues may have softened and broken down, and thus ulcerated cavities are formed. In other places the vesicles are shrunken and calcified, or the tissues are bile-stained. The distinct alveolar texture of the growth led to its being regarded as a tumour, and it was described as alveolar colloid of the liver. VIRCHOW (Verh. d. phys. med. Ges. zu, Wurzburg vi, 1855) was the first to make out its real nature, and he showed that the colloid masses were made up of echinococcus-cysts. The smallest vesicles merely contain granular matter, the larger contain liquid. The granular pseudo-parenchymatous covering of the cuticle seldom contains scolices, most of the cysts being sterile. E. multilocularis is possibly an abnormal variety or ' sport ' from the exogenous form. Eeferences : VIRCHOW, Virch. Arch. vol. 6 ; LEUCKART, Parasiten vol. I ; KLEBS, Handb. d. path. Anat. ; BOLLINGER, Deutsche Zeitsch. f. Thiermed. n, 1875 -f. PROUJEANSKY, Die tmdtiloculare Echitiococcusgeschiuulst In. Diss. Zurich 1873;-MoRiN, Deux cos de tumeurs d e'chinocoques In. Diss. Berne 1875; HuBEfo, Arch. f. klin. Med. i, iv, v, xxix. WALDSTEIN ( Virch. Arch. vol. 83, with beautiful illustrations) brings forward evidence to show that the dis- semination of the echinococcus may be effected through the lymphatics of the liver. He gives full references to previous memoirs. 248. The occurrence of hydatids in man implies that the eggs of the corresponding canine tape-worm have somehow gained access to his body. The liver is the commonest seat, but hydatids are found in all organs. Apart from the local inflammation and fibrous hyperplasia they induce, they often cause no trouble to the patient. When a hydatid reaches a certain size, it sometimes dies and the cyst shrivels up. Its contents are changed to a fatty or cheesy mass, often becoming mortar-like as it calcifies. The hooks remain for a long time unchanged. In other cases the hydatid becomes larger, especially when it forms exogenous or endogenous daughter-cysts. It may then become dangerous by its mere size. Sometimes if the cyst is wounded or bursts, its contents pass into one or other of the body-cavities and set up severe inflammation. It may even break into a blood-vessel. In the most favourable case it breaks into the intestine or upon the exterior of the body. The Echinococci are widely diffused, but not very frequent : they are commonest in Iceland, where the inhabitants are in constant contact with their dogs. It is somewhat surprising that the multilocular variety is chiefly observed in Switzerland and Southern Germany. NEISSER gives a summary of the various cases of hydatids that have been published (Die Echinococcus-krankheit Berlin 1877). See also PERLS, Handb, d. allg. Path. n. 344 PARASITES. [SECT. vn. 249. Bothriocephalus latus is the largest of human tape- worms. It measures 5 to 8 metres in length, and consists of three to four thousand short wide seg- ments (Fig. 115). The largest segment is about 3'5 mm. long and 10 to 12 mm. broad. To- wards the 'tail' the breadth diminishes and the length in- creases. The body is thin and flattened like a ribbon. The central part of each segment pro- jects somewhat; it is here that the uterus lies, in the form of a simple tube coiled into numerous convolutions. When this is full of eggs the coils lie in contiguous loops, forming a kind of rosette. The genital openings are in the mesial line of the ventral surface, somewhat anteriorly ; the female opening being close behind the male. The testis consists of a series of sacculations lying along the lateral margins of the central layer of the body. The general structure of the body resembles that of the Taeniada. Anteriorly the worm becomes gradually more and more slender and at length thread-like. The head, which is 2 '5 mm. long and 1 mm. broad, is club-shaped or oval in outline, and somewhat flattened. Along each lateral margin is a chink-like suctorial groove. The eggs (Fig. 116) are oval; they measure 0'07 mm.byO'045 mm. They have a thin brown shell furnished at the anterior pole with a lid or cap, which is in general easily seen. B. latus occurs chiefly in Switzerland and in the north-east of Europe : it is occasionally met with in Ireland. It lives like the Taeniada in the small intestine. The first development of the eggs takes place in water. After some months an embryo is hatched, which is pro- (LEUCKART) vided with six booklets and a ciliated cuticle. One is emptied of its contents and shows the lid. FIG. 115. FRAGMENTS OF A BOTHRIOCEPHALUS LATUS. (From LEUCKART: natural size) CHAP. XXXII.] PROTOZOA. 345 This enters the body of the pike, the trout, or the eel-pout (Lota vulgaris) (BRAUN, Virch. Arch. vol. 88), and developes in the muscles or viscera into an asexual tape-worm. If it thence reach the alimentary canal of man, it proceeds to develope further and becomes sexually mature. It has been maintained that B. lotus represents the mature form of the cestoid of the trout, known as Ligula nodosa. See DUCHAMP, Les Ligules Paris 1876 ; KIESSLING, TroscheVs Arch. 1882. In Greenland another form, B. cordatus, occurs. It is only 1 metre long and has a heart- shaped head. B. cristatus, 2 to 3 metres long, with a crest-like rostellum, has been found in France. Protozoa. 250. Protozoa are not rarely found in the cavities of the body accessible from without, such as the mouth, lungs, intestine, vagina, &c. : they are most common in patients suffering from chronic disease. The forms observed belong to the Rhizopoda, Infusoria, and Psorospermia or Sporozoa, respectively. Of parasitic Amoebae one species only has been described, the Amtfsba coli. It occurs in the intestine, and is simply a motile cell with a granular protoplasm containing a nucleus and several vacuoles. LOSCH and Soxsixo found the Amoeba coli in the dejections of a patient suffering from dysentery. Among Infusoria the Giliata and the Flagellata are repre- sented. Paramoecium (or Balantidium) coli is a large ciliated organism occasionally met with in the large intestine and in the faeces. Cercomonas intestinalis (DAVAINE) is a pyriform infusorian, with a spine-like process at its smaller end and a flagellum at its larger end. It is found in the intestine in cases of catarrh, of typhoid, and of cholera. KANNENBERG discovered Cercomonas in the sputa from a patient affected with gangrene of the lungs. In the same sputa he also found Monas lens, a spherical flagellate infusorian. Trichomonas is another flagellate infusorian ; it is oval in shape and provided with a comb-like row of cilia. One species (T. vaginalis) is found in the vagina, another (T. intestinalis) in the intestine. These protozoa are not to be regarded as the exciting cause of the affections with which they are associated. They may possibly however maintain or intensify the morbid processes, when present in considerable numbers. Of parasitic Psorospermia we have here to mention the Coccidia. According to LEUCKART, they are when young simple non-capsulated inhabitants of the epithelial cells. When they reach maturity they become invested with a kind of mem- branous capsule. In this condition they leave their first lodging, and generally their host at the same time. Their contents are 346 PARASITES. [SECT. vii. then transformed into ' spores ' containing granular masses and peculiar rod-like embryonic forms. The spores are round or ovoid. Coccidium oviforme (Fig. 117) is a parasite of the intestine and bile-ducts, especially those of the rabbit. In a few cases it has been found in the human subject. It leads in the liver of the rabbit to the formation of whitish nodules, which may be as large as a hazel-nut. The nodules consist of a puriform or cheesy mass, containing multitudes of coccidia. The granular contents of the coccidium are uniformly spread throughout its body, or rolled into a ball in the middle of it. The changes produced in the human liver by the presence of the para- site in the few cases observed have been similar to those met with in the rabbit. Our knowledge of the organ- isms known as 'Miescher's cylinders' or ' Rainey's corpuscles ' is still very defective. They are cylindrical or tube-like bodies found not infre- quently in the muscles of the pig, ox, sheep, and mouse. They con- tain an innumerable multitude of small oval or reniform corpuscles. Nothing is known of their effect on the human system. References to memoirs on Coccidia and Psorospermia generally : LEUCKART, Die Parasiten des Menschen, 2nd Ed. ; LIEBERKUHN, Arch.f. Anat. u. Phys. 1854 ; EIMER, Ueber die ei- oder kugelformigen Psorospermien der Wirbelthiere Wurzburg 1870 ; KLEBS, Virch. Arch. vol. 32; STIEDA, Ueb. die Psorospermien d. Kaninchenleber, Virch. Arch. vol. 32 ; WALDENBURG, ibidem vol. 40 ; RIVOLTA, Deiparasiti vegetali Turin 1873. According to our present information the parasitic protozoa take no important share in the production of human disease. It is however not impossible that further research may considerably alter our views in this regard. This is perhaps suggested by the fact that animal parasites are every now and then detected in the blood of vertebrate animals. Thus RATTIG (In. Diss. Berlin 1875) describes a ciliated infusorian in frog's blood. KLEBS (Eulenburg's Realencyclop. Art. Flagellata) has found in the blood of scurvy- patients very minute organisms, which he refers to the Infusoria and names Cercomonas globulus and C. navicula. LIEBERKUHN (Ueb. Bewegung. d. Zellen Marburg 1870) found an amoeba (A. rotatoria] in frog's blood. LEWIS (Quart. Journ. micros. Science xix, 1879) found in rat's blood, and WITTICH (Centralb. f. med. Wiss. 4, 1881) in hamster's blood, a mobile organism resembling the spermatozoon of the frog. KOCH (Mitth. a. d. k. Gesundh. Berlin 1881) describes a fusiform granular-looking structure with one or two flagella found in hamster's blood. He regards it as a flagellate infusorian. FlG. 117. COCCIDIA FROM THE HUMAN LIVER. (From LEVCKAR 1 ?) a is magnified 300-fold, b and c 1000-fold INDEX OF AUTHORS CITED (The numbers refer to the articles) Abelin 10 Boll 177 Ackermann 7 Bollinger 125, 127, 133, 134, 135, 197, Adams 11 206, 221, 247 Addison 96 Boser 196 Ahlfeld 1, 5, 9, 12, 13, 179 Bostrom 153 Albrecht 206 Bottcher 79, 99, 108 Anderson 18 Bouley 201 Andral 94 Bowman 94 Anger 152 Bozzolo 231 Appert 96 Braidwood 204 Arloing 206 Brauell 206 Armauer-Hansen 117, 131, 185, 206 Braun 249 Arndt 63 Braune 13 Arnold 13, 27, 74, 84, 86, 89, 97 Brefeld 186, 212, 215, 217, 219, 223 Arnstein 152 Brieger 191, 192, 197, 201, 204 Aufrecht 85, 108, 127, 206 Bristowe 153 Auspitz 128 Brodowski 109, 153 Briicke 94 v. Baer 11 Bruns 154 Baillie 118 Buchholtz 190 Baker-Brown 10 Buchner 186, 190, 193, 201, 209, 211 Balfour 74, 75, 86, 89 Budge 94 Ballard 206 Bugnion 231 Bambeke 10 Buhl 9, 11, 120, 206 Bancroft 235 Burkhard 84 Barbieri 54 Burow 61 Earth 235 Busch 18, 88 Bary (de) 216, 220 Butlin 165 Bauer 52 Baumgarten 8, 108, 127 Caton 96 Baumler 128 Carter 201, 207, 222 Bavle 118 Cayley 31 v. Becker 61 Ceci 193 Bence-Jones 52 Chamberland 188 Bergmann 191, 197, 201 Charcot 28 Bezold 221 Chauveau 42, 125, 127, 201 Bilharz 231, 239 Cheyne 201, 204 Billroth 86, 109, 149, 156, 159, 161, 163, Chiari 179 171, 183, 184, 185, 209 Christoph 145 Binz 52 Cienkowsky 223 Birch-Hirschfeld 69, 204, 206, 209 Claudius 13 Bizzozero 35, 81, 108, 114, 156 Clelland 5 Blix 10 Cobbold 226, 228, 233, 234, 235, 239, Block 222 240 Bogehold 177 Cohn 183, 184, 185, 186, 189, 191, 192, Bohm 13 211 348 INDEX OF AUTHORS CITED. Cohnheim 18, 19, 21, 22, 25, 27, 30, 33, 36, 47, 62, 79, 80, 84, 94, 95, 97, 99, 117, 119, 125, 136, 140, 153, 177, 179, 180, 221 Colin 127, 201 Cordua 68 Cornevin 206 Cornil 58, 66, 76, 84, 120, 128, 156, 206 Courty 153 Coze 204, 211 Creighton 127, 174 Cuboni 206 Cullen 94 Cunningham 74, 193, 222 Curling 18 Curnow 31 Czerny 154 Dallinger 185 Danzel 178 Dareste 3, 7, 10 Davaine 204, 206, 209, 226, 230, 231, 234, 235, 240, 250 Day 31 De la Croix 190 Demnrie 42 Depaul 13 Dickinson 58, 62 Dittmer 5 Donitz 5 Drasch 74 Drysdale 185 Duchamp 249 Duclaux 191, 201, 219 Duzan 179 Eberth 56, 59, 74, 79, 84, 87, 99, 153, 204, 206 Ebstein 28 Ecker 17 Ehrlich 127 Eidam 189 Eimer 55, 250 Eisenmann 94 Emmert 94 Engelmann 190 Eppinger 63, 161, 204 Etard 191 Ewart 184, 186, 189, 204, 207 Ewetzky 87, 108, 163 62 Feltz 125, 204 Fischer 18 Fischl 206 Fitz 211, 219 Fleming 133 Flemming 46, 74, 75, 84 Foerster 1, 4, 5, 7, 10, 13 Fokker 209 Formad 204 Fox (Wilson) 125, 178 Fraenkel 125 Friedberg 18 Friedlander 204, 206 Friedreich 18, 58, 59, 61, 221 Frisch 199 Fronista 174 Fuerst 3 Furbringer 221 Gaffky 189, 204, 205, 206, 209, 211 Galen 93 Gamgee 35, 54, 68 Gannet 135 Gartner 190 Gaule 120 Gautier 191 Geddes 207 Gee 120 Gerlach 5, 17, 127 Gibbes 127, 206 Gjorgewic 152 Glax97 Glazier 233 Gluge 112 Golubew 86 Goodsir 87, 94, 174 Gordon 178 Grancher 118 Grassi 231 Grawitz 11, 214, 219, 222, 223, 224 Greenfield 130, 204, 206 Griesinger 231, 239 Griffine 84 Grohe 219, 222 Gruber 10, 11, 75 Guillebeau 37 Guillemard 239 Gull 63 Giinther 127 Gurlt 1, 5 Gussenbauer 67, 174 Haab 204 Haberkorn 185 Haffter 178 Haller 3, 94 Hallier 185, 186, 218 Hallwachs 115 Hamilton 27, 96, 108, 120 Hamlet 190 Harms 127 Hartig 220 Hasse 180 Hayem 35 Hebra 152 Hegar 115 Heidenhain 108, 115 Hein 240 Heine 94 Heller 226, 229, 233, 243 Henle 94 Hennings 62 Heppel 61 Bering 27, 97, 120 Hermann 52 INDEX OF AUTHORS CITED. Hertwig 89 Heschl 59, 178 Heubner 130 Heusinger 8 Heydenreich 207 Hickmann 11 Hill 31 Killer 191, 197, 201, 223, 226, 233 Hink 135 Hirsch 125, 146 Hoffman, F. A. 94, 96 Hoppe-Seyler 52, 96, 191 Horwath 190 Houston 13 Huber 153, 162, 206, 247 Hueter 11, 204 Hunter 94 Immermann 28 Israel 134, 135 Jehn28 Jensen 3 Johne 35 Joubert 188 Julliard 10 Jiirgens 29 Kannenberg 249 Kaposi 152 Kassowitz 87, 88 Kaufmann 219 Keating 204 Keber 204 KekuleSS' Kern 186 Kessler 18 Key 79, 99 Kiener 125 Kiessling 249 Kitt 221 Klebs 84, 117, 125, 127, 128, 145, 161, 174, 178, 183, 184, 185, 186, 188, 201, 204, 206, 209, 226, 247, 250 Klein 63, 74, 76, 86, 119, 120, 125, 186, 206, 209, 211 Klemensiewicz 97 Kobner 131 Koch 94, 117, 120, 125, 127, 183, 184, 185, 186, 188, 189, 190, 193, 196, 199, 201, 204, 206, 208, 209, 211, 219, 222, 250 Kocher 153, 171, 177, 204 Kohlrausch 178 Kolaczek 161 Kolliker 5, 7, 88, 115 Konig 11 Koster 119, 120, 143, 163, 171, 204 Kraske 89 Kronlein 11, 177 Kiichenmeister 221, 226, 246 Kiihne 58, 69 Kunkel 67, 68, 69 Kiiss 107 Kussmaul 206 Kyber 58, 61, 62, 64 Laennec 118 Lancereaux 130 Langhans 61, 67, 68, 82, 115, 119, 120, 125, 153 Lankester 185 Lassar 25, 96 Laveran 206 Laycock 67 Lebedeff 9 Leber 61, 219, 221 Lebert 125, 173, 178 Leichtenstern 17 Leopold 140, 179 Letzerich 204 Leube 194, 206 Leuckart 225, 226, 228, 231, 233, 234, 235, 245, 246, 247, 250 Lewin 52 Lewis 222, 235, 250 Lichtheim 25, 219, 221 Lieberkiihn 250 Liebermann 231 Liebig 190 Lippe 125 Lister 94, 97, 185, 186, 194 Litten 30, 37, 64 Little 18 Lockwood 9 Loffler 189, 201, 219 Long 231 Lowne 1 Lubbock 94 Lubimoff 63, 120 Lucae 161 Lucas 18 Liicke 136, 149, 171, 173, 178, 204 Ludwig 55 Lukkomsky 204 Liitkemiiller 13 Maas 88, 140, 179, 180 Macewen 88 Maier 152, 156, 161, 163, 204 Maizel 74 Hanson 235 Maragliano 206 Marchand 5, 7, 153, 206 Marchiafava 206 Martin 74, 125, 126 Martini 178 Maurer 161 Mayer 223 McConnell 231 Meckel 5, 8 Megnin 231 Meier 136 Miquel 193 Mitchell-Bruce 17 Moczutkowsky 207 Moleschott 35 350 INDEX OF AUTHORS CITED. Monod 18, 149 Hontegazza 35 Moore 181 Morin 247 Moxon 165, 174 Miiller 127, 147, 165, 206, 226 Nageli 186, 188, 190, 191, 192, 193, 201, 204, 209, 211, 223 Nassiloff 204 Naunyn 246 Nauwerck 204 Neelsen 63 Neisser 117, 131, 204, 206, 248 v. Nencki 183, 184, 191, 194, 197 Nepveu 204 Neumann 8, 79, 85, 89, 161 Nieden 152 Normand 231 Obermeyer 207 Oellacher 5 Oemler 201 Oertel 204 Oldham 153 Oordt (Van) 128 Orth 1, 8, 13, 69, 114, 125, 127, 204 Owen 233 Pagenstecher 221 Paget 42, 71, 80, 86, 89, 94, 107, 136, 146, 147, 149, 165, 171, 173, 178, 181, 233 Pagliani 231 Panum 3, 5, 7, 13, 178, 190, 197 Parona 231 Pasteur 183, 186, 188, 191, 201, 206, 209, 223 Paulizky 61 Payne 150 Perls 1, 3, 7, 9, 12, 13, 68, 85, 153, 154, 156, 173, 174, 194, 199, 204, 226, 231, 248 Perroncito 226, 261 Peters 63 Pflug 135 Pinner 152 Poland 133 PoUender 206 Ponfick 81, 114, 135 Pospelow 152 Prazmowski 186, 188 Proujeansky 247 Priestley 74 Piitz 133 Quain 52 Banvier 52, 66, 76, 84, 89, 120, 128, 146, 156 Battig 250 Eauber 5 Eaynand 204 v. Eecklinghausen 63, 99, 154, 205 Eedfern 87 Eeess 219, 223 Eehn 8 Eeichel 13, 152 Eeidl8 Eeinhardt 51 Eeinke 190 Bemak 76, 174, 178 Betzius 79 Beuss 96 Beverdin 84 Bichard 206 Eiess 204 Eindfleisch 42, 59, 66, 76, 81, 84, 85, 86, 109, 114, 117, 119, 120, 125, 150, 165, 173, 174, 204 Bivolta 250 Boberts 190, 194 Bohrer 179 Eokitansky 58, 149 Bosenbach 194 Bosenberger 115, 196, 211 Eossbach 196 Boszahegyi 201 Both 9 Boustan 125 Budneff 58 Bumler 143 Eyneck 97 Sachs 212, 215, 218, 220, 223 Salkowski 191, 197 Samuel 80, 94, 95, 96, 97 Sanderson (Burdon) 94, 95, 99, 119, 120, 125, 183, 186, 189 Sattler 163 Schede 8, 108 Schklarewsky 27, 96 Schmidt 35 Schmiedeberg 191, 197 Schotte 190 Schroeter 191 Schron 171 Schuller 132 Schultze 5 Schulz 52 Schulze 54 Schiippel 119, 120, 127 Schutzenberger 223 Schweninger 84, 125 Semmer 196, 201, 204, 209 Senftleben 108, 115 v. Siebold 225 Simon 94, 125, 174 Simpson 14 Smith 154 Sokolow 156 Sonderegger 231 Sonnenburg 13 Sonsino 239 Soyka 154, 193 Spear 206 Stein 226 Sternberg 194, 204, 206 INDEX OF AUTHORS CITED. 351 Steudener 88, 156 St Hilaire (Geoffrey) 3, 5, 7 Stieda 250 Stilling 94 Strasburger 74, 75, 76, 84 Strelzoff 88 Strieker 79, 86, 95, 99 Struck 208 Struthers 17 Suchard 205 Sutton 63 Tappeiner 125 Thiersch 109, 171, 181 Thoma 95, 96, 97, 131 Thomas 206 Tiegel 185 v. Tieghem 185, 186, 189 Tillmanns 5, 11, 85, 108, 109, 115, 204 Tills 85 Tizzoni 204, 206 Tommasi-Crudeli 204, 206 Toussaint 201, 206 Traube 101 Travers 86 Trelat 18 Trendelenburg 204 Treves 120 Turne* 17, 62 Tyndall 193 Unna 128 Urlichs 209 Vacca 95 Vacher 204 Vallierme 11 Valsuani 11 Vandyke Carter 222 Verneuil 13, 154 Villemin 125, 133 Virchow 5, 8, 13, 14, 30, 35, 48, 56, 58, 61, 62, 68, 72, 76, 77, 78, 80, 81, 84, 85, 87, 89, 90, 94, 114, 117, 118, 125, 127, 128, 131, 136, 138, 145, 146, 147, 149, 150, 152, 153, 154, 156, 165, 171, 177, 179, 201, 221, 233, 247 Vogel 94 Vogt 179 Voigt 10 Voit 52, 191. 201 Vrolik 1 Wagner 56, 59, 62, 120, 128, 129, 206 Waldenburg 118, 125, 250 Walder 206 Waldeyer 84, 161, 171, 173, 178, 204, 206 Waldstein 247 Waller 96 Walk's 99 Wartman 87 Wasserthal 13 Weber 86, 125 Wedl9 Wegner 115, 120, 152 Weigert 13, 36, 96, 123, 179, 204, 207 Weil 174 Weissgerber 194 Welcker 17 Wendt 161, 233 Wernich 193, 201, 209, 211 Wieger 63 Wilks 165, 181 Williams 96, 153 Wilson 125 v. Winiwarter 97, 117 Winslow 3 Wittich 250 Wolff 88, 177, 197, 201, 204, 209 Wolffhugel 189, 190 Wood 204 Wooldridge 35 Wucherer 231 v. Wyss 84, 108, 125, 206 Yeo (Burney) 125 Youatt 133 Zahn 61, 140, 179 Zangger 206 Zenker 38, 153, 222, 229, 233, 243 Ziegler 28, 37, 59, 61, 68, 85, 86, 88, 108, 109, 110, 115, 119, 120, 123, 140, 145, 150, 156, 173, 174, 179, 184, 193, 204 Ziilzer 204 Ziirn 226 INDEX OF SUBJECTS (The numbers refer to the articles) abrachius 10 abscess 102, 116 metastatic 116 aeardiacus 13 acarus folliculorum 225 scabiei 225 achirus 10 achorion Schonleinii 222 acrania 7 actinomyces 222 actinomycosis 134, 135, 222 acute miliary tuberculosis 123 acute atrophy of the liver 204 adenocarcinoma 169, 173 adenoma 166, 167 sqq adipose tissue, growth of 85 adiposity 50 aecidium elatinum 220 aerobious fungi 188, 206 agnathia 8 agrotis segetum 222 air, bacteria in the 193 albuminoids, putrefaction of 191, l'J2 alcoholic fermentation 212 set up by mucor 219 yeasts 223 algae 212 alternation in mould-fungi 218 alveolar colloid 247 sarcoma 161 amelus 10 amoeba coli 250 rotatoria 250 amputation, intrauterine 10 amputational neuroma 154 amyloid concretions 61 amyloid degeneration ch. xm results of 60 seat of 59, 62 substance, nature of 59, 62 reactions of 58 anaemic necrosis 40 anaemia 19 collateral 22 anaerobious fungi 188 anasarca 23 anastomotic varix 151 anencephalia 7 aneurysm by anastomosis 151 anchylostoma duodenale 231 angioma 148 lymphatic 152 congenital 179 angiosarcoma, plexiform 161 myxomatodes 163 anguillula stercoralis (rhabditis) 231 anomaly, congenital 1 anthrax (see bacillus anthracis) 199 symptomatic 206 genesis of 206 history of 206 vaccination in 201 antheridium 218 aplasia of the limbs 10 apoplexy 27 aprosopia 8 apus 10 arachnida 225 argyrism 70 arsenic, causing fatty change 52 arteries, syphilis in 130 arthrppoda 225 sqq ascaris lumbricoides 228 mystax 228 ascites 23 chylous 31 ascococcus 185 ascogonium 216 ascospore 213, 216 ascus 216 aspergillus glaucus 216, 221 flavescens &c. 219, 222 atheromata (congenital) 8 atrophic proliferation 46 atrophy, active 47 of inaction 47 passive 47 pigmentary 45, 46 serous 46 simple 43, 45 trophoneurotic 47 attenuation of virus 201, 211 attraction theory of inflammation 94 autosite 13 INDEX OF SUBJECTS. 353 bacillus amylobacter 188 anthracis 185, 186, 188, 190, 199, 206 transmutation of 211 leprae 131, 185, 186, 206 malariae 185, 206 oedematis 206 of typhoid 206 - subtilis 185, 186, 211 tuberculosis 120, 127, 186, 206 (Fig. 80) detection of 127 bacon-liver 57 bacteria ch. xxx biology of 188 sqq classification of 183 diffusion of 193 effect of agitation on 190 effect of heat on 189 effect of light on 190 effect of poisons on 190 effect on nutrient liquid 191 in air, soil &c. 193 inflammationexcitedby 198, 199 iu health 194 mutability of 192, 208, 209, 211 non-pathogenous 197 -. pathogenous 195, 196, 198 specific nature of 208, 209 textural changes caused by 200 bacterial action, theories of 210 bacterium lineola 195, 20o subtile 211 termo 185, 189, 192, 205 balantidium coli 250 bei-bug 226 bed-sores 33 bile-pigments 69 bilharzia haematobia 239 birds'-nest body 172 blastomycetes 223 sqq bleeders 28 blood-pigments 63 blood-vessels, growth of new 86 Blut-pliittchen 35 bones, growth of 88 metaplasia of 91 regeneration of 88 bothriocephalus cordatus 241 cristatus 249 latus 249 botrytis bassiana 222 ' bots ' 226 bovine tuberculosis 127, 206 bronzing 67 brood-capsules (echinococcus) 245 brood-cells 76 cachexia of tumour 141 cadaveric poison 197 calcaneus (talipes) 11 calcareous deposits 64, 65 calcification, after necrosis 34 cancellous osteoma 147 M. cancer-cells 170 cancer-stroma 170 canker in cattle 135 capillaries, growth of 86 carcinoma 166, 170 sqq aetiology of 181 growth of 171 metastases in 174 varieties of 173 carpogonium 216 carrier-cells 114 cartilage, growth of 87 metaplasia of, 91 caseation 39 after necrosis 34 in tubercle 118 catarrh 55 desquamative 103 purulent 102 serous 102 cavernous angioma 150 metamorphosis 150 cells, division of 74, 75 multiplication of 80, 81 cell-nests 170, 172 cellulitis, micrococci in 204 cercaria 236, 239 cercomonas 250 cestoda 240 sqq chalky concretions 65 chancre 128 cheilognathopalatoschisis 8 chigoe or chigger 226 chionyphe Carter! 222 chloroma 162 chlorosis, Egyptian 231 cholesteatoma 161 cholesterin 54 chondroma 146 chylous hydrothorax 31, 235 ascites 31 chyluria, from filariae 235 cicatricial tissue 82, 105 growth of 108, 109 cicatrix, after necrosis 34 ciliata 250 cimex lectuarius 226 cleft palate 8 ' clegg ' 226 clostridium butyricum 186, 188, 192 cloudy swelling 48 club-foot 11 coagulative necrosis 35, 36 coccidium 250 coccobacteria 185 Cohnheim's embryonic theory of tumours 177 sqq colliquative necrosis 40 colloid degeneration 56 concentric globes 172 condyloma 129 congenital hypertrophy 18 tumours 178 congestion 21 354 INDEX OF SUBJECTS. conidia 213 conidiophore 215 connective tissue, regeneration of 85 metaplasia of 91 connective-tissue tumour 138 contagious disease 202 evidence of organic nature of virus in 203 cordyceps militaris 222 cornea, mould-fungi on 221 crab-louse 226 craniopagus 12 craniorachischisis 7 cranioschisis 7 croupous exudation 102 culicida 226 cultivation of bacteria 186, 211 cuniculi in scabies 225 cyclopia 7 cyclops, host of Guinea-worm 234 cylindrical epithelial cancer 173 cylindroma 163, 173 cystadenoma 168 cysticercus cellulosae 242, 244 racemosus 243 cystoma 168 cysts 71 dermoid 178 following necrosis 34 daughter-cysts (echinococcus) 246 Davaine's septicaemia 204 decubitus 33 definitive inflammation 34 degeneration, amyloid 57 colloid 56 dropsical 49 fatty 50 hyaline 63 ' hyalin-fibrous ' 63 lardaceous 57 mucoid 55 parenchymatous 48 vitreous 63 waxy 38 demarcation, line of 34, 41, 115 demodex 225 dermoid cysts 71. 178 desmobacteria 183, 186, 206 desquamative catarrh 103 development of blood-vessels 86 diapedesis 27, 96 dicephalus 14 diphtheria, coagnlative necrosis in 38 micrococci in 204 diphtheritic inflammation 38, 103 diplobacteria 185 diplococcus 184, 185 diprosopus 14 dipygus 15 direct cell-division 76 disinfectants 190 disinfection by heat 189 disintegration, cysts of 71 dislocation, congenital 11 dispora Caucasica 186 distoma haematobium 239 hepaticum 237 lanceolatum 238 dochmius duodenalis 231 dracontiasis 234 dracunculus medinensis 234 dropsical degeneration 49 dropsy 23 dry-rot 220 duplicitas anterior 14 posterior 15 duplication of limbs 17 mammary glands 17 viscera 17 dwarfs 6, 43 ear, mould-fungi in the 221 eburnated osteoma 147 ecchondroses 146 ecchymoses 26 echinococcus cysts 245 granulosus 246 hydatidosus 246 multilocularis 247 scolecipariens 246 taenia 245 veterinorum 246 ectogenous virus 203 ectophytes 182 ectopia cordis 9 (ecstrophia) vesicae 9 ectozoa 182 effusions 26 Egyptian chlorosis 231 elephantiasis graecorum 131 embolic infarction 37 embolism 29 embryonic hypothesis 177 sqq tissue 180 empusa 222 encephalocele 7 encephaloid cancer 173 enchondroma 146 endocarditis, micrococci in 201 endogenous gemmation 76 virus 203 endosporium 215 endothelioma 161 engastrius 13 engorgement 21 enostosis 147 entophytes 182 entozoa 182 epidermic globes 172 epigastrius 13 epignathus 13 epipygus 13, 14 epistaxis 26 epithelial tumours 138, ch. xxvn epithelioid cells in granulations 108 in tubercle 119 epithelioma 170, 172 INDEX OF SUBJECTS. 355 epithelium, growth of 84 regeneration of 84 epizoa 182 equinus (pes) 11 erectile tumours 150 erysipelas, micrococci in 204 eurotium aspergillus 21G, 221 eustrongylus gigas 231 excitability of cells 78 exosporium 215 exostosis 147 extravasation 26 cysts of 71 exudation-corpuscles 112 exudations, inflammatory 96 - - re -absorption of 112 varieties of 102 false membrane 35, 102 farcy 133 fatty degeneration ch. xi cause of 52 infiltration 50, 53 favus 222 fermentation (see bacteria) 191, 223, 224 .fibrin 35 fibrinaus exudation 102 necrosis 35, 36 fibroblasts 85 in granulations 108, 109 fibroid, uterine 142, 153 fibroma 142 fibromyoma 153 fibroplastic degeneration 135 fibrosarcoma 157, 160 fibrous tissue, growth of 85 regeneration of 85 filaria medinensis 234 sanguinis hominis 235 filobacteria 186 , fissura abdominalis 9 fistula colli congenita 8 fixed tissue-cells in cicatrisation 111 flagellata 250 flea 226 flukes 236 foetus papyraceus 13 fomites 202 foreign substances, re-absorption of 113, 114, 115 fowl-cholera 201, 204 fungi, classification of 212 fungous tumour 137 fungus-disease of India 222 fur of the tongue 221 gangrene, dry 41 moist 42 gangrenous emphysema 42 gastroschisis 9 gattine 204 gemination in cells 76 in yeasts 223 genesis of tumours ch. xxvnr germ-theory, evidence for 203 giant-celled cancer 173 giant-cells 76 in granulations 108 in tubercle 119 in syphilis 128 glanders 133 gliacoccus 185 glioma 145 Grluge's corpuscles 112 gonorrhoea 204 gout, deposits in 66 granulation-tissue 105 growth of 108 granule-carrying cells 51 grauuloma 117 granulomata, infective ch. xxiv Guinea-worm 234 gumma 129 gummatous node 130 gynaecophoric canal 239 haematemesis 26 haematin 68 haematoblasts 35 haematocele 26 haematoidin 68 haematoma 26 haematometra 26 haematopota pluvialis 226 haematuria 26 endemic 239 from filariae 235 haemoglobin 68 haemopericardium 26 haemophilia 28 neonatorum 28, 204 baemoptoe or haemoptysis 26 haemorrhage 26 by rupture (apoplexy) 27 haemorrhagic diathesis 28 exudation 102 infarct 26 haemorrhoids 149 haemothorax 26 ' hard sore ' 128 hare-lip 8 hay-bacilli, transmutation of (see bacillus subtilis) 211 head of tape-worm 240 hemicephalus 7 hernia cerebri 7 funis 9 heterologous tumour 133 heteroplasia 83 heteroplastic tumour 138 histioid tumour 138 homoeoplastic tumour 138 homologous tumour 138 hyaline degeneration 63 necrosis 35, 36 356 INDEX OF SUBJECTS. ' hyalin-fibrous ' degeneration 63 hydatid cyst 245, 248 hydatids 240, 245 hydraemic plethora 25 hydrobilirubin 68 hydrocele colli 8 hydrocephalus (causing acrania) 7 hydroencephalocele 7 hydrops 23 hydrorachis 7 hydro thorax, chylous 31 hyperaemia 19 appearances of 20 collateral 21 . idiopathic 21 passive 21 hyperostosis 147 hyperplasia, cell-processes in, ch. xvm hypertrophy, congenital 18 cell-processes in, ch. xvn numerical 72 simple 72 hyphae 213 hyphomycetes ch. xxxi hypostasis 21 icterus 69 neonatorum 69 inclusio foetalis 13 incrustation 64 indirect cell-division 74 infarct 26, 30 infarction, embolic 37 infective diseases, classification of 202 organisms in 203 infective granulomata ch. xxiv infectiveness, marks of 117 infiltrating tumour 137 infiltration with salts 64 inflammation chs. xxi, xxn altered blood-current in 96 attraction theory 94 causes of 98 definition of 93 diapedesis in 96 . dilated vessels in 96 exudation in 96 later stages of ch. xxn migration of blood-cells in necrosis after 100 neuropathic theories of 94 recovery after 104 repair after 98 stasis in 96 symptoms of 93 temperature in 97 terminology of 101 textural changes in 99, 103 varieties of 101 vascular changes in 95, 96 inflammatory infiltration 101 oedema 102 stimulus 99 inflammatory tissue 105 infusoria 250 inoculation in anthrax 201 . fowl-cholera 201 septicaemia 196, 201 insecta 226 intention, first 110 second 110 interstitial inflammation 101 intestinal diverticula 9 mycosis 206 jnversio vesicae 9 iron in morbid pigmentation 68 Irritabilitat 78 ischaernia 21 ischiopagus 12 itch-insect 225 ixodes ricinus 225 janiceps 12 jaundice 69 karyokinetic cell-division 74 karyolytic figures 75 lardaceous degeneration 57 leaf-rust 220 leiomyoma 153 leprosy (see bacillus leprae) 131, 206 leptothrix 186 leptus autumnalis 225 leucocytes, diapedesis of 96 . dissolve in infective diseases 201 in granulations 108 migration of 96, 99, 108 peripheral disposition of 96 leukaemia 52 lice 226 lichenes 212 ligula nodosa 249 lipofibroma 144 lipoma 144 lipomatosis 50 lipomyxoma 144 liquefaction, after necrosis 40 lithopaedium 6, 64 liver, acute atrophy of 204 cavernous tumour of 150 liver-fluke 237 livores 21 lupus 132 lymph, transudation of 23 lymphadenoma 155 lymphaugioma 152 lymphatic glands, tubercle in 122 lymphatics in oedema 24 lymphoma 155 lymphorrhagia 31 lymphorrhoea 152 lymphosarcoma 155, 158 madura-foot 222 INDEX OF SUBJECTS. 357 maggot-worm 229 malaria (see bacillus malariae) 206 malformations, artificially produced 3, 5 congenital Sect. I fissural 7, 8, 9 of the organs 11 origin of 2, 3, 12 malignant oedema 188, 204, 206 malposition of the organs 11 margaric acid 54 margarin-crystals 54 matter or pus 102, 108 maw-worm 228 measle of pork 242, 243 meat-poisoning 206 Meckel's diverticulum 9 medullary cancer 173 melanin 67 melanocarcinoma 173 melanoma 162 melauosarcoma 162 meningitis 204 meuingocele 7 merulius lacrirnans 220. mesoblastic tumour 138, ch. xxvi metamorphosis (see degeneration) metaplasia ch. xx metastases in cancer 174 metritis 204 metrorrhagia 26 miasmatic disease 202 miasmo-contagious disease 202 microbacteria 183, 185, 205 microbrachius 10 micrococci in lupus 132 pathogenous 204 micrococcus 184 cyaneus 191 diphtheriticus 185 erysipelatis 204 luteus 184, 191, 195 prodigiosus 191, 211 . septicus 185, 199, 204 . variolae 204 micromelus 10 microparasitic theory of contagium 203 micropus 10 microsporina 185 microsporon furfur 222 Miescher's cylinders 250 migration of leucocytes 96, 99, 108 mikrosomia 6 mildew (vine) 220 miliary tubercle 118 tumours 137 miner's lung 70 mixed connective-tissue tumours 164 sqq cancerous tumours 17G mole, congenital 179 fleshy 6 hydatidiform 6 molluscum, fibroma 142 monadina 185 monas haeiuorrhagicum 204 monobrachius 10 inonopus 10 monsters, double 1, 5, ch. in - --- origin of 5, 12 -- single 1, ch. n monstrosities by defect 3 -- by perversion 4 mortification (see gangrene) mosquitoes 226 - hosts of filaria 235 mould-fungi ch. xxxi --- in invertebrates 222 -- in moist gangrene 42 -- mutability of 219 -- pathology of 221 -- reproduction of 218 mucoid degeneration 55 mucor racemosus 219 - mucdo 215, 221 - - -- mutability of 219 mucous membranes, tubercle of 124 - patch 129 - tissue, growth of 85 multiplication of cells, causes of 80, 81 mummification 41 muscle, growth of 89 - regeneration of 89 mutability of bacteria 208 sqq mycelium 213 mycetoma 222 mycoderma 223 mycomycetes 212 mycoprotein 183, 184 mycosis, intestinal 206 -- of lungs 221 myeloid cancer 173 - sarcoma 159 153 myosarcoma 153 myxosarcoma 163 myxoma 143 myxofibroma 143 myxolipoma 143 myxomycetes 212 naevi 149 nanosomia 6 necrosis ch. vm - after inflammation 100 - anaemic 33, 40 - coagulative 35, 36 colliquative 40 necrotic inflammation 103 nematoda 227 sqq nerve-tissue, growth of 89 -- regeneration of 89 neuroglia, growth of 85 neuroma 154 neuropathic theories of inflammation 94 new blood-vessels, growth of 86 --- in granulations 109 'nightingale' (two-headed) 14 node, syphilitic 130 nodular tumour 137 358 INDEX OF SUBJECTS. non-pathogenous bacteria 197 nosema bombycis 20-4 nuclear figures 74, 75 nucleolus (nuclear or nucleolar corpuscle) 74 nucleus-division 74 nucleus, structure of 74 obesity 50 oedema 23 cachectic 25 hydraemic 25 inflammatory 25, 102 malignant 206 purulent 102 varieties of 24 oedema-bacilli 206 transmutation of 211 oestrida 226 oldium 214, 220, 222 identical with mycoderma 224 oil-drops in fatty degeneration 51 oligaemia 21 omphalopagi 12 ondontoma 147 onychomycosis 222 oogonium 218 oosphere 218 oospore 218 ' organisation ' 86 organoid tumour 138 osteoblasts 88 osteoclasts 115 osteoid chondroma 165 osteoma 147 osteophyte 147 osteosarcoma 165 ovigenous organ in taenia 241 oxyuris vermicular is 229 packing-cells 216 papilloma 137 paramoecium coli 250 parasites Sect. VII - animal ch. xxxn vegetable chs. xxx, xxxi parasitic twin 13 parenchymatous inflammation 101 parostoses 147 Pasteur's septicaemia 188, 204, 206 pathogenous bacteria 195, 196, 198, 210 sqq pearly disease 127, 206 tumour 161 pebrine 204 pediculi 226 penicillium glaucum 217 pentastoma constrictum 225 denticulatum 225 taeniodes 225 perodactylus 10, 18 peiiostitis, infective 204 peripheral disposition of leucocytes 96 perithecium 216 perobrachius 10 perochirus 10 peromelus 10 peronospora infestans 220 petaVoacterium 185 petalococcus 185 petechiae 26 petrificatiou 64 phocomelus 10 phosphorus, causing fatty change 52 phthisis, bacilli in sputum of 206 phycomyces 215 phycomycetes 212 pigmentary atrophy 45 pigments, haematogenous 68 normal 67 pigment-spots, congenital 179 piles 149 pityriasis 222 plagues 203 pleomorphism in fungi 218 pneumonia, catarrhal 204 croupous 204 pollinodium 216 polymelia 15 polymorphism in fungi 212, 218 polypous tumour 137 post-mortem staining 21 potato-disease 220 proglottis 240 proliferation, cell-processes in 73 factors of 80, 81 proscolices 240 prostatic concretions 61 protection by inoculation 201 protophyta 223 protozoa 250 psammoma 162 pseudo-parenchyma 216 psorospermia 250 puerperal peritonitis 204 pulex irritans 226 penetrans 226 purulent catarrh 102, 204 exudation 102 oedema 102 pus, origin of 99, 102, 107, 108, 112 putrefaction in moist gangrene 42 putrefactive diseases 204 putrid decomposition 191, 192, 197 exudation 102 pyaemia 204 pyelitis, micrococci in 204 pygopagus 14 Rainey's corpuscles 250 re-absorption 104 imperfect ch. xxni recovery after inflammation 104 regeneration after inflammation 104 necrosis 34 cell-processes in, ch. xvm relapsing fever, spirillum of (see spiro- chaeta Obermeyeri) 207 INDEX OF SUBJECTS. 350 resting-spore 215 retention, cysts of 71 Eeverdin's skin-grafting 84 rhabdomyoma 153 rhizopoda 250 rigor caloris in bacteria 189 frigoris in bacteria 189 ringworm 222 roestelia cancellata 220 rostellum of taenia 241 1 rot ' in sheep 237 round-celled sarcoma 153 round-worm 228 saccharomyces 223 sago- spleen 57 saliva, causing septicaemia 204 sanious exudation 102 saprophytes 221 sarcina 184, 185, 204 sarcoma 156 sqq alveolar 161 myeloid 159 myxomatodes 163 peculiar 161 round-celled 158 * spindle-celled 160 'varieties of 157 sarcoptes 225 scarlatina, micrococci in 204 schistomycetes ch. xxx schistoprosopia 8 schizomycetes ch. xxx, 212 scirrhous cancer 173 sclerosis (fibrous hyperplasia) 82, 111, 129 sclerotium 217 scolecida 227 sqq scolex 242 scrofula 127 seat-worm 229 senile retrogression 45 sepsiu 191, 197 septicaemia, Davaine's 204 from saliva 204 micrococci in 204 of mice 201, 204 Pasteur's 188, 204, 206 septic poison 191, 197 sequestrum 115 serous catarrh 102 exudation 102 Siamese twins 12 silkworm-diseases 204 silver- staining 70 simple cancer 173 siren-monster 10 situs transversus (in versus) 11 skin-diseases, fungi in 222 skin-grafting 84 slough 115 small-pox, micrococci in 204 softening 40 soil, anthrax-spores in, 206 soil, bacteria in 193 somatic death 32 ' specific inflammations ' 117 specific nature of tissues 77 spermatozoid 218 sphacelus 42 sphaerobacteria 184 spina bifida 7 spina ventosa 135 spirillum of relapsing fever (see spiro- chaeta Obermeyeri) 207 tenue 187 undula 187 volutans 185, 187 spirobacteria 184, 187, 207 spirochaeta denticola 187 Obermeyeri 185, 187, 207 sporangia 214, 215 sporaugiophore 215 spores of mould-fungi 213 sporozoa 250 squamous epithelial cancer 173 staining, post-mortem 21 stasis (as a cause of necrosis) 33 sterigma 216 sternopagi 12 St Gothard tunnel, anchylostoma in 231 stigmata 27, 97 stimuli, action of, on cells 79 stomach, fungi in the 221 stomata 27, 97 stomoxys calcitrans 226 storage-fat 53 streptobacteria 185 streptococci 185 strongylus duoienalis 231 longevaginatus (bronchialis) 231 strumous inflammations 204 suctorial worms 236 sugillations 26 supernumerary bones and muscles 16 mammae 16 suppuration (see pus) 112 symptomatic anthrax 206 sympus 10 syncephalus 12 syndactylus 10 synophthalmia 7 synotia 8 syphilis 128 sqq micrococci in 206 tabanida 226 taenia cucnrnerina 244 echinococcus 245 elliptica244 malformations of 243, 244 mediocanellata 244 nana 244 saginata 244 solium 241 tape- worms 240 sqq tarichium megaspermum 222 INDEX OF SUBJECTS. tatooing 70 telangiectasis 152 temperature, effect on bacteria 189 moulds 219 teratoma 13, 178, 179 textural changes in inflammation 99 varieties of 103 thallophytes 212 thoracic duct, rupture of 31 thoracogastroschisis 9 thoracopagus 12 parasiticus 13 thread-worm 229 thrombosis 29 ' thrush ' 224 tinea 222 tipulida 226 torula 223 trematoda 236 tricephali 16 trichina spiralis 232, 233 trichocephalus dispar 239 trichomonas 250 trichophyton tonsurans 222 triplets, homologous 16 tuberaceae 216 tubercle 118 sqq clinical characters of 125 crude 121 definition of 118 inoculability of 125 miliary 118 tuberculosis (see bacillus tuberculosis) 118 sqq acute miliary 123 , bacillus of 120, 127, 186, 206 diffusion of 121, 122, 124 of lymphatic glands 122 transmissibility of 125 tuberous tumour 137 tumours Sect. VI aetiology of, ch. xxvm cachexia of 141 Cohnheim's theory of 177 . congenital 178 definition of 136 . growth of 139 malignancy of 140 . metastasis of 140 tumours, varieties of form in 137 twins, homologous 12 typhoid fever, bacilli in 206 tyrosis 39 ulcer 102, 115, 116 cancerous 175 tuberculous 121 sqq umbilical cord, withering of 41 umbilication in cancer 175 urobilinuria 68 uterine fibroid 142, 153 vaccination 201 in anthrax 201 vaccinia, micrococci in 204 valgus (pes) 11 varicocele 151 variola, micrococci in 204 varix, anastomotic 151 varus (pes) 11 vibrio 186 serpens 185 vibrion bittyrique 186 vessels, dilated in inflammation 96 vessel-walls in inflammation 97, 98 virus, attenuation of 201, 211 of tubercle 126, 127 viscera, transposition of 11 vitelligenous organ in taenia 241 vitreous degeneration 63 warts, congenital 156, 179 waxy degeneration 38 liver 57 whip-worm 230 witches' -brooms 220 wood-tick 225 woolsorters' disease 206 worms 227 sqq wound-infection 204 wounds, healing of 107 xiphopagi 12 yeast-fungi 223, 224 zoogloea 184 zygospore 213, 215 CAMBRIDGE: PRINTED BY c. J. CLAY, M.A. Jt SON AT THE UNIVERSITY PRESS. University ot California C , L|TY "**&V3SSZ%*