•;-,^>,', ":':•':■•■. : «:s<^^^V:♦^^ %*<':'*.';•;'': 'i';^.'''*.«'i'/';': . . . . .HS Vu BonV ,7? 7 IS CogyiightN?- COP«!IGHT DEPOSnv PRINCIPLES OF MEDICAL PATHOLOGY BY G. H. ROGER PROFESSOR EXTRAORDINARY IN THE FACULTY OF MEDICINE OF PARIS MEMBER OF THE BIOLOGICAL SOCIETY PHYSICIAN TO THE HOSPITAL OF PORTE-D'AUBERVILLIERS AUTHORIZED TRANSLATION BY M. S. GABRIEL, M.D. WITH ADDITIONS BY THE AUTHOR NEW YORK AND LONDON D. APPLETON AND COMPANY 1905 --1^1 [ Lf B RAfTYcfGOhiGRiss Two Copies Heceivecf -iAN 4 1905 Coi»yfi£rit Sfstry ^'^ 3,190 6" ii-HS3 a xxc. Npi COPY 8. COPTBIGHT, 1905, bt d. appleton and company PRINTED AT THB APPLETON PRESa NEW YORK, U. S. A. * INTRODUCTION TO THE STUDY OF MEDICINE Copyright, 1901, by D. Appleton and Company TEANSLATOR'S PEEFACE The quick demand for a second edition of Professor Eoger's work proves the highly appreciative welcome it has met among his American confreres. Koger is one of Bouchard^s foremost disciples, and he is the master's right hand in the preparation of his monumental work in six volumes, now in course of publication in Paris under the title, Traite de Pathol- ogic Generale. Eoger bears to Bouchard the same relation in the 'Faculty of Medicine. Bouchard occupies the chair of General Pathol- ogy and Therapeutics, and year after year treats of a special subject. The Faculty thought that another course of lectures should be insti- tuted by the side of Bouchard's, including the whole field of General Pathology and Therapeutics. This task was intrusted to Roger, who is, like Bouchard, not merely a professor, but a cultivator of the med- ical sciences. His experience, both with experimental pathology and clinical medicine, is of the widest range. No wonder, therefore, that he was able to condense, in the course of his lectures, a tremendous amount of solid knowledge; no wonder that this book, reproducing the lectures, has proved to be of exceptional value to the profession, in that it combines so masterfully theoretical with practical interests. The volume was entitled Introduction to the Study of Medicine; but, in reality, it is far more than that. The several chapters on Evolution of Diseases, Examination of the Sick, Clinical Application of Scientific Procedures, Diagnosis and Prognosis, and Therapeutics, covering two hundred pages, are of a character to engage the attention even of practitioners of considerable experience. I was not surprised, therefore, when some of our clinicians of the highest reputation wrote to me of the profound interest with which they had perused this translation of Roger's work. In view of these facts, and with the consent of the author, I have substituted in this edition, for the original title. Introduction to the Study of Medicine, the more exact one. Principles of Medical Pathol- ogy, and I trust that it will be equally welcomed by both advanced students and practitioners. M. S. Gabriel, M. D. New York. iii AUTHOE'S PEEFACE TO THE SECOND ENGLISH EDITION In order to guide himself in the practice of medicine, I think it is indispensable to a physician to possess certain general conceptions enabling him to interpret the symptoms observed, and to oppose them with a rational treatment. It is hardly possible, in fact, to know where we are standing in the midst of the innumerable phenomena revealed by the clinics, to classify and co-ordinate them, and to establish their respective values; it is hardly possible to make a choice among the multitudinous proceedings offered by modern therapeutics — unless we have constantly in mind certain rules that guide the judgment and command the interventions. General pathology and therapeutics do not present merely a speculative interest, they do not appeal to the theorist in quest of new hypotheses nor to the scientist devoted to abstract studies; on the contrary, they have a constant bearing upon daily practice. Inspired with these ideas, the Faculty of Medicine of the Uiiiver- sity of Paris instituted the course of lectures that was intrusted to me and that I publish herewith. In this book will be found the general data applicable to the study of clinical medicine. I have endeavored to condense all the knowledge that is useful to the student who under- takes the study of medicine, as well as to the practitioner who should desire up-to-date information about the great morbid processes. The plan I have adopted is a very simple one. After having ex- plained why and how an individual becomes sick, I have described the morbific causes that constantly tend to modify the unstable state of health. These causes, through the lesions they determine and the re-actions to which they give rise, produce phenomena some of which are appreciable during life, while others are found out only after death. We are thus led to study the mode of re-action of the organism, namely, pathological physiology; to describe the organic alterations — viz., pathological anatomy; and to consider, finally, the functional disturb- ances the description of which forms one of the most important chapters of medicine, that is, semeiology. In the one hundred pages which I have devoted to the clinical examination of the sick, I have attempted to condense the rules that VI AUTHOR'S PREFACE are to guide the physician in his practice, and I hope to have shown that he can and must make a diagnosis and prognosis by the simple procedures within the reach of all. At the bedside, the physician must get along by means of clinical procedures. It is only in rare instances that he is obliged to resort to more delicate methods, to utilize the data of micrography, bacteri- oscopy, and various laboratory procedures. I certainly do not wish to appear as though I were doubting the interest of such scientific inves- tigations; I only mean that indispensable as they are for the progress of medicine, they are too complicated and delicate to enter into the current procedures of daily practice. Likewise, the indications that must guide therapeutics are to be derived from clinical study. The last chapter of this work is devoted to the general rules of treatment and have closed the book with a few considerations on hygiene and prophylaxis. From these explanations it can be seen that I have followed the course of morbid processes step by step, and have constructed a frame in which the descriptions of special pathology can readily be placed. Addressing especially practitioners and students, I have excluded, as a rule, all theoretical discussions, discarded doubtful hypotheses and moot conceptions, and have reported only those results that seem to be final. Demonstrated theories and well-established facts become inde- pendent of those who make them known. In proportion as science is brought to perfection, it becomes impersonal ; hence, to a great extent, I have been able to ignore citations of proper names, confining myself to final achievements. I have explicitly mentioned only those old authorities who have made some important discovery, advanced some particular theory, or recorded some observation of consequence. Although on several occasions I have mentioned researches pursued by myself, following the above rule I have reported them just as I have those of other authorities, without indicating their origin. This appears to me to be the only way to avoid the petty questions too often raised by discussions of priority. Owing to the rapid progress of medicine, books quickly grow old. Therefore I have made a certain number of modifications and additions to the French edition, from which this translation was made. Hence, this book represents the second edition of my work. I take pleasure in further stating that Dr. Gabriel's translation is of perfect accuracy, and that I am very happy to see my thoughts rendered with such strict fidelity and precision. CONTENTS CHAPTER PAOS Translator's preface iii Author's preface v I. — Introductory remarks 1 II. — Mechanical agents 13 III. — Physical agents 34 IV. — Chemical agents 61 V. — Animate agents 81 VI. — Animate agents (continued) 93 VII. — Animate agents (concluded) 119 VIII. — General etiology of infections 133 IX. — General pathogenesis of the infectious diseases . . . .158 X. — Nervous reactions • . .173 XI. — DlSTURBAJ^CES OF NUTRITION 184 XII. — Disturbances of nutrition (continued) — Auto-intoxications . . 196 XIII. — Pathology of the fcetus — Heredity 310 XIV. — Inflammation 243 XV. — Septicemia and pyemia 285 XVI. — Evolution of inflammations— Sclerosis 295 XVII.— Tumours 305 XVIII. — Cellular degenerations 317 XIX. — Functional synergies and morbid sympathies 328 XX. — Evolution of diseases 355 XXI.— Examination of the sick 403 XXII. — Clinical application of scientific procedures .... 492 XXIII. — Diagnosis and prognosis 513 XXIV.— Therapeutics 522 Tables for reducing the metric system into the English . . 537 Index 539 vii PRINCIPLES OF MEDICAL PATHOLOGY CHAPTER I INTBODTJCTOIIY BEMABKS Definition of the words medicine, health, disease — Disease and affection— The causes of diseases : division, according to the nature of the pathogenic agent, into mechanical, chemical, and animate causes; division, according to the action on the organism, into eflB.cient, accessory, predisposing causes — Object of the various branches of pathology — The bases of therapeutics. Medicine is sometimes considered as a science, sometimes as an art. Both conceptions are correct ; all depends upon the view point at which we place ourselves. Medicine is a science hy its means of study; it is an art by its applications. We are thus led to the following two defi- nitions : The object of medical science is the study of disease. The aim of medical art is to restore and maintain health. That part of medical science which studies disease is called pathol- ogy (Trddos, suffering, ailment). The teaching of the medical art, as it is done at the sick bed, constitutes climes (kXivikos, from Kkuvrj, bed). Pathology comprises the following chapters : Etiology (atrta, cause), which investigates the morbific causes; pathogeny, which explains by what mechanism these causes act on the living organism to disturb its state of health or abolish its existence; pathological physiology, which shows how the organism reacts (morbid reactions) under the influence of pathogenic causes ; pathological anatomy, which unveils the structural modifications resulting from the morbid actions and reac- tions; symptomatology, which gives an account of the disturbances and lesions appreciable during life; nosology, which describes and classi- fies diseases. To these different branches, which constitute the medical science, should be added two others concerning rather the medical art — namely, the technical side (rexyrj, art) of medicine; I refer to diagnosis and prognosis. Diagnosis (discrimination, from Sio, through, and yiyv hand, and epyov, work). Prophylaxis ( 7r/oo<^vXao-o-€tv, to watch) whose principal part is repre- sented by hygiene (vyteta, health), dictates the precepts to be followed for avoiding disease. Dietetics (SiatTo, regime) indicates the diet con- ducive to the restoration or preservation of health. Pathology embraces, then, nearly all of medicine. There is a mani- fest disproportion between its vastness and the limitations of the human mind; hence the necessity of dividing its study into several distinct branches. The following divisions are generally admitted: Special or descriptive pathology, which makes an analytical study of diseases and comprises internal or medical pathology and external or surgical pathology; comparative pathology, which takes into consideration dis- eases in man, in animals, and even in vegetables ; experimental pathol- ogy, which proposes to modify the evolution of spontaneous diseases and to reproduce, with a view of explaining and combating them better, the disturbances, lesions, and diseases with which we have been ac- quainted through observation; finally, general pathology, which defines the terms and fixes their meaning, determines the laws of morbid phe- nomena, investigates the causes, processes, and symptoms, and classifies them. It outlines the rules of nosology, and prepares the frames in which special pathology will place its descriptions. Although general pathology is often considered as the synthesis, that is, the loftiest part of medical science, and often rises to sublime conceptions well calculated to seduce and captivate the mind, it may well be contented with more modest views ; it may be elementary and furnish the begin- ners with rules to guide in their studies of diseases. When we know which are the morbific causes most frequently intervening, when we are sure of their mode of action and have understood the mechanism of morbid reactions, derangements, symptoms, and lesions, we are pre- pared to understand and appreciate particular cases. We have repeatedly made use of the words health and disease. These two words are currently employed ; but, while there is a universal agree- ment as to their meaning, there arises considerable difficulty when an inquiry is made into the precise nature of phenomena designated by these terms. The same is true of all abstract ideas : only those subjects are well defined whose limits can be comprehended by the mind. Health and disease (or hygid state and morbid state) are connected INTRODUCTORY REMARKS 3 by a multitude of disturbances more or less well characterized; it is therefore very difficult, not to say impossible, to draw a sharp line be- tween these two states, which, absolutely different in their highest expressions, approach and unite with each other in their attenuated manifestations. The difficulty is rendered greater by the fact that perfect health does not exist; living organisms are always in a state of unstable equilibrium, which finds its explanation and cause in the very conditions of life. It is known, in fact, that living matter is the seat of a series of acts which do not depend, as was once believed, upon a vital force animating matter, but should be considered as reactions produced by the variations of external agents. Let us suppose for a moment that no modification whatever is pro- duced in the cosmic forces, no change at all in the relations of a being with the objects that environ it: equilibrium will soon be established between this being and the surrounding world. Of course, life is not annihilated under these conditions ; but it remains latent, as was once said, or, to speak more correctly, remains in a static state. But the moment an external variation occurs, the equilibrium is broken; the living organism, to adapt itself to the new conditions, presents a series of reactions making life again apparent — ^that is, causing it to pass into the dynamic state. Now, in reality, the cosmic forces constantly vary, the objects are displaced and modified; the world we live in changes, and, life being but an adaptation to medium, living matter is incessantly agitated by reactionary oscillations calculated to counter- balance the influence of the external agencies. Thus is explained the unstable state just referred to. If neighbouring variations are slight and slow, adjustment is read- ily made and health preserved. Should they be intense and sudden, compensation becomes more difficult, often resulting in indisposition, sickness, or death. Let us suppose, for example, a man placed in a room with a fixed temperature of 20° C. ; the organism of this man is regulated so that the production and dissipation of heat maintain his organic temperature at 37° C. As the medium is supposed to be constant, heat production will be managed also in an invariable way. Suppose, now, that the temperature of the room rises or falls one degree; the equilibrium is disturbed and thermogenesis modified. In order that his temperature may always remain at 37° C, he must either produce more heat or expend less. When the variation is light and progressive, adjustment is made easily and unconsciously; the organic modifications are not perceived and do not cause any trouble. But if the temperature of the room should suddenly rise from 20° to 80° C, or fall to — 40° C, this change of 60° in plus or minus would 4 INTRODUCTORY REMARKS completely upset the thermogenic equilibrium of the organism and provoke a series of disorders resulting in disease or a fatal ter- mination. What we say about heat can be repeated with regard to other phys- ical agents. Barometric variations, imperceptible when slight, give rise to indisposition when intense. If it is a question of considerable change of pressure — for instance, when making a balloon ascent, or when one is submitted to the action of compressed air, and especially when one is caught in a gas explosion— the accidents may prove very serious, or even fatal. Physical variations are not the only ones capable of impressing the organism ; all modifications occurring in our relations with surrounding objects and beings may produce the same effect. It is therefore possible to transport into medicine the classical data of the physical and natural sciences and divide the pathogenic agents simply into four groups : Me- chanical agents; physical agents; chemical agents, including the caustics and the toxics; animate agents, subdivided into parasitic and infectious (the latter including most of the pathogenic bacteria). This enumera- tion shows that diseases are not provoked by new, special, mysterious causes, but by the ordinary cosmic agents — ^by the objects and beings that surround us. When impressed by these various agents, the organ- ism, as above noted, does not remain indifferent; it responds by reac- tions, whose purpose, if not the effect, is to bring the economy to a state compatible with life. Therefore two orders of phenomena are to be noticed in every disease : those due directly to the cause and those refer- able to the reaction of the organism. The latter are far more important than the former. In a good definition, however, we must, following Dr. Bouchard, take into account both series of morbid manifestations. We are thus led to the following definition : " Disease is the ensemble of the phenomena which are produced in an organism undergoing the action of a morbific cause and reacting against it." We have thus far supposed this morbific cause to be exogenous — i. e., outside of the organism. But authors often attribute disease to inter- nal or endogenous causes — that is, causes taking origin within the organism. We have excluded this etiological group for the reason that it is no longer acceptable ; all diseases, indeed, proceed from an external cause. The opposite view is due to a persistent confusion of disease with affection. Take, for instance, a man suffering from typhoid fever. The disease being over, the organism is restored to health. But the restoration is only apparently perfect ; modifications persist which, too slight to be perceived, follow nevertheless their progressive evolution. Ten, fifteen. INTRODUCTORY REMARKS 5 twenty years later, new manifestations break out — ^for example, some disturbances due to heart lesion. By that time the disease is almost forgotten, and, as no intermediate bond connects the actual manifesta- tions with the disease left far behind, considerable difficulty is experi- enced in tracing the succession — some sort of repugnance to connect this cardiopathy with the long expired typhoid fever. In another case the subject will have been through a number of different diseases, and the physician will be at a loss as to which of them to attribute the new visceral disorder. From a philosophical point of view it is essential to reascend to the first disease. From a practical standpoint this inquiry is often use- less. Whatever the etiological conditions may have been, the effect is the same. Organic affections are simply cicatrices; disengaged from the initial cause, they become autonomous and develop on their own account. Let us take up the example above referred to. Suppose a man suf- fering with a cardiac affection. Whatever the starting point of the car- diopathy may have been, whether rheumatism, typhoid fever, or any other disease, the effects are identical. The new morbid manifestations derive no particular character from their origin. The etiological notion is of no practical importance, but is indispensable to the nosologist who will even refuse to consider the affections of the organs as diseases. What is true of the heart is true of all the viscera. Their affections take origin from some antecedent cause. For a long time this very simple truth has not been understood because the initial disease is not always easily found out ; the visceral derangement may be the first outward manifestation, leading to the belief that it is making its appear- ance spontaneously. To those who should wonder how a visceral lesion is capable of devel- oping silently for twenty or thirty years without giving rise to any symptom, we can answer by the well-known example of gonorrhoea. A man has a urethral discharge at the age of twenty ; he recovers in a few months, and seems to be completely cured. Toward the age of forty or fifty micturition grows difficult, and a urethral stricture is discovered, which nobody hesitates to connect with the former attack of gonorrhoea. It is a remnant of the infectious process, a cicatrix that has shrunken little by little. Why, then, should we regard as doubtful in the case of the viscera and organs that which is so readily admitted to be true as regards the urethra ? The process is alike in both cases ; it is one of cicatricial evolution, slow and progressive. We can therefore, in the presence of these tardy manifestations, sequelae of diseases, isolate the exciting cause ; but on condition of being 6 INTRODtJCTOEY REMARKS mindful of the fact that the actual disorders are due to an anterior cause which voluntarily we disregard. When the actual morbid process is considered without taking into account its initial cause, the name disease can not be applied to it. It is preferable to employ the term affection. We shall define, there- fore: ^^ Disease is the morbid process considered in its entire evo- lution, from its initial cause to its final consequences; affection is a morbid process considered in its actual manifestations, apart from its cause." It is improper to speak of diseases of organs ; affection is the proper term. Some authors use, in this sense, the term pathy as a sufifix following the name of the organ. The word thus created indicates an affection of this organ, without prejudging the disease. This procedure, strongly advocated by Dr. Landouzy, is perfectly rational. The words cardiopathy, pneumopathy, etc., have the advantage of being both well constructed and very suggestive ; " cardiopathy " is simpler than ^^ car- diac affection" and more exact than "heart disease." This nomen- clature would put an end to the confusion that has been established and maintained between disease and affection. Another condition further complicating the problem is the fact that the modifications produced by diseases and affections may influence the descendants. Thus is created morbid heredity, which may be transmitted through a great number of generations, and may explain the develop- ment of pathological families. Variously tainted children are brought into the world, presenting a defective nutrition and predisposition to certain diseases. In this event the disturbances of health are autoge- nous so far as the sufferers themselves are considered, but in reality they are exogenous in that they are the result of external influences exerted upon their parents. In pathology, as in biology, the successive series of livings beings must be considered as a single being eternally existent. We shall consider at length, in a later chapter, the role of heredity, which explains a group of causes which, at first sight, seem to form an exception and to depend upon an internal origin. I refer to psychical causes. Psychical phenomena, the highest manifestations of life, appear to be independent of the external medium. In reality, though more complex, they do not differ essentially from bodily phenomena; they are equally dependent upon external agents which have acted upon the person himself or his ancestors. These considerations amply authorize us to reject absolutely the division of morbific causes into internal and external. The initial causes are always to be looked for outside the organism. In view of their nature they may, as we have said, be classified into four groups: INTRODUCTORY REMARKS f Mechanical, physical, chemical, and animate causes. In view of their action upon the organism, it is possible to divide them into efficient and predisposing causes. The efficient causes are always necessary; at times they are suffi- cient by themselves. Let us take, for example, the anthrax bacillus, which is one of the microbes best studied by experimenters. Let us introduce it beneath the skin of a guinea pig. The animal contracts the disease and dies within three or four days. In this case the efficient cause has proved sufficient. Let us make the same inoculation into a more resistant animal, the white rat. No disorder will be produced. But let us submit this white rat to some fatiguing exertion, or inject into it some toxic substance. The intervention of such an accessory cause will favour the action of the efficient cause: the anthrax will develop. The more we study pathology and get an insight into the history of infections, the better we understand the importance of auxiliary causes. There are certain microbes which develop as soon as they are deposited on a wound or even a healthy mucous mem- brane, but they are exceptions. In most instances various causes must come to their assistance. This is especially true of the microbes inhabiting our normal bodies. Our integuments and mucous mem- branes swarm with innumerable pathogenic agents, which vegetate as simple innocent parasites until the day when an auxiliary or, as some still say, a determining cause permits them to overcome our resistance and exercise their noxious influence ; then appear a series of acts ending in indisposition and disease. Pneumonia, for example, is an infection induced by a microbe frequently present in the mouth of healthy per- sons ; so long, however, as the organism is in a normal state the microbe can not develop. But let some common cause — fatigue, cold, or inhala- tion of irritating vapours — reduce the resisting power; the microbe, until then harmless, becomes pathogenic. This well-known example proves that the co-operation of the two orders of causes is indispensable. Let us not fall into the error of the first bacteriologists, who thought the microbe was sufficient to explain all; an error less excusable than that of the ancient authorities, who, having no idea of the role of animate agents, explained morbid phenomena by the intervention of auxiliary causes alone ; and hence they believed also in morbid spontaneity. They believed in it also because they did not understand the nature and mechanism of predisposing causes. They assigned to predisposition an internal origin instead of seeing in it the resultant of impressions made upon the subject or his progenitors by external causes having acted antecedently. Predisposing causes are antecedent causes with respect to present disorders; efficient and auxiliary causes are present causes. 2 8 INTRODUCTORY REMARKS Each pathogenic agent may play alternately the part of efficient cause and of auxiliary cause ; heat and cold, for instance, in mortifying a tissue, act as efficient causes, but they fall into the order of auxiliary causes when they favour the development of a microbe. Likewise a microbe or a poison may produce a disease or aid another pathogenic agent. We should never lose sight of the possibility of these etiological associations, these morbid synergies which play a part extremely impor- tant in pathology. According to the mode and extent of their action, the pathogenic causes are often divided into local causes and general causes. The for- mer act on a limited point of the organism, the others act on the entire economy, or rather on numerous points thereof. The same pathogenic agent may enter into either of these groups. For example, streptococ- cus, a kind of microbe, when inoculated subcutaneously, produces a local lesion — erysipelas ; when injected into the veins, it gives rise to a general infection — i. e., septicaemia. Every local lesion presents to study two orders of phenomena: those occurring at the point of application of the cause and those pro- duced in distant parts. At the point where the agent acts, the cellular elements are irri- tated, altered, or destroyed. These first disturbances, provoked directly by the pathogenic agents, give rise secondarily to responsive phenom- ena in the elements that remain alive. These manifestations con- stitute what Dr. Bouchard calls primitive autonomous elementary dystrophies. But the organism is so constituted that a lesion can by no means remain local; it soon arouses a series of secondary manifestations, of which some are due to nervous reactions, others are caused by the absorption and penetration of anomalous substances produced at the primary focus. These secondary morbid manifestations represent pathogenic processes of a second order. They result in the formation of new lesions and the production of new disturbances, which become themselves the starting point of manifestations of a third order, and so on. The pathological process is thus liable to become extremely com- plicated. These successive manifestations are of course of an internal order; only the starting point (the primum movens) of the morbid series has been an external cause. The study of morbid reactions, of which we have outlined the mech- anism, constitutes physiological pathology. It is not to be supposed, however, that these reactions are essentially different from those ob- served in a physiological state. Biological laws are the same in both morbid and normal phenomena. It would be an error to believe that the living being is able to dispose of different manifestations, some of INTRODUCTORY REMARKS 9 them intended for normal conditions, others for pathological condi- tions. The mode of reaction is ever the same; the results vary only in their intensity, but they are directed toward the same end — i. e., they always tend to counterbalance the action of external forces. In other words, health is organic reaction in fixed and pre-established condi- tions; disease is represented by reactions of the same nature, but pro- duced in variable and new conditions. While the causes vary, the reac- tions may remain the same in their essence, notwithstanding the dis- similarity of their manifestations. Pathological physiology must not, therefore, be opposed to, but simply considered as the consequence of, normal physiology. The morbid actions and reactions express themselves by functional modifications and structural lesions, which may be recognised during life or discovered only after death. The structural lesions, the study of which constitutes pathological anatomy, must be considered as the result of functional disturbances; as we are taught in general biology that it is the function that creates the organ, so in pathology it is proved that the disturbance of the function is responsible for the organic lesion. Disturbances and lesions may, as above stated, be disclosed during life; they then constitute the symptoms and signs of the disease, and, according as they are perceived by the patient or recognised only by the observer, are divided into subjective phenomena and objective phenom- ena. In order to study them, we usually begin by interrogating the patient and making a list of his subjective symptoms ; next we proceed to observe the objective signs by passing systematically in review all the apparatus and all the organs. Then comes the task of resolving the final problem: the symptoms presented by the patient being given, to recognise the disease. A difficult problem, indeed, because error may be owing to a bad determination of symptoms as well as to faulty interpre- tation of their relative value. Doubtless there are certain cases in which the recognition of a single phenomenon suffices to settle the diagnosis ; the symptom is then called pathognomonic. But this is exceptional. The relative significance of the different symptoms must be determined, or, as is sometimes said, their semiological value established. When we are through with the methodical analysis of the patient, we must make the synthesis of the disease, connecting each trouble with its immediate cause, determining the nature and mechanism of the latter, and thus ascending the entire scale of successive manifestations until we reach the affection or disease which has been the point of departure of the morbid series. Let us take an example : A man is complaining of pain in the side. This subjective phenomenon leads to an examination of the respiratory 10 INTRODUCTORY REMARKS organs. On auscultation, rales are heard at the base of the lung, indi- cating congestion. But pulmonary congestion is not a disease; the cause of the trouble is to be looked for. So, pursuing the examination, we find out that this man has a cardiac lesion and that the pulmonary manifestations are due to the insufficiency of the heart. If we had seen no more than the congestion of the lung we might, by treating this organ, have done some good to the patient, but we would not have cured him. Having recognised that all depends upon the heart, we may act upon the cause of the disturbances and obtain far better results. By making the diagnosis of cardiopathy, the clinician has thus far done enough for practice, but the nosologist has not completed his task. He knows there is no organic disease ; he must, therefore, discover the cause of the cardiac lesion. Questioning the patient brings to light the fact that he has once suffered from an infectious disease, typhoid fever or acute articular rheumatism, which has given rise to endo- carditis ; this explains all. We have discovered the primary disease, of which the present affection is but the sequel. So far, however, as treatment is concerned, this disease is of no importance; the patient is not suffering from typhoid fever or rheumatism, but from a cardi- opathy, and the medication will be the same, no matter what may have been the cause of the affection. It is not to be supposed, however, that it is useless to inquire into the causes. Here is a man who has lost the faculty of speech; he is attacked with aphasia. Now, aphasia is dependent upon a lesion of the third frontal circonvolution of the left side. Taking our stand upon antecedent or concomitant troubles, we diagnosticate a tumour pressing upon the cortical centre of speech. If we stop there in our diagnosis, we shall have recognised a cerebral affection, and might tell the patient there is no efficacious treatment for it. But, pushing farther our analysis, we discover on the skin old cicatrices revealing the existence of an ancient syphilis. At this point our diagnosis is complete, and leads us to institute the specific treatment which will cure the patient. In this case inquiry into the causative disease has led to the etiological therapeutics which alone could be successful. The determination of an exact and complete diagnosis is attended by that satisfaction which is always experienced when a difficult problem is solved; but, what is of greater consequence, it furnishes the precise indications of treatment. Unfortunately, in practice, the physician is not appreciated according to his skill in determining the nature of a sickness. What the patient and his friends, require of him is prognosis ; they are, of course, unable to verify his diagnosis, but they witness the course and termination of the sickness, and according as his predictions are realized or not they conclude that the doctor was right or mistaken. INTRODUCTORY REMARKS H In a great number of instances prognosis and diagnosis are con- nected. A child, for example, presents certain symptoms which lead ns to diagnosticate tubercular meningitis ; the prognosis is then well-nigh fatal. On a more careful examination, some rather odd phenom- ena might be discovered, and, auscultating more attentively, there might be heard a tubal murmur in the thorax. It was not, therefore, a ques- tion of meningitis, but simply meningeal accidents dependent upon pneumonia. The termination will be altogether different — the patient will recover. In this case the error of prognosis is connected with the error in diagnosis. , Prognosis is not always deducible from diagnosis. Besides diseases with a well-nigh fixed prognosis, there are others in which prognosis totally varies with the forms, the epidemics, the concomitant phenom- ena, and the previous state of the subject. On all these questions there can be given some general notions that may materially help, but for the matter of prognosis, as well as of diagnosis, books and lectures are inadequate. The medical art may be learned only by practice. It is only by seeing many patients and comparing different cases that one acquires the habit of weighing the value of signs which lead to correct diagnosis and prognosis. In establishing the prognosis, the expected influence of the treat- ment should also be taken into account. The therapeutic indica- tions are derived from the study of symptoms, causation, pathogenic process, and pathological physiology. We may, then, according to the indications which serve as our basis of treatment, admit a symptomatic, an etiological, a pathogenical, and a physiological thera- peutics. Symptomatic therapeutics aims to relieve painful symptoms, func- tional disorders, and to combat immediate accidents; it appeases and assuages, but seldom cures. Etiological therapeutics fights the very cause of the evil ; it furnishes antidotes, vermifuges, antiseptics. The method of treatment is etiolog- ical when specific remedies, such as mercury for syphilis, quinine for intermittent fever, and salicylate of sodium for rheumatism are pre- scribed. The morbific cause is often beyond our reach, either because we are unable to touch it by our present procedures or because its action has been transitory ; we must therefore act on the mechanism set in action by the cause or on the reactions presented by the organism. This would be pathogenical or physiological medication. This is what is realized when an attempt is made to restore to the normal rate nutrition disturbed by various causes, or to modify nervous reactions, or to neu- tralize the effects of microbic toxines. 12 INTRODUCTORY REMARKS The therapeutic ideal is to realize these rational medications. But at present, while it is easy to lay down general indications, it is often- times impossible to fulfil them ; the physician must content himself with symptomatic treatment, at times even with empiricism. He must still resort to statistics, whose data are indispensable in reassuring him as to the value of treatments; he thus secures some tentative results, which he will abandon as soon as the advance of science enables him to sub- stitute rational for empirical medication. We conclude, therefore, that the interest of the study of general pathology is not merely a speculative one. It alone can supply guiding ideas which will serve as the basis of the medical art. CHAPTEK II MECHANICAL AGENTS Medical definition of mechanical agents— Mechanical agents acting by pressure: punctures, cuts, contused wounds — Commotion — Compression — Mechanical agents acting by distention— General reactions — The influence of passive movements — Seasickness. Fkom a medical standpoint, mechanical agents may be defined as ^^all those that tend to modify the state of rest or motion of a por- tion or the entirety of a living body — i. e., to modify its position in space/' There may be three examples : 1. The mechanical agent is a body in motion; it encounters a living being opposing a resistance to it. 2. The mechanical agent represents the resistance, and the human body the power. Such is the case when a man falls from a certain height. In these two instances, although the mechanism is different, the result is the same. There is a conflict between power and resistance. 3. The third group, of far less importance, comprises those agents tending to impart motion to the whole body, as occurs when we find ourselves on a moving object or a boat agitated by the sea. Let us consider first the results of the conflict ensuing between an agent in motion and a living being. It is said in mechanics that such an agent is endowed with kinetic energy. This force is equal to half the product of its mass into the square of its velocity, as expressed by if F' the well-known formula — E = . 2 This formula has considerable interest for us. Let us suppose a missile having a mass equal to a unit whose speed at the moment it reaches the living body is equal to 1 ; the energy will evidently be represented by ^. If the mass becomes 20, 100, 1,000 times greater, the velocity re- maining the same, the energy increases as half of these flgures and be- comes 10, 50, 500 times greater. 13 14 DEFINITION OF MECHANICAL AGENTS If the velocity increases in the proportion of 20, 100, 1,000, the energy increases as half of the square of these figures — i. e., as 200, 5,000, 500,000. Thus, while the mass increases as 1,000, the energy increases as 500 ; the velocity increasing as 1,000, the energy increases as 500,000. This clearly shows that the effects produced by the wound- ing body are directly in relation to the velocity acquired. Here is the whole secret of the action of mechanical agents, and notably of fire- arms. A bullet of the Lebel rifle is 8 millimetres in diameter and weighs 15 grammes; the ravages which it produces depend merely upon its velocity, which, at the starting point, is 631 metres per second and is expressed by an energy of 344 kilogrammetres. In order to understand the action of mechanical agents, we must take into account two factors : their power — i. e., their energy — and their direction. The power of a wounding agent is easily determined. Besides its speed, we have to consider its mass or, what is simpler, its weight, its density, and its volume. We must, moreover, take into account its form, and the projections or inequalities of its surface. We can not dwell upon the importance of the various conditions just enumerated ; it is not difficult to understand their multiple effects. In the case of a war projectile it is quite certain that, assuming the energy to be the same, the injury produced will be the less serious the less voluminous, the smoother, and more resisting the wounding body is, so as to pass through the tissues without bursting. The effects vary also according to the direction of the mechanical agent — i. e., according to the angle at which it strikes the living being. A projectile may enter a member of the body perpendicularly, obliquely, or parallel to its axis. The oblique course is evidently longer and causes far greater injury. In the case of a parallel course, the projectile may simply run beneath the skin without touching any important part. In order to introduce harmony into the study of mechanical agents, it has been necessary to adopt a certain number of divisions. Two great classes may be admitted, according as the pathogenic agent acts by pressure or by traction. Mechanical Agents acting by Pressure The mechanical agents acting by pressure are the most important. They are divided into three groups, according to the extent of their surface of contact. According as they terminate in a point, a line, or a plane, they are designated as puncturing, incising, or contusing agents. Punctures. — A puncture may be produced by very slender objects, as needles, pins, cannulae of hypodermic syringes, by splinters, or the MECHANICAL AGENTS 15 sting of certain animals, insects, arachnida, and scorpions. In other cases they are due to instruments with an abrupt enlargement above their termination — e. g., swords. The effects differ, of course, accord- ing as the puncture is a small or a large one. In the first instance no notable accident is generally produced. The puncture with a needle, or a pin, or a splinter causes slight pain, loss of a drop or two of blood, and then cicatrization is rapidly effected. No greater harm results when the objects are a little more voluminous, as bodkins or various instruments employed in the industries. The only danger is that the pricking agent may be charged with toxic sub- stances (poisonous punctures, poisoned arrows) or contaminated with microbes, which invade the little wound. Such punctures, designated as septic, will be considered in connection with infections. It may also happen that the instrument remains in the wound, as is particularly the case when it breaks. The foreign body may remain for years in the tissues without giving rise to any inconvenience. Some- times the agent wanders in the organism and finally protrudes in a region often very far removed from the point through which it origi- nally entered. In a general way, it may be stated that the tissues tolerate for- eign bodies that have merely a mechanical action. The exceptions to this rule are only apparent. Several experimenters have seen nodular lesions, analogous to tubercles, develop around grains of lycopodium, Cayenne pepper, and oyster shells. It must be ad- mitted that in such instances the foreign body had not acted in a merely mechanical manner; an infinitesimal part underwent solution and excited irritation in the neighbourhood. Although it may be ob- jected that the question is often one of insoluble bodies, it must be remembered that numerous researches have established the fact that living cells are influenced by quantities of substances so minute that no chemical test can detect them. Bodies reputed to be insoluble may in reality be dissolved in a quantity sufficient to give rise to reactions on the part of the organism. It is well to recall here the brilliant experiments of Raulin, who proved that the aspergillus can not grow in a silver vessel. The liquid contained in the vessel dissolves an amount of the metal which no re- agent except the living cell can reveal. Naegeli likewise established the fact that a gold coin placed in a glass of water diffuses sufficient copper to arrest the development of spirogyra. One part of a copper salt per 1,000,000,000 suffices to cause the plant to perish. These results are not only of interest to the naturalist ; they lead to the admission that foreign bodies, whatever they may be, exert no pathogenic action except when they pass into solution. A foreign body which remains 16 PUNCTURES absolutely insoluble will be tolerated by the tissues and call forth no reaction. To return to the mechanical action of pricking bodies. We have to consider the effects produced by them on various parts of the organism. Let us first direct attention to the blood vessels. Punctures are well borne by these structures. Blood is quite frequently drawn from veins for diagnostic purposes. A Pravaz syringe cannula, for instance, is introduced and a small amount of blood withdrawn. This method, which had already been employed by Davaine, is often employed at pres- ent, and never causes any accident when the needle is aseptic. Like- wise, intravenous injections may be practised on man, as well as on ani- mals, by the introduction of a cannula through the unbroken integu- ments. A little ecchymosis, if anything, is produced, which, however, is of no importance. Puncture of arteries is Just as harmless. The muscular coats of these vessels insure perfect closure. Intra-arterial injections may be made in this manner in animals, at least in dogs. In rabbits, however, the musculature is insufficient, and puncture of an artery by means of a Pravaz needle gives rise to very grave hemorrhages. In man, puncture of aneurismal sacs is frequently practised. Very fine needles, called Japanese needles, electrodes, and watch springs are introduced. The wound is too small to allow the escape of blood. Even the heart has been punctured. The experiments of Sanc- torius, of Plater, and especially those of Bretonneau and Velpeau, estab- lished the possibility of the introduction of needles into the heart of animals without danger. At the present day experimenters in physio- logical laboratories frequently make use of long needles terminating in a little flag. These are thrust into the cardiac cavities in order to observe the movements of this organ. Practised on dogs and rabbits, this experiment is unattended by bad effects, and it does not even seem to be painful. In view of these experimental results, it has been pro- posed to practise abstraction of blood from the heart in man. This therapeutic measure, consisting in the introduction into the right ven- tricle of a thin needle connected with an aspirating apparatus, can not be accepted without reservation. For even if it be true that in most cases puncture of the heart is harmless, that pins and sword points have been found in this organ which endured them without inconven- ience, still such is not always the case. Some persons have suddenly succumbed in consequence of a simple, nonpenetrating wound (as in the famous case of Latour d'Auvergne). An observation of Dr. Magnan is very interesting in this connection : An insane woman succeeded in com- mitting suicide by means of a pin, three centimetres long, which she drove into her heart at the level of the apex. At the autopsy it was MECHANICAL AGENTS 17 seen that she had made eight punctures in her heart, but none of them had traversed the muscle. Puncture of a nerve causes intense pain, and, what is of more importance, it may be followed in certain instances by a rebellious neuralgia. Puncture of the nervous centres is not serious except when it touches the point described by Flourens under the name nosud vital. Then it causes sudden death through arrest of respiration. In several instances criminals have killed their victims by puncturing them at this point. In this manner, also, a certain number of infanticides have been per- petrated. Punctures of the viscera do not generally produce any accident. For purposes of clinical exploration or therapeutic intervention, the spleen, liver, and lungs have often been punctured. In emptying a hydrocele the trocar has perchance been driven into the testicle without any harm resulting. Even when a reservoir full of liquid is punctured, closure is easily effected. In cases of retention of urine, the bladder is frequently punc- tured, and even the intestine has been submitted to the same operation. In the latter case the puncture is closed by a little hernia of the intes- tinal mucous membrane; not a single drop of the intestinal contents escapes into the peritoneum. This fact has been applied with benefit in the treatment of tympanites caused by intestinal obstruction. But the procedure is not altogether free from danger, and it has therefore been abandoned. Lastly, from a medico-legal standpoint, it is well to remember that puncture of the foetal membranes by means of a needle introduced through the cervix of a gravid uterus is one of the proced- ures most frequently adopted to induce criminal abortion. In the case of large punctures, such as those produced by a sword thrust, the effects are often without gravity, especially when the wound is situated in a limb. Wounds of the two great cavities of the body are divided into non- penetrating and penetrating, according as the wounding agent stops in the wall or traverses it. In the latter case the wounds are designated as simple or complicated^ according as the viscera are involved or not. In some instances swords have passed through the thorax or the abdo- men without touching the organs. Such occurred in the case of a young man presented by Despres at the clinics of Berard (1843) . He fell from a cherry tree, 3 metres high, upon a prop which penetrated the back and made its exit above the pubes, fixing itself farther in the thigh. Passers-by removed him from the pole and he was taken to a hospital, where he rapidly recovered. A sword may pass through the thorax, making its way across the 18 CUTS pleura without separating its layers or giving rise to a pneumothorax. In certain cases the sword may strike the vertebral column and there be broken. It may then become encysted at this point without incon- venience, even though it has passed through the lung. Velpeau had the opportunity of making an autopsy upon the body of a man who had had a foil broken in his thorax fifteen years before. He found in the interior of the lung the iron blade, which measured 8.5 centimetres in length. However, when the organs are injured certain disturbances are generally produced, among which two phenomena are most important — namely, hemorrhage, sometimes sufficiently profuse to cause death, and, in case of injury to intra-abdominal reservoirs, escape of the liquid con- tents from within the wounded organ. Cuts. — Cuts are solutions of continuity produced by instruments, such as knives, saws, sabres, and also by splinters of glass and pottery. In this group are to be included the cuts sometimes caused by a sheet of paper or a tensely stretched wire. Finally, although the mechanism is more complex and the cut may be complicated with contusions, we may add to this list the great damage caused by the horns of animals, notably of cattle. In order to recognise the nature and gravity of the accidents pro- duced by cutting agents, we must take into account their weight, the force with which they strike, and also their direction. If a knife is simply thrust into the tissues the wound produced is much less grave than when care is taken to modify its direction after introduction — i. e., to raise or lower the handle. Under such circumstances the person using the knife is more certain to strike some important organ and to injure it to a great extent. All tissues are not affected in the same manner by cutting instru- ments. In this regard the following rules have been established: Tensely stretched parts are incised ; soft parts are crushed ; hard parts break. These formulae, however, are not absolute. In certain instances a bone, instead of breaking, is penetrated by the cutting instrument, and the latter may even break off and remain in the osseous tissue. Unlike punctures, cuts often involve the blood vessels and may give rise to hemorrhages. The hemorrhages are the more profuse the cleaner the incision is, the more firmly the vessel is fixed to the neigh- bouring parts, and, consequently, the less tendency it manifests to con- tract. In certain regions — e. g., in the neck — the veins being held open by the cervical aponeurosis, air may enter and produce accidents, which will be referred to in connection with gas emboli. When the cutting instrument incises a nerve we observe, in addition to the immediate pain, an anaesthesia or a paralysis affecting the region MECHANICAL AGENTS 19 to which the nerve is distributed. These accidents are not incurable; for, on the one hand, the severed ends of the nerve may again be united, and, on the other, a functional supply is re-established through the agency of the numerous anastomoses connecting the various portions of the nervous system. When any one of the great cavities is incised, the wound, as in the case of punctures, may be nonpenetrating or penetrating, and in the latter instance it may be simple or complicated. Even though the wound does not involve any organ, it is much graver than a puncture, because it exposes the individual to a new accident, to hernia — i. e., the escape of the viscera. If the thorax is wounded, the lungs may pro- trude; if the abdomen is incised, the intestines and the omentum; at times the stomach, spleen, and bladder may escape. It is hardly neces- sary to say that such complications are of a grave nature, since they lead to contamination and infection of the protruded parts. When a limb is incised, the solution of continuity leads to modifica- tions, which must be well recognised, and which are explained by the contractility of the tissues. Suppose a limb is cut off in a plane per- pendicular to its long axis ; the resulting stump assumes the aspect of a cone the apex of which is represented by the bone and the base by the skin. This result is to be explained as follows : The bone is, of course, not displaced ; the deeper muscles adhering to the bone and retained in position by the aponeuroses have retracted very little; the superficial muscles, being more loosely attached, have retracted, and the skin, being far more contractile than the other tissues, has shrunken to a degree greater than all the subjacent parts. Therefore, in order to avoid a conical stump, it is necessary to incise the skin at a point farther down the limb than where the superficial muscles are severed, the latter farther down than the more deeply situated muscles, and the deeply laid muscles just beyond the cut end of the bone. In retracting, the muscles cause the cut ends of the tendons to recede into their sheaths, so that it is often difficult to bring their severed portions into contact. The contractility of tissues does not always act unfavourably. The contractility of the coats of the vessels plays an important part in hemostasis. When an artery is severed the external coat does not change its position; the middle coat, however, retracts, and in this manner diminishes the calibre of the vessel, thus favouring the forma- tion of an occluding clot. In other instances the contractility of the tissues hinders repara- tion. This is what happens when the trachea is incised. On transverse or even incomplete section of this structure the two lips of the wound retract, and this naturally prevents cicatrization. With the intestines 20 CONTUSED WOUNDS the effects are similar but far graver, for the gaping of the wound permits the escape of faecal matter into the peritoneal cavity. When incisions are quite clean they very readily heal as soon as the separated parts are united and retained in position by sutures. It is then said that the wound heals by first intention. Such wounds, how- ever, may become infected and open a route for bacteria. Such an oc- currence is comparatively rare, for the clean-cut tissues preserve a very high degree of vitality and oppose the development of pathogenic agents, as when under normal conditions. Between what obtains here and in the case of contused wounds there is a very decided dif- ference. Contused Wounds. — Wounds caused by Firearms, — As already stated, the contusing agents are those which come in contact with our bodies by a blunt surface. Of contused wounds, the most interesting are those produced by firearms. Let us, therefore, begin with their study. After having indi- cated some general principles applicable to all firearms, we shall con- sider the effects caused by the new projectiles. In every wound caused by a bullet three parts are to be taken into consideration — ^namely, the point of entrance, the tract, and the point of exit. When the ball has lodged in the body there is evidently but one orifice, and the tract is therefore said to be blind. The wound at the point of entrance is always smaller than at the point of exit; it is even smaller than the diameter of the projectile. This phenomenon is due to the elasticity of the tissues. On the other hand, the aperture of exit is larger than the diameter of the ball; its diameter may be two to three times greater, and may attain to from 10 to 15 centimetres. The wound at the point of entrance is regular, with clean edges; the wound of exit is lacerated and often gives out particles of muscle and fragments and granules of bone. The tract of the bullet is direct or tortuous. It is direct when the missile is driven with great force through all the parts it encounters; it is tortuous when the speed of the bullet has been reduced and it ricochets over a bone. After having fractured a bone, a ball may impart to the fragments sufficient force to cause them to act as glancing missiles and aggravate the lesion by enlarging the wound. Fragments and granules of bone and particles of muscle are real foreign bodies, which must be eliminated in order to make cicatrization possible. The wound may also be con- taminated by solid substances, such as pieces of clothing, stones, and sand, which have been introduced from without. Moreover, the pro- jectile may lodge in the tissues ; it not infrequently breaks up, and each fragment then produces further disorganization in diverse directions; or a fragment may escape outward, thus leaving an aperture of exit MECHANICAL AGENTS 21 and giving rise to the erroneous assumption that the projectile is no longer to be looked for in the wound. Bullets may produce three types of fractures in bones. In some instances the bone is simply perforated. If the cranium is the seat of injury there may be found two clean orifices, one corresponding to the point of entrance, the other to the point of exit of the projectile, the latter by far the larger. At other times the bone breaks by contact ; the fracture may be clean, as if cut with a sharp instrument; oftener it is comminuted — i. e., the fracture at times consists of a considerable number of fragments, or, as is frequently stated, of splinters. In higher degrees there is a true bursting of bone. Lastly, the third variety is produced when the bullet strikes the bone in a direction almost paral- lel to its long axis and cuts a veritable groove in the diaphysis. It is readily understood that a projectile moving at a low rate of speed, instead of breaking a bone, may lodge in it and flatten out ; in other instances it may be diverted from its course, as is often the case when a revolver is discharged at close range at the thorax or the skull. Under such circumstances the bullet may follow a rib or a bone of the cranium without penetrating the cavity. In such instances it produces a subcutaneous '^ set on wound,^^ which readily heals. Wounds of the arteries give rise to very grave hemorrhages. The statistics of the Crimean War show that in 18 out of 100 cases death (vas due to this cause. Finally, when a ball strikes an organ it may produce three varieties of lesions: a perforation, a laceration, or a crushing of tissue, which is then truly pulpified. Several hypotheses have been advanced to explain the action of projectiles. Melsens attributes an important role to the stratum of air which forms a kind of sheath around the ball, at least when its velocity exceeds 340 metres. Kocher compares the resistance of tissues, particularly of bones with cavities containing marrow and blood, to that of a wooden barrel filled with liquid. If an empty barrel is shot at, the ball passes through, making simply two orifices ; if, however, the barrel is full of water, the energy transmitted to the incompressible liquid causes dis- ruption and bursting of the constituent parts. This conception unques- tionably contains a grain of truth and accounts for certain phenomena. But there is here no more than an accessory condition; the real cause of the commotion caused by the projectiles depends upon their great velocity. The terrible effects of the arms of war are thus explained. The great revolution in military art by the introduction of organic explosives and powders has led to the transformation of armament and 22 CONTUSED WOUNDS to the utilization of projectiles of small calibre. The ball of the Chasse- pot and Gras rifles, which was formerly 11 millimetres in diameter, has been reduced to 8 millimetres; its weight also has been decreased from 25 to 15 grammes. On the other hand, the velocity has been increased. Instead of 450 metres the Lebel ball travels with an initial velocity of 631 metres per second. The rotary motion, which formerly amounted to 800 turns per second, is now 2,550. Since force depends upon velocity far more than upon weight, it will readily be understood that the Lebel ball, projected with a greater force, should be more effective. Its power is stated as 344.192 kilogrammetres, whereas in the Gras rifle it did not exceed 257.175 kilogrammetres. The truly active work accomplished — i. e., the coefficient of pressure per square millimetre — is three times greater: from 2.61 kilogrammetres it is raised to 6.847. CoxmTRY. Model of rifle. Calibre. Weight of bullet. Length of bullet. Sheath of bullet. Speed at 25 m. mm. grammes. mm. metres. France 1886 8 15 30 German silver. 600 Germany . . Mauser-Mannlicher (1888) 7.9 14.7 31.6 Steel covered with German silver. 630 England . . . Lee-Medfort (1889). 7.7 14 31.6 Id. 635 Austria Mannlicher (1888). 8 15.8 31.8 Id. 630 Roumania. . Mannlicher (1893). 6.5 10.3 31.4 Steel covered with nickel. 700 Russia 1891 7.63 13.86 30.48 German silver. 615 Switzerland Ruhin-Schmidt (1889) 7.5 18.7 30 Copper. 600 The great velocity of projectiles and the reduction of their calibre have necessitated a change in their construction. In order to avoid the fouling of the barrel of rifles with lead and to prevent alteration in their form, and also to assure greater penetration, it has been found neces- sary to use projectiles having a nucleus of lead guarded by a layer of German silver. They are ogival cylinders measuring 30 millimetres in length; the anterior part, instead of tapering, bears the letter S. The various European countries have modified their armaments in the same direction as has France. The question having a certain amount of real interest, we present in tabular form on this page the particular features of the principal models. It will be seen that the differences are, on the whole, of little importance. The new projectiles were first experimented upon by Bruns, and later by Habart and Keger. These observers employed reduced charges and shot at cadavers placed at limited distances. They found that the pro- jectiles passed through the tissues and bone without being distorted or divided, and they never remained in the wound. They were, in fact, ideal projectiles of war; there seemed nothing to be done except to MECHANICAL AGENTS 23 arrest bleeding and to close the wound, since there were no foreign bod- ies or splinters to be looked for. However, the researches of Chauvel and Nimier, Delorme and Cha- vasse, and Bogdanick led to less optimistic conclusions. The brilliant work of Demosthen conclusively established that the new projectiles are capable of producing fearful injuries, and his views were confirmed by von Coler and Schjerning, and by Labat. The difference in results is due to the fact that the first experiment- ers employed reduced charges. They were thus able to fix at will the speed of projection; but in reducing the charge they diminished the speed of rotation. Now, the latter remains almost constant through- out the entire flight of the projectile; it is decreased hardly any with distance. It is to this factor, therefore, that the injuries produced by the new firearms are largely to be attributed. Experimenting under actual conditions, it was recognised that, con- trary to the assertions of several authorities, the new projectiles were easily distorted and fractured. Delorme and Chavasse admit the fol- lowing classification in this respect : deformation of the point, lateral deformation, partial separation of the envelope, fragmentation with separation of the lead nucleus and of the envelope. These altera- tions may be produced on contact with bones, or when the ball rolls over after having struck a resistant plane, such as a gun, a piece of equipment, a carriage, or a wall. Thus deformed, a ball causes consid- erable damage and often lodges in the wound. Thus we find that all the lesions which the old arms produced are noted here. While the Chassepot projectiles cause no serious injury at 1,200 metres, the new projectiles are effective at more than 1,500 metres ; at 2,000 metres their velocity is still 197 metres per second. In former days a ball exhausted its effects upon the object with which it came in contact. At the present day the projectile can penetrate six cadavers at the beginning of its flight ; at 1,500 metres it retains suffi- cient force to penetrate one. Finally, as Demosthen has shown, the lesions produced are not merely perforations. In the cranium a genu- ine shattering of the bones is induced ; in the bones of the limbs, even when the projectile is discharged at a distance of 1,500 metres, com^ minuted fractures with 15 to 20 fragments are observed. Along the track of the missile the muscles are contused and mixed with fragments of osseous substance. It may be added that osseous fragments, receiv- ing a certain amount of energy from the ball, may inflict glancing blows to the tissues ; that cleanly cut vessels bleed to an alarming extent. If we remember that the effects are always less marked on the cadaver than on the living body, we arrive at the conclusion that the new pro- jectiles are capable of causing lesions incomparably more serious than 24: EXPLOSIONS the older types. It is then sad irony to designate as humane pro- jectiles those bullets whose field of action is of wider range and whose destructive power is so much more extensive ! Explosions. — It is useless to dwell upon the various conditions under which explosions take place. The ignition of illuminating gas, the bursting of a vapour or compressed-air engine, the explosion of fire damp, the ignition of substances employed in the industries or used for criminal purposes, such as fulminate of mercury, dynamite, picrate, acetylene, represent a series of well-known examples. The accidents produced by explosives are more complex than those caused by projectiles. Aside from the mechanical effects, the increase of pressure and the modification of temperature are to be considered. In some instances the temperature reaches 2,000° C. In other in- stances — for example, when an apparatus containing compressed air explodes — there results such a degree of cold as to induce death of the integument by freezing. Moreover, certain gases are deleterious, and to their mechanical and physical effects is added toxic action. The first result of an explosion is an increase of pressure. In the case of illuminating gas, a mixture with air of one sixth of its volume gives a pressure of 18 atmospheres in the open and 23 atmospheres in a closed room. With explosive substances the figures are far higher; fulminate of mercury exploded in its own volume gives a pressure of 18,750 kilogrammes to the square centimetre ! Under the influence of these enormous pressures, a person stationed within the dangerous zone is violently thrown and flattened against the walls. In order to avoid this accident in factories where explosives are handled, the shops are made of wood. In the event of an explosion, the feebly resistant walls give way, leaving a free passage for projected individuals. A second danger lies in the fall of walls and ceilings. But the most fearful accidents are those produced by dispersion of a multitude of small fragments of glass, wood, stone, and metal. Thrown with great force, these bodies, however minute, may cause ter- rible destruction. This is easily understood from the following two facts borrowed from Brouardel : An explosion occurring in a shop in Beranger Street, where ful- minate of mercury destined for the manufacture of children's toys was stored, destroyed fourteen lives. Among the victims was an individual whose abdomen and thorax were torn open ; the intestines, lungs, and heart were as though they had been minced. These frightful lesions were simply due to the projection of pieces of pasteboard used in the manufacture of cartridges. The small foreign bodies had lacerated the viscera, and the force of penetration was such that several fragments had entered the vertebral column to a depth of 4 to 5 millimetres. Mechanical ageni^s 2g In the dynamite outrage which took place in the Boulevard Ma- genta, one of the victims received more than a thousand wounds pro- duced by sand, splinters of glass, and wood. Some idea of the force acquired by the minutest objects is given by the fact that in this same explosion a glass candlestick was found perforated through and through by a match. Finally, cartridges of dynamite sometimes explode in the hands of workmen in arsenals. In such instances the bones of the hand then act as so many projectiles which penetrate the abdomen or the thorax. In a case observed by Bouchard a finger nail was driven with sufficient force to penetrate the muscles of the thorax and pierce the lung. The various objects thus thrown are generally soiled with microbes, which may give rise to fatal infection. Thus, the man referred to in connection with the Magenta outrage died from the infections which developed in his wounds. Simple Contusions and Contused Wounds, — We now come to the consideration of the less terrible but more common agents of contusion. Let us note, for example, the ejffects produced by blows from a club, kicks of either man or animals, collapse of buildings, or falls. There may result a simple contusion or a contused wound. There is contusion when attrition of soft parts is produced without wound or fracture. There is a contused wound when the soft parts are torn. In bones, three kinds of fractures may be observed : 1. Fracture at the point of application of the cause. For instance, when a traumatism — a blow of a club or a kick of a horse — ^breaks the bone at the point where it is struck. 2. Fracture at a distance. Here a curvature of the bone occurs, which gives way at its point of least resistance. 3. Fracture by contre-coup. A blow on the top of the skull, for example, causes a fracture at the base. These three varieties of fractures may be observed when an indi- vidual falls on his heels. According to a multitude of concomitant conditions, a fracture of the calcaneum or of the leg, of the body or neck of the femur, of the pelvis, the spine, or the base of the skull may occur. If the wounding agent is less active it causes a simple fissure, at times but microscopic fissures. These lesions readily heal ; but they may be followed by persistent pain, and even by the development of hyper- ostoses as a result of too active reparative processes (Gussenbauer). When a contusing body acts on the viscera, the lesions produced vary according to the resistance offered by the latter. In the case of the brain, the tissue is often reduced to a pulp ; in that of the liver or the 26 SIMPLE CONTUSIONS spleen, simple or radiate fissures are produced, which are capable of giving rise to profuse hemorrhages. If the contusing agent strikes an organ provided with a thick cap- sule — -e. g., the testicle — the effects differ. The experiments of Monod and Terrillon have shown that the testicle is capable of resisting great pressure. A force of 50 kilogrammes is required to burst its envel- ope, which then yields and ruptures abruptly. Notwithstanding all the injury inflicted by contusing agents, in most instances they do no more than dissociate the cells without de- stroying them. For this reason the bruised tissues, if transplanted beneath the skin of an animal, may retain their vitality and be ingrafted. (Gussenbauer), and this also explains why repair is so easily effected. When a hollow organ is subjected to slight contusion, nothing be- yond simple ecchymosis or a slight attrition of the walls occurs. In severe cases a rupture may take place. This accident generally results from compression of the organ between the wounding agent and some resistant part of the body — viz., a part of the skeleton. The kick of a horse perforates the intestine by pushing this organ against the spine; it is this bone that produces the perforation. Likewise, in falls upon the perineum, rupture of the urethra is due to the pressure of the latter against the ischio-pubic branch of the pelvis. Finally, if an organ full of liquid is contused, it bursts ; such is par- ticularly the case with the bladder. Eupture of the blood vessels naturally gives rise to hemorrhages, which may occur either immediately or subsequently to the injury, in the form of simple ecchymoses or interstitial effusions; or they may take place inside of some visceral cavity. Interstitial hemorrhages, when profuse, give origin to genuine tumours — ^hematomata. These may be circumscribed or diffuse. While they are, as a rule, limited, they may subsequently increase in size. Moreover, they may often become the starting point of suppurations. In addition to effusions of blood, those of serum and oil are to be mentioned ; and if the traumatic focus communicates with the exterior or with a neighbouring organ, effusions of gas or organic liquids may occur. The secondary effects of contusions will be studied in another chap- ter. These are sphacelus and inflammation of the focus, and in some instances the formation of emboli in the diseased tissues. Commotion. — An interesting variety of contusion is represented by the phenomena described as commotion. Two principal varieties are admitted — cerebral and medullary commotion. They will be treated of in connection with nervous reactions. It may be noted here, how- ever, that the effects are in some instances accounted for by mechan- MECHANICAL AGENTS 27 ical lesions. Under the influence of a blow dealt at the anterior part of the cranium, the cerebro-spinal fluid, being driven abruptly, pro- duces suflBcient lesions in the floor of the fourth ventricle to explain the symptoms. Compression. — We have hitherto supposed that mechanical agents acted by sudden pressure, and that they were endowed with a great amount of energy. In other cases the morbific agent exerts a con- tinuous pressure, tending to diminish the bulk of the organs and to prevent their free expansion. Such a condition is spoken of as com- pression. Compression may be produced by tight clothing, notably by shoes. It is often connected with the occupation of the individual, and is then attended by friction. In other cases it may result from improper ad- justment of a surgical apparatus, or the use of crutches, etc. Compression may also result from the development or displacement of certain parts of the organism. The head of the foetus, when it rests too long in the parturient canal, may compress the nerves of the pelvis or the walls of the utero-vaginal canal. Fragments of splintered bone, effusion of blood, and tumours push away neighbouring parts and cause disturbances and alterations. The simplest cases are those in which the epidermis is compressed and becomes the seat of callosities. If a mucous membrane is com- pressed in a marked and persistent manner the result is an ulceration which may terminate in necrosis, gangrene, or perforation. In the case of a vein, compression produces a stasis, which is compensated by the development of a collateral circulation. The collateral circula- tion, however, is at times insufficient, and, as a consequence, oedema or, in very rare cases, even gangrene may appear. The latter is a far more frequent complication in those instances in which ischsemia results from compression of an artery — a state highly favourable to the devel- opment of microbes. Finally, compression may affect a nerve, as is sometimes the case where crutches are used. The same thing occurs when a person falls asleep while supporting his head with him arm. In this case the radial nerve is compressed by the head at the groove of torsion. Formication is first felt, then sensation diminishes and disappears, and finally move- ment becomes impossible. If compression has lasted but a short time the paralysis soon disappears, and sensation returns, preceded by quite painful formication. It is of importance to know these facts. Paralysis of the radial nerve was formerly attributed to the action of cold. It was said to occur when a person slept in the open air or with the window open. Dr. Panas has justly opposed this view. He has pointed out that paral- 28 • COMPRESSION ysis does not attack the limb exposed to the air, hut the one that is compressed by the head. Compression of the viscera by external agents is more rarely ob- served. We need but mention the effects produced by too tight belts and, above all, by corsets, which give rise to deformities of the stomach and liver. At autopsies it is not rare to find upon the surface of these organs the furrows which plainly show the impression left by the ribs pressed inward by the corset. The corset is even believed to play a part in displacement of the kidney. Renal ectopy, which is observed chiefly in women, and nearly always upon the right side, is attributed to the action of the liver, which, being pushed by the corset, presses the kidney out of place. Mechanical Agents acting by Distention All those agents which we have thus far studied exert pressure. We shall presently consider those that act by distention. Disregarding distention of the esophagus by a too bulky bolus of food, and the therapeutic procedure employed in the treatment of a stricture by abrupt or progressive dilatation, we see that mechanical agents may act in two ways : In some cases the individual is fixed and the wounding agent tends to distend and to tear off a part of his body ; in other cases a part of the body is held motionless by the external agent and the individual causes distention by an abrupt movement. As principal illustrations it suffices here to refer to the severance of a limb from the body by a revolving wheel or a power belt or the jaws of an animal. There are instances on record in which limbs were torn off by the surgeon in the course of mechanical manoeuvres for reducing a luxation. When a limb is strongly stretched it becomes distended. The limit of extensibility being reached, a rupture is produced. The rupture, how- ever, does not occur simultaneously in all the tissues. The skin, by virtue of its elasticity, is almost the last to yield, the nerve trunks alone resisting longer. Separation having been effected, the tendons remain attached to the part torn off, carrying at their free ends some fragments of the muscles into which they were inserted. The ligaments behave in a manner similar to the tendons and separate the apophysis to which they were fixed. The muscles rupture at varying heights. According to Polaillon, the extensibility is overcome and then the relaxed muscle is torn. The majority of surgeons, however, are of the opinion that rupture occurs in consequence of a reflex contraction — i. e., the muscle ruptures itself. In regard to the skeleton, rupture sometimes takes place by separation of articulations ; at other times, especially when the cause has acted obliquely, a comminuted fracture is observed. MECHANICAL AGENTS 29 It is a remarkable fact that wounds produced by distentions are not, as a rule, very painful and do not cause profuse hemorrhages. The latter phenomenon is explained as follows : The arteries being strongly distended, the inner and middle tunics are the first to give way; the outer coat becomes elongated and narrow, and when it breaks it be- comes twisted so as to obliterate the lumen of the vessel and prevent bleeding. A most interesting observation in this connection is recorded by Morand : A man employed in a mill was caught by a power belt and his arm torn off. The enormous wound thus inflicted was attended by hardly any hemorrhage, so that he was able to walk to and consult a physician. He recovered in two months. As already stated, nervous tissue resists to a high degree. In cer- tain instances a severed limb is held only by the nerve trunks. The lat- ter, before rupturing, admit of considerable elongation. The median and ulnar nerves may be stretched to an additional length of 15 to 20 centimetres. The results of Tillaux and Trombetta demonstrated the fact that very great force is required to rupture a nerve. On the cada- ver it is possible to raise the entire body by pulling the sciatic. From 50 (Tillaux) to 84 kilogrammes (Trombetta) are required to cause rupture. Even for less voluminous nerves considerable traction is requisite before rupture occurs — 38 kilogrammes for the median, from 20 to 25 for the ulnar, and for a little filament like the supraorbital nerve 2.5 kilogrammes. Eupture does not occur at the point of application of the force. It is generally produced at the points of flexion. In the sciatic, for exam- ple, it occurs behind the ischium. In some cases the roots themselves are torn and detached from the spinal cord. Eesistance and Reaction of the Organism In studying the mechanical agents, two factors are always to be taken into account — namely, the action of the wounding body, the importance of which we have sufficiently shown, and the resistance of the organism, which will now be considered in a few words. Since the human body is a nonhomogeneous structure susceptible to numerous reactions, and notably to muscular contractions, which modify the effects of resistance, the problem is quite a difficult one. There are, however, certain influences which have been well determined. One is the age of the subject. Under similar given conditions chil- dren resist better than adults, and the latter better than the aged. In children, very energetic causes are necessary to produce marked dis- turbances and fractures. The incomplete ossification and the flexibility 30 REACTION OF THE ORGANISM of the bones explain their great resistance, as evidenced by the fact that a child may fall from a very great height without harm. On the other hand, in the aged the bones are rarefied and brittle. They are affected by what is called osteoporosis, and on the slightest cause they break. An abrupt movement in bed may cause a fracture of the neck of the femur, or a paroxysm of coughing may provoke a fracture of the ribs. The resistance of the blood vessels is no less variable. In women, the slightest shocks are often sufficient to give rise to ecchymoses. Cer- tain subjects, affected by a morbid state called hemophilia, have very grave hemorrhages from the slightest abrasion. Finally, arteriosclero- sis, by diminishing the elasticity of the arteries, favours their rupture. In this connection may be mentioned aortic insufficiency caused by a blow on the thorax; the sigmoid valves rupture because they were already diseased. Such illustrations might easily be multiplied, but these are sufficient to indicate the influence exercised by previous organic lesions upon the effects of traumatic agents. General Eeactions. — In addition to local lesions, we must take into consideration the general manifestations occasioned by traumatism — namely, the various reactions in distant parts. The question whether a traumatic lesion can give rise to fever has of late been a matter of much discussion. After numerous experi- mental researches, the question seems to have been solved in the affirma- tive. Aseptic fevers are slight and transitory. Whenever the febrile movement is continuous, we should always look for some complication of an infectious nature. Wounds attended by great mortification of tissues and extensive contusion are especially liable to invasion by microbes. The clean-cut wounds — for example, those produced by sharp instruments — are less frequently subject to infection. This is not due to the fact that the bacteria do not contaminate them, but, on the contrary, the tissues possess sufficient vitality to oppose their development and prevent their multiplication. In a great number of subjects traumatic lesions give rise to intense nervous reactions, agitations, and delirium, and when violent may bring about a very grave and often fatal morbid complication — namely, nerv- ous shock. Aside from these transitory disturbances, a series of perma- nent affections may appear. Hysteria and, more rarely, chorea and paralysis agitans have been produced in predisposed subjects by even slight traumatism. These disorders of external origin, as has just been indicated, may be transmitted by heredity. In this connection nothing is more interesting than the classic experiment of Brown- Sequard. The great physiologist severed the sciatic nerve in a guinea MECHANICAL AGENTS 31 pig ; this traumatism gave rise to epileptiform convulsions, which were transmitted to the offspring. In certain cases traumatism may be followed by permanent dis- orders, especially when nerves are involved. We here refer to trophic disorders, such as keloids, periostoses, exostoses, glistening state of the skin, small ulcers called by W. Mitchell causalgia, or nervous disturb- ances, such as neuralgia and painful cicatrices. In other cases trau- matism proves to be an occasional cause of morbid localizations. In consequence of a blow upon the toe a paroxysm of gout may be observed, or perhaps a microbic localization, or even the development of a neo- plasm. Max Schuller's classical experiment is well known. He inocu- lated tuberculosis beneath the skin of a guinea pig. At the same time a traumatism was produced at the knee. The pathogenic agent migrated to the wounded joint, and there gave rise to the formation of white swelling — tumor alhus. Such facts are daily observed in clinics. Tubercular arthritis and meningitis are often referable to traumatic causes. Perroud observed in the boatmen of the Khone a unilateral tuberculosis, the localization of which is due to the fact that these men propel the boats by means of a long pole which they press against one of their clavicles. Influence of Passive Movements. — We have hitherto supposed that mechanical agents tended to modify the situation of a part of our bodies. The result is a sort of conflict the consequences of which we have already considered. In many cases a mechanical agent displaces the subject entirely, and, by a movement passively transmitted, it carries him into space. If the displaced individual finds himself in a locality absolutely inclosed and endowed with uniform motion, and if all the surrounding objects move with him, he will not be conscious of movement and will not present any physiological or pathological reac- tion. In fact, it is easy to understand that we perceive our displace- ment through the changes occurring in our relations to the surrounding objects or our situation toward them. When we undergo passive movement, a series of manifestations occur around us which, if slight, make us aware simply of our dis- placement; but when they are intense they give rise to pathological phenomena. The first of these consists in variations of the blood circulation. By virtue of centrifugal force the blood tends to move in a reverse order to the movement which we undergo. The changes occurring in the circulation can be perceived through the peculiar sen- sation which we experience when the movement suddenly ceases — for example, when a train suddenly stops under the influence of the air brake. No matter how perfectly the vehicle may be equipped with devices to avoid jarring, the adjustment is never so complete as to secure 32 PASSIVE MOVEMENTS us against all agitation. Here is a new cause of disturbance. Serious disorders may at last appear, as in the case with railroad employees, particularly engineers. However, the agitation may also produce some favourable results. Patients suffering from paralysis agitans have often been improved by travelling or riding in automobile car- riages. Impressed with this fact, Charcot conceived the idea of apply- ing agitation or commotion to the treatment of this neurosis. It is a matter of common observation that great oscillations, even when rhythmical, may occasion nervous disturbances. Such is the case with the swing. The dizziness resulting from its use is due to numerous causes. At each oscillation the centrifugal force tends to modify the circulatory hydraulics; the resistance of the air produces excitation in the mucous membranes and the skin; the displacement of objects acts upon the organs of vision; and, lastly, changes in the fluid of the labyrinth take place which affect the semicircular canals. Since the observations of Flourens and Cyon, it is known that an important part is played by this portion of the internal ear in equili- bration. An analogous mechanism serves to explain one of the most inter- esting disturbances of this order — namely, seasickness. In this case, however, the phenomena are more complex, since they are of a com- bined nature. We must take into consideration the oscillations of the vessel from side to side as well as those from stem to stern, and, in the case of steamers, to these must be added the vibrations produced by the engines. The results are disturbances of a sensitivo-sensory nature, modifications of the circulation, and displacement of the abdominal viscera. It is to the latter factor that the majority of authors attribute the most important role in the production of the manifestations. The visual disturbances, secondary though they be, should not be ignored, for it is often possible to avoid seasickness by fixing the vision upon distant objects. Objects that are constantly in motion should not be looked at. It is a well-known fact that when at rest we may experience malaise and dizziness by simply fixing our eyes upon moving objects. This, however, is only an auxiliary cause, since an individual may suffer from seasickness while the eyes are closed, and, moreover, the blind are not exempt from it. The influence of visual excitation upon the causation of dizziness is also made manifest when the gaze is fixed upon the water or ground over which we move while riding on a river boat, in a carriage, or train. Yet, contrary to what would naturally be expected, no dizziness is expe- rienced during the ascent of a balloon, no matter from what point the aeronaut may look. In conclusion, it should be borne in mind that mechanical agents MECHANICAL AGENTS 33 may serve to &x us in a determined position. They then oppose our movements, and thus cause death. When, for example, an individual is caught in the ruins of a building, the debris resting upon him prevents the movements of the thorax, and thus causes asphyxia. In other in- stances mechanical agents fix the body in such positions as to com- pletely modify the circulation. The human subject bears these changes fairly well, and, except when the head is placed too low, the circulation is carried on in a normal manner. In animals adaptation is not so readily accomplished ; an animal fixed vertically soon dies from cerebral anaemia, since the heart is unable to cope with gravity and to send to the nerve centres a sufficient amount of blood. CHAPTER III PHYSICAL AGENTS Atmospheric pressure — Influence of its variations — Mountain sickness — Altitude cure — Heat — Burns — Heat stroke and sunstroke — Cold — Frostbites — Light, its local and general effects — Braidism — Sound — Electricity — Physiological action of currents — Fulguration and sideration — Electrocution — Practical applica- tions of electricity. Physical agents represent different forms of energy; they are five in number : atmospheric pressure, heat, light, sound, and electricity. Atmospheric Pressure The air exerts upon the earth a pressure of 1.03 kilogramme per square centimetre, or a total pressure of 18,000 kilogrammes for the human body. We are able to support this enormous pressure only because it is distributed in a uniform manner. The variations of atmospheric pressure can influence our state of health. When they are large and abrupt, and especially when rapid depressions of the barometer take place, nervous disturbances are ob- served in certain subjects, constituting barometric neurosis. Doubtless this expression is not perfect. Along with the variations of pressure, there occur changes in temperature, in humidity, in the solar radiations, and in the direction of winds which must play a part in the final result. Nevertheless, the barometric disturbances are most easily ap- preciable and have served to designate the morbid manifestations. The same influences may intervene to modify the resistance of living beings to infectious agents ; they explain the development of seasonal maladies and play an important part in what is called the epidemic temperament (le genie epidemique). In order to distinguish the influence of atmospheric pressure from other factors, it is necessary to consider what takes place when climbing a mountain or making a balloon ascent. Such a study has a double interest: through the serious accidents which it brings to our knowl- edge, it gives us an idea of the beneficial effects of a sojourn in high regions and of the mechanism of altitude cures. 84 PHYSICAL AGENTS 35 It is a well-known fact that during an ascent the pressure decreases. The following figures, taken from the remarkable work of Regnard, give an idea of the variation of pressure with altitude. The sea level, upon which there is a pressure of 76 centimetres of mercury, is taken as a standard. The sea Orthez Aigle-Bains Chamounix St. Bernard The observatory of Mont Blanc The pass of Parang (the highest point habit- ually visited by man) Mount Everest (the highest point of the globe) The ascents of Croce-Spinelli and Sivel The ascents of Glaisher Barometric height. Altitude (in metres). 76 75 105 71 540 67 1,050 56 2,370 42 4,810 37 5,835 24.8 8,840 26 8,600 24.8 8,838 In ascending in the atmosphere a number of disturbances are expe- rienced which may prove fatal. It is an error to attribute these symptoms to modifications in the constitution of the atmosphere. Whatever the altitude, the composition of the air is always the same; it always consists of 21 parts of oxygen, 78.06 of nitrogen, and 0.94 of argon. By means of a balloon sound Cail- letet, the aerophile, was able to collect a sample of air at a height of 15,500 metres. The anlysis made by Muntz and Schloesing, Jr., gave 20.79 parts of oxygen, 78.27 of nitrogen, 0.94 of argon, and 0.0033 of carbonic acid. The somewhat low figure for oxygen is explained by the conditions of the experiment — a small quantity of this gas was absorbed by the copper plugs and by the oxidizable grease used to facilitate their working. The only modification of the air in high regions is a notable in- crease in ozone; and this possibly is the explanation of certain thera- peutic effects. A recent analysis made by Maurice de Thierry makes the variations of this gas quite evident : At the same hour of the same day, air gathered at Paris yielded 2.3 milligrammes of ozone; at Cha- mounix (1,050 metres) it yielded 3.5 milligrammes; and, finally, at Grands Mulcts, on the slope of Mont Blanc (3,020 metres), 9.4 milli- grammes. Since the variations in the chemical composition of the air do not explain the harmful effects of altitudes, let us consider other modifica- tions which take place on mountains. There is, in the first place, a fall in the temperature. It is regarded as a law that the temperature diminishes one degree centigrade for each rise of 160 metres, a figure which may be retained, although it may not 36 ATMOSPHERIC PRESSURE be very exact. Cailletet's apparatus indicated, at a height of 15,500 metres, a temperature of — 60°, while the calculation gave — 83° C. What is of greater importance from a medical standpoint is that the cold is quite tolerable in high regions. This result is for the most part due to the action of the sun's rays, which strike more perpendicu- larly than on the plain; and this explains also the considerable differ- ences which are obtained according as the temperature is taken in the shade or in the sun. At Davos, for instance, which is situated at an altitude of 1,560 metres, and is a winter resort for many consumptives, it is not unusual to observe the thermometer stand at — 5° C. in the shade and -j- 12° C. in the sun. If the bulb be covered with blackened cotton, in order to prevent radiation, the thermometer records + 30° C. There is then a difference of 35° C. between localities exposed to the sun and those lying in the shade. The snow, however, does not melt, because the air does not grow warm and the rays of the sun are all reflected by the white surface, which acts as a perfect mirror. The proof of this is that if the surface of the snow be covered with a black body, such as a simple dead leaf, the snow melts at that point, because a storing up of heat rays occurs there. Our clothes play the same part; they retain the heat and pre- vent us from feeling the cold, even on the snow. Again, another condition favourable to life without suffering in high regions is the absence of wind and humidity. Mountain air is so dry that putrefaction does not occur. In the Valais, for example, when it is desired to preserve eatables, they are exposed to the sun without being salted. Desiccation is effected before putrefaction can set in. At St. Bernard the corpses of men and ani- mals never decay, and, as it is impossible to dig graves in the rocky Boil where the monastery is situated, they are placed in a morgue, where they are preserved indefinitely. The rarefaction of the air explains also a phenomenon which often causes irritation to patients — namely, the absence of noise. No sound is heard among the mountains because the air is no longer dense enough to transmit it; this phenomenon makes so vivid an impression upon certain persons that it produces a deep feeling of sadness. Let us now consider the therapeutic effects of altitudes, and let us first study the influence of moderate altitudes. Suppose, for example, a man who undertakes to receive, for thera- peutic purposes, an air cure on a mountain from 2,000 to 4,000 metres high. What will be the results ? Having arrived at the locality where he is to stay, that man will pass through a first period, that of acclimation ; he will first feel a warmth quite noticeable on his skin. His lips will be redder than in the normal state and his conjunctivae PHYSICAL AGENTS ^^ flushed. For two or three days he will have insomnia; he will occa- sionally experience palpitation, dyspnoea, dizziness, and, more rarely, headache. The urine is dark, constipation is the rule, and, finally, from the start, appetite is increased. These first phenomena last for a week. At the end of this period the man is acclimated. The external appearance is changed; the skin assumes a tan colour ; the integuments and hair are so dry that poma- tum or vaseline must be used. The appetite has further increased, as has also the muscular strength, and the longest walks do not produce fatigue. When afterward he comes down to the plain the skin becomes warm, burning, it splits and peels, but the favourable manifestations persist; the strength and appetite remain increased, at least for some time. Mountain Sickness. — If we consider the effects of great altitudes, we find a series of disturbances which are collectively called mountain sickness. It is frequent at an elevation of 3,000 metres, but at 4,000 it is almost unavoidable. But it does not occur equally in all countries ; it is more common in the Alps than in the Andes and the Himalayas. In Mexico an ascent of 4,000 metres may be made without incurring any sickness. Jourdanet reports that in the Andes villages may be seen at heights greater than 3,000 metres. On the basis of these facts, it has been stated that the higher the zone of perpetual snow the slower are the symptoms. In fact, cold is one of the principal elements in the genesis of the disturbances. All climbers are not equally subject to mountain sickness. Train- ing and temperament must always be taken into account. The quicker the ascent the greater the risk of being affected. If the ascent is made slowly, by short stages, acclimation is more readily effected. By repeating the ascents, the climber becomes proof against sjrmp- toms which a beginner can seldom escape. It is, however, important to know that the experience of the same person may be quite different in two successive journeys. An explanation of this fact is often found in his physical condition. When the evening repast has been poorly digested; when the sleep has been insufficient, agitated, disturbed, or interrupted, mountain sickness is likely to occur. The guides are not deceived in that respect, and from the appearance of the climber they predict to him how he will come out of his excursion. Indeed, fatigue is one of the most important factors, and this explains why mountain sickness is more common among climbers than among aeronauts. The symptoms characteristic of mountain sickness are quite analo- gous to those of seasickness. The first phenomenon is a feeling of gen- eral weakness ; the person has pains in the lower extremities, especially in the knees; soon saliva comes in great abundance into the mouth; 38 MOUNTAIN SICKNESS then nausea is felt, followed by alimentary vomiting, and, in grave cases, bilious and hemorrhagic vomiting. At a more advanced stage, the person has colic and diarrhoea ; at the same time his body becomes cov- ered with cold sweat. If he is examined at this moment his respiration is found to be very rapid, and the pulse irregular, rapid, and feeble. If the person continues his ascent, he feels worse; dizziness, daz- zling, humming in the ears, and a violent headache supervene. He falls into a state of indifference, an absolute apathy. He asks to be left undisturbed; he is not able to walk, his will is completely annihilated. He can not resist an invincible desire to fall asleep. In serious cases all movement soon becomes impossible, and profound exhaustion is produced, which terminates in death. Many hypotheses have been proposed to account for mountain sickness; it has been attributed to the changes in the constitution of the air, but we have seen that this explanation is contrary to the facts ; and it has been ascribed to an action comparable to that of cupping, which is also absolutely untrue. The true theory, or at least the one that is to-day generally accepted as true, was put forward by Jourdanet and advocated by Paul Bert and by Regnard. According to these authors, mountain sickness is due simply to the rarefaction of the air — that is, the diminution of oxygen. There is, according to Jourdanet's expression, a barometric disoxygena- tion. Paul Bert made several very important experiments on this sub- ject. He first submitted to analysis the blood taken from animals which had been kept in rarefied air. He observed that the quantity of the oxygen in the blood diminishes as the atmospheric pressure is lessened. If the rarefaction corresponds to the pressure existing at 2,000 metres of altitude, the oxygen diminishes 13 per cent; at 3,000, 21 per cent ; at 6,500, 43 per cent ; and at 8,500, 50 per cent. It is this lack of oxygen that causes death. In fact, if, as the air is rarefied, the proportion of oxygen in it be increased, the animal does not succumb ; it does live at a low pressure, provided the air be supplied with a suffi- cient amount of oxygen. Starting from this principle, Paul Bert experimented upon him- self. He inclosed himself in a large bell in company with a bird and a rat. The air was gradually rarefied ; the pressure fell to 24 centi- metres, realizing the condition at the highest summit of the globe, at a height of 8,800 metres. Under these conditions the bird and the rat succumbed. Paul Bert himself was allowed, by a special contrivance, to breathe superoxygenated air; in that way he experienced no disturb- ance, but as soon as he tried to breathe the rarefied air in the bell, symptoms were manifested which disappeared under the influence of oxygen. PHYSICAL AGENTS 39 Croce-Spinelli, who witnessed the experiment, hoped to profit by it. In a balloon ascent which he made a few days later with Sivel he rose to a height of 8,600 metres. The aeronauts had taken with them re- ceivers full of oxygen, but when about to make use of them, paralyzed by the cold and exhausted by altitude sickness, they were unable to reach their apparatus, and succumbed under the same conditions of aeration as those under which Paul Bert had survived. The theory just expounded explains perfectly why one can resist better in making a balloon ascent than in climbing up a mountain ; for in the latter case the muscular exertion, which is inevitable, requires the consumption of a considerable amount of oxygen to provide for the more active oxidation ; therefore the effects produced by the diminu- tion of this gas are felt much more rapidly. Along with this principal factor we must take into consideration certain other conditions. The surrounding air being rarefied, intestinal gases expand and produce tympanites. At the same time the blood rushes toward the skin, and from this results anaemia of the internal organs. But it is quite certain that these diverse disorders play an altogether accessory part. Acclimation and Altitude Cure. — When a person remains for a while on the mountains, three kinds of modifications take place in his blood; an increase in the capacity for absorbing oxygen, an increase in the number of red corpuscles, and an increase in the iron content. Among the experiments upon which the foregoing conclusions are based we must cite those of M. Muntz, who operated on rabbits of the same brood, some of which had been left on the plain and others transported to the mountain, to the Pic du Midi. At the end of seven years, M. Muntz analyzed the blood of these two classes of animals, or rather of their descendants. M. Eegnard made a similar experiment on guinea pigs. Instead of transporting some of them to a mountain, however, he made them live in rarefied air having the same pressure as at an elevation of 3,000 metres; the experiment lasted one month. Finally, M. Viault applied himself to the study of the red corpuscles, which he counted in the animals which had been transported, like those of Muntz, to the Pic du Midi. Here are the results obtained : Animals U^ \^^^ Pj^?V ( On the heights. Oxygen absorbed in 100 grammes of blood. Cubic centimetres. Muntz. Regnard. 9.56 14 17.28 21 Iron contained in 100 grammes of blood. Milligrammes. Muntz. 40.5 70.2 Corpuscles in 1 cubic milligramme of blood. Viault. 4.000,000 to 5,000.000 6,000,000 to 7,000,000 40 ALTITUDE These figures, which are in satisfactory agreement, possess great practical interest and fully justify the use of altitude cures for those suffering from anaemia, and especially chlorosis. A sojourn in the mountains is the best means of modifying the blood, increasing its richness in red corpuscles and iron, and heightening its power of oxidation. Increase of Pressure. — Like the diminutions, the increases in pres- sure are an interesting subject to study, on account of the symptoms they cause and the therapeutic effects they produce. Workmen who labour under water, whether for the purpose of gathering sponges, pearls, or corals, or laying the foundation of a bridge, find themselves in receivers in which the air is compressed to two or sometimes three atmospheres. The first phenomena consist of buzzing in the ears, due to the difference of pressure between the two surfaces of the tym- panum; in the cavity of the tympanum the air but slowly attains the same pressure as in the exterior. The difference may be sufficiently great to cause rupture of the membrane of the tympanum; therefore individuals who have a catarrh in the Eustachian tube should be cau- tioned against remaining in compressed air. At the same time a slackening and sometimes an irregularity in the respiratory movements are observed. The pulse, at first rapid, grows slow. Finally, the urinary secretion is notably increased. All these phenomena are on the whole quite harmless. The grave symptoms occur at the moment when pressure is removed; the more rapidly this is done the more frequent the manifestations become. When these appear it is sufficient, in order to stop them, to compress some more air into the receiver, and afterward to reduce the pressure gradually. The pressure at the outside diminishing, while it remains increased in the cavity of the tympanum, it is readily understood that, by a mechanism diametrically opposed, auditory disorders occur as be- fore. The person experiences buzzing in the ear; in certain cases the symptoms go further: hemorrhage results and the membrane of the tympanum may rupture. At other times the subjects complain of great fatigue and a tendency to fainting. If the reduction of the pressure is rapid, blood flows from the nose, ears, and lungs. On the skin, little punctiform hemorrhages will develop, which workmen des- ignate under the expressive term of flea bites (puces). In serious cases paralysis may be observed, which generally attacks the lower extrem- ities, often reaching the bladder and rectum, and which, if it lasts over forty-eight hours, may be regarded as almost incurable. Finally, a still more rapid reduction of the pressure may cause sudden death. These various phenomena are readily explained on making an autopsy. All the vessels are filled with gas bubbles, because during PHYSICAL AGENTS 41 compression the nitrogen is in great quantity dissolved in the blood; on reduction of the pressure, if effected slowly, the nitrogen is grad- ually eliminated by the lungs; if the pressure be reduced rapidly, the abrupt changes in external pressure cause the liberation of the gas, the bubbles of which obstruct the vessels and arrest the operation of the heart, lungs, brain, medulla, and the pons. The great variations of pressure occurring in case of explosion explain certain mechanical phenomena, and particularly the projection of small objects which, by their kinetic energy, cause more serious accidents. The increase of pressure, which sometimes does not exceed 20 atmospheres, may reach 1,500. But at the moment explosion takes place it first makes a depression that is an almost absolute vacuum around the victims; this is why they are shorn of their clothes. The air gathered between the clothes and the body expands and tears the clothes to pieces. Only such articles as shoes, garters, and corsets, which stick close to the body, may remain. Heat Heat may act on the entire person, or on a portion of the body, in which latter case it may cause a burn. In a general way, we may say that heat is not so well endured as cold. It is sufficient that the surrounding temperature rise to 40° C. for us to feel uncomfortable; we suffer from this temperature, which is 3° above that of our bodies ; while the low temperatures of — 10° C. and — 15° C. — that is, from 47° to 52° below the temperature of our bodies — produce no inconvenience. It is true that life may be maintained in countries where the tem- perature reaches, as in Senegal, 50° or 53° C, but it must be acknowl- edged that acclimation is there quite difficult. The majority of Euro- peans who emigrate to those regions succumb ; their children pine and the race becomes extinct. On the contrary, in the case of emigration to cold countries, the organism easily adapts itself to the new conditions. The differences are similar when we consider the variations of ani- mal heat. When our bodily temperature rises 4° or 5° C, the situation is regarded as very serious, and survival is quite exceptional after 43° in the rectum is reached. Diminution of temperature is, on the con- trary, much better endured, and it has been observed that animals readily recover after their temperature has been reduced, by abstraction of heat, to 20° and even 16° C. We are not to believe, however, that we are unable to stand heat at a high temperature. It is possible to live in places having a tempera- ture of 100° C. Blagden entered an oven showing 129° C, and staid there nine minutes. 42 HEAT The organism is able to resist these high temperatures because it possesses several means of protection. In the first place, internal combustion diminishes. Then the vessels dilate, and the blood rushes to the surface of the skin, and this facili- tates the loss of heat. Finally, and this third mode of resistance is the most important, sweating sets in and the evaporation of the secreted liquid produces a notable cooling effect. This is why dry heat can be endured much better than humid heat. In those animals which do not perspire, such as the dog, evaporation takes place through the mouth; the animal puts out its tongue and executes rapid respiratory movements. If, as was done by Eichet, the evaporation of the liquid is prevented by tightly muzzling the mouth, the animal succumbs to heat stroke; but the control, which breathes freely, resists. For a systematic study of heat, we must successively consider its local and general effects. Burns. — The local effects of heat are called bums and scalds. These may be produced by radiation, as is occasionally observed in cer- tain trades, among glass blowers, for example. More often they are produced by contact with a hot body, liquid or solid. If it is a gas, the burns are superficial but extensive, and we shall presently see that the extent is of greater consequence than the depth. If it is a liquid, the scalds are deeper. Their extent varies according to circumstances. They may affect the entire skin of a person who falls into a vat of boil- ing liquid. A circumstance often increasing the seriousness of these scalds is that the clothes are impregnated with the burning liquid and prolong the action. In certain cases the phenomena of calefaction hinder the action of the liquid body; hence the possibility of plunging the hand or the arm, without inconvenience, into molten metal at a temperature of 1,000° C. The burns produced by solid bodies are, in general, very deep, but limited, and consequently less serious. In order to have an accurate idea of the effects of burns, we shall recall the well-known experiments of Cohnheim. This author plunged the ear of a rabbit into hot water. He states that a temperature of 42° or 44° C. produces but a transitory hyperaemia. At 48° or 49° C, the ear tumefies ; oedema is produced. At 50° to 52° C, from the effusion of serum beneath the cuticle, blisters appear. At 56° to 60° C, gan- grene of the ear sets in. Similar results are observed in man and allow us to separate burns into a certain number of categories or degrees. It is usual, since Dupuytren, to admit six degrees of burns. The first degree is erythema; this is a simple redness of the skin, produced under the influence of the radiant heat of a gas, of a liquid. PHYSICAL AGENTS 43 or of a solid whose temperature is not very high. In certain workmen, in glass blowers, for example, the erythema may assume a chronic char- acter ; the skin thickens and splits on the face and hands. In the second degree the skin rises in blisters filled with serum. In both cases the lesions are superficial; they usually heal without leaving any traces. Nevertheless, especially as a result of blisters, a certain indelible pigmentation may persist. The remaining four degrees differ from the preceding in that they are attended by the destruction of the parts and give rise to the forma- tion of cicatrices. In the third degree the epidermis is disorganized and the mucous layer of Malpighi is reached. In the fourth degree the destruction of the skin is complete. In the fifth degree black masses are formed, involving soft parts to a greater or less depth. Finally, the sixth degree is reached, when the whole thickness of a limb is carbonized. The extent is of far greater importance than the depth. If limited, a burn of the fourth, or even of the fifth degree is not serious ; while a burn or a scald of the first degree may be fatal if it covers the entire skin. A person who falls into a vat of hot water and is immediately drawn out presents cutaneous lesions in appearance harmless, but he will succumb from the development of general manifestations. These differ entirely in their mechanism and symptoms, according as they appear soon after the accident or tardily. The immediate general phenomena are manifested in the following manner : There is, in the first place, a rise of temperature, which is explained by the application of heat; then, little by little, the temperature de- scends, falls below the normal, and may become very low. The respira- tion is slow, superficial, irregular, often intermittent with long pauses. The pulse is small, feeble, slow. Finally, the victim, indifferent to everything, falls into a comatose state, and succumbs with a progressive depression of the temperature. These immediate consequences are observed especially in cases of extensive and superficial burns. The remote phenomena are met with when the lesions are deep. The urine contains hemoglobin as the result of the breaking up of the red corpuscles. Sometimes hemorrhages occur, which are espe- cially marked in the intestines and lungs. At the autopsy, nephritis and duodenal ulcerations are found, the former of which, at least, suf- fices to account for death. The early symptoms are reflex manifestations, produced by the too violent excitation of the nerve endings ; it is a variety of nervous shock. 44 BURNS The evils arising later are due to self-poisoning ; there is an insufficient depuration in consequence of the suppression of the cutaneous emunc- tory and the increase of autogenous poison. Experiments have demon- strated that burned tissues are very poisonous. In a great many cases skin burns are accompanied by burns of the mucous membranes ; these are due, in general, to the direct inhalation of flames, or may be caused by the ingestion of boiling liquids, as is the case with English children, who very often burn the mucous mem- branes of their throat and larynx by imbibing hot tea from the spout of the teapot. The results are the same as those observed on the skin, except that the effects are much more serious, for the resulting oedema impedes the play of the organs, and, if the patient does not succumb, the consequent scars may ultimately cause strictures in certain pas- sages, particularly the esophagus. In cases of fire, the phenomena are more complex. For we must first take note of the great quantity of gas produced. It has been calculated that 1 kilogramme of burning wood suddenly yields by a silent explosion 200 litres of gas, which, under the influence of heat, expands to 10,000 or 20,000 litres. The temperature at this moment is very high ; at the focus of the conflagration it is not rare to find 1,000° to 2,000° C. Death may be due to poisoning by gases produced, and particularly by carbonic oxide, which, causing asthenia or paralysis, prevents the victims from escaping. At the autopsy the blood is found to be bright in colour, and it can be shown by the spectroscope that the hemoglobin is no longer reducible by sulphhydrate of ammonia. In those who succumb under the influence of heat are found, be- sides burns of the skin, intrapulmonary coagula, appearing in the form of small casts. When the temperature is very high the thoracic cavity is largely open, by a clean cut, as if by a cutting instru- ment. The heart is hard, rigid, containing coagulated and dark blood. With these great burns caused by fire we may parallel those produced in explosions of fire damp. The lesions reach the respiratory mucous membrane and are explained by the following mechanism: The fire damp, mixed with the air which the miner breathes, fills his lungs ; the external explosion propagates itself to the interior of the respiratory apparatus and produces burns in the trachea and bronchi, ecchymoses, and pulmonary hemorrhages. In mines where there is no fire damp there may be observed, as Eiembault has shown, a sudden deflagration of coal dust, which flies in the air and fills the respiratory passages ; in this case also internal burns of a very serious nature are produced. PHYSICAL AGENTS 45 Heat Stroke; Sunstrohe. — Besides its local action, the heat may give rise to a series of general manifestations which constitute heat stroke ; this may be compared to sunstroke. Heat stroke is most frequently observed in those workmen who labour in overheated places, among glass blowers, foundrymen, firemen, and particularly those employed in the firerooms of steamships. In the Eed Sea, which lies between abrupt mountains, the heat of the climate, added to that of the engine, intensifies the symptoms to such a degree that it has been necessary to replace European by negro fire- men, who can better resist high temperatures. The sun claims numerous victims even in our own country. During the summer, cases of sunstroke are often observed among harvestmen, especially when they sleep in the sun. But it is soldiers that are most frequently affected. To the action of heat is added that of fatigue; hence accidents are much more frequent among the infantry than the cavalrymen, and occur mostly on the occasion of great manoeuvres or reviews. We must note also the humidity of the air in order to take into account its effects. Dry heat is, as already stated, far more easily resisted. Lastly, we must not forget that the most serious accidents occur when the heat or the sun acts upon the head. This is a fact of observation confirmed by experiment. By circulating hot water through a rubber bag Dr. Vallin was not able to produce symptoms except when he applied the apparatus to the heads of the dogs under experiment. We must also take into account our clothes, which may store up heat. After an hour's promenade in Paris, in the month of July, on a very sunny day, Vallin found under his hat a temperature of 46° C. At the end of a review in the sun the helmets of cavalrymen are often hot enough to burn the hand. With a view of better analyzing the symptoms of heat stroke, Vallin subjected dogs to the action of the sun. The symptoms manifested themselves in three periods. At first the animal struggled and ejected saliva abundantly (it is known that the dog does not perspire) ; the temperature of the rectum rose from 39.5° (the normal temperature of dogs) to 42° or 43° C. Eespiration reached the high rate of 200 per minute. In the second period the breathing became slow — it fell to 80 or 60; the agitation was followed by a complete prostration. The third period was characterized by convulsions, which terminated in death; at this moment the temperature of the rectum reached 44° or 46° C. With man the evolution is less clear. We may, with Dr. Lacassagne, admit three periods. The first period, the least serious, is announced by certain premonitory symptoms — uneasiness, feebleness, heaviness in 46 SUNSTROKE the limbs. If the sufferer rests, all these symptoms disappear; if he continues to walk and expose himself to the heat, the lower extremities grow weak; respiration becomes difficult, dyspnoic; the thorax aches; the face is flushed; the cutaneous vessels become turgid. This is the asphyxial form. In other instances, always in the first degree, the heat affects the circulation and gives rise to a syncopal form. The onset is abrupt ; in the midst of a conversation, for example, the person is suddenly at- tacked ; the face is deadly pale. As a rule, the first degree is not serious; as soon as the patient is put in a cool place the symptoms disappear. The essential characteristic of the second degree is the addition of nervous phenomena; there are dizziness and delirium; finally, coma ensues, and in certain cases death. The third degree is that which causes rapid or sudden death, and is particularly observed in tropical lands. Kecovery, even in slight cases, is not always complete. Various disorders may persist, notably neuralgia, headache, and sometimes sub- delirious ideas. The prognosis of sunstroke changes totally with latitudes ; in tem- perate countries recovery is the rule; in countries where the tempera- ture rises over 40° C. two thirds of the persons affected succumb. Several theories have been suggested to explain the mechanism of the symptoms. The first idea attributed them to the coagulation of the myosin, which is produced at 45° C, but at the autopsy the mus- cular tissue is found acid and rigid, and notably the heart is contracted and hard. This view, advocated by Vallin, is being abandoned. In fact, it is established that the muscles are able to stand heat much better than was believed. Atanasiu, Carvalho, and Eichet injected into the veins or peritoneum of dogs salt water heated to 60° C. without producing any disturbance. This burning liquid is perfectly well borne by the tissues and the heart. Therefore, it is more just to ascribe the disorders to an action upon the nervous centres, which are, in fact, the most delicate parts of the organism, and hence also the first to feel the influence of a rise of temperature. This theory, developed by Drs. Laveran and Eegnard, seems to harmonize more satisfactorily with clinical and experimental results. Cold Cold climates, as above stated, are much more healthful than warm climates. Explorers who have been in polar regions state that they stood without any suffering temperatures from 40° to 45° C. below zero, provided there was no wind. Life may be maintained at even much PHYSICAL AGENTS 47 lower temperatures : at — 60° and — 70° C. However, the facts should not be exaggerated. In Eussia, for instance, about seven hun- dred persons perish yearly through cold. All ages are not equally fitted to stand severe cold. The adult resists best. The aged, whose nutrition is weakened, need a warm tem- perature. Children are very quickly chilled, but their tissues stand very well the loss of heat, and they survive depressions of temperature to which an adult would have succumbed. M. Edwards exposed to cold newborn dogs; the central temperature fell to 14° and even 13° C. ; the animals, on being warmed again in a slow and gradual manner, recovered. Sensibility to cold is increased by all causes which weaken organic resistance. Misery, overwork, starvation, and depressing moral influences must be mentioned first. This is the reason why cold acts so dreadfully upon a routed army. During the retreat from Russia, of which Larrey and Desgenettes have left us such striking accounts, the greater part of the soldiers died from the cold; the army, which comprised 400,000 men at its departure, was reduced to 3,000 when it returned to Germany. Even in warm countries symptoms may be produced by exposure to cold, at least during the night. This is what happened during the African wars. In 1870, on the other hand, the accidents were mostly due to local freezing. Another agency which frequently co-operates with cold is alcohol. In cold countries the inhabitants, especially cabmen, are very often seen entering wine shops to warm themselves. If they consume hot infusions, as tea, they can resist the outer temperature more easily; but if they take alcoholic drinks, and particularly brandy, as they do in Russia, on going out to the street, they often suffer from serious dis- turbances, and sometimes fall dead. In order to fully recognise the action of cold, we must also take into account the wind and the humidity. The wind aggravates the cold, for it drives away the warm air surrounding the body. The humidity increases the loss of heat. Finally, melting snow is borne with diffi- culty, for it absorbs a great quantity of heat. Furthermore, daily observation establishes the fact that cooling, when it is gradual and not abrupt, is more easily endured. An experi- ment of Paul Bert evidences this fact. Fish die when they are trans- ported, without any transition, from water at 28° C. to water at 12° C. The converse is also true, demonstrating the danger of rapid warming. As in the case of heat, we shall successively consider the influence of the local and general action of cold. 48 COLD The local action is utilized in therapeutics. When it is desired to make a small operation, the diseased part is cooled, either by a mixture of ice and salt or by a vaporization of chloride of ethyl or methyl; the skin becomes white, bloodless, and insensible. When the cold application is stopped, reactionary phenomena are produced; the skin becomes red, congested, and the sensibility is exaggerated. The same method is applied, as is known, in the treatment of neuralgia. The vaso- constrictive action of cold is also utilized for the purpose of arresting hemorrhages or soothing inflammatory phenomena. Frostbite. — When the action of the cold is more intense or more prolonged it produces various manifestations known as frostbite. In the clinic three degrees are known. In the first degree, there are erythema and rubef action; sometimes the cutaneous irritation is sufficiently marked to produce, as a sequela, a durable pigmentation. Some examples of this have been observed as the result of the use of chloride of methyl. When the irritation is repeated, the skin thickens, remains red, and sometimes cracks. Such is the erythema pernio, popularly known as chilblain, and is par- ticularly observed among lymphatic persons. In the second degree, the skin is ulcerated. In the third, eschars are formed, entailing the loss of the affected parts. These destructive lesions are particularly frequent in thin and exposed regions : at the lobe of the ear, at the tip of the nose, and at the ends of the fingers. The different lesions characterizing frostbite are due, for the most part, to reactions of great violence ; they are not caused directly by the action of cold, but by secondary phenomena produced by this patho- genic agent. They may therefore be avoided by moderating the reac- tions. It is a well-known fact in northern countries that a person suffering from cold should not be brought into a hot room. Circula- tion must be restored in the affected parts by mechanical means — by hard rubbing, rubbing with snow being the preferable mode. During the retreat from Russia a great number of soldiers suc- cumbed to terrible symptoms when they were transported into warm rooms. The affected parts were tumefied, distended by a considerable amount of serum ; there was a disengagement of gas ; the skin, swollen, was sphacelated, and death ensued in a few hours. The greater the intensity of cold suffered the more serious are its effects. Operating upon the ear of a rabbit, Cohnheim obtained the following results : A freezing mixture at — 3° or — 4° C. excites sec- ondarily a transient hyperaemia; at — 7° or — 8° C. it causes oedema; at — 10° or — 12° C, swelling ; at — 18° or — 20° C, gangrene. The mechanism of the accidents just indicated is easy to understand. Under the influence of cold the circulation grows slow; then, if the PHYSICAL AGENTS 49 temperature of the tissues falls to — 15° C, the blood and the lymph coagulate. The red corpuscles become indented, burst, and their con- tents are set free. The hemoglobin passes into the urine; the stroma forms little foreign bodies, which obstruct the vessels and become the starting points of thromboses. When reaction is produced, the blood returns in abundance, and, unable to pass through the obstructed ves- sels, it transudes through the walls, causing oedema, while the most peripheral parts, deprived of the nourishing juice, soon sphacelate. If the person succumbs, the same lesions are found as in those who have been burned. They depend on the same mechanism — ^that is, on a self-poisoning by the altered and destroyed red blood corpuscles and cellular elements. They are expressed also by gastrointestinal ulcera- tions, congestion, and sometimes hemorrhages of the abdominal vis- cera, lungs, and nervous centres. General Effects of Cold. — The general effects of cold are quite com- plex; we must discriminate between ailments produced by cold itself and those in which cold plays an auxiliary part. The first phenomenon consists in a general weakness, a feeling of fatigue, and an irresistible tendency to sleep. During the retreat from Eussia the soldiers used to pray to be allowed to rest and sleep a few minutes ; and yet they could see that those of their comrades who fell asleep never woke up again ! This state of apathy is sometimes interrupted by cerebral derange- ments, delirium, or by epileptiform convulsions. As Brown-Sequard has shown, when the body temperature falls to 22° C. there is pro- duced, probably by the paralysis of superior centres, a medullary exci- tation, which is expressed by an exaggeration of reflexes, just as in animals poisoned by strychnine. At the start, the organism tries to struggle by means of a more active combustion; until 30° C. is reached the exhalation of carbonic acid is increased. But when the temperature falls below 26° C, the organism abandons itself; nutrition grows slow or is arrested; the exhalation of carbonic acid is reduced, or at least its formation dimin- ishes, since the blood in the veins becomes red, sugar ceases to be consumed, and glycosuria sets in. Still, in most cases, death does not result from arrest of general nutrition; it is due to arrest of the hearths action. This is a point to which Drs. Eichet and Eondeau have called attention; they have shown that it is possible to revive beings apparently dead through cold if, even half an hour after the cessation of manifestations of life, artificial respiration be practised, provided, however, that this is pro- longed for a while, often for a very long time. The practical impor- tance of this demonstration is readily understood. 50 GENERAL EFFECTS OF COLD In cases which we have thus far studied cold did not act solely hy producing a loss of heat; it caused at the same time an excitation of the nervous terminations. The phenomena are, in fact, very complex, for it is possible to inject into the veins large quantities of ice water without producing any symptoms. This experiment is the reverse of the one we have recalled with reference to heat. We may also introduce as much as 100 and 160 cubic centimetres of ice water per kilogramme without giving rise to any disorder. The internal temperature falls 2° to 5° C. ; at the end of one or two hours it returns to the normal ; then it rises from 1° to 1.5° C. above the initial figure. Thus is pro- duced a reactionary hyperthermia, which is, however, transitory. Intraperitoneal injections of ice water are equally well borne and produce no disorder, not even diarrhoea. On the contrary, in injecting the liquid by the central end of the carotid artery, we often see con- vulsions, nystagmus, and movements of rotation or manege supervene. This is because the icy liquid passes through the carotid and vertebral arteries, reaches the nervous centres, and gives rise to the formation of softening foci in the brain, the cerebellum, and the peduncles. Whatever the mode of introduction, the ice water has never caused diarrhoea, pulmonary alterations, or urinary symptoms. These mor- bid symptoms are indeed often observed after an attack of cold. In this case, however, the cold does not produce simply a reduction of heat; it gives rise to extremely violent and sometimes rapidly fatal nervous excitations. A guinea pig plunged into water at 4° C, care being taken to keep the head in the air, ceases to breathe and succumbs within a few minutes. This result is important from a medico-legal standpoint. Some individuals have survived after having remained quite a long time under water, while others, brought out sooner to the air, could not be restored to life. The differ- ence depends largely upon the temperature; if the liquid is not too cold, the subject breathes, water is introduced into his lungs, and he is asphyxiated. If, on the contrary, the water is intensely cold, a car- diac and respiratory syncope takes place and the water does not pene- trate the bronchi. In the first instance the drowned person is blue; in the second he is white (white asphyxia of certain authors), and, if artificial respiration be practised, he survives even if he had remained in the water for ten or fifteen minutes. In order to put a little system into our study, we shall divide the morbid occurrences occasioned by cold into five groups : Cold may produce painful phenomena. In many cases, particularly with arthritic subjects, a simple draught of air causes a facial neural- gia, often accompanied by an outbreak of herpes. In other instances motor disorders are produced — for example, a facial, perhaps even a PHYSICAL AGENTS 51 radial paralysis, although in the latter case, as already stated, it is generally due to a process of compression. Finally, with certain per- sons, extended paralysis has been observed, assuming usually the form of paraplegia. A second group of phenomena consists of reflex disorders affecting mostly the vasomotor system. It is admitted that cutaneous cooling, involving a contraction of the superficial vessels, produces as a com- pensation a congestion of the deeper organs. As an example, reference is made to the results discovered at the autopsy of alcoholics dead under the influence of cold; a very marked congestion is found, and sometimes hemorrhages in the brain and lungs. Even in such cases the phenomena are complex, and congestive manifestations may be regarded as secondary. In fact, it is a matter of frequent observation that cooling of the skin excites vaso-constriction in the deeper tis- sues. Fredericq has given experimental proof of this. By submitting the cranial skin of a dog to cold, a vaso-constriction of the meningeal vessels is produced. The phenomenon is too rapid to be attributed possibly to a reduction of heat; it is a case of reflex action. On the ground of this result it may be questioned whether pulmonary conges- tion, which is attributed to cold, is not a secondary manifestation, preceded by an initial vaso-constriction. We shall return to this ques- tion when treating of infections and nervous reactions. In the third group are ranged the hypercrinic phenomena. Water- ing of the eyes, nasal catarrh, polyuria, and diarrhoea represent the best-known manifestations. The fourth group consists of those cases in which the cold serves as an auxiliary cause to an infectious agent ; it diminishes our resistance, and thus favours the development of bacteria, which live on our bodies as simple parasites. Hence, exposure to cold may be followed by angina, laryngitis, or pneumonia. In other cases cold provokes a relapse ; such is the case with a person who, recovering from erysipelas, leaves his room too soon and is again attacked by the disease. Finally, cold may cause the development of complications in the course of a pre-existing disease by provoking secondary infections in the respiratory passages. The last group, the least well known, comprises those very curious cases in which the cold gives rise to an attack of gout, or to the repro- duction of an ascites in cirrhotic subjects. Finally, though in a man- ner as yet unexplained, cold may cause also paroxysmal hemoglobinuria. With certain subjects the urine contains hemoglobin as soon as there is a cutaneous cooling, even over a limited region. The phenomenon may thus be provoked at will. It is a remarkable fact that cold does not seem to act any longer after a certain limit. Pictet demonstrated that one may descend into 52 LIGHT a well showing a temperature of — 100° or — 110° C, the head remain- ing out. After staying there ten minutes the appetite is strongly aroused and the previous dyspepsia is notably decreased. Choisat and Cordes utilized this result in therapeutics, and LetuUe and Eibard conceived the ingenious idea of treating the anorexia of consumptives by the aplication upon the abdomen of carbonic snow at about — 80° C. Let us remember also that Dr. d'Arsonval has shown that the finger can be dipped with impunity in liquid air, or some of it poured upon a mucous membrane. It is more than probable that still lower temperatures would be even better supported. The human body would become wholly diathermanous, and the radiations would traverse it without making any kind of impression upon it. Light Light has a very marked influence on all living beings. It may sometimes become destructive; microbes perish under its influence. Most frequently its action appears by the very notable modifications of nutrition in plants as well as in animals. In the higher animals it stimulates the nerve ends, thus enhancing the nutritive activity. From this results an increase of resistance to pathogenic causes, a more energetic working of the organs, a notable improvement in ideas and feelings. Joy and cheerfulness are proverbial in sunny countries. Certain experiments were made confirming these data. Let us rep- resent by 100 the carbonic acid exhaled through the skin and lungs by a person shut in darkness. If this man is brought to the light, keeping his eyes shaded, the quantity of carbonic acid exhaled rises to 112. If the light is brought to bear upon the eyes, carbonic acid rises to 114. If the light acts at the same time on the body and visual apparatus, the acid reaches 136 — that is, an increase exceeding the sum of the two preceding partial results. This increase of carbonic acid obviously indicates a nutritive overactivity; it coincides with an elevation of the bodily temperature. The result is particularly evident in children; their temperature rises from 0.1° to 0.5° C. when they are brought from darkness into daylight. Light may, however, produce certain disturbances. The solar rays, arriving directly or after being reflected upon surrounding objects, cause an erythema, sometimes accompanied by a slight elevation of the epi- dermis by serous liquid. Electric light gives rise to analogous effects. In the south of France and in Spain a disease is observed— i. e., pellagra, which is characterized by a chronic erythema occupying the exposed parts. There has been a good deal of discussion concerning the pathogeny of this affection ; it seems to be due to the co-operative action PHYSICAL AGENTS 53 of different causes. In fact, it is observed in persons who consume spoiled maize. The ahmentary poisoning engenders various nervous ailments and serious manifestations of a general character ; at the same time it diminishes the resistance of the skin to the action of the solar rays. The eruption does not appear over parts protected by the clothes. The notion that the harmful effects of the sun may be avoided by protecting the skin by means of blue or black glasses is a familiar one. Freckles act in the same way ; the solar erythema does not appear where freckles are present. The mucous membranes are even more sensitive to the action of light than the skin. The blepharitis and ophthalmia which are ob- served in hot countries and in those lands where the sun strikes the eye after-being reflected from snow are well-known proofs of the fact. The pathogenic action is due to the chemical rays of the spectrum — namely, to the violet and ultraviolet rays. Dr. Bouchard has demon- strated this fact by causing a ray of sunlight decomposed by a prism to fall upon the skin of his arm; the erythema appeared only in those parts that were exposed to the chemical rays. The light may also give rise to reflex phenomena. On passing from darkness to daylight one is seized with sneezing. By gazing at a luminous object for a long while an artificial slumber may be induced, known by the name hraidism, in honour of the author who discovered this phenomenon. The subject under experiment is found sufficiently asleep to make it possible, without awakening him, to perform painful operations upon him. By this procedure, even animals, particularly pheasants, may be made to fall asleep. If the light shine brightly, it may produce more complex phenomena in predisposed subjects. When a magnesium lamp is lighted, catalepsy is caused; the person remains motionless in the very situation which he occupied, no matter how fantastic. If the light is suddenly put out, catalepsy gives way to lethargy. The action of light may be compared to that exerted by the Rontgen rays. Their prolonged application has caused skin lesions, simply erythematous in most cases, but sometimes liable to end in the forma- tion of small eschars. At the same time modifications in the general nutrition are induced, which are perhaps the result of the excitation of nerve terminations in the skin. This is a process comparable with that known in therapeutics as revulsion, and explains the effects ob- tained by the use of cathodic rays in the treatment of certain diseases. Sound The vibrations of sound sometimes produce intense mechanical lesions, even a perforation of the tympanum. More often they act 54 ELECTRICITY by reflex action and stimulate activity in the nerve centres. N'othing is more restful than the absence of noise in the country or in the mountains, at least for certain persons, for, in others, silence may engender sadness and melancholy. Noises, if intense, may produce disturbances in the predisposed. At the strike of a gong, hysterical persons fall into catalepsy. Finally, it has been thought that harmonious sounds might serve as therapeutic agents, and that music might be used in the treatment of certain diseases. It is well established that music exerts a consid- erable influence over the nervous system. Its action deserves to be studied anew. Electricity To appreciate the action of an electric current two factors must be considered : the energy of the current and the resistance of the bodies it traverses. The unit of electric resistance is the ohm ; it is the resistance of a cylindrical column of mercury, one metre long and one square milli- metre in cross section, at a temperature of 0° C. The resistance of the human body is, on an average, 1,000 ohms ; this figure is obviously subject to great variations. Moreover, it must be noted that the re- sistance is not always the same during the passage of the current, and that it diminishes as the electric energy is increased. Again, the resistance varies according as the current passes by this or that part of the body. Stone finds that the resistance, which amounts to 939 ohms when the current passes from one foot to the other, falls to 905 when it passes from the hand to the foot. The second factor to be taken into account is the energy. In order to make it clear we may represent the form of the current graphically. Let us suppose a continuous current passing in a nonelectrified body — viz., a body whose electric potential is equal _ to 0. We may distinguish in the elec- ^ ^ -^ ^ trie wave (Fig. 1) three periods: a Fig. i.-Eiectric wave continuous -^^ ^f increase, a stationary period, current. C', line of zero poten- ^ • t p -, mi \» tiai ; A B, period of increase ; and a period of decrease. The first and 5 (7, stationary period ; OD.ipe- third periods, which Correspond to the riod of decrease: B F, measure beginning and the end of the passage of of electric energy, difference of *^ *^ . potential. the wave, constitute variable states; the stationary period is called the per- manent state. Measuring by a perpendicular the distance which separates the permanent state from the line whence the current starts, we shall have the energy of the current; this is the difference of the PHYSICAL AGENTS 65 O A D C O Fig. 2. — Electric impulse. 0, line of zero poten- tial ; A B, the period of increase ; £ C, period of decrease ; no stationary- period ; £ B, difference of potential. potential existing on the body considered before and during the passage of the wave, and if the useful effect is considered, it is called electro- motive force. The unit employed to measure electro-motive force is the volt; this is nearly the electro-motive force of a Daniell cell, which is taken as a standard on account of its great constancy. The ratio between the electro-motive force of a current and the resistance E of a body is called the intensity of the current. The formula I = b allows us to determine easily this new unit, which is known as the ampere. The resistance of the human body being equal to 1,000 ohms, we must always, in our calculations, divide the number of volts by 1,000 to find the intensity. Consequently, it has been found simple in electro-physiology to meas- ure by milliamperes. Let us return to the form of the current. Suppose the permanent state is suppressed; a single impulse (Fig. 2) will be obtained; this is what is realized in the electric spark, the dis- charge of a Ley den jar, and the lightning flash. Again let us suppose that in a continuous current a series of breaks is made; then an in- terrupted current will be the result. But while continuous or interrupted currents are used they do not cause electri- cal effects only. Chemical effects are at the same time produced, owing to the electrolytic phenomena to which the current gives rise in the body, as in saline solutions. This chemical action may be suppressed by the use of alternate currents, the most important of which are the sinusoidal currents (Fig. 3). Each wave moves in a direction opposite to the preceding one; the successive figures are added, and, as they are in opposite directions, they neutralize each other. These currents therefore exercise a purely electrical ac- tion. The number of waves pro- duced in one second is called fre- quency; double waves — i. e., two waves of opposite directions — are called periods. It is to be noted that in currents of this kind the body at each period undergoes a diminution of potential equal to twice the energy of the current. If, for example, the current is one of 500 volts, the two successive waves 5 Fig. 3. — An alternating sinusoidal current. 0, line of zero potential ; AB JB, wave of positive electricity ; B F 0, & similar but negative wave ; A B and B <7, length of waves ; A C, length of a period ; D E, F 6r, difference of potential with reference to the line 0\ D F^ measure of " deni- vellation " of potential at each period. 56 ELECTRICITY being of opposite directions, there would be between them a difference of potential of 1,000 volts. We shall have finished these few preliminary remarks when we have added that the action of currents on the living organisms depends upon the form of the waves. When the waves are similar the effects are identical, whatever may be the electrical source. If the organism is subjected to the action of a single wave, such as is realized in a lightning flash, sudden death may be the result, which is due to anatomical lesions and hemorrhages produced in the nerve centres, particularly in the medulla. If the victim does not succumb, paralyses may persist, some of which are due to a material lesion, while others belong to the category of hysterical phenomena, called by Charcot herauno paralyses (herau- nos, lightning). Continuous currents act upon the organism only when the potential is being modified; that is, during the variable periods — the closing or the break of the current. So long as the permanent state lasts no phenomena occur, excepting, of course, the disturbances due to elec- trolysis. If an animal is subjected to the action of a continuous current of sufficiently high potential — for example, 400 volts — at the closing and opening of the current a muscular contraction is produced. If the shocks be repeated a great number of times the animal is killed. But, as d'Arsonval has shown, in such a case death is due to the large amount of heat generated by muscular work; for, if this experiment be repeated upon an animal plunged into a cold bath survival is the rule. Very powerful continuous currents, amounting, for instance, to several thousands of volts, may produce a fatal shock. In the indus- tries, continuous currents furnished by dynamos are much more dan- gerous than currents supplied by batteries; for the break currents give rise to phenomena of self-induction and to the production of extra currents which, if the voltage is high, produce sideration. A current short of 300 volts produces but one shock; between 300 and 1,000 volts it causes a very painful sensation; at 3,000 volts it may, though not always, entail death. From a physiological standpoint the most interesting currents are the alternating currents, the effects of which were thoroughly stud- ied by Tesla and d'Arsonval. Let us suppose a sinusoidal alternating current having no chemical action; if the potential is low, and if the frequency is also low, the current produces no notable effect upon the human body; it modifies only the nutrition, as may be shown by analyzing the urine. PHYSICAL AGENTS 57 At a moderate potential and a moderate frequency the current produces a muscular contraction which is not painful. If the potential is raised, and if the frequency is from 100 to 200 per second, sinusoidal currents give rise to serious and even fatal accidents. These currents have been most extensively utilized in indus- tries and are also used in America for electrocution. Let us now assume that the potential and the frequency are in- creased. The action will be more and more marked, and then, for an instant, the effects on the organism will no longer vary ; beginning from 2,500 to 5,000 excitations per second, the manifestations diminish. When the frequency reaches several hundred millions or several billions, whatever be the voltage, the currents become harmless. The following experiment, repeated a great many times in Professor d'ArsonvaFs laboratory, well illustrates this point. A steam engine furnished a current which was used for electric illumination and which accidentally caused the death of a man. This current, when trans- formed to an alternating sinusoidal current at high frequency, can harmlessly traverse the human body. Two men desire to be experi- mented upon; each one puts himself in contact with one of the poles. Then the two men are joined by a metallic conductor bearing six in- candescent lamps; the six lamps are lighted, while the men do not experience the slightest sensation. And yet, if the frequency was diminished, the two persons would soon be killed. To explain the innocuous character of high-frequency currents. Professor d^Arsonval has advanced two h3rpotheses. We may admit that the current has no power of penetration and that it simply glides over the surface of the body. On the other hand, we may suppose that the nervous system ceases to be influenced when electric vibrations become too frequent. In support of this conception the cases of light and of sound are recalled. The auditory nerve is impressed only when the waves have more than 30 and less than 30,000 vibrations per second. The retina perceives but those rays whose vibrations are comprised between 497,000,000,000 and 728,000,000,000 per second. Below or above these figures there is no stimulation. Why, then, should we not admit for electricity what is demonstrated for sound and light ? Currents of moderate frequency used in the industries have caused a number of accidents, many of which have been fatal. But, in view of the extent which electrical industries have reached, we must recognise that the number of fatal cases is by no means very considerable. Biraud, in his excellent thesis, was not able to collect more than 10 such cases in France and 20 in England. In America, where the use of electricity is so extensive, he found only 200 cases. In factories a number of precautions are observed which, if well 5g JiLECTRiCiTf followed, would be entirely efficacious. Workmen must protect thQit hands by the use of rubber gloves. It is to be remembered, howevei*| that the rubber, in getting old> may crack and let the electricity pass. Another precaution consists in not wearing shoes with nails, and in using rubber soles. This measure is excellent, for the most serious accidents have been those which are caused by currents passing from the hands to the earth. Finally, the tools are provided with insulating handles. If, through neglect of these precautions, an accident happens, the effects vary according to the extent of the contact, the condition of the parts affected, and the position of the body with respect to the current. It is quite evident, in the first place, that the more extended the contact, and the better conductors the parts through which the cur- rent enters or leaves, the more serious will be the injury. The humid- ity of the hands, for instance, favours considerably the penetration. But it is especially the position of the body with respect to the cur- rent that modifies the results. Three events are possible. The two hands touch two points of a conducting wire, thus completing the circuit. The resistance of the body being higher than that of the wire, the effects will not in general be serious. In other cases, the entire current passes through the body — ^for example, when a workman takes the two ends of a broken wire to mend them. If the current does not reach the ground, the effects are often almost harmless. Finally, when the current reaches the ground, the phenomena of sideration supervene; currents of 2,000 volts may bring about death, while in the preceding cases currents of 3,000 volts caused some shaking. The effects produced by currents may be divided into two groups. Some of them are local manifestations — burns which are more or less intense, according to the degree of resistance. They are therefore observed in relatively harmless cases, when, for example, very dry hands resist penetration. If, on the contrary, the hands are moist, they are good conductors and the phenomena of sideration are pro- duced. These are very simple; the person falls as if struck by light- ning and his respiration is arrested. Yet the accidents are not irre- mediable; it is only a case of apparent deatli, a variety of nervous shock, and if artificial respiration is practised for a sufficient length of time he is restored to life. But sometimes there occur irremediable hemorrhages in the nervous centres. These lesions, which were the rule in the case of fulguration, are rarer in sideration. This is one PHYSICAL AGENTS 59 difference between the two states. There is another difference. The kerauno paralyses of Charcot are observed only after fulguration; they do not appear after sideration. Electrocution. — The idea of utilizing electricity in capital execu- tions seems to belong to a French senator, but the experiments were made in America. Brown and Kenelly were asked to determine the fatal effects of the electric fluid on animals. They used currents of 200 to 280 alternations per second, and succeeded in killing a dog with 200 volts ; 700 volts killed a horse. The first experiment on a human being took place on August 6, 1890, in the prison at Auburn, IST. Y. The condemned person was seated on a wooden chair and tied fast. A casque was put on the head and a wet sponge on the sacrum; the preparations took three minutes. Then a current of 2,376 volts was passed for seventeen seconds; the person seemed to be dead, but a few minutes afterward the pulse revived, and at the end of thirty seconds a slow movement of the thorax seemed to be noticeable. The current was again applied for seventy seconds, and this time he succumbed. The following year, on the same day, there was occasion to make four capital executions. With the first condemned one, a current of 1,548 volts, passing from the head to the calf for 37 seconds, did not prove fatal, and a second contact of 36 seconds became necessary. For the three others, currents of 1,845 volts were used; for each one three successive contacts of from ten to eighteen seconds were required. These results appeared excellent, and in 1892 it was considered proper to invite to the execution a number of persons, especially jour- nalists. After a lecture delivered by the physician in charge of the operation, the condemned man was brought in. They dipped his hands in acidulated water, and, as a precaution, in case the new system should not succeed, the casque was applied to his head and the wet sponge to his calf. The current, of 1,600 volts, passed through the hands for fifty seconds. By this time the water had evaporated and the hands were carbonized. Yet the heart was beating; then the mouth opened and saliva was thrown out, certain movements were produced, and several spectators heard a groaning. Then the cur- rent was applied from the head to the calf for thirty seconds, and he succumbed. At a subsequent execution it was decided to verify the value of artificial respiration, advocated by Professor d'Arsonval as a treat- ment of sideration. The experiment met with a marvellous success and saved the life of the condemned. This fact is obviously very important from a practical standpoint, and is perhaps the best result furnished thus far by electrocution. 60 ELECTRICITY Practical Applications of Electricity. — The practical medical appli- cations of electricity are very mimerous. It may be used for diag= nostic as well as for therapeutic purposes. The study of electro- muscular contractility plays a very great part in nervous semeiology. Therapeutists use the electric fluid in all its forms, static electricity, continuous and broken currents, and currents at high frequency. It is particularly in nervous affections that electricity is of service; it is of real utility against paralyses and muscular atrophies; it is equally valuable in combatting tics, cramps, and neuralgia. It is used in cases of atony of organs supplied with unstriated muscular fibres. Many successes have been obtained even by the use of electrical baths in cases of intestinal occlusion. Finally, whether by static electricity or by currents at high fre- quency, success in modifying nutrition or calming general disorders, such as those which characterize neurasthenia, has been obtained. Electricity may also be used for producing electrolysis. When an electric current is passed through saline solutions it causes decompo- sition; the acids are attracted toward the positive pole and the bases toward the negative pole. The same phenomena occur in the organ- ism, and have been turned to use in therapeutics. Electrolysis is em- ployed to destroy certain pathological tissues. Although it has been abandoned in the treatment of aneurism, it is resorted to in the treat- ment of erectile tumours, uterine fibromata, and strictures of the urethra. It is also employed for destroying the hair. A last application of electricity is the galvano-cautery ; but in this case it is not the electric fluid itself that is concerned, but the heat which it develops. CHAPTER IV - CHEMICAL AGENTS Caustics — The toxines — Exogenous poisons: alimentary poisons, air poisons, poison- ing due to occupation — Criminal, suicidal, and accidental poisoning — Venoms — Mode of penetration of poisons — Transformation, elimination, and accumu- lation of poisons — The toxic equivalents: their variations — Habit — Anatomical lesions of toxic origin. In studying the physical agents we considered the contingent prop- erties of bodies, those that are independent of their constitution. We have viewed the world of energy. With the chemical agents we enter the world of matter. We are now about to study those properties which depend upon the molecular structure of bodies. Chemical agents are divided into two groups ; caustics and toxines. Caustics Caustics are bodies which, by virtue of their chemical affinities, are capable of altering and destroying the living part with which they come in contact. The action of 'caustics is known as mortification ; the result is called eschar. Mortification is the more energetic the greater the chemical affinity of the caustic for albuminoid substances. The organism presents various means of protection against the action of caustics. The skin is covered with a coating of grease, which shields the subjacent stratified epithelium; this resists fairly well. If it be reached, alkaline albuminoid secretions are produced which neutralize certain substances and form insoluble combinations with others. Caustics were formerly divided into mild and escharotic or strong caustics. To-day they are divided, according to Mialhe, into coagu- lating and liquefying caustics. Coagulating caustics are represented by metallic salts, acids, and some essences. Metallic salts, among which silver nitrate, acid nitrate of mer- cury, and zinc chloride deserve especial mention, give rise to two types 61 62 CAUSTICS of lesions. Applied to superficial parts, they cause instantaneous death of the cells — that is, mortification; they destroy them without modification of their normal histological characters. In the deeper tissues they produce fatty degeneration of the anatomical elements. Acids, of which sulphuric, hydrochloric, nitric, and chromic are the most important, often produce very extensive eschars. Although their action is diminished by the water they absorb from the tissues and by their union with the alkaline fluids, the lesions caused by them are generally profound. The aspect varies according to the substance. The eschar produced by nitric acid is yellow, owing to the formation of xantho-proteic acid. Sulphuric acid produces black eschars, the colour being due to an alteration of the colouring matter of the blood and to the liberation of carbon contained in the cells. Lastly, essences, notably those of cinnamon, bergamot, and meadow sweet, possess, according to Dr. Pilliet, the power of causing on the surface of mucous membranes lesions similar to those produced by sulphuric acid. Liquefying caustics comprise the bases potash, soda, and am- monia, and an acid — arsenious acid. The bases act by dehydrating the tissues and forming soluble soaps by union with fatty substances, also by decomposing nitrogenous substances. The eschars are soft, and, on separating, leave the blood vessels exposed, frequently causing grave hemorrhages. The cicatrices produced by various caustics are often severe, and may be followed by contractions interfering with motion. Functional troubles are particularly frequent when mucous membranes are in- volved. For example, strictures in the esophagus result, necessitating the establishment of a gastric fistula. TOXINES Many definitions of toxic substances have been given. Aside from those found in the codes, and which have no scientific value, we believe that a much broader meaning should be assigned to this term than is usually done. Therefore, we propose the following formula : Toxines are those substances which, when introduced into or formed within the organism, are capable of disturbing or abolishing the life of anatomical elements by either directly or indirectly modi- fying the liquid medium containing them. We include in this definition the very important group of toxic substances formed within the organism — the endogenous poisons — among which those concerned in auto-intoxication have been best studied. We repeat, that poisons act by disturbing the medium in which the anatomical elements live. This is a characteristic distin- CHEMICAL AGENTS 63 guishing the toxines from all other agents heretofore studied — in fact, all the others altered the parts with which they came in contact. Toxines, on the contrary, do not act until they have been absorbed, have penetrated into the blood and interstitial fluids, and have modi- fied their chemical composition. Our definition naturally leads to the division of the toxines into two groups : exogenous, altogether formed before their penetration into our organism; endogenous, which are generated within our own bodies. Endogenous poisons are subdivided into heterogenous and autoge- nous. The former are produced by parasites or microbes accidentally or normally lodging in our bodies ; the latter result from the very life of our cells. It is a general law that all living cells constantly pro- duce substances which, if not eliminated on the one hand while formed on the other, derange and arrest the manifestations of life. The following table will give an idea of this division: r v^r.rr^r^r.-,-,c i Habitual. Exogenous -j ( Accidental. Poison. Heterogenous ] Parasites. Endogenous -j < Infectious agents. ( Autogenous, by cellular life. Aside from the endogenous poisons, the history of which will be presented when treating of parasites, microbes, and nutritive disturb- ances, we shall consider exclusively the exogenous substances. We shall review in succession alimentary poisons, air poisons, poisoning due to occupation, accidental intoxications — whether criminal or vol- untary — and conclude with the history of venoms. Alimentary Poisons. — Among the common exogenous poisons are to be noted, first, the alimentary poisons, and chief of these the potash salts. These salts are useful, indispensable. Dogs fed on meat freed from potash salts succumb at the end of ten days — that is to say, much sooner than under the influence of absolute starvation. If great quan- tities are ingested, the excess is readily eliminated through the urine. But if the kidneys are altered, potassaemia results; and some authors hold that an accumulation of potash salts is responsible for the phe- nomena of uraemia. Side by side with the potash salts are often placed the albuminoid substances contained in the tissues. It is certain that their intra- venous injection speedily causes death. As a matter of fact, however, these substances are transformed into peptones in the digestive tract. The peptones, being dehydrated in their passage through the intes- tinal membranes, form new albumins adapted for the nourishment 64 TOXINES of the cells. It may possibly happen that, in the case of certain lesions of the intestinal membranes, peptones penetrate as such into the organism; they are then found in the urine. There has been a great deal of discussion in reference to the toxicity of peptones. It would seem that, if not peptones, at least albumoses produce noxious ejffects ; at all events, when injected into the veins, they can render the blood noncoagulable for several hours ; at least, that is what occurs in the dog. A last cause of habitual intoxication is represented by the putre- faction which occurs in the intestinal contents under the influence of microbes. We shall again refer to this when studying the bacterial agents. Alcoholism. — Toxic substances are found in beverages even more than in aliments. Water contains mineral salts, and, most important of all, the products of putrefaction of organic matter, which render it injurious. At the present day plain water is seldom drunk ; alcoholic beverages are largely consumed which, without exception, are toxic, and in cer- tain doses may speedily cause death. One litre of rum is estimated to be a fatal dose for an adult. In children, serious accidents occur with far smaller doses. Taylor reports the case of a child of seven years who died from the effects produced by drinking 100 grammes of brandy. We most frequently have to deal with chronic alcoholism. It is not necessary to state that this form of intoxication is steadily on the increase in the majority of countries. In 1830 France annually con- sumed a quantity of beverages corresponding to 1 litre of absolute alcohol per capita ; in 1885 the consumption had risen to 3 litres, and in 1891 to 4 litres per capita. This figure is still below the actual consumption. This is established by official statistics, which give for each year and for all France 1,545,045 taxed hectolitres. The amount of alcohol passing fraudulently is estimated at 500,000 hectolitres. The annual consumption for each inhabitant may then be estimated at 5 litres, which correspond to 13 litres of brandy. Moreover, if we reflect that there are many who consume no alcohol and that children drink hardly any, we must acknowledge that the figures are very high. Statistics further demonstrate the existence of a striking parallel- ism between the advance of alcoholism and the increase of insanity, suicides, and crime. We have said that alcoholism is on the increase in almost every country. In Denmark, the consumption of alcohol is 8 litres, and in Belgium 12 litres per capita. In some countries, owing to certain measures adopted, the advance of this evil is being checked. In the United States the consumption has fallen to 3 litres, and in CHEMICAL AGENTS 65 Norway, where alcohol once made fearful ravages, it does not exceed 2 litres per capita. The universally used expression " alcoholism " is incorrect in that it takes the part for the whole ; for in the so-called alcoholic beverages ethylic alcohol is certainly the least toxic ingredient. According to a law which offers very few exceptions, the toxicity of alcohols increases with their atomic weight. Alcohols of high atomicity — propylic, bu- tylic, amylic, oenanthylic — which are met with in most beverages, and particularly in brandy, are far more noxious than the alcohol of wine. Besides alcohols, we must mention aldehydes, and, among these, pyronic aldehyde or furfurol, all of which are convulsive poisons, and are found in vermouth and bitters. There are also ethers, acetone, vari- ous volatile bases, hydrocyanic acid, and, last but not least, essential oils. Absinthe contains nine different essences, all toxic substances. We must make special mention of a product too often considered as inoffensive — namely, aqua melissae. Women particularly make use and abuse of this preparation, which often gives rise to very grave disturbances, notably to paralysis, the nature of which is not always easily determined. We may state in conclusion that alcoholism is a complex intoxica- tion, hence the variability and multiplicity of the disturbances. Accidental Alimentary Poisons. — In addition to the toxines which we ingest in consequence of our social habits, others exist which can be regarded as accidental. At the head of the list stands lead, Nearly all beverages, water not excepted, contain more or less consid- erable quantities of this metal. In cities the water pipes are of lead, and water dissolves traces of it. In this event danger is not great, as the lime salts contained in the water are deposited inside the pipes in such a manner as to form a sort of protective coating. Lead is found especially in cistern water, which is pure and aerated, and in water containing organic substances in a state of decomposi- tion. Although opposed to each other, these two conditions are most favourable for the solution of the metal. In other cases lead comes from reservoirs painted with vermilion, from earthenware varnished with substances containing lead, and, in carbonic waters, from metallic vessels. According to Dr. Moissan, Seltzer water may contain as much as 0.9 milligramme of lead to the litre. Alcoholic beverages especially are oftenest contaminated with lead. The different pieces of the retorts and presses may leave traces. Un- scrupulous manufacturers add litharge to diminish the acidity of wine and cider, and acetate of lead to clarify beverages. We must also take 66 LEAD into account the grains of shot that may be left at the bottom of bottles after cleansing. Aliments are no less contaminated. Take, for example, bread. The millstones present small holes which are filled with lead; the tubes which conduct the flour to the bolter contain some lead; in the bakery refuse wood painted with white lead is sometimes used for heating the ovens, which wood gives off small amounts of this metal under the influence of the heat. Among other aliments, butter col- oured with chromate of lead may be mentioned, and also preserved game killed by leaden bullets. Preserves are worthy of particular attention. The pewter which is used to solder the boxes contains a considerable amount of lead, which is readily dissolved in preserves containing oil; in peas, only 2 milligrammes of lead are found to the kilogramme; in sardines, 40 to 50 milligrammes; in preserved beef, particularly in that intended for use at sea, Schutzenberger and Boutmy detected as much as 1.48 gramme per kilogramme. Most of the disturbances described as dry colic of hot countries have been shown by Amedee Lefevre to be cases of lead poisoning. Among other sources of saturnine intoxication we must note pot- tery, oilcloths, tinned utensils, the pewter foil surrounding chocolate and tea, the grinding machines of the butcher, the oilcloths painted with chromate of lead and used for packing ham and cheese, and nursing bottles with lead nipples. This enumeration sufficiently establishes the fact that people ingest daily a certain amount of lead; consequently, traces of it are often found in the urine. Putnam was able to find some lead in 17 per cent of the healthy subjects he examined. In the sick the proportion is as high as 50 per cent. Although the continual absorption of lead at times provokes gas- trointestinal disturbances, indigestion, and colic, it most often causes chronic manifestations. Arteriosclerosis and interstitial nephritis, so frequently observed after a certain age, are very often the results of a slow and progressive intoxication by this metal. Copper is perhaps as widely diffused as lead, but it is less danger- ous. It is found in bread, and especially in wine, since Bordeaux hou- illie has been employed instead of mildew. Wine, cider, and beer, even without the aid of heat, rapidly attack copper. Condiments prepared with vinegar and pickles always contain some. Some is also met with in vegetables, which, in fact, possess the property of taking up the metal contained in the soil; and notable quantities of it are found in the hulls of various grains. It is easy to understand that copper might invade the organism of herbivorous animals from the vegetables eaten. That is why we find CHEMICAL AGENTS 67 some in the meat we consume. Dr. Gautier thinks that one can toler- ate 18 to 20 milligrammes per kilo, but these quantities are often ex- ceeded. As much as 200 or 210 milligrammes of copper salts may exist in one kilogramme of preserved substances. It can be said, then, that we ingest some copper and lead every day. Dr. Gautier estimates the minimum at 1 to 7 milligrammes and the maximum at 20 to 30 milligrammes. These salts, however, are of little toxicity. Taken in large doses they are rejected by vomiting; in small doses they are well supported. Dr. Galippe has given some to dogs, and he himself, his family, and friends have ingested these substances during months and years without observing the least dis- turbance. Another and far more toxic substance is arsenic, which is often found in wine. In 1881 four hundred persons were poisoned at Hyeres and Havre by arsenical wines. Again, it is in preserves that arsenic is mostly found. This substance is introduced because of its anti- fermentative properties. The gastrointestinal disturbances provoked by it are of frequent occurrence in Russia, where preserved fish is extensively used. Finally, foods may contain other metals given off by cooking uten- sils and vessels made of pewter and nickel, which, however, do not seem to be dangerous. Among the toxic substances found in foods it is well to mention the aniline colours, which too often contain arsenic and which are used to colour wines, bonbons, and sirups. Of all poisonous substances added to foods, one of the most exten- sively used is salicylic acid. This acid, employed to prevent putrefac- tion, is well supported by normal persons ; but it often induces grave manifestations in those whose kidneys are more or less markedly al- tered, and therefore unequal to the task of eliminating it by the urine. To sum up, three substances claim our attention — namely, arsenic, salicylic acid, and, above all, the lead salts. Poisoning may also be occasioned by the use of nonedible vege- tables or animals. We hardly need refer to the frequency of disturb- ances caused every year by poisonous mushrooms or toadstools, the action of which is due to three poisons — namely, choline, muscarine, and phalline. Accidents have sometimes been observed as the result of the use of sprouting potatoes sold as new; in fact, upon the skins there is found a violent poison — namely, solanine. It is mainly in hot countries that venomous animals are encoun- tered. In our latitudes the accidents are produced by the eggs of certain fish, such as herring, pike, molluscs, oysters, and sometimes certain Crustacea. 68 ANIMAL POISONS Fish eggs provoke choleriform phenomena — ^that is, vomiting and diarrhoea accompanied by general prostration; afterward cutaneous manifestations appear, such as erythema and urticaria. Recovery is the rule. The toxicity of fish is due, it seems, to their having lived in water containing putrefying matters, notably near coral reefs. A similar explanation may be given for the action of molluscs. Poisonous oysters are those that have lived in unwholesome surroundings — for example, near the outlets of sewers. Shellfish may be particularly dan- gerous. It was once asserted that they became toxic when they lived upon the sides of ships sheathed with copper. Even when healthy, shellfish are not good food. The inhabitants of Tierra del Fuego, who consume as much as 5 to 15 kilogrammes a day, are affected with a special hepatic cirrhosis attributed to this form of diet. Under certain circumstances the flesh of animals may become toxic — for example, when they are overworked. This is due either to the fact that overwork provokes the development of noxious substances or because it permits the intestinal microbes to pass into the tissues. Thus it is with good reason that animals destined for food are allowed to rest for at least twenty-four hours before they are slaughtered. Accidents have been provoked by the use of the flesh of animals receiving toxic substances. This is not always the case, however, as savages consume the beasts killed by poisoned arrows. Nevertheless, morbid manifestations may appear when use is made of the flesh of mammalia which have received high doses of arsenic for therapeutic purposes. In the course of diseases, and notably of infections, toxic sub- stances may be produced which are again met with in the tissues or the secretions. The flesh and milk of animals dead from indigestion, dropsical cachexia, various infections, and particularly puerperal fever, should be absolutely rejected. Aliments of vegetable origin may produce disturbances, either be- cause they come from diseased plants or because they have been invaded by various parasites. Numerous epidemics, which have been described as ergotism, feu Saint- Ant oine, raphania, are known to be provoked by ergot — Clavi- ceps purpurea. The disturbances are due to various substances, of which one, sphacelic acid, causes gangrene of the extremities, and another, comutine, produces convulsions. The disease in man assumes two different types, which may either have a gangrenous or a convul- sive form. Among the alterations of cereals, it is sufficient to mention nigella CHEMICAL AGENTS 69 and the wheat rot, the mixture of flour and Lolium temulentum (bearded darnel), and the copper green of Indian corn, which plays an important part in the etiology of pellagra. Volatile Poisons. Poisons of the Air. — Apart from alimentary poisons, numerous others are daily met with. Volatile poisons are found in the atmosphere. Confined air, vitiated by the respiration of several individuals, soon becomes toxic and produces indisposition and giddiness. When a great number of persons are inclosed in a small room, death may supervene. It is not merely a question of diminution of oxygen or accumulation of carbonic-acid gas, but one in which the toxic substances are of organic origin and impart to the air a well- known nauseating odour. Air may be polluted by products of combustion — for example, by carbonic-acid gas, which is not very dangerous, and especially by car- bonic oxide. Poisoning by the latter gas occurs quite frequently when movable stoves with slow combustion are employed. In this way as high as 16 per cent of carbonic oxide is produced (Moissan). When there is little or no draught, the slightest puff of wind drives the deleterious gas into the room or even into the adjoining apartments. This is also a source of poisoning, manifesting itself by constant headache, loss of memory, and anaemia, and one which, in certain cases, may assume an acute course, resulting in death. The combustion of illuminants also produces carbonic oxide. The oil lamp, however, gives off almost exclusively carbonic-acid gas. Illuminating gas is very toxic, because it contains from 7 to 20 per cent of carbonic oxide. In Paris 150,000,000 cubic metres of it are manufactured. Ten per cent, say 15,000,000 cubic metres, are lost in consequence of defects and infiltrate the soil. On approaching a trench opened in the street we smell the strong odour of gas. It is no wonder, therefore, that the atmosphere of Paris contains 1 per 10,000 of carbonic oxide. A much greater proportion seems to exist in apart- ments which, by virtue of their high temperature, draw the gas dis- tributed to the soil. The air of apartments may also be polluted by substances emanat- ing from paintings and tapestry. This was formerly a frequent occur- rence when arsenical greens were extensively used. Finally, as if all these causes of intoxication were not enough, the majority of men poison themselves by the daily use of tobacco. Every year 2,000,000,000 kilogrammes of this plant are consumed. In France the consumption exceeds 30,000,000 kilogrammes. In the smoking of tobacco carbonic acid, carbonic oxide, sulphuretted hydro- gen, hydrocyanic acid, traces of nicotine, and especially pyridic bases are inhaled. The last-mentioned substances are the most dangerous 70 VOLATILE POISONS of all; they are particularly abundant in a slow and incomplete com- bustion — as, for example, in pipe smoking. Generally, the habit is quickly formed, but the abuse of tobacco gives rise to many disturbances — namely, diminution of memory, espe- cially for proper names, dyspepsia, palpitation, spells of angina pec- toris, which, though generally harmless, sometimes kill, as happened in a case reported by Dr. Letulle. While those who smoke are poisoned, chewers are far worse affected, because they ingest the various toxic substances contained in tobacco, notably nicotine. In those who are not accustomed to its use dis- turbances rapidly appear. Some persons have been seen to succumb from the effects of chewing half a cigar. In Oriental countries the smoking of opium replaces that of tobacco. In China they begin to smoke at about the age of eighteen; it is not, however, in their own homes that they give themselves up to this occupation; it is in more or less luxurious dens where they assemble or remain isolated. They very quickly become accustomed to the poison, and soon reach daily doses of from 5 to 6 grammes of the extract. The habit does not seem to be very pernicious ; it is much less so than the practice of eating opium. Eaters of opium and of theriaca, especially numerous in Turkey and Persia, present a premature decrepitude. In European countries opium is nowadays causing great ravages under the form of morphine injections. It is on the occasion of a pain, a neuralgia, or an insomnia that the first injection is resorted to ; then the habit is formed, and very considerable doses are reached — 0.5 to 1 gramme, and even 4 to 5 grammes daily. Morphinomania is prevalent mainly among the higher classes. It is of very frequent occurrence in persons who can easily procure mor- phine. In the statistics of Dr. Pichon, comprising 66 subjects, there were 17 physicians, 7 students of medicine, 5 druggists, and 3 students of pharmacy; out of 56 women, 12 were married to physicians. Other poisons may be employed for the agreeable sensations they produce. Such are ether, cocaine, chloral, and especially hasheesh, pre- pared with the leaves of Cannahis indica, which is used by 200,000,000 to 300,000,000 people in Africa, India, and Turkey. In Oriental Asia an inebriating beverage is prepared from a poison- ous mushroom — the false orange. Poisonings due to Occupation. — In approaching the study of poi- sonings due to occupation we again meet the poison with which we have become familiar — namely, lead. Disorders may be produced dur- ing the extraction of the mineral from the earth. The miners die young, their average age not exceeding forty-two, and their mortality CHEMICAL AGENTS 71 amounts to 18 per cent a year. In France the disorders are mostly observed in workers in white lead and in painters. A few years ago the workmen in the factory at Clichy (France) entered the hospital on an average of four times a year. Owing to the introduction of bet- ter sanitary conditions, accidents are now of much less frequent occur- rence. They occur mainly among painters, who are first attacked with lead colic and later with arteriosclerosis, paralysis, interstitial nephri- tis, and gout. Arteriosclerosis is a pernicious manifestation, and when the arteries of a young man are found to be very hard, saturnine poisoning can almost certainly be diagnosticated. Mercury^ like lead, also produces grave disturbances in workmen employed in its extraction. The miners of Almaden, in Idria, are affected with a special gingivitis resulting in shedding of the teeth. There has been a good deal of loud talk of late, and with just reason, in reference to the disturbances caused by phosphorus. The workmen in match factories are affected with an extremely serious necrosis located in their lower maxillary bones. This lesion is com- paratively rare to-day, owing to a better equipment of the factories, and especially to the use of the harmless red phosphorus, which is gradually tending to replace the white phosphorus. The combustion of coal may produce two kinds of intoxication : one due to arsenic, the other to carbonic oxide. Coal always contains some arsenic, which passes into the smoke, and, in the neighbourhood of fac- tories, especially of furnaces, is deposited on the soil and vegetables, and thus may produce poisoning in man and animals. Carbonic oxide is much more widely diffused. It intervenes very often in the habitual conditions of life. Cooks and laundresses, who breathe it constantly, are affected with anaemia and disturbances of memory. There are records of several cases of persons having been killed as the result of lying down near a furnace. There are other deleterious gases to be pointed out, such as nitrous vapours, chlorine disengaged in the bleaching of paper, and gases emanating from animal matters undergoing putrefaction. This is what is called mephitism. Accidents produced by these emanations were formerly very fre- quent among workers in sewers ; but to-day the ventilation of sewers is so perfect that the danger has disappeared. The same is true of cess- pools, where accidents are no longer observed except in time of repairs. In detaching the crusts covering the walls of sewers and cesspools, hydrosulphate of ammonia is disengaged, the inhalation of which causes rapidly fatal accidents. We may also mention the volatile products emanating from putrid organic matters in tanneries, catgut and glue factories, and the like. 6 72 POISONING BY DRUGS Poisoning by Drugs. — Another group of toxic causes comprises the medicinal substances. To say nothing of errors of dosage, there are poisonings caused by the impurities of certain products. Grlycerine may contain arsenic; strontium salts are not always free from baryta. It should be remembered that tinctures and extracts, even when well prepared, are very unreliable, as they contain variable proportions of the active principles. Hence, the tendency is to substitute for them alkaloids and glucosides, which are quite definite from a chemical point of view; they do not, however, always manifest the same action as the more complex and less purified products. Accidents are often brought about by the use of medicine for too long a period. It was once believed that mercury did not produce its effects until it gave rise to salivation. At the present day accidents of this nature are no longer observed; but toxic manifestations are some- times produced by injections of bichloride of mercury and the long- continued administration of digitalis. It may be well to here remark that the stomach does not easily bear most of the medicines introduced into it. In many cases chronic gastritis is simply the result of abuse of therapeutic substances, and a good many of the troubles due to alcohol are traceable to the use of so-called tonic or rejuvenant wines. Anaesthetics have caused a certain number of deaths. Nitrous oxide seems to be harmless when used for very short operations and inhaled only a few seconds. Out of 30,000 cases reported in America there is not a single death. On the contrary, according to Morgan's statistics, chloroform has produced 34 deaths out of 100,000 cases, and ether only 4 for the same figure. In America these results have led to the substitution of ether for chloroform in surgical anaesthesia; in France, also, a similar tendency is now observed. Criminal Poisoning; Suicide; Accidents. — Poisons are frequently employed for criminal or suicidal purposes. Arsenic was formerly the one most frequently made use of. It was the basis of the Borgia poison, and was employed by the Marquise of Brinvilliers. Nowadays the progress of chemistry leads criminals to avoid the use of mineral poisons, since they are easily detected. The vegetable alkaloids are preferred, because they induce no lesions and are with great difficulty distinguished from cadaveric ptomaines. For this reason experts are often unable to arrive at a positive conclusion. Suicide is often committed by means of alkaloids or cyanide of potassium. In France the fumes of coal — that is, carbonic oxide — are resorted to. As a matter of fact, 185 cases of asphyxia have been reported as against 52 poisonings. In other countries the proportions are quite different. In Italy, for example, there were 44 cases of CHEMICAL AGENTS Y3 asphyxia and 132 poisonings; in Prussia, 11 to 20; in England, out of 225 cases of poisoning there was not a single example of carbonic asphyxia. Poisons have also been utilized for judicial purposes. In Greece, the condemned persons were made to drink hemlock. The countries that we call barbarous had poisons of trial. For example, in Mada- gascar, on certain days the extract of Calabar bean was administered to 500 to 600 persons. Those who did not die were declared innocent. The same method was used to decide legal questions. The system, however, soon became modified: each adversary was represented by a dog; the two animals drank the poison, and the owner of the one that died was pronounced guilty and condemned. Venoms. — Venomous animals are those possessing venom glands, the contents of which can be exuded. These should not be confounded with poisonous animals. The latter contain toxic substances in their blood and tissues. We have spoken of them in treating of alimentary intoxications. Among the venomous animals the most dangerous are represented by the ophidia. All snakes are possessed of a venom gland; but in some of them, as in the case of couleuvres, the gland being deprived of an excretory duct, the poison can not be poured out. The Mont- pellier adder, whose gland opens at the bottom of the buccal cavity, is harmless for man and for animals of great size ; it can kill only small animals, which it seizes by one of the limbs. The venomous species of France are three in number: the Vipera aspis, which must not be confounded with the asp of Egypt, the Vipera ammodytes, and the Pelias herus. Our (France) indigenous vipers are more dangerous in the south than in the north, and on the left than on the right bank of the river Loire. Their bite may occa- sion the death of an adult, and more readily that of a child; but even when the bite is healed, it is in many cases followed by persistent neuralgia, recurring sometimes at certain seasons. Although serpents are not very dangerous in our (France) lati- tudes, they constitute a veritable evil in hot countries. In India 20,000 persons die each year from their bites. The effects provoked by serpents are divided into local and general disturbances. Locally, oedema appears, especially marked when the venom is not very active; it is also observed as a result of the bites of our vipers. (Edema has developed sufficiently in certain regions of the body to mechanically cause a fatal termination. The general disturbances are characterized either by progressive asphyxia (proteroglyphes) or by convulsive phenomena (soleno- glyphes). 74 VENOMS After much discussion, it is acknowledged that snake poison con- sists essentially of proteid matters and albumoses. To combat its effects, the first thing to do is to oppose its absorption. Tying the bitten limb and suction of the wound are well-known procedures, Next, we resort to cauterization and hypodermic injection of sub- stances that neutralize the venom — for example, potassium perman- ganate, gold chloride, and, above all, calcium and sodium hypochloride. Lastly, it has been recognised of late that it is possible to accustom animals to progressively increasing doses of venom; their blood ac- quires curative properties and their serum has been used with success. The names of Phisalix, Bertrand, and Calmette are connected with this discovery. The other animals capable of producing venom are less important. In European countries there are the toad, triton, and, above all, the salamander. Among fish there are trachinidce (weever, stingfish), which secrete themselves in the sand, and the bite of which may pro- duce in bathers phlegmons and gangrene, often of very grave character. Venomous insects are very disagreeable, but generally not very dangerous. The bites of gnats, bedbugs, fleas, and ants are without gravity. It is estimated, however, that six to eight hornets can kill a man. In some cases a wasp has bitten in a region where the conse- quent swelling has caused death — for example, at the base of the tongue or in the pharynx. The active principle of the venom of the bee and hornet consists of formic acid united to a hydrocarbon — ^undecane, the formula of which is C11H24. Finally, we may mention the scorpion of the south of France, the bite of which is of little gravity. Modes of Penetration of Poisons. — Poisons can penetrate our or- ganism in several ways. They enter mostly by the digestive canal, which is provided with certain means of protection. The disagreeable, acrid, or burning taste of certain substances causes one to expectorate immediately, and at the same time provokes a salivary secretion, which cleanses the buccal cavity. If some of the poisonous substance has been swallowed, antagonism is manifested in the stomach : First, by an abundant secretion, which hinders absorption, dilutes the poison, and neutralizes certain principles ; next, by rejection through vomiting. Finally, when the poison reaches the intestine, similar phenomena are produced — namely, an increase of secretion and evacuating diarrhoea. It may be remarked, however, that the diarrhoea which supervenes in cases of poisoning is mainly in connection with the secondary elimina- tion through the mucous membrane of the intestine. The poison may find in the digestive canal conditions favourable CHEMICAL AGENTS 75 for its harmful action. For example, fatty matters dissolve phos- phorus and hasten its absorption; the hydrochloric acid of the stom- ach transforms calomel into corrosive sublimate, and the insoluble car- bonates into soluble chlorides; it also decomposes potassium cyanide and thus gives rise to hydrocyanic acid. Hence it is that the action of the substance last mentioned is less marked when the stomach is empty than during digestion. If the poison be a gas, other protective phenomena intervene. The odour, the pricking of the mucous membranes, the irritation that pro- vokes lachrymation, sneezing, or coughing, warn us of danger. These reactions are not constant, however, and absorption does take place. Gases penetrate very easily through the lungs ; even liquids introduced by this route can be absorbed, provided they are introduced very slowly. Volatile substances can also penetrate through the skin. For exam- ple, mercury, iodine, turpentine, and methyl salicylate are readily ab- sorbed in this way. Certain solids, especially when they are incor- porated with fats, can also pass through the integument. Absorption by the urinary apparatus has been a subject of much discussion. The prevailing opinion is that the bladder does not absorb; contrary results are due to the fact that too strong solutions have been injected, which alter the epithelial lining and abolish its protective function. Another cause of error capable of vitiating ex- perimental results is that the posterior urethra absorbs very well; a drop flowing from the bladder can occasion poisoning. Very little, if any, absorption can take place in the ureters, but it doubtless occurs in the calices. In women, the vagina, and still more the uterus, may serve as routes of penetration for poisons; and in numerous cases accidents have occurred as the result of the too prolonged or contin- ued use of corrosive sublimate. The subcutaneous route is daily used in the therapeutic introduc- tion of medicines. Absorption is the slower the thicker the subcu- taneous fatty tissue is, and it varies also according to regions. The different parts of the body may be classified as follows: First, the temples and cheeks; second, the epigastric region, the inner surfaces of the thorax, the external surfaces of the arms and thighs, the foot, and, last of all, the back. From a practical standpoint these results are evidently very important. Absorption can also take place in ex- posed mucous membranes, such as the conjunctiva, and in serous memhranes, such as the pleura or the peritoneum. Among the conditions antagonizing or favouring absorption we must note certain modifications of a physical order. A decrease of pressure upon the integuments retards absorption. This is what is realized by suction or by dry cupping. If, however, pressure in the Y6 PENETRATION OF POISONS abdominal cavity be increased, the passage of colloids, like the albu- mins, is hindered, while that of crystalloids is enhanced. This result, which has greatly surprised certain authorities, is altogether in accord- ance with physical laws. The same effects are observed when a liquid is made to pass through a porcelain filter: the increased pressure hastens the passage of the water and of the salts dissolved in it, but causes a dissociation of albumins, which are not carried off by the cur- rent but retained on the filter. Since the time of Magendie it is admitted that bloodletting favours absorption, while intravenous injections of salt water delay the passage of substances by increasing the mass of blood. These results are exact, although far more complex than was believed. The effect of injections of water is notably to modify the reactional power of the nervous centres and the secretory role of the kidneys. This is what renders the problem so difficult and the interpretations so very delicate. The absorption of toxic substances is determined chiefly by the venous system. Magendie has perfectly demonstrated this by an ex- periment which has become classical. He divided the thigh of a dog and united the two ends of the severed artery and vein by glass tubes ; he introduced poison into the paw thus connected with the rest of the body, and toxic manifestations were produced. The poison could not have penetrated except by the blood vessels, since the lymphatics no longer existed. Transformation, Elimination, and Accumulation of Poisons. — After reaching the blood, poisons act differently, according to the manner of entrance. If they enter through the digestive tract, they pass into the mesenteric and portal veins and arrive first at the liver. Placed as a barrier in the path of all substances coming from the gastro- intestinal apparatus, the liver exerts on them a selective action; it allows some to pass on, retains others, and, after having stored them up for some time, permits them to gradually pass again in harmless amounts; it eliminates some of them through the bile, and, finally, it submits many others to chemical transformations, depriving them of their toxicity. These modifications are especially brought to bear upon the alkaloids, so that a poison loses about half of its toxicity in pass- ing through the hepatic gland. Here, then, is an important protective role to which we shall more than once refer. When it has passed through the liver, or when it has penetrated directly through the skin or subcutaneous tissue, the poison reaches the vena cava, passes through the heart, and arrives at the lungs. Here is another protecting organ. It acts upon certain alkaloids, no- tably upon strychnine; but it especially eliminates volatile substances. Sulphuretted hydrogen, for instance, which is very toxic when inhaled, CHEMICAL AGENTS ^1 can be introduced by the stomach or the rectum without inconvenience ; it is exhaled by the air as fast as it penetrates. Phosphorus is also eliminated by the lungs, and imparts to the expired air the property of luminosity in the dark. The other gaseous substances follow the same route, since it is possible to notice them by the characteristic odour of the breath. After passing the pulmonary barrier, poisons arrive at the left heart, and from there pass on through the aorta to be distributed to the different parts of the organism. They reach the nervous system, where they produce the principal disturbances due to their action. Part of the poison, however, passes through certain protective organs, such as the sanguineous vascular glands; another part encounters organs which throw it out. Poisons thus pass into secretions — sweat, milk, tears, and especially the urine. The .kidney, in fact, represents the principal route of elimination for the majority of toxic substances. Finally, a certain amount of poison may return to the stomach and intestine by the mesenteric arteries and coeliac axis, and be eliminated by the glands of the digestive canal. Morphine, for example, passes into the gastric secretion ; there- fore, in cases of poisoning by this alkaloid, it is well to wash out the stomach even when the poison is introduced by the hypodermic route. The poisons passing out by way of the intestines may produce diar- rhoea and sometimes alter the mucous membrane, which is then placed at the mercy of the numerous intestinal microbes. Thus a gangrenous enteritis results under the influence of corrosive sublimate. It is a lesion induced by the elimination of mercury and determined by the intestinal bacteria. Certain conditions intervene to favour or hinder the elimination of poisons. In children, the kidneys work with extraordinary energy, and this is why poisons which can be eliminated by the urine are so well borne by children. The same doses of salicylate of sodium given to an adult can be given a child of six years. In the old, on the contrary, elimination is slow. Much caution, therefore, is to be exercised in the administration of active medicines to the aged. Finally, elimination is modified during the course of various or- ganic affections — for example, in nephritis, the urinary function being insufficient, active substances easily provoke disturbances. Poisons accumulate mainly in two parts of the economy — ^namely, in the liver and the osseous system. The analyses of toxicologists teach us that arsenic, lead, and mercury are able thus to remain for years. Hence the possibility of disturbances breaking out long after the use of a poison has been suspended. Kussmaul reports that two 78 TOXIC EQUIVALENTS persons developed salivation on the occasion of a sulphur treatment four and twelve months respectively after having ceased the employ- ment of mercury. The possibility of these accumulations should not be lost sight of in practising therapeutics ; doses perfectly well borne at first may pro- duce disturbances at the end of a few days; such is the case with digitalis. Toxic Equivalents: their Variations. — The considerations we have presented already explain that a toxic substance does not always pro- duce the same phenomena in the same doses. In the first place, there are variations dependent upon the species. Take nicotine, for example. The fatal dose of this alkaloid, reduced to the proportion of 1 kilogramme of animal, is represented by the fol- lowing figures : 35 milligrammes for the frog, 12 milligrammes for the guinea pig, 7 milligrammes for the rabbit, 5 milligrammes for the dog, and 0.5 milligramme for man. As a rule, the higher the being is in the animal scale, the keener is its susceptibility. In the next place, variations according to races are to be taken into account. Darwin furnishes numerous examples : the white sheep and hog are more sensitive to certain poisons than those of dark col- our. In man, morphine calms a European, while it excites and drives a Malay to homicide. Fatal doses vary also according to age: more poison is required, weight for vveight, for killing a child than an adult, and especially an old man. The influence of sex is quite evident in the following figures, given by Preyer: To kill a male guinea pig 8 milligrammes of curare are required; for a female, 13 milligrammes; and in the case of a preg- nant female, as much as 17 milligrammes. A condition of another order is represented by the temperature of the body. Thermal elevation favours the action of poisons. The surrounding temperature may have variable effects; it renders the organism more sensitive to convulsive poisons, but facilitates the elimination of certain substances. If we give the same dose of chloral to three guinea pigs, we see the one left in the open air die in four hours; the second, wrapped in cotton, will survive after a sleep of twenty-four hours; the third, placed in an oven, will recover in seven hours. By cooling certain animals, and by heating others, we can further vary the fatal doses. The state of fasting or digestion should also be taken into con- sideration, and likewise the integrity or lesions of various organs, particularly those that are concerned in the transformation and elimi- nation of toxic substances. Finally, there exist particular idiosyn- crasies, resulting from a series of inappreciable causes which impart CHEMICAL AGENTS 79 to beings a resistance and predisposition impossible to determine in advance. It may be understood how difficult it is to exactly establish the fatal dose of a substance. A great many attempts have, however, been made in this direction, and have already led to results of much inter- est. By operating on animals and injecting poison into the veins, it has been possible to determine the deadly dose. Dr. Bouchard pro- poses to designate the quantity of poison capable of killing a kilo- gramme of animal by intravenous injection as the toxic equivalent. It is evident that the toxic equivalent is applicable only to the species on which the operation has been made, and that it would not be exact to transfer the results from the animal to man. We can only obtain interesting indications. If figures determined in experimenting upon animals are fairly concordant, effects observed in man are far more variable. Thus, in certain cases, 0.3 gramme of extract of opium has proved fatal; in other cases, 1.5 gramme has been endured. The results are the same for morphine: 0.4 may kill and 2 grammes may not cause death; 1 centigramme of atropine sulphate generally represents a deadly dose, whereas some persons have tolerated 25 or 30 centigrammes; and with cocaine, 4 centigrammes have killed in one case; 1.25 gramme has not done so in another. Habit. — Finally, it should not be forgotten that one soon becomes accustomed to certain poisons. Tobacco, alcohol, and morphine, which first arouse painful reactions, are very well borne after some time and even seem to become indispensable to life. A familiar illustration is afforded by the history of the amoeba, which can gradually be habitu- ated to water containing 2 per cent of sea salt; it becomes so accus- tomed to the new conditions that it perishes when again brought back into ordinary water. Under the influence of poisons frequently intro- duced, a modification of cellular nutrition is effected, with consequent humoral changes : the humours become antitoxic in nature — i. e., they acquire the property of neutralizing the noxious effects of substances to which they have become habituated. Here a new field is opened to therapeutics. Anatomical Lesions of Toxic Origfin. — In producing functional troubles, poisons gradually modify the structure of cells — i. e., give rise to anatomical lesions in them. They may produce local manifes- tations, pus, or sloughing. In other cases they induce alterations in organs or tissues. Among these, some are common manifestations: hemorrhages, muscular ruptures provoked by contractures and convul- sions, emphysema due to respiratory disorder, and subpleural or sub- pericardial ecchymoses induced by asphyxia. Others are to be con- 80 ANATOMICAL LESIONS nected directly with the action of poisons. If it is true that functional disturbance always precedes the anatomical lesion, it is easy to under- stand that the poison will exert its effects first upon the most clearly differentiated elements — i. e., upon those that act effectively. The lesions of connective tissue will be but secondary. In the kidney, for instance, it is always the epithelium that is first attacked ; in the liver, the hepatic or biliary cells; in the spinal cord, the great nerve cells. If among these affected cells some should succumb, the defect thus produced will be supplied by connective tissue. Thus what is called sclerosis is developed. The function of the connective tissue not being deranged, we can not conceive it to be the seat of primary lesion. Its development is a phenomenon of reparation, comparable to a cicatrix. Finally, in cases of chronic intoxications, nutritive modifications are produced, sometimes finding expression in emaciation (morphino- mania), sometimes in obesity (alcoholism), and in still other cases in some curious phenomenon, as uricaemia and gout (saturnine). The various disturbances provoked by toxic agents may be trans- mitted to descendants. It is thus that beings come into the world with organic taints and nutritive vices ; and, as the morbid impression will have acted on young and easily impressionable cells, the disorders acquired by parents will often be found exaggerated in their offspring. CHAPTER V ANIMATE AGENTS Parasites and infectious agents — Definition of infectious diseases — History — Spon- taneous generation, fermentations — The work of Spallanzani, Davaine, Pas- teur — Division and cultivation of infectious agents — Bacteria: their classifica- tion, their variability. The animate agents are usually divided into two groups — parasites and infectious agents. Some writers have thought that natural history could be taken as a basis for this distinction. According to them, infectious diseases are those caused by bacteria. This conception, however, seems scarce- ly admissible, for the group of infectious diseases was created before the discovery of bacteria, and hence was of necessity established upon the data of clinical observation. It is only by comparing the morbid processes, by taking into account the conditions of their development, the manifestations they have presented, and the evolution they have followed, that it has been possible to draw closer together certain diseases and group them. The bases of the classification, therefore, have been symptomatic. It was and still is the only possible classi- fication. Since the apparent signs are to be traced to hidden occur- rences, it has been and it always will be necessary to start from what we see — namely, from clinical manifestations — and it is only by de- duction that the cause of observed disorders can be affirmed. When the animate nature of pathogenic agents was discovered, it was desired to establish a relation between infectious diseases, as they have been defined, and the microbes which were disclosed. But such relations do not exist. Malarial fever, which everybody classes among infections, is due not to a bacterium, but a sporozoid. The type of infectious diseases, tuberculosis, seems to depend upon a relatively high fungus or a streptothrix akin to actinomyces. Yet no one would dare maintain that malaria and tuberculosis must be thrown out of the class of infectious diseases. 81 82 INFECTIOUS AGENTS We therefore conclude that infectious agents may belong to classes other than bacteria, and that there is no constant relationship between their taxonomic position and their action on living beings. What, then, is the difference between parasitic and infectious agents ? A chief distinction is furnished by the way in which the two kinds of agents act toward the individual upon whom they live. The para- site spares his host ; it does him the least harm possible ; it draws ex- actly what it needs for its own subsistence ; it understands that it is to its own interest to preserve for the longest possible time the individual upon whom it lives. The infectious agent does not take all these precautions. It acts with brutality: develops rapidly, tends to invade the entire organ- ism, disturbs its functions, excites very intense reactions. It engages in a terrible struggle, the issue of which varies according to a number of secondary circumstances. The parasite is satisfied with the corner where it vegetates ; it grows slowly, expands very little, and it hardly, if ever, invades the economy; and if, at a certain moment, it causes death, it is, as it were, acci- dentally, unwittingly. Example: The intestinal worm when it makes its way into the air passages. In this way the parasite, satisfied with little, is easily supported; it does not give rise to violent reac- tions; often it remains even unnoticed. It may, however, grow, and when its volume becomes considerable, it may produce various dis- turbances. Such is the case with a hydatid. But the phenomena pro- voked here are due to compression; they are of a mechanical order. On the contrary, infectious agents act chiefly by the fermentations which they produce and by the toxic substances which they engender. There precisely lies the chief difference. No doubt, as in all distinc- tions, this is not an absolute one. Parasites also produce toxic sub- stances ; some are found in the liquid of hydatids. It is always a ques- tion of more or of less. But, with parasites, intoxication is reduced to a minimum; with infectious agents, it becomes predominant and ex- plains all the reactionary phenomena. Infectious diseases may there- fore be defined, " Diseases developed under the influence of toxines produced by certain parasitic agents" Infection, then, is nothing else than a chapter of intoxication. History. — Three terms characterize all infections : an animate agent, a fermentation, an intoxication. These three terms are en- countered in the writings of the most ancient observers. From Varro and Columelle to Linnaeus, only beings relatively high in organization were considered capable of producing infectious dis- eases. This gross parasitism which attributed a pathogenic action to ANIMATE AGENTS 83 worms, insects, or arachnidas, attained its height with the theories of Kaspail on sarcoptogenesis. With the idea of comparing viruses to poisons evolved simultane- ously, typhic or paludal intoxication was spoken of, though without attaching a very precise meaning to these expressions. There was only a tendency to consider certain miasms as volatile poisons. Finally, since Rhazes, who likened smallpox to the fermenting must of grapes, many physicians — Hoffman, Braconnot, Bouillaud — compared the infectious to the fermentative process. It was the com- parison of an unknown phenomenon with another which was no better known. Up to recent years the nature of these two great processes was completely obscured, and whenever a happy chance permitted the discovery of a living being in a diseased organism, in putrescent mat- ter, or in a fermenting liquid, it was simply supposed to be a case of spontaneous generation. The first author who revolted against the nefarious yoke of the belief in spontaneous generation, which had dominated since Aristotle, was a naturalist of the seventeenth century, F. Redi. The experiment which he realized, no matter how childish it may seem to-day, pos- sessed at that epoch vast importance. Redi established the fact that the larvaB of flies were not born spontaneously through putrefaction of meat. By means of a gauze, he prevented the insects from deposit- ing their eggs, and henceforth the larvas did not develop. A few years later, in 1678, van Leeuwenhoek, examining vegetable infusions, observed the presence of microscopic beings, which Wris- berg, in order to recall their origin, named infusoria. Van Leeuwen- hoek understood that these beings were not born by the decomposition of matters, but that they proceeded from pre-existing germs, spread in the atmosphere. This very same idea was again taken up in the following century and developed, in a series of admirable studies, by Spallanzani. Stimulated by numerous attacks directed against him by Needham, Spallanzani multiplied his researches and established the fact that there is no fermentation when the liquids are protected from air. This great discovery was confirmed by Schultze and by Schwann. Finally, in 1837, Cagniard-Latour showed that during alcoholic fer- mentation yeast increases and multiplies absolutely like a vegetable. Yet, despite the observations made by van Leeuwenhoek, Spallan- zani, and Cagniard-Latour, the question of fermentations remained very obscure. The progress of discoveries was arrested by the belief in spontaneous generation, which still persisted, and by the false theories that had been accepted upon Liebig's authority. The fermentative pro- cess was attributed to a particular condition of matter, exercising some kind of a catalytic action. 84 HISTORY It was then that Pasteur undertook the study of the problem. Completing the researches of Spallanzani, he demonstrated that innu- merable germs are hovering in the atmosphere, and that, falling into certain liquids, if they there find the conditions favourable for their development, they determine fermentation. Pasteur then conceived the brilliant idea of isolating and cultivating these germs, and he thus succeeded in describing successively, in 1857, the lactic ferment; in 1860, the alcoholic ferment; in 1861, the but3rrie ferment. This last ferment differed from all beings known up to that time by the fact that it lived without oxygen; it was the first example of anaerobiosis. These works aroused numerous protestations on the part of chem- ists. Physicians took no interest in them, as they failed to see the applications which they could make of them to medicine. Only one man saw clearly: that was Davaine. In 1850 Davaine discovered the first pathogenic microbe that had ever been seen. Examining the blood of sheep dead from anthrax, he discovered small motionless and refractive rods, of which he did not suspect either the nature or the meaning, and to which he only attrib- uted a diagnostic value. These same elements were again found in 1855 by Pollender, and in 1857 by Brauell, who observed them in the blood drawn from the living animal. In 1860 Delafond, by a spark of genius, determined that these rods were vegetables. He made some attempts to cultivate them in the blood, saw the rods grow in the form of filaments, and it even occurred to him to look for spores, which he failed, however, to bring to light. The following year appeared Pasteur's work on butyric ferment. Its perusal threw light on Davaine's mind and brought him back to the study of the vegetable which he had seen in the blood of animals suffering with anthrax. He learned that infectious diseases were pro- duced by microbes, just as are fermentations. He undertook a series of researches, the results of which he published in 1863. This brought down upon him an avalanche of criticism and gave occasion to con- tradictory experiments. Signol, Leplat and Jaillard, Sanson and Bouley, to cite only the principals, endeavoured to prove that the bac- teridia of Davaine are not found exclusively in the blood of animals affected with anthrax ; that they had no specific value, and that putrid blood swarmed with similar microbes, equally capable of killing animals. Davaine had no trouble in refuting these objections. He showed that his adversaries were mistaken; that they confounded anthrax and septicaemia, and that the microbes found in putrid blood are the agents of a special process of which he made a remarkable study. ANIMATE AGENTS 85 We can not help admiring Davaine when we think of the work achieved by him under the most unfavourable conditions ! A simple practising physician, Davaine could only work in his small property in Garches or in caves placed at his disposal by a friend. It was under these defective and discouraging conditions that Davaine took up and solved the principal problems relating to infectious diseases. Is it not really a great pity that such discoveries were not appreciated enough to give their author an official position or to create for him a laboratory ? However, the impulse was given. On all sides the study of the pathogenic problem was taken up. It was Villemin who first estab- lished, in 1866, the inoeulability of tuberculosis. In 1867, Chauveau demonstrated that in virulent liquids the active part does not pass through a porcelain filter. In 1872, Coze and Feltz published a series of researches on infections, and had the merit of perceiving the strepto- coccus of puerperal fever. Simultaneously, in Germany, Cohn and Nageli isolated a series of saprophytic microbes and indicated the means of cultivating them. In 1875, Koch entered upon the scene with the discovery of the anthrax spores. Prepared as he was by his researches on fermentations, Pasteur undertook the study of diseases. He first took up the lower beings and published researches on the diseases of silkworms highly instruc- tive for human pathology, but to which the medical world paid no attention. Passing then to the diseases of mammalia, Pasteur under- took the study of anthrax. In 1877, he supported with his authority Davaine's researches, and made known the means for the cultivation of pathogenic bacteria. He thus created the fundamental methods of bacteriology, a field which Koch was soon to perfect by the use of solid media. These procedures, so simple and so sure, permitted the isola- tion successively of a whole series of pathogenic agents, and rendered it possible to obtain them in pure cultures and to reproduce in animals the diseases observed in man. The first discoveries gave rise to vigorous opposition; but, little by little, the adversaries were silenced, and were forced to yield to the accumulating works and to bow before the achieved results. In less than twenty years this great scientific revolution was accomplished, with Davaine as its pioneer and Pasteur as its artisan. Division of Infectious Agents. — The first bacteriological discover- ies led to a conception which for a moment nearly impeded all prog- ress. By an induction easy to understand, it was believed that every disease was caused by a well-defined, special microbe. We know to-day that this is not so, and we can in this regard formulate the two fol- lowing laws, which govern the whole history of infectious diseases : 86 DIVISION OF INFECTIOUS AGENTS The same microbe may produce diseases the clinical manifestations of which are absolutely different. A disease, clinically well defined, may be produced by different microbes. Let us take, for example, a widespread microbe, streptococcus: it produces pus, erysipelas, septicaemia, pyaemia, lymphangitis, pseudo- membranes, gangrene, visceral inflammations, etc. Eeciprocally, a well-defined affection, like broncho-pneumonia, may be due to most varied microbes, as streptococcus, staphylococcus, pneu- mococcus, pneumobacillus, coli bacillus, etc. Therefore there is no necessary and constant relation between dis- eases as they are clinically determined and pathogenic agents as they are made known by bacteriology. Such results must not surprise us; they do not differ from those observed in studying other pathogenic agents, notably the poisons. Alcohol, for instance, produces inebriation, delirium tremens, hepatic cirrhosis, pachymeningitis, peripheral neuritis, etc. It is always the same poison, except that it acts under different conditions. On the other hand, the manifestations just mentioned may be ref- erable to most diverse toxines; peripheral neuritis, for instance, may be engendered by lead as well as by alcohol. We are thus led to admit that, from a medical point of view, in- fectious agents may be divided into two groups : specific and nonspe- cific agents. The former are those which determine diseases always similar to themselves, or at least diseases which present common characteristics enough to enable us to relate to each other the various clinical forms ; such is the case with typhoid fever, anthrax, glanders, and tuberculosis. The second group, numerically the more important, comprises agents apt to produce the most dissimilar clinical types. They are, as Peter said, all-round microbes (microhes a bout faire). Let us take, for instance, Staphylococcus aureus. According to its localization, it will produce a boil, an osteomyelitis, an ulcerative endocarditis, a sep- ticaemia, a pyaemia, etc. ; the diverse manifestations produced by it are dependent both upon the general soil where it evolves and upon its localization. We have already said that we must not take as synonyms the expressions " infectious agents " and " microbic agents." Infectious diseases may be produced by beings which are very different from the standpoint of natural history. They may be classed in four catesrories : 1. Bacteria, which belong to the family of alijae, and come under the group of schizomycetes (Nageli), or, better, schizophycetes. ANIMA'fE AGENTS g^ 2. Pathogenic Fungi, or hyphomycetes, of which the most inter- esting are represented by aspergillus and streptothrix. The latter form a transition between fungi and bacteria. Actinomyces is arranged here, and there is a tendency now to include also the agent of tuberculosis. 3. Pathogenic Yeasts, or Uastomycetes, which, however, could find their place in the group of fungi. 4. Animal Microbes, and particularly protozoa. Cultivation of Infectious Agents. — The majority of these patho- genic agents may be isolated and cultivated on artificial liquid or solid media. As liquid media, mineral solutions have been used, for which a good many formulae have been given since the first researches of Cohn and Nageli. Vegetable infusions may also be employed, and liquids pre- pared with hay, straw, barley, malt, etc., are often utilized. In most eases we have recourse to animal substances; we use bouillon with or without peptone. Preference is sometimes given to natural products, such as defibrinized blood, serum, urine, milk, acetic fluid, aqueous humour, the white of egg, and the like. The second procedure consists in cultivating microbes on solid media. A vegetable or animal infusion is taken and solidified by the addition of gelatine ; this solid medium liquefies at 23° C, and there- fore it can not be placed in the incubator. In order to make cultures at a temperature of 37° to 38° C, we replace gelatine by another sub- stance, agar-agar. In the case of strongly albuminous natural liquids it suffices, in order to solidify them, to coagulate them by heat. This is what is done with blood serum, defibrinized blood, and the white of egg. Finally, we frequently utilize slices of cooked vegetables, such as potatoes, carrots, artichokes, etc. The media may also be modified by the addition of various sub- stances — e. g., glucose, glycerine, aniline colours, and tincture of litmus. When the agent under study has been deposited on the medium adapted to it, the culture may be left alone at the surrounding tem- perature. Usually it is put into incubators regulated at 37° or 38° C. According to the element under observation, cultures are made with free access to air or protected from air. In the latter case use is made of tubes from which the air has been extracted by means of a pump, or which have been filled with an inert gas. It is often sufficient to cover the medium with a layer of sterilized oil, or simply to deposit the microbe at the bottom of a tube containing a sufficient amount of agar-agar. The air does not penetrate into the deep parts. Finally, one may resort to an arrangement which permits the absorption of oxygen by pyrogallic acid. 7 88 BACTERIA Division of Bacteria. — The various procedures above indicated per- mit the cultivation not only of bacteria, but also of the majority of fungi and yeasts. In general, cultures are not attended with success in the case of animal microbes, except, perhaps, the amoebae. In order to determine what kind of microbes we are dealing with, we must take into account a whole series of characteristics. With few exceptions, the appearance of the colonies upon a medium is not suf- ficient ; we must multiply and vary the cultures, and complete, by micro- scopic examination and inoculation in animals, the first results thus obtained. Since the researches of Weigert, Koch, and Ehrlich, it is customary to stain microbes with aniline colours. The reactions produced by col- ouring matters may serve in diagnosis. There are microbes which re- B c8> ® / ^>^t c kS- Fio. 4.— Schematic aspect of the various species of bacteria. A^ monococci ; B^ diplococci ; (7, streptococci; i>, tetracocci; JE^ staphylococci; F, bacilli; 6^^, bacteria; E^ leptothrix; /, cladothrix ; J", spirilla. tain them strongly; others part with them readily. Several are easily discolorized by alcohol, after the action of iodo-iodide reagent ; this is what constitutes Gram's method. Microbes have been classified most often after their morphological aspect. Now, when less importance is attached to morphology than formerly, the old classifications have been simplified. There are now but two great groups admitted : sphero-bacteria, called cocci or micro- cocci, and staff-shaped bacteria, called bacilli or rods. Micrococci are small spheres, which are generally nonmotile, unpro- vided with vibratile flagella, reproduced by fission, and bear no spores. Bacilli are small rods, often motile and provided with vibratile ANIMATE AGENTS 89 cilia, reproduced by fission and often by sporulation. Generally spom- lation occurs in the form of endospores, seldom of arthrospores, which are distinguished by their remarkable refracting power and their great resistance to colouring reagents. According to their groupings (Fig. 4), micrococci have been divided as follows : 1. Monococci — presenting themselves under the form of small spheres well isolated from each other. 2. Diplococci — consisting of two cocci, joined. 3. Streptococci — more or less long chains, consisting of 3 or 4 to 40 or 50 individuals; their appearance may be compared to a pearl necklace. 4. Tetracocci or tetragenus — formed of four cocci or tetrads, and placed on the same plane. 5. Sarcince — in which the division is made in all directions. These are small cubes having four cocci on each side. 6. Zooglea — represented by masses of micrococci united by a sort of jelly. 7. Staphylococci — a variety of zooglea presenting the aspect of grape bunches. Bacilli have frequently been divided into three groups: 1. Bacilli, properly so called — slender rods and often motile. 2. Bacteria — larger rods. 3. Bacteridia — large and nonmotile rods. The anthrax bacillus comes under this group. However, though we say "anthrax bacteridium," the distinctions that we have just indicated are no longer admitted to-day. The gen- erally admitted classification is as follows : 1. Bacilli, properly so called. 2. Leptothrix — long, segmented filaments. 3. Beggiatoa — long, thicker filaments. 4. Cladothrix — bacteria which appear branched. In reality the branchings are false. The elements, being born by fission, remain close side by side at their points of origin, the primitive element con- tinuing to grow. One might believe, at first sight, that there is a lateral ramification. 5. Spirilla — curved bacteria receiving sometimes the name of vibrios, when the element is bent, and spirilla when the microbe repre- sents a rolled filament. The term spirochceta, applied to long and flex- ible spirilla, is now abandoned. Variations of Bacteria. — The classification of bacteria is, as can be seen by these examples, based entirely on their forms. It would have been a good one if the forms were invariable. But such is not the case. 90 VARIATIONS OF BACTERIA The doctrine of monomorphism, supported by Cohn, had to give way to the conception of polymorphism developed by Nageli and supported by Pasteur. It is to-day a familiar truth that the form of bacteria, especially of bacilli, is being constantly modified; the same is true of other pathogenic vegetables. Streptothrix and yeasts present, ac- cording to a great number of circumstances, very marked variations. In this respect, two orders of modifications are to be distin- guished. Microbes change their form at certain periods of their develop- ment; such is the case with the colon bacillus, which presents itself first under the form of filaments, then of rods, and finally of oval ele- ments, short enough to simulate micrococci. Modifications no less notable are observed in old cultures where certain elements, often swollen into a club shape, constitute what are called involution forms. In other cases, variations are produced because the medium has been changed. The anthrax bacillus forms small rods in the blood of animals and long filaments in culture media; soon these filaments inclose spores, while these organs of reproduction are never met with in the blood. Likewise, different forms are obtained by sowing microbes in diverse media, such as bouillon, agar-agar, or potato. Finally, adding small amounts of antiseptics, we may observe the development of new forms, which often do not at all resemble the primitive stock. This polymorphism, though very well marked, is not surprising. It is a particular case of the great laws of evolution. The surrounding medium having changed, the being could not remain identical. Simi- lar modifications are observed with certain yeasts, which, according to the media, appear under the form of oval elements or mycelial fila- ments. The same variations are also noted in the case of actinomy- cetes, which at one time are composed of masses of radiate filaments terminating in club form, and at another arranged in the forms of small rods similar to bacilli. A still more curious example is furnished by the tubercle microbe, which under certain conditions offers morpho- logical characteristics 'that have sometimes led to its being considered a streptothrix akin to actinomyces. Certain bacteria possess the property of being surrounded by a cap- sule. This is the case with pneumococcus, pneumobacillus, and tetra- genus. But this characteristic is not any more constant than the others. Bacteria lose their capsules in certain media; some may ac- quire them accidentally, as does, for instance, the streptococcus. The sporogenic property is not any more fixed. By certain con- trivances there are created new races, called asporogenic. The bac- terium of anthrax, after being cultivated in bouillon to which chromate ANIMATE AGENTS 91 of potassium is added, loses its sporogenic property in the following generations, even if it be replaced in ordinary media. Under the impulse of Pasteur's ideas, it was thought that a basis of classification could be found in the study of fermentations pro- duced by microbes. Many objections may be made to this view. Let us take, for instance, the colon bacillus. Here is an agent which engenders lactic acid and indol. There exist microbes having the same biological characters, but which do not produce these fermenta- tions. Chemists look upon them as different species, and the majority of bacteriologists make of them simple varieties, under the name para- colon bacilli. What gives a certain amount of support to this opinion is that modifications may occur in the fermentative power of certain samples; there are cases on record where a paracolon bacillus, after a series of cultures in artificial media, has acquired the ability to produce lactic acid and to coagulate milk. Nor can we classify microbes on the basis of their chromogenic function. Some of them produce various pigments — green, red, yel- low, violet; but, by placing them under unfavourable conditions, by submitting them to high temperatures, to the influence of compressed oxygen, or to the action of antiseptic substances, it is possible to suppress this function, sometimes permanently. A final characteristic remains, and the most important from a medical point of view. Microbes have been divided into three groups — saprophytes, parasites, and pathogenies. Saprophytes are those which multiply on dead matter; parasites exist on living beings, without notably harming them. The pathogenies provoke the development of diseases. This distinction is not yet absolute. Certain saprophytes, falling accidentally on a living organism, may, so to speak, become accustomed to this new medium and rise to the rank of parasites or of pathogenic agents. The parasites that we bear on our bodies are equally modified by a great number of circumstances. The exaltation of our habitual guests is one of the principal causes of infectious diseases, and, vice versa, the most virulent agents lose, at certain moments, their pathogenic action and revert to the rank of parasites and saprophytes. It is exactly upon these functional variations that the great principle of the attenuation of viruses and of vaccination is based. Lastly, we must remember that cultures are never homogeneous. Microbes, as living beings, have their individuality. In any given col- ony there are always certain individuals more fully developed or more resistant than others. This explains why small doses of antiseptics do not kill all microbes at the same time, but only decrease their number; it is the weakest that perish. In the same way a colony of 92 VARIATIONS OF BACTERIA chromogenic microbes largely spread on a nutrient surface will give birth to new colonies, some of which will be deeply coloured and some colourless. The same remarks are applicable to pathogenic properties. Functional variations, attenuations, and exaltations are individual modifications. We shall therefore conclude that, in order to determine the species of a microbe and its place in the classification, we must pursue very long investigations, because we must take into account a whole series of characters. We must thoroughly study its morphology, its reac- tions toward colouring reagents, the appearance of its cultures on various media, its fermentative properties, and its pathogenic action. It is only upon the ensemble of the properties of a microbe that a con- clusion can be founded. Still, in certain cases, it will be impossible to decide and to recognise the species under examination. / CHAPTER VI ANIMATE AGENTS (Continued) The animal parasites — The vegetable parasites — The infectious agents — Bacteria: their division into specific and nonspecific — Phycomycetes — Mycomycetes — Protozoa — Medical classification of infectious agents. Without having the intention of describing, even briefly, the para- sites and infectious agents actually known, we believe it useful to indicate the species most frequently encountered, or at least those most interesting from a medical point of view. Animal Parasites * The animal parasites are all invertebrates, which enter into the group of annelida and that of protozoa. Insects. — The parasite insects belong to the order of diptera or hemiptera. Diptera. — Among the diptera we shall simply note the flea, the chigoe, the oestrum, and the muscides. The larvae of certain insects may live beneath the skin or in the natural cavities of man. The best known of the skin larvas are the moyoquil worm of Mexico, the macaco worm of New Grenada, and the Cayor worm. The cavity larvae {Lu- cilia macellaria, Sarcophaga magnifica, carnaria) develop in the sinuses of the face and may produce very grave disturbances. Hemiptera. — Hemiptera comprise the bedbug, and especially the louse, of which three varieties are admitted: the head louse (Pedicu- lus capitis), the clothes louse (Pediculus vestimenti) , and the crab louse (Phthirius pubis). The latter occasions, through a liquid which it secretes, the production upon the skin of slaty blue spots, peculiarly abundant when some intercurrent infection modifies the chemical con- stitution of the blood. Hence, these spots were first described in febrile diseases, and considered as an eruptive manifestation. * In preparing this chapter we have largely drawn from Dr. R. Blanchard's works on medical zoology. 93 94 ANIMAL PARASITES It is very curious, from a point of view of general pathology, to note that these three species of lice live in determined regions, which they hardly ever leave. Evidently they find among the various parts of the body differences which we are unable to perceive. Acarina. — The principal species, from a medical point of view, is Sar copies scahie% the agent of scabies or itch. This group comprises Ixodes — ^the Ixodes ricinus, which is quite innocent, and the Argas persicus, which produces, it is said, grave lesions. The Tromhidium holosericum produces a larva of a beautiful red colour, known under the names red flea, harvest bug, or Leptus autumnalis, which fixes itself beneath the skin and gives rise to small papules attended by intense pruritus. Recovery supervenes spon- taneously in six or seven days. The Demodex foUiculorum is fre- quently observed in the sebaceous glands, mainly in the ala of the nose; it is believed to be the cause of acne punctata. The linguatulce, which are now looked upon as degraded acarina, are encountered in man in two states. As adults, they may invade the nasal fossae ; in the larval state, they have been observed in the abdom- inal organs, and particularly in the liver. Helminthes. — The great group of helminthes, so important from a medical point of view, comprises a large number of species, parasites of man. We present in the following table those that are most common. Platyelminthes. Cestodes. TcBniadcB. Tasnia solium. " saginata. " echinococcTis. BothriocepTialidcB. Bothriocephalus latus. Trematodes. FasciolidcB. Fasciola hepatica. Schistosomum haematobium. Nemathelminthes. Nematodes. AscaridcB. Ascarides lumbricoides. Oxyurus vermicularis. StrongylidcB. Eustrongylus visceralis. Uncinaria duodenalis. ANIMATE AGENTS 95 TrichotrachelidcB, Trichocephalus trichiurus. Trichinella spiralis. Fila/rid(B. Filaria medinensis. " sanguinis. AngiostomidcB. Strongyloides intestinalis. Tcenia solium, Tcenia saginata, and Bothriocephalus latus repre- sent the three great tapeworms of man. The bothriocephalus is the least common; it is mostly met with in the regions of the lakes of Geneva and Neufchatel. In certain cases man is affected with ele- phantiasis, characterized by the development of numerous cysticerci occupying the subcutaneous cellular tissue, exceptionally the brain and the eyeball. As many as 2,000 tumours have been counted in one patient. Tcenia echinococcus is, when mature, a parasite of the dog, whose intestinal canal it inhabits. The eggs, swallowed by man, give birth to a hexacanth embryo, which penetrates into the organism, and, fixing itself in some organ or tissue, generally in the liver, produces a hydatid cyst. The latter grows, often reaching enormous proportions; but, although its contents include toxic substances, it acts chiefly in a mechanical manner, by compressing the neighbouring parts. Fasciola hepatica, distoma of the liver, inhabits the biliary pas- sages. It causes grave disturbances — pain, icterus, and a cachexia which finally ends in death. There exists a very grave disease, bilharziosis, which is chiefly ob- served in Egjrpt, and is due to Schistoma or Distoma hcematohium, Bilharzia hcematohia. The parasite lives in the blood, on which it nour- ishes itself, but causes no disturbance; only it produces eggs pro- vided with spurs, which, stopping in the capillaries, tear them, and give rise to very grave hemorrhages. These sometimes occur as hema- turias (hematuria of Egypt), sometimes enterorrhagias. At the autopsy as many as 500 worms may be found in the portal system. The evolution is very long; it may persist for ten or fifteen years. Of the nematodes, Ascarides lumhricoides represent, as is known, worms extremely common. They are often found in great numbers in the intestine, as many as 5,000 in a case recorded by Fauconneau- Dufresne. Generally well borne, they may produce accidents of a reflex or even febrile nature, accompanied by grave general manifestations, described as typhoid lumbricosis. Oxyures are also very frequent. They are mostly met with in chil- dren, in the anus and the vulva, where they occasion intense itching. 7!^ 96 ANIMAL PARASITES Eustrongylus visceralis is a very rare parasite, inhabiting the urinary passages, whence it may be voided with the urine. It produces grave disturbances, notably hematuria. On the contrary, Uncinaria duodenalis is very prevalent. It lives upon the intestinal mucous membrane, and there causes small hemor- rhages. The latter, by their repetition, soon give rise to a quite grave anaemic condition. To this worm is to be attributed the endemic anaemia which is observed in miners (anaemia of St. Gothard, of the coal mines of the Loire, in the north of France), and in those working in rice fields or in clay. We shall not dwell on the trichocephalus, which is frequently found in the digestive canal, where it is introduced through the drinking water. Generally inoffensive, it sometimes produces quite serious reflex phenomena. Otherwise important is Trichina spiralis, which produces the dis- ease known under the name trichinosis. Man is infected by eating insufficiently cooked pork. The parasites at first multiply in the intestine and produce diarrhoea and general disturbances resembling those of typhoid fever. Then they penetrate by the chyliferous ves- sels, invade the mesenteric glands, pass into the thoracic duct, reach the blood, and, after passing through the lung, arrive at the capil- laries ; others penetrate directly from the intestine into the blood, and yet others pass through the walls of the alimentary canal. The tri- chinae then become encysted in the muscles, and, in case they attack the respiratory muscles in great numbers, they bring about a fatal termination by asphyxia. While of very frequent occurrence in Ger- many, trichinosis is exceptional in France. The threadworm of Medina produces a disease called dracontiasis, characterized by the production of abscesses aJffecting particularly the legs and feet. When the abscesses are opened, one may see the para- site rolled up at the bottom of the wound. It may be extracted by drawing it out and coiling it around a small stick. The operation should be done with great care, for the rupture of the worm, probably giving issue to a toxic substance, is followed by very grave disturbances. The name Filaria sanguinis is a collective term applied to diverse filariae living in the human blood. These parasites are encountered exclusively in hot countries. A great number of species are recognised, the four principal ones being Filaria nocturna or Bancrofti, Filaria diurna or loa, Filaria perstans, and Filaria Demarquayi. Filaria nocturna lives in the lymphatic vessels; it produces lym- phatic abscesses on the limbs, lymphatic tumours in the scrotum, and, according to Manson, elephantiasis of the Arabs. Filaria diurna lodges itself ordinarily between the conjunctiva and the eyeball. ANIMATE AGENTS 97 Filaria perstans produces a peculiar affection, observed in negroes and described under the name " sleeping sickness." Strongyloides intestinalis is observed in patients suffering with the diarrhoea of Cochin China. Protozoa. — Very numerous parasites belonging to the group of pro- tozoa may be met with in man. We find, first, among the infusoria, Balantidium coli, which is encountered in diarrhoeal stools. This parasite has been seen about forty times, but it has never been encountered in France. Flagellata comprise three interesting species : Cystomonas urinaria, found in the urine ; Trichomonas vaginalis, which is very common, and has been met with in the vagina, the bladder, the alimentary canal, and in the expectorations of patients suffering with pulmonary gangrene; and Cercomonas or Lamhlia intestinalis, which vegetates also in diar- rhoeal matter. We shall leave out of consideration for the present the other pro- tozoa, the coccidia, hemosporidia, and rhizopoda, since all that is important to know about them will be treated of in connection with infections. Vegetable Parasites Among vegetable parasites, we shall note, first, those concerned in the production of tinea. These are Trichophyton tonsurans, the agent of tinea tonsurans, herpes zoster, and parasitic sycosis, and Achorion Schonleinii, the agent of favus. The study of these fungi has been pursued with great care in recent years, especially by Sabou- raud, Sabrazes, and Bodin, who have well shown the necessity of dividing them into a great number of species upon which we do not need to dwell here. Then comes the group of microsporon, comprising the Micro- sporon furfur, the cause of pityriasis versicolor; the Microsporon Audouini, to which alopecia is attributed; the Microsporon minutissi- mum, which is found in erythrasma; and the Microsporon anomoeon, which produces pityriasis circinata. The other vegetables which we must now study may live under three different states. They are, according to circumstances, saprophytes, parasites, or infectious. We shall take them up when studying infec- tious agents. We shall only note them here. These vegetables are divided into two groups : Mycomycet^, com- paratively high fungi, and Phycomycet^, which constitute a transi- tion between fungi and algae. Among Mycomycet^ we find aspergillus and eurotium, penicil- Hum and blast omycetes, or yeasts. 98 VEGETABLE PARASITES The Phycomycet^ include the important group of mucors. Mu- cor niger produces on the tongue a very tenacious black coating. The Mucors corymhifer, septatus, and ramosus enjoy with Aspergillus fumigatus and flavus and Eurotium repens and malignum the prop- erty of living as parasites. They are often met with in the auditory canal, where they give rise to the affections grouped under the general name otomycosis. Let us note also Cercosphcera Addisoni, which is found in various skin diseases and in certain alopecias. Finally, there have been described under the name leptomitus para- sites which are divided, according to the point of the organism where they were encountered, into leptomitus of the epidermis, of the urine, of the uterus, of the vagina, and of the aqueous humour. Infectious Agents Bacteria. — While bacteria are not the only parasites capable of producing infections, they incontestably hold the first place and repre- sent the true types of infectious agents. Their number is so considerable that we can not study all of them. We shall only note the principal species. According to the division which we have already admitted, we shall successively consider the micrococci and the hacilli, and in each group we shall study the common nonspecific and specific species. Nonspecific Micrococci. — The nonspecific micrococci are not very numerous. It suffices to know four of them: staphylococcus, strepto- coccus, pneumococcus, and tetragenus. Staphylococcus (Rosenbach, 1884), the most prevalent of all, is represented by small rounded elements, measuring from 0.7 micron to 1.2 micron, sometimes isolated, oftener united. They assume the form of diplococci when they are developed in a liquid medium. If we take a particle of a colony vegetating on some solid medium, we see that the grains form masses that have been compared, more or less exactly, to bunches of grapes. Hence the name given to this species. In many cases, however, the grains are in masses or in the form of long bands, sometimes even of small chains. This microbe develops readily upon the various media employed in bacteriology. On agar-agar, it forms a thick, moist growth; gelatine is rapidly liquefied, and the bottom of the tube contains colonies united in flocculent masses. Bouillon becomes uniformly turbid and often contains a mucous deposit. Milk coagulates in about eight days. Solidified serum liquefies slowly. The colour of the cultures varies notably according to circum- stances. Therefore three great varieties of staphylococci have been ANIMATE AGENTS 99 admitted: Staphylococcus aureus, producing on agar-agar and pota- toes colonies of a superb orange-yellow colour; Staphylococcus citreus, whose name sufficiently indicates the colour; and Staphylococcus albus. It has long been a matter of discussion whether the three staphylo- cocci represent distinct species or but varieties of the same species. The latter opinion tends to prevail, since the different types are fre- quently found associated in the same morbid focus and numerous transitions are observed between well-differentiated samples. Finally, by certain experimental contrivances, we may easily cause the Staphy- lococcus aureus to lose its chromogenic power; it is thus transformed into the white variety. Staphylococci are found as saprophytes in soil, water, ice, air, dust, and various objects. They vegetate as parasites upon our in- teguments and mucous membranes, particularly upon the buccal mucous membrane, less frequently upon that of the intestine. They may penetrate into the excretory ducts of the glands ; even in the milk of healthy women, the white variety is almost constantly present. When they attain the rank of pathogenic agents, staphylococci, in most cases, give rise to suppurations. In general, it may be admitted that the chromogenic varieties are more virulent than the white vari- ety. According to the seat of the lesions and the activity of the germ, the effects vary greatly. In some cases, simple acneform pustules are observed; in others, boils or so-called carbuncle, or some affection peculiar to hot climates, the button of Bishra; elsewhere, it may as- sume the type of impetigo; at times, circumscribed or diffused phleg- mons, sometimes even gangrene. When the deeper structures are reached, suppurating foci will be observed either in the viscera or in the tissues. Osteomyelitis, for instance, is, in most cases, due to Staphy- lococcus aureus. In certain cases, instead of suppuration there is destruction of the affected parts (ulcerative endocarditis). In other cases, the infection becomes generalized ; a number of microbic centres are produced, ending in the formation of numerous small abscesses. This is the purulent infection or pyaemia. If the microbe is very virulent, no reactions are produced; the individual succumbs and the necropsy reveals no lesions. This is the process known as septicaemia. Streptococcus, observed by Coze and Feltz, by Pasteur and Do- leris, isolated from erysipelas by Fehleisen (1883) and from suppu- rations by Rosenbach (1884), is a micrococcus measuring from 0.3 to 1 micron. They have the very characteristic property of grouping themselves into more or less long chains. Some chains are made up of 3 or 4 elements, others of 30 to 40, and present then the form of a rosary or pearl necklace. In certain cases, diplococci only are found; in others, the streptococci overlap each other and LofC. 100 INFECTIOUS AGENTS agglomerate so as to form colonies which, on superficial examination, appear to be staphylococci. In general, all the elements of the same chain are of equal size; in certain cases, a few are more voluminous and break the uniform contour which is usually observed. This microbe, a facultative anaerobe, produces on agar-agar small, slightly elevated, almost translucent, rounded colonies ; the appearance is similar on gelatine, which is not liquefied. Bouillon is at first uni- formly turbid, but soon becomes clear; the microbes fall to the bottom of the tube, where they collect into small granules or even small masses, which are readily scattered when the liquid is agitated. The streptococcus develops readily on potatoes, but, as a rule, does not produce colonies visible to the naked eye. Its action on milk is inconstant; in most cases this medium is coagulated by it. The most luxuriant cultures are obtained in serum or in the liquid of ascites, either pure or mixed with bouillon ; it is also in this medium that the microbe attains its maximum degree of virulence. Like the staphylococcus, the streptococcus is widely distributed. It is found in the air, in water, and in the soil; it readily invades putrescible matters, and is frequently met with upon the skin, in the buccal cavity, where it is constant, and at times in the intestinal canal, where it inhabits mainly the duodenum. This microbe may produce four orders of morbid manifestations: oedema, suppuration, pseudo-membranes, and gangrene. Erysipelas is an inflammatory oedema par excellence', at times the dermatitis terminates at some points in the formation of small ab- scesses. This fact has been made use of to prove the identity of the streptococci of erysipelas and of suppuration. Between exudative and suppurative inflammations we find lym- phangitis, which occupies a position intermediate between erysipelas and phlegmon. Among the suppurative lesions we must mention the adeno-phlegmons, and particularly the diffuse phlegmons, which are nearly always due to streptococcus. When it is localized in the viscera, streptococcus still gives rise to the same lesions — e. g., in the kidney it produces an acute nephritis; in the lung, broncho-pneu- monias ; while in the other organs or in the serous membranes it causes more or less extended suppurations. If it attacks the inner coat of the circulatory system, it causes arteritis, phlebitis, and endocarditis, espe- cially ulcerative endocarditis. Finally, becoming generalized, it may, like the staphylococcus, per- haps oftener than the latter, produce pyaemia or septicaemia. Puer- peral septicaemia is nearly always dependent upon the streptococcus. The part played by the streptococcus in the formation of false ANIMATE AGENTS 101 membranes has been well established by numerous observations of diphtheroid sore throats, in which this microbe is met with predomi- nantly or almost exclusively. The same is true of other parts of the organism, notably of the vulva and vagina, which may in cases of puerperal infection become covered with false membranes caused by streptococcus. Lastly, streptococcus may produce gangrene. This is observed in the patches of erysipelas, as well as in gangrene of the extremities con- secutive to acute arteritis; the same microbe, it seems, may of itself provoke pulmonary gangrene, without the intervention of other germs. Many authorities have admitted a great number of varieties or species of streptococci. The present tendency is to draw closer to- gether and to unite the different species. It should not be forgotten, however, that different species are distinguished from each other by certain biological properties. It is well demonstrated, for example, that the serum of animals immunized against one variety of strepto- coccus often exerts no influence upon other varieties. Without con- cluding from this fact that there are specific differences, we must, nevertheless, admit that there are modifications sufficiently distinct to be expressed by peculiar biological characteristics. The third micrococcus that we must mention is the Pneumo- coccus. It was discovered in pneumonia by Talamon, thoroughly studied by Fraenkel, who identified it with the microbe of sputum septicaemia of Pasteur, Vulpian, and Sternberg, and subsequently by Weichselbaum. The pneumococcus is designated in France under the name of Talamon-Fraenkel, in Germany as Diplococcus pneumoniw (Fraenkel), and in Austria as the Fraenkel-Weichselbaum diplococcus. It has been called by Gamaleia Streptococcus Pasteuri. This microbe presents itself under the form of small lanceolate granules, comparable to the grains of barley, measuring from 1 to 1.5 micron. It is sometimes isolated, oftener united in pairs or in short chains, comparable to those of streptococcus (Streptococcus pneu- monice). The individual cocci are remarkable for the clear capsule that surrounds them. This capsule is especially apparent when the microbe is developed in a medium rich in albumin — viz., in the living organism and in the blood serum. More delicate than the preceding species, the pneumococcus does not develop at ordinary temperature; its development begins at about 24° C. On solid media, such as agar-agar or gelatinized serum, it gives rise to minute colonies resembling dewdrops, scarcely visible to the naked eye. Gelatine is not liquefied. In bouillon extremely small granules are observed. The best media are represented by blood serum, and particularly defibrinated blood, coagulated by heat. On the latter 102 BACILLI mediiun, proposed by Gilbert and Fournier, the microbe develops lux- uriantly and decolourizes the colouring matter of the blood, which is changed from brown to yellowish white. This phenomenon appears to be characteristic. The pneumococcus, though somewhat less widely distributed than the preceding microbes, has been encountered in the air and in dust, but it is a parasite rather than a saprophyte; 20 out of 100 healthy individuals harbour it in their saliva. It may also be found in the nasal mucus and even in the intestine. First encountered in fibrinous pneumonia, pneumococcus may pro- duce, even in the respiratory apparatus, very diverse affections — ^bron- cho-pneumonias and bronchites. It frequently induces suppuration in the serous membranes: meningitis, pericarditis, pleurisy, perito- nitis, which are characterized by the presence of thick, greenish, semi- solid exudations, extremely rich in fibrin. It may also produce arthritis, otitis, parotiditis, and localize itself upon the endocardium and cause vegetative or ulcerative endocarditis. Less frequently it invades the whole organism and induces septicaemia. Very closely related to, if not identical with, the pneumococcus is Micrococcus intracellularis meningitidis, which is the cause of cerebro- spinal meningitis. Of late, attention has been drawn to Tetragenus {Micrococcus tetragenus, Gaffky, 1883). Morphologically, it is made up of 4 micro- cocci, united on the same plane and often surrounded by a capsule. It produces, in various media, moist, white colonies (a yellow variety also has been described). It does not liquefy gelatine; forms in bou- illon a thick deposit. This microbe is frequently met with in the mouth. It takes a prominent part in the development of " sore throats," in which, by cultivation on agar-agar, it is found in three fourths of the cases. From the buccal cavity, tetragenus may invade the neighbouring parts : in this way it causes dental abscesses and adeno-phlegmons of the cervical region ; making its way into the ear, it produces otitis or mas- toiditis. At other times, carried toward the respiratory apparatus, it produces a purulent bronchitis a pulmonary abscess, or contributes to the formation of tubercular cavities. Its presence has also been proved in cases of septicaemia and pyaemia, as well as in the urine of patients suffering with scarlatinal nephritis. Nonspecific Bacilli. — At the head of the least of nonspecific ba- cilli is placed the Colon Bacillus (Bacillus coli communis. Bac- terium coli commune), discovered by Escherich. Very variable in its morphology, the colon bacillus presents itself sometimes under the form of small, motile rods measuring from 2 to 4 microns; some- ANIMATE AGENTS 103 times under that of oval elements, which might easily be mistaken for micrococci, and at times under the form of quite long filaments. It is a facultative anaerobic motile bacillus, provided with from 4 to 10 vibratile ciliae. It develops readily between 15° and 46° C. in all the media employed in bacteriology. On agar-agar or serum it forms a whitish layer ; on gelatine, ovoid, transparent, or opaque colonies, which do not liquefy the medium. Potato is covered with a thick brown coating, and artichoke assumes a beautiful greenish tinge. Milk, in consequence of the fermentation of the lactose, becomes acid and coag- ulates more or less rapidly. Bouillon becomes uniformly turbid, and quite often contains little flocculi; in peptonized bouillon notable quantities of indol are formed. On the various media the cultures emit a disagreeable odour, some- times recalling that arising from decomposed urine, sometimes that of putrefaction. Gas is sometimes abundantly produced in milk, potatoes, and gela- tine. It is then due to a variety long considered to be a particular species — namely, Bacillus lactis aerogenes. Certain varieties of colon bacilli do not ferment lactose or produce indol; these are called paracolon bacilli. Experimenters have several times succeeded in inducing, by serial cultures in milk, the fermenta- tive power, which was previously lacking. The colon bacillus is a very prevalent microbe, perhaps the most widely distributed of all. It is found in the air, soil, and water, and it is constantly met with in the alimentary canal of man and of ani- mals, in the mouth, in the stomach, and particularly in the intestine. Discharged with the faecal matter, it readily soils the external genitals, where its presence is also almost constant. In certain animals it affects the mammary glands, as is notably the case with the cow; hence, the colon bacillus is encountered in the milk, where Pasteur described it under the name lactic ferment. When this microbe attains virulence, it produces very various lesions. It is the principal agent of intestinal infections — e. g., acute or chronic enteritis, infantile cholera, cholera nostras, colitis, and appendicitis very frequently depend upon it. In cases of dysentery of hot countries, and at times in dysentery nostras, the stools contain in great abundance a variety of colon bacillus which has been consid- ered the cause of the disease. From the intestine the microbe may make its way to the excretory ducts, and produce suppuration in the biHary passages or inflammation in the pancreas; or else, passing through the walls of the intestine, it gives rise to peritonitis ; or, again, passing by the portal vein, it localizes itself in the liver, and there in- duces infections, degenerations, and often grave icterus. 104 ' NONSPECIFIC BACILLI Less frequently it acts in the mouth, produces sore throat, or reaches the neighbouring parts, notably the parotids. While it assumes a very important role in intestinal pathology, its etiological significance in urinary pathology is by no means inconsid- erable. It produces cystitis, and may spread from the bladder toward the kidney, where it frequently induces lesions terminating in renal insufficiency. It is the great agent of death in patients suffering from urinary disorders. Lastly, in women, it has several times produced a variety of puer- peral septicaemia. It must be remembered that, in order to affirm that a certain lesion is due to the colon bacillus, it does not suffice to prove its presence in the cadaver. After death, or rather during the agony, the colon bacil- lus often leaves the alimentary canal, particularly in those cases where the intestine has suffered alteration or ulceration, and invades the other organs, especially the liver. It has not always been possible to refer to the colon bacillus group the microbes encountered in the various lesions above mentioned. Therefore authors have described as distinct species a whole series of agents, which are at present identified. Besides the Bacillus lactis aerogenes and the lactic ferment, which we have already noted, we must class with the group of colon bacilli Bacillus neopolitanus, found by Emmerich in the organs of cholera subjects. Bacillus pyogenes fcetidus of Passet, the septic bacterium (Clado), and the pyogenic bacterium (Albarran and Halle) of urinary infections, the bacillus of dysentery of Chantemesse and Widal, the bacillus of ulcerative endocarditis of Gilbert and Lion, etc. We may also class this microbe with the bacillus of psittacosis, described by Nocard, Gilbert, and Fournier. This is a microbe very common among parrots, and produces in man extremely grave broncho- pneumonia. Some authors consider as a variety of colon bacillus the pneumo- hacillus of Friedldnder, which should not be confounded with the pneumococcus. It differs from the colon bacillus by the presence of a capsule, which, however, is not constant. It produces in man sore throat, broncho-pneumonia, and septicaemia. Another septicaemic agent. Bacillus septicus putidus, encountered for the first time in a patient dead of septicaemia consecutive to cholera, deserves to be placed close to colon bacillus. It clearly differs from the latter by a very important characteristic : it liquefies gelatine. Pathogenic for animals, it has served for various experimental inves- tigations. Three other nonspecific bacteria may be met with, which are of ANIMATE AGENTS 105 great importance in experimental and comparative pathology. These are the hacillus of hemorrhagic septiccemia, Proteus vulgaris, and Ba- cillus pyocyaneus. The latter^ discovered by Gessard in 1882 and well studied by Charrin, possesses the interesting property of engendering a blue colouring matter, pyocyanin, which may be obtained in a crystal- line state. Leptothrix. — In the group of leptothrix we shall only mention Leptothrix Ijuccalis, which may produce in man anginas (pharyngo- mycoses) of a particular character, abscesses, and even invade the economy. The characteristic common to the various bacteria thus far noted lies in the fact that all produce analogous inflammatory processes. The dominant feature, from a clinical point of view, is the localiza- tion. The evolution of the morbid phenomena, their innocence or gravity, is dependent upon the tissue or organ attacked and upon the extent of the parts involved. Finally, these same agents may invade the economy, causing septicaemia or pyaemia, according as in- flammatory reactions are present or absent. Specific Micrococci. — The specific bacteria comprise but two micrococci. The best known is the microbe of gonorrhoea, the GoNOCOCCUS, dis- covered by ISTeisser in 1879. The appearance of this coccus is quite characteristic. In examining the pus of gonorrhoea, we find the gono- cocci made up of two segments coupled, presenting somewhat the form of two beans, arranged with their concave surfaces toward each other. These microbes lie free or are inclosed within pus cells or epithelial cells; in most cases the same cell incloses a great number of them. They are not stained by Gramas method, and this fact serves to dif- ferentiate them from the common pus cocci. The cultivation of gonococcus is a matter of difliculty. For a long time human blood serum was used as a medium. At present it is known that this coccus may develop in the serum of the rabbit ; upon glycerine agar-agar, where it forms white, thin, transparent colonies; or on potatoes, where it produces minute drops. This microbe causes a specific suppuration in the urethra, in the vagina, and at times in the rectum, the nose, and the conjunctiva. It is the usual causative agent in purulent ophthalmia of the newborn. In cases of urethral or vaginal gonorrhoea, the gonococcus mani- fests hardly any tendency to leave the genital mucous membranes. Even though it locates itself with great tenacity in the cells and the glandular crypts, it only exceptionally invades the neighbouring glands, and but rarely enters the blood. The complications of gonor- rhoea, the arthropathies, are due to secondary infections. In most cases 106 SPECIFIC BACILLI the gonococcus simply opens the way to the common pyogenic bacteria. The rheumatism of gonorrhoea must be considered as an attenuated pyaemia. Gonococcal arthropathies do exist, but they appear to be rare, although they are more frequent than was formerly believed. The second specific micrococcus has been little studied; it is the Microbe of Mumps, described by Laveran and Catrin. The Specific Bacilli. — The specific bacilli are more numerous. There are thirteen of them, of which ten are aerobic and three ana- erobic. The specific aerobic bacilli are headed by the Bacillus Anthracis (bacteridie charhonneuse) , discovered by Davaine in 1850. The latter is found in the blood of animals which have succumbed to the disease. It appears in the form of small nonmotile rods, measuring from 5 to 6 microns in length and 1 to 1.5 micron in breadth; the rods are some- times surrounded with a capsule, and the ends are cut at right angles and slightly sinuous. In artificial media, particularly in liquid media, these rods become elongated in the form of segmented filaments, often very long, which soon produce spores. Spores are never found in the animal organism ot in cultures grown in blood serum. Bacillus anthracis readily develops in the presence of oxygen. It grows between 10° and 45° C. On agar-agar it gives rise to white colonies, on gelatine to granular colonies, which rapidly liquefy the medium and form a deposit analogous to a mass of rolled thread. Potatoes becomes covered with a thick coating. Bouillon, at first turbid, later becomes clear, the microbes falling to the bottom of the tube in the form of dense white flocculi. The action on milk is quite variable. If the milk is put in a tube, the bacillus, living only in the upper layers, secretes a casease, which is diffused and produces coagulation. If, on the contrary, aeration is ample — viz., if the milk is put in a large vessel, at the bottom of which it forms a thin layer — the casein is digested and transformed into pep- tone as fast as it is coagulated; the milk assumes the character of a thick and brownish liquid. Owing to the nature of its spores. Bacillus anthracis easily resists destruction. It persists for a very great length of time in the soil and water, thus causing very deadily epidemics and epizootics. We must recognise, however, that in most cases contamination takes places otherwise. Man is most often affected in dealing with the cadavers of anthrax animals, or by manipulating the products derived from them — wool, horns, skin, etc. Another bacillus, which also plays a part in man and animals, is the Bacillus of Glanders, Bacillus mallei, well described by Loeffler and Schutz in 1883. ANIMATE AGENTS 107 This organism occurs in the form of long, slender, motile rods, measuring from 2 to 5 microns, often inclosing in their interior feebly coloured vacuoles. They grow very readily on agar-agar with glycer- ine ; in bouillon, in which they form a viscous precipitate, and on pota- toes, on which they produce a thick coating of a greenish-blue colour, the appearance of which is almost characteristic. The disease generally attacks the horse, which transmits it to man. The feeble resistance of the microbe explains why direct contagion is observed as a rule. The Typhoid Bacillus, described by Eberth in 1880, presents itself in the form of cylindrical rods, measuring 0.6 to 1 by 2 to 4 microns. In old cultures it produces filaments and forms of invo- lution. In many respects this microbe resembles the colon bacillus. It differs from it in certain important characters. It is more motile, this being due to the fact that it is provided with a greater number of ciliae, 8 to 24. Colonies on agar-agar and gelatine are more trans- parent; on potatoes they are hardly visible, or form a light, whitish coating. Contrary to the colon bacillus, the typhoid bacillus does not yield a green colour when cultivated on slices of artichoke. It produces no indol in peptonized bouillon, does not ferment lactose, or coagulate milk. It resists much less the action of antiseptics — carbolic or arseni- ous acid. However, these characteristics have not an absolute value; in the group of paracolon bacilli are found numerous species which seem to establish an insensible transition between the bacillus of Eberth and that of Escherich. A final characteristic, derived from serum reaction, has lately been spoken of. It has been noted that the serum of animals immunized against the typhoid bacillus, or that of individuals attacked by typhoid fever, agglutinates the typhoid bacillus, but never the colon bacillus. This fact, although disputed, is interesting ; but it is not of such great value as might be supposed, for similar reactions are observed with varieties of one and the same species. This is what occurs notably with the cholera vibrios. It is then conceivable that several authorities persist in believing that the typhoid bacillus is but a variety of the colon bacillus. This theory, enunciated and sustained by Rodet and G. Roux, has appeared very seductive, for it explains the cases in which typhoid fever is gen- erated spontaneously — that is, without any contagion. However, the idea of the specificity of the typhoid bacillus has just found a new argument in the researches of Reumlinger and Schneider. These authors have proved that the typhoid bacillus is met with in the intes- 108 DIPHTHERIA BACILLUS tines of normal individuals. It might then bring abont the disease on the occasion of debilitating causes, and notably of overwork. Thus excited, it produces a case which is apparently spontaneously devel- oped, and it becomes the starting point of an epidemic which is propa- gated through contagion. Infection takes place mostly through the agency of water, excep- tionally through the soil or the air. The aqueous origin of typhoid fever is no longer questionable. Numerous observations have established that the disease undergoes recrudescence when the drinking waters are polluted, and diminishes when hygienic measures are enforced. The precautions taken in recent years against unhealthful water are therefore praiseworthy; but if observations are very conclusive, experiments are much less so. The difficulty of distinguishing the typhoid bacillus from the colon bacillus does not enable one to admit the majority of analyses in which the typhoid bacillus is said to have been found in the water. The colon bacillus exists in all waters, and thus renders researches very difficult. This is what resulted from an experiment of Grimbert: This author introduced into 1,000 cubic centimetres of water 1 cubic centimetre of a culture of the colon bacillus and 1 cubic centimetre of a typhoid culture. He agitated the mixture and showed that it is impossible to recover the typhoid bacillus or to isolate and differentiate it from the colon bacillus. The Bacillus of Diphtheria, observed by Klebs in 1883, and fully described by Loeffler in 1884, is a nonmotile rod, straight or rounded, measuring 0.7 by 2.5 to 3.5 microns. The elements are iso- lated or united in couplets, often well aligned, and, as is said, placed in range of battle'. In old cultures we frequently meet with involution forms presenting the contour of clubs or spindles. The diphtheritic bacillus develops at a temperature of about 24° C. ; its growth is arrested at 42° C. and is particularly luxuriant between 35° and 37° C. On agar-agar quite distinct colonies or gray- ish streaks are seen ; on gelatine, small spherical colonies ; in bouillon, masses that fall to the bottom of the culture tube. The bacillus does not develop on potatoes. The most characteristic cultures are ob- tained by inoculation upon gelatinized blood serum. At the end of twelve hours the nutrient medium, maintained at 38° C, is covered with small white or gray colonies, about the size of a pin's head. It is, as is known, by means of cultures on serum that one can readily establish the bacteriological diagnosis of diphtheria. This microbe may be encountered as a saprophyte, a parasite, or a pathogenic agent. As a saprophyte, it may live in dung and rags; as a parasite, it vegetates in the buccal cavity of healthy individuals; ANIMATE AGENTS 109 as a pathogenic agent, it produces pseudo-membranous lesions, occu- pying generally the throat, invading the larynx and the nasal cavities, less frequently the conjunctiva, and exceptionally the bronchi. It may also attack other mucous membranes exposed to the air, notably the genital mucous membrane or the skin. Eapidly destroyed by the rays of the sun, the diphtheria bacillus retains its vitality for a very great length of time when sheltered from light. There are cases on record in which the clothing of a child dead with diphtheria was packed in a drawer, and when, a year or two later, it was taken out, caused the infection to reappear. The Bacillus of Influenza or Grippe, discovered by Pfeiffer in 1890, is one of the smallest that is known; it is a nonmotile, recti- lineal rod, 0.5 micron long, separate or in chains of three or four elements. It develops upon agar-agar covered with a layer of the blood of man or of the pigeon, in the form of small, homogeneous colonies, visible only under a magnifying glass. The growth is some- what more abundant on glycerine agar-agar; in bouillon with blood it assumes the form of small flocculi. We now come to one of the most important microbes — namely, the Tubercle Bacillus — discovered by Koch in 1882. This bacillus oc- curs in the form of nonmotile rods, from 2 to 4 microns in length. The bacilli possess a tinctorial reaction altogether characteristic. They are penetrated with great difficulty by the aniline colours. One must employ energetic mordants and leave the microbes in the colouring bath during twenty-four hours, or else heat the liquid until it gives off vapours; the staining is then produced within a few minutes. Once stained, the microbes retain the dye tenaciously, resisting the action of nitric acid in the proportion of one third, which decolourizes the other bacteria. They appear alone in preparations thus treated. The tubercle bacillus readily develops in blood serum, in bou- illon and agar-agar mixed with glycerine or various sugars, and on potatoes with glycerine. On solid media it forms dry or slightly moist scales ; on liquid media, scaly, wrinkled films or pellicles, which, at the end of a certain time, fall to the bottom of the culture tube. Eecent researches demonstrate that in certain conditions the tubercle bacillus undergoes remarkable morphological modifications. Projections and ramifications appear, which at times terminate in club-shaped swellings. The microbe is therefore much more highly organized than was at first believed. But no conclusion has as yet been reached as to its proper position in botanical classification. Some authors, considering the lateral buddings as true ramifications, place it in the group of streptothrix, by the side of actinomyces. Oth- ers, arguing that the ramifications are false, class it among the bac- 110 TUBERCLE BACILLUS teria, in the group of cladothrix. It is at times considered to be referable to a somewhat special kind, that of crenothrix. To conform to usage, we have left the agent of tuberculosis among the bacteria. If it finally be ranked with streptothrix, this would be the best argu- ment against those who still maintain that all infectious diseases are of bacterial origin. The tubercle bacillus is remarkable for its high pathogenic power. It attacks equally man, mammalia, birds, and even cold-blooded ani- mals — the ophidia and fish. As in the case of many other microbes, there exist several varieties of tubercle bacilli. Three principal vari- eties have been described: (1) The bacillus of human tuberculosis, which is met with in man, mammalia, and, among the birds, in par- rots; (2) the bacillus of avian tuberculosis, which attacks particu- larly the gallinae; (3) the bacillus of fish tuberculosis. Struck with these differences, some authors claimed to see in these three agents three distinct species. At the present day all have agreed to consider them simply as varieties that may be transformed one into the other. The tubercle bacillus is endowed with a very great vitality and easily resists causes of destruction. This fact alone explains its great prevalence. None of the mammalia are entirely immune to it. It is the veritable scourge of our epoch. In Paris tuberculosis is respon- sible for 4.9 deaths out of each 1,000 inhabitants; in cities with less than 5,000 souls the figure is 1.81. Among animals, the bovine species are the most frequently attacked. Contrary to popular opinion, tuber- culosis is of very frequent occurrence in the domestic carnivora, nota- bly in the dog (Cadiot). Tuberculosis may be transmitted from animals to man. More fre- quently infection takes place from man to man, and may give rise to true epidemic centres. In the majority of cases inoculation occurs in the respiratory passages; it is through the sputa that the bacilli are transmitted. They represent a real social danger against which a struggle has justly been inaugurated in recent years. The other pathogenic bacilli are less important for our studies; they require but brief mention. First is the Bacillus of Leprosy, discovered by Hansen, whose morphological and tinctorial characteristics are quite analogous to those of Koch's tubercle bacillus. Let us mention the Bacillus of Plague, recently discovered by Yersin and Kitasato ; a bacillus analogous to the colon bacillus, de- scribed by Sanarelli, under the name Bacillus icteroides, as the agent of Yellow Fever; and a bacillus encountered by Roger and isolated by Lemoine and by Barbier and Tollemer from the stools of patients suffering from Dysenteriform Enteritis. The latter bacillus is ANIMATE AGENTS 111 very virulent; it can in certain cases give rise, in animals under ex- periment, to intestinal ulcerations analogous to those of dysentery and to hepatic abscesses. Lastly, the Bacillus of Soft Chancre (Du- crey, 1889), a thick and short bacillus, often constricted in the middle, sometimes arranged in the form of chains, which no one has succeeded in cultivating. Among the microbes thus far studied, several are facultative ana^ erobics. We have yet to mention three which vegetate only when ex- cluded from air. These are the bacilli of tetanus, of gaseous gan- grene, and of rheumatism. The Bacillus of Tetanus or Bacillus of Nicolaier (1884) is represented by very slender elements, from 2 to 5 microns long, motile, and generally provided with a large terminal spore, which gives them the appearance of pins. Sown on agar-agar and protected from air, they produce flocculent colonies and cause a liberation of gas, which splits the medium. Gelatine is rapidly liquefied and filled with gas bubbles. Bouillon is at first made turbid, but subsequently becomes clear, the microbes falling to the bottom of the tube, where they form a granular deposit. The culture has a very strong and disagreeable odour. Owing to its spores, the tetanus bacillus is very resistant and very widely distributed. It is found in the soil, in mud, in dung, and dust ; it is also met with in the digestive canal of herbivora, and is passed in abundance in their excreta. When it assumes pathogenic properties it develops at the point of infection, where it remains, and causes an intoxication of the organism by the substances which it secretes. There have been observed in man and in horses epidemics and epizootics of tetanus, which are explained by the transportation of the germs through badly disinfected instruments. The second anaerobic microbe was discovered by Pasteur, who de- scribed it, in 1885, under the name of septic vibrio. This quite improper designation has give rise to an error which has found expres- sion in certain didactic articles. It has been stated that this microbe is the cause of septicaemias, in opposition to staphylococcus, which is generally believed to be the causative agent in pyaemias. The designa- tion of this microbe as the bacillus of gangrenous septicaemia, a term adopted by the school of Lyons, is not any better. The name bacillus of malignant oedema, used in Germany, can not be accepted, for in France one of the clinical forms of anthrax is thus designated. It is therefore better to abandon all these terms and to adopt the name Bacillus of Gaseous Gangrene, which has the advantage of avoid- ing all confusion and of immediately recalling the nature and appear- ance of the lesions. 112 BACILLUS OF GASEOUS GANGRENE This bacillus presents itself at times under the form of small motile rods, isolated or in couplets, measuring from 3 to 5 microns and often including a terminal or median spore; at other times under the form of filaments measuring from 15 to 40 microns and never con- taining any spores. Sown on agar-agar, the bacillus of gaseous gangrene produces a cloudy colony with arborization; it liquefies gelatine and blood serum by evolving gas; bouillon is at first turbid, but subsequently becomes clear and full of gas bubbles. Like the tetanus bacillus, with which it is frequently associated, the bacillus of gaseous gangrene is very widely distributed. It is almost constantly present in the soil, in dung, in the mud of waters; and it is often met with in the alimentary canal of man and animals. It is a very resistant microbe. Introduced into a wound, it pro- duces a large focus of gangrene with evolution of gas which infiltrates the surrounding tissue. The lesion manifests a great tendency to extension, and death supervenes through intoxication. This microbe, like that of tetanus, remains localized at the point of introduction, and acts through the medium of the toxines which it produces. Very closely related to, if not identical with, this bacillus is the bacillus of symptomatic anthrax. The morphological characters and the appearance of the cultures are similar. The differences lie in their pathogenic action. This microbe attacks cattle, in which it produces a disease called symptomatic or emphysematous or bacterial anthrax. It is of no importance in human pathology, but has acquired great interest because of the numerous researches in general pathology for which it has served. It may not be useless to add that there exists no relation whatever between symptomatic anthrax and the ordinary or bacterial anthrax. We have yet to mention among the anaerobics the bacillus of Acute Articular Rheumatism. Achalme and Thiroloix have found in the blood of rheumatic patients an anaerobic bacillus which, by its morphological characteristics, is allied to the anthrax bacterium. Tri- boulet and Coyon have also found a bacillus, but differing from the preceding. These observations are too recent to permit an opinion as to the part played by these microbes. Spirilla. — Two spirilla must be studied. The first known is the Spirillum of Recurrent Fever, discovered by Obermeier in 1873. It presents itself under the form of very motile elements, having 15 to 20 spiral turns and measuring from 15 to 50 microns. It is seen during the paroxysms in the blood of the patient, or of the monkey experimentally inoculated. This parasite has not yet been success- fully cultivated. ANIMATE AGENTS 113 The microbe of Cholera, called also spirillum of cholera^ cholera vibrio, and comma tacillus, was isolated and cultivated by Koch in 1884. It occurs in the form of a half parenthesis, of an S, or of the Greek character w ; at times, however, certain individuals are recti- lineal or drawn out into filaments. In old cultures spherical involu- tion forms are found. This microbe is motile, owing to the presence of numerous cilia. It develops readily in various culture media; in gelatine it pro- duces small colonies; inoculated by stab culture in a tube, it pro- duces a spherical excavation terminating in a rectilineal prolonga- tion. This appearance is almost characteristic. The microbe liquefies coagulated serum with equal rapidity. Upon agar-agar it forms a white and thick layer; on potatoes, a brown layer. Bouillon becomes turbid and covered with a thin pellicle. Milk does not coagulate. The development is very readily effected in peptonized water. This medium, which is often employed for its bacterial diagnosis, is charged with a great quantity of indol; treated with nitric acid, the liquid of the culture assumes a violet-red colour. This is the reaction called " Cholera-roth'^ ^ The cholera bacillus lives as a saproph5rte in water, and as a para- site in the alimentary canal of healthy human individuals. When it becomes excited, it multiplies within the intestinal cavity, which it manifests no tendency to leave; the lesions which it provokes must be attributed to the absorption of toxines to which it gives rise. Phycomyces. — Close to those bacteria capable of producing infec- tious diseases is reserved an important place for the parasites of a higher order. The latter are headed by a group of streptothrix, also called Oospora or Nocardia. The most important of this kind is the Strepto- thrix hovis or actinomyces, which produces in man and in animals a dis- ease described under the name Actinomycosis. Observed in the bovine species by Eivolta (1868 and 1875), who looked upon them simply as crystals, actinomycetes have been better studied by Perroncito, Bol- linger, and particularly by Harz and Israel, who proposed the term now adopted to recall their vegetable nature and their radiate form aKTts), tVos = rays, /avact^s = fungus ) . The first cases observed in man were published by Israel (1878) and Ponfick (1879-1882). Actinomyces gives rise to two kinds of lesions : to productions of sarcomatous appearance and to suppurative foci. In both cases yel- low granules have been found, resembling sulphur flowers. The para- site is readily seen on microscopical examination of one of the gran- ules. It is essentially formed in the following manner: a central part, made up of a felting of mycelial filaments, which irradiate like 114 PHYCOMYCES the spokes of a wheel and terminate in swellings of a club-shaped form or elongated in a pyriform manner. This vegetable, a facultative anaerobic, may be cultivated, although with difficulty, in various media, such as solidified serum, glycerine agar-agar, milk, bouillon, and vegetable infusions. It lives as a saprophyte upon vegetables, and especially upon the graminaceae. The herbivora are infected by grazing on the plants. The disease is particularly frequent in cattle, but it is also observed in swine, sheep, dogs, and the horse, although in the latter animal a some- what different fungus is generally found, known under the name Botryomyces. Man is at times infected from the bovine species, excep- tionally by a human subject, nearly always through the grain which he has chewed or with which he has been pricked. The studies of recent years have had a tendency to divide the his- tory of actinomycosis, or at least to admit the action of a whole series of analogous but not identical parasites. Poncet and Dor have cited facts of this kind. Vincent has shown that the disease desig- nated by the name of pied de Madura, Madura foot, particularly fre- quent in India, Algeria, and America, is due to an analogous vegetable parasite, Streptothrix Madurce. Among the principal pathogenic streptothrices we shall simply men- tion Streptothrix asteroides (Eppinger), which has been quite fre- quently observed in abscesses of the brain, of the meninges, and of the kidneys; Streptothrix Foersteri, found in the form of agglomerated filaments in the calcareous concretions of the lachrjrmal duct; and particularly Streptothrix farcinosa (Nocard), which produces in cattle a disease improperly called farcy (glanders), which is not to be confounded with the glanders of the horse or of man. The MucoK group also contains a few pathogenic species which are of interest. Such is Mucor corymhifer, well studied experimentally by Lichtheim, and found in man by Paltauf . Mycomycetae. — Mycomycetae comprise aspergillus, penicillium, and saccharomyces. The most important among Aspergilli is As- pergillus fumigatus. It vegetates as a simple saprophyte on hemp, and induces pulmonary lesions in those subjects who chew the grains for feeding 'pigeons. A few but exceptional cases of aspergillosis of the kidneys, skin, cornea, nose, and pharynx have been recorded in man. In a pulmonary abscess presenting certain of the characters of actinomycosis, Wheaton found a parasite which he compares with Aspergillus niger. This species is not generally considered pathogenic. Observations and experiments nearly always show that it is Asper- gillus fumigatus or glaucus that is concerned. A widely distributed vegetable, Penicillium glaucum, which is gen- ANIMATE AGENTS 115 erally a simple parasite, may, however, occasion general infections. The spores injected into the veins of a rabbit give rise to the develop- ment of a pseudo-tuberculosis. Recent studies have drawn attention to the pathogenic role of Blastomycet^. We have long known the action of one of them, Oidiuni albicans or Saccharomyces albicans. This parasite produces upon the mucous membrane of the mouth a lesion described under the name of aphthae or thrush. It is a local affection. However, in certain cases, oidium invades the organism, and in man produces a true general infection. At the autopsy, oidium nodules are found in the brain, kidneys, and lungs. Similar results have been obtained in animals, and these findings have thrown considerable light upon the mechan- ism of nonbacterial infections. The interest of blastomycetae is increased by recently published researches which establish the fact that these fungi are encountered in man much more frequently than was formerly believed. It will be seen in another chapter what an important role is attributed to them in the genesis of tumours. Protozoa. — Along with vegetable microbes are to be classed the animal microbes. We must place in this group the rhizopods and sporozoa, which alone are of importance in human pathology. Among the Rhizopods we shall mention amoebce, which have been met with in the tartar of the teeth, in gingival abscesses, and in the vagina. Their importance has increased since the studies of Loesch, and particularly of Kartulis, have shown their presence in the intes- tines of dysenteric patients. Is it to be concluded that the Amoeba coli is the cause of dysentery, and that it is also capable of producing the hepatic abscess consecutive thereto? This question is not yet solved, although an answer in the affirmative is quite probable. The Sporozoa are divided into the gregarinae and psorospermiae. The gregarinae represent parasites which are mostly found in in- vertebrates. Of late they have been observed in mammalia. Pfeiffer says he has found them in man in cases of smallpox, in vaccinia, scarlet fever, and herpes zoster ; but their pathogenic function is by no means established. Psorospermiae possess much greater interest. With this group are classed the coccidia* which were first studied in animals. They are * Besides the coccidia, psorospermiae include : (1) Myxosporidia, which are encountered in fish and which we have observed in the liver of a mouse. (2) Sarcosporidia (Miescher's tubes, Rainey's tubes), which invade the muscles of various mammalia. Rosenbergen found them in the myocardium of a woman forty years old. (3) Microsporidia, which inhabit worms and insects, and produce in silkworms the disease designated by the name of pebrine. 116 PROTOZOA frequently met with in the liver of rabbits, where they invade the biliary passages and give rise to epithelial and connective-tissue pro- liferations. Observed several times in the intestine, liver, kidneys, and pleura of man, coccidia are at present often looked upon as the cause of cancer. This conclusion, to which we shall again refer when speaking of tumours, is supported only by histological proofs. No one has as yet succeeded in cultivating the parasites, still less in inoculat- ing them. Lively discussions have therefore arisen on the subject, many scientists considering that the forms described as coccidia repre- sent simply degenerated cells. It is with a group allied to the coccidia that most naturalists class the parasite of malaria, Laveran^s liematozoon, Plasmodium malarice; Laverania malarice, as it is justly called in foreign countries. Al- though it has not been possible to isolate and cultivate the parasite, observations are now so numerous that there can no longer be any doubt as to its etiological significance. The element discovered by Laveran certainly is the causative agent of malaria. It lives within the red blood corpuscles and presents itself under the various forms of spherical bodies, spherical flagellated bodies, and also of crescents and rosettes. Summary and Classification of the Infectious Ag^ents. — If we con- sider the results which have been obtained by the study of patho- genic agents in infectious diseases, we may conclude that wonderful discoveries have been made. To-day nearly all diseases have their microbe. Those diseases in which the pathogenic agent is as yet unknown are not numerous, but, curiously enough, they belong to that class the infectious nature of which is not a matter of much doubt, and whose contagion is best established — e. g., the eruptive fevers, measles, scarlet fever, smallpox, varicella, vaccinia, the clearly infectious skin diseases like herpes zoster and polymorphous ery- thema, and those diseases which are never transmitted otherwise than by direct contact — rabies and syphilis. A. Nonspecific Bacteria. Micrococci. Staphylococcus. Aureus. Citreus. Albus. Streptococcus. Pneumococcus. Tetragenus. ANIMATE AGENTS 117 Bacilli. Colon bacillus. Paracolon bacillus. Bacillus of psittacosis. Pneumobacillus. Bacillus septicus putidus. Bacillus of hemorrhagic septicaemia.. Proteus vulgaris. Bacillus pyocyaneus. Leptothrix buccalis. Specific Bacteeia. Micrococci. Gonococcus. Micrococcus of mumps. Bacilli. Bacillus anthracis. Bacillus of glanders. Bacillus of typhoid. Bacillus of diphtheria. Bacillus of influenza. Bacillus of tuberculosis. Bacillus of human tuberculosis. Bacillus of avian tuberculosis. Bacillus of fish tuberculosis. Bacillus of leprosy. Bacillus of bubonic plague. Bacillus of yellow fever. Bacillus of soft chancre. Bacillus of tetanus. Bacillus of gaseous gangrene. Bacillus of symptomatic anthrax. Bacillus of rheumatism. Spirillum of recurrent fever. Bacillus of cholera. B. Phycomycet^. Streptothrix. Streptothrix bovis (actinomyces). Streptothrix Madurse, asteroides, Foersteri. Streptothrix farcinosa. Mucor. Mucor corymbifer. C. Mycomycet^. Aspergillus. Aspergillus fumigatus. Aspergillus glaucus. 118 CLASSIFICATION Penicillium. Pencillium glalicum. Saccharomyces. Saccharomyces or Oidium albicans. D. Protozoa. Rhizopoda. Amoeba coli. Sporozoa. Coccidia. Hematozoa. Plasmodium malariae. CHAPTEE VII ANIMATE AGENTS (Concluded) Distribution of microbes in water, soil, and air — Resistance of microbes to exter- nal agents — Antiseptics — Distribution of microbes in living beings — E,61e of microbes normally inhabiting the organism — The microbes of the alimentary canal — Gastrointestinal fermentations and putrefactions. Distribution" of Miceobes Water, as is well known, contains a great number of microbes; rain, snowflakes, and hailstones collect some of them in the atmos- phere. There is no pure water except spring water at its source. Water containing from 50 to 160 bacteria per cubic centimetre is considered an excellent drinking water. These figures are much ex- ceeded in the majority of rivers, especially when they have passed through a city; these water courses, however, possess the property of spontaneously purifying themselves. A very simple observation proves this : it suffices to examine the Seine below the collector of Asnieres ; the water, overcharged with organic matters, is brownish, of a dis- agreeable odour, and at every moment gas bubbles burst on its sur- face, evidencing the intensity of fermentations going on. A few kilo- metres farther down the water again becomes limpid. The following figures offer examples in this regard: The Isar, before passing through Munich, contains 305 bacteria per cubic centi- metre; at its issue from the city, when it has received the products of sewers, it contains 12,600; 13 kilometres farther down, without having received any tributary, the figures fall to 2,400 per cubic centimetre. Natural depuration is produced equally in reservoirs. The water of the Thames, for example, contains 1,437 bacteria. It contains only 318 after its passage into a first reservoir and 177 at its issue from a second. In rivers the agitation of the waters causes the microbes to unite with solid particles, and thus some are destroyed. If we take water containing 155 bacteria and agitate it with some chalk added in the 9 119 120 DISTRIBUTION OF MICROBES proportion of one fifths there will remain only 10; with charcoal pow- der, the quantity falls from 8,000 to 60 ; with pulverized chalk, the re- sults are still more striking — the water is sterilized, even when the number of microbes was so great that it was impossible to count them. More important is the action of the sun, the rays of which exert an inhibitory influence on bacteria, as has been proved by a great num- ber of experimenters. Pansini introduced a few drops of a culture of asporogenic anthrax into water which he submitted to the action of the sun; then the number of bacteria per cubic centimetre was 2,520; at the end of twenty minutes it fell to 130 ; at the end of half an hour, to 44; after forty-five minutes there were none found. The results are identical with other microbes. Procaccini took sewer water containing from 300,000 to 420,000 bacteria per cubic centimetre and submitted it to the action of the sun. At the end of the day the liquid was sterile. Here is another experiment, which realizes the conditions perfectly. The water of the Isar, before its passage to Munich, was studied by Buchner at different hours of the same day. The highest figure was found at 4 a. m. ; bacteria had multiplied during the night and their number reached 520 per cubic centimetre. The minimum was ob- taned at 8 p. m. ; sunned all day, the water did not contain more than five bacteria per cubic centimetre. Among the pathogenic microbes most frequently encountered in water, we must mention the colon bacillus, typhoid bacillus, staphylo- coccus, streptococcus, the bacillus of gaseous gangrene, and, in certain cases, the anthrax bacterium, the vibrio of cholera, etc. Once in water, microbes can not come out of it ; consequently, they can not get access to our organism except through ingestion. When the level sinks, they are deposited upon the uncovered soil and are then easily disseminated. Pettenkoffer has made an application of this result to his celebrated theory on the variations in the level of subterranean waters. Accord- ing to him, when the level sinks, typhoid fever increases; when it rises, it decreases. Unfortunately, many exceptions have been re- corded; in some cases the variations of typhoid fever have occurred just in the contrary order. The soil contains a great number of bacteria, some of which are indispensable to vegetation. The works of Schloesing, Muntz, and Winogradsky have established their intervention in nitrification. For us, as we are considering the pathogenic phenomena, it suffices to know that pathogenic microbes are found in the soil: the bacilli of tetanus and of gaseous gangrene, the microbes of suppuration, and in certain cases the bacilli of typhoid fever, of tuberculosis, of anthrax, and of cholera. To this list should be added the saprophyte agents, which, ANIMATE AGENTS 121 although inoffensive of themselves, may, when they enter onr tissues, favour the development of pathogenic agents. It is easy to understand that in most cases the soil is contaminated with products emanating from diseased men and animals; that it is not more infected, is due to the germicidal action of the sun's rays, which rapidly destroy the microbes remaining on the surface ; but they act with less energy upon those which have sunk into a certain depth. One might believe that the latter are no longer capable of harm; un- fortunately, this is not so, for they may, under certain conditions, be brought up to the surface. This is what was brought out by the celebrated researches pursued by Pasteur on the etiology of anthrax in the infected districts of Beauce, then designated under the name " cursed fields.^' It is to be noted first that animals or their cadavers affected by anthrax never contain spores; the bac- teria would then be speedily destroyed, if blood or liquids con- taining them were not spread on the external mucous membranes and integuments and did not at the same time fall on the soil. Once out of the organism, bacilli rapidly give birth to spores, some of which con- taminate the soil; others, developing on the cadavers, are buried with them. Then, according to a theory, arrive the earthworms, which ingest the spores, raise them to the surface, and, depositing them in their excretions, spread them upon the surface of the soil. They may afterward be transported and disseminated far off by wandering ani- mals like the slugs, which in one day travel a great deal (Karlinski) ; or they may be swallowed by insects, some of which, provided with a sting, act as agents to inoculate man. Being thus spread upon the surface, the spores contaminate the vegetable growth; so herbivorous animals are infected by eating the plants. The infection takes place in the mouth when the mucous membrane is scratched by the spikes, or in the intestine. The researches which have been made with the typhoid bacillus have established that this microbe is quickly destroyed on the surface of the soil. It does not resist the action of the sun, but at 50 centi- metres of depth it finds excellent conditions of resistance and may retain its vitality for over five months. The number of microbes diminishes in proportion to the depth below the surface; the maximum is at 50 centimetres, and below 3.5 or 4 metres there are none to be found. There remains a last question. Can the microbes of the soil invade vegetables? They can, according to Dr. Galippe. He has recorded a great number of experiments which have raised lively controversies. The problem is not yet solved; but, in view of its great practical in- terest, it deserves to be studied anew. 122 DISTRIBUTION OF MICROBES The dust of apartments, tapestry, woodwork, and floors contain numerous pathogenic microbes. In hospital wards, in cases of epi- demics, there have been found between the planks of the floor the microbes of tetanus, erysipelas, pneumonia, and diphtheria. The same is true as regards tuberculosis; every author cites the researches of Cornet, who, in a room occupied by a consumptive, found that the dust obtained by scratching the wall, when inoculated into the peritoneum of a guinea pig, induced tuberculosis. The air serves much less to transmit infections than the soil, and still less than the water. It contains, however, a great number of microbes, as shown by the following figures, obtained by Dr. Miquel, which at the same time show clearly the considerable variations of the numbers depending upon the place : In the sea, at 100 kilometres from the coast 0.6 Altitude of 2,000 metres 3 Summit of Pantheon 200 Observatory of Montsouris 480 Rivoli Street (in Paris) 3,480 New house 4,500 The air of sewers of Paris 6,000 Oldhouse 36,000 Hotel-Dieu (hospital) 40,000 Pitie Hospital 79,000 One may be surprised, in perusing this list, to see that the air of sewers contains but a slightly greater number of microbes than the air of a new house, and six times less than that of an old house. It is because the innumerable bacteria contained in water can not invade the air. It has been experimentally shown that a current of air pass- ing over a contaminated liquid is not charged with microbes. The reverse opinion once prevailed; it was at one time believed that the air served as an intermediary between the water and our organism, and in support of this idea the events of an infectious character consequent on the inhalation of gases escaping from sewers or cess- pools were cited. In reality, the mechanism is more complex: the gases act by disturbing the economy and by reducing its resist- ance; they thus permit the development and exaltation of patho- genic germs which, until then, vegetated as simple, inoffensive parasites. The various results above recorded have but a relative value; very notable variations occur every day in the same place. During the hot season microbes increase, to reach their highest figure in the month of July; the minimum occurs in December. Their numbers diminish after a rainfall which carries them toward the soil; they diminish ANIMATE AGENTS 123 equally under the influence of the sun's rays, the germicidal power of which has already been referred to. Eesearches have in most cases been limited to a simple counting of the microbes of the air, regardless of the proportion of pathogenic agents. But clinical observations suffice to inform us in this regard. It is admitted that typhoid fever may be transmitted through the air far more rarely than by water. The same applies to eruptive fevers, but it is to be noted that this mode of propagation is rare and occurs within a restricted zone. The virus of measles hardly extends beyond 4 metres, that of scarlet fever is perhaps a little more diffusible. As to smallpox, the better we study the march of epidemics the more we are convinced that contamination takes place in most cases, if not always, by direct contact. One of the infections which are transmitted most frequently through air is tuberculosis. The particles of desiccated expectoration are swept by the wind and penetrate the respiratory channels, and this accounts for the frequency of pulmonary lesions. The air has often been supposed to play a part in the transmission of surgical infections ; it is to-day demonstrated that erysipelas, septi- caemia, and gangrene are generally propagated, not through the air, but by the hands of the surgeon and his assistants, by the instru- ments and dressing material. The same is true of puerperal fever: women attacked with erysipelas may be confined, even in an isolation ward devoted to the treatment of this infection, without becoming septicaemic, provided necessary care and precautions be taken. One of the infections most frequently propagated by the air is ma- laria. The hematozoon may be transported to great distances from the marshes where it led its saprophytic life; but an obstacle of land, a wall, a cluster of trees suffices to arrest its passage. Eesistance of Microbes Microbes are submitted to a certain number of destructive causes, which may, according to their intensity, produce three different effects: functional modifications, a diminution in numbers, or a com- plete destruction. It is because the cultures are not homogeneous that the number can decrease; if all the individuals possessed the same vitality, all would perish at the same time. The resistance of microbes varies, on the other hand, according as the cultures do or do not contain spores : if they do not, resistance is, as is known, much less marked. The agents capable of doing harm to bacteria are also divisible into four groups : Mechanical, physical, chemical, and animate agents. Contrary to what has often been asserted, mechanical agents pos- 124 RESISTANCE OF MICROBES sess but little action. We can not admit, for example, that the varia- tions of atmospheric pressure can modify the activity of the patho- genic bacteria, increase or diminish their virulence, and thus explain the epidemic temperament {genie epidemique) . The contrary opinion finds its origin in the erroneous interpretation of exact experiments. It has been shown, in fact, that certain compressed gases exert a noxious action on microbes; but in this case the effect is not simply due to an increase of pressure; the phenomena are much more com- plex. If, for example, we make the oxygen act under a pressure of 10 atmospheres, we may kill the Bacillus anthracis; still, it is necessary to prolong the contact for a very long time. When the microbe is not a spore-bearing one, less than eight days will not suffice; when it does bear spores, death does not occur even at the end of twenty- one days. Carbonic acid appears to be more energetic. According to Fraenkel, Seltzer water is sterilized in the siphons. D'Arsonval has seen a certain number of bacteria perish under a pressure of 60 atmos- pheres. From all these researches it may be concluded that ox3^gen and car- bonic acid can kill microbes, provided the pressure be considerable. To make evident the true action of pressure, we have inclosed vari- ous microbes in rubber tubes which have been plunged in water or in oil. By compressing the liquid to 2,000 kilogrammes per square centi- metre, we observed no modification of the four species employed: streptococcus, staphylococcus, colon bacillus, non-spore-bearing and spore-bearing anthrax. Going up to the strongest pressures which one could reach — ^that is, to 3,000 kilogrammes (2,903 atmospheres) — we obtained the follow- ing results: Colon bacillus and Staphylococcus aureus have experi- enced no disturbance; the non-spore-bearing anthrax, sown in a fresh medium, developed more slowly than it habitually does, and proved less virulent than before compression; the spore-bearing anthrax was slightly attenuated; streptococcus vegetated less luxuriantly, less rap- idly, and furthermore lost part of its toxic action. It is necessary, then, to reach colossal pressures in order to observe some, anyhow little marked, modifications in the vitality or the properties of bacteria. It had been thought, after the researches of Horvath, that slight movements or oscillations of the culture medium prevented the devel- opment of microbes. Further experiments have not confirmed this result ; the effects have been variable and inconstant. For our part, we have obtained no results by submitting cultures to repeated shocks reaching 200 to 250 kilogrammes per square centimetre. ANIMATE AGENTS 125 Physical agents have a far greater importance, at least some of them. Some, for instance cold, are very well borne. We have already said that microbes are found in ice. Dr. Eaoul Pictet submitted bac- teria to temperatures as low as — 110° and even — 200° C. without succeeding in killing them. Professor d^Arsonval plunged some into liquefied air, without causing them to lose their power to vegetate. It is possible, however, to do harm to bacteria even with less low tem- peratures, by submitting them to successive freezings and tha wings; their numbers notably diminish in these conditions. Heat has a much more marked action. There are undoubtedly cer- tain species, notably those of hot springs, which seek heat and vegetate best at a temperature of 70° and 74° C. This is, however, an excep- tion. Bacteria are easily destroyed by heat, but effects vary according to several conditions, as usually the spores prove much more resistant than the adults. All other conditions being the same as regards the culture, heat is more destructive when microbes are contained in a liquid medium than when they are dried up. Finally, the action of heat is considerably favoured by the presence of air, which produces oxidations unfavourable to bacteria. The multiplicity of conditions intervening at the same time as heat explain the often considerable differences obtained by experiment- ers. The figures given have but a relative value; they nevertheless present a certain interest. Let us take, for example, the tubercle bacillus : plunged into water at 60° C, it is still living at the end of twenty minutes ; into water at 70° C, at the end of ten minutes. Boiling water, at 100° C, kills it in five minutes. If dry heat is brought to act, the bacilli resist a tem- perature of 100° C. for several hours. The differences are the same for anthrax. According to Dr. Mo- ment, anthrax blood, desiccated in a vacuum, remains virulent after a sojourn of an hour and a half in an oven at 92° C. ; the moist blood is sterihzed at 55° C. in one hour. To kill the spores, we must submit them, according to Koch and Wolffhiigel, to 107° C. for five minutes, when they are moist; if dry, they resist 120° C. for four hours; to make their destruction sure, we must leave them three hours at 140° C. It is true that Massol finds less elevated figures. A temperature of 100° C. kills the spores at the end of five or six minutes. The influence of air is made apparent from Dr. Eoux's experiments. Submitted to the combined action of air and a temperature of 70° C, spores succumb in 60 hours; protected from air, they still live at the end of 165 hours. We have already shown, with respect to microbes of the soil, the important part played by light. The blue and violet rays act most 126 RESISTANCE OF MICROBES energetically; but, as in the ease of heat, the action of the light is favoured by moisture and by air. Dr. Momont has shown that anthrax spores perish after 48 hours of insolation when they are in contact with air; inclosed in a vacuum, they are still living after 110 hours. The action of light may be evidenced by the following experiment : A few drops of an anthrax culture are spread upon a gelatine plate, which is then covered with a glass upon which pieces of black paper are pasted; on exposure to the light, development takes place in the pro- tected parts and the bacteria exactly reproduce the designs figured by the pieces of paper. The action of light is more complex ; for, besides the noxious influ- ence exercised on bacteria, the modifications of the medium are to be taken into account ; sunned bouillon becomes unfit for cultivation. In cases where life persists, functional modifications supervene: chromogenic microbes cease to produce pigment, and pathogenic agents become attenuated. We shall not dwell upon the effects of electricity. In the old ex- periments the currents employed produced heat or electrolysis, and the effects obtained were of a thermal or chemical order. Those authors who have been on their guard against these causes of error have not been able to detect a direct action of electricity on microbes. The chemical agents that act upon bacteria are called antiseptic agents. Among the gaseous bodies, it suffices to mention ozone, which, as is known, is often found in the air in great quantities. Its action is very intense, at least on the adult elements; the non-spore-bearing anthrax is killed within five hours, but the spores perish only at the end of three or four days. The antiseptics, properly so called, when used in minute doses, have the very curious property of stimulating the activity of microbes; under their influence, the chromogenic bacteria produce a greater quan- tity of pigment. In increasing the dose of the antiseptic, we see the chromogenic power diminish and disappear; then vegetation grows slower, ceases, and finally the microbe is killed. Carbolic acid is one of the substances most frequently employed. In a 1-per-cent solution it kills the non-spore-bearing bacterium in ten seconds; if the element is spore-bearing, life persists after the continued intervention for thirty-seven days of a solution five times stronger. In order to increase the action of antiseptics, it is well to raise the temperature of the medium; this is an element of capital importance from a practical standpoint. For disinfecting purposes hot solutions must be employed. The anthrax spores, for example, resist 5-per-cent carbolic acid at the surrounding temperature, but they are killed in the ANIMATE AGENTS 127 same solution in two hours if the temperature reaches 55° C, and in three minutes if it is raised to 57° C. By submitting a microbe to the influence of antiseptics during sev- eral successive generations, we can permanently modify it and deprive it of some of its properties. Thus are created non-pigment-forming, non-spore-bearing varieties, and, what is more important, the virulence is made to disappear and vaccines are obtained. The action of animate agents upon bacteria now remains to be con- sidered. In a great number of cases, two or more microbes vegetate in the same medium. Sometimes they assist each other; thus, for example, an aerobic microbe, by appropriating to itself the oxygen, will facilitate the development of an anaerobic. More frequently they antagonize each other; in cultures originally polymicrobic one species will little by little predominate and finally stifle the others; a natural selection is effected. Moreover, microbes have frequently to struggle with the higher organisms, vegetable and animal, whether they occupy their integuments or penetrate into their interior. We are thus led to study the behaviour of bacteria toward higher beings. Distribution- of Bacteria in Living Organisms The distribution of microbes in the air, soil, and water suffices to explain their presence on all the exposed parts of our bodies. They are found in great number upon the shin; they live there as inoffensive parasites; the horny epidermis, further protected by a layer of fat, opposes to them an impassable barrier. With each inspiration, the air causes a great number of bacteria to penetrate the respiratory passages. They are retained by the hair in the nasal orifices and by the vibratile cilia of the mucous mem- brane. Others are fixed by secretions ; they become pasted, as it were, to the moist tissues. Therefore the farther we recede from the natu- ral orifices the smaller the number of bacteria do we find. At the level of the pulmonary alveoli, often at the level of the bronchi or even of the trachea, the air is bacteriologically pure. In again passing through the respiratory tract, at the moment of expiration, the air does not take up the parasites which it has deposited, for, as we have already said, these can never leave the liquid media which encompass them. The expired air, therefore, contains no microbes. It may be inquired : What is the fate of the bacteria that are thus deposited and that might become harmful, if only by their number? Fortunately, the respiratory apparatus is provided with various means of protection. The secretions act mechanically and wash, so to say, the mucous membrane; a certain number of bacteria are thus thrown out. Others are destroyed by the nasal mucus, which, as has been 128 DISTRIBUTION OF BACTERIA IN LIVING ORGANISMS shown by Lermoyez and Wurtz, possesses germicidal powers. In other words, the secretions exercise a sort of antiseptic action. The re- mainder are picked up and devoured by certain cells called phagocytes, which are very numerous in those localities where lymphoid tissue abounds, and at the level of the pulmonary alveoli. Bacteria are much more numerous in the digestive canal. Ingested with the food and beverages, they reach the stomach, where, according to certain authors, the acid has the property of destroying them. This assertion, based upon results obtained by means of artificial digestion, explains the frequency of infection when the subject is fasting, when the stomach is altered, or the gastric juice is neutralized by an alkali. It seems, however, that the protective role of the stomach has been somewhat exaggerated; for counts which have of late been made show that this portion of the digestive tract contains numerous bacteria, even more than the duodenum. Having reached the intestine, the microbes here find the best con- ditions for their existence. The aliments we ingest serve for their nutrition; the heat of our digestive tract offers them the advantages of a well-regulated oven; the secretions which flow are far from being germicidal, since they contain substances favourable to their develop- ment. We may therefore say that the alimentary canal is the paradise of microbes, and that they can multiply energetically, as is shown by the following figures, taken from the interesting researches of Gilbert and Dominici. There are found in the stomach 50,000 microbes per cubic millimetre; then the figure suddenly falls; at the origin of the duodenum there are only 30,000; the number progressively rises until the end of the bowel is reached, where it attains its highest point — namely, 100,000 per cubic millimetre. In the caecum another fall occurs; throughout the length of the large intestine there are only 25,000 to 30,000 microbes per cubic millimetre. By taking account of the quantity of matter contained in the digestive canal, we arrive at the respectable total of 411,000,000,000 microbes. Each day man rejects a certain number of bacteria in his fseces. In health the quantity varies from 12,000,000,000 (Gilbert and Domi- nici) to 40,000,000,000 (Vignal). According to some authors, these microbes play a salutary part; they perform a second digestion, complementary to that accomplished by the digestive juices. This idea, developed by Dr. Duclaux, has led to the supposition that perhaps life would be impossible without the aid of these collaborators, which are to animals what the microbes of nitrification are to plants. The hypothesis is seductive, and it is doubtless very interesting to study what would become of animal life without the intervention of bacteria. An experiment, difficult to real- ANIMATE AGENTS 129 ize, has, however, been conducted by Nuttal and Thierfelder. By means of a very ingenious contrivance these authors succeeded in breeding two guinea pigs protected from microbes. Unfortunately, the experiment lasted but eight days ; during this time, however, these ani- mals flourished just as well as the control animals left in the free air. It is evidently impossible to conclude what would happen later. These researches are worthy of repetition. Whatever be the solution employed, it is incontestable that mi- crobes cause our aliments to undergo profound transformations, some of which are similar to those of digestion, others differing therefrom in that the modification of substances is greater. The albumens are peptonized, but at the same time there are pro- duced amido agents, leucine, tyrosine, and particularly aromatic bodies, indol, phenol, and skatol. The last-named, slightly soluble, remains almost entirely in the faeces and gives to them their peculiar odour. Indol and phenol are reabsorbed, and, after certain modifications within the organism, are eliminated in the urine. Coincident ly, there are produced volatile substances, carbonic acid, ammonia, sulphuretted hydrogen, methylmercaptan (a substance with a nauseous smell, enter- ing into ebullition at 21° C), of which one part is expelled by the anus, and another, being reabsorbed, is eliminated by the respiratory apparatus and the skin. Finally, there are formed ptomaines, which, from their chemical constitution, are analogous to vegetable alkaloids. With a view of recalling their origin and their toxic effects, the princi- pal ones have been denominated ptomatoatropine and ptomatomusca- rine. It is then easily understood that fsecal matters are toxic. Ac- cording to Bouchard, the extract of 17 grammes suffices to kill 1 kilo- gramme of animal. The action on the other groups of aliments is less important from a pathological standpoint. The carbohydrates are transformed into alcohol — and this explains the presence of this substance in the organ- ism of animals — and into acids. The cellulose is attacked and the fats are broken up. Certain aliments, like milk, hinder fermentation; others favour it. Bouillon, meat, particularly veal, offer excellent culture media for bac- teria. Putrefactions reach their highest intensity when tainted ali- mentary substances are ingested. The use of venison, or of dishes made with ill-preserved cold meat, may often produce grave disturb- ances. These are particularly frequent in Germany, where they are described under the name botulism or allantiasis. They result from the ingestion of very large sausages, the central portions of which are incompletely cooked. This element contains perfectly formed pto- maines as well as microbes. Ptomaines chiefly serve to diminish the 130 DISTRIBUTION OF BACTERIA IN LIVING ORGANISMS resistance of the organism ; they favour the multiplication of microbes, and, after an incubation period of from twelve to fifteen hours, disturb- ances make their appearance. These are manifested by vomiting, a horribly fetid diarrhoea, and, in the grave forms, cutaneous eruptions, nervous manifestations, dizziness, and diplopia. Lastly, in certain cases, the temperature falls, the extremities grow cold, and the patient succumbs in collapse. Poisonings have been occasioned by the use of preserves. The cen- tral parts of the boxes are not always sufficiently heated and may con- tain dangerous microbes. Preserved fish, and particularly preserved lobster, have thus caused serious disturbances. The same is true of salted codfish; its dangerous character is indicated by the rosy colour which it presents and which is due to a fungus — viz., Beggiatoa roseo-perniciosa — which is not dan- gerous by itself, but is accompanied by putrefactive bacteria. Milk may also be altered; it contains a poison studied by Vaughan — tyrotoxine — which produces serious disturbances, notably in chil- dren. The intestinal putrefactions, when exaggerated by some cause or another, occasion a whole series of disturbances. Locally, an irritation of the bowel is produced, which is expressed by expulsive colics and diarrhoea, and nauseous evacuations. Part of the volatile principles is absorbed and is eliminated by the breath and by the sweat, which takes on a fetid odour; there are present at the same time lassitude, dizzi- ness, and headache — all phenomena denoting intoxication of the organism. Eeciprocally, in case of constipation, the intestinal products are reabsorbed; the manifestations are similar, but less marked, for the faecal matters are harder and absorption is less easily effected; the symptoms are again dizziness, headache, fatigue, and fetid breath and sweat. Generally these disorders are not of serious import in normal individuals; but not so with certain patients, notably those having re- cently undergone an operation, and, above all, with puerperal women. A febrile state is observed, at times disquieting, which yields to the influence of an enema, a purgative, or an antiseptic. In still severer cases there occurs intestinal obstruction, in which, among numerous disturbances, several are referable to the reabsorption of toxines. When the stomach is profoundly affected, and notably in dilatation of this organ, the exaggeration of putrefaction gives rise to a series of morbid manifestations. On awakening, the patient feels more tired than at bedtime. He suffers from headache and dizziness ; the passage ANIMATE AGENTS 131 of toxines through the kidneys induces albuminuria; their action on the bones produces various alterations, such as nodes at the level of the second phalanx, and osteoporosis. In childhood rickets is the eon- sequence of disturbances of intestinal digestion which are so frequent at that age. Two still graver sjntnptoms may depend upon exaggerated gastric fermentation : tetany, which is sometimes fatal, and diacetaemic coma, which we shall study more fully in connection with diabetes. It is easy to understand that in a great number of general dis- eases, markedly in infections, intestinal putrefactions increase by reason of the fact that the means we possess for preventing them decrease. The digestive canal can expel microbes by the same procedures as other parts of the organism; the intestinal and pancreatic juices and the bile, although not possessing any antiseptic property, act as cleans- ing agents and at once reject microbes and toxines. If bacilli tend to pass through the mucous membrane, they are arrested by the lym- phoid organs — solitary glands and Peyer's patches — and by numerous leucocytes, which constantly travel in these regions, and can even make their way into the cavity of the intestine. If they escape these causes of destruction, microbes reach the lym- phatic glands and the liver, where new means of defence are found. If they pass beyond, they reach the lungs, which are also endowed with germicidal power. We thus see how many precautions are accumulated against the microbes of the bowels. Protection against microbic toxines is assured by the digestive secretions, which transform some of them, throw out others, and par- ticularly by a very special action of the intestinal mucous membrane. Taking up an idea of Stich, Denys and Brion have proved that the epithelial cells of the intestine destroy the microbic toxines; those that escape pass through the liver, which neutralizes some of them. But the protective function of this gland is quite variable. It is very pronounced with the toxines of certain varieties of the colon bacillus, but does not seem to be exercised upon poisons produced by other species. So, in many cases, the poisons pass onward, and are elimi- nated by the kidneys. Thus the toxicity of the urine chiefly depends upon intestinal putrefaction ; it varies parallel to this. There yet remain the volatile substances, sulphuretted hydrogen and methylmercaptan, which are eliminated by the lungs and the skin, imparting a foul odour to the breath and the sweat. It is to be noted that the liver intervenes here with great energy ; numerous experiments prove that it retains and neutralizes considerable quantities of sulphu- retted hydrogen. 132 DISTRIBUTION OF BACTERIA IN LIVING ORGANISMS Intestinal fermentation may be overcome by dietetics and by thera- peutics. It suffices to confine one's self to a milk diet in order to restrict putrefaction in the bowels. Gilbert and Dominici found in the faecal matters of a normal man 67,000 bacteria per cubic millimetre; after two days of milk diet, there were no more than 14,000; at the end of three days, 8,000, and of five, 2,250. Sterilized milk, by the way, gives no better results ; at the end of ten days the stools contain 3,000 bac- teria per cubic millimetre. These differences, already very notable, appear still more marked when account is taken of the quantity of matters discharged. Placed upon a mixed diet, a man passes 175 grammes of faeces, containing 12,000,000,000 bacteria; under the influence of milk diet, the quantity falls to 73 grammes containing only 164,250,000 bacteria — ^that is, -^ of the original figure. Of the procedures furnished by therapeutics, we must first men- tion purgatives, the infiuence of which has been demonstrated by numerous experiments ; one may employ saline purgatives, which expel the microbes, as well as calomel, which has the advantage of possessing a notable antiseptic action. To inhibit the development of microbes, one may resort to insolu- ble antiseptics which traverse the digestive canal without being ab- sorbed : naphthol, benzonaphthol, and betol are the substances gener- ally used. In order to prolong their action, it would be well to pre- scribe them in fractional doses. Benzonaphthol and betol are less active than naphthol, but they do not possess the acrid and burning taste of the latter. So they may be used in the cases of children. To these substances is often added subnitrate or salicylate of bis- muth. The subnitrate renders the stools thicker and exerts a chemical action. In contact with sulphuretted hydrogen, it is decomposed and gives rise to sulphide of bismuth, an insoluble body that neutralizes the harmful action of sulphuretted hydrogen. Salicylate of bismuth does not act quite as well, but it has the advantage of furnishing infor- mation concerning the intestinal putrefactions. The salt is decom- posed and the salicylic acid resulting therefrom passes into the urine, where it is easily detected by the addition of perchloride of iron, which yields a beautiful violet colour. This reaction does not occur when the production of sulphuretted hydrogen has ceased. CHAPTEE VIII GENERAL ETIOLOGY OF INFECTIONS Hetero- and auto -infections — Morbid contagion and spontaneity — Causes favour- ing infection: immunity and predisposition — Microbic associations — Modes of entrance of microbes — Modes of protection of the organism — Local lesion — Part played by lymphoid productions — Protective part played by certain organs— Importance of the liver and the lungs — Causes explaining microbic localizations: mode of entrance; physiological and pathological state of the organs. Infectious diseases may be produced in two ways : they may result either from the introduction into our organism of virulent germs com- ing from without, or they may be due to microbes that have their lodging within our bodies, and which become exalted under the influ- ence of various intercurrent causes. Infections may therefore be divided into two groups : Hetero-infections, recognising an external origin, and auto-infections, of which we carry the germs in ourselves, even under normal conditions. This division, which may be retained, has not an absolute value. It is evident that all microbes that live in us come from outside. But once introduced into our organism, they behave differently. Some remain in the condition of harmless parasites until the time when a morbific cause, diminishing our resistance, enables them to induce a disease. Others act immediately, and their introduction is soon fol- lowed by the appearance of morbid manifestations. Yet others hold a position intermediary between the two preceding groups. When they reach us, instead of remaining altogether inoffensive, they provoke a slight, circumscribed lesion, which is sometimes latent and often cur- able. While the pathogenic agent remains thus localized, even when nothing reveals its presence, the organism is always threatened by acci- dents ; on the slightest occasion the microbe becomes again aggressive and the local lesion is made the starting point of a more or less serious infection. Let us take some examples. Among the pathogenic microbes that may live for a very long time without occasioning any disorder, we find 133 134 MORBID CONTAGION AND SPONTANEITY staphylococcus, streptococcus, pneumococcus, and colon bacillus. Of microbes producing infection soon after they penetrate an organism, we may cite the agents of anthrax, hydrophobia, syphilis, and soft chancre. In the last group is placed the tubercle bacillus, which may for years locate itself in a ganglion without giving rise to any notable result. It is further to be noted that the same infection may be brought about in several different ways. Pneumonia, for instance, is due to pneumococcus, which vegetates in the mouth as a harmless parasite; let some accessory cause decrease the resistance of the organism, the microbe will invade the lung and provoke pneumonia. From this moment the exalted germ is able to attack other persons ; in this man- ner the disease born by auto-infection spreads by hetero-infection. Pathogenic microbes may be introduced in several different ways. There is, in the first place, direct inoculation. A virulent microbe comes to soil the surface of a wound, or penetrated with an instrument into the tissues. All wounds are not equally apt to be invaded by bac- teria. Those clean cut are seldom infected ; not that microbes are lack- ing on their surface, but they do not find conditions favourable for their development. Contused wounds represent, on the other hand, an excellent medium of culture ; the tissues being affected in their vitality, the cells are unable to prevent the multiplication of morbid agents. The microbes of suppuration, gangrene, and tetanus develop rather in the contused wounds. For other more virulent agents the slightest abrasion suffices for infecting the economy; such is the case with an- thrax, glanders, hydrophobia, syphilis, and soft chancre. Against these viruses our resistance is very weak, and inoculation is too fre- quently positive. There are, nevertheless, some very curious examples of immunity. Certain individuals do not contract venereal diseases, although they do not fail to expose themselves to contagion; others prove rebellious to vaccine, and, in this case, clinical observation has the value of a laboratory experiment. The second mode of transmission of disease is represented by con- tagion. The microbe does not break in, but penetrates through the natural channels. Contamination may occur in different ways. In some cases there is contact of the healthy subject with the sick. In other instances the transmission is indirect ; it takes place through the atmosphere, objects, or persons who carry the microbe without being themselves con- taminated. Immediate contagion is a matter of evidence; but transportation by air is more conjectural. The latter has been imagined to explain the course of epidemics; as regards influenza particularly, it has been GENERAL ETIOLOGY OF INFECTIONS 135 said that atmospheric transmission made it possible for this disease to pass in twenty-four hours from Berlin to Paris. In analyzing the facts, however, we perceive that epidemics do not go any quicker than our means of communication; they are propagated, not by the wind, but by direct contagion. Individuals who have taken care of patients, or simply approached them, may transport the disease. Certain epidemics of puerperal fever recognise no other cause. Still more frequently are the surgeon or his assistants to blame, who have not very carefully cleaned their hands, or have used dressing material, especially instruments, not well disinfected. In other cases contagion is explained by the persistence of morbid germs in rooms, on papers, tapestry, rugs, floor, and especially in clothing; sometimes also in vehicles which have served to transport patients. Hence the excellent measures taken for the disinfection of carriages and wagons. Disease may be transported also through let- ters. Graves's observation is well known: A young lady contracted scarlet fever through a letter which had been addressed to her by a friend of hers convalescent from this disease; the microbe had been transmitted through particles of scales falling from her hands. So in the isolation hospital of Aubervilliers letters are disinfected before they are sent to the post office : after perforating them by means of pins they submit them to the action of sulphur fumes. Although less frequent, transportation through the atmosphere is undeniable. Intermittent fever is thus transmitted; the majority of cases of pulmonary tuberculosis acknowledge the same origin. Lastly, the soil, and, above all, water are often contaminated with microbes proceeding from patients, and play a considerable part in the development of certain infections. It is through water that typhoid fever, cholera, and dysentery are propagated; it is in the soil that the germs of tetanus, gaseous gangrene, and anthrax spread them- selves. In cases of auto-infection there is no contagion; as already stated, the malady is generated spontaneously. Though the fact is of rare occurrence, it may be true as regards specific diseases, typhoid fever, for example. Military physicians have reported observations which seem to be absolutely demonstrative; soldiers have been seen to depart for manoeuvres and lodge in villages where typhoid fever had not been observed for years past; in consequence of fatigue, a sol- dier is attacked by the fever, then another, then a third, and a small epidemic takes place. The same fact is observed in permanent camps ; at the end of five or six weeks typhoid fever makes its appear- ance. A striking example is reported by Dr. Kelsch. During the war 136 AUTO-INFECTION of 1870 the' German army was camping on both banks of the Moselle ; the contingent on the right bank suffered from t3rphoid fever in the proportion of only 12 per 1,000; the one on the left bank in the pro- portion of 27 per 1,000. Yet the conditions of air, earth, and water were the same, except that on the left bank there was more crowding, a greater mass of men, and therefore worse sanitary conditions. What seems to be still more conclusive is the fact that typhoid fever has been seen to make its appearance on board a ship five or six weeks after it had left the land. Certain authors, convinced contagionists, have doubted the reality of these facts; others have attempted to explain them by a very seductive theory. Drs. Rodet and Roux have argued that the typhoid bacillus is but a variety of colon bacillus, this common guest of our alimentary canal. If the resistance of the organ- ism be diminished, the disease sets in, spontaneously in appearance, but in reality by the exaltation of this parasite until then inoffensive. This ingenious conception has occasioned a great number of contra- dictory studies. But to-day we no longer need such a hypothesis, as, according to Reumlinger and Schneider, the typhic bacillus is found in the intestinal contents and faecal matters of persons in good health ; this fact explains the apparently spontaneous development of the dis- ease, and its future transmission by contagion. Other well-defined infections may also appear spontaneously — for instance, diphtheria. Its development is perhaps explained by the pres- ence, in the buccal cavity, of a bacillus designated pseudo-diphtheric, which is often considered to be an attenuated variety of the Loeffler bacillus. The question has been put even with regard to gonorrhoea. Straus published a case alleged to have occurred without any con- tagion. But it is not safe in such cases to trust the assertions of pa- tients who, too often, are unwilling to confess how they have been con- taminated. It must be acknowledged that, even for diseases whose contagion is most frequently admitted, it is not always possible to discover the method of contamination. If a great number of persons attacked by measles, and especially by scarlet fever, were questioned, the majority would be unable to say where and how they contracted the germ of their disease. Hence some physicians think that scarlet fever, which they see occurring without any contamination, may originate spontaneously; they have attempted to eliminate this eruptive fever from the class of specific infections and to admit that it is owing to a common microbe — to streptococcus, for instance — which, according to their view, becomes exalted and acquires certain special properties; it preserves its new qualities for a certain length of time, and this ex- plains the further propagation of the disease. GENERAL ETIOLOGY OF INFECTIONS 137 Nearly all of the infections that originate spontaneously — viz., without any contagion whatever — are due to common bacteria, which become more virulent when our resistance grows fainter. Thus staphy- lococcus, an habitual guest of the skin, gives rise spontaneously, as it were, to abscesses, boils, and anthrax; streptococcus, vegetating in the mouth, provokes erysipelas and sore throat; pneumococcus produces bronchitis, broncho-pneumonia, and lobar pneumonia; colon bacillus causes enteritis, or, making its way into the liver, induces suppurative angiocholitis, etc. Microbes thus become educated ; they learn how to overcome the resistance of the organism, and in the end constitute par- ticular races, apt to reproduce in others an affection analogous to or identical with the one which they have in the first instance provoked. Streptococcus, for example, which has acquired the property of causing erysipelas, will produce erysipelas by contagion. That which has de- termined angina, will reproduce angina. Although there are instances of a different evolution, it seems that, while being exalted, microbes acquire a certain specific power — that is, a certain aptitude for repro- ducing accidents of similar location and evolution. In this manner at the present day is morbid spontaneity explained, and the ulterior trans- mission of a first case, arising without any contagion, accounted for. Causes Favourable to Infection. — We are thus led to investigate the causes which, by diminishing our resistance, permit the develop- ment of infections. There is, first, a series of extrinsic causes in connection with re- gions and seasons. In some countries a certain infectious malady prevails endemically ; in others the disease can not become acclimated. Yellow fever, which fearfully ravages some countries of America, has never reached the Old World. If, perchance, a patient is found on board a ship arriving at a European port, no cases occur in the city. In some instances the exotic disease gets a foothold, as is the case with cholera; at times it assumes a character of exceptional malig- nancy ; such proved to be the case of measles transported to the Faroe and Fiji Islands. The influence of the seasons has long been recognised. It has been indicated by Hippocrates, and is clearly brought out by modern statis- tics. In a general way, infectious diseases, notably eruptive fevers, are specially frequent from March to July ; the minimum extends from Sep- tember to December. During the hot season gastrointestinal mani- festations are more frequently observed; during the cold season, tho- racic disorders. The hygienic condition of a country is a factor of obvious impor- tance. The number of infectious diseases has considerably decreased 138 CAUSES FAVOUKABLE TO INFECTION since the progress accomplished in the disinfection of lodgings and clothing, the creation of special hospitals for the isolation of patients, and the improvement of drinking water. Even typhoid fever has be- come less frequent. Morbid aptitude varies considerably with different races. The negroes are immune from certain infections, as yellow fever; even the mulattoes are safe, and in countries where the disease is endemic it is customary to say that a drop of black blood is the best of preservatives. The negroes are likewise little subject to malaria. They are, on the other hand, very susceptible to tetanus, and much inclined to develop chancroids on the slightest suppuration. The yellow race is predisposed to smallpox, which rages as an en- demic; their susceptibility is so marked that it is not rare to see re- lapses of this infection. Acute articular rheumatism is, so to say, allotted to the Caucasian race. Predispositions and immunities no less remarkable may be noted among different peoples of the same race. The Anglo-Saxons are very liable to sudor Anglicus, and especially to scarlet fever. But what is more curious is that the sensibility of the English to scarlet fever is of recent date. Sydenham, who was the first to describe this infection, considered it as very benign, hardly deserving the name disease — " vix morhi nomen.'^ Graves also held the same view, but he, at a later period, saw the disease change its aspect and become very fatal. It is not right, therefore, to repeat that the gravity of scarlet fever is de- pendent on the race, since the disease was formerly benign. Nor can it be attributed to climatic modifications, for the English, when in France, are attacked by serious scarlet fever, while the French going to England develop a benign form. Veterinary medicine, even more than human medicine, furnishes numerous instances of predisposition and immunity characteristic of race. Algerian sheep are refractory to anthrax, and the black sheep of Bretagne are immune from murr. This last example brings us back to human medicine. Dr. Landouzy has much insisted on the frequency of tuberculosis among those inhabitants of Paris who present the char- acter of the Venetian type — that is, fine skin and reddish hair. If we pass from race to family, we meet with similar facts. There are families in which tuberculosis, or diphtheria, or erysipelas is notably frequent, and we speak, of course, only of cases of infections which develop without family contagion. There exist also numerous individual variations; persons have often exposed themselves to contagion, even to inoculation, without being contaminated. Vaccine has failed in a great number of cases. GENERAL ETIOLOGY OF INFECTIONS 139 So in laboratories we see from time to time an animal that resists, while others apparently similar, placed iinder identical conditions and inoculated in the same way, all succumb. In certain cases individual immunity may be explained by what has been very justly called insensible vaccination. The inhabitants of Paris, for instance, do not, as a rule, contract typhoid fever; but indi- viduals arriving from the country are often attacked by it. It is be- cause Parisians, from infancy, have been little by little impregnated with the morbid germ; thus becoming progressively habituated, they have either experienced no disturbance at all, or symptoms too slight and vaguely characterized to be attributed to their true cause. It is in this way we must explain the disappearance of epidemics; if the cases, at a given moment, grow less and less grave and more and more infrequent, it is because, little by little, the population has under- gone an insensible vaccination. The incontestable immunity of physi- cians is due to no other cause. We may ascribe to an analogous process the fact that an infection gradually loses its gravity in the course of centuries, or acquires an unusual malignancy when invading a population until then spared. Nothing is more interesting and instructive in this connection than the epidemics of measles of the Faroe Islands. The disease was imported there in 1846. Of the 7,782 inhabitants, 6,000 were attacked, only the old being spared. In 1875 the same disease invaded the Fiji Islands, and caused the death of 40,000 persons out of a population of 150,000. The resistance and predisposition of certain subjects are sometimes explained by their heredity. The sons of an arthritic person are pre- disposed to a series of nutritive affections, but they are refractory, or at least less susceptible, to tuberculosis. In certain cases, an individual comes into the world with an innate tendency, quite different from heredity; its cause is generally a par- ticular state of the parents at the moment of conception, and the state of the mother during gestation. We have observed, for example, a man and a woman of uncommon strength who had had three chil- dren : the firstborn and the youngest were very well constituted and had inherited the temperament of their generators ; the second was poorly developed, remained feeble, and at the age of twelve years contracted a tuberculosis of which he died. Why did this child present such an inborn diathesis ? Why had not the hereditary characters been trans- mitted ? Simply because at the moment of conception the father was convalescent from pneumonia, and this accidental sickness had suf- ficiently disturbed his organism to modify his progeny. Is there not in this observation, as conclusive as an experiment, the explanation of many a fact concerning family and race modifications ? 140 CAUSES FAVOURABLE TO INFECTION The aptitude for contracting infectious diseases varies considerably with age. During intra-uterine life the foetus is exposed to some dis- eases whose germs are transmitted through the placenta ; such are espe- cially syphilis, variola, septicaemia, exceptionally tuberculosis and typhoid fever. We shall again refer to these facts in the chapter on heredity. At the time of birth the individual presents a sufficient resistance to the majority of infections : vaccine does not take, eruptive fevers are altogether exceptional, also typhoid fever and diphtheria. This immu- nity should not, however, be exaggerated; the newborn catches ery- sipelas very easily, which localizes itself usually in the navel and is almost invariably fatal. It is especially during second infancy that infections are frequent. It may even be stated that at this epoch of life the tissues are particu- larly liable to let the parasites multiply. Pityriasis, for instance, has no hold on the aged and is spontaneously cured with the progress of years. With age, the frequency of infectious diseases diminishes; in the old, hardly any but vesical infections and pneumonia occur. One might suppose that the immunity of old age depends upon previous maladies and insensible vaccinations. The explanation is unsatisfac- tory; a certain part must be played by the modifications developed in the chemical constitution of the tissues and humours. This view is supported by the fact that, when measles prevailed in the Faroe Islands, only the old were spared by the disease; in this case, insen- sible habituation is out of the question, since the disease was unknown up to that time. The influence of sex is by no means less interesting. It seems that women are for a longer time than men predisposed to the infections of childhood. The eruptive fevers, notably varicella, extremely rare among men after twenty, are frequently observed among women be- tween twenty-five and thirty years of age. It is, above all, the different acts of genital life that give feminine pathology its peculiar character. Menstruation may be an occasional cause of infectious manifestations. Not to speak of herpes, whose nature is not well known, erysipelas, in some cases, appears at each period. Facts of this kind are seldom observed in hospitals, for men- strual erysipelas is benign ; it lasts two or three days and hardly neces- sitates a cessation of work; it thus returns for years. Certain women may have as many as 50 and 60 relapses. Pregnancy may modify the course of certain infections; in some cases it impresses them with a character of malignancy (infectious jaundice runs its course under the form of grave icterus) ; in other GENERAL ETIOLOGY OF INFECTIONS 141 cases it retards and may even momentarily stop their course. Not infrequently tuberculosis seems to stop, and, after confinement, the scene changes, the disease assuming a more rapid course. Last of all, we hardly need recall the frequency of puerperal infections. In this instance, however, the disease presents nothing special; the confined woman is in the same situation as a wounded one; it even seems, ac- cording to the researches of Straus and Sanchez-Toledo, that the uterus of the parturient opposes still a sufficiently strong resistance to infectious germs. All violations of the laws of hygiene predispose to infections. We have already spoken of the noxious effects of great agglomerations. In intrenched camps infections are frequent; they are equally so in armies in the country. It is always the same diseases that occur: scurvy, dysentery, typhus fever. The frequency varies with wars — ^in the Crimea, out of an effective of 309,000 men, 75,000 suffered. Crowding in prisons acts in the same way. Not many years ago deadly epidemics were of frequent occurrence in hospitals, decimating the convalescents ; in the wards devoted to cases of measles, pulmonary infections propagated to the despair of physicians. Mortality has greatly diminished since isolation has been practised. The infiuence exerted by previous or actual diseases is familiar. Some of them predispose to infections : Diabetes favours the develop- ment of pyogenesis of the tubercle bacillus; pneumonia, erysipelas, rheumatism, far from conferring immunity, predispose to new attacks. In most cases infections create a refractory state and prevent future attacks. But immunity is never absolute, save, perhaps, in the case of syphilis. Among causes which intervene to lessen for a moment individual resistance, it is well to note fasting and fatigue. The influence of fasting is evident ; it is a matter of common obser- vation, which has found a scientific confirmation in the experiments of Canalis and Morpurgo. More interesting is the role of overworJc. It has long been recog- nised by veterinarians that anthrax and glanders attack specially the overworked animals. It was once believed that excess of muscular work sufficed to create disease; it is known to-day that it only pre- disposes to infection, either by diminishing resistance to surrounding germs or by allowing the development of microbes contained in some point of the economy. That is what occurs in glanders ; before the fa- tigue, the animal supported, without any disturbance, some rare nodes. In human medicine examples abound. The fatigues imposed on troops lead to the development of various infections, from t)rphoid fever to tuberculosis. Do we not know that students of medicine do 142 CAUSES FAVOURABLE TO INFECTION not contract the infections to which they are daily exposed, except when they are weakened by fatigue or excesses ? The overworking of an organ may even explain certain clinical forms. Cerebral rheumatism is rare in hospitals, because it occurs only in individuals addicted to intellectual activity, in those whose nervous system has suffered from late hours, excesses, ambition, and disappointments. Likewise, in young subjects, growing bones are predisposed to microbic localiza- tions, as expressed by the development of osteomyelitis. Conversely, a nonactive organ does not present a rallying point for microbes ; chil- dren suffering from mumps do not develop orchitis; this localization is not observed until after puberty. External agents whose role we have already pointed out may inter- vene to favour the development of infections. We have already stated that great traumatisms, lacerations, and extensive contusions considerably diminish resistance to microbes. Inhalation of solid particles, such notably as silica and ferruginous dust, may produce small pulmonary erosions favourable to the devel- opment of tuberculosis. Among physical causes are to be cited, first, cold and heat. The action of these two factors is really very complex, and it is not by modifying our bodily temperature that they act. The fact that the chicken, by nature immune from anthrax, contracts this infection when it is exposed to cold, and that, on the contrary, the frog loses its immunity when it is heated, is not due to the modifications of the organic temperature thus produced in these animals. The immunity of the chicken is not due, as some had believed at first, to the fact that the bird possesses a temperature too high to permit the develop- ment of bacilli, for the pigeon is not endowed with the same power of resistance. The frog is refractory to anthrax, not because its tem- perature is too low, for the toad contracts the disease. In reality the phenomena are more complex; when the chicken is exposed to cold or the frog to heat, a whole series of modifications are provoked : nutri- tion is disturbed, the life of the cells, and consequently the constitu- tion of the humours, is altered, the nervous system, the heart, the leuco- cytes are acted upon. The abolition of immunity is the resultant of manifold factors. It is also through a very complex mechanism that cold or heat occasions in man the development of infections. Cold, for instance, does not act by subtracting heat, for its influence is at times too quick. It is often said that by provoking a cutaneous anaemia it determines a visceral congestion, which weakens resistance. This theory is not plausible. It is well established to-day that active congestions, far from favouring, hinder infections; it is anaemia that diminishes the GENERAL ETIOLOGY OF INFECTIONS 143 means of protection. It is then probable that peripheric cold produces pulmonary anemia, and that the blood is simply driven into the ab- dominal vessels; the congestion discovered after an attack of cold is already a reactionary phenomenon. A good many of the chemical substances, including those known as antiseptics, diminish the resistance of the tissues and favour the de- velopment of microbes. So the tendency is in surgery to substitute more and more asepsis for antisepsis. General intoxications play the most important part. Numerous clinical and experimental facts dem- onstrate that alcohol, chloroform, and chloral promote the development of infections. The inhalation of deleterious gases has a similar effect; it favours general infection or the invasion of the lung. It is well known that broncho-pneumonia may be produced by carbonic oxide, as pulmonary gangrene by the gas of cesspools. In being eliminated through the mucous membranes certain poisons destroy the epithelium and open the door to infectious agents. Mer- curial stomatitis is due to the development of microbes contained in the mouth; hence the conception that it may be cured by means of antiseptics, by washing the mouth with the liquor of Van Swieten; hence also the possiblity of its being sometimes transmitted "by con- tagion. The microbes of the buccal cavity are exalted to the point of overcoming the resistance of the normal tissues. The same mechanism presides over the development of mercurial enteritis ; this is also a case where mercury, in being thrown off through the intestines, has simply facilitated the invasion of the mucous membrane by ordinary bacteria. The more we study pathology, the greater we find the intervention of microbes in the majority of toxic processes. Hepatic cirrhosis is justly attributed to the action of alcohol; but it is possible that the poisons act simply by permitting the invasion of the liver by the microbes of the intestine; the sclerous process would be, in the last analysis, of infectious origin. We must recall also that, of the causes already considered as favouring infections, not a few act by inducing auto-intoxications; diabetes, as well as overwork, are of the number. One of the chief causes influencing infection is infection itself: there are microbes that invite each other, unite and help one another. We thus come to the study of microbic associations. MiCROBic Associations Here is, in the first place, an experimental fact which is of a char- acter to bring home to you the interest of the process. Take a culture of Bacillus prodigiosus — namely, a simple sapro- phyte — remarkable only for the beautiful red colour it gives the me- 144 MICROBIC ASSOCIATIONS dmm in which it develops. Inject a few drops of it beneath the skin of a rabbit; no trouble whatever will result. Then take a culture of symptomatic anthrax — that is, an anaerobic bacillus which produces in certain animals a gaseous gangrene (page 112) ; but the rabbit enjoys a natural immunity against this microbe, of which it can receive injections with impunity. Here, then, are two bacteria, both harmless for the rabbit. Take now a third rabbit; inject into it a mixture of the two cultures: gaseous gangrene will develop and entail a speedy death. Thus, two microbes which, taken separately, are harmless, occasion a deadly disease when they are united. In this instance the mi- crobe that favours the infection, Bacillus prodigiosus, acts by a soluble substance, which glycerine dissolves and alcohol precipitates, which resists a temperature of 120°, and, by all these characters, resembles peptotoxine. One drop of this injected into the veins of a rabbit of 2,000 grammes is sufficient to abolish its natural im- munity. Many analogous examples might be mentioned. Attenuated cul- tures of streptococcus or pneumococcus recover their virulence when they are mixed with the soluble products of Bacillus prodigiosus or of putrefaction bacteria; in the same way colon bacillus promotes the development of the typhoid bacillus. So far the results are perfectly concordant; we shall see presently some complicated facts. Let us take a culture of Bacillus anthracis — namely, of true an- thrax, which should not be confounded with the symptomatic anthrax above referred to. We are now dealing with a microbe which is equally pathogenic both for rabbit and guinea pig. Let us inject into ani- mals of these two species a few drops of an anthrax culture mixed with a living or sterilized culture of Bacillus prodigiosus. In the guinea pig the fatal termination will take place more speedily than if the anthrax culture alone had been injected; thus far the outcome is not surprising. In the rabbit, the anthrax infection will be thwarted and the animal will survive. Thus, the very same microbe. Bacillus pro- digiosus, according to the agent with which it is associated and the animal which is operated up^on, behaves altogether differently. This last result leads to a new conclusion: there are some microbes which hinder infection. These experiments will presently enable us to interpret clinical facts. Three different microbic associations may be observed in man: (1) Two infectious diseases develop side by side without influencing each other; (2) in some infections microbic association is the rule and GENERAL ETIOLOGY OF INFECTIONS 145 gives to the clinical tableau its peculiar aspect; (3) the superadded infection constitutes a true complication. The first eventuality is realized when two eruptive fevers coexist in one individual. Measles, scarlet fever, varicella, and smallpox may combine without influencing one another; likewise, vaccine and small- pox may develop together, as may measles and whooping cough. Each disease runs its course on its own account, as if it were alone. In other cases one disease starts, the other later follows it. To take a simple example, we shall cite vaccinal syphilis. Syphilis and vaccine are inoculated simultaneously; the vaccine pustule appears first, and when its evolution is over, instead of disappearing, it hard- ens and is transformed into a chancre. Likewise, the mixed chancre is due to the simultaneous inoculation of the viruses of chancroid and syphilis; the soft chancre, whose incubation is shorter, develops with its habitual features, and, later, is transformed into a hybrid lesion. Cases of pneumo-typhus may also be mentioned. The mixed infec- tion begins as a pneumonia; afterward, toward the ninth day, defer- vescence takes place, but, instead of being perfect, it is incomplete ; the fever changes its type, the typhoid infection, masked until then by the pulmonary infection, becomes apparent, and from that moment runs its accustomed course. Let us now come to the more interesting cases in which two microbes unite and constitute what is called, in natural history, a symbiosis. Thus, the germs of tetanus and of gaseous gangrene can not, if they are isolated, overcome the resistance of healthy tissues; they need the assistance of pus cocci, even simple saprophytes. That is just what happens when one is wounded by a dirty instrument; if the tetanus bacillus and that of gaseous gangrene are present, they will be able to develop only by the aid of the various bacteria that accompany them. Another example is afforded by the study of smallpox. The spe- cific agent of this disease is unknown, but it is evident that at a given moment the eruptive elements are invaded by pus cocci, markedly by staphylococci. The symbiosis is so very intimate that, if the organism be modified by a vaccination, the suppuration is cut short; the erup- tive elements become crusty and heal, whereas in the nonvaccinated an abundant suppuration sets in. The mere fact, therefore, that resist- ance against one of the microbes is strengthened has sufficed to hinder the development of the other. There are diseases in which microbic associations are well-nigh constant; they are almost inevitable when the process occupies parts largely exposed to the contact of air. In all the infections of the mouth the principal microbe is found united to numerous bacteria. 146 MICROBIC ASSOCIATIONS Diphtheria, for example, is never pure; in some cases the association of microbes plays but a very limited part and has hardly any effect on the final result, but none the less it exists. The same is true of the infections of the digestive canal: in cholera, typhoid fever, or dysen- tery the process is equally complex. Finally, in tuberculosis, at least at a certain period, numerous microbes invade th-e lungs and modify the clinical evolution : the tuberculous becomes a pyaemic patient. The third eventuality is realized in the very numerous cases where a second infection ingrafts itself upon a principal disease; boils, sup- purations, parotiditis, gangrenes — observed so often in the course of, and especially during convalescence from, grave infections — are due to common bacteria which have invaded the organism owing to the weak- ening produced by the chief disease. It is even possible that certain relapses are in reality only secondary septicaemias and not repetitions of the first infections. We may cite also the secondary infections of gonorrhoea, notably the arthropathies, which are caused by the common pus cocci; the pneumonias of erysipelas, which are almost always owing, not to the principal agent, but to pneumococcus ; the broncho-pneumonias of measles, the nephritis of scarlet fever, the endocarditis, arteritis, and phlebitis, which are, in the majority of cases, due to some superadded process. The secondary infection may sometimes modify the evolution of the principal disease to such an extent as to create a clinical form altogether special. Such is the case with hemorrhagic smallpox, whose very peculiar symptoms are due to an additional septicaemia — namely, the intervention of streptococcus. No wonder if vaccination, under such conditions, is of little efficacy; it does not insure against the secondary infection. These few examples, which could easily be multiplied, establish the fact that additional infections sometimes impart to the principal disease a particular course and a special character of malignancy; sometimes they represent simple complications, and sometimes ex- plain the development of new manifestations wrongly considered as relapses. Experimental pathology teaches us that, in some cases, microbic associations are able to exert a favourable action. Facts of this kind are very rare in human medicine; it is admitted, nevertheless, that in the malignant pustule the pus cocci that are found in the lesion hinder the development of the anthrax bacillus. Erysipelas undoubtedly has sometimes exerted a favourable action; cases are known where, under its influence, lupus, ulcerating and chan- crous wounds and tumours, particularly sarcoma, have retroceded and GENERAL ETIOLOGY OF INFECTIONS I4.7 healed. These facts have led to the application of inoculation with streptococcus, or injection of its toxines, to the treatment of these dis- eases. Some encouraging results have been reported. It seems that in all these cases the microbe of erysipelas acts by giving rise to an in- flammation — that is, by stimulating the slow organic reaction. Modes of Entrance of Microbes Microbes can penetrate by a great number of ways : First, through the skin; and we may well begin by inquiring whether the unbroken integument does at all permit the passage of bacteria. As a rule, it does not, but there are some exceptions. Anatomists are often at- tacked by small pustules, which develop where there is not the slight- est abrasion; the liquids of anatomical lacerations swarm with bac- teria, which have been able to invade a hair follicle. Garre and Zuck- ermann, operating upon themselves, have spread over their skin cultures of Staphylococcus aureus ; one of them developed an anthrax, the other a boil. Babes has likewise shown that the bacillus of glan- ders, incorporated with an ointment, passes through the skin of a guinea pig, at least when care is taken to rub the skin in such a man- ner as to facilitate penetration into the glands. Whether there be any small wound or not, microbes invading the skin often give rise to local and innocent manifestations only. Such is the case with the anatomical tubercle, which is readily healed by a simple curetting followed by iodoformic applications. Other forms of cuta- neous tuberculosis, including lupus, may give rise to terrible lesions, but, as a rule, scarcely disturb the health. The reason is, the bacillus does not find on the skin favourable conditions for development; the temperature is not high enough and the tissue is too dense. The anthrax bacillus, even in the most susceptible animals, such as the guinea pig, often produces nothing more than a curable lesion. If a culture is spread on the excised skin, nothing but a little oedema results, and that finally passes away. If the inoculation is made beneath the skin, the phenomena are quite different. Yet it is a fact that adipose tissue does not much favour the microbe; so that fat persons resist better than thin ones hypodermic injections of viruses. The profounder the inoculation, the greater are the chances for the infection to develop. The example of hydrophobia is, in this respect, altogether demonstrative. The mucous membranes, even when healthy, are more easily pene- trated by microbes than the skin. The tubercle bacilli can pass through the conjunctiva, the bronchial or intestinal mucous mem- brane, without leaving any trace of their passage; they proceed to locate themselves in the corresponding ganglia, in the neighbouring 148 MODES OP ENTRANCE OP MICROBES serous membranes, and excite specific manifestations which can not be traced to their origin. In other instances reactionary lesions break forth; pneumonia is the expression of the effort the organism makes for preventing the passage of the pneumococcus. Ingestion appears to be a less certain method of infection than inhalation. It is nevertheless through the alimentary canal that in- fection takes place in typhoid fever, in dysentery, or cholera, and some- times, especially with children, in tuberculosis. Hence arises the question whether the meat of infected animals is fit for consumption. To-day this question may confidently be answered : When there is gen- eralized infection, as in cases of anthrax and glanders, the seizure of the meat should be ordered. As regards tuberculosis, which is ob- served in 3.8 per cent of cattle slaughtered at Villette, the use of the meat is allowed when the lesions are local. It has been asserted also that milk propagates tubercular infection; but this liquid contains no bacilli unless the mammary glands are affected or the infection is extensive; therefore milk seems to be less dangerous than had at first been thought ; and is the less so as it is mixed with noncontaminated milk, for the dilution of the virus diminishes the chances of contagion. Infection by the genito-urinary passages, if we except venereal diseases, such as gonorrhoea, syphilis, and soft chancre, is quite rare. Under normal conditions, microbes do not go beyond the navicular fossa in men. In women they are very abundant in the vulva and vagina. But when pathogenic agents, such as streptococcus, are intro- duced into this canal, the germicidal liquids secreted by the mucous membrane destroy all the germs within forty-eight hours (Menge). At the time of confinement the resistance of the genital organs grows still stronger. Straus and Sanchez-Toledo established that the anthrax bacillus, introduced into the vaginal canal of a female guinea pig having just brought forth little ones, produces no trouble whatever in this animal, by nature so sensitive to anthrax. In the human species resistance is as well marked, for puerperal fever is, on the whole, quite rare; it is altogether exceptional in the country, notwith- standing the fact that the parturients take very few antiseptic pre- cautions. The serous membranes represent another entrance, open at times to infection; but despite oft-repeated assertions to the contrary, they are very well defended. Hence the possibility of great surgical operations ; for, in spite of all the precautions taken, morbid germs are always introduced; they are constantly found beneath the dressings. They are, however, in too small numbers to overcome the resistance of the organism. GENERAL ETIOLOGY OF INFECTIONS 149 Lastly, another passage for infection is the nervous system; the agent of hydrophobia propagates through the nerves, as has been admitted by Duboue, of Pan, on the basis of clinical experience, and as numerous experimental researches have demonstrated. In this manner the virus reaches the nerve centres; therefore, the nearer the affected nerve is to the bulb, the shorter the period of incu- bation; and furthermore, the first manifestations will vary with the region primarily contaminated. Protection" of the Organism against Microbes When microbes have passed the first barrier, and been introduced at some point of the economy, they will multiply and secrete injurious substances. Then three results are possible. 1. The microbe is not virulent, the leucocytes rush up and soon destroy it. Sometimes spores persist for a certain time, as when Ba- cillus suhtilis is injected, but they produce no disturbance. 2. If the microbe has a pathogenic action, a struggle is entered into at the point where the invasion is made; liquids are exuded, leu- cocytes come out of the blood vessels; a local lesion is formed which will endeavour to circumscribe the infection. 3. Lastly, when the microbe is very virulent, the organism is, as it were, struck with impotence; the cells which attempt to approach the pathogenic agent are repelled by secretions credited with a power called negative chemiotaxis ; the local lesion is wanting ; general infec- tion is produced. Whether or not a local lesion be created, the microbes penetrate always beyond their point of entrance, following either the lymphatic or the venous path. If they get into the lymphatic vessels, they meet with ganglia which can stay their course. The function of these little organs is revealed by some experimental researches and numerous clinical obser- vations. In the course of the most diverse infections — acute, subacute, or chronic inflammations, suppurations, as well as anthrax, tuberculosis, or syphilis — we observe the swelling of the ganglia corresponding to the affected regions. Modifications take place in them, analogous to those occurring at the point of inoculation; the cells rapidly multiply, and, in acute cases, a very extensive periganglionic exudation is sometimes produced. The lymphatic glands, especially in regions where they form chains, represent veritable fortresses which stop, finally or temporarily, the pathogenic agents. 150 PROTECTION AGAINST MICROBES The other lymphoid productions play a similar part. The fact is demonstrated with respect to the tonsils; it is equally certain for the closed follicles, isolated or agminate, that are found at the surface of our mucous membranes. This conception can even be extended to the serous membranes. Anatomists have described in these membranes formations which, by their arrangement and structure, represent ganglia flattened out, as it were. Such an organ is, for instance, the great omentum. Direct ex- periment demonstrates the protective role of this membrane. To be convinced of this, extirpate the omentum in rabbits and guinea pigs. Later, after a period of a month or two, inject into the abdominal cav- ity of the animals thus operated upon a few drops of a virulent culture of Staphylococcus aureus ; death supervenes in twenty-four hours, or at the latest within two or three days. Controls of the same weight, who, to make the conditions identical, have been subjected to a simple lapa- rotomy, receive the same amount of culture and all survive. It should not be concluded, however, that the suppression of the great omentum entirely destroys the resistance of the peritoneum. For the animals operated upon survive if they receive a very small dose of a virulent culture, or if an attenuated microbe be employed. In repeating the inoculation, however, we notice that the animal de- prived of the omentum is growing thin and cachectic, and finally suc- cumbs, while the control animals manifest no disturbance whatever. The role of the omentum must be especially marked in the young, because, with years, a fatty infiltration occurs that diminishes its activity. It is, however, in children that the peritoneum is frequently threatened by microbes, which swarm in the gastrointestinal canal, and so often cause inflammations there. Similar protective arrangements are likely to be met with in the other serous membranes ; but no experiments have been undertaken on the subject. Microbes invade the blood, either after having passed through the lymphatic glands or by directly penetrating into the capillaries or veins. If they enter by way of the stomach or intestines, they reach the portal vein and successively pass through the liver, right heart, lungs, and left heart, to be thrown thence into the general circulation. In all other cases they pass first through the lungs. No matter by what way they enter, the microbes that have reached the general circulation rapidly disappear from the principal vessels; at the end of ten or fifteen minutes they are no longer found in them, even when intravenous inoculation has been practised on the animal. The blood then represents an inhospitable medium for bacteria, which must abandon it and take refuge in the capillaries of the organs. GENERAL ETIOLOGY OP INFECTIONS 151 Here the battle between the organism and the pathogenic agents is fought out; the latter begin to multiply and secrete toxic substances, which should insure them victory, while the cells of the body en- deavour to exert their protective role, either by manufacturing germi- cidal or antitoxic products, or by picking up and digesting the microbes. Two hypotheses are possible. It may be assumed that the various phases of the struggle are alike in all the capillaries ; in which struggle, as the case may be, the microbe or the organism would triumph, and the ultimate result would be the sum of the partial results of the same character. Or it may be supposed that the phenomena vary from one capillary network to another; that the effects of the struggle are not the same in all the organs, but in some of them the microbe is victori- ous, in others the cell. If so, the phenomena become more complex; the final result will be the sum of the partial results of the different kinds. These theoretical considerations lead to the question whether there do not occur differences in the evolution of infectious diseases accord- ing to the vessel by which the culture is introduced. Protective Role of the Organs. — In most cases the experimenters inject the microbes through some peripheral vein; then the pathogenic agent first passes through the capillaries of the lung, to reach after- ward the general circulation. In order to bring out clearly the role of the pulmonary capillaries, an injection must be made at the very origin of the aorta ; for this, it suffices to introduce a cannula by the central end of the right common carotid. The differences which will be presented by the development of the disease in the two cases will enable us to appreciate the function of the lung. In other experiments the injection will be made by a branch of the portal vein to ascertain the action of the liver; by the distal end of the carotid artery to study the influence of the brain; by the femoral artery to notice what occurs in the less highly organized tissues. The results vary with the microbes employed. With anthrax cultures the animals inoculated by the aorta suc- cumb first; those injected through the peripheral veins survive a little longer, which indicates a slight action on the part of the lungs. But this protection is of little importance and vanishes when the virus is very active. Lastly, the injections made by the carotid allow a sur- vival somewhat longer than the intravenous inoculations. Thus far the dift'erences are not considerable : if some animals resist longer than others, all succumb ultimately. Altogether different are the results when the anthrax passes through the liver; thus, out of twelve animals having received con- 11 152 PROTECTIVE rClE OF THE ORGANS siderable doses of anthrax culture by the portal vein, only three have succumbed. The liver, then, has the property of arresting and killing the anthrax bacteria; it plays a very important part in the protection of the organism against anthrax infection. With a very virulent cul- ture, a dose of half a cubic millimetre injected through a peripheral vein kills a rabbit of 2 kilogrammes in thirty-eight hours. A dose of 8 cubic millimetres introduced through a portal vessel is incapable of killing a somewhat smaller rabbit. That is to say, a quantity of an- thrax bacilli 64 times that which is fatal by the peripheral veins is completely annihilated by the liver. The protective action of the liver, which is so conclusively shown by these experiments made with the anthrax bacillus, is just as easy to demonstrate with the Staphylococcus aureus. Let us take a virulent sample, and, after diluting it in bouillon, inject it, as we did anthrax, through five different vessels. Contrary to the preceding results, the animals inoculated through the distal end of the carotid artery succumb first; the brain therefore represents an excellent medium of culture for staphylococcus. Next, the animals injected through the aorta or femoral artery perish. Those that have received the virus through peripheral veins survive longer; those that have received it by the portal vein resist inoculation. However, the liver acts with less energy upon staphylococcus than upon the anthrax bacillus; it neutralizes 8 fatal doses, instead of 64. If we now pass to streptococcus, we find quite different results. The liver has no longer any power of protection; the microbes find in its parenchyma excellent conditions for vegetation, and animals in- jected through the portal vein are generally the first to succumb. A little later die those that have been inoculated through the aorta, the carotid, or the femoral artery. As to animals injected through the peripheral veins, they die slowly, or, if the virus be not a very active one, they may survive. The lung then represents a protective organ against streptococcus; it fulfils a role analogous to that exercised by the liver against Ba- cillus anthracis or Staphylococcus aureus, except that it destroys pathogenic agents with less energy; the lung hardly neutralizes more than one deadly dose. With colon bacillus the results are very variable. Experimenting with a microbe drawn from dysenteric stools, we have found a mani- fest action of the liver. On the contrary, in previous researches, pur- sued with another sample, the animals inoculated by the portal vein or the carotid artery succumbed first. The liver, far from destroying this microbe, affords it an excellent medium of culture. This result, while very deceiving from a teleological point of view, accounts well GENERAL ETIOLOGY OF INFECTIONS 153 for the frequency and gravity of hepatic infections of gastrointestinal origin. With the bacillus of dysenteriform enteritis, the results vary with the age of the culture. If the culture is recent — viz., if it is four or five hours old — it does not yet contain any toxines ; the liver then exercises a protective role: it arrests and destroys the microbe. If the culture is several days old, toxines have been produced in abundance; they annihilate the action of the liver and alter this gland; consequently the animals inoculated through the portal vein succumb first. Thus the liver acts upon the bacillus ; it destroys the figurate element, but has no action upon its products of secretion. Similar differences are observed in studying parasites of a higher order. Thus with cultures of Oidium albicans, the animals injected through the carotid perish first. The lung retards very slightly the course of the infection. The liver and kidneys arrest great numbers of the parasites and prevent the extension of the process; they pro- tect the economy very efficiently. The various results above indicated are summed up in the accom- panying tabular representation (page 154), showing in what order the animals succumb, according to the mode of introduction of the microbes. In brief, microbes injected in a blood vessel stop, in great num- bers, within the first capillary plexus they enter. This is perhaps but a mechanical phenomenon of molecular adhesion comparable to that which, in a porcelain filter, prevents the bacteria from passing through pores larger than themselves. It may be, however, that a vital process is called into play, an action of arrest exercised by the endothelium, for analogous phenomena occur when, instead of figurate elements, sol- uble substances are introduced ; injections made through different parts of the vascular system prove equally well the action of the organs both on poisons and on microbes. In both cases the most important role is that played by the liver. The action of this gland, however, is not exercised indiscriminately upon all the substances or all the bacteria that reach it; there are poisons which the liver retains and transforms, others which it allows to pass, and still others which seem to acquire in its interior an in- crease of activity. This is at least what results from the experiments of Teissier and Guinard on the diphtheria toxine. For microbes the results are the same : some stay there and perish, such as Bacillus anthracis, the staphylococcus, the bacillus of choleri- form enteritis, the oidium; others, as the streptococcus and colon bacillus, easily develop there and grow stronger. The action of the liver is more marked on microbes than on poi- 154 BACILLUS e3 O O o •I-l a. •1-1 P4 o I— t a P5 I M O -< o o to a •1-1 ■ 1— < ~, k. u ^ -u -;-3 t-l >s a^ 03 l-H d o 2 B o ed O) <1 O Pl4 • l-( o o3 O 03 O o a >■ o p^ 03 O <1 »4 o3 -^ ;-! o a 1— • c3 a> rd Pi • -H O) Ph a> O O o Ph eS u ed o p o u o o o Si -^•9 03 a O O (X) c3 (» o u ►i:^ fe J ^ e9 GENERAL ETIOLOGY OF INFECTIONS 155 sons. When a toxic alkaloid is injected through a portal branch, the animal experimented upon is killed, provided the dose introduced be double that which is fatal by way of peripheral veins. As to microbes, we have seen that the liver arrests 64 fatal doses of anthrax and 8 fatal doses of staphylococcus. Its action is then much more important, or at least more marked, in infections than intoxications. Furthermore, experiments demonstrate that other organs may also serve to protect the organism against infections. Such is the lung, which acts in a certain measure on the bacteridia of symptomatic an- thrax and upon the staphylococcus, and exerts an action still more efficacious upon the streptococcus. Moreover, the kidney can retain the oidium and prevent the dissemination of this parasite. We see, furthermore, from the experiments above reported, that blood is not a hospitable mediuna for microbes; the few which succeed in passing through the first capillary network do not circulate long; they lodge in the various organs, so that in a few minutes the blood again becomes sterilized. The localization of bacteria is controlled by the following three conditions : The mode of entrance, of which we have sufficiently shown the importance; the physiological and pathological conditions of the organs, of which we shall presently say a few words. The Causes which Explain Microbic Localizations Bacteria which have passed through the capillaries of the first organ encountered, and which circulate for a moment in the blood, have a great tendency to settle in parts endowed with a strong nutri- tive or functional activity. In the young they stop in the growing bones; but they always spare those organs, such as the testicles and ovaries, which have not yet entered upon active life. In the case of an individual who has overtired an organ — ^the brain, for example— the localization will take place in that organ. It is possible to fix at will the microbes in this or that part of the organism by producing traumatic or other lesions ; by weakening the resistance of a tissue we favour its colonization by pathogenic agents. We have already mentioned the well-known experiment of Max Schul- ler ; a traumatism at the knee of a guinea pig is followed by the devel- opment of a white swelling (tumeur hlanche) if, at the same time, tuberculosis be inoculated. Clinics abound in similar examples. Parents always trace the beginning of a coxalgia, a tubercular menin- gitis, or a Pott's disease to a blow received by their child or to a fall. The observation is often just; but the blow or the fall is not respon- sible for the lesion; it has only favoured the development and local- ization of tubercle bacilli, which were already present in the organism. 156 CAUSES WHICH EXPLAIN MICROBIC LOCALIZATIONS When microbes are localized in an organ or tissue, the struggle begins. The final result will depend upon the forces of each of the two parties present. It is readily understood that all causes disturb- ing the state of health — various mechanical, physical, chemical, or ani- mate agents ; bad nourishment, fasting, overwork, excesses — in a word, all the conditions which we have found to be favourable for the devel- opment of infections, are also those that will render their evolution more serious. In the case of microbes, we must first consider their number. It is altogether exceptional that a single microbe should be able to pro- duce a disease, though the case may be realized with extremely virulent anthrax cultures : one bacteridium kills a young guinea pig. In most cases, to overcome the resistance of the organism, large numbers of microbes are required. Thus the guinea pig, of all animals the most susceptible to tuberculosis, does not catch the infection unless 820 bacilli are introduced beneath its skin. This figure may already seem quite considerable; but with the pyogenics the required numbers are much greater. Operating with Proteus vulgaris , Watson Cheyne states that 5,000,000 to 6,000,000 microbes injected beneath the skin do not produce any lesion; 8,000,000 cause the formation of an abscess; 56,000,000 give rise to a phlegmon, to which the animal succumbs within five or six weeks; to cause death within twenty-four or thirty hours, 225,000,000 must be injected. The same author has studied the action of the staphylococcus upon the rabbit: for producing an abscess, 250,000,000 microbes are re- quired; for causing death, one milliard (1,000,000,000) is the requisite number. In all these experiments the microbes were injected beneath the skin. By varying the mode of entrance, different results are obtained. To occasion suppuration by Staphylococcus aureus, it has been neces- sary, in the researches of Herman, to inject 4 to 5.3 centimetres of the culture into the peritoneum, 0.75 to 1 beneath the skin, 0.25 into the pleura or arachnoid, 0.05 into the veins, 0.0001 into the anterior cham- ber of the eye. The anterior chamber is then the least protected part of the organism. The same is demonstrated also by the study of symptomatic anthrax; this virus, harmless for the rabbit when in- jected hypodermically, causes speedy death when introduced into this part of the eye. The figures given by the authors have of course but a relative value; for virulence differs much with different samples and its vari- ations constitute undoubtedly the most important factor that we have to study. GENERAL ETIOLOGY OF INFECTIONS 157 Microbes become attenuated when they are kept outside of the organism. In our artificial cultures they rapidly lose their virulence. We can even hasten their attenuation by placing them in unfavour- able media. By maintaining the culture at too high a temperature, by subjecting it to the action of compressed oxygen, by adding to the medium antiseptic substances, we can reduce its pathogenic power pro- gressively. To increase the virulence, we must reverse the conditions — make inoculations in animals, cultivate the microbe in favourable media, above all in bouillon to which some blood serum or liquid of ascites is added. The procedure of inoculations in series, already employed by Davaine, has enabled this scientist to obtain a virus sufiiciently active to kill guinea pigs into which one millionth of a drop was in- jected. Similar facts are observed in clinics. One of the parasites which we carry, pneumococcus, for example, when exalted, gives rise to pneumonia; it then can by contagion infect a second person, and, thus transmitted, produce a little epidemic. Let us note, however, that a microbe exalted for one animal species is not necessarily so for oth- ers; every day we see streptococci having caused mortal diseases in man prove hardly pathogenic at all for animals. We have studied a sample of anthrax which, after successive passages in rabbits, had become, contrary to the rule, far more virulent for this animal than for the guinea pig. CHAPTER IX GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES The mode of action of microbes upon the animal organism — Importance of microbic toxines— Putrid poisons— Poisons produced by pathogenic bacteria — Principal bacterial toxines — Toxines produced by nonbacterial infectious agents — ^Mode of action of toxines : reactions excited by them. In order to understand in what manner microbes accomplish in- jury to the organism, three principal hypotheses have been advanced. The first, which no longer has any but an historical interest, as- sumed that an obstruction of the capillaries by bacteria occurred. It was a mechanical theory. Secondly, a struggle for life was assumed. It was held by those entertaining this view that the microbes and cells vied with each other over the alimentary materials carried by the blood and lymph. Which- ever of the two elements succeeded in appropriating the most, reduced the other to starvation. The third and modern conception seems to be established in indisputable proofs, and regards the infectious process as an intoxica- tion. According to this view, the microbes act through the agency of the soluble substances which they contain or elaborate. Putrid Poisons Before the pathogenic microbes were known — ^i. e., at an epoch when the animate nature of putrefactive agents was not even sus- pected — important results had already been obtained. In 1758, Seybert demonstrated that the putrefaction of pus, serum, and infusions of meat developed in these fluids a high degree of patho- genicity. At the beginning of the present century the remarkable researches of Gaspard, completed by Magendie, Virchow, Stich, and especially by Panum, conclusively established the existence of putrid poisons. The substances originating in the course of putrefactions are very great in number. Gases, fatty acids, aromatic substances, and amido 158 GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 169 bodies are encountered, which, however, are not sufficiently numerous or active to be taken into account. Next, we meet with albuminoid substances and bases analogous to vegetable alkaloids. Panum ad- mitted that putrid poison was of an albuminoid nature; on the other hand, most authorities held a contrary view, and their opinions seemed to be definitely established by the results obtained through the re- searches of Gautier, Selmi, and Brieger. The putrefactive bases were called ptomaines (Selmi), or, what was etymologically more correct (irrwjLto, TTTw/tAaTos, cadaver), ptomatines (Kobert). A great number of cadaveric bases are now known. Some of these substances are chemically well defined : methylamine, trimethylamine, triethylamine, propyl, butyl, amylamine, neuridine, saprine, cadaverine, putrescine, neurine, choline, gadinine, collidine, etc. Others are distinguished by their toxicity, and are sometimes named according to the analogy of their action with that of certain alkaloids — e. g., mydaleine, ptomatropine, ptomatomuscarine, ptoma- tocurarine, ptomatoconicine, ptomatoveratrine, tyrotoxine, etc. Ptomaines differ notably according to the time at which the prod- ucts of putrefaction are studied. Some appear and later disappear, to be replaced by others. The chemical researches which have made us acquainted with these results, however interesting they may be, should have been completed by bacteriological researches. It is a question whether these different ptomaines are produced at the various phases of life of the same microbes, or whether their successive appearance and disappearance depend upon different microbes, which destroy or trans- form the substances already produced by their predecessors. Even though we do not exactly understand the role of ferments in the genesis of ptomaines, we are better acquainted with the part played by the media in which they are produced. We know that cer- tain bases are encountered in all putrefactions — for example, neuridine. On the contrary, neurine is found only in the putrefaction of the flesh of mammalia, and muscarine only in the putrefaction of the flesh of fish. Similarly, it is at the expense of fish that gadinine, ethylendia- mine, and trimethylamine are formed. Dimethylamine has so far been found only in the putrefaction of gelatine or of yeast. Tyrotoxine is the poison which is formed in decomposed milk and cheese. Drs. Kostiurine and Krainsky very justly remark that the toxicity of the products of putrefaction is in direct ratio to the chemical complexity of the matters undergoing putrefaction — e. g., more poison is yielded by meat than by bouillon, and more by bouillon than by saline solutions, indeed, the latter not yielding any. Thus far all the results seem to harmonize and to lead to the admission that the putrid poisons are of alkaloidal nature. There has 160 PUTRID POISONS been some question, however, whether this conclusion was justified. Chemists have been reproached with having created, as it were, the substances they isolate, or at least with having dissociated the true toxic molecule, which is more complex and unstable. The ptomaine, it is objected, does not pre-exist in the putrid liquid ; it enters into the constitution of a proteid substance, from which it is driven by analyt- ical procedures. The true poison, therefore, is an albuminoid. In favour of this view may be mentioned a great number of researches demonstrating that when putrid matters are treated with alcohol the substances precipitated by this solvent are the most toxic. The ques- tion, therefore, is deserving of further investigation, which would probably lead to the discovery in putrid matters of toxines, some be- longing to the group of toxalbumins and others to the peptotoxines and toxalbumoses. Poisons produced by Pathogenic Bacteria The putrid poisons are of great interest, not only because some are constantly formed in the digestive canal, as has already been stated, but also on account of the fact that their study is a suitable introduction to the history of the poisons produced by pathogenic micro-organisms. Davaine thought that the anthrax bacillus secreted a substance which agglutinated the red blood corpuscles, and Pasteur confirmed this hypothesis in studying the effects of filtered anthrax blood. Tous- saint, Chaveau, and especially Gautier, argued in favour of toxic secre- tions of bacteria. Pasteur finally offered a basis of demonstration by establishing the fact that filtered cultures of the bacillus of chicken cholera produced transitory somnolency in birds — i. e., it reproduced one of the symptoms of the disease. This symptom, however, was of no particular interest, and Pasteur therefore refrained from concluding that the microbe acted by toxines. The idea of a microbic intoxication was, however, fully accepted when it was demonstrated that infectious agents are capable of pro- voking a fatal disease even though they remain localized at some point of the organism. Loeffler sustained this hypothesis with reference to diphtheria; Koch accepted it as regards cholera, and there was no logical escape from its adoption with regard to tetanus, symptomatic anthrax, and emphysematous gangrene. Then Brieger, prepared as he was by his studies upon ptomaines and putrefaction, extended his researches to pathogenic microbes. In the impure cultures of tetanus bacillus with which he worked, and in those of typhoid bacillus, he found various ptomaines which he studied from the standpoint of chemistry and toxicology. From that moment GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 161 the way was open. Investigators hastened to engage in research and described a great number of toxic bases of microbic origin. Serious objections, however, were soon raised. It was pointed out that the ptomaines as extracted from cultures are far less powerful than the total cultures, and fail to produce the same phenomena. Pur- suing the study of microbic poisons, it was recognised that the most active substances, as in the case of putrid poisons, are not soluble in alcohol, but precipitated by it. The tendency was then to attribute the toxicity of cultures to substances considered successively as fer- ments, peptones, albumoses, toxalbumins, globulines, proteines, nucleo- albumins, etc. The idea of comparing the microbic toxines with ferments is based on chemical and toxicological facts. Like ferments, (a) toxines are precipitated by alcohol; (h) adhere to precipitates of calcium phos- phate which are produced in the liquids containing them; (c) are destroyed by heat; (d) they act in infinitesimal doses. This compari- son is acceptable, especially at the present day when there is a tend- ency to consider the fermentative power as a physical property of mat- ter; the albuminoid substance serves simply as the substratum of a mode of energy. That it may be deprived of its power by means of various procedures, notably by heating, is quite conceivable. The con- ditions would be the same as in the case of a magnet. The magnetic property is one of a physical order ; the magnetized iron has no special chemical constitution. With this conception the ferment is a complex material which has received from the living substance a certain degree of energy, possessing, as it were, a part of vital activity. It is said by Buchner to be a semiliving substance. At any rate, it is the highest expression of matter destitute of life. Thus understood, the action of toxines is no more mysterious than that of ordinary ferments. What render the study of microbic toxines more difficult are the varying results obtained according to a great variety of circumstances, in but few of which precision is possible. The action varies with the same microbe according to different samples. As a rule, it increases as the virulence becomes greater. The effects are modified in the same sample according to the cul- ture medium. The more complex the medium, the greater the amount of toxines produced. In this respect nothing is as good as the natural organic fluids, such as blood serum and ascitic fluid, under which con- ditions virulence is best preserved. In the same culture toxicity varies with age — i. e., with the time elapsing since the inoculation. Very often it increases steadily with age; in other instances the reverse is true. ISTo definite rules can be 162 POISONS PRODUCED BY PATHOGENIC BACTERIA fornmlated in this respect any more than with reference to the action of heat or air. The diphtheria bacillus, for example, produces more poison in well-aerated bouillon, while the reverse is true of the strepto- coccus. The variability of the results depends partly upon the plurality of toxines. In fact, there are toxic substances which exist in the bodies of bacteria. These are the proteines or nudeo-alhumins, which are dif- fused in the medium when the culture grows old — namely, when the microbes are destroyed and disintegrated. On the other hand, the medium contains substances which are in part due to a secretion of the bacteria themselves. Others are formed either by destruction of nutri- tive materials or by synthesis. These are the toxalhumins, the toxal- humoses, and the toxopeptones. As to the ptomaines, they are grad- ually being recognised as derivatives of true toxines. When introduced into a living organism, toxines do not at first produce any disorder. A period of latency elapses, varying from a. few hours to several days, before the appearance of morbid phenomena. On the other hand, with the poisons derived from true toxines — ^for example, the ptomaines — the manifestations are of immediate occur- rence, exactly as is the case when a vegetable alkaloid is injected. It has therefore been supposed that the primary poison is decomposed in the organism and parts with its toxic radical. This hypothesis is apparently quite plausible, since alkaloids are found in the urine; at any rate, substances which have an immediate action are detected there. However, this conception should not be admitted in all its sim- plicity, for the phenomena are probably more complicated, and the total toxine has perhaps already caused profound modifications in the organism. In general, it is difficult to say what are the phenomena provoked by toxines. The manifestations evidently vary from case to case. However, the events may be divided into three groups : (a) Some are seen at the point of introduction of the substance; these are the local manifestations. (&) Others express the impregnation of the entire economy; these are the general manifestations. (c) Finally, others point to a selective action on certain organs, apparatus, or tissues. Toxines may provoke at the point of introduction a lesion similar to that produced by the agent from which they are derived. First an inflammatory oedema is produced. For example, the erysipelas poison, like the living streptococcus, produces oedema in man as well as in animals — a fact convincingly manifested in subjects into whom steril- ized cultures of streptococcus were injected for therapeutic purposes. GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 163 Next, we have the suppuration so easily produced by the soluble prod- ucts of the streptococcus, staphylococcus, and gonococcus. Dr. Christ- mas injected into a normal urethra a trace of gonococcus toxine and produced a purulent discharge, which, however, disappeared within a few hours, as he did not continue to deposit the irritating substance on the mucous membrane. Likewise, the necrosis characterizing gangrene is induced by sol- uble products, as is proved by subcutaneous injections of toxines de- rived from the bacillus of emphysematous gangrene. The same is true of pseudo-diphtheritic membranes, which may be produced by intro- ducing into the trachea a few drops of the toxine generated by the Loeffler bacillus. In this manner all the local processes attributable to microbes can be reproduced by means of the toxines freed of the living germs. The general phenomena are due to the same mechanism. The injection of soluble products gives rise to fever with all its consequences — e. g., variations in combustion, respiration, and urinary secretion. When sterilized cultures of streptococcus are injected into man for therapeutic purposes, fever results, ushered in by chills and attended by general depression, dry tongue, and, in some cases, an often abun- dant outbreak of herpes labialis. The introduction of strong doses or repeated injections of toxines give rise to cachexia similar to that induced by prolonged infectious processes. Diarrhoea sets in, the cells of the organs degenerate, and death ensues from marasmus. In this respect the toxines of the tuber- cle bacillus are very interesting; they act like the microbe from which they are derived. If the course is slower, the manifestations may predominate in a viscus, thus constituting an affection which sometimes begins, and in most cases continues, long after the toxine injections have been suspended. In this way it is possible to reproduce visceral sclerosis, hepatic cirrhosis, nephritis, myocarditis, as well as paralysis and mus- cular atrophies often due to medullary lesions, predominating in the large cells of the anterior horns. Thus, toxines can reproduce all the lesions induced by microbes. We may, therefore, conclude that infection is but a chapter of intox- ications. Since microbes give rise to toxic substances during the course of diseases which they originate, some authorities have entertained the idea of searching for these poisons in the organism of the sick. The labours of Eumo and Bordoni have established their presence in the blood; Professor Bouchard's experiments have demonstrated their pas- sage into the urine. It should be remarked, however, that the phe- 164 PRINCIPAL BACTERIAL TOXINES nomena are in reality very complex. In an infected organism three kinds of poison are encountered : (a) The microbic toxines, engendered by the pathogenic agent. (&) The putrid poisons, originating in the intestine, where fer- mentations are often more intense than normally. (c) The cellular poisons, due to disturbance of assimilation, which is exaggerated and vitiated. If, in addition, the organs destructive to toxines are altered and incapable of fulfilling their role, which is often the case, we can under- stand how the sources of intoxication are multiplied. If the organism resists, it is owing to the fact that part of the toxines constantly escapes through the emunctories, notably by the kidneys; the urine becomes hypertoxic, and this hypertoxicity is a safeguard for the econ- omy. In many cases, however, there is a greater complexity of phe- nomena. In pneumonia, for instance, the urinary toxicity grows less as the disease progresses; the poisons accumulate in the organism, to be suddenly thrown out at the moment of defervescence; a urinary crisis is then observed, characterized by a strong polyuria and a tox- icity of the urine, which may exceed from five to six times the normal toxicity. The Principal Bacterial Toxines N"ot wishing to describe the microbic toxines thus far studied, we believe that it would be interesting to sum up in a few lines our present knowledge of the principal toxines. We must first consider those infections whose mechanism is inex- plicable otherwise than by admitting the action of a soluble poison. We here refer to those infections whose agent remains at the point of inoculation — e. g., diphtheria, tetanus, cholera, emphysematous gan- grene, and symptomatic anthrax. Diphtheria. — The diphtheritic toxine, discovered by Eoux and Yersin, can be obtained in such high degree of activity that -^ and even -g-J^ of a cubic centimetre kills a guinea pig of 500 grammes weight. If we remember that 1 cubic centimetre of the fluid gives 1 centigramme (0.01) of dry residue, say 0.0004 of organic matter, and that the toxine represents but one part of this matter, we are led to the conclusion that it can poison a living being 20,000,000 times greater than its own weight ! The active principle, insoluble in alcohol, is destroyed by light, heat, oxidizing agents, iodine water, and trichloride of iodine. Eoux and Yersin hold it to be a ferment ; Brieger and Fraenkel, a toxalbu- min ; Wassermann and Proskauer, an albumose, or, at least, intimately united with an albumose. GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 165 All living beings are not equally susceptible to the diphtheritic poison. Animals which are refractory to the living bacillus are equally so to the toxine. Of the animals easily poisoned we must mention the guinea pig. The rabbit is quite resistant, the dog much more so, and the mouse and the rat endure high doses. Subcutaneous injection produces oedema in the guinea pig and causes death within two or three days. The post-mortem changes noted are pulmonary congestion, pleural effusions, and hemorrhages in the suprarenal capsules. In the rabbit the predominant feature is cellular degeneration of the liver and kidneys. When deposited upon the surface of even a healthy mucous mem- brane the diphtheritic toxine gives rise to the formation of false mem- branes. In animals this result has been obtained in the larynx, the conjunctiva, and mucous membrane of the vulva. Injections of very small doses may give rise to paralysis with changes in the nervous system and myocarditis. Tetanus. — In the early studies of tetanus complex methods were employed. These were subsequently replaced by simpler procedures. Brieger isolated a whole series of bases : tetanine, tetanotoxine, spasmo- toxine— all three convulsivants, and one base stimulating the salivary and lachrymal secretions. These bodies act only in enormous doses. In fact, the true poison is an albuminoid substance discovered by Knud Faber, and studied by Brieger and Fraenkel, Tizzoni and Cattani, and especially by Vail- lard and Vincent. The poison obtained by filtration of the cultures is of such activity that ^ Q Q^^ of a cubic centimetre suffices to kill a mouse. Injected beneath the skin, it causes tetanus after a variable period of incubation. According to Courmont and Doyen, the poison acts indirectly; it causes the organism to produce a tetanizing poison. This very in- genious hypothesis has been the subject of lively discussions and can not as yet be considered as absolutely established. Two theories have been advanced to explain the mechanism of convulsive phenomena : Autokratov, Courmont, and Doyen admit an action of the poison upon the sensory nerves; Brunner admits a modification of the spinal cord similar to that produced by strychnine. Cholera. — The choleraic poison has been successively studied by Petri, who considered it a toxopeptone; by Hueppe and Scholl; by Gamaleia, who regards it as a nucleo-albumin contained in the bodies of the bacteria ; by Sanarelli, Brieger and Fraenkel, Pfeiffer, and espe- cially by Ransom. Ransom^s researches, completed by those of Metch- nikoff, Roux, and Salimbeni, demonstrate that the cholera poison, un- 166 ANTHRAX like the preceding ones, resists boiling. Injected into animals, it pro- duces prostration, meteorism, and diarrhoea; death supervenes with hyperpyrexia. At the autopsy, hypersemia of the intestines, peritoneal effusion, and congestion of the liver, kidneys, and, in the guinea pig, of the suprarenal capsules are found. Gaseous or Emphysematous Gangrene. — The toxine of emphysema- tous gangrene, prepared by Besson, produces oedema, which is often followed by a slough. In symptomatic anthrax there is found a toxine which was pointed out by Duenschmann. We now come to the group of microbes which have a tendency to invade the entire organism. Their chief representative is the Bacillus anthracis. Anthrax. — Considered as a ptomaine (Hoffa), a toxalbumin (Brieger and Fraenkel), an albumose (Sidney Martin), the anthrax toxine has been well studied by Marmier. It is primarily found in the bodies of the bacteria, and remains inclosed therein if the culture is made under favourable conditions; if not, it abandons them and is diffused in the surrounding medium. Injected into animals, it produces fever and diarrhoea, and causes death by hyperpyrexia and final con- vulsions. This poison resists heat quite well ; it is attenuated by hypochlorites and the iodo-iodide reagent. Septicaemia. — It is to the group of bacilli producing hemorrhagic septicaemia that the microbe of chicken cholera belongs. We have already referred to Pasteur's experiment upon the narcotic poison con- tained in bouillon cultures. It may be well to mention some researches demonstrating that the various microbes of this group likewise pro- duce toxic albuminoids (Schweinitz, Voges). Similar demonstrations have been made regarding the Bacillus pro- teus vulgaris, Bacillus pyocyaneus, and Bacillus septicus putidus. Colibacillosis. — The important part played by the colon bacillus group, even in normal states of the organism, renders necessary a spe- cial mention of it in the rapid review here presented. The soluble products of the microbes belonging to this group have been studied by Denys and Brion, and especially by Gilbert. Their action is the more marked the stronger the virulence of the germ em- ployed and the older the culture. Nevertheless, to bring about a fatal termination, quite high doses are generally necessary, varying from 37 to 74 cubic centimetres per kilogramme. In the animals under ex- periment the result is very marked nervous phenomena, notably tetani- form convulsions. With a sample derived from dysenteric stools, we obtained an GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 167 extremely active toxine : a dose of half a cubic centimetre injected into the veins of a rabbit of 2 kilogrammes weight caused death with an intense diarrhoea and fever. Greater doses, as high as 15 to 20 cubic centimetres, administered to animals caused death with hypothermia. Under normal conditions the colon bacillus constantly secretes in the alimentary canal poisons which are partly destroyed by the intes- tinal epithelium, partly arrested by the liver, and the excess contributes to the toxicity of the urine. This is observed in quite a number of general diseases, even when the intestines are not involved, in which the colon bacillus becomes more active and produces a greater amount of toxic substances by virtue of organic disturbances. Typhoid Fever. — The typhoid toxine has been studied by a great number of investigators, among whom it is convenient to cite espe- cially Chantemesse and Widal, Sanarelli, Brieger, and Fraenkel. Chantemesse utilizes a special medium: it is a cold maceration of spleen and bone marrow to which is added a small amount of human blood. The maximum of toxicity is observed from the fifth to the sixth day. Inoculated into animals, this toxine produces different effects according to the dosage: A large dose causes diarrhoea and produces death with h3rpothermia. With a weaker dose, the first phe- nomenon is a paroxysm of fever, and the animal succumbs by cachexia. At the autopsy, abundant yellowish diarrhoeal fluid is found in the intestines; the spleen is highly coloured. The urine is seldom albu- minous. Streptococcus. — Cultures of streptococcus, especially when pro- tected from air, contain substances which exert a marked action upon the nervous system, bringing in its train rapid emaciation, paralyses, and death within two or three days. The active substance is precipi- tated by alcohol ; it is partly destroyed by heat. Staphylococcus. — Staphylococcus generates multiple toxic products, of which Eodet and Courmont have made an excellent study. Its cultures contain a pyogenic substance precipitable by alcohol, and substances soluble in this liquid, which predispose to infection, and others which provoke a vaso-dilatation. The substances precipita- ble by alcohol provoke trembling, tetaniform convulsions, and produce death within a few hours. The substances soluble in alcohol produce anaesthesia and kill by arrest of the heart's action. Glanders. — The soluble products of the bacillus of glanders, stud- ied first by Finger, produce rapid death, or, if the dose be less strong, provoke paralyses and death by cachexia. One of the most important properties of the sterilized cultures is that their injection causes a very notable rise of temperature in ani- 168 TUBERCULOSIS mals affected with glanders. This result, discovered by Kalning, has been turned to use in practice. A lymph is prepared and frequently employed in veterinary medicine for the diagnosis of latent or sus- pected lesions. Tuberculosis. — The action of glanders lymph may be compared to the action exercised by Koch's lymph or tuberculin. The injection of the latter is also followed by a reaction in tubercular subjects. But tuberculin, prepared by concentrating the cultures or by triturating the bacilli, does not represent the true soluble products — that is, the pri- mary substances. Of the latter there are many. There are a hypo- thermizing toxalbumin; a ptomaine, which causes dyspnoea, hyper- pyrexia, and produces death within two or three days; a toxalbumin, producing foci of necrosis at the site of injection ; and a toxalbumose, which lowers the temperature of healthy animals and gives rise to con- gestive and febrile reactions in tubercular subjects. There also have been found in cultures or extracts prepared from the organs of tuber- cular animals substances the injection of which has been followed by a progressive emaciation. Besides the matters contained in the cultures, we must mention those encountered in the protoplasm of the bacilli; Koch has discovered therein a pyogenic substance. Prudden and Hodenpyl have shown that the dead bacilli possess the property of causing the formation of granulations similar to tubercles. TOXINES PRODUCED BY NONBACTERIAL INFECTIOUS AgENTS The investigation of toxines produced by infectious agents higher than bacteria has seldom been undertaken. This is due to the fact that most authors, persuaded that the bacteria have a monopoly of producing infections, have not attached sufficient importance to the problem. Those who have attempted experiments have generally arrived at negative conclusions. It is to be remarked, first, that every parasite causing the develop- ment of a lesion secretes or contains a toxic substance; otherwise, it would have been perfectly endured by the tissues. This remark is applicable even to inanimate substances; they do not act unless they are soluble. On the other hand, the fact that toxines are absent from a culture bouillon does not warrant the conclusion that they are not produced in the living organism. In the case of a great number of pathogenic bacteria, in order to prove the presence of a toxine, it is necessary to utilize the most complex media and vary the procedures of sterilization. In ordinary bouillon, most bacilli produce no appre- ciable quantity of poisons. When we see a parasite induce grave or fatal disorders, even when it remains localized at some point of the organism, we are forced to GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 169 admit that it has engendered some soluble product. In this respect nothing is more instructive than the histor}- of Oidium albicans. This vegetable, inoculated beneath the skin or in the peritoneum, can pro- duce nervous troubles — paralysis or movements of rotation around the longitudinal axis. The animals succumb within from three to fifteen days; the autopsy proves the absence of all visceral lesions, and that the parasite has not left the point where it was introduced. It is therefore impossible to explain the phenomena and death except by the absorption of some toxic matter. In order to render the hypothesis incontrovertible, the poison must be discovered in the cultures. In injecting into rabbits cultures steril- ized by heat, it is found that the more virulent the specimen employed the greater is the toxicity. With a less active parasite, 10 or 12 cubic centimetres will provoke no trouble whatever; with an intensified vege- table, 5 cubic centimetres will cause death. The dose is doubtless very high, if it be compared with the one which kills in cases of diphtheria or tetanus; but it is not greater than that which must be employed when the typhoid bacillus is used. Moreover, the parallelism existing between the increase in virulence and the toxicity is a good demonstra- tion of the role played by the oidium poison in the production of the phenomena caused by the living cultures. On the whole, it seems to us permissible to attribute a general bearing to the facts that have been observed, and to conclude that all infectious agents act by toxic substances. The latter are not, in most cases, sufiiciently known from the chemical point of view. The results of experimentation have demonstrated their existence and plu- rality. The fact heretofore referred to, that the toxicity of the blood and the urine is augmented in the course of infectious diseases, is a further proof of the formation and importance of microbic poisons. Action of Toxines. Eeaction of the Organism The toxines, the origin of which we have briefly indicated, produce, as we have said, a local lesion, and, at the same time, may impregnate the entire economy. Locally, they alter the cells with which they come in contact. If they be very energetic, they destroy them ; if they be less active, they induce degenerations followed by reactionary phenomena. The por- tion of soluble substances that passes into the circulation will effect similar modifications in the rest of the organism. According to the activity of toxines, the cells of the organs and of the tissues will perish or present more or less profound degenerations. We have thus far supposed that the organism was absolutely pas- sive — that it did not interfere with the devolpment of the microbe any 170 ACTION OF TOXINES more than an inert liquid would; in reality, the phenomena are mucli more complex. When a microbe penetrates some point of the organism, it finds itself plunged into fluids endowed with a certan antiseptic power. This is what is designated as germicidal action. If the microbe is but slightly resistant, it will be completely destroyed ; if it is more vigorous, it will be only weakened, and after a first defeat will gain the upper hand and begin to multiply. Then a new mode of defence sets in. The leucocytes contained in the blood do an incessant patrolling; they guard the integuments and mucous membranes, run to wherever there is the slightest abrasion, and even pass through the mucous membranes to penetrate into the cavities, there to exercise their role of protectors. Every microbe tending to invade an organism will then find itself in the presence of migrating cells, always ready to re-enforce the fixed tells and exercise a phagocytic role. If the microbe is very virulent, its multiplication is scarcely hin- dered; it develops and secretes noxious substances. The cells nearest the microbic focus may perish ; the others will present reactionary phe- nomena often ending in a proliferation, with a return to the embryonic state and in a reappearance of their phagocytic power. The local reac- tions thus result in the increase of one of the defensive measures of the organism. At the same time the toxines which invade the organism by absorp- tion modify the nutrition of the cells, and the latter begin to elaborate their products on a new plan. It is known that the humours of the organism represent the product of the cellular secretions ; there is thus a production of substances useful to the organism, some as germicides, others as antitoxines. The germicidal substances which exist in small amounts under normal conditions render the medium unfavourable to the microbe; they exercise on it five species of actions: {a) They destroy it; (&) hinder its evolution; (c) or at least modify its form; {d) disturb its functions; and (e) cause its attenuation. The antitoxic substances are those which no longer act on the microbe, to lessen its pathogenic potency, but upon the animal organism, to strengthen its resistance. They impregnate the cells, and thus shield them against the influence of toxines. They act, then, in a complex manner, by a roundabout mechanism, and not, as was once supposed, by neutralizing the toxines as an acid neu- tralizes a base. If these favourable secretions be not called into play too late, and if they be produced with energy, the course of the disease will be hin- dered or arrested. If, however, their appearance be tardy and their GENERAL PATHOGENESIS OF THE INFECTIOUS DISEASES 171 quantity insufficient, the organism will succumb in spite of the devel- opment of a certain degree of bactericidal power. The humoral modifications, the mechanism of which has just been indicated, bring about a weakening of the microbes and favour the protective action of the cells. We have already stated that at the point where the microbe is in- troduced cellular proliferations occur; at the same time certain cells succumb; they then assume the nature of foreign bodies, excite the nervous system, and induce a vaso-dilatation at the invaded site through reflex action. The leucocytes, according to the process discov- ered by Cohnheim, leave the blood vessels and migrate to the affected region; they are attracted by the microbic products and cellular waste, which possess the property of so-called positive chemiotaxis. Then a struggle ensues between the cells and the microbes, the successive phases of which have been unveiled by Metchnikoff in a series of ad- mirable investigations. The cells take up the microbes, incorporate them, and cause them to disappear by a process of intracellular diges- tion. This is what is designated as phagocytosis. Unfortunately, the phagocyte is not always the stronger; overcharged with microbes, it may perish, sometimes after having again entered into the circulation; the auxiliary of a while ago will then transport germs and serve to dis- seminate infection. The fixed cells of the tissues may come to the assistance of the leucocytes; the round cells of the connective tissues, Eanvier's clas- matocytes, having returned to their embryonic form, and certain cells of the hepatic or renal parenchyma, and the vascular endothelium, exercise a similar phagocytic role. It remains to view the cases in which the microbe invading the organism is endowed with extreme virulence. Here no struggle is possible. The microbe finds in the humours an excellent medium for its development; it increases, produces negative chemiotactic sub- stances — ^that is, substances capable of repelling the leucocytes — and gives rise to toxines which overwhelm the economy. No defensive reac- tion whatever can occur. It is quite certain that between these different modes of infection innumerable transitions exist. It is possible, nevertheless, to sum up the various events as follows : 1. Nonvirulent microbe : Destruction by fluids normally germicidal. JTo disturbance. 2. Slightly virulent microbe : Destruction commenced by the germi- cidal humours and completed by the phagocytes; local lesion without gravity. 3. Virulent microbe: Formation of local lesion not constant; im- 172 REACTION OF THE ORGANISMS \ --'•V pregnation of the cells of the organism; cellular reaction resulting in the production of germicidal substances — i. e., increasing the resistance of the cells. The germs, overcome by the humours, are destroyed by the phagocytes attracted by the positive chemiotactic properties of microbic products and cellular waste. 4. Very virulent microbe : Defeat of the organism. Very little or no cellular reaction; little, if any, humoral modification. Phagocytes repelled by the microbic secretions, which are endowed with negative chemiotactic power. We shall consider all these phenomena, especially when treating of inflammation, immunity, and vaccinations. CHAPTER X NERVOUS REACTIONS Role of nervous reactions in physiology and in pathology — Local and general reac- tions : causes of their variations — The different varieties of nervous reactions : psychical, sensory, motor, vasomotor, nutritive reactions — Nervous fever — Nervous shock. All vital acts are but reactions aroused by external agents. Cer- tain reactions are produced at the very point where the stimulus acts ; these Dr. Bouchard calls autonomous elementary reactions. Others, more complex, are caused by modifications in the nervous system ; these are the reflex actions properly so called. Their points of departure are all the terminations of centripetal nerves — i. e., nerves of general, spe- cial, or visceral sensibility. They result in psychic, sensory, motor, vasomotor, secretory, and trophic modifications, which are produced either at the point of departure by a sort of reflection comparable to that of a shuttle, or ending in more or less distant and multiple points. The stimulations which serve as starting points for nervous reac- tions are continual, though often unconscious; they are indispensable for the regular performance of vital actions ; they maintain the nerv- ous centres in activity. Even under normal conditions they present incessant variations. The modifications of the barometer and ther- mometer influence considerably our psychical and physical aptitudes. It is a fact of common observation that one has not the same ideas, feelings, and energy at different seasons, even at different hours of the day. Rainy weather or excessive heat diminishes muscular energy; fresh air, and notably sea air, increases our activity. On the other hand, psychic influences can modify considerably the state of our organ- ism, and, conversely, the derangements of our organs reflect on our ideas. The slightest gastrointestinal disorder engenders sadness and melancholy. All these variations are yet of a normal order; they do not constitute sickness, but often predispose to it. Local and General Reactions. — The results of nervous reactions should be studied, as already stated, both at the point of their depar- ture and at a distance from it. 173 174 LOCAL AND GENERAL REACTIONS V. Locally, a stimulation is expressed, in certain cases, by an abrupt and unconscious movement. When a hot object is touched unwittingly, the finger is withdrawn often even before the painful sensation has been felt. In other instances, a vasomotor modification takes place. Under the influence of a cold application the vessels contract and the part becomes bloodless. In case of a hot application, the reverse takes place. Finally, if an irritating agent enters the tissues, the result is an active congestion followed by oedema and diapedesis. Along with the local manifestations, which are all of a defensive character, modifications occur at distant points, sometimes at sym- metrical points. Taking up an experiment of W. Edwards, Brown- Sequard and Tholozan demonstrated that if one hand is dipped in cold water the temperature of the other hand goes down. The effect is not due to a loss of heat, but to an homologous and symmetrical reflex action. In certain cases the phenomena are dissimilar; an equilibrium is produced between the peripheral and central circulation. In still other cases the manifestations are more complex; the section of a nerve may produce zones of anaesthesia or hypersesthesia at points having no connection with the distribution of the sectioned nerve. There remains a third group, which comprises the general reactions following a local disorder: these are chills, delirium, convulsions, syn- cope, fever, and nervous shock. Conditions causing Variations in Nervous Eeactions. — The phe- nomena of reaction vary in intensity according to their point of de- parture. They are the more marked as the region stimulated is the more richly supplied with nerves. If, for example, the snout of a rabbit is briskly dipped in cold water, a respiratory syncope results; if its hind legs are plunged in — that is, a region more extensive but less rich in nerve endings — no notable trouble is observed. It is readily understood that the intensity of reactions increases as does the excitability of centripetal terminations ; frictions, the applica- tion of sinapism, the action of heat, by flushing the skin, render the sensibility keener and the reactions more energetic; conversely, cool- ing and local anaesthetics, such as cocaine, diminish or suppress the effects of reaction. It must only be added that, under these various conditions, the phenomena are more complex than might be supposed. When the nerve terminations are modified, there are modified thereby the stimulations which maintain the tension of the nervous centres and their reactionary aptitude. We may, in reality, act upon the centres by acting on the periphery. We may also directly act upon them, for instance, by means of sections which, by abolishing certain restraining influences, increase the re- sponsive power of other parts. Likewise, under the direct influence of NERVOUS REACTIONS 175 heat or cold, the nervous centres become more or less apt to act. It is, however, the toxic substances that generally intervene: the bromides, opium, and chloral hydrate exercise a well-known sedative influence, while strychnine causes spinal excitability to so high a pitch that the slightest stimulation provokes violent tonic convulsions. Alterations of the pathways of transmission are by no means less important. If they affect the centripetal paths the result is retarda- tion or trouble in the perceptions and reactions. If the centrifugal paths are the seat of alterations, at times cramps or contractures, and at other times trembling and irregular or insufficient movements, are observed. In other instances the organs in which the reflex action ends are altered and present very grave disorders under the influence of the slightest peripheral stimulation. The most striking example is offered by cardiac pathology : a slight impression, which provokes simply some palpitation in a healthy man, may in a person affected by myocarditis or aortic insufficiency give rise to a fatal syncope. Even in the normal state, nervous responses vary with a great number of predisposing conditions, which we must now rapidly pass in review. It is, in the first place, the influence of the species. The higher the being, the more energetic are the reactions. Stimulations that elicit no response in animals may cause accidents in man: a violent blow on the testicles is well endured by a dog; in man it not infre- quently causes a lipothymia or a syncope. The nervous shock is like- wise rare in animals, or occurs only under the influence of exceedingly violent causes. To confine ourselves to the human species, we shall first note the influence of sex. In women, nervous reactions are far more easily called forth than in men; women blush or grow pale, laugh or cry, on the slightest pretext. In order, however, to fully appreciate the differ- ences, we must consider the genital period. In young children the nervous system is always of a feminine character; it is a matter of common observation that with them reactions are quick, mobile, and excessive. At an advanced age sexual differences become less marked: from a physiological as well as a psychical standpoint the old man is a being who reacts little ; the strongest impressions leave him almost indifferent. Likewise, when an infectious disease breaks out, the reac- tions, so tumultuous in the child, so marked in the adult, are hardly noticeable in the aged, and we are greatly surprised, at the autopsy, to find, for instance, a pneumonia arrived at the stage of gray hepati- zation without its existence having been revealed by any symptom whatever. 176 VARIATIONS IN NERVOUS REACTIONS Age and sex diiferences aside, there are numerous factors which intervene to impress the nervous system with special reactionary apti- tudes, and thus confer on the individual a personality. The most important are the hereditary and inborn influences. Psychical characteristics and reactionary tendencies are transmitted from parents to children. Of this we shall treat at length in the fol- lowing chapters. All the children of the same family are not abso- lutely alike ; their responsive aptitudes are often very different, because the state of the nervous system in the parents has not been the same at the different periods of life. The nervous system of a child repro- duces the nervous systems of the parents, such as they were at the epoch at which conception took place. In general, children born of young parents are more apt to react; they are more lively and more cheerful. But when the generators are older, and have experienced disappointments and disillusions which are almost unavoidable, and their nervous systems have undergone the shocks of external events and they have acquired that sort of sadness which characterizes mature age, then the child comes to the world calmer; it will not have the illusions and enthusiasms of those bom before it ; it will often be inclined to melancholy. If conception is still more tardy, the child will be recognised by its lack of youthfulness, its precocious senility, which seems to continue the senility of its parents. In the next place, the state of mind, the physical and psychical con- ditions that existed at the moment of conception or during gestation must be noted. In these cases the influence of the father is naturally less marked, as it acts only during the period of formation of the spermatozoids ; while the mother's influence makes itself felt alike during the development of the ovum and the entire duration of preg- nancy. It even seems that the disturbances of infectious or neuro- pathic origin occurring during gestation have a far greater influ- ence on the product than those existing at the moment of conception. The incessant modifications transmitted by heredity explain the de- velopment of races and the influence of civilization. The effect of the latter is to diminish the intensity and fatality of nervous reactions. It can be said of the savage what Virchow said of the child: he is a medullary being. In the civilized adult the brain is predominant and rules the subjacent centres ; thus is created the will which becomes capable of arresting various reactions, even the vasomotor reactions; it becomes possible to refrain from crying under the influence of pain, and from flushing or getting pale under the influence of emotion. It happens, however, that at a certain moment the will, even the most energetic, undergoes more or less lengthened eclipses. In the course of diseases or during convalescence the highest psychical manifesta- NERVOUS REACTIONS 177 tions are weakened, and, consequently, nervous reactions assume that character of fatality which they seemed to have lost in the superior races. Nature of Nervous Eeactions Psychical Reactions. — In their highest manifestations nervous re- actions are expressed by phenomena of an intellectual order. We have already established that all ideas have an external origin. According to the old adage, so passionately criticised by the spiritualist school, it can still be maintained that all our present acquisitions have origi- nated from sensitive and sensorial impressions. But while rejecting the existence of innate ideas, we must recognise that the human brain presents from birth certain special aptitudes. We inherit, to a certain extent, the experience acquired by our parents. It is quite certain that the brain of a child born of civilized parents must not have the same intellectual predispositions as the brain of one born of savage parents, and it is hardly probable that the son of the primitive man, if he were possibly transported into our world, would be able to acquire the knowledge inculcated in the children of our epoch. The intellectual and moral properties thus developed in races and families may become perverted in a great number of diseases. At the present day we no longer question the influence of the body on the mind. It is a commonplace truth that character, intelligence, and capacity for work are considerably modified in the course of most diverse diseases. The sadness and hypochondriasis of individuals suf- fering from gastric, intestinal, hepatic, or genito-urinary affections and the delirium incident to febrile diseases are facts so open to common observation that we do not need to dwell on them. Eeciprocally, psy- chical impressions modify our bodily state. Emotion provokes polyuria or diarrhoea and arrests digestion. It even suffices that the mind should fix itself on an idea in order that there be produced a series of almost imperceptible movements which are but a tendency to the act. Hence by perception of such abortive movements the possibility for those endowed with a very keen tactile sensibility to read thoughts. Sensory Reactions. — Reactionary manifestations often affect the sensibility. A nervous excitation may produce anaesthetic or hyper- aesthetic phenomena : a superficial pain cures a profound pain. Brown- Sequard has shown that the projection of a current of carbonic acid on the larynx is followed by a cutaneous anaesthesia. In a subject with a predisposed nervous system, for instance an hysterical woman, even a slight traumatism may give rise to a sensitivo-sensorial hemi- anaesthesia — viz., to abolition of general and special sensibilities on one side of the body. 178 NATURE OF NERVOUS REACTIONS Motor Reactions. — Keactions occurring in the motor sphere are far more numerous. The best example is afforded by the tickling of the sole of the foot. At first, the leg is abruptly withdrawn, even in sleep; this is the plantar reflex. If the stimulation be kept up, the individual raises both feet : then a nervous rictus, spasms, and, finally, convulsions follow. If a more sensitive person is operated upon, con- vulsions appear far more readily. With children the slightest irrita- tion is enough — a fish bone fixed in the tonsil, an intestinal worm, and the pain of teething are familiar causes. Considering the same influences in an hysterical person, it must be noted that the most trifling excitement may call forth grave mani- festations. A slight shock may give rise to paralysis, trembling, or contracture. These various symptoms do not appear at once ; response is slow; the individual must muse on his accident, and induce, so to say, self-suggestion in order that morbid manifestations be aroused. In certain cases the frequent repetition of the same act is followed by contractures called functional cramps; such are the cramps of writers, telegraphers, and pianists that are observed in individuals pre- disposed by some nervous taint. Excitations also give rise to inhibitory phenomena, which are to be well distinguished from paralytic manifestations. Inhibition is an active phenomenon. For instance, the stimulation of the pneumogas- tric nerve causes arrest of the heart through inhibition. In medicine we often see a violent stimulation to determine an arrest of circula- tory or respiratory movements, or, as is commonly said, a circulatory or respiratory syncope. In the same order of ideas we may mention the impossibility of motion experienced by individuals when under the influence of a violent emotion. At a higher degree — that is, in a pre- disposed subject — an attack of catalepsy occurs. Vasomotor Reactions. — Another group of nervous responses is con- stituted by vasomotor reactions. Every stimulation, especially if pain- ful, determines a vaso-constriction, even when the subject is anaesthe- tized. Vasomotor modifications are observed every moment in physiol- ogy as in pathology. We need barely mention the well-known influ- ence of heat and cold. In the case of a chemical agent a congestion is produced, followed by an exudation, which dilutes or neutralizes the noxious substance. But it is in the struggle against infectious agents that the role of vasomotor responses intervenes most efficiently; the active congestion permits diapedesis, and thereby phagocytosis. When a vasomotor modification takes place at one point of the economy, others are generally produced in more or less distant parts. An equilibration is often admitted between the superficial and the profound circulations, and it is upon this idea that revulsive medica- NERVOUS REACTIONS 179 tion is based : dry cupping, by drawing the blood toward the skin, is supposed to relieve the congestion of the subjacent parts. The facts are real, but they are more complex than was formerly believed. In some instances the variations occur in the same direction; thus, the application of the ice bag to the cranium excites the vaso-constriction of the meningeal vessels. Fredericq, who has proved the fact experi- mentally, remarks that the phenomenon is produced too quickly to be attributed to a reduction of heat; it is a manifestation of a nervous order. Similar phenomena must occur in many cases, and it is prob- able that an attack of cold that gives rise to pneumonia must act by first producing a vaso-constriction of the pulmonary blood vessels. The congestion revealed by clinical examination represents already a phenomenon of reaction. Under the influence of a unilateral stimulation, symmetrical vaso- motor responses are often produced, whether of the same or of a con- trary kind. Thus, if one hand is exposed to cold, the other also grows cold. On the contrary, congestion of one of the kidneys induces anaemia in the other; extirpation of the superior cervical gland of the sympathetic, which produces vaso-dilatation in the enervated ear, de- termines vaso-constriction in the intact ear. In a great number of instances circulatory disturbances have their starting point in some distant organ. Stimulation of the biliary passages, as is realized by lithiasis, produces in the lungs vaso-con- striction, followed secondarily by congestion. It is a reflex action fol- lowing the sympathetic both as a centripetal and a centrifugal path. If the phenomena are very intense, the vessels overfilled with blood may burst. A cold bath has been able to produce cerebral hemorrhage, anger has been followed by epistaxis. Cerebral lesions are capable of producing subpericardiac and subpleural ecchymoses, or even veritable foci of pulmonary apoplexy. Vasomotor disturbances often terminate in the production of oedema. It is demonstrated that venous obstructions are generally insufficient to permit serous transudation; there must be, in addition, some vasomotor trouble. If the three veins of the base of the ear of a rabbit be tied, no disturbance is observed; but if we then extirpate the upper cervical gland of the sympathetic, oedema of the pavilion is produced. The vasomotor disturbance so decidedly represents the principal factor that, under certain pathological circumstances, it suffices to give rise to oedema. It is thus that a whole series of cutaneous manifesta- tions develops, especially urticaria and fluxions, which, in arthritics, are observed in the eyelids in consequence of a cold draught. Under similar circumstances arise also the pseudo-lipomata of rheumatics. 180 NUTRITIVE REACTIONS Secretory Reactions. — Whether there be or not any vasomotor modification^ the nervous system may call into action the glandular secretions. We have already referred to emotional polyuria and diar- rhoea; we shall add the sweats, and notably the cold perspirations, which represent the most remarkable example of dissociation between secretory and vasomotor phenomena. In other cases, the sweats, far from being increased, diminish or are suppressed: a violent emotion produces dryness in the throat ; a blow upon the abdomen or a crisis of hepatic colic gives rise to a transitory anuria. It may be stated that, as a rule, slight stimulations increase the secretions and that violent stimulations diminish them. This can be experimentally demonstrated by stimulating more or less the sciatic nerve. Neuralgia of this same nerve gives similar clinical results : if of moderate intensity, it increases diuresis; if violent, it gives rise to oliguria. Nutritive Reactions. — One of the most interesting functions of the nervous system consists in regulating the movements of nutrition. Its influence upon the carbohydrates has been easily recognised. An emo- tion produces a transitory glycosuria in certain individuals ; but if the unhealthful excitations be repeated, glycosuria becomes permanent: a nervous diabetes develops. Similar modifications occur in nitrogenous substances. There are albuminurias caused by nervous reactions ; they occur as the result of cutaneous stimulations — for instance, when an individual suffering with psoriasis scratches himself. They are observed also in consequence of strong psychical emotions. At other times the disturbance in the elaboration of nitrogenous substances is expressed by modifications in the urea. This result has been turned to account by therapeutists : in order to increase the production of urea, cutaneous frictions with horsehair gloves, douches, or a sojourn on the seashore are prescribed. Analysis of the urine demonstrates that sea air increases by 3 grammes daily the excretion of urea; sea bathing produces an increase of 1 gramme, and a bath in hot sea water 3 grammes. In all cases cutane- ous stimulation favours oxidation. Likewise, it has been demonstrated that pleasant impressions, joy, happiness, raise the quantity of urea. Bocker has seen an individual lose, under the influence of a great joy, 1,159 grammes of his weight and eliminate through his urine 40 grammes of urea in twenty-four hours. This loss, which expresses an increase in nutritive ex- changes, is followed by an increase of appetite and an energetic repa- ration. On the other hand, depressing causes, sad news, diminish oxidation and hinder assimilation; the sensation of hunger grows less lively and emaciation makes rapid progress. In certain instances nervous stimulation, whether physical or psychical, a blow upon the NERVOUS REACTIONS 181 head or an emotion, may engender a permanent disorder of nutri- tion — viz., azoturic diabetes. Although the fact is not demonstrated, it is probable that the nerv- ous system intervenes in the elaboration of uric acid, and, consequently, in the pathogenesis of gout, since fatigue, excesses, and anxieties play an important part in the causation of the disease. The trophic influence of the nervous system accounts for certain disturbances which one might at first be tempted to explain by an- other mechanism. Thus, articular lesions are followed by atrophy of the muscles subjacent to the diseased joint. The phenomenon is not due to the immobility of the member, but to a true reflex. By severing the posterior roots in a dog, Eaymond and Deroche found that the traumatism of the knee did not produce amyotrophy: they had sup- pressed the centripetal portion of the reflex arch. Trophic disturbances may also be responsible for pigmentary phe- nomena. Many a dyschromia is due to some nervous influence. The most curious instance is that recorded by Gubler: In a man suffering from trifacial neuralgia the hair grew without colour during the crisis, so that after a certain number of attacks it presented a zebralike appearance. By controlling nutrition, the nervous system also regulates the temperature. There are nervous fevers, of which hysterical fever is the most familiar type. When an individual is weakened by any cause whatever, and par- ticularly by a disease, the slightest excitement produces fever. An- noyance raises the temperature of the sick ; when patients hate to take cold baths, it is often observed that, after a forced immersion, the thermometer rises a few tenths of a degree, despite the loss of bodily heat. It is a familiar fact in hospitals that the temperature of the patients increases on visiting days. In the convalescents it slightly rises when they are permitted to make their own toilet or to read. Eeciprocally, nervous reactions may cause a diminution of tem- perature. This is at least what occurs under the influence of violent impressions, which often give rise at the same time to a series of mani- festations collectively called nervous shock. Nervous Shock. — Nervous shock is essentially characterized, from a pathologico-physiological standpoint, by arrest of exchanges between the cells and the plasmas (Brown-Sequard) ; in other words, it is an arrest, or rather a diminution, of nutritive activity occurring through reflex action, under the influence of a sudden and violent excitation. It is an active phenomenon, and not the result of nervous exhaustion. So it is readily understood that shock should be more frequent in men than in women, and in adults than in the young and the aged. It is to 182 NERVOUS SHOCK be noted, however, that when it is produced in the aged it assumes a character of exceptional gravity. Nervous overexcitement is favourable to the production of shock; during the Commune of Paris shock was far more frequently observed among the insurgents than the regular troops. On the other hand, nervous exhaustion is unfavourable to its development; hence a first shock is not aggravated by a fresh excitement. A grievously wounded man listens with indifference to the announcement of a catastrophe; it would not be so if shock, as is often said, were due to nervous ex- haustion. Among the causes of shock, great traumatisms must be put on the first line, then violent excitations of the cutaneous nerve terminations. Whether an immersion be made in boiling or cold liquids, the effect, from this point of view is the same. We shall not advert to this ques- tion, already referred to on page 43. We have likewise pointed out that sideration by electrical currents (page 58) belongs to the same order of phenomena. In the case of localized stimulation, the effects vary with the re- gions; they are the more marked as the part is the more richly sup- plied with nerves and more sensitive. It is not, however, the external parts alone than can be the starting point of nervous shock; hepatic or renal calculi, the colic of intestinal occlusion, and pulmonary or cerebral emboli can produce the same effects : these are veritable inter- nal traumatisms. Excitation may also be produced by chemical substances, and espe- cially by irritating vapours, acting upon the larynx and lungs. Thus, chloroform, the effects of which are, of course, complex, may, by stimu- lating the terminations of the laryngeal nerves, give rise to a series of inhibitory acts — namely, cardiac syncope, respiratory syncope, and arrest of nutritive exchanges. The last, but not the least, of causes of nervous shock must not be overlooked — viz., moral impressions. It is well known that Sopho- cles, Denys the tyrant, and Pitt succumbed to the sudden announce- ment of some startling news. A great joy or a great fright may cause sudden death, or the series of phenomena that characterizes shock. An individual suffering with this syndrom, a man, for instance, who is the victim of a grave traumatism (such is most frequently the case), is in a state of complete prostration. He is lying down, motion- less, absolutely indifferent to all his environment and often altogether unconscious; the skin is pale, covered with a cold, clammy sweat, the mucous membranes are bloodless, and the eyes half closed. When his eyelids are raised the pupils are found to be dilated. Sensation is ex- tinct, respiration irregular, pulse slow, irregular, and weak; the veins NERVOUS REACTIONS 183 contain but a small amount of blood, which presents a bright colour. Peripheral and central temperature goes down ; the thermometer placed in the rectum does not rise above 36° C. Death thus supervenes in adynamia and collapse. In grave cases, fatal termination occurs within a period varying from thirty minutes to twenty-four hours. When the evolution is to be favourable, the symptoms gradually disap- pear, but they sometimes leave as sequels various nervous disorders : disquietude, agitation, neurasthenia, and paralysis. Such cases are ob- served especially in consequence of railroad accidents. The explanation of these various phenomena is already pointed out by the analysis of the symptoms. The modifications of circulation and respiration, and the red colour of the venous blood, which, as the analyses made by d'Arsonval have shown, contains very little carbonic acid, sufficiently demonstrate the profound disturbance of nutrition. Cellular life is suspended and modified. The recent researches of Philippen established the fact that during shock a veritable auto- intoxication is produced as the result of disorders occurring in cellular nutrition. The toxic substances thus generated can not pass from the cells into the blood, and, on the other hand, toxic products no longer pass from the blood into the cells. The most active poisons can be in- troduced into the organism with impunity. It has been experimentally demonstrated that animals in a state of shock do not respond either to strychnine or veratrine ; and clinical experience establishes that it is in slight cases alone that alcohol causes semi-intoxication and opium induces sleep. 13 CHAPTER XI DISTURBANCES OF NUTRITION The two characteristic phenomena of nutrition : assimilation and disassimilation — Cellular nutrition : the six acts to assure it in the higher beings — Disturbances of nutrition — Starvation — Disturbances of digestion and absorption — Varia- tions of cellular nutrition in physiological and pathological conditions — Diatheses. NuTEiTiON is the principal property of living matter: it essen- tially characterizes life. It comprises two orders of phenomena : assimilation and disassimi- lation. Assimilation is represented by a phenomenon of organic synthesis. The cell seizes upon the nutritive materials placed at its disposal, and groups them together in such a manner as to form a very complex, and therefore very unstable, molecule. In order that these phenomena may be produced, a certain amount of force must be absorbed — i. e., pass into a state of latency. Then comes the second phenomenon, disassimilation. The formed molecule disaggregates and is reduced to simpler and, consequently, more stable elements ; at the same time a certain quantity of energy is liberated. Molecular destruction is thus attended with a disengage- ment of force ; the wearing out of the cell results in the manifestation of life. Thus goes on the process of a continual construction and de- struction, and thereby an incessant renovation. The substances of disassimilation have become useless. They are even harmful, for the cell does not reject them such as it has absorbed them; it abandons them in an altered state, unfit for its nutrition. They can, however, be utilized by other beings, who will cause them to undergo new transformations, and bring them back to their first state. So there is a real circulation of matter, which passes from being to being and returns to its point of departure. To take a concrete example, let us consider how animals and plants live. Of course, cellular life is alike in both cases. As Claude Bernard 184 DISTURBANCES OF NUTRITION 185 has shown^ there is not a vegetable physiology and an animal physi- ology. The laws of nutrition are the same: the plant cell liberates force, as does the animal cell, and, like it, produces then carbonic acid. But the plant spends much less energy, and the phenomena predomi- nant in it are those of assimilation. It seizes upon carbonic acid and unites it to water under the influence of solar rays, thus reconstitut- ing a hydrate of carbon, which furnishes the animal with vital force. It is, then, the sun that, through the plant, furnishes the necessary energy; the solar rays, as Herschell has pointed out, are the true cause of all nutritive phenomena and the source of all vital energy. When a living being is placed in a confined space, there comes a moment when the vital manifestations cease. It is not because the aliments are exhausted, for these can be supplied without restoring life; the vital arrest is due to an accumulation of useless matter — namely, to auto-intoxication. The being has poisoned itself by its own products. Let these be artificially eliminated, and life will con- tinue; let another being of a different nature, capable of turning to use the cellular wastes, be introduced into the same space, life will be resumed, and, in this manner, there will be realized what takes place in Nature. If we consider the life of the unicellular being, we see that nutri- tion is characterized by four series of phenomena: A physical phe- nomenon, endosmose, by which nutritive substances pass from the exterior to the interior of the cell; a chemical phenomenon, assimi- lation, characterized by an organic synthesis and the storing up of force ; another chemical phenomenon, the reverse of the preceding one, disassimilation, accompanied by a disengagement of accumulated en- ergy; finally, a physical phenomenon, exosmose, by which the matter which has become useless or harmful is thrown out of the cell. In order that endosmose and exosmose may be produced, the nutritive substances must be in a state of solution. We can conclude, therefore, that to a unicellular being life is possible only in a liquid medium. The same is true of the higher beings, so far at least as cellular life is concerned. An artifice permits life out of water; that is, the creation of an internal medium — blood, lymph, plasma — whence the cells draw the elements of their nutrition. In physiology, as in chem- istry, active manifestations can not take place unless the substances are dissolved. Aerial existence presents a new complication. In order that nutri- tive materials may reach the medium, and that the products of dis- assimilation may be eliminated, it is indispensable that there should exist a certain number of organs. Thus the phenomena of nutri- tion become complicated. New functions are added; some for the 186 ASSIMILATION entrance of alimentary substances, others for the rejection of waste products. We are thus led to admit six successive acts in the nutrition of higher beings : 1. Transmission of food by the digestive canal; transformation of aliments by the juices flowing into the gastrointestinal tract. The effect of these transformations is to hydrate the substances in order to render them dialyzable; the starch is saccharified, the albumins are peptonized, the fats are partly emulsified and partly decomposed into fatty acids and glycerine. 2. Absorption. The dialyzable substance passes through the intes- tinal walls. But the phenomena are not merely of a physical order; there is, at least in some measure, a vital process, in which the epi- thelial cells of the intestine take an active part. 3. Dehydration of the aliments that have been hydrated in the gastrointestinal cavity. Had the aliments preserved the power of diffu- sion acquired in the intestine, they would be eliminated as fast as they were introduced; they undergo, therefore, a process of dehydration, which, rendering them less readily dialyzable, adapts them either for nourishment or to be stored up in certain parts where they form reserves. Dehydration begins in the intestinal walls, where peptones form new albumins and the decomposed fats are combined anew; it is finished in the lymphatic glands, and especially in the liver, which arrests the fatty acids, the peptones, and the sugar. Glucose is dehy- drated and forms a matter analogous to starch — namely, glycogen — which accumulates in great quantities in various tissues, in the mus- cles, and chiefly in the liver. 4. Nutrition of cells, comprising the four acts above indicated in reference to unicellular beings. Only, it is not in the ambient medium but in the interstitial plasma that the cells appropriate the matter they want, and eject the waste substances. The latter pass into the blood and are eliminated. But, in order to easily leave the organism, they must become dialyzable. 5. Transformation of the products of disassimilation, which be- come dialyzable. The liver plays here a very important part ; it is in its parenchyma that nitrogenous products undergo the ultimate trans- formation which reduces them to the state of urea, a crystallizable body, which readily leaves the organism, and even acts as a diuretic ; it favours the renal emunction. 6. Eejection of the useless substances by the emunctories, chiefly by the lungs and kidneys, and next by the skin and the various glands with secretory ducts. It is possible, then, to find out, at least approximately, the nutritive DISTURBANCES OF NUTRITION 187 state of a man by examining his excreta. It has thus been established that an adult voids in twenty-four hours 250 grammes of carbon and 18 grammes of nitrogen; he must ingest, therefore, each day, aliments that will furnish the same quantities of these two substances. He will obtain the 18 grammes of nitrogen by consuming 500 grammes of meat, but for the 250 grammes of carbon he will need 2 kilogrammes of meat. These figures show the necessity of a mixed alimentation. If vegetables are added to the diet, the ration of maintenance is ob- tained by giving 5 parts of carbohydrates for 1 part of nitrogenous matters. When these conditions are not fulfilled, disturbances break out. To understand the mechanism, we must first consider what hap- pens in case of absolute inanition. Starvation. — When a being is deprived of nourishment, of the two acts characterizing cellular nutrition, only one is preserved; disas- similation continues, and death supervenes when the body has lost about 40 per cent of its weight. All the tissues do not equally take part in the emaciation. Fat diminishes in the proportion of 97 per cent. The viscera are affected in the following order : First, the spleen, and then the liver, the muscles, the kidneys ; the most resistant of all are the heart and the nerve centres. Their loss does not exceed 3 per cent of the initial weight. These various results are easily explained. At the beginning of starvation, the sufferer consumes the fat; when this is exhausted, he resorts to the nitrogenous substances. At this moment, urea increases in the urine, albuminuria sets in, the organic temperature falls, and then the situation becomes grave. Survival varies considerably, according as one takes or suppresses liquids. A dog deprived of nourishment and of beverages succumbs in twenty days; a dog deprived of food, but having water at its dis- posal, is still living at the end of thirty days, and, if fasting ceases, it may recover health. The same differences are observed in the case of man, and the celebrated fasters of recent years have always been care- ful to continue drinking. Water is beneficial because it washes the organism and carries off the products of disassimilation ; it prevents auto-intoxication. Man is seldom submitted to absolute fasting; there is generally an insufficiency of nourishment and a bad quality of food. This is what happened during the great famines which ravaged Europe in the Mid- dle Ages and until the eighteenth century; that is also what occurs during wars in besieged towns. On such occasions a whole series of disturbances is observed, mostly due to the secondary action of infec- tious germs. Bad nourishment weakens the organic resistance and leads to the development of epidemic diseases, markedly of typhus. Likewise, in clinics, those who are ill nourished, either in conse- 188 DISTURBANCES DUB TO DISORDERS OF DIGESTION quence of poverty or some organic lesion (a stricture of the esophagus or the pylorus), present a series of symptoms, some of which are the direct result of starvation, others are due to superadded infections, owing to the weakness of the organism. Among the former we shall indicate emaciation, anaemia, dropsy, and cardiac and cerebral dis- orders, notably delirium; among the latter, cutaneous eschars, pul- monary gangrene, blood infections, and especially tuberculosis. Nutritive Disturbances due to Disorders of Digestion. — For the study of the disturbances of nutrition, we shall review in succession the different acts which follow one another in the higher beings. It is first, as already stated, the action of the digestive juices which hydrate the ingesta. When the aliments are too abundant or of bad quality, when they are indigestible or not appropriate to the age, very complex disturbances result. The nondigested food falls an easy prey to the microbes swarming in the alimentary canal; the result is an increase in intestinal fermentation, catarrh, or inflammation of the digestive tube, and dilatation of its various parts, markedly of the stomach and large intestine. From a functional point of view, an attack of indigestion, dyspepsia, sometimes lientery, follows. The sub- ject gets thin, nervous manifestations appear, various tissues are dis- turbed in the nutrition, and often nodes develop around the second phalanges {nodosites de Bouchard) . At other times, it is the case of those who take in excess some particular kind of food ; some, for instance, abuse the carbohydrates : a too great amount of glucose is absorbed. The cells are unable to utilize all, and some of it passes into the urine ; thus is produced a first variety of alimentary glycosuria. In other instances the nitrogenous substances are too abundant; they are absorbed, but do not undergo their complete circle of evolution; they stop at the stage which pre- cedes the formation of urea. According to certain authors, uric acid is found in excess, and may pass into the urine or accumulate in vari- ous parts of the organism, thus giving rise, at least in some cases, to the affection called gout. We have already pointed out that the second act of nutrition could not be explained by the laws of physics alone, that a large part is due to the vital action of the epithelium and membranes of the intestine. The peptone, for example, becomes dehydrated while passing through the intestinal walls, so that none of it is ever found in the blood, not even in the portal vein. Under certain pathological conditions it no longer undergoes its transformation into albumin; it passes into the system, and, as it is no longer good for nutrition, it is found in the urine. In this manner is created the peptonuria of intestinal origin — the enterogen peptonuria of the German authorities. DISTURBANCES OF NUTRITION 189 Once absorbed, nutritive substances undergo a final transforma- tion in the mesenteric glands and the liver. Physiology has not taught us much respecting the function of the lymphatic glands, nor does pathology tell us anything about disturbances dependent upon their alterations. We are better informed as to the fate of all the substances which enter by the portal vein. The liver stops the traces of peptone which may have escaped the dehydrating action of the intestine, and it modifies the albumins that are not yet quite fitted for the renovation of the cells. No wonder, then, that there exist, in liver diseases, at one time peptonuria (hepatogenic peptonuria), at another albu- minuria. It is especially on the ternary substances that the liver ex- erts its action. It arrests the sugar which the portal vein contains in excess after meals; it dehydrates and stores it up under the form of glycogen, which it transforms into a new sugar, somewhat different from the ordinary glucose, and which it diffuses according to the needs of the organism. If the liver is altered, the sugar is not arrested; it passes into the blood and is eliminated by the urine. This glycosuria also is pro- duced after meals ; it is an alimentary glycosuria due to hepatic insuf- ficiency. Variation of Cellular Nutrition under Physiological Conditions, — The variations of cellular nutrition are exceedingly numerous, even in the normal state. There exists, nevertheless, a medium type of nutri- tion, which is modified, however, according to age. During the first years of life, assimilation predominates over dis- assimilation ; the child accumulates matter; it constructs, so to speak, its cells. If the alimentation of the infant is bad or insufficient or too copious, gastroenteritis occurs, the stools become green and acid, they provoke erythema of the buttocks, vulva, thighs, and even the heels. The child loses flesh, and has the aspect of a little old man; the skin loses its elasticity, and at the same time the abdomen grows large, the liver becomes hypertrophic, the scanty buccal secretion per- mits the development of various germs, and aphtha makes its appear- ance. Such are the disturbances described by Parrot, in so striking a manner, under the name athrepsia. In other cases a defective ossification and rachitis are the result. In some instances the phenomena are different, either because the digestive disorders are not identical, or because the child is born with a special inheritance, or because the evil effects of a vicious alimenta- tion are aggravated by lack of oxygen and the sun; at all events, the child becomes lymphatic or scrofulous. At the moment of puberty other disturbances are imminent. At 190 CELLULAR NUTRITION this period a profound modification in general nutrition takes place; if the individual is predisposed by a bad inheritance, if his organism is weakened by overexertion, if reparation is insuflacient, then a gen- eral affection — chlorosis — develops. Various hypotheses have been put forth concerning the patho- genesis of chlorosis. Eeferred by some to lesions of the vascular sys- tem, by others to genital disorders, by others to digestive perturbations, and described as a blood disease, chlorosis is most frequently observed in children born of tainted parents. Tuberculosis is found in the antecedents of three fourths of the patients. It is probable that the disorder transmitted by heredity strikes the hematopoietic organs, and hinders them from providing for the nutrition required by the addi- tional activity. Hence, chlorosis is particularly frequent among the young girls of the labouring class who are forced to do too much fatiguing work. In the male it is met with, on the contrary, as Dr. Hayen has pointed out, among the higher classes, the influence of cerebral exertion being, in fact, more detrimental than that of man- ual toil, for which man has a greater aptitude. We must not, however, deny the part which menstruation may play in the genesis of disturbances observed in young girls at puberty. At each menstrual period nutritive modifications occur, predisposing to disease. The urine contains more urates, the breath and sweat exhale a rather strong odour, which is due to an exaggerated production of volatile fatty acids. The nervous system, which intervenes so fre- quently in the production of nutritive disturbances, may also play a part in the development of chlorosis. Not infrequently this particular anaemia establishes itself suddenly, or at least in a few days, after a strong moral impression — a great fright or a violent sorrow. Woman's nutrition is also modified during pregnancy and lacta- tion. This is proved by the examination of the urine. With pregnant women the cellular wastes are more abundant than normally, and, if oxidation be insufficient, organic depuration becomes incomplete. This is explained by the frequent appearance of hepatic disorders, the pro- duction of albuminuria and peptonuria, and the variations in blood and urine toxicity. According to Bunge, important modifications occur in the distribution of the iron, previously stored up in the liver, where it formed provision for the development of the new being. We have already noted that during childhood assimilation pre- dominates over disassimilation. In the adult, the two acts of nutri- tion balance one another; in old age, disassimilation becomes pre- ponderant ; the cells are no longer capable of assimilation ; the cellular tissue, the skin, the organs, the skeleton itself, gradually atrophy; the integument loses its elasticity, the osseous substance rarefies and be- DISTURBANCES OF NUTRITION 191 comes porous ; hence fractures are easy, and may occur almost without cause. This decrease of nutrition predisposes the aged person to chilli- ness; moreover, it reduces his activity and energy and brings on both physical and psychical indifference. Variations of Nutrition under Pathological Conditions. — Along with the modifications occurring under normal conditions, we must place those observed in pathology. Nutrition may be accelerated, sluggish, or perverted. Setting aside the digestive disturbances already spoken of, we shall first consider the influence of the nervous system. We have cited many examples establishing the fact that general nutrition is profoundly modified through the nervous system. For the maintenance of its regularity, the continual influence of air and light on our skin is necessary; it is therefore disturbed when we live in a confined atmosphere, in badly ventilated or dark lodgings. It is not any less influenced by all causes affecting the nervous system. We have already pointed out the great importance, in this respect, of joy and sorrow, of activity and idle- ness. Where the influence of the nervous system upon nutrition appears most clearly is in the course of neuroses. In paralysis agitans, in neurasthenia, the nutritive disorder is expressed by an exaggerated excretion of phosphates. This phenomenon is most remarkable in hysteria. The amount of urea may fall to 2 grammes in twenty-four hours, and even to 75 centigrammes. There is, then, an almost absolute arrest of nutrition; hence it is that some hysterical women can refuse all nourishment without getting thin in a noticeable degree. In some cases modiflcation in the elimination of phosphates is observed. It is after an attack of hysteria that a very curious phe- nomenon takes place, discovered by Gilles de la Tourette and Cathe- lineau. We know that phosphoric acid is eliminated, being united to calcium and magnesium (earthy phosphates), to sodium and potas- sium (alkaline phosphates). Under normal conditions the proportion of the earthy to the alkaline phosphates is as one to three; after an attack of hysteria the earthy phosphates increase and correspond to half of the combined phosphoric acid. Such is the phenomenon con- stituting a reversion of the formula of phosphates. Nutritive modiflcations may be produced by toxic substances, acting on the cells directly, or indirectly through the nervous system. Cer- tain medicines, like iodide of potassium, excite disassimilation. Others, bromide of potassium, for instance, check it. Taken in large and long-continued doses, morphine produces ema- ciation ; under the same conditions, alcohol gives rise to obesity. Among the substances that produce the most curious effects, lead must be mentioned, which disturbs the metamorphosis of nitrogenous 192 PATHOLOGICAL CONDITIONS constituents, determines an accumulation of uric acid, and sometimes gives rise to gout (saturnine gout). We know that the microbes act by the poisons they secrete; no wonder, then, that infections should provoke numerous nutritive dis- turbances. To be convinced of this, it will suffice to remember the profound emaciation of the patients. It is, however, the study of the excreta that furnishes the demonstrative information. Carbonic acid is exhaled in greater quantity, the urine contains an excess of ex- tractive matters ; urea decreases, at least in its proportion to the total of nitrogen ; it is, in fact, replaced by less oxidized substances, by amido acids, and even by ammonia. In certain cases, however, cellular wastes remain stored up in the economy, and are rejected only at the moment of convalescence; it is under these circumstances that ema- ciation is mostly produced after the termination of the disease. But we have already stated that all modifications occurring in the organism are almost invariably followed by reverse actions. When infection is terminated, repair begins and often becomes more active than disassimilation had been; hence the notable fattening so fre- quently observed. The fact is of common occurrence after typhoid fever. Likewise, consumptives, when they are cured, become obese. It is well to mention, finally, that under the influence of microbic toxines humoral modifications are produced in the organism; germi- cidal and antitoxic substances are formed. All these changes must be attributed to a nutritive modification; the cells influenced by the microbic products react in a new fashion and modify the chemical constitution of the humours. It is possible at the present day to ally neoplastic with the infec- tious process. The influence of tumours upon nutrition is undeniable, as is evidenced by the emaciation, which is so marked and rapid. It appears even particularly to affect the transformation of nitrogenous substances. Eommelaere has insisted upon the diminution of urea, which can not be accounted for merely by starvation. His assertion has been acknowledged to be exact, but the interpretation is still under discussion. All the nutritive phenomena which we have thus far studied are produced under the influence of external causes ; once established, they may be transmitted by heredity. But the disorder is often more marked in the offspring than in the parents; the daughter cells, younger, and, consequently, more impressionable, exaggerate the nutri- tive disorders which external causes had induced in the mother cells. In this manner diatheses are developed. Diatheses. — The meaning attached to this term has considerably varied. Some authorities speak yet to-day of tubercular, syphilitic. DISTURBANCES OF NUTRITION 193 and cancerous diatheses. These expressions are evidently deplorable. Tuberculosis and syphilis are infectious ; cancer is a disease unknown in its essence, but does not enter into the group of diathesis. In order to leave to the word diathesis a precise meaning, we must, following Dr. Bouchard, define it as a morbid temperament; and this is, by the way, its traditional meaning. Hippocrates called diathesis the manner of being, and admitted a diathesis of health and a diathesis of sick- ness — that is, as we say to-day, a normal temperament and a morbid temperament. What, then, is temperament? It is the dynamic state of an indi- vidual as opposed to the constitution, which is applied to his static state or structure. Temperament is the expression of physiological activity — viz., nutritive activity. We are thus led to define diathesis as a particular mode of nutrition. Accordingly, the number of diatheses is considerably reduced. With Dr. Bouchard we admit two — scrofulosis and arthritism. Scrofulosis corresponds to what was formerly called lymphatic tem- perament ; for among the lesions once considered as scrofulous, several must in reality be referred to tuberculosis or hereditary syphilis, of which, until recent times, all the clinical varieties were not known. The scrofulous child has a special appearance, quite easily recog- nised. The characteristics are a fine white skin, flabby flesh, long, silky eyelashes, and a large and broad nose, punctuated by spots of acne. The tonsils are hypertrophied ; the eyelids are often the seat of ciliary blepharitis, subacute or chronic. These children are subject to torpid and tedious inflammations ; on the skin impetigo is frequent ; on the mucous membranes it is a tenacious coryza, rebellious bronchitis, and, in little girls, leucorrhoea. On the slightest lesion the Ijrmphatic glands enlarge and remain voluminous. Sooner or later these children become tuberculous. In some cases the glands are affected; in others, the bones, the joints; and yet in others, the lungs themselves, where the disease assumes certain peculiar features, described as scrofulous phthisis. An inquiry into the antecedents of these children shows that their parents were in ill health, generally tuberculous, often syphilitic, some- times simply weakened or too old. At all events, it is not a microbe, but a nutritive disturbance, resulting from various causes, that has been transmitted and exaggerated by heredity. Heredity does not, however, sufficiently explain all; in many cases, other factors have added their pernicious influence : I refer to all bad sanitary conditions, life in confined air without sun, confinement to boarding schools, and particularly orphanages. From these etiological conditions we may draw a good many therapeutical indications. To remedy the scrofulous 194: DIATHESES temperament, the children must live freely in the sun, submit them- selves freely to the influence of the open air, and particularly sea air; moreover, their nutrition should be stimulated by cutaneous excita- tions, by the use of certain medicines, like cod-liver oil and iodine, or by hypodermic injections of artificial serum. By the side of this first diathetic type is to be placed arthritism, including herpetism. Quite different in its causes and manifestations, arthritism is peculiar to the higher classes, and is observed mainly in countries of advanced civilization. It develops progressively under the new conditions imposed by civilization, and is intensified from genera- tion to generation. Little by little, the cerebral faculties become pre- dominant, engaging all the activity of the individual ; nutrition in the other parts declines ; hence arthritism has been considered a sluggish- ness of nutrition (Bouchard) or, after Dr. Landouz/s expression, a bradytrophy. Quite different from the scrofulous, an arthritic person is of a nerv- ous temperament ; his flesh is firm, his stoutness is greatly variable ; he may be lean, dry, or, on the contrary, fat; he is precociously bald; Lis character is sad, but his intelligence generally bright, and some- times remarkably so. In youth he is subject to migraine, the first visitation of which he will never forget. When a young man, he be- comes asthmatic; later, he has attacks of sibilant bronchitis. About the age of twenty-five digestive disorders set in; dyspepsia and consti- pation often determine hepatic hypertrophy; the fatty acids, produced by defective nutrition, are eliminated by the lungs and the skin, com- municating to the breath and sweat an odour of offensive character, and predisposing to various skin diseases, notably to eczema. The disorders of cellular nutrition bring in their train humoral modi- fications. Sugar introduced into, or produced within, the organism is not consumed; it remains in excess in the blood, and passes into the urine, thus giving rise to a special variety of diabetes mellitus — ^the diabetes of the arthritic, a fatty diabetes, which is liable to last years without causing notable symptoms. Nitrogenous substances are assimilated as poorly as, perhaps even more poorly than, carbohydrates; whence result other humoral dis- orders, recognised by the presence in the urine of an excess of phos- phates, uric and oxalic acids. These various products may even form deposits in certain parts of the organism, creating urinary or biliary calculi, or developing gout. Of course, all these accidents are only exceptionally the lot of the same subject; they may alternate, and be replaced in an individual or in his family. A gouty father gives birth to a son subject to migraine ; another is diabetic; a third asthmatic; yet another develops renal DISTURBANCES OF NUTRITION 195 lithiasis. We have here a series of disorders which, despite their dis- parity from a clinical standpoint, are, nevertheless, linked together by the fact that all originate from a nutritive disturbance characterizing the diathesis. In the last place, in distinction from the scrofulous, the arthritic is little disposed to tuberculosis. Should the bacillus, perchance, be implanted in his organism, the disease assumes a slow, torpid course; sclerosis tends to circumscribe the process, thus developing a fibrous phthisis, often curable. CHAPTER XII DISTUE.BANCES OF NUTRITION (Continued) Auto-intoxications under normal conditions — Organs eliminating or transforming toxic substances — Poisons normally contained in the tissues, blood, and urine — Importance of urinary toxicity — Pathological auto-intoxications — Role of alter- ations of the digestive canal, liver, lungs, skin, kidneys, and the nervous sys- tem — Auto-intoxications chemically defined. The study which we have just made of cellular nutrition must be completed by the act which, in the higher beings, terminates the series of nutritive mutations — namely, the rejection of the products of disassimilation. When this elimination is hindered, the substances abandoned by the cells accumulate in the system and engender dis- turbances which are often serious and sometimes fatal. The nutritive disturbance thus ends in processes of primordial interest in pathology : these are the auto-intoxications. Auto-intoxications under Normal Conditions The toxic substances which, as we have seen, are produced within the normal organism as the result of disassimilation and of gastro- intestinal fermentation may be eliminated through numerous emunc- tories. The bile and the gastrointestinal secretions remove certain useless principles; but a part of the products thus rejected are taken up by absorption and re-enter the economy. The true emunctories are repre- sented by the skin, the lungs, and especially the kidneys. Through the slcin are eliminated the volatile fatty acids and vari- ous autogenous toxic substances; through the lungs escape especially water, carbonic acid, and, in a general way, all the volatile substances introduced or formed in the economy. Most of the solid materials are eliminated through the kidneys, but in order that their elimination may take place, they must become dialyzable ; the nitrogenous products notably must be transformed into urea. Now, the cells reject lower oxidized bodies and ammonia, at the 196 DISTURBANCES OP NUTRITION 197 same time that they abandon a certain quantity of urea. The liver causes these different substances to undergo the final transformation which permits them to dialyze; the liver, then, is the collaborator of the kidneys. The result is that its disturbances profoundly modify the secretion of the urine; the urea, the true physiological diuretic, is replaced by bodies which are eliminated with difficulty, and by their passage may even produce lesions in the kidneys. In order that the various nutritive phenomena may be regularly produced, the intervention of the nervous system, of which we have already spoken, is necessary, as is also that of certain organs which have the property of regulating cellular nutrition, either by submitting the matter to a special elaboration or by supplying the organism with an internal secretion. Besides the liver, whose function we have de- scribed, we must mention the pancreas, the thyroid gland, the supra- renal capsules, the testicles, and the ovaries. The extirpation of the pancreas is followed, as Minkowski has shown, by the development of a permanent glycosuria and the habitual symptoms of lean diabetes (diahete maigre). Experimentation real- izes what clinical experience has established. It has been known since the investigations of Lancereaux that diabetes characterized by emacia- tion is connected with atrophy of the pancreas, and with a sclerosis which is often of tubercular origin (Carnot). The pancreas acts, not as a digestive gland, but as an organ endowed with an internal secre- tion; it thus regulates the secretion, either by governing hepatic gly- cogenesis, or, as is stated by Lepine, by destroying the sugar through the agency of a glycocolytic ferment. It is probable, however, that glycosuria of pancreatic origin is due to some secondary disorders of the hepatic functions. Physiology has clearly shown the relations existing between the pancreas and the liver in the regulation of the glycogenic function. Therapeutics has established that certain dia- betics are cured by the administration of hepatic pulp. If we now consider another gland, which is also endowed with an internal secretion — viz., the thyroid — we see that its total extirpation is followed by manifestations no less curious: sometimes tetany de- velops, in other cases a very peculiar nutritive disturbance, myxoedema. The difference in the symptoms is perhaps explained by the anatomical complexity of the thyroid apparatus, which comprises two orders of glands: the thyroids and the parathyroids, which are separated or united according to the particular animal species. It seems that the lesions of the thyroids are generally followed by disturbances of slow course, characterized by mucoid infiltration of the tissues, while the suppression of the parathyroids seems to be connected with acute manifestations. Myxoedema sometimes leaves the intellect intact and 198 NORMAL CONDITIONS at other times induces cerebral apathy or a cretinoid state. This is due, according to Brissaud, to the fact that, in the former case, the thyroids alone are affected; while in the latter case the whole appa- ratus is affected. Be that as it may, the thyroid gland acts by modi- fying cellular nutrition, and the disorders occasioned by its extirpa- tion are remedied when the patient ingests thyroid glands taken from an animal. One must be very circumspect, however, in this medica- tion; the ingestion of the thyroid body has produced various acci- dents, and in certain cases has caused death. Only small doses must be given daily, from 3 to 4 grammes at the most, which must be stopped as soon as the first disorders appear, such as trembling or albuminuria. That the thyroid gland acts on nutrition is well proved by the fact that its ingestion gives excellent results in the treatment of obesity, at least in certain cases; for the medication does not always succeed, which tends to prove that the mechanism of this morbid state is very complex. Analogous facts have been observed with regard to the suprarenal capsule. Lesions of this organ give rise to a particular syndrom — Addison's disease — characterized by two principal symptoms: me- lanodermia, which is rather dependent upon concomitant lesions of the solar plexus, and asthenia — general weakness — decidedly due to alteration of the capsules. In fact, it has been shown by certain physi- ological researches that the function of these organs is to neutralize the toxines which arise during contraction of the muscles. Attempts have been made to treat patients suffering from Addison's disease in the same manner as in myxoedema — that is, by the use of supra- renal capsules; the method is rational, but it has not as yet led to very clear results. It is a familiar fact that the extirpation of the testicles or ovaries, especially when practised on young subjects, is followed by very marked nutritive disorders. In the case of a boy, infantile or rather feminine forms are preserved; the pilous system remains rudimentary; the larynx does not develop; stoutness is very marked. Finally, veteri- narians teach us that in castrated horses the brain is smaller than in noncastrated horses of the same stature. In the case of women, double ovariotomy results in the develop- ment of the pilous system, and especially of rapid obesity. Most of these disorders are successfully treated by the use of ovarian extracts. Thus, the notions recently acquired in reference to the internal secretions of various organs and their role in nutrition have led to a new system of therapeutics — opotherapy — of which Brown-Sequard was the pioneer. DISTURBANCES OF NUTRITION 199 Toxic Substances of Normal Tissues of the Blood and Urine. — The second stage of nutrition, disassimilation, results in the introduc- tion into the blood of a certain quantity of useless and harmful waste products. Thus it has been possible to say that, even normally, the organism is a receptacle and a laboratory of poisons (Bouchard). All parts of the body contain some posions. These are, first, the tissues, the extracts of which prove rapidly fatal when injected into the veins. In making cold macerations of the liver or muscles in salt water, it is found that in order to kill 1 kilogramme of animal the extract of 14 to 20 grammes of liver or 90 to 95 grammes of muscle must be in- jected into the veins. The greatest part of the toxicity depends upon albuminoid matter; and hence the extracts prepared hot are far less toxic. In order to kill 1 kilogramme, the extract of 117 grammes of liver or of 216 grammes of muscle must be introduced. The substances thus entering into the constitution of the tissues pass into the blood more or less modified, but they only traverse this liquid. Hence the blood has very little, if any, toxicity, at least when it is transfused between animals of the same species ; for the blood or the serum of one species is toxic for animals of different species. In operating on rabbits, it has been possible to determine in the following way the toxicity of the serum — viz., the amount necessary for killing 1 kilogramme of animal by intravenous injection : * Horse serum 80 cubic centimetres. Chicken serum 20 " Calf serum 13 " Human serum 10 " Cattle serum 8 " Eel serum 0.05 " Now that therapeutics has so often recourse to serum injection these facts have a practical interest. It should be noted, however, that the results are not similar in man and in the rabbit. Horse serum, so well supported by the rabbit, produces in man numerous disturb- ances even in minute doses : arthropathies, fever, erythemata, albu- minuria. On the contrary, the cattle serum, five to ten times more toxic for the rabbit, seems to be better borne by man. Dr. Beclere has proved its innocuousness by injecting smallpox patients with the serum of vaccinated calves in doses as high as one fortieth of the body weight. This toxicity of the serum it is very important to know; but we * In all these experiments the injections were made into rabbits by the intra- venous route. All the results are based on the scale of the animal kilogramme, and the figures are obtained by dividing the dose which proved fatal by the weight of the rabbit. U 200 URINARY TOXICITY are not concerned with its study, for it is a question of the action of albumins of the foreign blood, albumins which evidently are not toxic for the animal from which they are derived. As to the true poisons, they should be looked for, not in the blood, where they do not so- journ, but in the fluids through which they are eliminated. From this point of view, it is the urine that has been most often studied. Urinary Toxicity. — The brilliant researches of Feltz and Ritter, and especially those of Dr. Bouchard, have finally established that the urine contains numerous toxic substances to which three sources may be assigned: alimentation, gastrointestinal fermentation, and disas- similation. In order to determine the toxicity of a urine, the whole amount passed in twenty-four hours is collected. The liquid having been filtered, it is then injected into a rabbit through a peripheral vein and at a uniform rate. When the animal is dead the amount of urine introduced is noted and the figure obtained is divided by the weight of the animal; thus is determined the dose fatal for 1 kilogramme. This is what is designated as a urotoxia. On an average, a man eliminates in twenty-four hours 1,200 cubic centimetres of urine, the toxicity of which is 40 cubic centimetres per kilogramme; the total urine kills ^|go — that is, 30 kilogrammes; therefore it represents 30 urotoxias. If the man weighs 65 kilogrammes, a very simple calculation shows that in fifty-two hours he eliminates an amount of poison sufficient to kill his own weight. In twenty-four hours 1 kilogramme of this man eliminates an amount of poison which would poison 0.460 kilo- gramme. This is the urotoxic coefficient, which is obtained by divid- ing the number of urotoxias passed in twenty-four hours by the weight of the individual; the average of numerous experiments made from this point of view has given the figure 0.461 kilogramme. The substances which give the urine its toxicity are not well known from a chemical point of view. It is only known that there exist a mineral toxic matter (potash), toxic colouring substances, and poisons similar to ptomaines ; it is also known that separation can be secured by means of solvents, such as alcohol, ether, or chloroform, or else through dialysis. It has thus been possible to determine that the urine contains at least ten toxic substances, which are well character- ized by their action on animals : 1. A diuretic substance, of little toxicity, even of some value, since it assures diuresis — viz., urea. 2. A narcotic substance, soluble in alcohol. 3. A sialagogue substance, equally soluble in alcohol. 4. A convulsive mineral substance, potash. DISTURBANCES OF NUTRITION 201 5. A convulsive organic substance, which is precipitated by alcohol. 6. A miotic substance, insoluble in alcohol. 7. A hypothermizing substance, which is not dialyzable. 8. A thermogenic substance, which is dialyzable. 9. A mineral poison, potash, arresting the heart. 10. An organic poison arresting the heart. The toxicity of the urine resulting from these diverse poisons varies considerably even under physiological conditions. It is possi- ble, in the first place, to restrain it by modifying alimentation, chiefly by diminishing the potash salts; by a milk diet, and, according to Marette, especially a diet composed of milk and rice notably dimin- ishes the urinary toxicity. On the other hand, we may obtain a similar result by favouring oxidation, either by submitting the subjects to the action of compressed air or by causing them to take moderate exer- cise. If, however, muscular work is pushed to the point of fatigue, cellular waste increases in great proportion and renders the urine very toxic. The examinations which have been made after long rides on the bicycle leave no doubt in this respect. In the experiments of Drs. Tissie and Sabrazes, the urotoxic coefficient in individuals who took part in the run from Paris to Bordeaux reached 2.35, which was five times greater than the normal. Without dwelling on the toxicity of other organic secretions, we shall only remark that the bile is toxic in doses of 4 to 6 cubic centi- metres per kilogramme; that the gastric juice, the pancreatic juice, and the sweat also give rise to disturbances when they are injected into the veins. Finally, according to Brown-Sequard and d'Arsonval, the expired air contains a poison similar to volatile ptomaines. Al- though it has been contradicted, this last result is interesting; it ex- plains the noxious effects of confined air. Now that we are acquainted with the toxic substances which are pro- duced under normal conditions, it will be easy to understand what occurs in pathological states. Pathological Auto-intoxications The digestive canal represents the principal apparatus for the pro- duction of auto-intoxication. The fermentations occurring therein are exaggerated under a great number of circumstances; in others, the toxines produced are not completely eliminated. Whether it be an attack of indigestion, dyspepsia, or a case of dilatation of the stomach, whether diarrhoea, constipation, or even intestinal obstruction be pro- duced, the results are the same. An auto-intoxication is induced, attended with numerous disturbances to which we have already re- ferred when speaking of digestive fermentations. There are headache, 202 PATHOLOGICAL AUTO-INTOXICATIONS weakness, a general exhaustion, sometimes more serious disorders, such as aphasia; and, lastly, two phenomena which have recently been well studied, tetany and diaceturia. Tetany, to which we have already referred in speaking of the thy- roid gland, is generally observed in cases of hyperchlorhydria. Hydro- chloric acid, when produced in excess, gives rise in nitrogenous matter to the development of toxic substances which Bouveret, Devic, and Gassaet have isolated. The disturbances have nothing special from a symptomatic point of view, but they are very often grave and have sometimes caused death. Diaceturia is also a phenomenon of a toxic order, giving rise to a very serious syndrome — namely, dyspeptic coma. We shall again refer to it when speaking of auto-intoxications of diabetic origin, where diaceturia is of more frequent occurrence. Auto-intoxications of Hepatic Origin. — The production of poisons being normal or exaggerated, disturbances may occur as the result of some derangement of the organs which neutralize or eliminate toxic substances. To the first group belongs the liver, which arrests, transforms, and neutralizes the substances brought to it by the portal vein. When the hepatic cells are altered, this protective role is diminished and some- times even abolished. We can recognise the power of the liver by several procedures. Numerous experiments have demonstrated that the various functions of the hepatic cell are united, interdependent: when one is disturbed the others are affected. At the same time that the liver ceases to arrest the poisons it no longer elaborates the biliary pigments in a normal manner and urobiline is found in the urine. It no longer acts on the nitrogenous matter, and the amount of urea is diminished, or at least the proportion between the nitrogen of urea and the total nitrogen ; albuminuria and peptonuria may be produced. But, chief of all, the liver ceases to retain the carbohydrates, and sugar passes into the urine when the portal vein contains an excess of it — that is, after meals — and alimentary glycosuria follows. The patient is given in the morning, before breakfast, 150 to 200 grammes of sirup; then the urine voided during the following four or five hours is collected ; if the liver is normal, no glucose is found; if the glycogenic function is dis- turbed, glucose will pass into the urine. But several conditions may interfere with the results. Although the liver may be insufficient, gly- cosuria may not make its appearance, either because the intestinal absorption is hindered or because the capacity of the cells for con- suming sugar is increased, or, finally, because the renal emunctories are not performing their work normally. DISTURBANCES OF NUTRITION 203 We may also determine the state of the liver by studying the elimination of various substances which this gland retains, at least partially, under normal conditions. Thus it is possible to investigate the manner in which the urine excretes the quinine salts, and espe- cially how the lungs eliminate sulphuretted hydrogen. The latter method has been employed thus far on animals only, but it has already afforded valuable information. It suffices to inject a certain amount of a solution of sulphuretted hydrogen into the rectum; the liver arrests this gas ; but, if this organ is altered, more or less considerable quantities pass into the expired air, where it is easily detected by means of lead-acetate paper placed before the nostrils. A procedure that gives good results, but which, unfortunately, is not practical, is the study of urinary toxicity. Researches pursued in this direction have demonstrated that, if the antitoxic power of the liver is preserved, the urine, even when charged with biliary pigment, is not more toxic than normally. When the cells are profoundly affected, the urine contains from four to five times more poisons; at least that is what occurs when the kidneys are permeable. If these glands are altered, the poisons are retained in the organism and quickly bring about a fatal termination. The fact that the urinary toxicity always increases whenever ali- mentary glycosuria exists further demonstrates the correlation exist- ing between the different functions of the liver, notably between the glycogenic and the antitoxic action. These physiological data in the role of the liver in intoxications find numerous applications; they explain one of the most interesting syndromes of pathology — namely, icterus gravis. Under this name is described a complex morbid state, including three varieties, according as it may be a question of an infectious, a toxic, or a dystrophic process. Infectious icterus gravis may be due to the most common microbes — streptococcus, and particularly the colon bacillus. It is observed in young subjects, sometimes in epidemic form, and in soldiers after overexertion. It may also occur in individuals exposed to mephitic vapours, or who have inhaled sewer gas, or have worked in the soil. In women, pregnancy and the puerperium represent indisputable predis- posing causes. The disease is essentially characterized by the occur- rence of an always serious icterus with fever, accompanied by disorders of the nervous system and hemorrhages, which indicate the profound intoxication of the organism. The first clinical form of icterus gravis is often cured, generally after a urinary crisis — i. e., a sudden increase of the renal secretion, which throws out the poisons accumulated dur- ing the course of the disease. 204 AUTO-INTOXICATIONS OF HEPATIC ORIGIN A second variety of icterus gravis is that which is induced by poi- sons capable of provoking degeneration of the hepatic cells, of which phosphorus is an example. Lastly, the third group comprises the secondary forms of icterus gravis, which terminate the evolution of the various affections of the liver — cirrhosis, hydatid cyst, cancer, and passive congestion of the liver. Disturbances which rapidly grow worse are developed, such as hemorrhages and nervous manifestations, and the individual finally succumbs to hepatic insufficiency. These three varieties, while quite distinct from an etiological stand- point, are similar in their clinical manifestations. In fact, they are all due to the same process. All the causes which we have mentioned induce degeneration of the hepatic cells. Although the point of de- parture is different, the results are alike; the process is always de- pendent upon suppression of the functions of the liver. It is therefore at present easy to explain the mechanism of icterus gravis. The ancient theory which assumed the passage of the bile into the blood is no longer tenable, for no one would be able to under- stand why mild icterus should exist. The idea of Frerichs, who sup- posed an accumulation within the organism, not of the bile, but of products which were to be elaborated in the liver for its formation, is not supported by conclusive proof. Impressed with the inadequacy of the hepatic theories, Whitla and Decaudin have attributed the prin- cipal role to concomitant alterations of the kidneys. There is some truth in this view. It is certain that in persons suffering with Bright^s disease, all cases of icterus are of a very serious prognosis. Nevertheless, there are cases in which the kidneys are permeable, and yet accidents occur. The principal role, therefore, is to be attributed to hepatic disorders. But it is not in the bile-producing function of the liver that an explanation of the disturbances is to be found, it is rather in the study of its antitoxic function. When the cells have become insufficient, the numerous toxic substances which should be retained and annihilated by the liver pass freely through the gland and impregnate the system. Icterus gravis may therefore be defined as an auto-intoxication dependent upon insufficiency of the liver. It is conceivable that the most varied causes may give rise to this syndrome ; all that is necessary is the production of a diffuse degen- eration of the hepatic cells. Auto-intoxications of Pulmonary, Cutaneous, and Renal Origin. — In addition to the liver, various glands are charged with the duty of preventing the intoxication of the organism. We have already indi- cated the role of the thyroid gland and of the suprarenal capsules. We shall now consider the organs concerned in the elimination of poisons. DISTURBANCES OF NUTRITION 205 The lungs and the skin belong to this group. The action of the lungs, however, is much more important than was once believed. At the present day it is known that the lungs not only eliminate volatile substances, but neutralize alkaloids, such as nicotine, the sulphates of strychnine and atropine, organic acids, and salts, such as arsenite of potash. Their action is not exercised unless respiration be normal. The process is probably one of oxidation. The skin seems to eliminate volatile substances only. When the exhalation of the skin is suppressed, as is the case when the body of an animal is varnished, death supervenes in coma accompanied by a fall of temperature, scanty urine, albuminuria, and sometimes hematuria. The effects are the same when an extensive, even though superficial, burn abolishes the action of the skin, or when the integument is the seat of extensive dermatoses. The kidneys also come to the assistance of the organism. To a certain extent they can make up for the cutaneous as well as for the hepatic insufficiency, and eliminate the excess of poisons. But, finally, in consequence of the excessive work imposed on them, or as the result of the continual passage through them of anomalous substances, they in turn become altered and incapable of depurating the organism. Then a new syndrome develops — namely, uraemia. Urcemia is to the kidney what icterus gravis is to the liver. It is a syndrome resulting from an auto-intoxication dependent upon renal insufficiency, which, of course, means that this morbid state may appear under the most dissimilar conditions, such as occur during the course of infections, intoxications, whether of exogenous or endogenous origin, and all processes capable of altering the epithelia of the kidneys. The mechanism of uraemia has long been a subject of discussion. It was once attributed to the systemic accumulation of urea ; but this substance, on the contrary, far from being toxic, serves to assure diu- resis, and its subcutaneous introduction gives good results in the treat- ment of certain cases of renal insufficiency. Urea being easily trans- formed into ammonium carbonate, this salt was next looked upon as the causative factor. This theory contans a great deal of truth, but it appears to be too exclusive. In reality, uraemia is a complex intoxi- cation, due to the retention of various poisons the presence of which in the urine has been demonstrated by experimental analysis. But we can understand that according to the nature, extent, and profundity of the renal alterations certain substances may be able to traverse the filter and that others may be retained. Probably this explains the diversity of the disturbances and the variability of the clinical manifestations, which have been grouped under three principal heads. 206 AUTO-INTOXICATIONS OF RENAL ORIGIN according as nervous, gastrointestinal, or dyspnoic phenomena pre- dominate. It would not, however, be proper to simplify the theory too much, or to imagine that uraemia is due to retention of urine, or that intravenous injection of this liquid produces in animals disturb- ances identical with those observed in man. In reality, the facts are more complex. The urinary poisons stored up gradually act upon the nutrition of the cells. Accumulating in the blood and the tissue fluids, they completely modify nutritive exchange. What proves this is that the blood serum contains albuminoid substances which differ in their toxic properties from those which are normally found there. In fact, it has been recognised that the blood of uraemic subjects is very toxic for the rabbit. This result does not at all demonstrate the accumulation of substances which should be eliminated by the urine, for the toxicity of the serum depends upon albuminoid substances — namely, substances which are not at all concerned in urinary toxicity. This, however, is not a sufficient reason to deny the accumulation of urinary poisons within the organism, for this secretion is very slightly toxic in cases of renal insufficiency ; we mean that only these poisons, once retained, induce profound modifications in the elaboration of albuminoid matter. Insufficiency of the liver and, secondarily, of the kidneys also explains the development of puerperal eclampsia. The presence of albumin in the urine of a pregnant woman often enables us to foretell the imminence of this formidable manifestation. The study of the serum establishes that this liquid is very toxic and can kill in minute doses of from 3 to 6 cubic centimetres. This toxicological research is not merely of speculative interest. Experience demonstrates that the prognosis remains good, despite the gravity of the symptoms, when the serum is feebly toxic. On the other hand, a very toxic serum must lead to a grave prognosis, even though the symptoms be mild. Auto-intoxications in Nervous Affections and Infections. — Ex- tremely interesting researches have also been pursued in connection with auto-intoxication in mental affections. As a rule, the toxicity of the urine is increased, and sometimes it presents particular character- istics connected with the state of the patients. According to Brugia, the urine of excited persons is convulsive, while that of depressed individuals produces prostration and considerable hypothermia. Fi- nally, turning his attention to a paroxysmal disease — viz., epilepsy — Dr. Fere established that the urine, which is very toxic and strongly convulsivant before an attack, afterward becomes feebly toxic and slightly convulsivant. DISTURBANCES OF NUTRITION 207 The study of infectious diseases has particularly given rise to numerous researches. We have already said that intoxication plays the principal part in all infections. Toxic substances are referable to three sources : Some are produced by the pathogenic agent ; others are derived from gastrointestinal fermentations, generally increased; and still others are due to exaggerated or perverted cellular disassimi- lation. If we remember that in every infectious disease there is an alteration of the glands charged with the destruction or elimination of poisons — that the liver, the kidneys, the thyroid gland, the supra- renal capsules, and the skin are more or less affected — we must conclude that all work together to prevent the depuration of the organism. The disorders in the elaboration of the materials of nutrition affect the composition of the urine, which is found to contain extractive matters and amido acids in excess, and often anomalous substances, such as serine, globulines, and albumoses. It is probable that the tox- icity so marked in the blood and urine is due to modification of albu- minoids. Even injected into beings of similar species, the urine de- rived from infected animals causes death in minute doses of from 10 to 15 cubic centimetres. By injecting into rabbits the serum of indi- viduals suffering from pneumonia, Eummo and Bordoni found that instead of 10 cubic centimetres, which is a fatal dose under normal con- ditions, the toxicity is from 5 to 6 cubic centimetres, and before defer- vescence may reach 0.8 cubic centimetre. In studying the serum of typhoid patients, the same authors observed that the fatal dose, which varies within normal limits during the first week of the disease, rises during the second week to a point represented by 2 cubic centimetres and even 1 cubic centimetre ; then it diminishes, and is again reduced to its usual figure during the following week. The variations in the toxicity of the urine are not necessarily par- allel with those of the toxicity of the serum. As a rule, they follow reverse directions. An especially striking example is seen in pneu- monia; while the serum becomes more and more toxic as the disease advances, the toxicity of the urine diminishes. On the eve of the crisis it falls to its minimum, then it abruptly rises. Therefore we may suppose that during the course of the disease nondialyzable sub- stances accumulate in the economy and impart to the blood its tox- icity. At the moment of convalescence these probably undergo a trans- formation, rendering them dialyzable ; there must be produced a dislo- cation of very unstable albuminoids, which fact explains why there are found in the urine ptomaines, which certainly are derived from the pri- mary poison, the presence of which in the blood is demonstrated by experiment. 208 AUTO-INTOXICATIONS CHEMICALLY DEFINED Auto-intoxication chemically defined. — Parallel with the auto-intox- ications which we have thus far studied, and in which the complex phenomena are due to various chemically ill-defined poisons, must be placed those intoxications due to well-determined substances. We shall note lacticaemia — i. e., the accumulation of lactic acid in the blood. It occurs when oxidation is hindered — e. g., in asphyxia, infectious diseases, and poisonings by phosphorus and carbonic oxide; it may also be observed in gastrointestinal affections and in diabetes, where lactic acid is found associated with diverse organic acids. This excess of acids in the blood explains the pains in the bones of dia- betics, and it also accounts for rickets induced by gastrointestinal disorders. In speaking of digestive auto-intoxication we noted a special syn- drome — i. e., the dyspeptic coma related to diaceturia. This syndrome is chiefly observed in diabetics, and particularly in those who, on the advice of their physician, eat too much meat. We then observe the various phenomena characterizing this morbid state, occurring in most eases in consequence of fatigue or a journey. At all events, the symp- toms are very simple and three in number : a sharp pain in the epigas- trium ; a progressive obnubilation, terminating in coma ; a respiratory type, designated KussmauFs coma, characterized by breathing divided into four periods — a brisk inspiration, a pause, a brisk expiration, and a pause. Along with these disorders, or prior to their appearance, a characteristic phenomenon is produced — that is, a special odour ex- haled by the breath and urine of the patient — a strong odour recalling that of chloroform. It is attributed to acetone, whence the name ace- tonsemia or acetonuria, often given to the syndrome. But if acetone is in fact produced under these circumstances, the disturbances are rather attributable to a similar body, ethyldiacetic or acetylacetic acid. It is this acid that is brought to light by the following test, which should always be resorted to in these cases : The urine being placed in a test tube, a few drops of perchloride of iron are poured along the side of the tube. The iron, by virtue of its density, falls to the bottom of the test tube, and if ethyldiacetic acid exists, the perchloride assumes a brownish-red colour, resembling that of Bordeaux wine. The reaction is not absolutely characteristic, for it is also produced when the pa- tient has ingested antipyrine. This source of error, however, is easily eliminated. Apart from ethyldiacetic acid, the urine contains other acids, such as lactic and ^-oxy butyric acids. This led to the belief that it would be possible to prevent accidents by neutralizing these acids, by intra- venous injections of solutions of sodium bicarbonate. The attempt was rational, but it has as yet given no results. DISTURBANCES OF NUTRITION 209 Aside from diabetes, diaceturia may be produced in the following conditions : In persons subsisting on a meat diet ; in certain forms of dyspepsia, where it engenders coma similar to diabetic coma, but dif- fering from the latter by the absence of KussmauFs respiration; in the course of certain infections, and in asphyxia. Among other chemically defined auto-intoxications must be men- tioned that caused by uric acid, which is derived from nuclein — that is, from cellular nuclei. The excessive production of this agent gives rise to the development of gout. We must also mention ammoniacal intoxication, which occurs in infectious diseases, and especially in affections of the digestive canal and of the liver; intoxication by anomalous albumins and the albumoses, which are produced under a great number of circumstances already referred to; intoxication by ptomaines, the genesis of which we have pointed out; and, finally, intoxication by volatile substances originating in the alimentary canal — sulphuretted hydrogen and methylmercaptan. If we consider the numerous data furnished by the study of au- togenous poisons, we see that the living organism is always in danger of intoxication, even under normal conditions. In diseased states poi- sons increase because new substances are produced by pathogenic agents, gastrointestinal putrefaction is exaggerated, and cellular dis- assimilation is more active and often deviates from the normal type. These chemically ill-defined poisons have been well studied experi- mentally. Moreover, it has been established that the organism pos- sesses several means of protection against them; it transforms and eliminates them and produces antitoxic substances which counter- balance and neutralize their effects. When one of the protective organs is attacked, others replace it; for instance, the liver and kidneys can replace each other to a certain extent. This study of auto-intoxications has demonstrated that numerous morbid phenomena originate within the organism. There is no excep- tion here, however, to the rules already laid down. In fact, the dis- turbances are secondary, and always referable to an external cause. There are thus produced, directly or indirectly through the nervous system, cellular disorders, which secondarily give rise to humoral modi- fications. These derangements and modifications may be transitory, or they may become permanent ; in a great number of cases they may be transmitted to descendants. We are thus led to the study of the pathology of the foetus and of heredity. CHAPTER XIII PATHOLOGY OF THE FOETUS— HEREDITY Pathology of the foetus— Passage of toxic substances and of microbes through the placenta— Congenital infections— Malformations— Transmission of certain acquired characters — Heredity — Influence of each generator— Consanguineous marriages — Maternal impregnation — Atavism— Heredity of nutritive disor- ders: diathesis— Heredity in toxic and infectious diseases— Nervous heredity- Superior and inferior degenerates— Genius, insanity, crime — Conclusions. Although protected in the uterine cavity, the foetus is not entirely beyond the reach of external agents. It may suffer traumatism; it may be exposed to the influence of the surrounding modifications of a physical order; it may be assailed by toxic substances or animate agents entering through the only channel which connects it with the external world — through the placenta and the umbilical vein. Diseases or lesions may thus be produced which must be considered as congeni- tal and not hereditary. Intoxications. — The passage of toxic substances from the mother to the foetus has been repeatedly studied. Since the old experiments of Mayer (1817) and Albers (1859) and those of Dr. Porak, a great many facts have been discovered throwing new light upon the question. We now know that lead, arsenic, the iodide and bromide of potassium, and phosphorus may pass through the placenta. The last-named sub- stance at times produces placental hemorrhages and causes a charac- teristic fatty degeneration in the liver of the foetus. Iron and mercury do not pass from the mother to the foetus, although mercury accumu- lates in the placenta. Most of the colouring substances do not impreg- nate the foetus; yet Flourens observed that the bones and teeth were red in a pig whose mother had ingested madder during gestation. The intraplacental transmission of alkaloids, opium, atropine, quinine, etc., is generally conceded to-day. Certain clinical and experimental facts also prove that carbonic oxide may reach the foetus; but the quantity contained in its blood is six times less than that found in the mother. This proportion, more- 210 PATHOLOGY OF THE FGBTUS— HEREDITY 211 over, expresses a general law : Weights being equal, the foetus contains a less amount of toxic substances than the mother, and its tissues offer a much greater resistance to intoxication. Living foetuses have been extracted from the uteri of women and animals killed by chloro- form, chloral, or asphyxiation. A very interesting experiment by Savory positively established this fact: If one of the foetuses be ex- tracted by laparotomy from the uterus of a pregnant female and be returned to the womb after having received a strong injection of strychnine, fatal convulsions will be produced in the mother in con- sequence of the passage of the alkaloid from the foetus to the mother through the placental circulation. The foetus is in no way affected, and, if sufficiently developed, a Cesarean operation may save it. It withstands, then, a much stronger dose of strychnine than suffices to kill the mother. The foetus may die in a case of poisoning, but its death is then brought about by the fall of blood pressure in the mother. Let us now consider the organs qualified to protect the foetus against poisons. As poisons are always brought in by the umbilical vein, they first travel through the liver. This organ acts as in the adult; it arrests and destroys the toxic substances, provided it contains glycogen. Now, the researches of Claude Bernard have shown that glycogen exists in the embryo at first only in a diffused state, and that it is only from the second half of gestation onward that it localizes itself in the liver; it is from this period that this organ exerts its protective functions. The poisons not destroyed by the liver leave the foetus by the umbilical artery and the placenta, and in this way return to the mother. It has been said that they are also eliminated by the kidneys. The experiments of Dr. Porak, however, do not confirm this assertion; the amniotic fluid does not contain the substances absorbed. If sali- cylate of sodium be given a few hours before parturition, no trace of the substance can be found in the urine of the newborn. Therefore it may be stated that renal elimination begins at birth and becomes effective only at the end of a few days. Infections of the Foetus. — Do microbes, like poisons, pass through the placenta ? The answer is not a matter of doubt ; the existence of congenital smallpox and syphilis is an incontrovertible demonstration of the passage of microbes from the mother to the product. The memorable experiments of Pasteur on silkworms furnish very interesting results in this connection. Two diseases exist among silk- worms, pebrine and flacherie. The germs of pebrine may pass from the mother to the eggs and to the young; the male does not transmit the disease, but produces a debilitated progeny. In flacherie, on the 212 INFECTIONS OF THE FCETUS contrary, neither the male nor the female can transmit the infection; but if one of them has contracted the disease, the offspring is weak and evinces a well-marked tendency to acquire the disease. Analogous facts are observed in man and in mammals. The first experimental researches, in this case as in all the others, were under- taken with anthrax. Brauell and Davaine, the experimenters who began the study of the question, obtained negative results only, and affirmed that the placenta is a perfect filter. This law of Brauell- Davaine is false, as Straus and Chamberland have shown. But the number of bacilli which pass through the placenta is minimal, and microscopic observation does not suffice to reveal their presence ; only cultures made with large quantities of liver will do so. In this manner positive results are obtained in about half the cases. The problem as to the cause of these inconstant results has been taken up by Dr. Mal- voz. According to this author, the Bacillus anthracis passes through the placenta only when this organ is altered. The problem, therefore, as to what are the causes of the localization of microbes in the pla- centa as well as in other organs resolves itself into a much wider ques- tion, and one which we can not satisfactorily solve, although we have some data bearing upon it. However this may be, the results are identical in man. In four published observations the foetus of a mother suffering from anthrax twice contained the bacterium (Mar- chand, Paltauf), twice it did not (Eppinger, Morisani). Among the other microbes which may produce foetal infection may be cited the pneumococcus, which may cause a much more serious dis- ease than in the mother. In an observation of Thorner, a woman was delivered the day after the defervescence of a pneumonia; the child died thirty-six hours later. The autopsy revealed hepatization of the lower lobe of the left lung and the presence of pneumococci. Netter has reported a case of congenital infection in which pneumococci in- vaded the lungs, the pleura, and the meninges. Eelatively numerous observations establish that the bacillus of Eberth may pass through the placenta; but it does not produce any lesion in the foetus, no alteration of Peyer's patches, and no splenic hypertrophy. It causes a true septicaemia. It is different with smallpox. There are on record a certain num- ber of observations of congenital smallpox in which the child came into the world with the pustules characteristic of the disease. In most cases it had not advanced so far in the child as in the mother. This proves that their infection had not been simultaneous. It goes without saying that contamination is not a constant occurrence; in twin birth one of the children has been known to be affected and the other not. Finally, vaccinated women living in an epidemic centre. PATHOLOGY OF THE FCETUS— HEREDITY 213 without being themselves affected, have given birth to children covered with pustules. The other eruptive fevers are also observed in the foetus, but only exceptionally. The transmission of various infections, such as glanders, hydro- phobia, cholera, and paludism, has also been observed. Although very interesting, these facts add nothing new to the history of congenital infections. On the other hand, highly important results have accrued from the study of two chronic infections — namely, syphilis and tuber- culosis. While the preceding diseases have a rapid evolution and can be communicated only by the mother, in syphilis and tuberculosis the influence of both parents must be taken into account. Hereditary Syphilis. — When the mother is syphilitic, there are sev- eral possibilities. In certain cases placental lesions exist and bring about abortion. The frequency of this occurrence is well known; and repeated abortions, if otherwise unexplained, must always suggest syphilis. In other cases the child is born with specific manifestations upon the skin and mucous membranes. A third class of facts is made up of those in which the child, normal at birth, shows syphilitic affec- tion toward the sixth week; various eruptions appear, particularly blebs of pemphigus, which, when located upon the soles of the feet, are absolutely characteristic. But the specific lesions may appear much later — for example, after fifteen or twenty years. This is what is known as retarded hereditary syphilis. When the father alone is syphilitic, the same possibilities exist, and abortions are particularly frequent. But, what is more remarkable, the foetus may be syphilitic while the mother remains sound. Neverthe- less, in such cases the maternal organism is altered, since it has acquired immunity from syphilis. This is known as the law of Colles, which, from a practical standpoint, may be expressed as follows: A woman who has been delivered of a syphilitic child, if she remains unaffected, can suckle her nursling without exposing herself to con- tamination. Several hypotheses have been advanced to explain this immunity. It has been maintained by some that a uterine chancre existed and passed unnoticed. If this were the case the immunity would be due simply to an infection. In support of this theory the unique obser- vation of Lewis is cited: A woman is fecundated by a syphilitic and gives birth to a contaminated child; she remains intact. Subse- quently she is impregnated by a healthy man and conceives another child, also syphilitic. Here is proof that the unknown microbe of syphilis had invaded the maternal organism. It is true that this fact admits of another explanation and could just as well be looked upon 214 HEREDITARY SYPHILIS as an instance of conceptional syphilis. Under this name are grouped those cases in which the organism of a woman bearing a syphilitic foetus is from the first invaded by the virus and a general infection occurs without primary lesions, but which is immediately expressed by secondary manifestations. In this case it is the microbe which has passed through the placenta from the foetus to the mother. When immunity alone is transmitted, it is generally admitted that only the soluble substances, and not the figurate elements, have traversed the filter and have conferred upon the mother a marked power of resist- ing infection. When the parents are not syphilitic and the mother contracts the disease during pregnancy, two results are possible: If contamination takes place before the seventh month, the chances are that the foetus will be infected ; after that time it will remain sound ; and this is easily understood, since the infection has not had time to spread, because it is still local. If a child born of a syphilitic mother manifests no trace of infec- tion at birth, it may be suckled by its mother without danger. It has acquired immunity. This is the law of Profeta, which may be placed by the side of the law of Colles. Hereditary Tuberculosis. — The observations made upon hereditary syphilis have been turned to account in the study of tuberculosis. At the present day it is an incontestable fact that tuberculosis is very fre- quent in early childhood. Dr. Landouzy, who has clearly brought this fact to light, is of the opinion that half the cases of death in newborn children are caused by this infection. Although an agreement has been reached on this first point, the operating mechanism is still a subject of contention. According to some, it is the germ which is transmitted; according to others, it is only a predisposed organism — the soil. In other words, the child may be born tubercular or with a tubercular tendency. Incontrovertible, if not numerous, instances in which tubercles con- taining the characteristic microbe were found in stillborn children have been cited in favour of intraplacental transmission. In some cases the lesions predominate in the liver, which is the first organ reached by the bacilli coming from the placenta. Analogies derived from syphilis have led to the admission that the microbe may remain inactive in some corner of the organism — in the marrow of the bones, for instance — and become active several years later, on the occasion of a traumatism or any other cause. A delayed form of hereditary tuberculosis, more or less analogous to hereditary syphilis, is often shown by the presence of osseous or articular manifestations. This idea is supported by experiments which PATHOLOGY OF THE FCETUS— HEREDITY 215 prove that apparently sound foetal organs may contain bacilli, and also by the researches of Maffucci, who, after introducing various microbes into hens' eggs, saw infection occur long after hatching. The transmissibility of the bacillus is an undeniable fact. Con- genital tuberculosis exists, but it is of exceptional occurrence. More frequently the tendency is transmitted : the child comes into the world with a vicious nutrition, which manifests itself in lymphatism, scrof- ula, or chlorosis, as the case may be, and creates a marked predisposi- tion to tubercular infection. Congenital Malformations. — Not infrequently infections become the starting point of congenital malformations. For instance, in car- diac infection the right heart, which is more active, is preferably affected. The microbes locate themselves upon the pulmonary valves, causing adhesions and consequent stricture of the orifice. The blood, unable to pass freely along its normal channel, makes its way through the temporary openings and prevents their closure. According to the period at which the lesion of the pulmonary artery has taken place, there result a permanency of the opening in the interventricular septum or of the foramen of Botal, persistence of the ductus arteriosus, com- pensatory development of the bronchial arteries, etc. Most cases of congenital malformations, however, arise from an- other mechanism; and they are connected with disturbances of fecun- dation, as has been shown by numerous researches, most of them made upon the lower animals. When a cell is about to divide, the nucleus presents several impor- tant modifications. The chromatic filament, constituting its principal part, increases in distinctness; it assumes a stellate form, and, finally, separates into a certain number of chromatic rods called chromosomes, each one shaped like a V. The number of chromosomes is fixed, and always the same for every cell of the same species. Let us suppose that they are eight in number. They arrange themselves in a circle and perpendicularly to the long axis of the cell, the vertex of the V toward the centre. In this position they form the equatorial plate. Meanwhile a light spot called centrosome has appeared at the two poles of the cell. Very soon the chromosomes divide longitudinally, thus making 16 half chromosomes in the equatorial plate. During this time filaments coming from the centrosomes have reached the apex of the divided rods, and, in contracting, draw them toward the poles. Eight half chromosomes are thus united to each centro- some, producing what has been called ampJiiaster. At this moment evolution is completed; the cellular protoplasm divides, while the chromosomes return to quiescence, fuse, and again form a chromatic filament. 15 216 CONGENITAL MALFORMATIONS Thus the two daughter cells will each have a chromatic filament made of 8 rods. Just as the mother cell. If we now turn our attention to the ovum, we find that the germi- nal vesicle, the part corresponding to the nucleus, migrates to the periphery of the ovum when it has reached maturity. A division of the nucleus then takes place and produces two nuclei, each containing 8 half chromosomes. One of these nuclei leaves the cell. This is the first polar globule. The remaining nucleus, instead of returning to quiescence, immediately divides. The chromatic filaments do not have time to grow, and, consequently, can not further subdivide. But the two nuclei come into existence in another way : The half rods arrange themselves in groups of 4 and form two semiamphiasters ; we thus have two half nuclei. One of them, the second polar glohule, located at the periphery, leaves the ovum; the other remains and constitutes the female pronucleus. Thus this cell, primarily containing 8 rods, first undergoes divi- sion, producing 16 half chromosomes. Eight of these leave the cell with the first polar globule, and 4 of the remaining 8 leave with the second polar globule. Four only remain in the ovum. Consequently, the ovum represents but half a cell. The spermatozoon also represents a half cell. It is born in a cell called male ovum, which, instead of dividing into two, splits into two twice in succession without interval of rest. Thus a male ovum pro- duces 4 spermatozoa, each possessing half of the chromatic rods be- longing to a normal cell. When fecundation takes place, a spermatozoon penetrates the ovum. This spermatozoon consists of a head corresponding to the chromosome, an intermediary part answering to the centrosome, and a tail, a mere organ of locomotion similar to the vibrating cilia of certain cells. As the result of a special attraction, the head and the body, making up the male pronucleus^ advance toward the female pro- nucleus, which has resumed its place at the centre of the ovum. When the two elements meet, the chromosomes unite, and from the fusion of the two half nuclei a complete nucleus with the required number of chromosomes results. As to the centrosomes, they divide into two; then, after performing an evolution of 90 degrees (quadrille of Fol), they come in contact. As a result of contact two new centrosomes composed of a male semicentrosome and a female semicentrosome are produced. Thus a complete nucleus is formed, called the yolk nucleus. This nucleus divides regularly. Every cell of the body is derived from it. Each one of these cells acquires the same number of chro- matic rods as the initial cell, and each of them also contains an exactly PATHOLOGY OF THE FCET US— HEREDITY 217 equal part of the male and female elements. The process of karyo- kinetic division insures the equal distribution of the two substances in every cell. Under normal conditions, one spermatozoon fertilizes the ovum, but under certain abnormal conditions several spermatozoa find their way into the egg. From two to ten have been observed in one ovum. Beyond this number the egg succumbs. Recent researches, particu- larly those of Fol, have made a successful beginning in the search for the cause of these anomalies of fecundation. Several spermatozoa may penetrate the ovum when fertilization takes place before perfect matu- rity of the egg. Under these conditions the enveloping membrane is not yet sufficiently resistant; it does not close in quickly enough after the passage of the male element, and through the opening thus left other fecundating cells may enter. The result is the same when ferti- lization occurs too late, since the enveloping membrane has then lost some of its strength. Moreover, hyperfecundation takes place when the egg comes from a weakened, sickly animal, or, as Fol has shown in his experiments on sea urchins, when it is anaesthetized by a current of car- bonic acid. If two spermatozoa penetrate the ovum in consequence of one of the causes just stated, segmentation of the germinal vesicle gives birth to four amphiasters, and, consequently, to two cells, which separate and become the centre of two embryos. It was formerly believed that this double fecundation was due to the existence of two nuclei in the same ovum; we now know that it is due to double fertilization of a single nucleus. The two primitive lines found in cases of double fecundation de- velop parallel to each other; from this a twin pregnancy results. The two beings have one and the same origin; they represent one being divided into two. It follows from this genesis that they are always of the same sex, and that a striking physical and moral likeness is to be expected. They may have the same thought at the same moment ; a sentence begun by one of them may be completed by the other. These cases must not be confounded with the twin births resulting from the intra-uterine fecundation of two ovules which produces two different beings of the same or of a different sex. This must be looked upon as the reappearance in man of a phenomenon which is of normal occur- rence in most animals. When two foetuses develop in the same ovule it may happen that the two primitive lines meet and fuse at a specific instant, thus occa- sioning the formation of a double monster. The several varieties observed under these circumstances may easily be brought back to a few types. 218 CONGENITAL MALFORMATIONS Let ns suppose that the two primitive lines are in a straight line. If they meet, the two beings unite at the vertex, the rest of the two bodies remaining independent. If they form an obtuse or a right angle, the heads and the upper parts of the trunk fuse and produce a monstrosity. The best known of this class is called Janiceps — i. e., a monster with a double face. The fusion having taken place when the head was open in front, the two beings have united along their anterior portions, so that each face is formed out of an equal part of each being. When the two primitive lines meet at an acute angle, the trunk, the neck, and the lower part of the head unite. Finally, if the lines are parallel, the fusion involves the trunk, and if they are slightly divergent, the lower extremities alone are joined. We have thus far supposed that the two beings developed equally, and that the monstrosity resulted from a simple accidental fusion. But it may happen that one of the embryos does not develop well ; a part necessary to life — the circulatory or the nervous system — may be missing, or the subject may remain in a quite rudimentary state. Unable to live of itself, it will ingraft itself upon its fellow and become a parasite, or it may penetrate into the abdominal cavity and thus become a sort of tumour. Aside from the facts just considered, monstrosities have been known to occur even with normal fecundation. The determination of these monstrosities has been brought into evidence by important re- searches initiated by Dr. Dareste. The experimenter can at will cause the birth of a monster. It suffices here, as everywhere else, to call into play external agents — mechanical, physical, chemical, or animate. For instance, if the egg, instead of being allowed to remain in its normal surroundings, be subjected to the influence of certain motions, say rapid vibrations; or if it be kept in abnormal positions — for in- stance, in a vertical position ; or if certain cellular groups be destroyed during their evolution, as was done by Chabry, a monster will be pro- duced. If one wants to use physical agents, the egg may be placed in an oven too hot or too cold; or, what is a still safer means, its surface may be unequally heated. Its growth may be modified even by light rays. Of late chemical substances have been used. Dr. Fere has pro- duced a great number of monstrosities by exposing hens' eggs to the influence of volatile poisons, such as ether, chloroform, vapours of mercury, or by injecting into the eggs toxic substances, living microbes, or soluble products obtained from microbic cultures. PATHOLOGY OF THE FCETUS— HEREDITY 219 Can these researches made upon oviparous animals be applied to mammals? This question can now be answered affirmatively. Mon- sters are the result of external causes acting either directly on the embryo, or, what is more frequently the case, indirectly through dis- turbances or lesions of the membranes of the egg. Alterations of the amnion, exaggerated or insufficient secretions of the amniotic fluid, lesions of the vascular area due to compression, or the trophic dis- turbances they provoke, induce irregular evolution of the foetus. The best example is that of syphilis, which frequently produces amniotic lesions and consecutively causes numerous malformations, such as spina bifida, harelip, and clubfoot. Every defect of structure and every monstrosity can be explained as partial arrest of development or as hypernutrition. In the first case certain parts are atrophied, others remain rudi- mentary, and unions fail to take place. In the second case certain parts develop excessively, or a normally transitory disposition becomes a permanent one. If it be remembered that ontogeny is the recapitula- tion of phylogeny, it becomes clear that the persistence of a transitory disposition represents a variation toward an existing type, or a type having existed in another species. Anomaly, then, is the reproduction of a state normal in other beings, whether living or extinct. Most, but not all, of these anomalies may be transmitted by hered- ity. The remark has even been made that the deepest and strangest transformations are generally those that hardly ever persist in the descendants. As a matter of fact, the malformations we have studied — namely, those resulting from a disturbance of the normal evolution — must be clearly distinguished from those in a way merely accidental. For instance, if the umbilical cord twists itself around one or several limbs and causes amputation by pressure, we have an accident which will not be transmitted. Similarly, when an infection has produced a pulmonary stricture resulting in persistence of the foramen of Botal or of the interventricular orifice, the cardiac malformation will not be found in the descendants. Accidental lesions, whether congenital or acquired, remain isolated; they do not affect the offspring. On the contrary, when there are defects in the evolution of the ovum and when the anatomical anomaly results from a functional deviation, the leading tendency which presides over the development of the being and assures the unity of the species seems to be profoundly altered. Several generations will be required before the normal type is repro- duced. We are thus led to ask why accidental anomalies are not trans- mitted, while those due to functional disturbances pass to the off- spring. This study brings us to the history of heredity. 220 HEREDITY Heredity Heredity, says M. Kibot, is the biological law according to which living beings tend to repeat themselves in their offspring and to trans- mit to them their properties. Two great laws seem to govern and explain heredity: the law of conservation of the ancestral type and the law of evolution. The species possesses a unity, or rather an individuality, and it preserves its fundamental characteristics through the ages in such a way that men of all times and of all countries resemble each other. The likeness, however, is not perfect; certain modifications have oc- curred, and it is quite certain that the civilized man of the nineteenth century is not identical with primitive man. An evolution has taken place. Its significance will be better comprehended if it be remembered that the species is ruled by the very laws that govern the individual. If we consider a being from birth up to advanced old age, we ob- serve in it the working of the two laws just mentioned. It is clear that the adult individual is no longer the same as in his childhood, and that he will still continue to alter as he advances in years. Never- theless, in spite of these continual changes, the individual type has been preserved, and in the midst of successive transformations the immu- table foundation which maintains the personality of the individual remains. The species is neither more nor less modifiable. It evolves as well as the individual, and also passes through the three phases of growth, climax, and decay. The species is preserved through the ages, and it maintains through heredity its resemblance to itself, just as person- ality preserves that of the individual. If we consider inferior beings, heredity seems much more perfect. But this is, in reality, an optical defect of our minds, if the expression be allowed. It is harder for us to grasp that which constitutes per- sonality than to perceive the common traits. Consequently, our atten- tion goes to the latter, and thus, because we do not see the differences, we believe that all individuals are identical and remain so. In superior beings, and particularly in man, we are in the habit of looking for the dissimilarities. On closer scrutiny, however, it is easy to convince one's self that the resemblances are always preponderant ; the common characteristics are more numerous than the points of difference. Con- sequently, it can be said that heredity is the rule and nonheredity the exception. The greatest naturalists and the most celebrated philosophers have taken up the study of heredity and have endeavoured to explain it. But most of their theories belong to the past. The gemmules of Dar- PATHOLOGY OF THE FCETUS— HEREDITY 221 win and the plastidules of Haeckel are now well forgotten. The ideas of Weissmann alone deserve our attention, although they have been vigorously criticised by most authors. Weissmann establishes a radical difference between the reproductive and the other cells of the body. The former are eternal ; they do not die, and thus they assure the perpetuity of the species. This state- ment, which may at first seem fantastic, finds support in the study of unicellular beings. Amoebae perpetuate themselves by fission. It is not exact to say that one animalcule has given birth to another. There is neither mother nor daughter, but there are two sisters. Amoebae are collateral beings ; and the amoeba of the nineteenth century is the same as the one which existed at the beginning of the world. If, perchance, a few amoebae die, or the pool in which they live dries up, their death is merely a matter of accident. Nothing in the evolution of this pro- tozoon doomed it to death. For it natural death does not exist. The same reasoning may be applied to the generation of the cells of higher animals. The only difference is that they produce two classes of cells : cells whose function is to maintain the life of the species, and which are consequently immortal, and cells that will constitute the body, the soma; and are therefore destined to die. This theory of the continuity of the germinal plasma explains per- fectly the preservation of the specific type. But Weissmann pushes his theory to its utmost limits and sets up an impassable barrier between the somatic and the generating cells. He does not admit that the former may have any influence upon the latter, and is led in conse- quence to the absolute denial of the transmissibility of acquired char- acters. At this point we must make a distinction which to us seems to be of fundamental importance. Acquired characters may be of two kinds : They may be accidental, and therefore not transmissible ; or they may be due to functional modifications, and then they are hereditary. This distinction leads us to the following new conclusion: Heredity is the transmission of functional hut not of anatomical modifications. Those who deny the transmissibility of acquired characters gener- ally cite the Jewish race. For more than three thousand years cir- cumcision has been practised among them, and yet the children con- tinue to be born with foreskins. In the same way the young of cer- tain dogs whose tails and ears have been clipped are born with these appendages developed just the same. On the other hand, let us consider a functional disturbance. Noth- ing is so instructive in this respect as the famous experiment of Brown- Sequard. If the sciatic nerve of a guinea pig be cut, the animal be- comes epileptic. If it be mated and brings forth young, these will 222 HEREDITY also become epileptic. What is it, then, that has been transmitted in this case? Is it the mutilation? Not at all. The sciatic nerve in the offspring is quite normal. It is the functional disturbance alone which has been fixed by heredity. As the development of an organ is regulated by exercise of that organ, it is conceivable that transmitted functional modifications may be accompanied by anatomical alterations as a consequence. Suppose, for example, a man to be gifted by heredity with a superior intelli- gence; he will come into the world with particular aptitudes which will call forth an unusual development of his cerebral cells. In other words, it is not because the brain is highly developed that the intelli- gence of the individual is remarkable; but the anatomical centres which serve as the substratum of the function have attained an unusual development because he has inherited a superior cerebral power. Our conception is also applicable to congenital malformations. Those resulting from accident — for instance, amputation by the um- bilical cord — are analogous to acquired traumatic lesions. They are not transmitted. Those produced by functional disorder, and those representing an arrest or an excess of development, or a return to some ancestral form, are transmitted to a certain number of generations. The ideas just expressed are nothing more than the application of the great law that the function precedes the organ, and explains, directs, and regulates its development. Functional changes alone are powerful enough to modify the conservative role of heredity. To sum up, we admit that the germ plasm goes through the ages without manifesting any tendency to modification. It preserves the individuality of the species. The somatic cells, on the contrary, un- dergo the influence of evolution. They are affected by external agents, and, reacting in their turn on the germinal cells, give them a new direction. They tend to modify the primitive type. After the preced- ing considerations, again taking up the two great laws already offered as accounting for evolution, we can say: The law of conservation of the ancestral type finds its explanation in the persistence of the germ plasm; the law of evolution finds its explanation in the modification of the somatic cells. Accidental changes are not transmissible, be- cause they reach the soma only. Functional disturbances are hered- itary when the somatic modifications they induce react upon the germinal cells. If, in this last case, anatomical changes appear, it is because the development and the structure of the organs are governed by the functions of which they are the material substratum. It is, we believe, in this way that heredity can be understood, and that a satisfactory basis can be found for the two laws of conservation and evolution by which it appears to be governed. PATHOLOGY OF THE FOETUS— HEREDITY 223 Eole of the Two Generators. — In superior beings heredity is de- pendent upon two factors. Theoretically, according to the date of embryogeny, each cell of the newborn animal contains the same quan- tity of male and female chromatine. Accordingly, it would seem that the two generators must influence the product in an equal degree. As a matter of fact, the results are not so simple. Neither the physical nor the moral resemblance is an average. One of the parents exerts a preponderant influence. Several hypotheses have been advanced to explain this result. Orchansky claims that the parent nearest maturity imparts its sex and its likeness to the offspring. It is easy to raise objections to this theory. It is, however, sufficient to remark that in twin pregnancy children are frequently of a different sex. This fact might readily be explained if the opinion entertained by breeders be accepted. Accord- ing to this view, fecundation gives a male or a female according as it occurs at the beginning or end of the catamenia. If the twins are not of the same sex, it is because two eggs have been fertilized at two different times. Among the disorders which, without doubt, must be attributed to the collaboration of the two parents, those due to consanguinity de- serve attention. It is a matter of common knowledge that marriages between relatives give bad results. Such unions are often sterile or the children suffer from malformations, polydactylism, albinism, pig- mentary retinitis, and especially from deaf-mutism. But this is not always the case, and in many instances children born of such mar- riages have been perfectly normal. As a matter of fact, the effects of consanguineous marriages are to be explained simply as the summation of common characters. As they belong to the same family, the chances are great that the parents pos- sess the same characteristics and the same physical or moral defects. They may be slight in each one of them, but they add themselves and increase in the descendants, as they are not corrected by different de- fects or qualities. We conclude, then, that marriage between relatives will give good results when the pair do not possess analogous defects. Otherwise, the least defect may be considerably exaggerated in the offspring. Consanguinity must be looked upon as cumulative con- verging heredity. The same remarks apply to marriages formed between individuals of the same social class, and consequently having the same aptitudes, tastes, and tendencies. It is a social consanguinity, which may be com- pared to family consanguinity. The results are evidently analogous. Heredity fixes and exaggerates various defects, but natural selection sooner or later interferes. It counterbalances the retrogressive effects 224 HEREDITY of social selection, and ends in the sterility of these degenerate fam- ilies. The influence of the father is not alone felt by the ovum he has impregnated. Individuals born later have been known to resemble the first generator in some particulars. Impregnation of the mother, as the phrase has it, has taken place. All breeders know that a bitch fecundated for the first time by a dog of a different race gives birth in the two successive litters to young resembling the first father, although the second impregnation was by a dog of the same race as the mother. Cases are also cited of women of the white race who, after having had a child by a negro, have subsequently, and as the result of inter- course with a man of their own race, given birth to children on the bodies of which a few black pigmentary spots could be seen. Lingard knew a man belonging to a family in which for several generations all the males were hypospadic. This man married and had three hypospadic children. After his death his wife remarried and had four children, all of whom were hypospadic, although her second husband was perfectly formed. These four children had in their turn eleven children, only one of whom suffered from hypospadia. The structural defect transmitted as a result of the maternal impregnation had, it appears, modified her organism less deeply, since it showed a strong tendency to disappear. These facts have such a mysterious aspect that certain authors, unable to understand them, have found it easier to deny their reality. Those who have tried to explain them have advanced three theories : One of them supposes that an imperfect fecundation of a few ova still in the ovary takes place at the time of the first fertilization. An- other admits a perfect fecundation, and, moreover, supposes that the ovum waited for conditions more favourable to its development. These two hypotheses are evidently not based upon any known fact. It seems more rational to admit an impregnation of the mother by the foetus. The latter has inherited the qualities of the father; its cells have received from the father a nutritional and functional direc- tion manifested by a particular humoral state. As a consequence of the continuous changes taking place through the placenta, certain sol- uble products reach the mother and impart to her various functional aptitudes resembling those of the father. After all, this theory does no more than extend to the several forms of impregnation the results derived from the study of syphilis. All acquired characters, fixed in this way by heredity, pass from generation to generation indefinitely, until a time arrives when a character long since modified, or even lost, reappears without ascer- tainable causes. PATHOLOGY OF THE FCETUS— HEREDITY 225 This is what is called atavism. Darwin has collected a large num- ber of examples establishing that certain characters may skip several generations. We shall again refer to these facts, which have often been put forward in an exaggerated form to explain certain nervous variations. Heredity of ^N'utritive Disorders. — Among the functions whose modifications may influence heredity, the one most general must first be mentioned: nutrition. We shall be brief on this subject, as it has already been considered under diathesis. We have seen what part was to be ascribed to hereditary modifications in the development of arthritis and of scrofula, and we have shown how a slight taint in the parents grows worse in the descendants. The fact is striking in arthritic persons, and it easily admits of an explanation. When arthritism develops under the influence of external causes, the latter influence adult cells, which are endowed with a well-defined mode of activity. The modification, therefore, is to affect conditions of many years' standing, whereas disturbances transmitted by heredity affect young cells not yet possessed of a nutritive direction, and therefore readily infiuenced by the impressions they receive. In this way we adapt to the history of heredity the conditions which are the very basis of children's education. In both cases young cells yield easily to influences which they would resist in their adult state. In considering a family of arthritics, we find in certain of its members clinical tendencies which may coexist or alternate. Among its most habitual manifestations, arthritism includes gout, eczema, nervous affections — from neuralgias and hemicrania to hypochondria and neurasthenia — fat diabetes, gravel, biliary lithiasis, etc. These various disorders may coexist in the same individual, but more fre- quently they alternate either in himself or in his descendants. For instance, a gouty father may have an asthmatic child. In other cases, an arthritic's son, suffering in his youth from hemicrania, becomes asthmatic when about fifteen; around thirty or forty he is afflicted with gout, and later on dies of cerebral hemorrhage. Heredity is termed similar when the child suffers from exactly the same dis- orders as the father — when they, for instance, are both asthmatic or gouty. It is called homologous when the manifestations are different. Arthritism is the inheritance of civilized people and of the upper classes. Most individuals gifted with a superior intelligence are tainted by it. Geniuses are often sad, fantastic, one-sided; their cere- bral aptitudes have developed unequally; they suffer from deficiencies and disorders which at times border upon insanity. In such subjects heredity may continue to emphasize the superior qualities. Much too 226 HEREDITY OF NUTRITIVE DISORDERS often it assures the predominance of the cerebral disorders and ends in mental degeneration or insanity. We shall return to these questions when treating of nervous heredity. The second diathesis, scrofula, is found, we have said, in children born of parents in bad health, suffering from some chronic intoxica- tion or infection: alcoholism, syphilis, and especially tuberculosis. They are weaklings with flaccid muscles, long and silky eyelashes, hypertrophied tonsils, and wide nose. During their first years they suffer from impetigo and spurious inflammations entailing voluminous adenopathies. In their youth they are in danger of falling a prey to osseous or articular tuberculosis, which soon generalizes and prema- turely ends their lives. In this way the races of degenerates disappear according to the great laws of natural selection. The disorders of nutrition determined by chronic intoxications fre- quently manifest their influence in the offspring. Children of dipso- maniacs are badly developed and present numerous stigmata. Their size is below the average. The statistics published by the recruiting stations show for each department an almost perfect parallelism be- tween the diminution of the size of the recruits and the quantity of alcohol absorbed. The evolutive disorder may go so far that young men eighteen or twenty years old may be no more developed than children of fourteen or fifteen. The pilous system is rudimentary and the sexual organs are small. In addition to this infantilism better marked malformations may exist, such as cranial or facial asymmetry, porencephalia, hydrocephalia, and neurogliar sclerosis of the nervous centres. If we pass from the anatomical study to that of the functions, we shall note numerous disturbances of the nervous system. Anaes- thetic and hyperaesthetic spots are observed, as well as exaggerated reflexes. Sleep may be disturbed by nightmares, terrors, and frequently by urinary incontinence. The disposition of the subject is sad, morose, and sensibility is exaggerated. Intelligence is often precocious, and may seem to an- nounce great intellectual qualities. But soon an arrest takes place, or, at least, a lack of equilibrium, weakness of attention and of will, and some oddities of ideas and behaviour will be noticeable. At times, however, a few aptitudes persist, particularly artistic talents. But even in this case the asthenia of the nervous system expresses itself in a deficient moral sense and in bad and irresistible impulses. Among these vicious impulses dipsomania takes a distinct place. It is frequently said that an abuse of liquors leads to alcoholism; but it is generally the reverse which is true. The first excess is only the occasion which sets in motion a predisposed nervous system. PATHOLOGY OF THE FCETTJS— HEREDITY 227 We must hasten to add that heredity is not inevitable. When the son of an alcoholic is preserved from the influence of occasional causes, the development of dipsomania is retarded or even definitely prevented. Unfortunately, the occasions are often almost unavoidable for the young man in the workshop, in the army, and, above all, in the colonies. Nothing will henceforth stop the person who, following his parents, has begun to drink. What we have just said of dipsomania also applies to misde- meanours, thefts, or crimes. Of late, moralists have justly insisted upon the increase of child criminality. If antecedents are looked for, it is found that most young criminals are sons of degenerates, and particularly of alcoholics. On the slightest provocation the nervous system reveals these innate aptitudes. Several other less serious disturbances have the same pathogenesis. Convulsions, which are too readily looked upon by parents as common reactions, take place chiefly in tainted children on account of a para- site, an intestinal worm, or an infection like pneumonia. In certain instances the disorder may become more serious. The infection may localize itself in the predisposed nervous system, particularly in the spinal cord, and provoke an infantile paralysis. In other cases an intercurrent cause may determine the appearance of a neurosis, of hysteria, and especially of epilepsy. In 80 out of 100 cases epileptics are born of parents tainted with alcoholism. The other chronic intoxications are equally apt to give rise to mor- bid disturbances in the descendants. First of all, saturnism may be cited. When the mother is poisoned, abortion is the result most fre- quently observed. When it is the father, accidents are not less fre- quent, as is shown by the following figures, taken from C. Paul : Out of a total of 141 cases, there were 82 abortions, 4 premature births, and 5 stillborn children. Of the 50 children born alive, 20 died in the course of a year, 15 died between the first and the third year, and 14 were still living. When they survive, such children suffer from various morbid manifestations already referred to: frequent convulsions on the slightest cause, various degenerations, and serious nervous disor- ders, such as epilepsy, imbecility, idiocy, etc. We need not insist upon the other intoxications. Concerning car- bonic oxide, mercury, and morphine, we could repeat what we have said about alcohol and lead; but, of whatever nature the intoxication be, when degeneration reaches a certain degree, sterility supervenes. Thus inferior and defective races disappear. Heredity in Infectious Diseases. — The study of intoxications leads us quite naturally to that of infections, since it is through their toxic products that the microbes act. 228 HEREDITY IN INFECTIOUS DISEASES We have already sketched the history of intrauterine infections ; we have shown how microbes pass from the mother to the foetus through the placenta and how, less frequently, the infection is com- municated by the father. In the cases where the pathogenic agent does not traverse the pla- centa, the product may present a series of accidents called para-infec- tiouSy studied particularly in syphilis. It may be, first, a special cachexia, sometimes causing the death of the foetus. Hence, the fre- quency of abortions. If it comes into the world at all, the child is weak and has a bad constitution. It develops slowly, teething is re- tarded and defective; at times the number of teeth is below the nor- mal, at other times it is higher; a supernumerary tooth introduces itself between the two superior incisors. The teeth are dwarfed, stri- ated, eroded ; the superior median incisors frequently suffer a particular deformation described by Hutchinson — ^namely, a notched depression in the cutting margin of the teeth. The bones are poor in lime salts; hence their deformations, which are especially noticeable in the frontal bones and the tibiae. Parrot even maintained that syphilis is the great cause of rickets. It may well be that it predisposes to digestive disturbances, upon which the development of this morbid state apparently depends. Other parts of the organism are also affected : keratitis and deaf- ness frequently exist. With the dental alterations they constitute the triad of Hutchinson. The bodily and intellectual development is slow, infantilism is frequent, the genitals remain rudimentary, puberty is retarded, intelligence is weak, sometimes nil, and convulsions are fre- quent. At times matters go even further. Besides the various stig- mata just named, congenital malformations may be observed, such as spina bifida, harelip, hydrocephalus, or microcephalus. It is chiefly maternal heredity which engenders the disturbances just indicated. Paternal influence shows itself preferably in abortion. Out of 103 cases of pregnancy due to male syphilitics, only 19 children survived; 43 of them died in early infancy, and 41 died in utero or were aborted. But we may take comfort in the fact that the pernicious effect of syphilis slowly decreases and ultimately disappears. It is generally admitted that after a treatment of two years there are already some chances of having healthy children. After three years, it is almost the rule. Children of tubercular parents do not fare much better than those of syphilitics. They particularly present thoracic malformations, as if the respiratory disorders of the parents reacted upon the develop- ment of their lungs. Their respiratory capacity is below the average, PATHOLOGY OF THE FCET US— HEREDITY 229 and their lungs are often affected with emphysema — an alteration which Virchow has long considered as congenital. It is probably on account of this pulmonary dystrophia that the thoracic cavity develops badly. The chest is narrow, lacking in depth, the shoulder blades project, and the respiratory muscles are small. Finally, in these, as in all children born of diseased parents, the following additional stigmata may be observed : Slow teething, insuffi- cient ossification, infantilism, defective development of the genital organs, of the circulatory apparatus, and particularly of the aorta. In the opinion of some authors, this last defect explains the frequency of chlorosis. Hanot has insisted on the lobulation of the liver and of the kidneys. When the parental infections do not go so far as to cause stig- mata or bodily lesions, they frequently impart particular nutritive habits to the cells of the child and give to their humours a particular composition. It is in this way that predispositions and familiar im- munities are produced. If we leave aside tuberculosis, which we have already considered, we may mention a large number of infections of remarkably frequent occurrence in certain families. Such is the case in diphtheria, and especially in erysipelas, which in 13 out of 100 cases is a family dis- ease. The child probably receives from one of its parents a particular mode of nutrition, rendering its organism favourable to the culture of a special microbe. Consequently these cases must not be regarded as similar to those in which one of the parents is diseased and pro- duces a child incapable of offering resistance to the first microbe it chances to meet. In the former case, the predisposition is specific ; in the latter, it is general. Conversely, heredity explains certain immunities. It is justly said that infections work havoc when they reach a population for the first time. Such was the case with measles in the Faroe and Fiji Islands. If these diseases are innocent in Europe, it is because our ancestors who had them have transmitted to us a part of the immu- nity they acquired. But these facts have slowly been evolved through long ages. It is relatively difficult to understand their mechanism. Let us rather consider what takes place when immunity has just been acquired by the parents. The first question is: What is the respective role of the two gen- erators? Let us begin with the simplest case: The mother suffers during gestation from an infectious disease. We may admit that the protective substances formed in her system traverse the placenta and confer a certain degree of passive immunity upon the product. Thus, a child born of a mother who has had smallpox during pregnancy has 230 HEREDITY IN INFECTIOUS DISEASES acquired immimity from this disease. If a woman be vaccinated just before the end of gestation the child will for a certain length of time resist the smallpox virus; but this immunity is feebly marked and does not last; moreover, it is not a constant result. Analogous facts observed upon animals inoculated for rot, symptomatic anthrax, or hydrophobia complete the proof of the existence of ovular inoculation (Toussaint), but they also demonstrate that the immunity thus ac- quired is not well marked and is of short duration. The second problem is more interesting. It can be formulated as follows : Is it possible for the generators to transmit the immunity acquired by them against an infectious disease? Ehrlich, who was the first to study this question experimentally, inoculated a certain number of animals against tetanus, abrine, or ricine. On mating these animals with noninoculated ones, he discov- ered that the inoculated females always transmitted a certain degree of immunity to their offspring, while the influence of the male was nil. Wernicke's researches on diphtheria have confirmed this conclusion. Nevertheless, Tizzoni and Centanni and Charrin and Gley hold that immunity may have a paternal origin, although, according to them, this is rarely the case. Vaillard, who again took up the ques- tion, making use of animals vaccinated for tetanus, cholera, and an- thrax, reached the same conclusions as Ehrlich — namely, the father exerts no influence, but the mother transmits a sKght immunity, which may be increased by suckling. Three theories have been offered to explain these facts: One of them is advanced by Duclaux and supported by Arloing, Charrin, and Gley. It is the cellular theory, the only acceptable one if it be ad- mitted that the father may transmit immunity. It supposes that under the influence of the disease the cells receive a new orientation, which persists in the descendants. If, following Ehrlich, Wernicke, and Vaillard, the paternal influ- ence be rejected, we are quite naturally led to admit that immunity in the child depends upon the passage through the placenta of protective substances produced in the maternal organism. The immunity of the foetus is of shorter duration than that of the mother, because it is a passive immunity, a simple impregnation. The theory of Vaillard is related to the preceding: The foetus is supposed to receive the soluble products, but, instead of simply soak- ing the cells, they act as a stimulant upon the phagocytes. This is to extend to the problems of heredity the theories of Metchnikoff con- cerning the mechanism of immunity. In conclusion, our study of heredity in cases of infection shows that six eventualities are possible: PATHOLOGY OF THE F(ETUS— HEREDITY 231 1. The microbe, coming from the mother, traverses the placenta and causes in the foetus a disease at times more serious than in the mother (pneumonia, typhoid fever, sometimes syphilis) ; at times sim- ilar (smallpox), but in some cases presenting special localizations (syphilis); at times different (typhoid fever, anthrax). The mani- festations are generally immediate, but they may be tardy (syphilis, perhaps tuberculosis). 2. The microbe comes from the father and invades the organism of the foetus, the mother remaining intact ; but she may acquire immu- nity against the infection afflicting the offspring (syphilis). 3. The microbe does not reach the foetus; but the child suffers from dystrophic disorders manifesting themselves in malformations, stigmata, degenerations, and infantilism. 4. The child seems normal, but it has received from its mother (or from its father?) an immunity, generally not well marked and of short duration. 5. The child receives from its father, or from its mother, a particu- lar nutrition, which predisposes it to certain infections. 6. The child is in no wise influenced by the infection of its parents. Thus every contingency may become a reality, from an infection leading to speedy death to the total absence of impregnation. The very important history of the heredity of neoplasms, and of cancer in particular, might find place in the study of chronic infec- tions. The question will be dealt with in the chapter devoted to tumours. Nervous Heredity. — We have several times had to bring in the influence of nervous heredity. We have seen in connection with intox- ications and infections that disorders caused by external agents could be transmitted to successive generations and manifest themselves in degenerations, disturbances, or lesions affecting chiefly the nervous sys- tem. Chronic alcoholism, saturnism, mercurialism, morphinism, and, among the infections, syphilis and tuberculosis, exercise a pernicious influence, which we have already considered. An acute intoxication may at times produce the same disturbances. For example, drunken- ness at the moment of conception is often a cause of degeneration. To it belongs a large share in the etiology of epilepsy. Moral impressions often exercise a marked effect upon the nervous system of children. When conception or gestation takes place under the depressing influence of mourning, of annoyances, or during the great emotions aroused by public calamities, the children are almost inevitably condemned to nervous degeneration. A striking illustra- tion is supplied by the case of the young men born during the siege of Paris or the Commune. 16 I 232 NERVOUS HEREDITY The age of the parents may also have a similar effect. In this regard both old age and immaturity exert an influence equally per- nicious. If the parents are too young, the first children will be degen- erates; those coming later on and conceived during full maturity will be normal. Then, as the years go by, the parents grow weak and bring forth children much inferior to their older brothers. It is con- ceivable that, under such circumstances, the children of the same family do not necessarily resemble each other, especially if we remem- ber that most of the causes of dejection, sorrows, terrors, as well as diseases, exert only a passing influence. They affect one of the chil- dren, not all. Although it is theoretically easy to perceive the influ- ence due to these various causes, in practice it is a much harder task. It is, therefore, no wonder if the ineluctable law determining heredity frequently escapes notice. We must also remember that the nervous manifestations grow worse in the descendants, and that, after a few generations, they become serious enough to entail sterility. This has very justly been called progressive morhid heredity. The inherited nervous manifestations are not always identical with those of the parents, not even always analogous. Three cases present themselves: At times there is perfect similarity. This is what fre- quently happens as regards hysteria. At times the manifestations are only homologous; the disturbances differ in their expression, but they are all disturbances of the nervous system. In other cases the symptoms seem quite different and their affiliation can not be under- stood except by taking into account the idea of diathesis. For in- stance, the case may be one of an arthritic whose parents, being gouty or diabetic, have had neuropathic children. These transformations are not too much to be wondered at. Long ago clinical experience taught us that nervous disorders are frequent in all arthritics. In this connection we may mention hypochondria, the insanity of gout, diabetic pseudo-tabes, and the insanity of rheumatism. It is one of these accessory and, in a way, superadded disorders in the parents which becomes predominant in the next generation. In order that the nervous manifestations to which heredity pre- disposes may come to light, an occasional cause must intervene. This is, by the way, a notion of capital importance from a prophylactic standpoint. The disturbances become apparent on the occasion of a traumatism, an infection, an excess, or a moral shock. It is the first drinking bout which is the starting point of dipsomania, and it is a common infection which, as it causes convulsions or delirium, reveals the congenital neuropathy. It may happen that these manifestations begin earlier in the children than in the parents. A father whose PATHOLOGY OF THE FCETUS— HEREDITY 233 neuropathic aptitudes do not reveal themselves until late in life may- have a child who, from his first months, has convulsions. In this case hereditary influence would be manifested only at a later date, and if the father dies too early — i. e., before having brought to light the taints which slumbered in his organism — the problem remains un- solved and the child's disorders will seem to be spontaneous. Although the parents generally communicate to their descendants a mere aptitude, they may at times transmit to them a true disease, connected, it seems, with an evolutive disorder. It is a kind of ovular affection. As an illustration, we may mention the hereditary ataxia of Friedreich, the cerebellar hereditary ataxia of Marie, the progressive myopathy of Landouzy-Dejerine, the disease of Thomsen, the so- called hereditary trembling. These various diseases have in common the following traits : They appear at the same age in the parents and in the children; they occur without any occasional cause, and they reproduce themselves with uniform aspects. In most cases heredity transmits a certain tendency to nervous manifestations, and to ordinary reactions which occur on the occa- sion of a traumatism, an insolation, an infection, or an intoxication. Pneumonia, which in children is so often accompanied by cerebral disturbances that an eclamptic and a meningeal form have justly been described, so acts, however, only upon predisposed children. It may be stated that, even in cases where nervous manifestations seem in- evitable, their frequency, intensity, and other characters are governed by predisposition. Drunkenness, for instance, is not necessarily ac- companied by cerebral accidents. There are men who can absorb great quantities of liquor: their reason remains unaffected; and they suffer from digestive disorders. Others, on the contrary, prepared by their heredity, become delirious at the slightest departure from their ordi- nary regimen. What we have said in reference to alcoholic poisoning may be repeated concerning endogenous intoxications. In uraemia, for in- stance, the manifestations vary so much that three clinical forms of it have been described according as the accidents involve the digestive apparatus, the respiratory apparatus, or the nervous system. It is generally admitted that the variability of the symptoms depends upon the multiplicity of the poisons, and that the manifestations differ ac- cording to the substance which accumulates. We accept this concep- tion, but it seems to us that the role of hereditary dispositions must be taken into account: The localizations are determined by the state of the organs. Uraemia is only an occasional cause that brings to light morbid dispositions which until then had remained latent. In a certain number of cases the nervous taint explains the devel- 234 NERVOUS HEREDITY opment of the disorders which appear during or after a disease and persist for a very long time. This is the ease with chorea, hysteria, epilepsy, and paralysis agitans. Chorea, for instance, occurs fre- quently after an attack of rheumatism, but only when the subject is hereditarily predisposed to neuropathia. The same is true of the other neuroses. The expressions traumatic hysteria, infectious hysteria, used quite frequently, point to this double tendency. It is not that hys- teria differs in its symptoms, for they are always the same; but it is brought about by a number of occasional causes, all of which act on predisposed subjects. It would be easy to add analogous considerations with regard to all infections which become localized in the nervous system, whether it be meningeal tuberculosis, cerebral rheumatism, infantile paral- ysis, locotomor ataxia, or general paralysis. In the last two cases the role of syphilis, the influence of which is undeniable, must be supplemented by the effect of hereditary predisposition, which alone explains the localization. It is not only in pathology, but also in psychology and sociology, that nervous heredity offers an interesting subject of study. Intel- lectual aptitudes are transmitted for several generations. There are on record families of scientists, of writers, of musicians, and of paint- ers. Oftentimes a quality is exaggerated, and, becoming predominant, explains the appearance of superior individuals. The power of atten- tion, the persistence of ideas, when intensifi.ed in the descendants, may culminate in a genius. It is also by an insensible increase of the familiar qualities that the aptitude for cerebral work develops in civ- ilized races, and mental overtaxation becomes possible. It is quite certain that it is not every one who can indulge in mental overwork. In order to do this one must have been prepared by heredity. Reciprocally, a slight disorder may deviate and grow. The tendency to fixed ideas may breed melancholia. Cerebral activity may be excessive and excite in the child the most varied neuroses. As defects increase with age, it frequently happens that children are the more degenerate the later they have been conceived. Here is an observation which, in this connection, is highly instructive. A woman in whom the neurotic tendency was at first little marked, but had grown with age, had an attack of influenza when fifty-four years old. The nervous symptoms at that time assumed a more serious character; she imagined that her soul left her body and sat down by her side. This woman had married an intelligent and well-balanced man, and had four children. The eldest is thirty years of age ; she is a woman of a superior intelligence, but marked as a degenerate by two PATHOLOGY OF THE FCETUS— HEREDITY 235 physical stigmata: facial asymmetry and strabismus. Although now married for eight years, she has no children. Her brother, twenty-six years old, has a bright but childish intelligence ; he busies himself with table tipping and spirit communications. The third one, nineteen years of age, is a somnambulist. The fourth, sixteen years old, is a hypochondriac with morbid impulses; he several times tried to com- mit suicide, and one day attempted striking one of his brothers with a knife. In this family the accidents have gone on increasing as the mother has grown older. The last of her children is in a condition bordering upon insanity. The statement that insanity is often hereditary is a commonplace truth. According to the statistics of Hutchinson, it is hereditary in the proportion of 22.6 per cent. Consequently here, as everywhere else, heredity is not inevitable. It is more frequent when the mother is insane, and it decreases in fre- quency as the cerebral disorders become manifest in the parents after the birth of the children. Aside from similar heredity, the influence of the conditions in which the parents are found must be taken into account. Chronic alcoholism and drunkenness at the time of conception play the same part as the other defects of the nervous system. To these factors must be added two others : Overwork on the one hand, and arthritism on the other, contribute their part and account for the growth of the number of insane persons in the civilized races. The increasing com- plications of life, exacerbation of discomfitures and disappointments, overtaxation of mental powers, and predominance of the nervous sys- tem, sufficiently explain the progress of mental disorders. Thus endowed with an hereditary predisposition, the individual waits for an occasional cause and then succumbs to insanity- The breaking down may happen at the great periods of growth. There is an insanity of puberty and, in women, an insanity of the menopause. Or the occasion may be childbirth, an external influence, a nervous shock, a violent moral impression, an intoxication, or infection. It must be said, however, that the interpretation of the disorder is not always easy. Alcoholic or venereal excesses and overwork are very frequently not the cause of the mental disease, but represent only the first symptoms. This is unquestionably the case in general paralysis, in which the initial manifestations have often been mistaken for the starting point of the disease. If heredity is frequent in insanity, it is certainly not inevitable. In certain forms, as in chronic delirium, it is constantly found ; while it is quite rare in general paralysis. It has even been noticed that 236 GENIUS, INSANITY, AND CRIME the sons of general paralytics are frequently endowed witfi. a high order of intelligence and sometimes with genius. Genius, Insanity, and Crime. — In a book which created a sensa- tion, Moreau de Tours defined genius as a form of neurosis. Although this view can not be accepted, it must, at any rate, be admitted that cases of genius and insanity and of genius and neurosis are frequently found in the same family. It is also well established that a large number of highly gifted men present stigmata which, according to the happy appellation of M. Magnan, make of them superior degenerates. To speak but of the dead, it suffices to mention Socrates talking to his spirit, Pascal terrified by hallucinations, and J. J. Kousseau, a hypochondriac with secret vices (Confessions). The study of the psychic status of superior persons reveals an exaggerated or perverted sensibility, the absence of practical sense, queer superstitions and acci- dents bordering upon pathology, manias or phobias. This fact is becoming a matter of common observation, and has suggested the in- teresting researches of M. Toulouse on the mental state and the signs of degeneration of our most illustrious contemporaries. Eeciprocally, an insane person can have sparks of genius. The beginning of general paralysis affords abundant illustrations of this peculiarity. Tradition understood the relation existing between these two extremes and joined them in the term ^^ poetical delirium." How many superior men, artists, musicians, and scientists, are looked upon as " cracked " by their neighbours ! How many men called lunatics by their contemporaries hold the rank of geniuses in the eye of pos- terity ! This is because geniuses and lunatics differ from the sensible man in the same particular. Their ideas are opposed to those of the majority. It is this that makes the great difference between a talented man and a genius: the former continues and completes the ideas cur- rent about him; the latter departs from them and conceives different thoughts. It is no easy matter to determine when an idea springs from genius and when from insanity. It may even happen that they are analogous in both cases. Specialization in predisposed persons depends upon external circumstances. It has sometimes been said that relations exist between genius, insanity, and crime. In this form the statement is unacceptable. There are affinities between genius and insanity on the one hand, and insanity and crime on the other; but there are none between criminal- ity and genius. Men of genius are superior degenerates, criminals are inferior degenerates. For the sake of greater clearness, let us sup- pose an angle whose sides extend to an infinite distance: at the apex we place insanity, on the ascending side genius, and on the descend- ing side crime. Despite the point possessed in common by both PATHOLOGY OF THE FOETUS— HEREDITY 237 psychic states, they evidently diverge more and more from each other; their differences increase as the man of genius ascends and as the criminal sinks. The relationship between insanity and crime is so evident that the question of responsibility rises constantly. Many delinquents who formerly would unquestionably have been punished are to-day con- fined in asylums. The differentiation is, it hardly need be said, very difficult to make, and the idea of partial responsibility, so often ap- plied, serves only to indicate the existence of numerous transitions connecting insanity and crime. The differentiation can be made from two points of view. The public considers any crime as the work of a lunatic, and, as a rule, any act the motive of which can not be under- stood. The physician must judge differently; he must determine the bodily condition of the accused, seek for stigmata, reconstruct his past, discover his personal, and especially his hereditary, antecedents. In studying the families of criminals, we sometimes find direct heredity (25 per cent of youthful criminals are born of criminal parents), and sometimes indirect heredity — that is, neuroses, degen- erations, mental derangements, and alcoholism. As a rule, child criminals belong to families of alcoholics. .' If we turn from the family to the individual, we frequently observe stigmata of degeneration. The criminal is liable to irrational fits of anger, to night terrors; and at times the disorders are more severe. The frequency of insanity in workhouses and prisons is to be explained not by the peculiar circumstances under which the prisoner lives, but by his hereditary predispositions. Finally, in certain cases, the im- pulsive nature of the crime is tardily brought into evidence by the occurrence of an epileptic fit, which makes it possible to properly deter- mine the moral responsibility of the subject. Heredity is no more inevitable here than elsewhere; occasional causes, as is always the case, play a very important part. If the indi- vidual, predisposed by heredity, is brought up among honest people, his chances of not straying from the straight path are good. How many people have remained virtuous for the want of an occasional cause ! Consider from this point of view the influence exercised by the great social perturbations. Eeread, in Thucydides, the story of the Athenian plague or review the history of the more recent great revo- lutions ; it is always the same picture ; always the same licentiousness, hatred, violence, and murder. It is a particular state, perhaps a return to an ancestral condition, at any rate, a retrogressive movement, which is produced when the fear of punishment grows weak and when social hjrpocrisy is done away with. Contagion propagates the disorder, but it reaches those only who carry within them a latent predisposition. 238 PHYSICAL STIGMATA OF DEGENERATION If, on the other hand, criminality, as well as insanity, increases with civilization, it is because the growing complexity of life breeds overtaxation, and requires a new stimulation which seems to be favoured by the use of alcoholic beverages. Heredity expresses itself under these circumstances in an inability for sustained effort, which is the great cause of criminality. The facts above stated in a summary way appear conclusive when viewed in their entirety. A close relationship must be admitted to exist between crime and insanity. These two conditions are separated only by our social prejudices. Let us hasten to add that the conclusions to which we are led by an impartial consideration of the facts in no way affect the right of repression; they do no more than change the aspect of the question. The right of punishment must be looked upon as a right of defence. Physical Stigmata of Degeneration. — Can criminal hereditary pre- dispositions be recognised by means of particular bodily characteristics ? According to the theory of Lombroso, who answers this question in the affirmative, the born criminal presents various stigmata which bring him nearer to primitive man. The stigmata are less frequently ob- served in man than in woman, although she commits fewer crimes. Lombroso meets this objection by the statement that in woman pros- titution is the equivalent of crime; as a matter of fact, associations of criminals and of prostitutes are of frequent occurrence. Equally abnormal, these people come together just as other degenerates do. For it seems well established that the various stigmata enumerated by the Italian school do not characterize the tendency to criminality, but simply the degeneration of the race; they are found in degenerates of all kinds. The stigmata of degeneration are extremely numerous. We shall limit ourselves to the mention of a few of them: Deformation of the cranium and of the face, their asymmetry, existence of abnormal sutures, protrusion of the superior or of the inferior maxillary, deep- ening of the palate, irregularities in the development of the teeth and their speedy decay, harelip, hollow thorax, absence of one or of two pectorals, short fingers, lumbar hypertrichosis, exaggerated develop- ment of the pilous system in woman and the reverse in man, imper- fect development of the genitals, delayed descent of the testicles, bi- partite or imperforate vagina. As regards the organs of sense, stra- bismus, pigmentary choroiditis, daltonism, deformities of the iris, deaf-mutism, anomalous development of the ears, adhesion of the lobe, absence of the marginal fold, and anomalies of the helix, which in some cases joins the antihelix; among the nervous disorders, stam- mering, tics, etc. PATHOLOGY OF THE FOETUS— HEREDITY 239 If we consider the intellectual development, we find all imaginable t3rpes. At the foot of the ladder, idiocy; the cerebral functions are so reduced that we may consider the subject as a mere medullary being. Nevertheless, one faculty may persist: idiots have been known who were excellent musicians or astonishing calculators. A little higher we find imbecility, and still higher mental debility. Above these we find very intelligent, even superior, persons, but they are in some way defective ; they are odd, eccentric, gifted at times with a partial supe- riority, but their character betrays asthenia: defect of judgment, inability to look after themselves in life. There are men of genius whose mental degeneration is expressed by the absence of practical common sense, or by some little defect which astonishes, or by some fantastic mania, or incomprehensible phobia. Every degenerate, whether superior or inferior, whether bordering upon genius, insanity, or crime, very frequently shows an invincible tendency to suicide. At times this is the only stigma, or at least the most apparent one. They sometimes use childish means, but gen- erally they repeat the attempt with increasing earnestness, and gener- ally succeed in destroying their lives. This tendency to suicide may be transmitted, and, curiously enough, each member of the same family uses the same means and at the same age. Hammond relates the case of a man who, at thirty-five, killed himself in a bath by cutting his throat with a razor. He had two sons who committed suicide at the same age and in the same way. One of them had a daughter who killed herself at thirty-four, and her son put an end to his life when thirty-one years of age. The considerations we have presented concerning nervous heredity directly suggest practical applications. Prophylaxis may prevent the development of the manifestations to which the child is predisposed. As above stated, an occasion is required to determine the occurrence of the accidents. Consequently, the child should be removed from his family; and this becomes an imperative duty when the parents are alcoholics. We have shown that the first intoxication is the starting point of dipsomania. It is here that the temperance societies are use- ful. We must remember that coercion in any form — punishment, in- timidation, or repression — never succeed. The effective treatment is to place the child in the country in the family of honest and quiet people. Moral guidance saves a large number of predisposed sub- jects, and even a few delinquents. We do not speak of the hardened cases; they are incorrigible. It is in this manner that effects of heredity may be successfully antagonized, effects which — we can not repeat it too often — do not rest upon the race as an unavoidable fatality. 240 CONCLUSION It is not impossible for a man to escape from his inheritance; it is even possible for him to differ entirely from his ancestors or col- laterals. There are cases which appear to defy all our laws and the- ories. Occasionally a genius, a lunatic, or a criminal appears alto- gether unexpectedly; nothing of his character precedes or follows him. No doubt the anomaly is only an apparent one, but its causa- tion escapes detection. Perhaps we have failed to take notice of a particular influence that has been in action. It is perhaps a return to an ancestral type, as in the curious case reported by Darwin in which a pigeon of a peculiar colour appears suddenly in a race appar- ently fixed by long selection. Conclusion. — The study of heredity completes the history of eti- ology. If the causes of diseases must always be looked for outside of the organism, the modes of its reactions are governed by predispo- sition, aptitude, and resistance transmitted by the parents. The func- tional modifications accidentally brought about are communicated to the offspring and are often exaggerated in successive generations. Ac- cording as the attendant circumstances are favourable or detrimental, the family, the race, or the species will show a corresponding improve- ment or deterioration. By an abuse of expression, it is often asserted that the affections of the organs — the heart, the liver, the kidneys, and the nervous sys- tem — are hereditary. What is transmitted in most cases is a func- tional disturbance — i. e., a simple disposition, which becomes appar- ent only under the influence of exciting causes. Children born of parents suffering from cardiac, hepatic, or pul- monary disorders or from Bright's disease are more likely than others to develop lesions of the heart, liver, lungs, or kidneys. But an occa- sion will be required in order to make actual the inherited tendency ; a new influence, an intoxication, an infection, or an anomalous nervous reaction will have to interfere in order that the organ be affected. It is in this way that the heredity of visceropathies must be understood. It is even probable that what in many cases appears to be hereditary pulmonary tuberculosis is due rather to the fact that the offspring of tubercular subjects suffer from insufficient respiratory activity, their breathing capacity being below the normal. Heredity must not be mistaken for " innateness.'^ The latter ex- pression designates those cases in which the child comes to life pre- senting certain morbid aptitudes, the point of departure of which is to be found in some accidental causes having exerted their influence directly or indirectly during conception or gestation. Innateness is the conclusion of foetal pathology, while heredity is a chapter of the pathology of the species. Innateness results from ex- PATHOLOGY OF THE FGETUS— HEREDITY 241 ternal causes which have acted upon the foetus through the enveloping membranes. More frequently it arises from toxic or infectious agents transmitted through the placenta. At times it proceeds simply from bodily or psychic disorders in the parents. A well-constituted person generating a child during convalescence from an intercurrent disease, a woman under depressing influences during pregnancy, would produce an offspring with a particular innateness. It might exhibit nutritive disorders or stigmata of degeneration; it would be predisposed to neuropathies and easily contract infections. The morbid influence having acted upon cells that are young, and, so to speak, malleable, would leave an indelible imprint. The disorder would be permanent in the child, even though temporary in the parents. Innateness frequently results from causes so slight that they escape notice. If the great laws of heredity at times seem to fail, it is because we do not always perceive the circumstances modifying their action. In cases of organic as well as of nervous affections, it is a predis- position which is transmitted in the majority of instances. Hence, the importance of prophylaxis and education. Hereditary taints are only too often aggravated by education. The sons of neuropathic or alcoholic parents are incited by the examples they see in their families to deeds which seal their doom. If, instead, they were placed from early youth under the care of persons able to start them in a good direction, the effects of heredity would be re- sisted, and even completely overcome. Unfortunately, it is but seldom that education is used for this purpose. Moreover, its influence may be insufficient. If that be the case, the disorders of the parents will go on increasing. It is in this manner that pathological families are created. If to this be added the fact that the same defects are frequent in the same classes, it is easy to see how marriages between persons having the same aptitudes will still more tend to magnify the hereditary disorders. On the other hand, social selection frequently brings about the survival of the weak and degenerate. It then seems to supplant natural selection, but it does so only temporarily. Infecundity or increasing debility brings about the extinction of degenerates. We are thus brought back to the great laws regulating the whole evolution, and we are led to look upon social selection as a mere chapter of natural selection, sociology being simply a chapter of biology. As it transmits and fixes certain characteristics, heredity explains the evolution of races, their diverse aspects at different epochs and in various countries, and by this very reason accounts for their patho- logical variations. Diseases are not the same all over the globe; they 24:2 CONCLUSION differ also according to the period. The variations of pathology in time and in space find their explanation in the incessant changes oc- curring in the cosmic agents, in the animate beings, and notably in the human species. This is the reason why the diseases we observe differ from those observed by our fathers, just as they differ from those which will come to the notice of our descendants. We can now clearly understand the variability of clinical types. The various localizations taking place during infections and intoxica- tions, the diverse nervous reactions happening on the occasion of a traumatism, are not the work of chance. They everywhere and always proceed from numerous causes which have influenced the subject or his generators. If the varied circumstances intervening before and after birth could be traced out, if precise information regarding heredity and innate- ness could be obtained, and if the external causes playing upon the foetus could be known, the future of each individual could be foreseen, and its physiological, pathological, and moral history written out in advance. For it is quite certain that as all the activities of living beings are nothing more than reactions provoked by external agents, they must all be interrelated just as systematically as the other cosmic phenomena. Only it is impossible to discern the innumerable inter- vening causes. It is for this reason that the freedom of living beings has been so long admitted. Our belief in morbid spontaneity, just as our belief in free will, is grounded upon no other foundation than an incomplete knowledge of the numerous causes acting upon us. CHAPTEE XIV INFLAMMATION Definition — Part played by local lesion — Mode of formation of inflammatory foci — Active congestion — Diapedesis — Liquid exudation — Modification of the fixed cells — Chemical study of serous exudates — Principal inflammatory processes — Pseudo-membranous processes — Suppuration — Chemical and histological con- stitution of pus — Principal pyogenic agents — Microbic and nonmicrobic suppu- rations — Transformation of pus — Symptoms and course of purulent collections — Gangrene — Part played by microbes — Importance of accessory causes — Part played by circulatory, nervous, and dystrophic disturbances — Principal ana- tomical and clinical varieties of gangrene — Infectious nodes — Tubercles — Ana- tomical varieties and histogenesis of tubercles — Principal clinical forms of human tuberculosis — Tuberculosis of animals — Unity of tuberculosis — Pseudo- tubercles : their varieties and importance. Definition. — When a pathogenic cause acts upon any point of the organism, it occasions two orders of responsive manifestations, some local and others general. Local reactions are due to cellular modifica- tions induced at the point of application of the cause, and to modifica- tions of a reflex order. General reactions are referable to nervous influences or to the absorption of toxines. Let us consider, for example, a mechanical agent which has pro- duced a cut: The edges of the wound are slightly separated, and the open vessels are bleeding. The first reactions will arrest the hemor- rhage; on the one hand, the calibre of the vessels will contract in consequence of the direct excitation of the nonstriated muscular fibres entering into the structure of their walls, and on the other hand as the result of a reflex constriction. The blood, flowing with less force, will coagulate ; fibrine will be formed, and its effect will be to occlude the vessel, to assure hemostasis, and to unite the edges of the wound, and then serve as nutrition and as a guide to cells which will insure reparation. The second act then begins. The cellular elements lining the solution of continuity begin to proliferate and form a cicatrix. At the same time leucocytes enter the field, some to take part in the for- mation of tissues, others to carry away the dead cells and to clear up the ground. 243 244: DEFINITION When a toxic substance is deposited upon the skin, two results are possible : In some cases the poison is absorbed without giving rise to any local irritation; in others, a reactionary lesion is produced at the point of its introduction. The poison has destroyed the cells, and these cause a vaso-dilatation, a serous exudation, and oedema by reflex action. Thus formed, the local lesion dilutes the toxine, prevents its absorption, and in this way protects the organism. Let us now suppose that the process is due to a microbe — for exam- ple, a pus coccus. When it finds itself in favourable conditions, it de- velops. If it only acted mechanically, it might multiply and produce a voluminous colony without exciting any general reaction. But, at the same time that it multiplies, it engenders toxines which cause the death of cells with which they come in contact. Thus is produced a necrobiotic zone, which is later surrounded by a proliferative zone. Around the cells that have been killed the elements develop in such a manner as to circumscribe the infection, to struggle against the microbe, and to replace the destroyed parts. Coincidently with the occurrence of these first phenomena, the nervous terminations are aroused by the microbie toxines and by the dead cells. Their excita- tion gives rise to a series of reflex acts which, ending in the active dilatation of the vessels at the invaded point, are followed by migra- tion of leucocytes and the formation of a serous exudate. In this way a local lesion is produced. In order that these various phenomena may be produced, the microbe must possess a virulence of medium intensity. If it is inof- fensive, it can not multiply, and is soon destroyed by the cells. The local lesion does not appear, and the infection is aborted. If the microbe is too powerful, it secretes a series of substances which pre- vent vaso-dilatation, the issue of plasma and leucocytes. The local lesion is again absent, but general infection is at once produced. The local lesion then represents a fortunate process, and is a bar- rier opposed to invasion. Its effect is to circumscribe infection and prevent extension and generalization of the process. It may, however, have its disadvantages. In certain cases the organism disturbed by the arrival of the microbe mobilizes more forces than are required and provokes a local lesion liable to become dangerous. Thus, in the larynx, under the influence of an infection, as in the case of a bum, cedema of the glottis may be produced which will cause death mechan- ically. In the lung, active congestion caused by a microbe may bring about grave accidents. The animal organism is not capable of pro- portioning its intervention to the action of the cause. Hence it is that, for a little tubercle situated under the pleura, it will secrete three or four pounds of serous liquid. This exudation will hinder the INFLAMMATION 245 development of tuberculosis by the compression it exerts, but its abundance will produce accidents, and if timely thoracentesis be not resorted to it will in some cases cause death. The disproportion between cause and effect is well brought to light by a very ingenious experiment of Gamaleia. Two rabbits were taken and their cornea slightly cauterized; one of them was kept as a con- trol, and soon presented a white spot at the point of traumatism. In the other the development of the inflammatory phenomenon was pre- vented by injecting into the veins strong salt water. The healing was obtained without a cicatrix. It is easy to understand the importance of these facts in therapeutics, for we possess the means of stimulating or preventing reactions, and notably congestive phenomena. Whether there be a local lesion or not, microbes can pass into the blood. This liquid, however, is not favourable for them, so they rap- idly deposit themselves in the tissues. They develop there, and again secrete their toxines, and thus give origin to secondary foci, whose mechanism is analogous to that presiding over the formation of the primitive focus. These two types of foci, primary and secondary, constitute the process described under the name inflammation. There is no term in medical language that has been more variously defined, no process that has been more diversely interpreted. Among the numerous conceptions that have been put forth three deserve to be mentioned: The first, by order of date, is that of Virchow. According to the celebrated pathological anatomist, inflammatory phenomena consist in degenerations and proliferations bearing on the fixed cells of the affected tissues. The vascular changes produced in the morbid foci seemed to him secondary. Cohnheim's conception was quite different. The vascular modifica- tions were considered by him to be the initial phenomena; the effect of vaso-dilatation was to permit the escape of white blood corpuscles through the vascular walls, according to a process called diapedesis (migration). This conception, based on unassailable experiments, gave occasion to lively discussion. It was of late completed by Metchnikoff, who holds inflammatory reaction to be salutary, as its end is to permit the leucocytes to devour and digest the invading microbes — namely, to fulfil their phagocytic function. Each of these three theories contains a great amount of truth. We consider, in fact, that inflammation is " the ensemble of reac- tionary phenomena produced at the irritated points by a pathogenic agent.'' In most cases the agent is a microbe, but in some it is a 246 MODE OF FORMATION OF INFLAMMATORY LESIONS mechanical, a physical, or a chemical agent. Inflammations occa- sioned by a foreign body, by insolation, or by the application of cantharides are well-known examples. Mode of Formation of Inflammatory Lesions. — Inflammation is essentially characterized by four orders of phenomena: vascular dis- orders, which may be wanting in the case of a tissue destitute of ves- sels, like the cornea; liquid exudations; diapedesis; local cellular alterations. Congestion and Diapedesis. — The first phenomenon, at least that which first attracts the attention of the observer, is represented by re- flex vascular manifestations. The cells, irritated by the toxines, excite the nervous system, and thus cause an active vaso-dilatation. The arterial blood arrives in great quantity, quickly passes through the capillaries, and, in consequence of its abundance and rapidity, reaches the veins, having nearly preserved its characters. The amount of car- bonic acid, although exceeding the normal, is diluted in so great a quantity of blood that the liquid remains red in the veins, and, if one is bled, it flows in jerks, by reason of the dilated condition of the arterioles and capillaries. At this moment the patient is sensible of the congestive phenom- ena by the heat he experiences, and especially by a sensation of pulsa- tion isochronous to the pulse. In the second stage the sensation is modified : there is a feeling of heaviness, of swelling, and of painful tension. In fact, the local condition is changed; the course of the blood current has become slower, and there is produced a set of phenomena which have been experimentally studied by Cohnheim. In order to observe them, one must operate on a frog, draw out an intestinal con- volution, and examine the vessels of the mesentery under the micro- scope. After a transitory stage of initial constriction, they are seen to dilate; then the rapidity of the blood current lessens; the leuco- cytes, which were at first carried off by the current, come to adhere to the endothelium of the vascular walls. This margination of leuco- cytes, to use an expression of Cohnheim, can not occur in the arteries, for the too rapid current carries on the few cells which try to fix them- selves ; it takes place in the capillaries, and chiefly in the small veins. Once fixed, the leucocytes change their form, send out processes, which engage between the endothelial cells, separate the walls of the vessel, and thus produce an opening through which they pass out of the circu- latory system. This is diapedesis. When the leucocytes have passed out of the capillary, the hole that they leave behind them again closes up, but not quickly enough to prevent a few red blood corpus- cles from passing into the surrounding tissue. INFLAMMATION 247 The leucocytes are not all equally apt to pass out from the vessels by diapedesis. It is especially those that belong to the varieties known as mononuclear and pol3rQuclear neutrophiles that are en- dowed with the most active movements and emigrate most easily. The process of diapedesis requires the presence of oxygen, which stimulates the activity and motility of leucocjrtes. It stops if a vein is compressed — namely, if an accumulation of carbonic acid is pro- duced; conversely, it is accelerated when the flow of arterial blood is favoured. Three orders of experiments demonstrate the reality of this fact. If the streptococcus or erysipelas be inoculated into the ear of two rabbits, and if in one of them the flow of arterial blood be accelerated by cutting off the superior cervical ganglion of the great sympathetic, it will be seen that exudation is more abundant and diapedesis much more intense in the ear deprived of the nerve. On drawing a little drop of the exudation there are found in the operated animal, at the end of three or four hours, forty times as many leucocytes as in the control. This quicker production of oedema and this more rapid arrival of leucocytes render the inflammation much more acute at the outset, but they precipitate its evolution; the erysipelas is healed more quickly and more completely. The results are similar when, instead of exciting a streptococcic inflammation, physical or chemical agents are resorted to; when, for example, the ears of a rabbit are plunged into boiling water, or are rubbed with croton oil. Another procedure also brings to light the favourable side of active congestion. Filhene inoculated streptococcus in the ear of two rabbits ; then, in one of the animals, he surrounded the ear with a small rubber bag in which hot water was circulating. The elevation of temperature favoured congestion and diapedesis and thus hastened the cure. Finally, as was done by Dr. Carnot, acute congestion may be accel- erated by vaso-dilating substances, such as amyl nitrite; the result, however, is still the same. Although congestion favours the exit of leucocytes, it does not suffice to explain it; nor is the irritation produced by the air — in Cohnheim's experiment a sufficient condition. Eepeating the experi- ment, and taking care to place the frog in sterilized air, Zahn ob- served vaso-dilatation ; but the phenomena did not go any further. Therefore, if diapedesis is produced under other circumstances it is because the white blood corpuscles are excited to emigration by the numerous bacteria that fall upon the peritoneum from the air. What is more curious is the fact that once out of the vessels the leucocytes do not travel at random. Urged by a mysterious force, they direct themselves toward the place where the microbes are multiplying. It is assumed that they are attracted by substances secreted by the 17 248 SEROUS EXUDATION bacteria, and by those 3delded by the organic cells, which perish in the struggle. These various substances exercise an attraction which has been called positive chemio taxis. When the microbe is very virulent it produces poisons which, unlike the preceding, repel the leucocytes, and are said to possess a negative chemiotactic power. Serous Exudation. — Coincidently with the emigration of the mor- phological elements an exudation of liquids takes place. The exuda- tions may be attributed to most diverse causes. Sometimes it is a traumatism that determines an often intense oedema in the subcu- taneous integuments. More frequently it is physical agents, sunstroke or heat stroke, cold or burning, that excite a serous swelling. A good many chemical agents act similarly. The action of slight caustics or energetic revulsives is well known ; it suffices to mention the blister of epispastics. As in all other cases, the most numerous and varied illus- trations are found in the group of infections. Abundant serous exu- dations are produced at the point where anthrax is inoculated; also at the seat of and around diphtheritic lesions and in corresponding ganglia. They are also formed under the influence of staphylococcus, and especially of streptococcus. Lastly, it is very common to see in serous membranes exudations referable to a tubercle situated in the neighbourhood. From a mechanical standpoint, liquid exudations are often divided into two groups, according as they are of inflammatory or chemical origin. In the latter case some hindrance to the venous circulation is admitted. The fact is undeniable : quite tight compression of a limb is sufficient to cause a serous exudation in the cellular tissue. But, in order to produce this phenomenon, the constriction must be brought to bear on all the vessels; anastomoses are in fact so numerous that the constriction of one vein is followed by no effect. If oedema is produced in certain cases it is because the influence of another factor is added to the mechanical action — for example, a microbic toxine or an active congestion. Ligation of the three principal veins of the ear in a rabbit, for instance, does not provoke oedema unless a few drops of a sterilized culture of a microbe, like Proteus vulgaris, be injected at the same time beneath the skin, or unless the superior cervical gan- glion of the great sympathetic be severed. In man, a phlebitis, even when it affects a vein of little importance, often causes considerable oedema. The fact is striking in the case of varicose phlebitis; but this is not a mechanical phenomenon, since ligature of the same vessel produces absolutely nothing. It may be asked, therefore, whether a great number of exudations attributed to mechanical influences are not due to more complex pro- INFLAMMATION 249 cesses. It may be questioned whether the cedema oecurring in cardiac and Bright's disease patients is not often favoured by the develop- ment of the microbes of the skin, which tend to penetrate into the integuments under the influence of malnutrition. The same remark applies to the viscera. It is very probable that pulmonary cedema is often due to the action of external germs, which tend to develop in a lung not sufficiently supplied with blood. The same remarks are applicable to serous membranes. The ascites of cirrhotic patients is not always to be ascribed merely to a circulatory difficulty; it is probable that venous stasis permits the escape of intestinal microbes, which irritate the walls of the portal vein or even of the peritoneal serous membrane. The hydrothorax of cardiac patients seem still more frequently to be referable to bastard pleuro-pulmonary infec- tions. In a word, in order that exudations be produced, it is in most cases necessary that an additional process be established to complete the mechanical action of venous stasis. The chemical distinctions which it has been attempted to establish between inflammatory and mechanical exudations seem very fragile, since there exist numerous transitions between the results obtained. It is asserted that inflammatory exudations are denser ; the areometer shows 1,020 instead of 1,010 to 1,015; they contain more proteid matters, more fibrinogen, and they often coagulate spontaneously. Mechanical exudations, on the contrary, do not coagulate, for they contain little of the cellular elements capable of furnishing the fibrin ferment. Pleural exudations especially have served for the investigations of chemists. Mehu found notable differences, according as the exudation was inflammatory or mechanical. Here are some figures, borrowed from Halliburton, which give the particulars : Density Proteid matters Fibrine Globuline Serine Mineral salts . . Pleurisy. (Acute inflammation.) Hydrothorax, (Torpid inflammation.) 1,012 -1,016 13 - 0.06- 4 - 7 - 7.3 - 25 per 1,000 0.1 " 7 « 18 " 9 " These figures show that exudations are never due to simple transudation; they would then have a fixed composition. The min- eral salts alone seem to escape by exosmosis, since they do not vary. The organic matters escape by a process of true secretion; it is a question of a vital phenomenon connected with the irritation of endo- thelium. 250 MODIFICATIONS OF THE FIXED CELLS But it is also easy to convince one's self that there are not radical differences between the two varieties of transudations. Numerous figures of transition prove that the process is always complex, and that in most cases inflammation is added to mechanical action. Modifications of the Fixed Cells. — While the various modifications just described are being produced, changes by no means less interest- ing occur in the cells of inflamed tissues. The endothelia of the ves- sels swell up; the cells of mesodermic origin — namely, the fixed cells of connective tissue — the clasmatocytes of Kanvier, and even the cells of adipose tissue, return to their embryonal state, recover their round form, and recuperate their motility and contractility. The proper cells of tissues, the epithelial cells, are more highly developed, and hence more fragile. Many of them perish. Some- times, as if overwhelmed by the action of toxines, they are from the outset struck by death and undergo coagulation necrosis. In other in- stances they first become hypertrophied ; their protoplasm becomes translucent, then atrophies and undergoes granular, hyaline, colloid, vitreous, and fatty degeneration. Those situated around the inflamed zone resist better, and their irritation is expressed by karyokinesis and proliferation. Evolution of Inflammation. — If the inflammatory phenomena are not too intense, the round cells, of mesodermic origin, tend toward organization; infectious nodules are formed, the most highly devel- oped types of which are represented by tubercles and syphiloma. On the part of epithelial cells are observed nodular formations, adenoma, perhaps also epithelioma. We shall return to this question, which touches the much-disputed problem of relationships between inflamma- tions and neoplasms. If inflammation is intense the cells are killed. According to the nature of the agent and the condition of the organism, and according to the elements attacked, granulo-fatty degeneration, necrosis, false membrane, in which a tendency toward organization still persists, sup- puration, and gangrene are observed. The clinical manifestations of these various anatomical processes are extremely variable. However, in the case of free acute inflamma- tion we observe a certain number of interesting disorders. These are, first, the four cardinal signs of inflammation — pain, heat, redness, and swelling {dolor , calor, ruler, tumour) — which occur at the invaded point. We shall make a complete study of these in con- nection with suppuration. There is produced at the same time an increased functional activity having for its centre the affected point. On the part of neighbouring glands an increased secretion will be pro- duced. But the liquid is often altered and contains only mucus. In INFLAMMATION 251 more intense cases the disturbance is expressed by a reverse phenome- non — namely, a dryness of the parts, in consequence of arrested secretion. In the cases where evolution is favourable, the elements that have perished are eliminated, thrown out, carried away by wandering cells, or are destroyed by neighbouring cells. Their disappearance is fol- lowed by the development of a tissue that will fill up the empty place. This is sclerotic tissue, veritable cicatricial tissue. As in all other cases, the effects may exceed the end. The sclerotic tissue may be exuberant and form veritable tumours, designated under the name keloids; or, obeying its retractile tendency, it will contract, compress the neighbouring parts, interfere with their activity, and thus provoke new disturbances. General Reactions. — The local phenomena of which we have just indicated the mechanism are frequently attended by general manifesta- tions. Whenever the local inflammation is somewhat intense, numer- ous disturbances become manifest. The temperature of the subject rises suddenly or slowly, the appetite is lost, the tongue is coated, digestive disorders set in, and respiration is accelerated. The patient experiences a feeling of malaise and of lassitude; he often complains of headache, and becomes incapable of continuing his occupation or of fixing his attention. At times matters go still further: quiet or vio- lent delirium occurs, the tongue becomes dry, and the lips are fuligi- nous. The condition is disquieting, notwithstanding the fact that the lesion has remained absolutely local. We shall again refer to all these manifestations, which are for the most part dependent upon intoxication. The soluble products, pro- duced at the morbid focus, thus profoundly modify the organism and give rise to general reactions, including fever. These reactions repre- sent the most striking example of the relations existing between the various parts of the economy under pathological as well as under nor- mal conditions. We shall make a special study of this when describing the functional synergies and morbid sympathies (Chapter XIX). We shall now consider the mode of formation and the meaning of the principal inflammatory processes. Pseudo-membranous Processes Pseudo-membranous processes are usually divided by German au- thors into two groups. They describe under the name croupous exu- dation that form which is superficial, and under the name diphtheritic exudations that form which is more profound — namely, interstitial. These expressions are bad ; they lead to confusion, and must be aban- doned. But they correspond to a just idea, or at least to a necessary 252 PSEUDO-MEMBRANOUS PROCESSES distinction. Two varieties of pseudo-membranous processes are to be admitted. In some cases it is a question of the formation of a new membrane covering up a mucous membrane, of which it reaches the most superficial parts only. In others, the pseudo-membranous appear- ance results from a necrosis, from a more or less profound diphtheroid gangrene. The former process is realized by certain microbes, notably by the bacillus of diphtheria; the latter characterizes the destructive affections of toxic or microbic origin. Caustics, like nitrate of silver, and the most varied microbes may produce lesions of membranous appearance. Such is the case in stomatitis, known as ulcero-mem- branous stomatitis, which were better called superficial gangrene of the mouth; such is also the case in muco-membranous enteritis. In these two affections the so-called false membranes are nothing else than parts or shreds of the altered mucous membrane. There is, then, a capital difference between the two processes. The first is dependent upon a general reaction of the organism ; the second is the work of a pathogenic agent. The former is characterized by the development of a concrete exudation at the surface of the mucous membrane; the latter by the exfoliation and expulsion of a pre-exist- ing necrosed part. Leaving aside the history of diphtheroid gangrenes, to which we shall hereafter refer, let us consider only the true pseudo-membranous process. In the habitual conditions of life this process may be considered as always dependent upon a microbic infection. However, a specific diphtherogenic microbe does not exist. The false membrane repre- sents a quite common reaction, which may be called forth by a great number of bacteria. It suffices to consider what occurs in the throat. Pseudo-membranous sore throats may be produced by numerous microbes. Along with Loeffler's diphtheritic bacillus, which holds the first place, are to be ranked streptococcus, pneumococcus, pneumo- bacillus, tetragenes, etc. On the other hand, an agent capable of giving rise to the forma- tion of a false membrane may in other cases produce an edematous exudation or a purulent focus : witness streptococcus or pneumococcus. The latter microbe produces false membranes, exudations very rich in fibrine, or true suppurations. The difference depends upon the virulence of the microbe, upon the seat of the lesion, and upon the condition of the subject. Secondary influences intervene in all cases, even in the case of Loeffler's bacillus. The diphtherogenic action of this microbe is manifested only on parts in contact with air; subcu- taneous inoculations produce only redema rich in fibrine, but no false membranes. INFLAMMATION 263 It is a law well established to-day that the morphological ele- ments do not act except by their secretions. This law may be applied to the pseudo-membranous processes. It has for a long time been believed that false membranes were not produced except under the influence of living bacteria acting upon an altered mucous membrane. At present it is demonstrated, at least as regards the diphtheritic bacillus (the only microbe that has been studied from this point of view), that the false membrane is due to the action of toxines. It has been possible to reproduce laryngitis, bronchitis, conjunctivitis, and vulvitis, all pseudo-membranous, by simply depositing the pure toxine of the diphtheria bacillus upon the mucous membrane; but as this had already been established with regard to suppurations, the more slowly the poison is applied the greater will be the success. It is probable that the microbic toxine acts by primarily altering the cells with which it comes in contact; but this action is slow. If vibratile cells of the trachea are taken and placed in toxine and in simple bouillon for comparison, their movements are seen to persist in both cases for almost the same length of time. The altered cells secondarily provoke a vaso-dilatation, and then a diapedesis of leucocytes. Thus far the phenomena have nothing special. Subsequently, within twenty-four to forty-eight hours, the false membrane develops. To explain the production of the latter, several theories have been advanced. The simplest idea is to assume an exudation of a fibrino- genic substance which coagulates on contact with the air. Wagner sus- tains the view that false membranes are produced by the cells of the tissue, which unite by means of prolongations. To-day the consensus of opinion is that exudation is consti- tuted, on the one hand, of fibrinogenic substance, and, on the other, of altered cells. The fibrinogenic substance escapes from the vessels, and finds itself in the best conditions for coagulating ; it is in contact with the air, it meets with dead leucocytes, which here, as everywhere else, play a great part in coagulation ; it is spread out upon a mucous membrane whose cells are diseased. Now it is known, from Cohn- heim and Weigert, that the epithelial as well as the endothelial cells do not oppose coagulation of exudations except when they are intact. Finally, a certain role is to be attributed to the cells of tissues, which become fibrinified according to the process described by Weigert under the name of coagulation necrosis. Thus made up at the expense of the fibrine of blood and of the cells, false membranes present quite variable aspects. They may be seen in serous exudations, where they float in the liquid; elsewhere more abundant, they line the two surfaces of the serous membrane and 254 PSEUDO-MEMBRANOUS PROCESSES may bring them to adhesion. Finally, they frequently have their seat upon the surface of a mucous membrane, to which they adhere more or less intimately. Should one of these false membranes be stripped off, the ulcerated surface becomes exposed, slightly bleeding; and this proves that we are in the presence not of a simple deposit, but of a profounder process. The detached false membrane is quite resistant; it does not disin- tegrate when agitated in the water, thus being distinguished from pultaceous layers or mucous concretions. It is dissolved by lime water and by hypochlorite of soda; its richness in fibrine explains why it decomposes oxygenated water. Examined microscopically, it is found to be composed of anasto- mosed fibrinous threads, sending out prolongations which attach them- selves to the subendothelial tissues by a series of arcades; this ex- plains why the production is adherent. The fibrine appears under the form of lamellae, compact masses, or spiral threads. In the midst of the fibrine are seen fat, mucine, degenerated cells, and, in most cases, numerous microbes. Thus constituted, the false membrane may grow by the addition of new layers of fibrine and be reproduced when it is stripped off. The considerable quantity of fibrine which may thus be eliminated is not to be wondered at. Dr. Dastre has shown that this substance is very rapidly produced in the organism. If the greater part of the blood of a dog be defibrinated and again introduced into the vessels, it will soon be found that the blood is as rich in fibrine as normally. When a false membrane occupies the surface of a mucous mem- brane — ^that of the throat, for example — a moment will arrive in for- tunate cases when the secretions of the subjacent glands will detach the pathological productions and bring about their exfoliation; the remaining adherent debris will be picked up by the phagocytes. This process may be assisted by means of pilocarpine, which, by favouring glandular secretion, hastens exfoliation of the false membranes. In some cases the latter disappear in consequence of a histochemical transformation; they undergo a granular or a hyaline degeneration. In other cases, in tissues, and particularly in serous membranes, the false membrane, far from disappearing, becomes organized. The fixed cells and the wandering cells proliferate, following the false membrane, which serves them as a guide. Simultaneously the tissue becomes vascularized. In this way adhesions are formed, which may subsequently be absorbed, undergo sclerotic transformation, or become infiltrated with calcareous salts. The production of false membranes is to be considered as a re- sponsive process of defence. It is a barrier opposed to the penetration INFLAMMATION 255 of microbes or of toxines. In some cases it is a re-enforcement of tis- sues, which prevents their destruction under the influence of patho- logical causes. The false membranes developed upon serous mem- branes are intended for the same end. Reactions often exceed the end, or, after having been useful, become harmful. The diphtheritic false membrane may by its seat produce grave and fatal mechanical disturbances. The adhesions of serous membranes embarrass the movements of subjacent viscera, cause de- formities, compress important organs or excretory passages, and thus give rise to a whole series of new morbid manifestations. Suppuration Suppuration is one of the terminations of inflammation. It is characterized by the production of a liquid exudation, containing numerous necrosed cells, designated by the name pyocytes or pus cells. Characters of Pus. — According to the microscopical aspect, three varieties of pus are usually admitted : Phlegmonous pus, the laudable pus of the old authors, is a yellow- ish-white, creamy, thick, odourless liquid. It is met with in phlegmons and in purulent pleurisies. Caseous pus is more consistent. It resembles certain soft cheeses; hence the name given to it. Lastly, thin pus is formed of a serous liquid floating upon clots and frequently containing necrosed or sphacelated elements and fatty acids ; it often exhales a disagreeable or fetid odour. The colour of pus is no less variable. Usually yellowish, it may be of orange, brownish-red, or greenish colour. As to blue pus, the expression is bad; there is no suppuration presenting this colour. Under this name have been designated cases where dressing materials have imbibed a colouring matter — pyocyanine of Fordos— produced by a special bacillus {Bacillus pyocyaneus) which is not pyogenic by itself. No relationship exists between the aspect or the colour of pus and the cause which has determined its development. We shall make an exception only of the suppuration of pneumococcic origin, which is thick, greenish, and rich in fibrine, often having the aspect of false membranes. It is rather owing to the points where it is developed that suppuration presents particular characters. In subcutaneous or pleural collections the pus is phlegmonous, thick; in the meningeal membranes of the brain it is greenish ; in the liver, of chocolate colour ; and reddish in the lung. When it is of osseous origin it often con- tains fat and small splinters of bone. If it takes origin in the glands of the skin it produces a furuncle or a carbuncle — a lesion remark- 256 SUPPURATION able for the presence of sphacelated fragments of cellular tissue, which constitute the core. There may also be found in pus foreign bodies, tissue fragments, elastic fibres, animal or vegetable parasites, hydatids, actinomycetes, organic liquids, bile, milk, urine, faecal matters, and alimentary frag- ments. These various substances are of great importance from a semeiological standpoint; they inform us as to the origin of pus and as to the possibility of organic fistulas. It is generally easy to recognise pus. In case there should be any difficulty, for example, in the presence of inspissated mucus or of ste- atomatous contents of certain sebaceous cysts, it suffices to make a microscopical examination. The same method of exploration is useful in determining the presence of pus in certain organic liquids. In the urine, for example, it may be recognised by the addition of ammonia, which causes a curdled precipitate. In certain cases, to which we shall again refer, serous membranes contain chyliform exudations, which are formed of an emulsion of fatty matter. It is easy to recognise the nature of the latter. The microscope reveals the absence of pus cells, and ether completes the demonstration by dissolving the fat. Ether may also aid in the recognition of certain collections rich in choles- terine ; it dissolves this substance, and, on evaporation, leaves a deposit of crystalline lamellae the shining aspect of which is very charac- teristic. Histology of Pus. — Microscopic examination, which is to be re- sorted to in doubtful cases, shows in pus a great number of cells known under the generic name pyocytes (pus cells). According to their aspect and origin, they are divided into two groups: A. Large cells — namely (1) leucocytes, of which three varieties are admitted: mononuclear, polynuclear, and eosinophilic leucocytes; (2) Gluge's corpuscles, made up of the union in spherical masses of fatty granules arising from the destruction of cells; and (3) spheral cells derived from connective tissue. B. Small cells, including (1) small white globules, called lympho- cytes; (2) round cells derived from connective tissue; and (3) perhaps free nuclei. Chemical Constitution of Pus, — Chemically, pus is a neutral liquid, sometimes alkaline, exceptionally acid. Its density varies from 1,020 to 1,040. Allowed to stand, it does not coagulate, but sepa- rates into two layers: a superficial layer, the pus serum, and a pro- found layer, containing cells. In general, there are 700 or 800 parts of serum to 200 or 300 parts of globules, but these figures are very variable. In some instances pus contains only 25 per 1,000 of mor- phological elements. INFLAMMATION 257 Pus includes various albuminoid matters — serum, globuline, nucleo- albumin, albumose or peptone, fat, lecithine, and, in old foci, choles- terine. It also contains glycogen, which is contained in its cells ; pto- maines, ferments possessing the property of peptonizing gelatine ; and pigments derived probably from the colouring matters of blood and of tissues. It contains no urea and no sugar, except perhaps in cases of diabetes. Mechanism of Suppuration. — The origin of the liquid constituting the pus serum is evidently to be traced to the blood serum. That exudation depends upon a process of osmosis is inadmissible. In fact, in this hypothesis it would invariably have the same chemical constitution and contain the same elements as the blood plasma and in the same proportions. The differences observed from one case to another indicate that we have to deal with a true secretion : the altered cells draw certain substances in an elective manner; the vascular endothelia, disturbed in their function by the pathogenic cause which provokes suppuration, now allow one substance, now another, to pass. When the exudation is formed, its composition is subject to modi- fication by neighbouring cells or those which enter into it, and by pathogenic agents, particularly by the microbes which multiply in it. This is why albumoses and peptones are almost constantly present. These bodies, which are not found in the blood, have a local origin as the result of the action exercised by cells or microbes upon albu- minoid matters. At any rate, it is useless to dwell upon these facts, as we have already studied an analogous question in presenting the general history of inflammatory exudations. The cells that are found in pus are derived from two sources. The smallest number originate locally; the cells of connective tissue, the adipose cells, perhaps even some differentiated cells, are trans- formed into round elements. But the majority of purulent cells are of hemic origin. These are leucocytes, which, having collected in great numbers, escape from the vessels by diapedesis and accumulate at the point attacked. Some of these cells remain living; the majority suc- cumb in the struggle they sustain against the pathogenic agent — i. e., the cause of inflammation. It is precisely this death of the cells that characterizes suppuration. Hence the exudation comprises innumer^ able cellular elements, which, no longer of any use, represent nothing more than true foreign bodies, which are to be reabsorbed or elimi- nated. It is under these circumstances that the physician frequently intervenes, and, by an incision, permits the escape of the purulent collection. In many instances such collections are again formed, often with extraordinary rapidity: within forty-eight hours a pleuritic exudation of one or several litres may be reproduced. Now, if we 258 . MECHANISM OF SUPPURATION remember the number of leucocytes present in such an exudation, we can not but be astonished at so great a multitude of cells which the blood can furnish. Under normal circumstances the blood contains 6,000 leucocytes to the cubic millimetre, which, for the 5 litres contained in the human body, amounts to 30,000,000,000. Pus, having on an average 125,000 white blood corpuscles to the cubic millimetre, contains 125,000,000,000 to the litre, and that means that it contains four times more than the blood mass. We are thus led to ask. Whence come the innumerable leucocytes which are found in the exudation? Their presence seems to be ac- counted for by a previous leucocytosis. Instead of the normal figure of 6,000, the blood contains 15,000 to 20,000, and even 36,000 leucocytes per cubic millimetre. These leucocytes are produced in the hemato- poietic organs — in the spleen, which is often increased in volume; in the lymphatic glands, which are swollen ; and, above all, in the mar- row of the bones. The osteomedullary tissue, overcharged with fat in a state of rest, is modified as soon as the organism is in need of leucocytes. The pathogenic agent, which locally determines an in- flammation tending to become suppurative, directly or indirectly stimulates the vitality of the marrow of bones; the fat is absorbed, the cells are multiplied and fill up all the tissue. These modifications, so marked under a histological examination, are already appreciable to the naked eye: the marrow assumes a red colour, recalling the aspect which it presents at birth, where it is very rich in cells. This is a return to the foetal condition. The microscopic examination of pus, by showing the pathogenic agent, also informs as to the cause which has given rise to the pro- cess. In the majority of instances the development of suppuration is dependent upon the presence of microbes which may be brought to light by simple microscopic preparations. In order to obtain precise information, however, it is indispensable to have recourse to bacteri- ological cultures. Pyogenic Agents. — ^It has thus been recognised that suppuration may be caused by very numerous microscopic agents, which we shall divide into five groups : 1. Bacteria habitually Pyogenic, — They are normally encountered upon our integuments, and, although they may give rise to very varied manifestations, they especially provoke suppuration. These are Staphylococcus aureus and alhus, streptococcus, pneumococcus, colon bacillus, and Micrococcus tetragenes. 2. Specific Pyogenic Bacteria. — They produce suppurations which, from a clinical standpoint, present a particular evolution. Only three INFLAMMATION 259 microbes enter into this group : gonococcus, the bacillus of soft chan- cre, and the bacillus of glanders. 3. Bacteria accidentally Pyogenic. — This group comprises quite numerous species, which produce more or less well-differentiated le- sions, and may in certain cases cause suppuration. These are, for example, the tubercle bacillus, which causes most of the cold abscesses, and the typhoid bacillus, which may also produce pus, notably in bones. 4. Vegetahles capahle of becoming Pyogenic. — Here it is a question of parasites more elevated than bacteria. Such are streptothrix (of which Streptothrix hovis or actinomycetes is the most important), as- pergillus, and oidium. 5. Finally, the last group comprises the animal pyogenic parasites — namely, the sporozoa capable of inducing suppuration. The most important is the amoeba of dysentery, which, it seems, may cause abscesses in the liver. Of all these pathogenic agents, staphylococci and streptococci are most frequently encountered. In bringing together a certain number of well-prepared statistics, it is found that, out of 144 cases, staphylo- coccus has been discovered 114 times and streptococcus 26. Fre- quently, several species are met with united in the same focus : staphy- lococcus and streptococcus often coexist; they may further be asso- ciated with pneumococcus and with colon bacillus. Such polymicrobic foci are generally transitory, for one species gradually attains the upper hand, commonly staphylococcus, and the others disappear. When a pyogenic species is introduced into an organism suppura- tion develops, especially if the bacteria are numerous. We have already cited figures given by different authors. W. Cheyne finds that 250,- 000,000 cocci must be injected in order to produce an abscess. Bujwid declares that 1,000,000,000 is insufficient. The differences are ex- plained by the variability of virulence. In order that suppuration may appear, microbes of a medium activity are required. If too attenuated, they are destroyed without having produced any disturbance; if too energetic, they at once invade the economy and provoke a general in- fection, as septicaemia ; in both cases the local lesion is wanting. The effects also vary according to the point where microbes are intro- duced. In cartilages suppuration is very rare. What is more curious is the fact that tissues whose structure is nearly identical behave very differently : abscesses are frequent in the brain but exceptional in the spinal cord. Among the muscles, only three are generally affected: the deltoid, the sterno-cleido-mastoid, and the iliac psoas. The lung does not easily suppurate, at least the healthy lung; but when it is already altered, pus cocci develop in it with the greatest facility. The 260 MECHANISM OF SUPPURATION digestive canal is often traversed by the same cocci, which, if the mucous membrane is intact, are able to develop and produce no acci- dent whatever. The most sensitive part of the organism is the anterior chamber of the eye ; it is 8,600 times less resistant than the subcutaneous cellu- lar tissue. As regards the serous membranes, the variations are quite considerable: the arachnoid and the pleura easily suppurate; the peritoneum is endowed with a very powerful antimicrobic action. The pyogenic agents may be directly introduced into our tissues — for example, by an instrument charged with microbes. But in con- nection with mechanical agents there is a fact of considerable impor- tance on which we have already dwelt. A clean-cut wound, even when it is contaminated, often unites by first intention. This is true of nearly all wounds, even of operative wounds which appear the most perfect. Ideal asepsis, therefore, is an illusion. Numerous pyogenic microbes which produce no disturbance are found under the best dressings. . If, on the contrary, the wound is contused, or the borders lacerated, or the tissues mangled, the microbes develop with the great- est facility. Suppuration is also favoured by the presence of a foreign body. For example, the extraction of such a body often suffices to arrest the discharge without any other intervention. Chemical agents exert upon the tissues an analogous action, which therapeutists have turned to account: Thus, Croton oil, when spread upon the surface of the integuments, gives rise to the formation of pustules. Antiseptic substances, if too concentrated, favour suppura- tion. Before killing the microbe they cause death of the cells, and consequently diminish the resistance of the organism; they produce an effect which is just the reverse of the one expected. In cases where suppuration seems to appear spontaneously — name- ly, without traumatism or direct inoculation — it is often dependent upon a modification in the normal secretions, which, being diminished, are no longer capable of sweeping the excretory passages. The bac- teria enter them and develop. Their action is often favoured by the presence of some foreign body obstructing the canal. Thus, a hepatic calculus, by plugging the bile duct, permits the colon bacillus to invade the biliary channels and induce a suppurative angiocholitis. Likewise, if the cavity of the ileocaecal appendix becomes obstructed, the microbes contained in it will be apt to exercise a pyogenic role. This appendi- citis may be experimentally produced in the rabbit. Ligation of the appendix is sufficient to transform it into a purulent pouch. But if a cutaneous fistula be formed at the same time the ligature is applied, thus permitting the escape of the liquid produced within the intes- 4 INFLAMMATION 261 tine, no suppuration will appear, no matter how small this opening may be. In the course of infectious diseases the secretions are often dimin- ished or suppressed. In typhoid fever, for example, the mouth is dry. Formerly, when no antiseptic precautions were taken, the bacteria of the buccal cavity entered Steno^s duct and quite often caused paro- tiditis. As is known, this event has at present become altogether ex- ceptional. Finally, the pus cocci manifest a great tendency to invade parts already diseased. Lesions of the skin and mucous membranes and pulmonary alterations easily become the seat of suppuration. Vari- ous poisons probably favour the development of suppuration by alter- ing the tissues through which they are eliminated. The pustules of acne and the furuncles observed in cases of iodism and bromism may be explained in this manner. It is perhaps convenient to admit a more complex process. These substances cause digestive disturbances ending in an exaggeration of gastrointestinal putrefactions. Now, it is demonstrated that substances thus taking their origin may cause furunculosis (Bouchard). This form of cutaneous infection is easily cured by the administration of certain insoluble antiseptics — ^benzo- naphthol or beta-naphthol ; the fermentations decrease, and the cuta- neous glands, no longer having to eliminate an excess of toxines, be- come capable of resisting microbic invasion. Likewise, diabetes favours suppuration in consequence of humoral modifications. Clinics abound in illustrations, and experimental pathology furnishes similar results. A number of staphylococci, which produce nothing when injected beneath the skin, cause an abscess if a cubic centimetre of a 25-per-cent solution of glucose be introduced with the microbe. They cause a phlegmon if the sugar is injected into the veins. Lastly, all causes which weaken the organism favour suppuration. It is well known how frequently abscesses occur during convalescence from grave diseases. The suppurative focus, of which we have just studied the consti- tution and mode of development, may remain local or give rise to sec- ondary foci. In order for the microbic process to become generalized, the pathogenic germs must of necessity invade the circulatory system. In certain cases their passage into the blood is preceded by the devel- opment of a phlebitis. The microbe alters the walls of a vein, and the blood coagulates there. The clot invaded by the pathogenic agents subsequently breaks down, and its debris^ serving as vehicles for the microbes, gives rise to suppurative lesions at different points. In other instances the pus cocci reach the blood either by passing through the 262 MECHANISM OF SUPPURATION venous walls without occasioning previous coagulation, or after having penetrated the lymphatics and traversed the glands, which have been able to retain them for an instant. Once in the blood, the microbes do not remain there, as this medium is unfavourable for them. They therefore deposit themselves in the various tissues. From that moment three results are possible : The microbes may be destroyed by phagocytes; they may be at least partially eliminated by the sweat and the urine ; or they may multiply and produce visceral abscesses according to a procedure identical to that which explains the formation of the primary abscess. When a focus is developed, whether primary or secondary, sub- cutaneous or visceral, the organism tries to react : it forms a barrier which tends to circumscribe the infection. In fortunate cases the microbes diminish and in the end disappear, so that the focus passes through five successive phases : It at first contains living and virulent microbes ; then living, but attenuated ones ; then cadavers of microbes which are still visible under the microscope, but which can no longer be cultivated; at last it no longer contains any bacteria, but it is sterile. The nonmicrobic suppurations are frequently observed in old lesions, provided there be no communication with the exterior. They are often met with in the Fallopian tubes ; in the liver, in which about forty observations have been collected; and more rarely in the brain and around the kidney. Generally well borne, these foci may, however, give rise to various accidents, despite the absence of living microbes, notably to paroxysms of fever, but once opened up they heal with the greatest facility. In view of the fact that purulent collections may in time become sterile, we may inquire whether in certain cases pus could not develop under the influence of simple chemical substances without the inter- vention of any living element whatever. This question, which has given rise to most animated controversies, is to-day solved. Numerous experiments made in animals and therapeutic inoculations practised in man have established that pyogenic properties may be attributed to a great number of substances, of which we shall mention metallic mer- cury, calomel, silver nitrate, turpentine, Croton oil, antipyrine, solvines, sapotoxine, digitoxine, etc. The chances for suppuration to be effected will be the greater the larger the quantity of substances injected, the more concentrated the solutions used, and the more slowly they are introduced. Five drops of turpentine injected at once does not pro- duce any pus; the same quantity introduced from a small celluloid pouch, from which it should flow slowly, will give rise to its appear- ance. The latter experiment, which we owe to Poliakoff, undoubtedly INFLAMMATION 263 explains a great many discordant results. Other contradictions are due to the fact that effects vary according to the animal species. Non- microbic suppuration is produced in the rabbit with much more diffi- culty than in the dog. Thus it is seen that generalization of particu- lar cases has, as always, led to error. When it is remembered that the microbes themselves act only through the agency of the soluble matters which they produce, it is not astonishing that certain chemical compounds should have a pyo- genic action. The cultures of Staphylococcus aureus contain an alka- loidal substance, Leber's phlogosine, which is probably nothing else than a product of the true toxine, an albuminoid matter, isolated by Christmas, the injection of which causes suppuration. Similar results have been obtained with the cultures of strepto- coccus, with the extracts of putrid meats, and with ptomaines like cadaverine. Behring has demonstrated that the pyogenic power of the soluble products is annihilated by iodoform. Thus is explained the action of this drug, which, although feebly antiseptic, exercises such a favourable influence upon suppuration. Finally, from the important researches of Buchner, it appears that the protoplasm of bacteria contains pyogenic substances. It may be concluded from this fact that when microbes are destroyed and dis- integrated the pyogenic substance contained in them is given off, spreads in the focus, and may favour its extension. To sum up, suppuration is a common process which may be due to a great number of chemical substances and animate agents. Clin- ically, pus is almost always produced by microbes. But the latter act only through the agency of the soluble products which they secrete or through the substances contained in their protoplasm. We must there- fore conclude that suppuration is always occasioned by chemical sub- stances. Evolution of Purulent Foci. — Once formed, the purulent collection tends to make its way in the organism. It advances and extends by means of the ferments which the pus contains and which digest the tis- sues. It thus directs itself toward the exterior or toward a hollow organ, preferably following the paths half traced by the aponeurotic or muscular interstices, and the vascular or nervous sheaths. Then the collection opens and the pus flows out. At the same time a work of reparation begins, which in abscesses experimentally caused is already appreciable on the second day. Buds are formed, which tend to fill up the suppurating cavity; they con- tain voluminous cells, destined to free the focus from the cellular cadavers that may be found there. The buds that come in contact unite and give origin to a soft or hardened cicatrix, which is some- 18 264 EVOLUTION OF PURULENT FOCI times exuberant. In the latter case it constitutes a sort of tumour called keloid. In certain cases pus becomes encysted, and may undergo fatty de- generation and assume the aspect of chyle. Chyliform collections have chiefly been observed in serous mem- branes. They have been the subject of numerous discussions. In certain cases there has been, it seems, a true collection of chyle, due to rupture of an important vessel or even of the thoracic duct. In most cases it is a primarily purulent collection whose microbes have succumbed, and whose cells, having undergone granulo-fatty degen- eration, have completely disintegrated; the freed fat has been emulsi- fied and has imparted to the liquid a milky aspect. Such collections are mainly observed in the pleura, peritoneum, and tunica vaginalis. If the liquid part is absorbed, there remain thick, caseous masses, which may become infiltrated with calcareous salts. Symptoms. — The development of a purulent focus is expressed by a series of symptoms, the principal ones being the four so-called cardinal symptoms, namely, pain, heat, redness, and swelling. Pain is generally the first phenomenon by date. It is due to an increased flow of blood and to active congestion occasioned by the introduction of a pyogenic agent. The arrival of arterial blood is expressed by a slight hypersesthesia of the skin and by a sensation of throbbing synchronous with the pulse. At the end of a certain time the pulsatile pain gives place to a sensation of constriction, due to dis- tention of the resisting parts and to stretching of the nervous ter- minations. Subsequently, when the purulent collection is produced, the spontaneous pain disappears, and profound pain is caused only on pressure. Shortly after the beginning of the painful manifestations, some- times at the same time, more rarely before, pain and redness appear. These two phenomena are less constant; they are wanting when the focus is profound — for example, when it is inclosed in the cavity of a bone. Therefore, particularly appreciable in cases of superficial lesions, they are related to the increased circulation of blood and to karyo- kinesis. However, even in cases of profound suppurations, the tem- perature may rise in those regions of the skin which cover the parts attacked. Local thermometry reveals a rise of temperature by a few tenths of a degree. The fourth phenomenon, swelling, is evidently appreciable only in cases of foci superficially situated or tending to bulge outward. However, even if the collection is profound, one may often observe a sometimes considerable oedema in the integuments which cover it. The semeiological importance of this phenomenon is very great. In INFLAMMATION 265 cases of pleurisy, for instance, the oedema of the thoracic wall indi- cates almost surely the purulent nature of the exudation; similarly, in cases of suppurative osteomyelitis, the integuments are frequently infiltrated with an abundant serous exudate. Besides the four cardinal phenomena above indicated, there are functional disturbances to be considered. The glands in the neigh- bourhood of the focus may secrete in exaggerated amounts or give origin to liquids of an anomalous constitution; in other cases, on the contrary, the secretion stops. The muscles often lose their power. Stokes has made known the paralysis of the diaphragm occasioned by purulent exudations of the diaphragmatic pleura. The palate is equally impotent in cases of intense phlegmonous angina. Finally, in peritonitis, tympanites is likewise explained by a paralysis of the nonstriated muscular fibres of the intestine. The natural tendency of purulent collections is to make their way outward and be evacuated. Once open, the course is toward a cure; but a favourable evolution may be hindered by manifold causes. The opening may be insufficient; then the pus tends to propagate toward other regions and causes channels and cavities; or the fistula will now and then close up, with the result that various accidents will occur, due to the retention of the pus; or the opening will be made into an important organ and be followed by grave or fatal accidents; or, finally, the focus will be secondarily invaded by germs, which will induce putrid fermentations. When the evolution seems to be on the point of terminating, an accidental cause may revive the process. Transitory indisposition, in- digestion, fatigue, nervous shock, moral impression, sometimes un- timely intervention, will determine the spread of the suppuration. From the standpoint of their course, abscesses are often divided into two groups : hot abscesses and cold abscesses. Hot abscesses include circumscribed phlegmon and diffused phlegmon. Circumscribed phlegmon is a collected, well-defined suppuration, generally surrounded by a membrane called pyogenic. Diffused phlegmon, badly limited, tends to extend and invade the neighbour- ing parts; it is accompanied by grave phenomena, and in some re- spects it resembles erysipelas; at any rate, it is streptococcus which intervenes in both cases. Cold abscesses are at present often considered as tuberculous ab- scesses. It is quite certain that tuberculosis is the principal cause of the suppurations which are designated as " cold," because they arouse no local or general reaction. But the same process may be 266 EVOLUTION OF PURULENT FOCI referable to very numerous agents. The Staphylococcus aureus may produce, especially in the skin, chronic abscesses, the evolution of which in every way recalls that of a tuberculous focus. These abscesses are mainly observed in children: their nature has been demonstrated, on the one hand, by cultures which have revealed the presence of the staphylococcus, and, on the other hand, by direct inoculation of the virulent products into guinea pigs — inoculation that has not been fol- lowed by the development of tuberculous lesions. Staphylococcus has exceptionally been able to produce analogous lesions. The typhoid bacillus especially locates itself in the marrow of bones in convalescents from typhoid fever, and causes chronic osteo- myelitis, which, without the assistance of bacteriology, one would be tempted to consider tubercular. There exists a last variety of nontubereulous cold abscesses : these are produced by actinomycetes. It has exactly the same course as in tuberculosis. Error will be avoided by a careful examination of the pus. There will be found in it small yellow grains, which have been rightly compared to the flower of sulphur. Examined under the micro- scope, these small masses appear to be formed of radiated filaments terminating by clublike swellings at their periphery. Gangrene Definition. — -Gangrene is a morbid process essentially characterized by the mortification and putrefaction of tissues. Mortification does not suffice to define the process. If it exists alone, the condition is designated as necrobiosis. In order that gan- grene may occur there must be putrefaction in addition to necro- biosis. Now there can be no putrefaction without microbes. There- fore gangrene is always of microbic origin, while necrobiosis may be produced by most varied agents. Let us suppose, for example, that the principal artery of one of the lower extremities is obliterated and the circulation interrupted: gangrene will appear, for the microbes of the integuments will invade the parts deprived of circulation. Without the intervention of microbes there would be only a simple necrobiosis. In fact, if the obliterated artery be that of a part inaccessible to air — one of the cere- bral arteries, for example — the tissue will degenerate ; in this particu- lar case there will be softening, but, owing to the absence of microbes, no gangrene. The microbes causing gangrene act upon the altered tissues as they would upon the tissues of cadavers. Between gangrene and cadaveric putrefaction, however, there are decided differences. First, the affected parts are still the seat of certain reactions. There is an influx of INFLAMMATION 267 serum, Ij^niph, and blood pigment ; the bacteria, attacking the exudate, produce new fermentations therein. On the other hand, whatever may be the extent of the lesions which give origin to the gangrene, it is inadmissible to assume that all the cells are attacked. Some of them survive, at least those that are in the peritoneum, and these are able to react and thus impart a special character to the process. We shall state, therefore, that cadaveric putrefaction is a fermenta- tion in dead tissues. Gangrene is a putrefactive fermentation in tis- sues altered but not completely deprived of life. EflSicient and Accessory Causes. — There is no gangrene microbe. A great number of bacteria may give rise to this process. Pathogenic agents have been divided by some authors into two groups : those capable of inducing gangrene in healthy tissues — name- ly, the two successive stages of necrobiosis and of putrefaction — and those which require the pre-existence of necrobiosis and which are simply putrefactive. This division, which possesses a certain importance, is not perfect, for, even in the case of the most active agents, accessory or predis- posing causes play a considerable part. It is altogether exceptional to see healthy tissues invaded by gangrene. The causes favouring the development of gangrene may be divided into two groups, according as they act directly on the tissue to lessen its vitality, or indirectly, by means of the vessels, the nervous system, or the blood. Each group comprises a certain number of secondary causes, which may be classified in the following manner : Agents. J Mechanical. Direct alterations of tis- J Physical. sues by j Chemical. [ Animate. ^. , , r Vascular compressions and obliterations. Circulatory I ^^^^^.^.^^ Indirect alterations by disturbances. (Edema. r Encephalo-myelitic alterations. , , < JSeuritis. disturbances. '^ Raynaud's disease, r Humoral alterations. Dystrophic J Auto-intoxications, disturbances. 1 Exogenous intoxications. y Infections. The influence of alterations produced by various traumatic agents is evident. Ragged, contused wounds, mechanical compressions and lesions of vessels and nerves, and comminuted fractures considerably favour the development of all microbes in general, and of those of gangrene in particular. 268 GANGRENE Intense heat and cold act in the same way by diminishing the re- sistance of the cells and disturbing the circulation. Chemical agents are still more important. Caustics, venoms, organic liquids, and bile or urine abolish the resistance of the tissues in which they spread. Urinary infiltration, consecutive to rupture of the urethra, for exam- ple, greatly predisposes to suppuration and gangrene. The interven- tion of animate agents which prepare the way for the action of gan- grenous agents is much more complex, and seems to be concerned not in a local lesion, but in a disturbance of the entire organism. At the head of causes acting indirectly we shall first of all cite those which disturb the blood circulation, notably those diminishing the supply of arterial blood. Whether arteriosclerosis, acute arteritis, thrombosis, or embolism be present, gangrene can not appear without the intervention of microbes. This is demonstrated by the classical experiment of Chauveau on twisting the testicle. This operation en- tails a simple atrophy of the testicle; but if before practising it microbes be injected into the veins, the organ deprived of its vessels will become an easy prey and will be attacked by gangrene. The arterial obliteration does not need to be complete. A simple stricture suffices, especially when connected with an infectious process. The microbes located in the vessel walls secrete substances which com- plete the annihilation of the resistance of the surrounding tissues. Vascular spasm may have the same effect. In symmetrical gangrene of the extremities, or Eaynaud's disease, simply a vaso-constriction is produced, followed by small patches of gangrene, which are to be attributed to the microbes of the skin. Disturbances of the venous system are much less important, be- cause either the re-establishment of the circulation is easier or the accumulation of dark blood is less harmful to the tissues than the absence of arterial blood. QEdemas, for example, even when abundant, are rarely invaded by gangrene ; phlebites are almost never followed by this accident. The influence of the nervous system is evidenced by numerous facts; the eschar, which rapidly ensues in hemiplegic or paraplegic patients, is explained by the nutritive disorders which permit microbic invasion. Lesion of a nerve may have the same effect. Brown-Sequard has shown that section of the sciatic nerve in the guinea pig is fol- lowed by gangrenous phenomena in the extremities. Here it is a mat- ter of secondary infection, which is avoided by protecting the paw against the action of the external germs. The inoculation of strepto- coccus beneath the skin of the ear of a rabbit no longer produces a simple erysipelas, but a gangrenous inflammation, provided the au- riculo-cervical nerve, which furnishes sensibility to the region, be sev- INFLAMMATION 269 ered at the same time. In man, confirmation of these facts is found in those cases in which peripheral nenrites produce sphacelus and at times massive gangrene. Finally, modifications in the composition of the blood play a con- siderable predisposing part. It suffices to mention the influence of diabetes and the frequency of gangrene in this affection. In other cases it may be a poison — ergot or mercury, for example — which, by modifying the circulation or the vitality of the cells, permits the devel- opment of the gangrene germs. As to infections, their influence is complex. They act by disturbing the circulation, paralyzing the nervous system, causing auto-intoxica- tion, altering the various protective organs, diminishing the secre- tions, and by disturbing nutrition. Gangrene results from the synergic action .of these various factors. Bacteriology of Gangrene. — The microbes capable of producing gangrene are divided into two groups. There are, first, those which especially possess this power. The chief representative is a bacillus described by Pasteur under the name septic vibrion, also known to the school of Lyons as bacillus of gangrenous septicemia, and by the German authors as bacillus of malignant oedema, but better termed bacillus of gaseous gangrene (page 111). The disturbances caused by this bacillus in man have been vari- ously designated as malignant oedema (Pirogoff), acute purulent oedema, swift gangrene {gangrene foudroyante, Maisonneuve), invad- ing traumatic gangrene (Bottini), and as gangrenous septicsemia (Chauveau). These various expressions can not be accepted, since they give rise to confusion. The terms gangrenous septicaemia, and that of septic vibrion, applied to the microbe, have only served to lead to numerous errors. It is therefore better to adopt the expression gaseous gangrene, which has the advantage of recalling the nature of the phenomena observed. As is known, the microbe of gaseous gangrene is an anaerobic ba- cillus. It is very widely distributed, and is found abundantly in the soil, on vegetables, and in the mud of waters; it is encountered almost constantly in the residue upon porcelain filters. Poincare and Mace have found it in alimentary preserves, vegetable or animal. This ubiquity explains its presence in the bodies of living beings. It may be found in the saliva, and it is often met with in the intes- tine, especially in the horse. Discharged with the faecal matters, it is spread in abundance upon the soil. Being anaerobic, the bacillus can not develop on solution of con- tinuity exposed to the air; it can only vegetate in ragged ones and in 270 BACTERIOLOGY OF GANGRENE contused tissues. The recent investigations of Penzo and of Besson have even established that the spores of this bacillus, freed from tox- ine, do not produce any disorder; they do not act except when another microbe is injected with them, or when profound lesions are produced in the tissue. Thus, that which occurs under natural conditions where the gangrenous bacillus is introduced into wounds along with foreign bodies, earth, and numerous microbic germs, can be experi- mentally produced. There exist other microbes that may behave like the bacillus of gaseous gangrene, but they have mainly an experimental interest. A few of them, however, have been encountered in man, but in an ex- ceptional manner. The second group which we must study is represented by a series of bacteria which are gangrenous only on occasion. These are the pyogenic microbes, notably streptococcus, staphylococcus and proteus. We have shown that these agents begin by exciting necrosis at the point of their introduction. If, however, the organ is vigorous, re- action appears and is expressed by suppuration. On the other hand, if the organ is weakened, altered, or incapable of sufficient reaction, necrosis attains the upper hand and gangrene develops. Reciprocally, the bacteria which produce gangrene, like the bacillus of gaseous gan- grene, only cause abscesses in resisting animals. There are, then, numerous transitions between suppuration and gangrene; the exist- ence of gangrenous phlegmons is the clinical proof thereof. The ex- perimental proof is furnished by a well-known experiment of Bujwid ; Staphylococcus, the pyogenic agent par excellence, causes gangrene when sugar is conjointly introduced into the organism. localization of Gangrenous Process. — All parts of the body may be attacked by gangrene, provided they communicate directly or indi- rectly with the exterior. The shin is often attacked; the most diverse lesions, such as ery- sipelas, impetigo, herpes zoster, the pustules of smallpox and vari- cella, at times even simple abrasions, may be followed by gangrenous patches. But in order that this eventuality may be realized, a special debilitation is required in the subject, whether he be a convalescent or suffering with a chronic affection. Thus are developed the eschars upon the sacrum, following some minute lesion, in convalescents from grave fever, and notably from typhoid fever. In certain cases gangrene is accounted for by the previous pro- duction of an arteritis, which, obliterating the principal vessel of a limb, abolishes the resistance of the parts depending upon it. Some- times arterial alteration is due to a localization of the agent of the principal disease; oftener it depends upon a secondary infection. It INFLAMMATION 2Y1 is generally streptococcus that is met with, and this microbe may be found in the condition of purity in the vascular clot and the sphace- lated tissue. In other instances it is a chronic arteritis which, by a similar mechanism, causes gangrene; by producing obstruction of a blood vessel it permits the development of the skin microbes. Such par- ticularly is the process which explains senile gangrene. The focus comprises various bacteria, some of them common, others less com- mon, as was the one found by Tricomi in a case of this kind. Analogous considerations are applicable to mucous membranes. In the mouth the gangrene called noma, which is to-day extremely rare, occurs in consequence of infectious diseases, especially of mea- sles, attacking weak and poorly kept children. The lesion is occasioned by slender bacilli ( Schimmelbuch, Babes), more frequently by strepto- cocci. It is to the same common bacteria, to ordinary pyogenic microbes, and to saprophytes that the patches of sphacelus often observed in grave diphtheria cases are to be attributed. In gangrenous parotidites Girode has found the pneumococcus associated with a slender bacillus. The respiratory apparatus is quite frequently attacked; necrotic laryngites have been noted during convalescence from serious infec- tions, measles, and typhoid fever. The lung especially deserves to be studied; it may be the seat of two orders of lesions. In a certain number of cases gangrene reaches the bronchial terminations ; this is gangrenous hroncliitis, the curable gangrene of the bronchial terminations. In persons suffering with chronic bronchitis, it is noticed that at a certain moment the expectoration and breath assume a characteristic odour, but the general condition remains good; the lesion is superfi- cial, and is easily cured under the influence of eucalyptus and hypo- sulphite of soda. As to the microbes encountered, they are staphylo- cocci, streptococci, pneumococci, a long, spore-bearing bacillus de- scribed by Lumnitzer, at times higher parasites, such as leptothrix, oidium, and actinomycetes. The same microbes, although the evolution be different, are met with in parenchymatous gangrene of the lung. These are pneumo- cocci, streptococci, tetragenus, leptothrix, spirilla, and agents of putre- faction. There are certain cases where bacteriological examination reveals the exclusive or predominating presence of a streptococcus or of Staphylococcus aureus. With the latter microbe Bonome has been able to reproduce in the rabbit gangrenous foci, which he quite rightly compares to anthrax of the lung. In other cases streptococci have almost exclusively been found. The bacteria multiplying in a morbid focus increase in virulence, 272 LOCALIZATION OF GANGRENOUS PROCESS and when once excited they may reach a certain number of individ- uals. In this way small epidemics are developed, notably in hospital wards. But what well demonstrates the part played by accessory causes is the fact that individuals with previous lesions of the lung are the only ones attacked. It is very important to know that, in a certain number of cases, the microbes of the gangrenous focus possess no virulence for ani- mals. The injection into rabbits and guinea pigs of liquids derived from pulmonary gangrene and containing numerous bacteria does not often produce any disturbance. Therefore it seems that, once set in motion, the process continues despite the weakening of the pathogenic agents, which, although capable of causing death in a diseased organism, lose all action when they are transported into a normal body. The study of pulmonary gangrene has made especially prominent the part played by predisposing causes. Cachexias, diabetes, chronic alcoholism, and inhalation of deleterious gases favour the development of the gangrenous process. The latter may develop at once, or may be consecutive to another pulmonary lesion. From Laennec to Gri- solle, it has always been admitted that pulmonary gangrene should not be considered as a consequence of simple pneumonia. Authorities have endeavoured to find signs of differentiation between the two pro- cesses, such as more diffuse pain in the side, more intense dyspnoea, and more marked prostration. The distinction was subtle, and has not been confirmed. It is to-day admitted that the pneumonic form of pulmonary gangrene is in reality a pneumonia terminated in gan- grene. The statistics of Middlesex Hospital are very interesting in this regard. Out of thirty-four cases of pulmonary gangrene, we find that the process occurred fourteen times in consequence of simple pneumonia, nine times consecutively to cancer of the neighbourhood, and notably to a cancer of the esophagus, six times in the course of chronic pneumonias, four times as the result of embolism, twice in dilatation of the bronchi; lastly, in the other three cases, it was con- secutive to cerebral hemiplegia, aneurism of the aorta, and tubercu- losis of bronchial ganglia. To complete the etiology, we must add gangrene of traumatic origin and that which supervenes, notably in insane persons, when a bolus of food charged with microbes penetrates into the respiratory passages. In cases of embolism, it is often a question of transportation of microbic agents started from a gangrenous focus toward the lung. The process is easy to comprehend; the secondary focus is identical with the primary one. But the latter may be simply suppurated. If the pulmonary lesion becomes gangrenous, it is because it is invaded INFLAMMATION 273 secondarily by saprophytes, which penetrate with the air and add a putrefactive process to the pyogenic. A gangrenous focus developed in the lung may reach the pleura by propagation. In other cases gangrenous pleurisy will follow a pulmonary abscess, the opening of a tubercular cavity, or as a conse- quence of the proximity of a tracheal, pulmonary, and especially esophageal cancer. Again, it may be consecutive to suppuration of some distant organ — the liver, the spleen, or the kidney. There is observed in all these cases the development of a sanious, brownish, fetid exudation, comprising the various microbes which we have already seen in the lung. In other cases gangrenous pleurisy may be caused by known microbes — to Proteus vulgaris or to Bacillus coli. The abdominal portion of the digestive canal is rarely attacked by gangrene; the superficial necroses of the gastrointestinal mucous membrane are hardly deserving of this name, except in certain cases of dysentery. The true intestinal gangrenes are those that recognise a mechanical cause: internal or hernial strangulation permits the invasion of the walls by the numerous microbes of the digestive tube and speedily ends in mortification. As pulmonary lesions frequently extend into the pleura, so intes- tinal lesions are often followed by a putrid peritonitis. They may also give birth to emboli, which locate themselves in the liver and there provoke gangrenous abscesses, as is at times observed in the course of dysentery. Of the other varieties of gangrene, it is convenient to also cite the swift gangrene of the penis, which may cause the death of the organ within a few days. The bacteriology of this frightful affection is not known. Division of Gangrene. — Clinically, two forms of gangrene are admitted — dry gangrene and moist gangrene — which are related to each other by numerous intermediaries. In dry gangrene, putrefaction is less intense and the odour much less marked. Such is the case in senile gangrene and certain forms of pulmonary gangrene in diabetes. Chemical analyses have shown that dry gangrene differs from moist gangrene in the smaller amount of water and greater amount of carbon. The odour of the foci is due to the presence of volatile fatty acids, butyric acid, and especially valerianic acid, and of gases, ammonia, and sulphuretted hydrogen. Besides these odorant matters are found leucine, tyrosine, and particularly ferments that seemingly play a very important part. There is one, analogous to trypsine, which digests elastic fibres, and this explains why they are often want- ing in the expectoration. 274 TUBERCLES Of the various known or unknown substances contained in a gan- grenous focus, some are absorbed and produce the grave phenomena attending the process. It is, as always, a true intoxication of the organism; the general as well as local manifestations of gangrene are explained by the action of the secretions and the microbic fermen- tations. Infectious Nodules In suppuration, as well as in gangrene, it is a question of de- structive inflammatory process, without any tendency toward organi- zation. When infection is less violent, the round cells proceeding from the tissues or emigrating from the blood vessels remain living, agglomerate, and constitute little nodules. The latter, in a great number of cases, are not visible to the naked eye; it is the microscope that reveals their presence in the bosom of principal organs — e. g., the liver, spleen, kidneys, and lungs. They form small embryonal produc- tions, which seem to have developed around a microbic colony; but it is not the microbe as a morphological element that acts, since the same lesion may be produced experimentally by injections of toxines. When the nodule is voluminous and becomes visible to the unas- sisted eye, it appears under the aspect of granulations that are di- visible into two groups : pseudo-typical or nontypical tubercles, which may be produced by the most varied agents, by inanimate foreign bodies as well as by living parasites, animal, vegetable, or microbic; and true tubercles, which are referable to Koch's bacillus and are specific inflammatory nodules. Tubercles Anatomical Characters. — Leaving aside the history of pseudo- tubercular granulations, let us consider the development of true tuber- cles — that is, those caused by the bacillus of Koch (page 109). From an anatomical standpoint, the tubercle presents itself under three different aspects : gray granulation, Laennec's tubercle, and caseous mass. Gray granulation is represented by small, hard, protruding, non- enucleable nodosities, often surrounded by a reddish vascular zone. Their dimensions vary from 0.5 millimetre to 2 or 3 millimetres; at first translucent, they subsequently become opaque and yellowish. Laennec's tubercle is more voluminous; it is a round, gray or yellow mass, having the volume of a pea, a hazelnut, or even of a walnut. The caseous masses are greenish-yellow deposits, presenting the aspect of certain cheeses, notably of Roquefort cheese. INFLAMMATION 2Y5 These lesions, differing in their macroscopic characters, are con- stituted on the same plan; they result from the fusion of several ele- mentary lesions designated under the name tubercular follicles. The main characteristic of a tubercular follicle is not such or such a cellular element, but the mutual arrangement of the various ele- ments entering into its constitution. Theoretically, a tubercular follicle is formed of three zones. In the centre is found a giant cell, the Riesenzelle of German authors. Eound or polygonal in shape and provided with numerous projections, this nodule contains 20 to 30 oval and nucleolated nuclei, disposed in wreath form in its periphery. The second zone is composed of epithelioid cells, quite voluminous, with an abundant and somewhat granular protoplasm. The peripheral zone is represented by embryonal round cells with voluminous nucleus. These cells are very numerous and crowded together. The various cells constituting the elementary tubercle are united by an intermediary reticulum of a fibrillary nature. Throughout the whole extent of the neoplasm no blood vessel is found, and this is a fact of great importance. The elementary follicle is not always complete. At first but a mass of round cells is found; at a more advanced period the epitheli- oid cells may be wanting. The bacilli are encountered in great number in the giant cells ; some are well coloured, others are colourless or surrounded by a cap- sule. The epithelioid cells often contain one or two of them, but they succumb when a greater number of bacilli penetrate into their interior. To constitute the various lesions visible to the naked eye, several follicles unite and come to fusion; the agglomeration thus formed represents an individual the centre of which degenerates. A vitreous degeneration at first appears ; the cells become homogeneous, unite, and form a translucent and fissured mass ; then the mass becomes opaque. This is caseous transformation, in which morphological elements are no longer perceived, not even bacilli. Around this mass there will again be found the characteristic lesions, the follicles, or the giant cells. So, simply by means of histological examination, Grancher and Thaon have been able to re-establish the unity of tuberculosis, which the studies of Virchow and of Reinhard seemed to have caused to be aban- doned. At present there is no longer any doubt in this respect. Ville- min has demonstrated that . caseous masses as well as granulations give rise to the development of a miliary tuberculosis when inoculated into animals. The discovery of Koch has completed the demonstra- 276 LOCALIZATION AND EVOLUTION OF TUBERCLES tion by permitting the detection of the same bacillus in the various anatomico-pathological productions. The cells entering into the constitution of the tubercle have been considered by some to arise from the fixed cells of the invaded tissue (Baumgarten), and by others to be migratory cells. The latter theory, sustained by Koch and by Metschnikoff, is now tending to prevail. It seems, however, somewhat too exclusive. Histologically, all cells unite to form the tubercle. As regards the phagocytic struggle against the germ, the principal action is referable to the mesodermic elements — namely, to the fixed cells of connective tissue and to leucocytes. The polynuclear leucocytes are the first to arrive, but they rapidly die and are replaced by mononuclear leucocytes, some of which are trans- formed into epithelioid cells. As to the giant cell, it is produced either by the hypertrophy of a leucocyte, whose nuclei then increase in number and form a wreath at the periphery of the element, or by the coalescence of several cells. Finally, in certain cases the aspect observed is due to the penetration of leucocytes into a mass of degenerated protoplasm. Thus constituted, the tubercle progresses toward caseation; it may then soften and open exteriorly. In other cases it undergoes fibrous or calcareous transformation. This is a mode of healing which is expressed by a simple cicatrix. Localization and Evolution of Tubercles. — Tuberculosis appears in man under very different clinical aspects. Pathogenically, the mani- festations that are observed may be grouped under three headings: lesions by inoculation, produced at the point where the bacillus enters the organism, lesions by propagation, and lesions by infection. In the last-named case generalization takes place through the blood; it is the hematogenic tubercles which, contrary to the preceding ones, evolve from within outward. The principal tuberculosis of inocu- lation is precisely the manifestation that is most frequently observed: common pulmonary tuberculosis. The bacilli introduced with the inspired air, generally protected by the organic particles containing them, ingraft themselves in the apices of the lungs. This localization is to be attributed to the limited expansion of the thoracic cage in the upper parts, and, according to Hanau, especially to the weakness of expiratory movements. The pulmonary foci, largely communicating with the exterior, are invaded by a considerable number of bacteria, the effects of which are added to those of the principal agent. There occur streptococcus, staphylococcus, pneumococcus, tetragenes, colon bacillus and pneumo- bacillus, Micrococcits pneumonice (Ortner), etc. All these agents work to the destruction of the lung, to the formation of cavities ; the INFLAMMATION 277 soluble products which they produce play a considerable part in the appearance of cachexia and in the development of hectic fever. The other parts of the respiratory tracts are reached with more difficulty than the lungs. Primary tuberculosis is exceptional in the nasal cavities and quite rare in the larynx. If the current of air passes through the mouth, protection against microbes is still suffi- cient, and even though the tonsils often contain bacilli at their sur- face, they are very rarely affected by them. Next to the respiratory, the digestive apparatus is the most ac- cessible to the bacillus. In most cases, however, the intestinal lesions, as those of the mouth and the larynx, are secondary, and are to be accounted for by the passage or deglutition of expectorations. In the statistics published by the Anatomico-pathological Institute of Mu- nich, out of 1,000 tuberculous individuals, we find 566 cases of sec- ondary tubercular lesions of the intestine, and only 19 of primary lesions. As the aliments are to be accused in the latter case, this etiology is rare in the adult, and more frequent in children who may be nourished with cow's milk containing bacilli. The existence of intestinal tuberculosis may be looked upon as proved when bacilli are found in the stools ; since, in the majority of cases, the microbes swallowed do not pass into the faecal matters if the intestine is intact. The diagnosis is reached also by the presence of blood in the stools. In cases of tuberculous ulcerations not a week passes without some blood being found in the stools. Inoculations may also be produced in the skin. The results are local lesions of little virulence, containing few bacilli and manifesting hardly any tendency to generalization. Often primary, these lesions are sometimes due to a secondary inoculation. In a person suffering from common tuberculosis, a particle of expectoration may be acci- dentally deposited upon a slight abrasion ; in other cases, a cutaneous tuberculosis is developed around a tuberculous fistula. As is known, cutaneous tuberculosis assumes several forms. We may mention the anatomical tubercle ; tuberculous lupus ; perhaps ery- thematous lupus, although the last one does not present the histo- logical structure of tubercle, and no bacilli have thus far been found in it; warty tuberculosis of the skin, which is mostly observed in the hands and fingers ; and, finally, cutaneous foci. In profoundly affected tuberculous patients, auto-inoculation has been seen to be followed by rebellious ulcerations upon the tongue or the lips, and in cases of in- testinal or genito-urinary tuberculosis, in the anus, in the vulva, and in the penis. It is a kind of tuberculous chancre, analogous to that observed in animals experimentally inoculated. Finally, there remains the genito-urinary apparatus, which may 278 LOCALIZATION AND EVOLUTION OF TUBERCLES also be invaded primarily. In the man, the manifestations generally begin in the head of the epididymis, whence the infection spreads suc- cessively into the testicle, cords, vesicles, prostate gland, and bladder. At times the bladder or the prostate is reached primarily. In women, the lesions mostly affect the Fallopian tubes, then the ovaries, and the uterus. In both sexes the bacilli may make their way from the blad- der to the kidney, and there produce caseous masses and a destructive process extending from the papillae toward the cortical substance. This aspect permits a distinction between ascending hematogenic and renal lesions. But it is to be noted that genito-urinary localizations that are met with in 1 out of 50 autopsies are in most cases due to a hematogenic origin. In short, primary or secondary foci of inoculation may be observed in any part of the organism exposed to the contact of the external world. The bacilli, being generally transported by the air, in most cases invade the respiratory passages ; the digestive apparatus is more rarely reached, at least in the adult ; the skin is quite frequently affected, while primary tuberculosis of the genito-urinary organs is extremely rare. The focus thus developed may remain isolated, constituting a local lesion, often curable. In other cases it causes inflammation in the neighbouring parts. In the case of organs like the lung, the intestine, the Fallopian tubes, or the seminal vesicles, the adjacent serous mem- brane may soon be invaded and present manifestations so intense as to dominate all the morbid process. Nothing in this connection is as instructive as the history of pleurisy. The investigations of Landouzy, Kelsch and Vaillard, and those more recent of Le Damany, have demonstrated that serous pleurisies, except those depending upon a subjacent pulmonary lesion, are always of a tubercular nature. The liquid contains only few bacilli, and these not constantly; hence its inoculation into guinea pigs rarely produces tuberculosis. On the other hand, it quite frequently contains ordinary bacteria, whose presence does not seem to very much modify the evo- lution of the process. Tuberculous pleurisy often assumes a purulent form. The affec- tion is remarkable for its long duration, for the little reaction it pro- vokes, and for the possibility of a chylous transformation. Bacteri- ological examination is of great diagnostic importance, since by these means it is possible to decide the tuberculous nature of any empyema in which no ordinary pus cocci are present. The peritoneum, like the pleura, is frequently reached by the tuber- culous process. If, in some cases, the propagation is easily followed INFLAMMATION 279 up, and if the lesions of the serous membrane have their origin in previous alterations of the alimentary canal or genital organs, in other cases the peritoneal manifestations seem to be primary. The intes- tinal route of entrance is cicatrized and can no longer be found, even by an attentive examination. Tuberculosis may not only propagate by contiguity into the serous system, but also by the circulatory system — lymphatic or sanguineous. Baumgarten considered as a law the formation of a local lesion at the point where the tubercle bacillus penetrated into the organism. This conception, which is for the most part true, suffers from excep- tions. Thus is explained the passage of the bacilli into the lymphatic system from the respiratory tract and from the alimentary canal, and their apparently primary localization in the lymphatic glands. Cer- vical adenopathies, so frequent in young subjects, develop without our being able to find the entrance of the pathogenic agent. It is chiefly in the bronchial glands that this fact occurs. In chil- dren it is not infrequent to observe very intense tracheo-bronchial adenopathies, with caseous swelling, while the most attentive examina- tion fails to reveal the slightest pulmonary alteration. In some cases the evolution is the reverse of what might have been supposed: the bacilli, having traversed the pulmonary tissue without leaving any trace, reach the glands and there produce extensive lesions and sec- ondarily invade the lung. In such cases pulmonary tuberculosis is consecutive to ganglionic tuberculosis. Until recently it was believed that facts of this kind are observed only in children. As a result of the researches of Loomis and Pizzini, it is now known that in the adult apparently normal bronchial glands may contain Koch's bacilli. It is hardly necessary to say that this important fact may explain many cases of tubercularization of obscure mechanism. The same thing may be true with regard to the mesenteric glands, at least in children, since Pizzini has never found the bacilli in these glands in the adult. In children, on the contrary, mesenteric phthisis, or, as it was formerly called, tabes mesenterica, is very frequent, and may develop without any appreciable lesion in the intestine. Ex- perimental pathology furnishes similar facts. In the guinea pig, mes- enteric tuberculosis may follow the ingestion of tubercle bacilli with- out any intestinal lesion. In other cases the bacilli directly penetrate into the blood circula- tion, generally after having occasioned a phlebitis, which explains the dissemination of the pathogenic agents. Here two results are pos- sible: The microbes, arriving in small numbers and finding the organism sufficiently resisting, may locate themselves in some organs: 19 280 LOCALIZATION AND EVOLUTION OF TUBERCLES or, in great numbers invading an organism incapable of destroying them, they may spread throughout the economy and give rise to a general disease, evolving as a pyrexia — namely, acute miliary tuber- culosis. In the former case there may be found but a single focus (some- times a bone only is affected, or an articulation, or a viscus, like the testicle, easily explored). If the initial lesion of the lung has been slight enough to heal, there will be found a focus apparently primary. In other cases it is an ordinary tuberculous individual in whom vari- ous organs have been invaded. The liver is almost always attacked at an advanced period of the disease, but its lesions are not generally appreciable except under the microscope. The spleen is more rarely affected. The kidney is quite often attacked, and this hematogenic tuberculosis is expressed by granulations disseminated in its cortical substance, in this way assuming an aspect very different from the one presented by ascending renal tuberculosis. It is at present admitted that acute miliary tuberculosis is almost always consecutive to a primary focus — i. e., to a cheesy mass, which must be looked for with great care at the autopsy. The penetration of the bacilli is preceded, as already stated, by a specific phlebitis. Weigert was the first to call attention to this mechanism and to show the existence of a tuberculous infection, generally affecting the pul- monary veins and explaining the propagation of the bacilli by a series of microbic emboli. In some rare cases an artery has played the same role (Koch). The bacilli, thus thrown into the circulation, have sometimes been recovered in the blood. Villemin proved the virulence of this liquid, and Weichselbaum, Meisch, Lustig, and Eutimeyer demonstrated the presence in it of the specific agent. The germs deposit themselves in all the organs and tissues, and, according to a great number of acces- sory circumstances, lodge preferably in one or several organs, which in part explains the different clinical forms observed: typhoid, gas- tric, latent, bronchial, suffocating, pleural, peritoneal, meningeal, artic- ular, and renal form. In short, aside from the very rare cases of congenital tuberculosis, the various modes of tuberculous infection may be easily classified in the following manner : 1. Tuberculosis by inoculation, occupying the respiratory passages, more rarely the digestive canal, genito-urinary apparatus, skin, and exceptionally the conjunctiva. 2. Absence of lesions at the point of entrance, or presence of a minute, scarcely perceptible, lesion. In this case secondary localiza- tions are considered as primary. INFLAMMATION 281 3. Secondary localizations, whether with or without appreciable primary lesion. The secondary localizations are divided into three groups : a. Secondary tuberculosis by propagation. The most frequent types are represented by tuberculous pleurisy or peritonitis. In some cases the propagation reaches the osseous system, the biliary passages, and, in case of cutaneous fistula, the skin. h. Secondary tuberculosis through lymphatic infection, character- ized by adenopathies which seem primary and most often occupy the cervical region, where they suppurate quite frequently, and the tracheo- bronchial or mesenteric glands. In the latter case the affection has been described under the name tabes mesenterica. c. Secondary tuberculosis through blood infection. This is hemato- genie tuberculosis, explained by the presence of a specific phlebitis or arteritis; it is expressed either by an external lesion, or by a mono- visceral or polyvisceral localization, or by a generalized infection, acute miliary or granular tuberculosis. Tuberculosis of Animals. — Tuberculosis constitutes the greatest scourge not only for man, but also for the animals surrounding him — namely, mammals and birds. Among mammals, those most frequently affected are the Bovidce; the proportion rises to 3 or 4 per cent in the slaughterhouses of the great cities of Europe. The lesions may be reduced to three principal types. Sometimes it is a generalized miliary tuberculosis; in this case the meat is seized. Sometimes it is a local lesion affecting an organ or gland or both; the diseased part is then cut off and the re- mainder is sold. Sometimes — and this is most frequently the case — it is a pulmonary lesion similar to the human. It appears under the form of voluminous masses, often infiltrated with calcareous salts ; in certain cases a whole lobe is involved, weighing 5, 6, and even 10 kilo- grammes. In cases of pulmonary tuberculosis, police regulations order the seizure of the affected parts and authorize the sale of the meat. The most important lesion of local tuberculosis is that of the mammary glands, since the milk then contains bacilli. Fortunately, however, mammary tuberculosis is rather infrequent, and, as in other cases, the bacilli but rarely pass into the milk, the danger of contami- nation through this secretion seems to have been somewhat exagger- ated. Tuberculosis, rare in the sheep and the goat, is frequent in the pig, where it varies between 0.1 and 1 per 1,000. The horse is rarely affected. Contrary to an old opinion, the small rodents, such as rabbits and guinea pigs, although very apt to contract the disease by inoculation, are almost never attacked spontaneously. 282 TUBERCULOSIS OF ANIMALS Among domestic animals, the monkey, the cat, and especially the dog, must be cited. Since the careful investigations of Cadiot, we know that tuber- culosis is frequent in the dog, but it is not always easily recognised, as the lesions often appear under the form of cancer. The confusion is easy to understand, as microscopic examination may reveal a struc- ture similar to that of cancer. These facts are important to know, for the dog may serve to transmit tuberculosis through his saliva, and especially by his urine, which is often rich in bacilli. To-day the world agrees in considering all cases of tuberculosis in mammals as due to the same microbe. In consequence of some ex- perimental researches, it was believed that tuberculosis of birds de- pended upon a special agent, a bacillus of a particular species. This opinion, which has been the subject of much lively discussion, seems to have been finally abandoned. The avian bacillus is nothing but a special variety. It will be considered separately in the Gallince and in the Psittaci, Tuberculosis of the fowls (GalUnce) is very frequent, since it forms one tenth of the total mortality of aviary birds ; it is spread through the excrements, which are rich in bacilli. The infection takes place by the digestive canal, and is expressed by numerous granulations in the liver and spleen. The lesions thus developed are easily inoculated into the rabbit, but with more difficulty into the guinea pig. Recipro- cally, tuberculosis of mammals, despite the contrary assertions of writers, may be transmitted to chickens. In accordance with the re- sults of experimentation, inquiries demonstrate that the GalUnce are in most cases contaminated by the expectorations of tuberculous persons. The histological study of avian tuberculosis leads to quite unex- pected results. The tubercle has a special structure, different in ani- mals akin to each other, like the chicken and the pheasant. In the chicken the lesion consists of a vitreous mass bordered by epithelioid cells; in the pheasant it is an accumulation of epithelioid cells lim- ited by a ring of connective tissue, which becomes infiltrated with amyloid matter. In the Psittaci tuberculosis is a frequent affection, generally of human origin, which in most cases is expressed by cutaneous lesions; on the head are seen vegetations, sometimes horns 2 and even 5 centi- metres long. At times the lesions occupy the claws, and produce deformities similar to those described as gout of birds. The bacilli are found in great numbers in the cutaneous produc- tions, saliva, nasal liquid, and excrements; they possess very great virulence for the guinea pig. So tuberculous parrots represent a very serious danger for man. , INFLAMMATION 283 Finally, there has recently been described a tuberculosis of fish, proceeding from another variety of tubercle bacillus. But these are, at any rate, three varieties of one and the same species. NONTUBEKCULOUS ISTODULAR LeSIONS Nodular lesions are observed in a great number of infections. In syphilis we meet with gummatous productions which in some respects recall tubercle. We shall not dwell on these lesions, or on those of glanders, leprosy, or fungoid mycosis. They are well known and everywhere well described. Finally, there exists a series of very dis- 09 o >^ p o n H o Q P » P4 By inanimate substances. By animal parasites. By vegetable parasites. r Cantharides, lycopodium, Cayenne pepper (Martin). < Oyster scales (Cornil and Toupet). I Stony cells of pears (Hanau). OUulanus tricuspis. Pseudalius ovis pulmonalis. Strongylus vasorum. Strongylus rufescens. Distome. Oospora bovis or actinomyceta. Oospora farcinosa. Oospora asteroides. Mucor. Aspergillus f umigatus. Aspergillus glaucus. Oidium albicans. Coccian tuberculosis of the cow (Toussaint). Zoogloeic tuberculosis (Malassez and Vignal). Bacillary pseudo-tuberculosis (Charrin and Roger). Of bacterial origin. Pseudo- tuberculosis (zooglceic f) of the guinea pig (Zagari). of the rabbit (Dor), of the hare (Megnin and Mosny). of the antelope (Cornil and Toupet). Fetid bacillary pseudo-tuberculosis (Parietti). Bacillary pseudo-tuberculosis of sheep (Preisz and Guinard). Bacillary pseudo-tuberculosis of oxen (Courmont). of Du Cazal and Vaillard. of Hayem and Lesage. of J. Courmont. of P. Courmont. Human bacillary pseudo- tuberculosis similar facts, which have been embraced under the name pseudo-tuber- culosis. In this way are designated all lesions which are characterized by the production of granulations whose macroscopic aspect recalls that of tubercle. The most diverse causes may give rise to them. These are sometimes inanimate substances, more often animate para- sites, such as strongylus; comparatively highly organized vegetable parasites, like Aspergillus fumigatus or actinomycetes, and finally 284: NONTUBERCULOUS NODULAR LESIONS microbes. The first example of mierobic pseudo-tuberculosis without Koch^s bacilli was published by Malassez and Vignal under the name zoogloeic tuberculosis. This affection, which, it seems, had already been perceived by Toussaint, has since been well studied. At the same time numerous observations regarding man and animals have been brought together which seem to establish the existence of several vari- eties or species of pseudo-tuberculosis. But, following the descrip- tions, it is not always easy to classify the published facts. The tabular representations on page 283 will show the great num- ber of pseudo-tuberculoses actually known. Among the vegetable parasites that may produce lesions similar to tuberculosis a special place is to be given to actinomycetes (page 113). Its introduction into the organism sometimes provokes a spe- cial suppuration characterized by the presence of yellow grains, and sometimes the production of tumours similar to sarcoma. Very frequent in Bovidce, where it is encountered in the proportion of 5 per cent (Russia, Germany), 8 per cent (England), 1 per 1,000 (Lyons), 0.7 per 1,000 (Paris), actinomycosis is not absolutely rare in man. Contamination occurs by contact of diseased animals, more often as the result of penetration beneath the skin or in some mucous membrane of a spike of grain or barley on which the parasite vege- tates. It is mostly about the mouth that infection takes place; it is favoured by the presence of carious teeth. According to its location, the parasite gives rise to various mani- festations. There have been described cervico-facial, thoracic, abdom- inal, cerebral, cutaneous, and pyaemic forms. The phenomena recall those of tuberculosis or syphilis. Confusion with the latter disease is easy, as in both cases iodide of potassium exerts a specific action. The clinical analogy with tuberculosis is confirmed by bacteriology. We have already cited numerous researches tending to demonstrate that the bacillary form of the tubercular microbe is but a transition form, and that in certain conditions the parasite assumes a special aspect, similar to that of actinomyces. CHAPTER XV SEFTICiEMIA AND PYEMIA Definition of the terms septicaemia, pyaemia, bacteriaemia, bacterio-toxaemia — Cryptogenetic, consecutive, and secondary bacteriaemia— Septicaemic forms of infections or specific septicaemia — The agents of septicaemia and pyaemia — Ana- tomical distinction between the two processes; clinical and bacteriological analogies — Etiological division of septicaemias and pyaemias — Principal clin- ical characters — Evolution — Importance and frequency of attenuated forms. Definition and Division of Septicaemia and Pyaemia. — Septicsemia and pyaemia constitute two morbid processes, which must be drawn nearer and united under the name hactericemia. In fact, the patho- genic agent tends to invade the entire organism and to develop there without causing special lesions (septicaemia) ; or it locates itself in certain viscera or tissues and gives rise to the formation of purulent foci (pysemia). In the latter case a considerable number of small abscesses are generally found, at the autopsy, occupying the liver, kid- neys, lungs, heart, etc. These are designated by the quite improper name metastatic abscesses. Bacteriaemia must be distinguished from hacterio-toxcBmia, in which the pathogenic agent remains localized and excites general dis- turbances by means of the toxines it secretes. In bacteriaemia there is general infection; in bacterio-toxaemia, intoxication. Bacteriaemia therefore includes both septicaemia and pyaemia. The expression septicemia, created by Piorry, was applied by him to every alteration produced in the blood by septic or putrid matters, whatever their origin. After having been employed in most diverse senses, the term was adopted by bacteriologists, who have not been able to offer any better definition than clinicians. Confusion was further increased when the bacillus of gaseous gangrene was called septic vibrio, and the disease induced by it gangrenous septiccemia. These inaccurate terms led to great errors and nosological confusion. Thus, for example, deceived by these words, some authors believed that septicaemia and pyaemia should be separated on the ground of the different characters 285 286 DEFINITION OF TERMS of their pathogenic agents. Following the expressions used by bacteri- ologists, they believed that the former of these two processes was due to an anaerobic bacillus — i. e., septic vibrio — remaining at the point of introduction; the latter to aerobic microbes invading the organism, and there producing secondary abscesses. A word evidently having no other sense than that given it by an author may be employed, provided it be well defined. The term sep- ticaemia, then, might be reserved for gaseous gangrene and similar processes. This, however, would be a notable departure from the pre- vailing tendency, as logically it would be necessary to consider all local diseases which kill by intoxication as septicaemia, and also to include tetanus, diphtheria, cholera, etc., in this group. In these in- fections, as in gaseous gangrene, the microbes remain localized at one point, and it is their soluble products that excite general reactions. The disease is therefore of a toxic nature. This is why these diverse processes constitute a separate group — i. e., bacterio-toxaemia — and why gangrenous septicaemia must be excluded from the group of true septicaemias. Thus limited, bacteriaemia represents a nosological class, which is as yet artificial. Nevertheless, its existence may be justified by the fol- lowing considerations. In cases of septicaemia the microbe is present in every part of the organism. It may often be detected in the blood during life, and always after death. The lesions are those common to all intense infections. The blood is disintegrated and dark in colour; numerous ecchymoses are observed in the viscera and tissues. At times hemor- rhages are so abundant that the process deserves to be designated as hemorrhagic septiccemia. The microscope reveals small vascular thromboses, cellular degenerations, and occasionally embryonic foci, indicating a reactionary tendency on the part of the organism. These foci, however, are limited, and are not visible to the naked eye. At the end of a variable time, however, the microbes become local- ized in certain portions of the economy. Septicaemia then loses the character of a general infection, and visceral localizations become prominent. Consisting at times of simple inflammatory lesions, the secondary foci may, in other instances, undergo purulent transfor- mation. Under these circumstances the process is sometimes called septico-pycemia, which represents a transition with pyaemia properly so called. Pyaemia is distinguished from septicaemia by the tendency of the infectious agent to localize itself from the beginning in certain vis- cera or tissues, and there give rise to the formation of purulent foci. The pathogenic agent transported by the blood quickly leaves this SEPTICEMIA AND PYEMIA 287 medium; hence certain authors admit that in true pyaemia the microbes are encountered exclusively in the tissues. When they are found at the same time in the blood the process is known as septico- pyaemia. We will soon see that this last distinction is of a rather subtle nature. Septicaemia and pyaemia may produce anatomical lesions, and they may also be consecutive to some local lesion. According to their apparent point of departure, two varieties may be admitted. The first is characterized by invasion at once of the entire organism; the point of entrance of the microbe and the initial lesion are wanting or remain unperceived. Under these circumstances the infection is said to be spontaneous or cryptogenetic. The latter terms, introduced by von Leube and accepted by Jiirgensen, is now frequently employed in Ger- many. In the second case general infection is preceded by a local lesion. Here two events are possible: Sometimes the primary focus contains the microbes which will invade the economy, in which in- stance bacteriaemia deserves the name consecutive. Sometimes, on the other hand, the primary focus is due to specific or nonspecific agents, which only prepare a route of entry for the microbe of general infec- tion, in which case bacteriaemia is said to be secondary. According to the few considerations just presented, we may classify the various types of septicaemia and pyaemic infections as follows: Classification of Septicemias and Pyemias According to their Origin. Primary j Traumatic. ( Cryptogenetic. Consecutive. Secondary. According to their Evolution, Without special localization (true septicsemias). With inflammatory visceral localiza- tions. With suppurative j Septico-pyaemias. localizations. ( Pyaemias. It may be asked whether general infection is not always consecu- tive to a local lesion which in some instances is so minute as to escape detection. Such an occurrence is frequent, but the reality of primary general infection seems demonstrated by numerous surgical observations and experimental researches. Clinically, disturbances have been seen to follow an accidental, an operative, or an obstetrical wound which seemed perfect. It is the same with animals. When an extremely virulent microbe — a certain streptococcus, for example — is inoculated beneath the skin, death supervenes from bacteriaemia without there being any trace of local lesion. Furthermore, under a very great number of circumstances, the microbes located upon or within our bodies, notably those of the digestive canal, may penetrate 288 DEFINITION OF TERMS into the economy, and, if the system is sufficiently weakened, it is com- prehensible that they may at once create a general disease. In such cases it is impossible to find a trace of their passage. No local lesion exists. If it were always possible to determine the mechanism of the infection, facts of this kind should be grouped under the name auto- hactericemia. Consecutive general infections, however, are the most frequent and important, since they include the great majority of surgical and obstet- rical septicaemias and pysemias. With these must also be included certain cases in which the primary lesions are of a medical order — i. e., occupying such parts of the organism and affecting such localities as to render operative intervention impracticable. It is not alone in suppurative lesions that this process is called into play. It is of constant occurrence in the course of the most diverse diseases. In this way, when an erysipelas or a plain pneu- monia terminates in death, the infection nearly always assumes a sep- ticaemic form. At the autopsy, and even during life, the microbe — streptococcus or pneumococcus — is found in the blood and all the organs. The same evolution is observable with highly differentiated bac- teria. For example, this takes place in anthrax. In man, the bacillus produces a local lesion — i. e., a malignant pustule. It too often crosses the barrier opposed to it by the organism and invades the entire economy. It is then said that the patient has died by anthrax sep- ticaemia. It may even happen, at least in animals, that the local lesion is wanting. In such cases anthrax manifests itself as a true sep- ticaemia. It is even said that such or such an infection assumes a septicaemic form in cases in which it develops without occasioning its usual mani- festations or lesions. Thus, a septicaemic form of typhoid fever has been described. It would therefore be easy to extend the limit of septicaemias so as to include almost all infections, at least in certain forms. To avoid the confusion which would result from such a conception, we are obliged to arbitrarily designate as septicaemias those bacteri- aemias that are due to ordinary agents, and to distinguish those cases in which a well-defined agent has from the first or consecutively in- vaded the entire organism and behaved as in true septicaemia, as sep- ticaemic forms or specific septiccemias. Thus, to take up the examples above referred to, we shall speak of a septicaemia with streptococcus and a septicaemia with staphylococcus; whereas, if the case be one of general infection by the Bacillus anthracis, we shall make use of the expressions specific septicaemia or septicaemic form of anthrax. By so SEPTICEMIA AND PYEMIA 289 doing we conform alike to clinical data and to the results of bac- teriology. We believe it proper sharply to separate the consecutive from the secondary infections. The distinction is equally justified by clinical experience and bacteriology. In consecutive infections the same microbe produces all the lesions. Let us take, for example, a purulent infection consecutive to a phlegmon. Clinically, it is the same pro- cess that has become generalized. Bacteriologically, the same microbe — staphylococcus or streptococcus — is found in the initial phlegmon and in the metastatic abscesses. Pyaemia is then said to be consecutive. On the other hand, let us assume that a diphtheritic angina exists. If the patient succumbs to septicaemia, we may say that this sep- ticaemia is secondary, as the latter will be produced by streptococcus, while the primary agent has remained localized in the throat. The process is one which has been secondarily superadded to the primary. Likewise, the arthrites of gonorrhoea may sometimes be produced by the gonococcus. Here the process is one of generalization due to the main infection, viz., a consecutive bacteriaemia. More often these arthrites are due to an infection superadded by a pyogenic agent which has simply profited by the urethral lesion and invaded the economy. This is a secondary bacteriaemia. Bacteriology. — It has seemed to us useful to unite septicaemia and pyaemia in one group. Although pathological anatomy sharply sepa- rates these two processes, clinical observation justifies their closer relation, and bacteriology confirms the results of observation by estab- lishing that the same pathogenic agents are concerned in the majority of cases. There exist a few microbes which thus far have been met with only in one of the two processes. This, however, is the exception. What is most often detected in cases of septicaemia or pyaemia is, first, strep- tococcus, then Staphylococcus aureus, more rarely pneumococcus, pneu- mobacillus, or tetragenus. Among the other septicaemia agents we may cite the colon bacillus, bacillus of psittacosis, bacillus of hemorrhagic septicaemia (important chiefly in animals). Bacillus pyocyaneus, Ba- cillus septicus putidus. Bacillus proteus vulgaris ^ etc. The agents of pyaemia are much more numerous. Besides the microbes already men- tioned, we shall note a special bacillus described by Levy. Parasites of a higher order, such as actinomyces, might also be cited; also the bacillus of glanders, which causes a true specific pyaemia justly de- scribed by authors in a separate chapter. General Etiology. — From a purely etiological standpoint, sep- ticaemias and pyaemias are divided into puerperal or obstetrical, surgi- cal, and medical. 290 GENERAL ETIOLOGY The streptococcus, which, as we have said, plays the principal part, is the almost constant agent of puerperal septicaemia and pyaemia. Clinical experience has prepared us for the acceptance of this fact revealed by bacteriology. Puerperal fever has more than once been contracted by patients treated in proximity to erysipelatous women. On the other hand, erysipelas has at times appeared in persons who had taken care of puerperal women. Finally, there are cases in which the two infectious manifestations coexist in the same subject. However, the bearing of these facts should not be exaggerated. Women suffering with erysipelas have often been confined without developing septicasmia, and erysipelas has appeared a few days after confinement and been perfectly cured. Contamination occurs mainly from one to another puerperal woman. The streptococcus then proves to be much more active, and seems to be endowed with special virulence. It is in such cases that infection may be transported to a distance through the agency of clothing, linen, and instruments. Lastly, the infection may appear spontaneously. It is explained by an auto-infection due to microbes normally inhabiting the exter- nal genitals. We shall not dwell upon the causes of surgical infections. Three conditions may be present. Sometimes, the wound being soiled by germs, general infection is established at once; sometimes a local lesion is first produced, which subsequently induces a general infec- tion; finally, infection follows a traumatism without there being any external wound. Facts entering into this last category are excep- tional. Wagner has recorded a remarkable example in a case of pyaemia consecutive to a fall upon the hip. When bacteriaemia is consecutive to a wound it is not at all neces- sary that the latter be extensive. Disturbances have been seen to occur in consequence of minute traumatisms. Dandois has reported a case in which pyaemia followed a leech bite. It should be remem- bered, however, that infection is always favoured by all causes pro- ducing great damage and profound attrition of the soft parts. Disin- fection of such wounds is difficult, and the microbes find conditions favourable for their development in the altered and contused tissues. Finally, in surgical as well as puerperal infections, the dominant eti- ological factor is the transportation of germs by the hands of the oper- ator or through badly sterilized instruments. At the present day these are commonplace facts, and need but to be mentioned. The last group, which belongs to the domain of both surgery and medicine, includes the cases in which bacteriaemia is consecutive to SEPTICEMIA AND PY-ffiMIA 291 some old lesions. These are suppurating wounds, oftener profound suppurations, whose disinfection is a diflScult matter. We have already shown in connection with suppuration that, in order to explain the generalization, it was necessary to assume a previous modification of the organism, probably under the influence of microbic products originating from the primary focus. We are, of course, unable to cite all the lesions that are liable to terminate in a general infection. Cutaneous or superficial alterations rarely have this effect, except in the newborn, in whom suppurations of the umbilical cord cause an omphalitis permitting microbic gener- alization. In adults, suppurations within cavities or the viscera are especially liable to give rise to general infection. It is true, however, that since the general adoption of antisepsis the number of cases of infection is constantly diminishing. In cases of otitis, for example, Chauvel found, out of a total of 1,137 observations, but 5 cases of sep- tico-pysemia, only 2 of which proved fatal. Likewise, in medical affections there is no constant relation be- tween the gravity of the primary lesion and its tendency to gen- eralization. Cutaneous suppurations, notably those of smallpox, alterations of the tonsils, intestinal ulcerations, lesions of the liver, urinary passages, and the lungs, are the most frequent causes of the infective process. The primary lesion is not necessarily suppurative. Diphtheritic or scarlatinal sore throat may open the door to pus cocci. We must give a special place to common infections, which are so frequently observed in the course of tuberculosis and which modify the progress and aspect of the disease. In examining during life the blood of patients attacked by febrile phthisis, Jakowski found microbes seven times : Staphylococcus aureus, five times, twice in a pure culture, twice associated with Staphylococcus albus, once with streptococcus; in the other two cases he discovered streptococcus. In an observation of Etienne and Specker, tuberculosis was complicated with a sep- ticaemia induced by a microbe related to the pneumococcus. These secondary infections play a great role in the mechanism of hectic fever, and in other cases may give rise to multiple suppurations, puru- lent arthritis, and visceral abscesses. Lastly, there remains the group of cryptogenetic septiccemias, in which general infection seems to supervene at once. This group may be divided into two secondary groups. At times the initial lesion passes unnoticed. During life it is not revealed by any appreciable symptom, but none the less it exists, and is found at the autopsy. It may be a visceral suppuration, an intestinal ulceration, an old focus having its seat in a ganglion, or a suppurative salpingitis, etc. 292 EVOLUTION In other cases, on the contrary, the minutest post-mortem exami- nation fails to reveal any internal lesion. Infection is produced from the beginning. In a good many cases it is explained by a previous weakening or decline of the organism. In fact, it is known that, on the slightest occasional cause, the germs which multiply upon the integuments or mucous membranes invade the economy. It is even probable that they constantly penetrate into the tissues under normal conditions. But those which enter a healthy organism are rapidly destroyed. It is no longer so, however, when the organism suffers from the influence of an accessory cause — for example, cold, fatigue, or overwork. The part played by overwork seems to us very impor- tant, and the clinical cases known under the name overwork fever (fievre de surmenage) must be considered as septicaemic. Excessive muscular work facilitates infection by lessening the alkalinity and diminishing the germicidal power of the humours. Infection occurs through the skin, perhaps more frequently through the intestinal mucous membrane. It is known with what facility germs pass through the walls of the digestive tract. F^cal stagnation, during only five or six hours, suffices to produce general infection (Arnd, Multanowski). It is then probable that a good many infections whose point of departure escapes our notice must be referred to an intestinal origin. However, it must be acknowledged that there are cases which defy all explanation. No cause whatever is found permitting us to under- stand their development. Evolution. — Infection may behave throughout its course as a sep- ticaemia without any localization. The characteristics of the disease are severe initial chills, high fever, and a very grave general state. If the evolution is rapid, death supervenes without any organ being especially affected. If the disease be prolonged, visceral localization may occur. General manifestations then become less, and the lesion which expresses the fixation of the process develops on its own ac- count. There exist numerous transitions between pure septicaemias and those where general infection, pushed into the background, may become so slight as to be hardly noticeable. And yet septicaemia has been an intermediary state between the primary lesion and the secondary localization in some viscus. Acute endocarditis, nephritis, or hepatitis are in many cases but septicaemias with a predominant localization. If the visceral localizations of septicaemia are expressed by the pro- duction of purulent foci, it is said that septicaemia terminates in pyaemia. In other cases pyaemia comes on at once. It is difficult to say why, under certain circumstances, a septicaemic agent gives rise to suppuration. The consensus of opinion assumes that, in the latter SEPTICEMIA AND PYEMIA 293 case, it is less virulent. Septicaemias seem mostly to be of a toxo- infectious nature. They occur when bacteria find in the organism conditions favourable for the production of toxines. In contrary cases they are in part destroyed, and the proteines of their cadavers cause the formation of pus. Pyaemias, primary or secondary, are expressed by multiple suppura- tions, which sometimes occupy superficial regions — skin or articula- tions — sometimes the viscera. The medical pyaemias with articular localizations, long confounded with acute articular rheumatism, have been described under the name arthrito-suppurative disease and infec- tious pseudo-rheumatism. The lesions have a great tendency to local- ize themselves in some Joints and to induce suppuration and anchy- losis. Pyaemias with cutaneous and subcutaneous determination are less frequent. In the former case infectious erythemata, purpura, pus- tules, and bullae full of pus develop ; in the latter case, multiple phleg- mons appear. It is also to pyaemia that German writers attribute the osteomye- litis of adolescents. This conception is perfectly acceptable, as it explains the gravity of general phenomena, and, as is often observed, their attenuation when localization of the process takes place. Ac- cordingly, osteomyelitis would be staphylococcic pyaemia of young subjects. As to visceral pyaemias, they are too well known to need a study here. Multiple abscesses are found chiefly in the kidneys, liver, spleen, lungs, and brain; and purulent collections in the serous membranes, purulent infiltrations in the heart, etc. It is not rare to see these various forms associated. In the ordinary surgical pyaemia foci exist simultaneously in the viscera and the joints. Attenuated Forms of Septiccemias and Pycemias. — The expressions septicaemia and pyaemia immediately suggest the idea of a grave and most often fatal process. However, along with the acute forms, we must admit a certain number of cases where the process becomes local- ized and tends to resolve. At times the manifestations may even be ephemeral. Traumatic fever and milk fever are nothing else than septicaemic fevers, so innocent that they may pass away within twenty- four or forty-eight hours. It is the same with certain urinary fevers, which have but a transitory duration. In other instances the evolu- tion, which had at first seemed very serious, becomes modified at a certain moment. This takes place when a visceral localization occurs. In the course of a puerperal septicaemia, for example, the disquieting manifestations will decrease and disappear when a phlebitis or a peri- uterine purulent focus develops. The lesion seems to be a point of 294 EVOLUTION attraction for the circulating microbes, and it is conceivable that cer- tain authors, like Dr. Fochier, should have proposed to suppress the infectious process by attempting to localize them by means of fixation abscesses. The same remarks are applicable to pyaemias. While the general- ized forms — those, at least, where numerous visceral foci exist — are in- evitably fatal, there exist benign pyaemias in which localization takes place in a tissue — e. g., in a joint. These cases can be cured after surgical intervention. In conclusion, along with acute generalized septicaemias it is con- venient to admit attenuated forms — ^transitory septicaemia (milk fever) ; innocent septicaemia with subacute or chronic course ; septi- caemia with a single secondary localization, suppurated or not ; pyaemia with a single or very few localizations. These various forms easily terminate in recovery. Even in grave cases the prognosis is not always fatal. There are on record cured cases of generalized infections. This fortunate result is observed chiefly in septicaemia because the latter is not attended by profound cellular lesions. In the case of general- ized visceral pyaemia, the attenuation or even destruction of the agents is of no consequence. The patient will succumb, not to the infection, but to the visceral lesions resulting therefrom. CHAPTEK XYI EVOLTTTION OF INFLAMMATIONS— SCLEB.OSIS Alterations of epithelial cells ; their degeneration — Proliferation of epithelial cells — Adenoma — Functional disturbances — Reparation of lesions — Sclerosis— Sig- nificance of the sclerotic process — Mode of formation of scleroses — Arterio- sclerosis; importance of this process; principal clinical forms — Notions of therapeutics. Alterations of Epithelial Cells. — In the study which we have thus far made of inflammation, we devoted our attention especially to the elements of connective tissue — namely, elements proceeding from the middle layer of the blastoderm. We have seen that these elements undergo two sorts of modifications — namely, phenomena of degenera- tion, which are not very pronounced, and reactionary phenomena, which are very intense and terminate in the production of various cells that are found in the exudations. We have also shown that proliferation is not a wholly local process. On the contrary, the entire organism becomes impregnated in consequence of the absorption of toxic products. Modifications also occur in the various tissues con- cerned in the production of leucocjrtes — ^i. e., in the spleen, lymphatic glands, and bone marrow. The changes produced in the epithelial cells are of an analogous nature, except that, contrary to what occurs with the mesodermic tis- sues, degeneration predominates over proliferation. These phenom- ena of degeneration are especially marked at the inflamed point, and, if the lesion be prolonged, they may be observed in distant parts and reach the principal viscera. Here, again, the question is one of a toxic process, of absorption from the focus of soluble substances, which induce various degenerations in the economy, notably fatty or amyloid degeneration. In its highest expression, the damage done to the vitality of the ^ells is manifested by the process designated by Weigert as coagula- tion necrosis or fibrinous degeneration. The cell is transformed into a small, dry, fragmented mass, similar to coagulated fibrine; the 20 295 296 ALTERATIONS OF EPITHELIAL CELLS nucleus disappears^ and nothing remains to recall the original structure. If the inflammation is less intense, a series of degenerations occurs, which we shall briefly indicate. First of these is fatty degeneration — namely, the production of small drops of fat in the protoplasm of the cell. This process, which is very clearly shown in the liver, kidney, and myocardium, should not be confounded with fatty infiltration. In the latter process a drop of fat is deposited in the cell and crowds the protoplasm, but the latter retains its vitality and functional activ- ity. In fatty degeneration the protoplasm itself undergoes meta- morphosis. Fatty degeneration is also indicative of an acute process. In less intense grades granular degeneration characterized by a cloudy meta- morphosis of the protoplasmic albumin, is observed, also colloid, vacu- olated, hyaline, and amyloid degenerations, the latter especially fre- quent in the vascular system; mucoid degeneration, and, finally, pig- mentary degeneration. All of these lesions will be discussed in a spe- cial chapter. While these various modifications are produced in the cell, changes of no less importance occur in the nucleus. If the process is very intense, as in coagulation necrosis, the nucleus disappears; if less in- tense, the nucleus atrophies, and in other cases it proliferates. This last modification is observed when the inflammation is not too intense, and it is also encountered at the periphery of the lesions — ^i. e., around the parts which degenerate and become necrosed. Cellular reactions may differ in the same organ, according to the system concerned. In the liver, for instance, the toxic or infectious substances produce degeneration of the hepatic cells, while the epi- thelia of the bile passages proliferate. The explanation is that the supporting cells of the excretory ducts are not as highly organized as the secretory cells; consequently, they are less delicate and more re- sistant. This is why a production of newly formed biliary canaliculi is observed along with degeneration of the hepatic cells in certain infections of the liver. If the inflammation is subacute or chronic, the hepatic cells them- selves may proliferate. In this way nodules are formed, the cells of which are grouped in such a manner as to constitute small tumours, sometimes described under the name adenoma. In slow inflammations of the skin and mucous membranes, hyper- plasia is also observed. In chronic gastritis, enteritis, or metritis the glands become elongated, develop, and form small tumours. In this manner are produced adenomata, which constitute a transition between inflammations and neoplasms. EVOLUTION OF INFLAMMATIONS— SCLEROSIS 291 The various alterations produced in the inflamed cells modify their volume, form, mutual relations, and functional activity. When de- generation is predominant, the cell, which at first may be hypertrophic, atrophies, and is no longer represented except by small, unrecognisable, cuboidal elements. When proliferative reaction predominates, the cell grows and hypertrophies. These changes of volume may of themselves modify the normal disposition of the tissues. On the other hand, the functional disturbances produced hinder the production of the cement substance which unites the cellular elements. This lesion, first de- scribed by Drs. Landouzy and Eenaut, is especially easy to study in the myocardium. The various cells of the myocardium become dissoci- ated and undergo segmentation. The process in the liver is probably similar to segmentary myocarditis, and explains the dislocation of the hepatic elements observed in grave infections of the liver. It can readily be understood that these various lesions lead to a profound modification of the functional activity of the cells. If the inflammation is very intense, function is abolished and secretion is arrested or considerably diminished. If, on the other hand, the in- flammation is slight, the epithelia are stimulated and secretion is increased, but the latter deviates from the normal type. In this manner are developed catarrhs characterized by the pro- duction of abundant fluids rich in mucine and containing numerous altered cells and colloid exudates derived from diseased elements. It will suffice to recall what takes place in the stomach, intestine, biliary passages, and especially in the kidneys. In the various forms of nephritis, for example, the urine contains numerous cells, isolated or united in cylinders, or exudations which are moulded in the tubules and constitute the so-called hyaline casts. Reparation of Lesions. — The alterations we have just indicated may resolve and disappear. Reparation, however, is seldom perfect; for whenever the process attains a somewhat intense character the affected cells disappear and are replaced by cicatricial tissue. There is a very curious difference between the evolution of trau- matic lesions and that of inflammatory lesions. The former are repaired with the greatest facility. Experimenters and surgeons have shown that the viscera regenerate. In animals it is possible to remove large portions of the liver, spleen, or kidneys. In such instances the mutilated organs are reproduced according to their normal type. The directing idea presiding over the development of the individual seems sufficiently strong to assure restoration and a return to the original or normal condition. The destruction of cells is often much less marked in inflammation than in traumatisms. The lesions are less extensive and less consid- 298 REPARATION OF LESIONS erable. In certain cases but a few cells are destroyed ; their reparative work seems easier, and yet it does not take place. The directing idea seems to have been inactive. The paradox distinguishing these two orders of facts may be com- pared to that offered by the study of heredity. We have seen that accidental traumatic mutilations are not transmitted to the offspring. On the contrary, lesions consecutive to functional disturbances are generally inheritable. The cause which has induced an anatomical alteration by producing a physiological change has been strong enough to modify the law of preservation of the ancestral type. That which appears so clearly concerning the succession of beings is also applicable to the individual. Traumatic lesions are accidents which do not mod- ify the normal evolutive type ; they may be repaired in the subject, and do not influence his descendants.' On the other hand, anatomical lesions dependent upon some functional disorder express an impreg- nation of the economy by a pathogenic agent; they are responsive manifestations resulting from a change in the organic direction, are repaired incompletely and with difficulty, and are transmitted by heredity. This is a new proof that the great laws which govern the life of the individual are the same as those which govern the life of the species. Eeparation takes place through the agency of the cells which have proliferated, chiefly the mesodermic and the migratory cells. In this way buds are formed which become vascularized. Sometimes the appearance of blood vessels is explained by the development of a vessel- forming cell, which communicates with neighbouring capillaries by means of prolongations. Sometimes solid cords are observed, which subsequently become hollow and join the capillaries. Most frequently, however, the capillaries themselves send out ramifications toward the tissues and re-establish the circulation. The cells increase in number through the supply of nutritive mate- rials furnished by the newly formed vessels. The differentiated ele- ments are reproduced, and clasmatocytes reappear. Finally, the parts that can not be reconstructed according to the normal type are re- placed by fibrous connective tissue. This is sclerosis. Sclerosis Well-constituted sclerotic tissue is feebly vascular. It is white, hard, resistant, and grates under the scalpel. Sometimes it is exuber- ant and gives to the viscera in which it occurs an exaggerated develop- ment. Such is the case with hypertrophic cirrhoses. Sometimes it appears under the form of a tumour — i. e., keloid. On the other hand, it sometimes manifests a notable tendency to retraction and to diminish EVOLUTION OF INFLAMMATIONS— SCLEROSIS 299 the bulk of the organs. If it occurs in a canal, it causes a progressive stricture, as, for example, in the esophagus and urethra. When it develops in a viscus, the sclerotic tissue leads to atrophy of the organ. The compressed soft parts protrude and impart a granular aspect to the organ. This fact explains Laennec^s granulations in atrophic cir- rhosis and Bright's granulations in interstitial nephritis. Simul- taneously with the evolution of these lesions, the parts that have re- mained healthy tend to replace the diseased parts. In this manner hyperplasias and compensating hypertrophies are produced which fur- ther modify the form of the organ. Sclerotic tissue may have other disadvantages. By lining parts which should unite, it may become the cause of fistulse; when it de- velops in parts anomalously in contact, it may give rise to adhesions. In other cases it causes vicious cicatrices and disturbs the func- tional activity of the organs. It compresses subjacent parts or it narrows the vessels supplying the organs, and thus interferes with their nutrition. Sclerotic tissue, therefore, fills up the vacant spaces left by degen- erated and dead cells. In other words, it is a substitution tissue. To a certain extent sclerotic tissue represents a conservative lesion, no matter whether it develops, as is generally admitted, at the expense of connective-tissue cells — i. e., is preceded by an embryonal stage — or progressively through hypertrophy of pre-existiivg fibres, as in certain cases seems undeniable; or, according to the recent views of Eetterer, as the result of a transformation of ectodermic and endodermic cells. However, while it remedies the primary accidents, it at the same time becomes the cause of new disturbances. It may be said, therefore, that sclerosis is both an end and a starting point. Sclerosis is the last stage of all pathogenic causes that have entered into the life of the individual, and this explains its great frequency in the aged. Exogenous intoxications, acute or chronic intoxications, auto-intoxications, including overwork, nutritive disturbances, and, above all, arthritism, are justly regarded as etiological factors in its production. Several of these same causes may induce cellular degenerations without sclerosis. In the liver, for example, alcoholic intoxication sometimes gives rise to diffuse steatosis, and sometimes it causes cir- rhosis. The same is true of infections. For example, tuberculosis produces either fatty degeneration, hypertrophic cirrhosis of the liver, or an atrophic cirrhosis comparable to that observed in drinkers. The different effects produced by the same etiological conditions cited in the chapters devoted to degenerations and scleroses are ex- plained by the varied degree of power possessed by the pathogenic 300 SCLEROSIS agent or by a dissimilar responsive aptitude on the part of the or- ganism. When the cause is very active or the organism weakened, degen- eration predominates ; when, on the other hand, the cause is less active or the organism more resistant, sclerosis prevails. Tuberculosis causes degeneration in predisposed individuals ; in subjects but slightly sensitive to this infection; in arthritics, for example, it manifests a tendency to produce fibroid changes. The same holds good in regard to intoxications. For example, alcohol, when administered in large doses, causes fatty degeneration; in small doses it produces cirrhosis. It has been possible to produce either of these processes in animals by giving similar doses of this poison. In order to obtain degeneration or sclerosis at will, all that is necessary is to place the subjects experi- mented upon under good or bad hygienic conditions and to furnish them copious or insufiicient nourishment. This has been realized with phosphorus in the case of the liver, and with cantharides in the case of the kidneys. Epithelial Origin of Sclerosis. — The preceding facts force us to admit that sclerosis is the cicatrix of cellular lesions, and lead us to reject the existence of primary scleroses. The consecutive tissue altera- tion is always preceded by a lesion bearing on the more highly organ- ized elements. Scleroses, therefore, are always of epithelial origin. For example, let us take an organ in which scleroses have fre- quently been studied — namely, the kidney. Two types of nephrites were formerly admitted, some epithelial, others interstitial — ^i. e., scle- rotic from the beginning. To each of these affections a different eti- ology, pathogenesis, and symptomatology were assigned. Little by lit- tle a change was wrought. It has finally become recognised that every nephritis starts with the epithelial elements, and that the process soon extends, so that nephritis is primarily diffuse and subsequently ad- vances toward different anatomical types, the two extremes of which are represented by the large white kidney, where epithelial lesions pre- dominate, and by the small, contracted red kidney in which sclerotic lesions prevail. Thus are produced sharply distinguished affections, which must be separated in anatomical and clinical descriptions. The starting point, however, is the same, but the final result differs because organisms are not similar. The same conception is applicable to hepatic cirrhoses. The origin must be looked for in a primary lesion of the hepatic or biliary cells. The still classical idea which attributes atrophic cirrhosis to a pri- mary alteration of the portal vein or to a periportal cirrhosis is based upon incomplete anatomical study. It is now demonstrated that the process is not as systematic as was formerly supposed. Sclerosis de- EVOLUTION OF INFLAMMATIONS— SCLEROSIS 301 velops simultaneously around the portal and hepatic veins and forms aberrant bands, defying all topography. On the other hand, a scle- rotic lesion is never seen to radiate toward neighbouring parts. It is probable, then, that poisons and microbes carried by the portal vein give rise to primary alterations in the hepatic cells. The marginal cells are the first to be reached and the most profoundly affected. Next to be attacked are the centrally located cells in the region where the blood which has passed through the radiate capillaries enters the central vein. In this way the topography of sclerotic lesions is ex- plained. As to the venous alterations, they seem most frequently to be secondary. It may, however, be admitted that they are sometimes primary, in which instance they produce sclerosis because the dis- turbances of circulation alter the nutrition of the cells. Even in this case the sclerotic process is not an irradiation of the periphlebitis; on the contrary, it is consecutive to a degenerative alteration of the hepatic cells. When the question is one of biliary hypertrophic cirrhosis, there can then be no doubt as to the primary lesion being located in the cells. It affects the epithelia of the biliary passages and seems to be caused by the colon bacillus coming from the intestine. It would be easy to present analogous examples with respect to other glands and various tissues. Therefore, sclerosis always comes to fill up a vacant space. Scleroses of the nervous tissue form no exception, since it is now known that scleroses of the neuroglia do not enter into the group of true scleroses. The neuroglia does not represent connective tissue; it is of ectodermic origin and a nervous tissue. It is not strange, therefore, that it should be the seat of systematic lesions to which the rules here laid down do not apply. It is a special process quite different from true mesodermic sclerosis. Arteriosclerosis. — Instead of being localized at a certain point, as in the preceding examples, sclerosis may be generalized, or at least distributed to a great part of the organism, affecting especially the vascular system and attacking several viscera at once. It is to the history of this morbid state that the law which we have above formulated especially applies. Arteriosclerosis is truly the last stage of all morbid, infectious, or toxic causes which have acted during life. The reason why the arteries are so often affected at a relatively early age and at a time when the organs are still quite healthy is that they serve to carry microbes and toxines and are constantly contami- nated by noxious substances. The most highly organized elements of the vessel walls, notably the muscle fibres, degenerate and sclerosis is produced. 302 ARTERIOSCLEROSIS Arteriosclerosis, which may commence at an early age, is almost never absent in the aged or even in adults. There are records of men whose arteries were supple at the age of eighty or ninety years. Such instances, however, are very rare. More frequently arterioscle- rosis is manifest as early as the thirtieth to the thirty-fifth year. Even when arteriosclerosis is extensive, it is not everywhere equally marked. The lesions predominate in the small arteries, where friction is more energetic, and near the angles, curves, and divisions, where the impact of the blood current is stronger. On the other hand, however, it seems that the process is essentially regional, and that the territories chiefly affected are those which correspond to the most active parts. Com- parative pathology has shown us that arteriosclerosis is frequent in animals. In the horse it is localized in the lower portion of the aorta — that is, in the vessel charged with the function of supplying blood to the most active muscles. Arteriosclerosis, while especially marked in the radial vessels of labourers, seems to affect the arteries of the head in men addicted to mental occupations, and quite often begins in the temporals. There are evidently many exceptions to these rules, which, however, appear to be sufficiently well established to warrant citation. An artery affected with sclerosis may be the seat of various disturb- ances. The disappearance of the muscular fibres from the walls of arteries lessens their resistance and often leads to dilatations, aneu- risms of calibre, or miliary aneurisms. The part thus affected may burst, as is frequently the case in miliary aneurisms. In other instances the blood coagulates in contact with the diseased vessel wall, particularly when the latter has suffered atheromatous or cal- careous degeneration. According to the diseased vessel, necrobiosis or gangrene will be produced. For example, in the brain a focus of softening will appear; and in the extremities, dry or senile gangrene. Simultaneously with the appearance of arteriosclerosis, analogous changes occur in the viscera. There has been much discussion as to the relations existing between arterial and visceral sclerosis. In this connection four principal the- ories have been advanced : Drs. Huchard and Weber assume the occur- rence of a periarteritis radiating from the affected artery toward the neighbouring tissues. Dr. Martin believes that a nutritive disorder due to deficient circulation exists. The most differentiated — i. e., the most delicate — parts are the first to degenerate and be replaced by fibrous tissue. Ziegler goes further, and states that there is an oblit- eration of the small vessels. According to this third hypothesis, scle- rosis would be a cicatrix of a necrosis of thrombotic origin. Finally, EVOLUTION OF INFLAMMATIONS— SCLEROSIS 303 according to Brault and Mcolle, scleroses of arteries and viscera are dependent upon the same causes; they are simply of simultaneous origin. Evolution and Clinical Forms of Arteriosclerosis. — Clinically arteriosclerosis develops in such a manner that three stages may be admitted : In the first stage the arterial phenomena predominate. This is the case in individuals who have passed the age of forty. One of the first and the most important manifestations experienced by them is dizziness. The subjects complain of dyspnoea, which is sometimes of an asthmatic character, somnolence after meals, and hemicrania. It is well to mistrust so-called asthmas and hemicranias occurring in per- sons of a certain age. These manifestations nearly always point to an arteriosclerosis and often announce an alteration of the kidneys. At the same time, especially in women, there are observed vasomotor disturbances, sudden congestions and sensations of heat, which are only too often charged to the menopause. If these first phenomena be well interpreted, they lead to an exami- nation of the circulatory apparatus. On auscultation of the heart a tympanitic click is heard accompanying the second sound, and at times even systolic and diastolic murmurs, which, however, are transient and intermittent. The arteries are somewhat hard; the sphygmograph shows a flattening at the summit of the line of ascension. The sphyg- momanometer indicates an elevated pressure — 20 centimetres on an average. In the second stage the manifestations are localized — i. e., pre- dominate in a viscus. The disturbances, however, are transitory and intermittent, and are produced only on the occasion of excessive func- tional activity. Professor Grasset has felicitously compared these phenomena to the intermittent claudication (limping) observed in old horses affected with atheroma of the lower portion of the aorta, and which occurs only at times of somewhat hard work. The muscles, sufficiently nourished when they are at rest, do not receive blood enough to enable them to continue their activity; being deficiently supplied, they contract badly. The same manifestations may be observed in man, in whom an intermittent claudication of the limbs is noted; but, according to Grasset's expression, an intermittent clau- dication of the organs more frequently exists. Such are transitory paroxysms of asystole, cerebral clouding, and slight accidents of uragmia with a little albumin. The third stage is characterized by the localization of the process, or at least by its predominance in an organ. According to the part affected, four clinical types may be admitted : 304: ARTERIOSCLEROSIS Arteriosclerosis of a cardiac type, in which the heart, invaded by sclerosis (sclerotic myocarditis), weakens progressively. The patient falls into a state of remarkable asystole, not as a result of the intensity of the symptoms, but owing to their persistence and the impossibility of a complete disappearance of the disturbances. Arteriosclerosis of an arterial type, characterized by the develop- ment of vascular dilatations, and particularly aneurisms. Arteriosclerosis of a cerebral type, starting with vertigo and hemi- crania and terminating in softening by obliteration of the diseased vessels, or in meningeal and cerebral hemorrhage resulting from rup- ture of a miliary aneurism. Arteriosclerosis of a renal type, anatomically characterized by an interstitial nephritis, and clinically by pol3raria, slight and often tran- sitory albuminuria, cardiac palpitations, arterial overtension — going as high as 25 centimetres — and a galloping murmur. It ends in death by ursemia, asystole, and sometimes by pulmonary apoplexy. Therapeutics. — It is difficult to combat the development of scle- rosis. Only one medicine seems capable of arresting the advance of the process, and that is potassium iodide. In order to obtain good results, this drug must be prescribed in small and long-continued doses. It may be given in daily doses of 20 or 25 centigrammes for about three weeks, to be resumed after an interruption of ten days or so. It should be continued in this way for a year and more. Simul- taneously, the circulation may be facilitated by stimulating dilatation of the vessels. To this end, three medicines are useful — namely, so- dium iodide, trinitrine, and amyl nitrite. Sodium iodide acts slowly, and is to be given in doses of 1 gramme daily. The action of trini- trine is more marked and rapid. It is prescribed in doses of 1 or 2 milligrammes. Amyl nitrite, on account of its instantaneous effects, best serves against such accidents as are to be combatted imme- diately. The inhalation of a few drops of it evaporated from a hand- kerchief may ward off the various paroxysms to which arteriosclerotic subjects are exposed, such as angina pectoris, vertigo, and asthmatic dyspnoea. CHAPTEE XVII TUMOURS Division and classification of tumours — Embryogenetic and histogenetic tumours — Benign and malignant tumours — Typical and atypical tumours — Develop- ment of tumours — Consideration on the etiology — Relationships between in- flammation and tumours — Pathogenetic theories — Parasitic theory — Thera- peutics. Tumours constitute an artificial group whose already well-ad- vanced divisions will be continued and completed with the progress of science. In his justly celebrated treatise, Virchow described the lesions of tuberculosis, glanders, and syphilis along with tumours. To-day these are held by all to be of infectious origin. For a long time actinomycosis was looked upon as sarcoma, and, in fact, the microscope revealed in actinomycotic lesions a structure justifying this conception. The discovery of the pathogenic agent, however, has brought the question to its proper position. Likewise, the various sarcomatoid lesions have been referred to tuberculosis as the result of bacteriological researches. In the dog, for example, Koch^s bacillus gives rise to lesions of a neoplastic character, which had long been considered as malignant tumours. Even quite highly organized parasites may give rise to the devel- opment of tumours. With Cadiot and Gilbert, we have observed in a female dog vaginal polypi due to the presence of acarus. Albarran and Bernard had the opportunity of studpng a tumour of the bladder which possessed all the characters of epithelioma, but which, in reality, was due to the eggs of Bilharzia hcematohia. A whole series of lesions of parasitic origin may at present be separated from the group of tumours ; the remainder comprise produc- tions the nature of which is absolutely unknown, but which, according to perfectly acceptable theories, seem to be referable to animate agents. Division and Classification of Tumours. — The insufficiency of path- ogenic data compels us to retain the old division of tumours into henign and malignant. This division is justified from both a clinical and pathologico-anatomical standpoint. 305 306 DIVISION AND CLASSIFICATION OF TUMOURS Benign tumours may be considered as hyperplasias of inflamma- tory origin; such are best exemplified by the keloid, an exuberant fibrous production developing in cicatrices. Histological examination demonstrates that benign tumours are made up of tissues having a normal arrangement, or at least preserving some of the characters recalling their origin. When adenoma is studied, it is found to have a glandular structure. The cells have proliferated and filled the alve- oli, but they have preserved their general arrangement; they remain inclosed by the limiting membrane, and manifest no tendency to invade the surrounding tissues. In malignant tumours, on the other hand, the disorder is absolute. The cells, which are of varied form and fantastic in aspect, are inclosed in alveoli of new formation; they penetrate the limiting membrane and invade the neighbouring tissues. Malignancy, therefore, is char- acterized histologically by irregularity of form and structure.. Ac- cording to the felicitous expression of Dr. Bard, the process is one of cellular anarchy. Embryological Tumours. — A group of productions sufficiently well defined is usually classed with the tumours. We refer to those which are due to defects of development — i. e., to embryogenetic disorders. We shall divide them into four groups: The first and second com- prise those tumours starting during the embryonal or foetal period of a being; the third and fourth consist in post-natal morbid processes occurring in the reproductive organs. Of the embryological tumours, we may first cite the parasitic grafts. In studying teratology, we have seen that two spermatozoa, penetrating into one ovule, give birth to two beings, which develop side by side. In many cases, one of the two develops in a normal manner, whereas the other remains rudimentary and constitutes a more or less deformed mass, which may become inclosed in its well- constituted fellow, and thus form a tumour. Critzmann has at- tempted to generalize this process and offer it as an explication of the development of all neoplasms. A second group is represented by defects of development, of which three types may be admitted. Under the influence of unknown causes, a bud springing from certain parts will become inclosed in neighbouring or subjacent parts. This process is observed especially in branchial clefts, where the ecto- dermic and endodermic layers come into contact. An irregular union of the clefts explains the development of dermoid cysts of the neck. This is also an instance of particular evolution, which Cohnheira has attempted to generalize, by assuming that all tumours can be explained by the theory of inclusion. TUMOURS 30T To the second variety belong cases of heterotopy. An aberrant lobe of an organ may produce a tumour by anomalous development. For example, accessory suprarenal capsules may penetrate into the kidney, vegetate there, and give rise to neoplasms. Lastly, in some cases transitory organs, such as the Wolffian duct and Muller's canal, persist, at least in a part of their extent, and thus give rise to a tumour. All the productions which we have thus far studied were connected with the development of the being; those of which we are presently to speak are dependent upon anomalies of fecundation. It is admitted that in certain instances tumours take their origin in the sexual glands. Facts of this kind are observed chiefly in the ovaries. Two theories are presented: one assumes an ovular fecunda- tion, the other parthenogenesis. According to the advocates of the first doctrine, a spermatozoon makes its way into the Fallopian tube, arrives at the ovary, and fecundates an ovule which enters upon segmentation. As it does not there find conditions favourable for its development, it gives birth to a monstrosity which constitutes a variety of dermoid cyst. Opposed to this theory is that of parthenogenesis. An ovule, stimulated perhaps by a normal concomitant or preceding fecundation, makes an abortive attempt at segmentation, which results in the production of a tumour. Although dermoid cysts are in most cases congenital tumours to be explained by inclusion, there are instances in which they seem to be developed after birth. In certain cases where the integrity of the ovary had been proved during a laparotomy, subsequent intervention has been necessitated by a dermoid cyst which did not exist at the time of the first intervention. Lastly, there remain two types of tumours dependent upon an incomplete development of the being. These tumours are observed in the uterus. One of them, known as mole, is produced by a myxomatous degeneration of the foetal meso- derm. This is an innocent lesion, curable by means of simple curet- tage. The other behaves as a malignant tumour. This is known as deciduoma, which develops at the expense of the placental epithelium and of the foetal ectoderm. Histogenetic Tumours. — Those tumours not of embryonic origin, and which, in contradistinction from the latter, we call histogenetic, may be divided into four groups, according as they develop from con- nective, muscular, nervous, or epithelial tissue. In each group there are to be admitted a certain number of vari- eties, which are very easily remembered, as each of them corresponds to a normal tissue. The tumours of the connective group may be of an embryonic 308 HISTOGENETIC TUMOURS nature. These are the sarcomata, which are remarkable for their tend- ency to extend. Clinicians have considered them as transitional be- tween the benign and cancerous tumours. They are tumours with a variable prognosis. The other connective-tissue varieties give origin to tumours whose tendency to spread will be the weaker the less vitality the tissue pos- sesses in its normal condition. Myxoma corresponds to mucous tissue, fibroma to fibrous, and lipoma to adipose tissue. The derivatives of connective tissue — ^i. e., cartilage and bone — give origin to chondroma and osteoma. Vascular tissue belongs to the same blastodermic layer. We may therefore include under the same group the sanguineous and lymphatic angiomata and endotheliomata produced at the expense of serous mem- branes, representing derivatives of the lymphatic system. Lymphoma may also be included here. Muscular tissue gives origin to but two species of tumours. These are leiomyomata and rhahdomyomata^ which correspond to the non- striated and the striated muscle fibres respectively. Two types of tumours may also take origin from nervous tissue — namely, neuroma and glioma. The latter has often been considered as sarcoma. This, however, is an error due to a false idea which, up to a recent date, prevailed in regard to the blastodermic origin of neu- roglia. At the time when the neuroglia was held to be the connective tissue of the nervous centres — ^that is, a mesodermic production — the comparison was acceptable. At the present time, however, it is known that the neuroglia is an ectodermic production. Glioma, therefore, is a tumour claiming its proper place. The most interesting facts are found in connection with tumours of epithelial origin. Passing by the papillomata, which are small tumours of little importance, due to an excessive development of the papillae of the skin and mucous membranes, and which might just as well be classed among tumours of connective-tissue origin, we come to the consideration of the two great categories of adenomata and epi- theliomata. Between the two we shall place cysts, which may be classed with one or the other group, as the case may be. Such, in its entirety, is the classification of tumours, according to the most recent investigations and the data obtained from embryology and histology. In order to facilitate recollection of the different types which we have here admitted, we give the following tabulated representation summarizing the general notions above referred to : TUMOURS 309 Tumours. Embryogenetic. Beginning during intrauterine life. Parasitic grafts. Defects of development... \ Inclusion. Heterotopy. ^ Persistence of a transitory part. Developing during the genital period. Acquired dermoid cysts. (Parthenogenesis %) T . . ( Mole. Intrauterme tumours | Deciduoma. Histogenetic. Of connectivo-vascular origin. Sarcoma. Myxoma. Fibroma. Lipoma. Chondroma. Osteoma. Hemangioma. Lymphangioma. Endothelioma. Lymphoma. Of muscular origin. Leiomyoma. Rhabdomyoma. Of nervous origin. Neuroma. Glioma. Of epithelial origin. Papilloma. Adenoma. i Epithelioma. \ ^y^^^' Between adenoma, a benign tumour, and epithelioma (a malignant tumour which corresponds to what is clinically called cancer) there exist numerous transitions. The typical cases, however, differ considerably. In order to comprehend the distinction, let us consider any gland. We find canals limited by a membrane which is lined with an epithelial layer. In adenomata the epithelium proliferates and new glandular alveoli appear. Sometimes the excretory orifice becomes obliterated and the glandular cavity is transformed into a cyst. However, be the evolution what it may, we always find the enveloping membrane as well as the epithelium with its fundamental and typical characters. In epithelioma, cellular proliferation is not necessarily more promi- nent than in adenoma. Indeed, at times this phenomenon is even 310 HISTOGENETIC TUMOURS less active. The characteristic feature of a malignant tumour lies in the disposition of the cells to penetrate or break through the basement membrane and invade the surrounding parts, behaving as true parasites. In studying certain tumours, all the transitions between adenoma- tous formation and epitheliomatous degeneration may be followed. In the mamma, histological sections are often highly demonstrative. At certain points the process is still circumscribed and clearly intra- canalicular ; in others, on the other hand, invasion has taken place and the tumour has assumed an epitheliomatous appearance. The former classical distinction between epithelioma and carcino- ma is no longer admitted. Carcinoma was at one time considered to be a tumour of connective-tissue origin, but at the present time its epi- thelial nature is no longer a matter of doubt. Carcinoma, therefore, is an epithelioma the cells of which are inclosed in a very plentiful stroma. According to the development of the interstices, the neoplasm is soft or hard. In the former instance it is designated as encephaloid, and in the latter as scirrhus. When the elastic fibres become abundant in the interstitial tissue, the volume of the tumour may be reduced by their retraction. This is known as atrophic scirrhus. Since the studies of Malassez, epitheliomata are divided into typi- cal, metatypical, and atypical. This division is an excellent one and may be applied to all tumours. Typical tumours present a structure recalling that of the tissue from which they develop. Thus, in the intestine, where cylindrical epi- thelium exists, the tumour will be an epithelioma with cylindrical cells; in the skin and buccal cavity it will be a pavement-celled epi- thelioma; and in the liver, a trabecular epithelioma. When the tumour is composed of a tissue having its analogue in some portion of the economy, but not occurring at the affected point, the term metatypical is applied to it. Thus, for example, chon- dromata are met with in the testicle or the parotid gland, and epi- theliomata in the maxillas. These facts, which at first sight are so astonishing, find an explanation in embryology. The cartilaginous tumours of the parotid are due to the persistence of remains of Meckel's cartilage; those of the testicles are due to the fact that this gland was at first located in front of the vertebral column, and that at that time some cartilaginous cells of the neighbourhood were in- closed in it. Similarly, epitheliomata of the maxillary bone originate from paradental epithelial remains. Atypical tumours are those in which cellular evolution has com- pletely deviated from the normal type and in which the cells often as- sume forms and arrangements which are without analogy in the or- ganism. TUMOURS ^11 Neoplasms may be seated in any part of the organism, but tbey are particularly frequent in localities where several types of tissue unite — a fact which has been made use of by advocates of the inclusion theory, according to which ectopy of one tissue toward another exists. Development of Tumours. — Tumours develop according to the same mechanism as normal tissues. The differences that have been noted are of but secondary importance. Thus, for example, anomalous karyokinetic figures are often found in epitheliomata. Instead of two amphiasters, there may be three, four, and even five; the nuclei are irregular; the cells are incompletely divided, and may acquire a co- lossal volume. Too much importance, however, should not be attached to these facts, since analogous phenomena are observed whenever proliferations are very active, as, for example, under the infiuence of chemical irrita- tions. The glycogenic infiltration of cells must also be referred to activity of development. In all proliferating tissues, in the embryo as well as in the adult, great quantities of glycogen are found. The activity of proliferation and the insufficiency of blood supply explain the frequency of cellular degeneration. Sometimes the cells undergo fatty degeneration, sometimes colloid degeneration, the latter being particularly frequent in the thjrroid gland, stomach, and intes- tines; sometimes mucous degeneration, horny transformation, and pigmentary (melanotic tumours) or calcareous infiltration occur. In other cases the central cells become necrotic and the tumour is trans- formed into a cyst. Etiology. — Tumours may be observed at all ages, but their fre- quency and nature vary considerably at different periods of life. In the embryo tumours are dependent upon defects of development. The most frequent are angiomata, though some exceptional cases of con- genital epitheliomata have been noted. During early infancy sarcomata are observed, located chiefly in the kidneys. At puberty, exostoses are frequent. In women, at a later period, ovarian cysts belonging to the group of adenomata and epitheliomata are encountered. From the age of fourteen onward epithelioma becomes more and more common, reaching its maximum of frequency between the age of fifty and fifty-five years. Age exercises no less influence upon the localization than upon the nature of tumours. In children they affect, in order of frequency, the eye, where melanotic sarcoma is met with, the kidney, testicles, spleen, and more rarely the other organs. In adults the portion of the body most frequently attacked is the stomach; then come the uterus,* the liver, the mamma, and the intestine, in the order named, * In America, according to Welch's statistics, the uterus stands first. 21 312 ETIOLOGY Among causes explaining the development of tumours, heredity stands first. Some authorities have admitted indirect heredity as well as direct heredity, which, according to Delbet's statistics, is ob- served in from 10 to 15 per cent of the cases, according to the theory of indirect heredity. Cancer is mainly observed in families of arthrit- ics, and this accounts for its frequency in civilized races. The great number of cases occurring in certain regions, local epidemics, and the influence of water are interesting questions which are still sub judice. The same statement may be made in regard to alimentation, certain authorities claiming that meat, and others that vegetables, exercise an influence in etiology. The development of a tumour is often referred by the patient to a previous traumatism. In spite of undoubted exaggeration, facts of this kind are too frequent to be ignored. It is certain that contusions have been the starting point of caseous sarcomata and of testicular or mammary tumours. Tumours are, perhaps, more frequently due to friction or repeated irritation. The cancer of the testicle and scrotum observed in chimney sweepers, and epithelioma of the lip in smokers, come under this group. It is well known, however, that the so-called smokers' cancer is also observed in individuals who have never made use of tobacco. Cancer has also been seen to develop at the seat of old cautery wounds and in ectopic testes. In certain cases chemical and not mechanical irritations inter- vene. According to Hoerting and Hesse, men employed in arsenical cobalt mines are often attacked with pulmonary sarcoma. Old affections of long duration keep up a chronic irritation, which is equally apt to favour the development of tumours. Old cutaneous lesions, such as psoriasis, lupus, and extensive cicatrices, especially those consecutive to burns, have been seen to undergo epitheliomatous transformation. The same phenomenon has been observed in mu- cous membranes. For example, buccal psoriasis may degenerate into epithelioma; and similar transformations occur in the vagina and uterus. In other instances cancer is developed at the seat of a lesion kept up by a foreign body. Whether the latter be of external origin or is formed within the organism, the result is the same. In the mouth, for example, a carious tooth will keep up a lingual ulceration, which, although at first simple, may subsequently become cancerous. In the stomach the exciting agent may be a foreign body which has acci- dentally been swallowed ; and in the biliary passage hepatic calculi may be the causative agents — a fact which explains the greater frequency of cancer in the biliary passages of women, who are more often TUMOURS 313 affected with lithiasis, whereas in men cancer of the liver is mainly encountered. Finally, lesions which were for a number of years dependent sim- ply upon a chronic inflammation may, at a given moment, terminate in cancer. Between simple inflammations and epitheliomata there are innumerable transitions. We have already shown the frequency of hyperplastic processes in all inflammations. When the stomach is affected, as is most frequently the case, glandular alveoli develop, undergo adenomatous transformation, and the adenoma is subse- quently transformed into cancer. This process is clearly observed in chronic gastritis, and still more clearly in cases of gastric ulcer. Examples of the same order may be presented in connection with other parts of the organism. In the intestine, for example, the phe- nomena are developed in the same manner as in the stomach; in the liver and kidneys epitheliomatous tumours, improperly called adenom- ata, have often been seen to ingraft themselves upon a cirrhosis or an interstitial nephritis. Pathogenesis. — In order to explain the development of tumours, and especially of cancer, many h3rpotheses have been advanced. By generalizing from a particular case, Cohnheim maintained that neo- plasms are due to inclusions occurring during the embryonal period, the masses of nonemployed cells developing at a later date, as a result of a lack of resistance on the part of neighbouring tissues. A good many objections may be raised in opposition to this theory. First, it necessitates two hypotheses — namely, on the one hand, inclusion, and, on the other, feebleness of parts surrounding the invaginated ele- ments. By admitting the reality of these two conditions, it is not readily understood why the cells remain inactive for years to become active at the moment of involution. Nor is it comprehensible why traumatism, organic lesions, and chronic inflammations serve as a starting point for the tumour. It would be necessary to maintain that foetal inclusion has occurred precisely at that point. Finally, tumours which we know to be of embryonic origin — e. g., dermoid cysts — behave quite differently, and the cells contained in them are of adult type, advanced in development, and not active cells, as are those in neoplasms. The same remarks are applicable to the views of Bard, who as- sumes the occurrence of monstrosity in the cellular development, and who thinks that the mutual induction exercised by the various cells upon each other is broken. It is evident that the reality of these various hypotheses should first be demonstrated. In contrast to the theories of Cohnheim and Bard, who assume a disturbance of development in tissues, and dropping out of considera- 314 PATHOGENESIS tion the theory of Eindfleisch, who explains the development of tumours by the absence of nerves, we find a more modern conception which, far from seeking the cause of the phenomena in an internal deviation, places it outside of the organism. This is the parasitic theory of cancer. In favour of this theory, it may be remarked that a great number of lesions formerly considered as tumours are to-day classed with the group of parasitic affections. Without referring to tubercle, it will suffice to mention actinomycosis. A second argument is drawn from the evolution of cancer. The cancerous cell behaves as a parasite; the lesions have an invading march and may spread in the manner of grafts. An epithelioma may propagate by contiguity from one lip to the other, and from the stom- ach to the liver or pancreas; it may invade the lymphatics or extend from one viscus to another through the process of embolism; it may become generalized and give rise to miliary carcinosis, the evolution of which recalls that of acute tuberculosis. There are on record certain facts which tend to prove even the inoculability of cancer, and in regard to subjects suffering from cancer the fact is unquestionable. The transmission of cancer from diseased to healthy man is, however, less well established, notwithstanding a few observations in which cancer of the penis has been observed in men whose wives were affected with carcinoma of the uterus. Experi- mental pathology does not confirm this result. Attempts to inocu- late human cancer into animals, or from one animal to another of a similar species, have thus far been wholly unsuccessful. The only positive results have been observed by Hanau and Moreau in rats and mice. According to Menetrier, inoculation is not successful unless practised upon animals of the same family, in which cancer has al- ready appeared, and subsequently manifests itself in several indi- viduals of that family. This is, as it were, making the inoculation upon the subject himself. In regard to innocent tumours, the trans- missibility of warts and vegetations occurring upon the genitals of man and animals is well established. The parasitic nature of tumours is not supported by sufficient proofs to warrant acceptance of this theory. The question is simply one of persuasion. To change the theory into a certainty, it is evi- dently necessary to discover the pathogenic agent, and attempts thus far made have resulted negatively. The microbes described by Eappin and Scheurlen in 1883 and 1887 respectively have quickly passed into oblivion. It may be asked whether the coccidia observed by Thomas and studied in the vege- tating follicular psorospermosis by Darier, Malassez, Albarran, Foa, TUMOURS 315 and Euffer are actually the cause of tumours. In reply to this ques- tion, it may be stated that the preparations and drawings furnished by these authors have not offered convincing evidence. On the contrary, many histologists maintain that the figures given as examples of intracellular coccidia are in reality dependent upon degenerations occurring in the cancerous cells. The discussion will last as long as the parasite eludes cultivation. Since the contributions of Busse, San Felice, and Maffucci, atten- tion has been directed to the blastomycetes. Yeasts have several times been found in tumours. Curtis was able to isolate and cultivate a species and also to produce tumours in animals by inoculation. Here, then, is another neoplastic production which passes into the group of parasitic lesions. It is probable, if not certain, that division will continue, and that in the near future all tumours will be considered as due to animate agents. This, however, is only a hypothesis which is supported by a small number of facts. Furthermore, what convinces us that the parasitic conception must be real is the fact that tumours not only propagate and become gen- eralized, as do infectious lesions, but they produce in the entire organ- ism modifications which can hardly be explained in the absence of this hjrpothesis. The rapid emaciation, special cachexia, visceral lesions, nutritive disturbances, and notably the diminution of urea (Komme- laere), seem to demonstrate the intervention of a parasitic cause. We are even naturally led to ask whether intoxication by products engendered in the tumour may not play an important role. Notwith- standing some positive results, it must be acknowledged that the majority of experimenters have failed to discover any toxic substance in the tissues of neoplasms. Whatever theoretical idea may be adopted, discussion is useless. Neoplasms must be treated as parasitic lesions; they must be extir- pated, and that, too, as soon as possible. Internal medication is absolutely valueless; there are no specifics or antiseptics which will oppose them. Interstitial injections, except possibly those of arsenic, have met with no better success. However, it has been observed that neoplasms, notably sarcomata, were apt to subside under the influence of an intercurrent erysipelas. Coley conceived the idea of turning this result to account in therapeutics. His method, which consists in injecting a mixture of sterilized cultures of streptococcus and Bacillus prodigiosus, seems to have met with some success, at least in the case of sarcomata. The procedure has been modified by Schoull, who employs the serum of animals infected with streptococcus. The re- sults have been too discordant to lead to any definite opinion. The 316 PATHOGENESIS same remark may be made concerning the method of Eichet and Hericourt^ who prepare a serum by injecting cancerous juice into animals. In brief, all these attempts, however interesting they may be, have as yet yielded no practical results. An early and radical extirpation of the affected part and corresponding ganglia must be resorted to, and it is well to remember that, in spite of all precautions, recur- rence too often supervenes at the end of a certain time. CHAPTER XVIII CELLULAR DEGENERATIONS Various forms of cellular degenerations — Cloudy swelling — Granulo-albuminous and granulo-fatty degenerations — Mucoid degeneration — Hyaline and amyloid degenerations — Griassy degeneration and coagulation necrosis — Caseous degen- eration — Pigmentary degeneration — General etiology and pathogenesis of de- generations — Special study of fatty, amyloid, and pigmentary degenerations. Division and Classification. — We have repeatedly pointed out the degenerations which occur in cells. In treating of inflammation and in describing tumonrs we show the frequency of alterations of cellular protoplasm. The first stage of cellular degeneration is marked by the occur- rence of cloudy swelling. The cells are swollen and filled with an albuminous or serous fluid holding small granules in suspension. The latter occur in two forms, namely, in granulo-albuminous degenera- tion, which is the first stage, and in granulo-fatty degeneration, which is the second stage. In the former instance acetic acid swells the granules and then dissolves them; in the latter the granules are col- oured dark by osmic acid. This morbid state is observed in a great number of inflammations; it affects the protoplasm and may attack the nucleus and nucleolus. At a more advanced stage we find fatty degeneration, properly so called, or steatosis. This process, which plays a considerable part in pathology, must not be confounded with fatty infiltration, which, for instance, is observed in obesity. In fatty infiltration there is simple deposition of fat in the interior of the cell ; the protoplasm may be pushed aside, but its activity is hardly disturbed. In steatosis or fatty degeneration, on the other hand, the protoplasm itself is trans- formed into fat. Under the influence of nutritive disorders, the pro- teid matter undergoes a special metamorphosis ; therefore the physio- logical activity of the element is also profoundly affected, weakened, or even completely lost. Mucoid or colloid degeneration is observed in the epithelial cells. It is characterized by the deposition of mucinoid substance in the 317 318 DIVISION AND CLASSIFICATION interior of the protoplasm. This may be compared with vacuolar de- generation, in which vacuoles appear to be present in the cell. This phenomenon is in reality due to the presence of small cysts filled with an albuminoid matter. In colloid degeneration the material elabo- rated in the diseased cell may be expelled. If it enters an excretory duct it will be eliminated from the organism. Such, for example, is what takes place in the kidney: the colloid masses exuded from the cells into the lumina of the tubules unite to form cylinders, or so- called casts, which are revealed in the urine on microscopical exami- nation. When the substance is retained at the point of elaboration, it gives rise to the development of more or less voluminous cysts. Thus are explained the cystic degenerations of the kidney and liver, the formation of colloid cysts in the thyroid gland, etc. The same process, however, may also affect the pathological cells — cysts may be produced in tumours. The ovarian cyst, for example, is looked upon as an adenoma or epithelioma accompanied by colloid degeneration. Another important variety of degeneration is represented by hya- line degeneration. It is essentially characterized by the production of refractive homogeneous masses. It is frequently observed in cer- tain forms of nephritis, in inflammation of the ovary, and in tubercu- losis; and it is not rare in the small aneurisms which are found in the walls of tubercular cavities. According to Armanni, hyaline degeneration is frequently observed in the tubes of Henle in diabetic kidneys. The alteration found here, however, should be carefully dis- tinguished from hyaline degeneration, for, as Ehrlich has shown, it is really due to an infiltration of the cells by glycogen. Parallel with hyaline degeneration may be placed transparent degeneration, observed by Hanot and Gilbert in the livers of persons dead of cholera. In this condition the protoplasm of the hepatic cells becomes completely transparent, the nucleus alone persisting. Finally, Zenker's waxy degeneration is generally considered to be the same as hyaline degeneration. It is an alteration attacking the striated muscles. It was first encountered in the myocardium in typhoid fever, and was subsequently observed in a great number of infections; it may also be experimentally produced by tetanization of the muscles. It is essentially characterized by swelling, hyaline meta- morphosis, and fragmentation of the muscular tissue. There is nothing precisely known concerning the nature of hyaline degeneration. It has been found that the substance which infiltrates the cells resists reagents. This fact has caused it to be compared to another variety of degeneration, which we shall study in a special manner — namely, amyloid degeneration. Hyaline degeneration must not be confounded with glassy degen- CELLULAR DEGENERATIONS 319 eration. The latter is essentially characterized by a transformation of the cell, all parts of which lose their histochemical properties. The protoplasm, nucleus, and nucleolus are no longer differentiated. It would seem, therefore, that this process should be identified with the one already described in the section on inflammation under the terms fibrinoid degeneration or coagulation necrosis. As we have already stated, this is a process similar to the one presiding over the coagula- tion of organic substances containing fibrine. It is often stated that glassy degeneration is the first stage of caseation. In fact, it seems certain that the cells are first attacked by coagulation necrosis before undergoing the transformation or, one might almost say, the special fermentation which ends in their caseous degeneration. This process, which is mainly observed *in tuberculosis and syphilis, has already been described in connection with the histo- genesis of tubercle. There still remains pigmentary degeneration, which is character- ized by a transformation of the protoplasm. It should not be con- founded with pigmentary infiltration, which is due to a simple accu- mulation of pigments transported to the cell. The difference here is the same as that between fatty degeneration and fatty infiltration. A sclerotic degeneration also is often spoken of. This is the process which we have already described as a mode of repair, a veritable cica- trization. Connective tissue develops in order to replace cells that have degenerated or disappeared. The cicatrized tissue is sometimes infiltrated with calcareous salts. This process is known as calcareous degeneration. Causes of Cellular Degenerations. — Although degenerations differ in their anatomical and clinical expression, and occur under condi- tions peculiar to each of them, and also have a dissimilar significance and evolution, the numerous varieties just described are, neverthe- less, united by analogous etiological and pathogenic conditions. Cellular degenerations always give expression to some nutritive disturbance. The latter may depend upon three distinct causes : (a) Deficient supply of materials destined for nutrition; (h) vitiation of the interstitial plasma — namely, an intoxication disturbing nutritive metabolism; and (c) disturbance or suppression of the functions of the cell. Thus viewed, it is easy to conceive the etiological conditions. At the head of the first group is naturally placed starvation. Now, it has been demonstrated by a great number of observations and experiments that suppression of alimentation is quite speedily fol- lowed by cellular degeneration. The form of degeneration produced under such circumstances is fatty metamorphosis. 320 CAUSES OF CELLULAR DEGENERATIONS The same effects are observed when the blood is altered, either because it no longer brings to the cells a sujSicient amount of aliment, or because it is not charged with a requisite amount of oxygen. The former condition is realized when the blood mass is lessened — for example, as the result of great hemorrhages; the latter occurs when the blood corpuscles are altered or decreased in number, as in anaemia. At all events, the cells soon undergo fatty degeneration, the frequency and extent of the lesions varying, however, according to the type of anaemia. While steatosis is exceptional in cases of chlo- rosis, it is constant in pernicious anaemia. General disturbances are not the only active factors ; local anaemias play a part which is by no means unimportant. Arterial strictures and obliterations cause degeneration of those parts insufficiently sup- plied with blood. It is stated that accumulation of carbonic acid in the tissues pro- duces the same effect as an insufficient supply of oxygen, and this explains the occurrence of degeneration in cases of venous oblitera- tion or cardio-pulmonary insufficiency. In this case, however, the process is rather one of intoxication, and we are thus led to our second group. It may be well to consider successively the role of exogenous and autogenous poisons. A very great number of mineral poisons give rise to cellular degenerations. It will suffice to mention arsenic, and especially phos- phorus. The latter substance produces diffused steatosis of all the anatomical elements, its action being particularly marked in the liver, which, in grave cases, undergoes complete degeneration. It is also by the production of cellular degenerations that other sub- stances give rise to cirrhoses. Sclerotic tissue makes its appearance to fill the vacancy created by the death of the more highly organized elements. The degenerations and scleroses consecutive to endogenous intoxi- cations are explained by the same mechanism. Whether the question be one of noxious products developed under the influence of cellular life or one of substances formed by bacteria normally or accidentally inhabiting our bodies, the result is the same. Let us assume, for ex- ample, that a calculus obstructs the exit of the bile. This secretion will excite a degeneration of the hepatic cells, and, passing into the circulation, will alter distant organs, particularly the kidney, in which it will give rise to a granulo-fatty degeneration of the epithelia. Let us now consider an exaggeration of gastrointestinal putrefaction. Under such circumstances a degeneration of the hepatic and renal cells will frequently be observed as the result of the absorption of the CELLULAR DEGENERATIONS 321 excessive amount of toxines formed. As a dyspeptic liver exists, there is reason for describing a dyspeptic kidney. A good many cases of Bright^s disease are referable to no other causation. Finally, we hardly need recall the fact that infection means intoxication, and that the soluble substances generated by the microbes produce numerous cellular degenerations. This result has been demonstrated by a large series of clinical observations and experiments. There is no subject which has been better studied. It is in the course of infectious diseases that the numerous varieties of degeneration above described are met with — namely, from cloudy swelling to steatosis, coagulation necrosis, and amyloid degeneration. We have stated that degeneration may be due to a suppression or disturbance of cellular activity. We must here introduce an impor- tant distinction. In cases of simple lack of function degeneration occurs, and not atrophy. The muscles of an individual who remains inactive diminish simply in volume; when a limb is placed in an immovable apparatus, it atrophies but does not degenerate. The same is true of glands which remain at rest. On the other hand, degenera- tion is produced when lack of activity results from functional dis- turbance. If, for example, a muscle or a gland remains at rest be- cause its nutrient vessels are altered, or because the nervous cells commanding the functions or the nerves transmitting the impulses are affected, it is not atrophy, but degeneration that occurs. Thus, section of a nerve does not act upon the muscle through the immobil- ity which it causes; on the contrary, the phenomena are more com- plex; there is a suppression of the necessary stimulus, and degenera- tion seems again to be connected with a trophic disorder. Without wishing to even briefly study the different varieties of degenerations, it may be well to give some complementary informa- tion concerning those most often met with and which have thus far only been alluded to — i. e., fatty degeneration and amyloid degenera- tion. We will then present some considerations relative to pigmen- tary degeneration. Fatty Degeneration. — Fatty degeneration or steatosis is essentially characterized by a fatty transformation of the nitrogenous matter which enters into the constitution of anatomical elements. As already stated, it should be carefully distinguished from fatty infiltration, which is in reality cellular obesity. A provision of fat is made in the cellular membrane, and, in order to make room for it, the protoplasm is slightly pushed aside. There is an addition of a new substance, and not metamorphosis of one already existing. From this point of view, the analyses of Perls are highly demonstrative. In fatty infiltration, the water contained in the tissues disappears and gives place to the fat ; 322 FATTY DEGENERATION in fatty degeneration, on the other hand, the albuminoid constituent yields its place to the fat element. Fatty degeneration may be established at once or follow another variety, such as granular degeneration, cloudy swelling, or albuminous infiltration. Under the microscope, in specimens fixed by means of osmic acid, fat appears in the form of small black coloured granules, isolated or united in masses, and particularly abundant around the nucleus. This steatosis is frequent in the liver, kidney, myocardium, and muscles. It originates under the most varied conditions. Nutri- tive disturbances produced by high temperatures are considered im- portant causative factors. The frequency of steatosis in infections is thus explained. It is well to note, however, that in this instance the problem is a very complicated one, since the alterations may more eas- ily be accounted for by a production of toxines than by thermal eleva- tion. Nevertheless, the intervention of the latter pathogenic condi- tion may be accepted, because fatty degeneration has been produced experimentally in animals whose temperature was mechanically raised by prolonged confinement in an oven. The alteration is supposed to be due to a lack of oxidation, since, under the influence of hyper- pyrexia, the red blood corpuscles take up less oxygen than normally. The steatosis occurring in grave anaemias, particularly that observed in progressive pernicious anaemia, has likewise been referred to a lack of oxidation. The same influence may be applied to other etiological conditions. The steatosis manifesting itself in the course of fevers, cachexias, and poisonings may always be explained by deficient oxidation. Finally, steatosis is observed when an organ is rendered inactive in consequence of suppression of nervous excitation, because metabo- lism does not progress in a normal manner. Nervous influence is in- dispensable for the regular performance of nutrition. If nutrition fails, oxidation diminishes and fatty degeneration is produced. The more active an organ is, the greater are its demands for oxygen. Con- sequently, if the supply of this gas be diminished, degeneration will affect first those parts which manifest the greatest physiological ac- tivity. Among the muscles, the myocardium is first attacked, then the diaphragm ; among the glands, the liver and the kidneys. It is well to note that steatosis occurs when there is diminution but not suppression of oxidations. Stricture of an artery produces fatty degeneration; its obliteration, if not partially compensated by collateral circulation, results in necrosis. Suppression of oxida- tion ends in the death of the cellular element. The effects of steatosis may vary according to the organ attacked and the extent of the lesions. It is therefore not practicable to give CELLULAR DEGENERATIONS 323 a general description of the process. In order to Rx the ideas, let us consider only what takes place in the liver. Fatty degeneration of the liver occurs in a great number of cir- rhoses. Although the distribution of connective tissue serves as the basis for anatomical classifications, and to a certain extent rules symptomatology, the condition of the cell accounts for the evolution of the process. Atrophic cirrhosis is essentially a chronic affection. Hanot has described a variety which runs a rapid course, and causes death within four or five months. In this instance cellular alteration is profound and widely diffused; hence, the disease is called fatty atrophic cirrhosis. Likewise, the gravity of the fatty hypertrophic cirrhosis of Hutinel and Sabourin is due to cellular degeneration, which suppresses the function of the liver^ and hence the process has sometimes been designated subacute icterus gravis. Although rapid, the evolution lasts for months in the examples just related. Such is no longer the case when a pathogenic cause in- duces an acute steatosis of the cells. The affection then runs its course in a few weeks, a few days, or even a few hours. This is what takes place in the process designated by the French as icterus gravis, and by the Germans as acute yellow atrophy of the liver. It is not a definite disease. As is well known, icterus gravis may occur in the most varied conditions and depend upon the most diverse causes (see page 203). Furthermore, an infectious or primary icterus gravis, a toxic icterus gravis, and a secondary icterus gravis occurring as a sequel of various affections of the liver, have been described. The classification of these dissimilar affections under one head is per- missible by virtue of the fact that the same lesion — namely, diffuse steatosis of the hepatic cells — exists in all of these morbid states. This lesion explains the symptoms. There is hepatic insufficiency, and the suppression of the functions of the liver, notably of its action on poisons, accounts for all the phenomena. The importance of fatty degeneration may be seen from these examples. It would be easy to repeat with respect to the various viscera what we have just stated concerning the liver. Amyloid Degeneration. — Amyloid degeneration was described by Eokitansky (1842) under the name lardaceous degeneration, by Christensen (1844) under the name waxy degeneration, and by Vir- chow (1853), who gave to it the name it now bears. In 1858 and 1859, Kekule and Schmidt showed that amyloid matter is not, as might be supposed, an amylaceous substance. On the contrary, it is an albuminoid — i. e., a nitrogenous substance. In whatever locality it may be found, it is recognised by means of certain very simple reactions. Under the influence of the iodo-iodide 324 AMYLOID DEGENERATION test it gives a mahogany-red colour, which becomes violet red by the addition of sulphuric acid. On contact with methyl violet it be- comes red. Amyloid matter is perhaps normally met with in certain parts of the organism. It often constitutes an epiphenomenon in the course of the most varied affections, notably of nephrites. In certain cases it may be so widely distributed that amyloidism represents the prin- cipal manifestation. In the prostate gland and central nervous system of normal indi- viduals there have been noted concentric masses giving a mahogany-red reaction with the iodo-iodide reagent. It may be asked, Was amyloid matter really present ? Is it not more probable that these masses are simply collections of glycogenic matter? In answer thereto, it may be stated that the latter opinion prevails at the present time. As an epiphenomenon, amyloid matter occurs in blood extravasa- tions and in cicatrices. It is especially frequent in the kidney during the course of various lesions affecting this organ and of different varieties of nephritis, and even in acute nephrites. In all these instances amyloid degeneration is not widely distrib- uted; it has no clinical importance. Such is not the case with the facts which we will presently consider. Cohnheim has related cases where amyloid degeneration had in- vaded the organism without any cause being revealed to account for this alteration. Such an event is exceptional. Amyloid degeneration is nearly always secondary to diseases which are liable to induce cachectic conditions, such as tuberculosis, syphilis, and multiple sup- purations. Tuberculosis stands at the head of the list. Amyloidism is chiefly observed in patients suffering with pulmonary cavities, extensive lesions of the intestine, articular or osseous suppurations, necrosis, and caries. The foci almost always communicate with the exterior. f Next comes syphilis, particularly hereditary syphilis, especially when the osseous system is involved. The spleen is the organ chiefly affected. Suppurations of long standing may give rise to amyloid degenera- tion. Sometimes arthropathies or osseous suppurations, sometimes visceral abscesses, dilatation of the bronchi, or multiple abscesses of the skin are the causative factors. Finally, of the rarer causes, we may mention cancer, especially ulcerated cancer, gout, rickets, alco- holism, and malaria. This etiological multiplicity makes it plain that all ages may be attacked. However, amyloidism is especially frequent in men and at the middle period of life — i. e., between twenty and thirty years. CELLULAR DEGENERATIONS 325 Animals are not exempt from this degeneration. As in man, it is encountered in tuberculosis and in chronic suppurations. Krakow has succeeded in producing it experimentally. It is constantly observed in tuberculous pheasants, in the livers of which the tubercles are sur- rounded by a ring of connective tissue infiltrated with amyloid matter. It is to-day almost universally agreed that amyloid matter should be classed as of nitrogenous origin ; but the mechanism presiding over its formation is as yet unknown. Wagner considers amyloid matter as intermediate between albumins and fats; and this view would explain the frequent coexistence of amyloid and fatty degenerations. Von Eecklinghausen believes a homogeneous matter is exuded from the cells, which coagulates on contact with the interstitial fluids. According to Ziegler, the diseased cells are unable to utilize the albu- mins escaping from the vessels, under which circumstances the albu- mins undergo a special metamorphosis. It is certain, however, that amyloid degeneration is decidedly analogous to fatty degeneration, for it is produced under the same conditions, and must therefore be considered as connected with a disturbance of albuminous nutrition. No further precision can be given to this somewhat vague formula. Amyloid degeneration affects the vessels and the connective tissue in a predominant if not an exclusive manner. In the arteries it begins in the inner coat, sparing the endothelium. It is especially marked in the middle coat. It extends to the capil- laries, which it transforms into vitreous, homogeneous tubes lined with endothelial cells, which remain intact. When it affects the organs, it presents three different macroscopic aspects. The totality of the greatest part of the organ is invaded; the tissue becomes homogeneous, semitransparent, lardaceous. At other times the process is limited to small foci having the appearance of sago grains. Finally, the lesions may be minute and recognisable only under the microscope or by transmitted light on thin sections treated with the usual reagents. The liver, which is the organ most frequently attacked, acquires a considerable volume. It becomes pasty, lardaceous, as if bloodless. Under the microscope, infiltration of the capillaries, hepatic artery, and, more rarely, of the portal vein is found. As to the changes in the cells themselves, discussion is still open. Some authors assert that degeneration occurs, others state that the vitreous masses encoun- tered are not altered cells, but amyloid masses that have exuded from the vessels. 326 AMYLOID DEGENERATION The localization is analogous in the other organs. In the spleen it is deposited in the Malpighian corpuscles ; in the kidney it is found in the vessels, glomeruli, connective tissue, and the walls of the uri- niferous tubules. The epithelial cells are frequently altered, but never amyloid. We may also mention the amyloid degeneration occurring in the lymphatic glands, the intestinal mucous membrane, and in the heart, where the muscle cells may be affected (Letulle and Nicolle). When amyloid degeneration is localized it does not give rise to any special symptoms. Thus, in parenchymatous nephritis, where it is almost constant, it is not expressed by any appreciable manifestation. When it is extensive it produces a certain number of phenomena, which vary according to its predominance in this or that organ. The first indications are paleness of the patient — i. e., paleness of the in- teguments and mucous membranes and loss of strength. Examination of the abdomen reveals considerable hypertrophy of the liver and spleen ; diarrhoea is very frequent ; the urine is remark- able for its abundance, pale colour, and the great amount of albumin which it contains, at least in certain cases. Though a fatal termination is the rule, it is, however, admitted that recovery is possible. The patient overcomes the cause that has produced the degeneration, and the latter subsides and finally disap- pears. Cohnheim, who has laid stress on this evolution, cites the following experiment: Fragments of amyloid matter, when intro- duced into the peritoneal cavity of an animal, are rapidly absorbed. Therefore, according to him, it must be concluded that absorption of this material may occur in the human organism. This experiment is interesting, since amjdoid matter is very re- sistant. It is not altered when submitted to artificial digestion with pepsine and hydrochloric acid. In fact, these are the means gen- erally employed for its preparation. Pigmentary Degeneration. — A distinction analogous to what has been admitted in regard to fat must also be made for the pigments. Sometimes there is simple infiltration, sometimes degeneration. The cells may be charged with colouring matters, particularly the leuco- cytes, which are often overloaded with carbon even under normal con- ditions. In other cases the cells may be infiltrated by more or less modified blood pigment derived from former hemorrhage. Lastly, various black pigments, apparently derived from the blood, may also accumulate in certain anatomical elements without disturbing their function. In the case of pigmentary degeneration, on the contrary, cellular alterations are found which account for the disorders observed dur- ing life. CELLULAR DEGENERATIONS 327 Pigmentary degeneration is essentially characterized by the accu- mulation within the cells of an okra matter {pigment ocre of Kelsch and Kiener, rubigine of Anscher and Lapicque), which has the prop- erty of turning black under the action of ammonium sulphydrate, or blue on addition of potassium ferrocyanide and dilute hydrochlo- ric acid. The latter reaction, which is very sensitive, is employed in histology. In preparations thus treated it may be seen that the pig- ment invades the protoplasm, pushes it aside, atrophies the nucleus, and causes its disappearance. All organs are not equally attacked. As is always the case, the frequency of the lesions is in proportion to functional activity. The liver is the organ most frequently invaded; next comes the kidney, then the myocardium and the pancreas. Pigmentary degeneration is chiefly observed in malaria, then in diabetes. It is much more rarely met with in pernicious anaemia, profound anaemias, and certain poisonings. It is a serious process, which, by virtue of the special cachexia it induces, may be placed parallel with amyloid degeneration. 22 CHAPTEE XIX FUNCTIONAL SYNEBGIES AND MOBBID SYMPATHIES Unity of the organism in its physiological state: functional synergies — Unity of the organism under pathological conditions: morbid sympathies — Study of functional synergies : anatomical unity and physiological unity — The contigu- ity of organs — Vascular connections: emboli — Nervous connections — Conclu- sion concerning the mechanism of general reactions and of fever. Living organisms are constructed in such a manner that all modi- fication occurring at one point of the economy influences the entire economy. This law is equally true in physiology and in pathology. Let us suppose, for example, that a muscular group contracts. Circulation becomes at that point more energetic, and occasions con- sequently an increase of cardiac activity. But, in contracting, mus- cles consume carbohydrates, and when their reserve is exhausted the liver undertakes to furnish them with the useful materials; here is another organ entering upon activity. Eespiration will accelerate, since it must cause a greater amount of oxygen to arrive and throw out the excess of carbonic acid proceeding from the transformation of carbohydrates. Other wastes will be eliminated through the urine, and that will increase the activity of the kidney. Then, should con- traction be somewhat prolonged, bodily temperature will tend to rise, and the various apparatus concerned in the regulation of thermo- genesis will soon be called into play; there will follow vasomotor modifications and changes in the secretions, notably in the sweat. Finally, general nutrition being also stimulated, the result will be a loss of ternary and nitrogenous matters, and a tendency to repara- tion, as expressed by hunger and thirst, and consequently a general increase in functional activity. Eeciprocally, if an organ languishes, if its activity diminishes, the result is a series of reverse modifications in the entire economy — viz., a diminution in all the vital manifestations. Along with the relations which exist between the various parts of the organism and which constitute what is called in physiology func- 328 FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 329 tional synergies, we find, in pathology, morhid sympathies or syner- gies. The disturbances may at first be local; on a superficial exami- nation, they seem to be limited to a part of the organism. In reality, a great number of modifications is necessarily produced in the whole economy. The reactions may be more or less marked, at times even imperceptible; they exist none the less. There is no disease that remains local. We are therefore led to inquire through what mechanism the lesions of an organ influence the remainder of the economy. For convenience of description, we may group in four classes the connec- tions uniting the various parts of the organism. These are func- tional synergies, contiguity of organs, vascular connections, nervous connections. Functional Synergies For the old idea, which assumed that each organ played a spe- cial and determined part, is substituted the more complex con- ception of functional synergies. We know at present that several organs collaborate in view of assuring the same function; that cer- tain organs may supply and replace each other in a more or less per- fect manner. As the result of physiological researches and clinical observations, parts which were separated by anatomical study have been united and grouped. Physiological unity does in no wise correspond to anatom- ical unity; thus, for example, the motor cell, the nerve, and the mus- cle represent the same physiological unity, whereas anatomy distin- guishes in them at least three different parts. Pathology confirms the data of physiology on this point, since the alteration of one of these parts influences the others : destruction of the cell, for instance, entails atrophy of the nerve and muscle. In general, secondary alterations, consecutive to a primary lesion, produce an aggravation of the disease; but they realize at times a favourable modification and represent a tendency to a new adapta- tion. In the latter case the secondary lesions obey one of the two following laws : suppression of what has become useless ; anatomical or functional modification of parts capable of compensating for the primary lesion. These two laws are easily understood when the teachings of natu- ral history are taken into consideration. It is known, in fact, that function exists before the organ and rep- resents simply a reaction to an external cause; in the evolution of beings, every change means an adjustment to new needs. If external conditions vary, reactions must be modified. New functions are thus 330 FUNCTIONAL SYNERGIES produced;, which in time give rise to anatomical modifications, to the transformation of a pre-existing organ, or to the production of a new one. On the other hand, the organ can not maintain itself in its actual state unless the function that has given rise to its production continues to be exercised. It is well known, for example, that the eyes of moles and of some burrowing rodents are rudimentary, or may even be completely covered with skin and hair. Several Crustacea living in the subterranean caves of Carniola and Kentucky are blind. Darwin reports that in certain oceanic islands, where no carnivorous animals exist, birds are met with whose wings have become rudimentary and who are inca- pable of flying. In domestic ducks, the leg bones are more developed and those of the wings less voluminous than in the wild: another illustration of the law of adjustment. If we wish to look for analogous facts in the domain of embry- ology or ontogeny, we see that a series of organs disappear when they have become useless. The metamorphoses of certain batrachia, the atrophy or transformation of the branchiae, when the animal passes from aquatic to aerial life, shows us simply this adjustment of the organ to the function. What in this way occurs in a being who evolves, or what is ac- quired in successive generations and transmitted by heredity, is not different, on the whole, from that which is produced in an individual when physiological unity is affected at some point. Let us first take some very simple examples; let us consider what happens in the vertebral column. Here is a physiological unity com- posed of a great number of independent pieces. Now, if one of these pieces be altered, as is the case in Pott's disease, there will consecu- tively be produced curves of compensation that will modify the shape of the whole vertebral column, will even reverberate in more distant parts — in the pelvis and thorax. These modifications are fortunate so far as they remedy the primary lesion and adjust the organism to new conditions, but they thus create a danger, and may become a cause of eardio-pulmonary accidents or of dystocia. Similar changes are observed consecutively to lesions of the hip, to the shortening of a member, to a defective position — that of the sciatic, for example — to some alteration of the skeleton ; there develop in the healthy parts more or less marked deviations of a compensative character, which respond to the first needs, but too often become the cause of new disturbances. The great systems, as the circulatory or the nervous, will furnish us illustrations of greater interest. Let us consider first what takes place in the circulatory system. FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 331 In the case of a limited lesion, of ligation or obliteration of the main blood vessel of a member, a network of collaterals will develop. This result is favourable, since it permits the re-establishment of the circulation, but it sometimes creates new dangers, of which one may easily be convinced by considering the cases where the obliteration occurs in the principal vessel of a viscns. Thus, in atrophic cirrhosis, the disturbance of portal circulation, forcing the blood to pass through the channels of derivation, may be the starting point of oesophageal varices, and consequently the cause of a mortal hematemesis. The importance of secondary lesions clearly appears in the study of cardiac malformations. Congenital stricture of the pulmonary artery occasions persistence of the foramen of Botal, sometimes of the interventricular opening of the arterial canal, and the develop- ment of bronchial arteries. These various modifications always follow the same law, equally true in pathology, in physiology, and in natural history: re-establishment of functions on new bases and new adjust- ment, liable to become the starting point of new accidents. It is especially in the study of the nervous system that the history of secondary modifications abounds in interesting facts. The simplest illustration is represented by the neuromuscular sys- tem, including the cerebral cell, the medullary cell and the cord which connects them, the nerve, and the muscle; the lesion of the cerebral or medullary nerve cells entails degeneration of the sub- jacent parts. Eeciprocally, suppression of the muscles affects the nerve and the cells ; an amputation, for instance, gives rise to atrophy of the psychomotor centres corresponding to the suppressed part. The centres atrophy, because their peripheral expansions no longer exist; they have no longer any reason for being. Munck has experimentally realized similar facts : he has shown that extirpation of the eye causes atrophy of the optic centres. We find similar synergies when we consider the other apparatuses of the economy, such as the digestive and the genital. Extirpation of the ovaries leads to atrophy of the uterus; double castration acts similarly upon the prostate gland. In certain cases functional synergy allies parts that seem quite distinct : such is the alliance between the liver and the kidneys. The liver prepares certain materials necessary for the urinary secretion: nitrogenous substances undergo there an ultimate transformation which reduces them to the state of urea — i. e., a crystallizable body, which readily diffuses and represents a true physiological diuretic. If the uropoietie function of the liver is disturbed, the urea will be replaced by less oxidized bodies, some of which will prove harmful to the renal epithelium and give rise to a secondary nephritis. The 332 FUNCTIONAL SYNERGIES hepatic lesion often leads to the passage into the general circulation of toxic substances, which the liver should have retained and trans- formed; or the principles of biliary secretion, salts and pigments, invade the economy; or else an excess of glucose reaches the blood. At all events, the kidney comes to the assistance of the organism and prevents intoxication; but the additional work imposed upon it may become the cause of epithelial alterations. These results, which we will study at greater length in connection with the lesions consecutive to dyscrasias, deserve to be alluded to here, since they clearly show what may be the consequences of functional synergies. These functional synergies are much more numerous than one might at first believe. As we are speaking of the liver, we know to-day that, through its glycogenic reserve, this gland plays a great part in nutrition; it regulates the supply for all the cells which con- sume sugar — ^namely, for all the cells of the organism. But it is especially with the muscles that the liver is in continual relation. As has been remarked by Chauveau and Kaufmann, "the liver is the indirect collaborator of the muscles in the execution of move- ments " ; when the muscle contracts, the liver pours the sugar more abundantly into the blood. It is then conceivable that disturbances of the glycogenic function should affect muscular contraction. Finally, there also exist altogether incomprehensible synergies be- tween various parts of the organism. Such is the relation existing between the genital apparatus on the one hand, and the pilous system, the larynx, and even the brain, on the other. It is known, for exam- ple, that the encephalon is far less developed in castrated than in entire horses. It is true that since the researches of Brown-Sequard there is a tendency to explain facts of this nature by internal secre- tions : the testicle or the ovaries are supposed to produce principles useful to the nutrition of these various parts of the organism. Some explain in the same manner the correlation which exists between the atrophy of the thyroid gland and myxoedema, the hypertrophy of this gland and exophthalmic goitre, the lesions of suprarenal capsules- and melanodermia. The theory is very seductive, but in some re- gards it may still seem inadequate; at all events, if it were general- ized it would account for one of the most interesting aspects of func- tional synergies and their consequences — morbid synergies. Contiguity of Organs. — The lesions of one organ may affect neighbouring organs by two quite different procedures. Sometimes the action is simply mechanical: a hypertrophied viscus compresses and pushes away surrounding parts; in other cases the affection has specific characters and excites in adjacent parts special disturbances or particular reactions. FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 333 It will suffice to reflect for a moment on the anatomical disposi- tions of organs and their mutual relations, in order to understand the eifects produced by the peculiar development of any of them. Illus- trations abound; we shall recall a few: The exudation of the left pleura compressing mechanically the heart and the vessels, may occa- sion serious disturbances and even sudden death; thyroidal tumours crush the trachea; tumours of the uterus and ovaries push aside the intestines and the diaphragm, and disturb the play of the lungs. Phenomena produced by compression may be grave — e. g., the syncope resulting from left pleurisy; but the disturbances often dis- appear with the pathogenic cause. If pleurisy be punctured, the heart resumes its situation; if the tumours of the thyroid gland, of the uterus, or of the ovary be excised, the secondary manifestations stop. However, such is not always the case. A simple mechanical disorder may entail irremediable effects : compression exercised upon excretory passages, vessels, and nerves may produce a series of highly important modifications. Compression of the excretory duct of a gland causes stagnation of the secreted liquid. If compression be of short duration, the dis- turbances will cease when the obstacle is removed; but if it be some- what prolonged, a series of modifications in the epithelia, and con- secutively in the connective tissue, will appear. The obstacle may subsequently be removed, still the glandular lesion will persist and develop on its own account. The examples of this process are exceed- ingly numerous : we hardly need mention the cirrhosis produced by the compression of the biliary passages, the hydronephrosis, the scle- rosis and atrophy of the kidney, resulting from the obliteration of the ureter, as in the case of cancer of the bladder or the uterus. Simi- lar occurrences have been reported with reference to the salivary glands and the pancreas. We may also mention in this connection what occurs as the result of compression or stricture of the larynx and of the trachea: the lung is affected with an incurable emphysema. Similar phenomena are observed in the blood vessels; as a rule, they are even more rapid and more serious. If compression bears on an artery, the territory supplied by it becomes ischaemic, resulting in the production of necrosis or gangrene. In case of a vein, the blood stasis engenders oedema, and subsequently sclerosis. Compression of the nerves is expressed by sensory modifications, neuralgias, spasms, paralyses, vasomotor or trophic disturbances, at times by speedily mortal infections, best exemplified by the pneu- monia consecutive to section or compression of the pneumogastric nerve. When a compressing organ is struck with some inflammatory or 334: VASCULAR CONNECTIONS neoplastic affection, it may, at the same time that it acts mechanically, exercise a specific influence. An inflamed tissue often occasions paralysis in subjacent parts. Stokes long ago established this fact as regards the diaphragm in cases of purulent pleurisy. Such is exactly the case when a phleg- monous angina causes paralysis of the palate. At other times^ though this is more rarely the case, it is an acute pericarditis that causes the paralysis of the myocardium. What is produced in the striated mus- cles is equally observed in the nonstriated; such is gastrointestinal paralysis occurring in peritonitis. Inflammatory centres may be propagated to the surrounding or- gans. There sometimes occurs an unexpected opening of a purulent collection into a contiguous cavity. In most cases the opening is pre- ceded by a preliminary step — a true extension of the inflammatory process, giving rise to a thickening of the tissues, then to ulceration and perforation ; the pus thus makes its way toward the exterior. The process is often favourable, since it leads to the evacuation of the morbific matter; but it may become the source of new dangers, such as the abscess of the liver that opens into the lung and thus produces a pulmonary gangrene. Apart from microbic lesions, there are only cancerous affections that may thus be propagated by contiguity. The cancer of the stomach may cause secondary nuclei in the adjacent parts of the liver and pancreas. The cancer of the mammary and lymphatic glands may invade the skin, etc. In most cases, however, the propagation of can- cerous lesions is not effected in that way; the neoplastic cells, like pathogenic microbes, strongly tend to take the vascular (sanguineous or lymphatic) route, and to give rise in this way to foci more or less distant from the primary lesion. One might believe, in some cases, that sclerotic lesions have ex- tended in the same manner ; sclerosis of the liver and lung have been seen to follow perihepatites and pleurisies. But the process is far more complex: the visceral lesions are due, in cases of this kind, either to the direct action of the morbific cause, which acts both on the serous membrane and on the subjacent organ, or to the compression of the nourishing vessels which supply the viscus; the consequent anaemia, by disturbing the nutrition of the noble element, brings about the compensating development of connective tissue. Vasculak Connections Cardiac Insufficiency. — Functional disturbances and lesions of the heart, leading to modification of the circulation of the blood, necessarily affect the entire organism. FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 335 Yascular lesions, even those which seem to be best compensated, are attended by a certain number of vascular disturbances, and con- sequently by nutritive disorders. Examination of the facies in a per- son suifering with aortic or mitral lesion suffices to demonstrate the influence of the heart over distant parts. The dystrophic influence of cardiopathies is especially marked when the lesion has begun in child- hood; it may be expressed by infantilism, as is at times observed as the result of aortic insufficiency. A better-known example is fur- nished by the history of simple mitral stenosis, giving the women affected with it a chlorotic appearance. However, where the pathogenic influence of circulatory disturb- ances appears most clearly is in cases of cardiac insufficiency or asystole. This process is essentially characterized, from an anatomical and clinical point of view, by a weakening of the myocardium and insuf- ficiency of the tricuspid valve; from the standpoint of pathological physiology, by a diminution in the arterial and an increase in the venous tension. The result is a stasis in the organs, the liver, kid- neys, and brain. If then treatment intervenes, if digitalis is admin- istered, the contractile energy of the myocardium increases, and all the symptoms disappear; the arterial tension returns to its normal condition; the liver, which had increased in volume, diminishes; the kidney no longer permits the escape of the albumin ; the urine returns to its normal quantity; the cedemas disappear. The patient be- lieves himself re-established and resumes his occupation, but after a certain period of time a second attack of asystole occurs, then a third, then a fourth. Finally, there comes a moment when no good result can be obtained from the administration of digitalis; the con- gestion of the organs admits of no relief, the liver remains hyper- trophic, the kidneys continue to pass out albumin, the cedemas per- sist. What has happened? In the former case, when all disappeared under the influence of cardiac medication, the question was of an individual in whom the functional modifications of the organs were under the influence of cardiac insufficiency; it was therefore sufficient to increase the en- ergy of the myocardium by means of digitalis, caffeine, or sparteine to see the accidents vanish. But when the morbid manifestations were repeated, they at length disturbed the function of the organs; the visceral congestions were followed by more profound alterations; the cells degenerated, and secondary scleroses were produced. Asys- tole has yielded to cardiac cachexia. Let us suppose that it was pos- sible to replace the diseased heart by a normal one; the symptoms would continue none the less, because the primary disturbances of 336 VASCULAR CONNECTIONS the circulation have created, secondarily, organic lesions which evolve on their own account; the cardiac has become a pulmonary, a cere- bral, a hepatic, or a renal patient. In many instances the secondary lesions are so predominant that the clinician is at a loss to trace the succession of the phenomena; in vain he endeavours to determine what has been the primum movens of the morbid series. Are these secondary accidents to be attributed to the venous stasis resulting from the cardiac insufficiency, and can they be accounted for merely by hydraulic modifications? If such were the case, the viscera would have been altered according to a determined order; the inferior cava system, which empties itself with more difficulty than the superior, would first be affected, and among the viscera that are annexed the liver would be the first to receive the blood reflux from the right auricle; it would, then, be affected before the kidneys, whereas the brain would be reached after the abdominal organs. Clin- ical experience shows that such is the case with children; in childhood visceral asystole begins with the liver, and albuminous urine is scarcely ever observed without hepatic hypertrophy. But such is not the course of events in adults. The reason of this divergence is easily comprehended. In the child the organs are healthy; they have not been altered by the numerous infectious or toxic agents which in the adult have left in the viscera traces of their passage. Previous diseases create local susceptibilities, particular vulnerabilities; hence, in presence of the same morbific cause, each organ suffers on its own account, with the result that more mutability of symptoms, more unexpected morbid reactions, and more variability in clinical types are observed. This is the reason why visceral lesions consecutive to cardiopathies do not follow, in the adult, the regular course observed in the child; that is why we meet with pulmonary, hepatic, renal, or cerebral partial asystoles. If we were able to know exactly the past of our patients, if we could find out what defects they have inherited, if we could succeed in determining what organs had been touched and to what degree altered, we would be in a position to predict assuredly what are to be the localizations of cardiac insuf- ficiency. We have hitherto supposed the cardiac lesion to be primary; but such is not always the case. Through the vessels terminating in or starting from it, the heart finds itself in communication with all the parts of the organism, and therefore it is readily influenced by them. If any disturbance is produced in the intrapulmonary circulation, as it occurs in bronchial dilatation and in pulmonary sclerosis or emphysema, the right heart, compelled to do some additional work. FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 337 will in the end dilate, and tricuspid insufficiency and the phenomena of asystole will follow. The same result is observed in tuberculosis, or, at least, in one of its forms known as fibrous phthisis; in this ease emphysema and bronchiectasis exist, and it is to these various lesions that the cardiac disturbances must be attributed. Asystole of pulmonary origin often presents, clinically, some par- ticular characters : the pulse may be strong, regular, and arterial ten- sion sufficiently high; there is then an evident discordance between the state of arterial circulation and the symptoms observed. The reason is that the hepatic hypertrophy, albuminuria, oedema of the lower extremities, depend upon the disorders of the right ventricle, and, in fact, it is the latter that is primarily affected, while the left ventricle continues to contract with sufficient energy. There is discord between the condition of the two halves of the heart. This fact explains why so little result is obtained from treatment with digitalis, which influences especially the left heart. Organs other than the lung may influence the heart and bring about through it a series of new disturbances; this is observed in the kidney and the liver. We see, for example, Brightics present cardiac disturbances as initial phenomena; others succumb to asys- tole. Part played by Peripheral Blood Vessels Outside of the heart, peripheral blood vessels establish numerous connections between the various parts of the organism, and explain a great number of secondary disturbances. Organs may be brought into relation by a particular blood sys- tem. Such is the case with the portal vein. It is conceivable, when the anatomical disposition is taken into account, that alterations affecting the spleen, the stomach, the intestine, may disturb the cir- culation of the liver. In most cases the reverse takes place — a hepatic cirrhosis causes congestion of the digestive canal, hypertrophy of the spleen, development of a collateral circulation, and production of ascites. In other instances, by far more numerous, the secondary disturb- ances result from the compression exercised on the vessels of an organ by the parts with which the latter are in relation. The effects evidently vary according as the compression is exer- cised on the afferent vessels (artery or portal system) or on the efferent (veins or lymphatic vessels). In the former case there is ischasmia or complete anaemia, in the latter a venous or lymphatic stasis. In consequence of this first stage, circulatory modifications may supervene, tending to re-establish the blood course and thus 338 PART PLAYED BY PERIPHEEAL BLOOD VESSELS remedying the first accidents. Otherwise, the compression will cause modifications of a trophic order : sometimes dystrophy will attack the vessel itself and produce hemorrhage; sometimes persistent ischsemia will terminate in necrobiosis and softening ; finally, in other instances, venous or lympatic stasis will engender sclerosis. But in the last case we must, perhaps, as we have done with regard to cardiac insuf- ficiency, assume the intervention of some superadded element — i. e., microbes or their toxines. Sclerosis would then depend upon an in- fection sufficiently attenuated not to give rise to any appreciable manifestations. Such is not always the case; vascular disturbances often favour the development of serious infections. They play an important part in the pathogeny of diffused phlegmons, of dry or moist gangrenes; they constantly intervene in the localization of even specific pro- cesses : such is caseous pneumonia in those cases where the pulmonary artery is narrowed and compressed by a tumour or aneurism of the aorta. In this manner, any lesion whatever which compresses the ves- sels of an organ produces a series of consecutive modifications, which may be summed up as follows : initial disturbances of circulation, anemia or passive congestion, more or less complete re-establishment of circulation, sometimes development of collateral networks, or con- secutive trophic disorders, necrobiosis, softening, sclerosis, and possibly pyogenic, gangrenous, or tuberculous secondary infections. The circulatory system plays also an important part in the propagation and diffusion of morbid processes, serving as a vehicle for soluble products or foreign bodies springing from a primary focus. We shall not dwell upon the diffusion of soluble products, of which we have already repeatedly spoken. We have shown that every cell constantly modifies the chemical constitution of the blood and thus infiuences the remainder of the economy. Each living element acts by seizing upon the substances necessary to its nutrition, by abandon- ing products of disassimilation, by secreting substances which con- tribute to the regulation of nutrition, finally (at least in certain cases), by neutralizing toxines and throwing them out or by producing antitoxic substances. All these products, favourable or unfavourable, are poured into the circulation and by means of vascular connections are carried to the various parts of the economy. They act on the first organ with which they come into contact. Thus, toxines proceeding from the digestive canal meet with the liver and occa- sion in this gknd congestion and sclerosis. But the arrest is not complete; a certain quantity crosses the first barrier and diffuses into the economy. Now there are certain organs better situated than FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 339 others for mutual influence; such is the case with the liver and kid- neys. The toxines originating from the liver easily go to alter the renal filter, as was demonstrated by the researches of Gouget; recip- rocally, the diseased kidney affects the liver, as was shown by Hanot and Gaume. Finally, recent researches have established the fact that the lesions of the lung rapidly produce secondary alterations in the liver. It would be easy to multiply the examples. Let us keep well in mind that through the circulatory system soluble substances are transported to the whole organism, but that they do not act equally upon all the parts. Their action is particularly manifest on the organs which are found in direct relation through the vessels, and on cer- tain cells belonging to different organs but allied to each other by virtue of functional synergies. Besides the soluble products, the circulatory system may carry solid bodies, which go on unobstructed until the moment when, meeting with too narrow a vessel, they are forced to stop at once. To this process has been given the name embolism; its importance leads us to describe it somewhat in detail. Embolism. — To Van Swieten is due the merit of having discovered embolism and made of it a complete study, both clinical and experi- mental. But men were not prepared for the new conception, and the labours of Van Swieten remained unnoticed or fell into oblivion; the discovery had arrived too soon. In the following century, when Virchow published his works on embolism (1845-'56), physicians, prepared therefor by some re- searches of Magendie, Gaspard, d'Arcet, and Cruveilhier, accepted with enthusiasm the ideas of the celebrated anatomico-pathologist. The question was taken up at the right moment; it led to a series of in- vestigations which secured a rapid progress for its study. Embolism is generally defined as sudden occlusion of a vessel by a foreign body travelling in the circulatory system. The meaning of the word has of late been modified; some have described under the same name incomplete obliterations, and others have spoken of microbic emboli, or of foreign bodies, extremely small, unable even to obstruct a capillary. The latter stop by virtue of a molecular adhe- sion which retains them, as are retained microbes in a porcelain filter whose pores are larger than they. We are thus conducted to the following definition: Embolism is essentially characterized by the sudden arrest of a foreign body car- ried by the sanguineous or lymphatic circulation. Emboli are divided, according to their volume, into emboli of large and small calibre and into capillary emboli; according to their point of departure, into exogenous and endogenous emboli. The former pro- 340 EMBOLISM ceed from the exterior, the latter originate within the economy. Finally, in view of their nature, they are divided into mechanical or inanimate and parasitic or living emboli. It is now easy to take into account the various divisions of the general classification. We are thus led to group emboli as follows : HiMBOLI Inanimate. Living. Of intravascular origin* Animal. Cardio-vascular. Vegetable. r Clot. Microbic. Sanguineous \ Globules. Cancerous. I Colouring matters. Of extravascular origin. Solid. Fatty. Cellular. Gaseous. Inanimate Emboli do not act, in most cases, except in a me- chanical way. They may be engendered in the walls of the heart or of blood vessels. Small vegetations emanating from an endocarditis, fragments of columns or of valves, atheromatous productions occu- pying the coats of large vessels, fall into their interior and are car- ried by the blood current. The second group is represented by blood clots detached from the inner surface of the heart or of blood vessels, where they had been deposited under various pathological conditions. In endocarditis, arteritis, and notably aortitis, cruoric or fibrinous clots, frequently lining the altered wall, may at a given moment engender emboli. The same process is quite often observed with the aged in the auricle. More frequently the difficulty is with a vein; its walls, invaded by a microbe, are inflamed, become rugged, and lead to the formation of a clot. The blood, stagnating behind this obstacle, coagulates in its turn, and engenders a secondary soft clot, the so-called elongated clot, which will extend to the point where the vein joins a main trunk. It will extend even beyond the junction, penetrating into the lumina of the vessel; in this way it forms a projection compared to the head of a nail, which, constantly beaten by the blood current, will easily be detached. In other cases there is an adhesion of one of the pri- mary or secondary clots, which is not sufficiently firm, and often, at the time when the patient is about to recover, when he moves and begins to rise, the clot breaks up. More or less voluminous fragments are detached and, being thrown into the circulation, give rise to embolism. Other varieties of emboli may be produced in the blood. Altered FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 341 red blood corpuscles represent veritable foreign bodies that will go to plug capillaries and occasion in the organs the most varied lesions. This is observed in cases of poisoning by oxide or sulphide of carbon, chlorate of potash, or chloroform. If the destroyed corpuscles are somewhat numerous, extended lesions are produced in certain viscera. In this way are explained the small centres of cerebral softening which occur quite frequently in intoxication by carbonic oxide. Globular emboli are produced also in extensive burns and frost- bites, and explain certain phenomena. In the focus, the red cor- puscles are altered, destroyed ; when carried by the blood current, they produce embolism. Their action is completed by the hematoblasts which contribute to the formation of venous thromboses, followed secondarily by visceral emboli. Matters derived from the red corpuscles may form emboli, as occurs, at least, in cases of malaria. Without admitting, with Fre- richs, that the genesis of the pernicious manifestations is due to pigmentary emboli, we must recognise that the pigment emanating from the spleen and from the marrow of bones may induce various alterations in other organs. Inanimate emboli, engendered outside of blood vessels, are repre- sented, first, by solid foreign bodies; this variety has but an experi- mental interest. In order to study the mechanism of emboli, experi- menters have repeatedly injected into the vessels little balls of wax and inert powders, especially lycopodium powder. An interesting group is represented by the cellular emboli that originate within the economy; they are due to the penetration of dead cells or even tissue fragments into the vessels. This is particularly observed as the result of great traumatisms. In cases of hepatic contusion particles of the wounded gland were seen to be carried to the heart and pulmonary artery. Similar phenomena have occurred in cases of puerperal eclampsia and have been explained by the existence of a hemorrhagic hepatitis. Euge has called attention to the emboli of cerebral matter which may occur in the lungs of the newborn, when the head has been strongly compressed by the forceps, especially in cases of narrow pelvis. In general, simply the contents of the cells, especially the fat, are thrown into the circulation. In this manner, according to Yirchow, are produced, during con- finement, fatty emboli in the kidney and lungs; they are supposed to be due to contusions of the cellular tissue of the abdomen and vagina. At times the fat starts from an organ that has undergone fatty degeneration — from the liver, for example — and gets fixed in a branch of the pulmonary artery or in the kidney. Fatty emboli are 342 GASEOUS EMBOLI particularly frequent in the lesions of the osseous system. They are produced in all fractures, according to Scriba. More frequently, they originate from osteomyelitis. Of slight gravity when they are not abundant, they may, when repeated, produce pulmonary accidents and sometimes entail speedy death. Fatty emboli have been observed also in diabetes, but their mech- anism is not understood; according to Hamilton and Saunders, ace- tonaemic coma is to be attributed to them. Gaseous emboli are nearly always exogenous. They have some- times been produced by the surgeon during a transfusion or an intra- venous injection. If the amount of air introduced is not too consid- erable, there results no harm whatever; if the air enters suddenly and in great quantity, the patient succumbs within a few minutes. Similar accidents have occurred when, in the course of an operation, one of the jugular veins is cut and, being maintained gaping by the cervical aponeuroses, suffers the effects of thoracic aspiration: the air enters into it with a special hissing sound. The same phenomenon has been observed in the uterus in cases of placent praevia : the air penetrates through the gaping sinuses. In some exceptional cases gaseous embolus has been endogenous. Jurgensen has seen, in the course of a round ulcer, gas penetrating the vessels; he was able, during life, to recognise its presence in the left temporal and the external jugular. Animate Emboli represent a group still more important than the one we have first studied. They explain the propagation of animal parasites, such as hydatid, strongylus, filaria, or Distoma Jiepaticum. In cases of hydatid the embryo passes from the digestive canal into a branch of the portal vein, and it is by a true embolic process that it will go to fix itself in the liver. The role of embolism in the evolution of lesions produced by vegetable parasites is not less notable. Let us take, for example, actinomycosis: the primary focus may give rise to secondary, sometimes multiple lesions, which in some cases are sufficiently numerous to make us think of pyaemia. The same is true of cases of aphtha, and this result is comprehensible, since Wagner has shown that the oidium sends out projections into the vessels of the mucous membrane. In this way is explained the formation of visceral foci, as such examples have been recorded by Zenker and Eibbert. But it is especially in the generalization of infectious lesions that embolism intervenes. If we can no longer admit, with Toussaint, that microbes cause death by plugging the capillaries, it is certain that they often produce, by this mechanism, secondary foci. This is what FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 343 takes place in cases of pyaemia. Starting from a primary lesion, pathogenic agents are capable of penetrating directly into the blood; in most cases they first give rise to phlebitis, whose importance in the dissemination of lesions and the production of purulent infec- tion was noticed by old observers. The clot which microbes have colonized breaks up and its particles are thrown into the circulation. Microscopic emboli are produced which do not act only in a mechan- ical manner; they carry living germs which give rise to the develop- ment of secondary foci; the latter present the same character as the primary focus. In certain instances, when the secondary lesion communicates with the external air, germs proceeding from the exterior may ultimately be introduced and transform the purulent into a gangrenous focus. This sometimes occurs in the lung. Many other infections are propagated by the same mechanism. Such is the case with glanders and, particularly, tuberculosis. In the acute miliary forms, generalization is often consecutive to an old caseous focus; at that point is produced a specific phlebitis which permits the dissemination of the germs. By the same process cancer is propagated. Whether this disease be, or not, parasitic, it is certain that the neoplastic cells behave exactly as parasites. They penetrate the more easily into the ves- sels, as they possess, when young, amoeboid movements (Waldeyer). The study of the secondary cancer of the liver permits us to under- stand this process and to follow the evolution of the cells arrested in the capillaries of the organ; as it has been well demonstrated by Hanot and Gilbert, it is the wall of the capillaries that forms the stroma of the neoplasm. The same mechanism may be applied to other secondary cancers, notably to those of the lung. We could easily multiply the examples ; they establish that the secondary foci, through the cells which they contain, repeat the primary focus, and, by their structure, recall the anatomical character of the organ in which they are developed. Course of EmholL — Whatever their nature, emboli follow a route traced in advance and governed by the laws of the circulatory me- chanics. From this point of view they may be divided into three groups: arterial emboli, pulmonary emboli, and emboli of the portal system. Arterial emboli start from some lesion of the pulmonary veins, of the left heart, of the aorta or one of the vessels emanating from it. If, as is most frequently the case, they are born before the aorta or at its origin, they pass generally into the left common carotid, whose direction continues that of the arch; they stop in the Sylvian 23 344: COURSE OF EMBOLI and produce right hemiplegia with aphasia. This takes place in half of the cases. In other instances, continuing its route in the aortic trunk, the embolus is arrested in the splenic, in the renal, at times in the iliac artery, especially in that of the left side, the blood current being, it is said, hindered in the right iliac by reason of the passage in front of it of the corresponding vein. More rarely, embolism will occur in the subclavian or in the mesenteric arteries, or in the coeliac axis ; it has exceptionally been observed in the bronchial arteries, in the hepatic artery, in the arteries of the bones, of the spinal cord, etc. If the embolus has taken rise in the peripheral venous system — for example, in the femoral vein — it is readily understood that it will go through the inferior vena cava and, passing through the right heart, will enter the pulmonary artery and stop in the capillaries of the lung. In this way is produced pulmonary embolism in con- nection with the lesions of the peripheral veins or of the right heart. Lastly, if the embolus starts from the intestine, it will enter the portal vein and go to the liver ; then, if the hepatic barrier is crossed, it will follow the same route as in the previous case. There will be secondary pulmonary embolism. Such is, as it were, the normal course of an embolus. There are, however, cases in which the foreign body does not follow the blood current. Such are the cases of paradoxical emboli. The embolus, starting from a vein, instead of stopping in the pulmonary vessels, reaches the aortic system. This fact has been ex- plained in two different ways. Weber supposes the existence of par- ticular canals connecting the pulmonary arteries and veins, which canals, being larger than the capillaries, are easily traversed by small foreign bodies. Others have assumed a different mechanism, accord- ing to which the embolus, originally very small, passes the lung, then, by a mechanism similar to that of a snowball, accumulates fibrine and acquires a size larger than that of the vessels through which it has passed. It seems, at present, that another explanation is to be accepted. Since the researches of Zahn, it is established that the foramen of Botal is not obliterated in one fifth of normal individuals (139 times out of 711 hearts examined). A communication, therefore, persists between the two auricles, which fact explains how an embolus caai easily pass from the pulmonary into the general circulation. Finally, there are described, under the name retrograde emholi, those whose course is in an opposite direction to the blood current. These are explained by the disturbances produced at the moment of thoracic aspiration, and particularly by efforts of coughing; it is thus FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 345 conceived how microbic emboli are quite often engendered in the hepatic veins. Lymphatic Emboli. — Side by side with blood emboli may well be placed lymphatic emboli. The latter may, from the standpoint of their nature, be divided into mechanical and animate. Among the former, we shall note only the colouring matters introduced beneath the skin by tattooing, and particles of carbon and dust inhaled by the lungs. Being carried into the lymphatic current, these small for- eign bodies are stopped in the glands. These organs thus play a protective part for the organism. Their intervention is still more marked in infections; the lymphatic glands often oppose to microbes a very resistant barrier. In the case of malignant pustule, for in- stance, the disease remains local and curable if the glands corre- sponding to the inoculated region resist; if they are crossed, blood infection is produced and entails death. Likewise, in tuberculosis, adenopathies tend to prevent the dissemination of the bacilli ; in many apparently healthy subjects there are found in the tracheo-bronchial glands tubercle bacilli which remain located there without giving rise to any bad results. The invasion of the glands, in cases of cancer, is explained by the same mechanism, and finds also its reason for being in a tendency of the economy to circumscribe the disease. Too often, however, the invasion of the glands is the starting point of new lesions; the neo- plasia diffuses out of the l3nnphatic apparatus; in this way cancerous foci may be produced in the pulmonary hilum, consecutively to adenopathies of the same character. Let us note, finally, that retrograde emboli may occur in the lymphatic as well as in the blood system; they are met with in the thorax, and are supposed to account for certain cases of pulmonary cancer. Effects of Embolism. — The effects of embolism vary according to the point where stops the foreign body. Arrest may occur in the heart, especially in the right heart. In this case sudden death is fre- quently observed. A reflex syncope is produced, owing to a violent excitation of the endocardium. More frequently the foreign body reaches the pulmonary artery. The effects vary with its size. If its proportions are considerable, the individual may succumb suddenly; a s5rQcope is produced by a reflex action starting from the liver. If the embolus is small, it stops in a branch of the pulmonary artery; the occlusion of the latter is followed by an intraparenchym- atous hemorrhage known as pulmonary apoplexy, or, still better, hemoptoic infarctus. 346 EFFECTS OF EMBOLISM In the majority of cases the infarcts are multiple, more numer- ous in the right than in the left, mostly in the lower and posterior parts of the lung. When they are cortical they have the form of a cone whose base is situated beneath the pleura; they are rounded in the interior of the parenchyma. These infarcts are easily recognised by their dark colour, comparable to that of truffles, and by the resist- ance they offer when palpation of the lung is practised. Three theories have been put forth to explain their formation. Virchow assumes a diapedesis of red corpuscles, Cohnheim a vascular rupture resulting from the venous stasis. Ranvier, whose opinion is generally admitted, thinks that there occurs a necrobiosis of the arterial wall, and, secondarily, a hemorrhagic sweeping off; it is thus conceivable that there should pass twenty-four to thirty-six hours between the occlusion of the vessel and the hemorrhage. The pulmonary infarcts are expressed by two classes of symp- toms; some of them make us suspect the lesion; the others permit us to affirm its existence. Among the signs of presumption we will mention dyspnoea, which sometimes assumes disquieting proportions. The physical signs are of little importance: at times a focus of rales with small bullae is found, and at other times a silent zone surrounded with small rales, and sometimes a murmur is heard. The true symptom, that which permits recognition of the lesion, is hemoptysis. The sputum of the patient is thick, dark, viscous, non- aerated, adhering to the cuspidor, and exhaling a sour odour com- parable to that of antiscorbutic sirup. This expectoration, so char- acteristic, lasts for five or six days, even when embolism does not recur. It differs considerably, therefore, from the bronchial hemop- tysis of the consumptives, which is characterized by the rejection of a red, aerated, spumous blood, and not continuing when hemorrhage has ceased. It may occur, finally, that the emboli be altogether minute ; they occasion in the lungs small punctiform hemorrhages, one interesting variety of which constitutes the festooned diffuse infarctus of Renault. These lesions are not rare in cardiac patients, and are expressed simply by the appearance or aggravation of dyspnoea. The various lesions produced by the emboli of the lungs may be- come cicatrized and infiltrated with calcareous salts. At times they are invaded by external microbes, become softened, or even — though this is exceptionally the case — undergo gangrenous transformation. The effects of arterial emholism differ from those observed in the system of the small circulation ; they vary also according to the organ under consideration. FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 347 In most cases, as already stated, the embolus enters the left com- mon carotid and is stopped in the Sylvian. If the occlusion occurs in the principal trunk, an extensive softening is the result; the hemisphere is transformed, as it were, into pap; the central parts, optic thalami, and corpora striata alone resist, because their circula- tion is assured by special blood vessels. In general, only one branch is affected. If it is one of the short arteries, destined for the cortical part of the brain, a superficial patch of cortical softening is formed; if a long artery is struck, the focus occupies the white substance. Clinical as well as experimental researches permit us to follow very regularly the mode of formation of the lesions. In the beginning a red softening is produced; subsequently, the colouring matter of the blood being transformed, the focus becomes yellow, and finally white. In the end, if its seat is on the surface, it assumes the aspect of yellow, hard, sclerous patches. If it is central, it suffers a more marked softening; the white substance liquefies and presents the appearance and consistency of lime milk ; at times the lesion becomes encysted and forms a sort of foreign body. Large cerebral emboli may give rise to a rapidly fatal attack of apo- plexy. Those of medium and small size often produce a transitory apo- plexy, followed by permanent disturbances which vary according to the site of the lesion; aphasia and paralysis of the face or the extremities are connected with the cerebral department which has been affected. Lastly, when emboli are extremely minute, only headache, dizzi- ness, and some mental disturbances are observed; however, should the emboli be repeated, they may entail coma and death. Of the other arterial emboli, we may cite that of the central artery of the retina, which is expressed by a sudden amaurosis ; on ophthal- moscopic examination, the papilla is found pale and the arteries con- tracted. If the embolus passes into the abdominal aorta, it may reach the spleen, where it produces an infarctus, expressed by a sufficiently in- tense pain in the left side. In other instances it stops in the kidney and causes lumbar pain and mild hematuria. Among the other vessels that may be affected, we will first cite the coronary arteries of the heart. If the embolus is small, it gives rise to angina pectoris, this syndrome appearing whenever cardiac circula- tion is hindered. If the embolus is more voluminous, the occlusion of the coronary results in sudden death by rupture of the heart. Finally, when the artery of a limb is obstructed, circulation stops there, the pulse is suppressed, the skin grows cold and pale and is in- vaded by external germs, which produce in it dry gangrene. 348 NERVOUS CONNECTIONS Among the emboli that act mechanically, the fatty and the gaseous deserve special mention. Fatty emboli are observed consecutively to osseous lesions. When a great traumatism has caused some serious fracture, fat often passes into the blood in considerable quantities; some of it stops in the lung, the remainder invades the general circulation, and may obstruct the vessels of the brain or bulb. Under these conditions a violent dysp- noea is observed, which, after a sudden onset, progressively increases and ends in death. Its differential diagnosis from nervous shock lies in the fact that in the latter ease the manifestations are at their maxi- mum at once, while in the former they progressively aggravate. Gaseous emboli are produced particularly when, in the course of an operation, air penetrates a vein. A characteristic hissing sound is then heard, the patient grows pale, and dies suddenly. If life is prolonged, there is sometimes heard, on auscultation of the heart, a special murmur (the so-called bruit de moulin) produced by the mingling of air with the blood. Generally attributed to obstructions of the pulmonary vessels, the symptoms of gaseous emboli have been ascribed by Brown-Sequard to bulbar emboli. It is certain that when operating upon animals we notice that the gas readily passes through the lung and invades the general circulation. The experiment succeeds well with the dog; by operating slowly one may, without causing any accident, introduce into the veins a considerable quantity of air. After the animal is killed, it is found, at the autopsy, that all the arterial system is filled with small gas bullas. Leaving aside the paradoxical and retrograde emboli, we resume in the tabular representation on the opposite page the course and effects of the principal mechanical emboli. Nervous Connection's Along with functional synergies, contiguity of organs, and vas- cular relations, we must take into account, as already stated, the con- nections established by means of the nervous system. After the de- tails given in connection with nervous reactions, we shall only briefly consider this last part of our subject. The lesion of an organ may, by compressing a nerve, give rise to disturbances in distant parts. A tumour of the mediastinum, an aneurism of the aorta, affecting the sympathetic or the recurrent, produce pupillary or laryngeal disorders, which might lead the inex- perienced to an error of diagnosis. In other instances the question is one of reflex phenomenon, ter- minating in motor, sensory, vasomotor, and secretory disturbances. FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 349 .5 .5 •1 ^ 'm 'C M ^ a cS • !3 O) I and hemopt blood. Asth :e dyspnoea. o "3 6 •r-l hemiplegia. L the left side 03 a o i-H -^3 ••-i (D P -i.3 a na pectoris, den death. a Oh e3 •S) -g ?3 I -S S pd ® e bo _2 «2 CQ C 08 -t-3 •^ 'S ,o i <5 Oh 13 CQ 03 bo P4 a S p B h^ '■^"r — Y • 02 a CO P^ bo ti C3 •cH d 1 . "3 1 "S O CO softenin nfarctio d o -1-3 08 emyocai of heari infarcti hemorr nfarctio 1 <1 ■g O Cerebral Splenic i c P^ Infarctusinth Rupture C Pulmonary ( Punctiform Hepatic i <'-^. -> — ^ -^r-- CO ^ o > *.H 1 < > d ts^ M {A -H > 3 03 • ^ IX) t-l O E? © H -fc3 ( 13 > -iS ■ r-^ Vl -4-3 >% -4-3 ti <» nary a Liver. * < r—l htSy inic a tS s 03 r£3 ( 5 +3 *( [ l8 03 li ^ 03 j -< o 3 t^ s 08 p^ P 3 ^ fe c ^ ^ 1—1 03 C ;> . -« jr , v-*-v-«.^ m ^ a .a a o • ^ -t^ H "S 03 p° e >■ >-. 1 s. oj times orta. m o s o ^ w s ^ ( O z; g e3 o ^ en •1.3 'a eart oft 1 t— 1 bo rP ^ ( 2 1 P-I 350 NERVOUS CONNECTIONS Thus, a neuralgia of the trigeminal nerve excites reflexly spas- modic contractions of the facial nerve (or, as is said, le tic dou- loureux of the face). The excitation starting from a viscus, from the biliary or urinary passages, gives rise by reflex action to disturb- ances in the muscles concerned in the act of vomiting. The excitation may also produce paralysis or inhibitory acts — e. g., syncope or sensory disorders — which are especially observed in predis- posed subjects — for example, in hysterical subjects — and are ex- pressed in their highest degree by a sensitivo-sensorial hemianaes- thesia. We have already repeatedly shown the frequency of vasomotor reactions in distant parts: redness of the cheek in pneumonia, pul- monary congestion in hepatic colic, and the vascular spasm of the myocardium resulting from excitation of the heart, lung, or stomach, and expressed by an attack of angina pectoris. Do we need to recall, among secretory disturbances, the salivation of gastric affections, the anuria consecutive to abdominal traumatisms, the polyuria or oliguria in sciatic neuralgia, according as the pain is slight or intense ? We could cite also various general reactions and psychical disturbances. In all these cases the manifestations seem to have no relation with the organ affected, but are easily explained by the mechanism of nervous reactions. Kesume. — If we consider in their ensemble the various results above recorded, we will understand that a lesion never remains local. As soon as a disturbance is produced, it gives rise to secondary mani- festations, which become themselves the starting point of reactions of a third order, etc. Let us take up an illustration to which we have often referred. A person has an attack of hepatic colic: the local disturbance causes changes in the circulation of the lung; then the heart is influenced, and auscultation reveals an exaggeration of the second pulmonary sound and a right galloping murmur. The heart may become insuffi- cient and dilate ; in this manner a little spell of asystole occurs, giv- ing rise to new symptoms, notably to oedema in the lower extremities. Likewise, it could readily be shown that the kidneys give rise to cardiac disturbances, which in their turn influence the lungs, the liver, and the kidneys themselves. Thus, the phenomena becoming more and more complicated, clin- ical types are constituted which are never so simple as might be sup- posed from the systematic descriptions found in treatises on pa- thology. In dealing with a patient, the duty of the physician is, therefore, to trace the succession of the various events. Only by an attentive FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 351 study and minute examination is it possible to reconstitute the mor- bid train and recognise which organ has been the starting point of the phenomena observed. Fever The connections which unite the different parts of the organism account also for the development of general symptoms in the course of the most varied affections. The secretory modifications, the dry- ness of the tongue, oliguria, respiratory or cardiac disturbances, nerv- ous manifestations, and notably delirium, are to-day easily explained. All these symptoms are due to reflex acts, and especially to the im- pregnation of the organism with soluble substances. The same theory is applicable to the changes produced in thermo- genesis. Sometimes, and this is most frequently the case, the tem- perature rises; it is then said that there is hyperpyrexia (hyper- thermia) or fever; sometimes it falls, that is hypothermia terminat- ing in grave cases in algid collapse. The expressions hjrperthermia and fever are not altogether synony- mous. The term hyperthermia means simply elevation of tempera- ture. The term fever is applied to a whole series of phenomena of which hyperthermia constitutes but one element. It implies the co- existence of the thermal elevation with secretory and nervous dis- turbances. The distinction is somewhat subtle. Of course, we must leave aside the hyperthermia produced by a sojourn in the oven. But when thermal elevation is of internal origin, the distinction between hyper- thermia and fever is difficult to establish. Without dwelling upon this question, which would carry us too far, we shall confine ourselves for a moment to the consideration of the mechanism of febrile hyper- thermia. Is fever, according to the old expression, a heat against nature? For our part, considering morbid phenomena as identical in their essence with normal phenomena, we can not accept such an idea. Fever appears to us to be an exaggeration of natural heat; and this view is corroborated by numerous facts forming a transition between that which might be called physiological fever and that which is des- ignated as pathological fever. In fact, let us consider the mechanism which explains animal heat and accounts for its regulation. It is known that the temperature of animals is higher than that of the surrounding medium, because living matter, in manifesting its vital activity, renders apparent the heat which it had stored up. The muscles and glands thus disengage a quantity of heat the more marked as their function is the more active. 352 FEVER The digestive canal, as a result of the chemical transformations and microbic fermentations taking place in it, also furnishes the organism with heat. Heat thus produced is dissipated by cutaneous radiation and by evaporation on the surface of the skin and certain mucous mem- branes, notably of the mouth. When the production or the elimination of heat varies, an auto- matic mode of regulation intervenes ; the nervous system increases or diminishes the organic combustions, or, through vasomotor modifica- tions, favours or hinders its loss. At the same time soluble substances, emanating from the cells and tissues, pass into the blood, and, directly or indirectly, through the nervous system, modify the production or the dissipation of it. However perfect the regulation may be, it may happen, even under physiological conditions, that the organism should fail to maintain a perfect balance. Therefore transitory thermal rises occur as the result of some violent muscular exertion, laborious digestion, painful excitation, prolonged intellectual contention, or emotion. At other times, hyperthermia results from too energetic a reaction — e. g., an individual is suddenly submitted to cold ; in order to remedy the loss of heat, the organism calls into play too intense reactions, and the hypothermia produced by the cold is followed by an exaggerated hyperthermia. In order, however, that the nervous system may be capable of raising the temperature by reaction, the excitation must not be too violent; for, in the latter case, inhibitory acts are pro- duced which terminate in coldness and collapse. Nervous shock is a well-known illustration of this eventuality. If we consider pathology, we see that the different varieties of fever may be brought under two pathogenic groups : fever hy nervous reaction and fever hy intoxication. We shall not dwell upon the former, which we have repeatedly studied. Three varieties of it may be admitted. These are, in the first place, the algid fevers, resulting from painful excitation. The so-called hepatalgic fever, accompanying hepatic colic when no symp- tom points to an infection of the biliary passages, is the best ex- ample of such fevers. It has also been experimentally produced in the dog by excitation of the biliary passages. We admit also reactionary fevers; consecutive to some hypothermizing action — for example, an individual has ingested carbolic acid; his central tem- perature falls to 35° C, but a few hours later it again rises and reaches 39° or 40° C. The third variety comprises the febrile move- ments caused by traumatisms bearing upon certain parts of the nerv- ous centres; their reality has been demonstrated by a few observa- FUNCTIONAL SYNERGIES AND MORBID SYMPATHIES 363 tions, notably by a case of meningeal hemorrhage recorded by Josue, and by experimental researches — for example, those by J. F. Gnyon. Hysterical fever may be embraced under this variety. Fevers of toxic origin are by far the most important. They include three varieties. At times febrile movement is consecutive to the introduction into the organism of completely formed toxic substances proceeding from without. The number of hyperthermizing substances is quite restricted; we shall cite strychnine, caffeine, and curare. At other times, fever is due to auto-intoxication, and, finally, to microbic intoxication. The existence of fevers hy auto-intoxication has been demonstrated by numerous experiments and rigorous clinical observations. With this group should be classed the fever of gouty and chlorotic patients, the fever consecutive to the absorption of traumatic sanguineous exu- dations, and to attrition of tissues, certain forms of fever due to over- exertion, and the fever of asphyxia. The fevers by microhic intoxication evidently constitute the most important class. As all the other infectious manifestations, fever depends, not upon the direct action of microbes, but upon the action exerted by their soluble products. It must be noted, however, that most of the microbic toxines, when injected in high doses, instead of raising, lower the temperature ; they entail death in algid collapse. This result is important, in the first place, because it explains certain clinical facts ; then, because it leads to a hypothesis regarding the pathogenesis of fever. It may, in fact, be questioned whether toxo-microbic fever is not due to a reaction of the organism, whether the soluble products of pathogenic agents do not always tend to lower the temperature. If such is the fact, they only excite fever as a reaction of a second order, which expresses a curative effort of the organism. Accordingly, fever is not directly caused by the microbe, but represents, on the contrary, a reaction against hypothermizing substances, and should, when not exceeding certain limits, be considered as salutary. It expresses, at all events, a sufficient energy on the part of the organism, and this view seems per- fectly in harmony with facts. One might, in support of this hypoth- esis, recall the frequency of chills in the beginning and in the course of infectious diseases. Chills represent a mode of reaction to which the organism resorts when it is cold: it is a means of getting warm. Its appearance would therefore be incomprehensible if toxines were heat-producing substances. Nothing is simpler, on the contrary, if we admit that microbic poisons tend to lower temperature ; the organ- ism reacts by chills and by hyperthermia. It is well to note, finally, that the gravest and the most rapidly fatal infections lower tempera- 354: FEVERS OF TOXIC ORIGIN ture. This is what occurs in cholera or even in choleralike diarrhoeas ; fever is, in this case, of a good diagnosis. Similarly, in most of the experimental infections, temperature sinks below the normal when precursory symptoms of death appear: at that moment the organism gives up the struggle and undergoes, without reacting, the action of hypothermizing toxines. If it is at present easy to conceive the pathogenesis of fever, it is quite difficult to explain its pathological physiology. It seems demonstrated that thermal elevation results from an augmentation of tissue wasting, but this tissue wasting does not take place in a regular way. In fact, it is seen from the researches of Dr. A. Eobin that if oxidation sometimes increases in simple phlegmasias, it always diminishes under typhoid conditions. It must therefore be admitted that tissue wasting is vitiated, and this is in harmony with all the results that we have thus far reported with respect to the chemical and toxic characteristics of the blood and urine. At the same time that the production of heat is increased, its dissipation also seems to be increased. There is, then, exaggeration of the two normal processes which assure thermal regulation; if the latter is disturbed, it is because production has exceeded dissipation. Such is the general idea one may form of fever, or, more exactly, of variations in plus or in minus of animal heat. The history of thermal variations is certainly one of the most interesting problems raised by the study of functional synergies ; it is the most remarkable illustration of morbid sympathies. CHAPTER XX EVOLUTION OF DISEASES Evolution of infectious diseases — Incubation : its variations — Invasion — Stationary period — Local and general manifestations — Different types of fevers — Clinical forms — Termination of infectious diseases: crises — Convalescence — Relapses — Recurrences — Passage of infections from an acute to a chronic state — Death in infections — Evolution of noninfectious diseases — Evolution of intoxications and visceral infections — Intermittence and periodicity — Latent diseases— Me- tastases — Recovery and death in general. We have repeatedly seen that disease depends upon two factors, namely, the action of a pathogenic cause and reaction of the organism. The action is immediate; the reaction may be delayed. Let ns con- sider, for example, the traumatic agents. The effects of these agents are produced instantly — e. g., fracture, dislocation, or hemorrhage is observed at once. It has long been recognised, however, that these are not instances of disease properly so called, and a distinction has justly been made between wounded and diseased individuals. Traumatism may, nevertheless, provoke either early or tardy reactionary manifestations. Syncope or nervous shock develops so rapidly that the interval between action and reaction — ^i. e., the latent period — passes unnoticed. On the other hand, traumatism is the point of departure of phenomena of cicatrization which are of more tardy appearance. Cellular proliferations are produced, leucocytes in- tervene, and thus reparation begins after a certain period of latency. In studying the physical agents we observe phenomena quite similar to the preceding. Under the influence of a very energetic agent, immediate destruction may occur. For example, an ignited mass fall- ing upon the integuments at once produces carbonization. At the same time instantaneous reactions are observed. Such, for instance, are nervous shock or syncope, occurring in individuals falling into either icy or boiling water, or who have been shocked by an electric current. More or less slow reactions are oftener produced by physical than by mechanical agents. In cases of sunstroke, erythema does 355 356 EVOLUTION OF INPECTIOtTS DISEASES not appear immediately. On the contrary, a certain period of latency elapses between the action of the cause and the development of symptoms. With chemical agents the effects are still slower. Without doubt certain caustics immediately produce destruction of the tissues, but this is exceptional. In most cases the alterations are slowly produced, as is noticed when a cauterant or vesicant is applied to a patient. The phenomena are still more striking with toxic substances. If we except a few extremely violent poisons, such as prussic acid, quite a long time elapses between their introduction and their effects. In cases of slow poisoning — ^i. e., repeated ingestion of small doses of a toxic substance — disturbances may not appear until the end of several days, months, or even years. The disturbances are mani- fested not because the dose has been increased, but because cumulative effects and inappreciable deviations from the normal have become apparent as the result of summation. A period of latency is also observed in acute poisonings. This period corresponds to the time required for the absorption and passage of the poison through those organs which may annihilate it and its arrival at those organs upon which it will exert its action. In certain instances the phenomena are still more complex. The poison, even when directly introduced into the blood, does not act immediately. Such, for example, is the case with phosphorus. In this instance a secondary auto-intoxication is established. The cells, having been disturbed in their function, produce toxic substances which give rise to symptoms. In other words, the poison acts in an indirect manner. This conception, which is as yet merely an hypothesis, has been extended to microbic poisons. Courmont maintained that the toxine of tetanus modifies the life of the cells, which, acting under its in- fluence, produce a convulsive substance. It is true that this theory has been severely criticised and is not as yet well established, but it is interesting and worthy of note. Parasitic causes, of which we must here say a word, are never productive of immediate effects. There is always a period of latency during which the pathogenic agent develops. It is for this period that the term incubation must be reserved. This expression is not applicable to other processes; it indicates that multiplication of the morbific agents is taking place. Thus, when a cause acts upon the organism, two events are pos- sible. These are: 1. Immediate effects are produced, as is nearly always the case EVOLUTION OF DISEASES 357 with mechanical agents, often with physical agents, and sometimes with chemical agents, but never with animate agents. 2. A period of latency exists which is rare with mechanical agents, frequent with physical and especially with chemical agents, and con- stant with parasitic agents. In the last case, and in this only, the period of latency should be designated as incubation. In order to avoid confusion by a too general study, let us first consider a well-defined group and note in what manner evolution occurs in infectious diseases. Evolution of Infectious Diseases In the evolution of infections, four stages or periods are generally admitted. These are: Incubation, which corresponds to the development of the patho- genic agents. Invasion, which indicates the beginning of reaction on the part of the organism. Stationary period, during which the disease remains stationary, presenting only more or less marked oscillations of aggravation or amelioration; and Decline, which is a rather inconstant period. We will now take up the study of each of these periods. Incubation. — As already stated, incubation corresponds to the time elapsing between the deposition of a morbid germ in the tissue and the first appearance of local or general manifestations of the disease. This definition is applicable only to hetero-infections, and must be slightly modified when the process is one of auto-infection. In the latter case the germ is not deposited in the organism from without, and therefore the stage of incubation begins at the moment when the dormant microbe, until then inoffensive, becomes pathogenic under the influence of any excitation whatever. It can readily be understood that if it is difiicult to determine the time of incubation in the former case, it is almost impossible to do so in the latter. During the period of incubation the organism does not always remain passive; on the contrary, it may endeavour to destroy the microbes invading it. Should it fail to do this, however, the disease becomes manifest. It is therefore incorrect to say that infectious disease is a reaction provoked by the introduction of a microbic agent, since morbid reaction does not necessarily occur in all cases. The microbe may be destroyed or remain quiescent at the point where it was deposited. In order that manifestations may appear, a period of preparation is required which represents a first defeat of the 358 INCUBATION organism. We are thus led to admit the occurrence of three succes- sive stages at the beginning of all infections, namely, introduction or exaltation of the microbe; a latent period of development, corre- sponding to incubation ; and a reaction of the organism correspond- ing to invasion — i. e., to the beginning of the disease. The period of incubation may be completely in abeyance and de- prived of all morbid manifestation. Then, at a given moment, reaction is produced, often quite suddenly. Such, for example, is the beginning of lobar pneumonia. It is a very curious fact that the microbe should be able to continue secreting its toxines in a progressive degree without provoking any disturbance on the part of the organism, and that the organism should act so tardily when it is, as it were, saturated with soluble toxic products. In other instances the be- ginning of the disease is manifested in a slow and insidious manner — e. g., as occurs in typhoid fever. Then the transition from a normal to a morbid condition is so insensibly effected that it is difficult to say at what moment the disease commenced. Even when the beginning is sudden it is often difficult, if not impossible, to determine the time of incubation, since we are not always able to decide as to the moment when contagion has taken place. Most frequently patients are unable to give any information. In the eruptive fevers— e. g., smallpox — ^it is very rarely possible to determine under what conditions contamination has occurred; in the majority of instances the disease seems to be spontaneously devel- oped. Observations made during three years in the hospital of La Porte d'Aubervillier give a total of 2,304 patients attacked with eruptive fevers. Minute interrogation showed that contagion could be traced in the following proportion: 21 per cent in measles, 12 per cent in scarlatina, 13 per cent in varicella, and 38 per cent in smallpox. Still, the fact remained that, in the majority of the cases, the information obtained was lacking in precision; it was impossible to determine exactly what day contamination had occurred. Finally, in the case of prolonged incubation there is always a question whether there has not been an ulterior contamination which has escaped notice. Consequently, in order to arrive at incontestable results, a series of circumstances that are seldom realized are required. The perusal of works published on incubation leads to the con- viction that an average duration, varying only within narrow limits, exists for the majority of diseases. It would be a grave error, how- ever, to overlook the fact that the period of incubation is at times shortened and at other times prolonged within considerable limits. Nothing in this regard is more demonstrative than the history of venereal diseases ; for it is in this class of affections that the moment EVOLUTION OF DISEASES 359 of contamination may be determined most exactly and that inter- pretation is easiest. With syphilis, for example, it is generally from twenty to thirty days after infecting intercourse that the chancre appears; this aver- age, which is sufficiently wide in its scope, does not, however, include those cases in which infection occurs at the end of ten days, nor those in which it has been delayed until the fortieth or even fiftieth day. The variability of this period is well illustrated by the fact that several indurated chancres, resulting from a single infection, may appear successively in the same individual at intervals of sev- eral days. The same variations occur in gonorrhoea. The average is from two to five days, but the discharge sometimes commences at the end of twenty-four hours or appears very tardily at the end of several weeks. In the latter case it is assumed that the microbes deposited in the balano-preputial furrow had not invaded the urethra until a certain time after coition. With the soft chancre incubation is more fixed and does not exceed twenty-four hours. This figure is confirmed by numerous inoculations practised upon subjects affected with suspicious ulcerations. Information is quite precise in cases of infection of traumatic origin. In the case of tetanus the period of incubation is from two to three days; but there are cases on record in which it is said not to have exceeded two hours. On the other hand, it has also been prolonged to thirty and thirty-five days. In hydrophobia the incubation period is still more variable, the average being thirty days, and the minimum fourteen. As to the maximum, a period of eighteen months has been admitted, although there are certain cases in which the period of incubation lasted two, three, and even four years. Erysipelas may be considered as occupying a position between traumatic diseases and those apparently spontaneous. Most of the classic treatises fix its period of incubation at three or four days, admitting that it may be reduced to two days or prolonged to twelve. In order to determine the duration of the period of latency, trau- matic cases must be considered. By an examination of 42 observa- tions we obtain the following figures : Incubation period from 7 to 18 hours 6 cases. 5 " 17 " 10 " 3 " 1 case. 24 24 « from 25 to 72 " " 4 to 8 days " 10 to 14 " 22 " 360 INCUBATION In eases of prolonged incubation it may always be questioned whether there has not been a second exposure. However, experi- mentation inclines ns to admit the accuracy of the figures furnished by clinical experience. The inoculation of a few drops of a culture of streptococcus beneath the skin of the ear of a rabbit is followed by the development of erysipelas after the elapse of a period varying from a few hours to eleven days. The study of nontraumatic diseases yields figures which are far more variable. Among the eruptive fevers, precise information is most easily obtained in smallpox. Its period of incubation is, on an average, twelve days, but it may vary between seven and fifteen. In scarlatina, Sevestre finds an almost invariable average of four to five days; but there are observations recorded in which the period of incubation lasted no longer than twenty-four (Trousseau), twelve (Sevestre), and even seven hours (Thomas). In other cases it has been prolonged to twelve, seventeen, and forty days (Eilliet and Barthez). The period of incubation seems to be shorter in surgical or puerperal scarlatina, in which it is hardly three days. This is probably due to the fact that traumatism lessens the resistance of the organism. The incubation period of measles is from eight to twelve days, with a minimum of four and a maximum of fourteen; that of rubeola is eighteen days; and that of smallpox from thirteen to nineteen days, etc. Of other infections we may mention diphtheria, which begins from two to four da)^s after contagion, and whooping cough, which appears from the second to the eighth day. It is stated that cholera has at times developed a few hours after contact, and that in typhus the attack has occurred even instantly. In such cases individuals approach a patient, feel a pain which alarms them, and are immedi- ately forced to lie down. The table on the opposite page, which indicates the average, maxi- mum, and minimum incubation periods, is based upon facts recorded by various authorities, upon statistics published by Williams on behalf of a London commission, and upon our own personal observations. Clinical experience suffices to establish that the duration of the incubation period is very variable, and experimental researches have demonstrated certain causes which precipitate or delay the beginning of a disease. Firstly, there is an idea which should never be lost sight of, and that is the variability in the action of viruses. Viruses may be divided into two groups — namely, fixed and variable. In this regard nothing EVOLUTION OF DISEASES 361 Incubation Anthrax Chancre, soft Cholera Diphtheria Erysipelas Glanders GonorrhcEa Influenza Mumps Malaria Measles Pest Rabies Rubeola Scarlatina Smallpox Sudor anglicus. . Syphilis Tetanus Typhoid (fever).. Typhus Vaccinia Varicella Whooping cough Average. 2 days, to 2 days, to 4 " 2 days, to 6 days, to 5 " to 5 " to 4 " 15 days. 6 to 10 days. 8 to 12 " Ito 3 " 20 to 60 " 18 days. 4 to 5 days. 12 days. 2 to 3 days. 20 to 30 " 2 to 3 " 14 days. 12 « 3 " 14 to 15 days. 8 days. Minimum. 1 1 1 2 7 24 day. days, hours. 1 (f) 2 days 1 day. 7 days. 99 hours. 4 days. 10 hours. 13 days. 5 " 7 hours. 7 days. 24 hours. 10 days. 2 hours. 2 days {% in 13 days. 2 " Maximum. months, to 7 weeks, days. 3 days. 3 " 6 " 15 " 22 3 1 5 30 Several months. 14 days. 4, 6 to 12 {1) days. 18 months. 21 days. 7 weeks. 15 days. (?) 50 days. 35 " 21 " 23 " 19 « 8 " is so instructive as the history of rabies. The variable virus is that found in an animal which has accidentally become rabid (rage des rues) ; the fixed virus is that which has acquired a definitely determined power by virtue of successive passages through animals. By inoculat- ing the virus into animals of the same species placed under the same conditions, the phenomena are made to appear after the elapse of a perfectly determined period of time. Such is not the case, however, in Nature, and the constant variations in virulence lead to modifications in the incubative period. The same result is observed in man. By virtue of its transmission by successive inoculations, vaccine has become a fixed virus ; its period of incubation is well-nigh invariable. In subjects vaccinated for the first time the eruption begins seventy-two hours after inoculation, and is well developed in the course of the fourth day. Even with this fixed virus, however, certain variations are observed. Dr. Saint- Yves Menard has kindly furnished us with interesting information upon this subject, which is as follows: The incubation period of vaccination quite often lasts four to five days, exceptionally six or seven. In this respect the following is a very curious result : Children are returned seven days after vaccination with a negative result ; they are vaccinated a second time, and in certain exceptional cases the first punctures as well as the second will be seen to be followed by the simultaneous development of pustules eleven days after the first inoculation. It 362 INVASION is thus seen that the vaccine virus is but slowly destroyed, and if the organism be profoundly modified by a new inoculation, such will suffice to cause the development of germs which seemed to have been destroyed. The soft chancre, which is transmitted by direct inoculation, has also acquired a sufficiently fixed power, exactly as in the case of ex- perimental virus. Therefore the lesion always begins to make its appearance twenty-four to forty-eight hours after infection. The occurrence of a longer period of incubation must be attributed to inaccurate observation. It can readily be understood that with viruses of variable potency the incubation period will be the shorter the greater the energy and number of microbes introduced. The period of incubation will also vary with the location of the wound. It will be longer if the affected region is provided with a dense cellular tissue and is poorly supplied with vessels and nerves. Such is strikingly the case in rabies. Finally, microbes develop more readily when they are introduced simultaneously with agents favouring their multiplication, such as irritating substances or other bacteria, even though the latter be simple saprophytes. As to the organism, all causes of weakening should be taken into account — extensive traumatism, laceration of tissues, modifications of the general condition by overexertion, excesses, alcoholism, intoxica- tions, and previous and present diseases. Lastly, we must not over- look the influence of moral impressions, whose power is well known with respect to rabies. For example, an individual who has been bitten by a rabid animal no longer thinks of his accident. All at once a word reminds him of the bite, and immediately manifestations of rabies appear and rapidly end in death. The duration of the period of incubation may also be modified by the responsive aptitudes of the subject. In persons with very sensitive nervous systems, the onset will be hastened. In this par- ticular case a short incubation period constitutes a favourable phe- nomenon. Invasion. — Invasion may be sudden, or slow and progressive. In the former instance the stationary period is quickly reached; in the latter it supervenes only at the end of a few days, and is thus pre- ceded by a prodromic period in which the symptoms are inadequate to determine the nature of the morbid process. As an example of infection with sudden onset, writers always cite pneumonia, and as an example of slow invasion, typhoid fever. These two illustrations are well chosen. Clinical phenomena are always so EVOLUTION OF DISEASES 363 variable, however, that exceptions may be mentioned. There are cases of pneumonia beginning in a slow and insidious manner, as often occurs in the aged ; and there are typhoid fevers which are mani- fested by a sudden onset, as is sometimes the case in children. It is not difficult to understand how a progressive invasion is effected. The noxious substances are secreted little by little by the microbes, become diffused in the organism and influence the cells; when the toxines are produced in greater amount, their constantly increasing accumulation gives rise to more and more marked dis- turbances. A sudden onset is more difficult to explain. Even in pneumonia it is possible that the morbid poison is secreted in a progressive man- ner, and at first sight the sudden appearance of the phenomena is not understood. The differences are probably due to the mode of action of poisons. This view is, of course, purely hypothetical, but it is supported by some facts. A first result which must be taken into account is that most microbic toxines, like the poisons properly so called, and notably alkaloids, exert no immediate action. Even when they are introduced into the blood no immediate symptom is produced, but after a period of latency of varying duration the morbid phenomena suddenly appear. This experimental result has a very important bearing upon our subject. In fact, it may be assumed that in certain cases microbic poisons act early and rapidly as they are formed. Under such conditions, disturbances begin slowly and follow a progressive course. In other instances an oversaturation of the organism will be required in order for reaction to be produced. This is the first effect of cumulative doses. Whatever be the mode of invasion, the general phenomena first bear on the nervous system. If invasion is slow and progressive, the disturbances are accentuated little by little. These are malaise, head- ache, dizziness, weakness of the extremities, and incapacity for all muscular or mental exertion. Delirium, if present, is of the mild, quiet type. Sleep is disturbed only by nightmares or vagaries. On the whole, the S5rmptoms are not intense, but are established gradually and aggravated in a slow and often regular manner. On the other hand, if invasion is sudden, the nervous symptoms will be intense and disquieting from the first. In fact, the pro- cess is of the nature of a true outbreak. These has been a silent accumulation of toxines, and all of a sudden a violent, impetuous, un- expected reaction occurs — i. e., intense chills or, in children, a con- vulsive attack. At the same time fever develops and rapidly reaches 39° or 40° C. Headache is intense, and delirium may be excessive from the first. Severe delirious phenomena are mostly, we might say 364: INVASION nearly always^ observed in diseases characterized by sudden onset and occurring in predisposed individuals. Delirium tremens is altogether exceptional in typhoid fever; it is not so rare in smallpox and ery- sipelas, but it is especially frequent in pneumonia. It expresses a profound nervous perturbation, and occurs in alcoholic subjects as the result of a toxomicrobic shock — such, for instance, as is induced by violent traumatism. Likewise, in diseases characterized by sudden invasion, a series of symptoms which might, perhaps, be connected with visceral lesions, but which seem to be dependent upon a disturbance of innervation, is observed from the very beginning. These are, vomiting without any apparent alteration of the stomach; diminution in the quantity of urine, at times transitory suppression, without the kidneys as yet being affected; intense dyspnoea, unexplained by the condition of the lungs; acceleration of the pulse, and arrhythmia, which are in nowise dependent upon cardiac lesions. There is a striking discord between the functional and the anatomical conditions. Thus far we have considered only the general symptoms. The local manifestations may appear from the beginning; at times they precede the general reactions, sometimes they accompany them, and sometimes they run their course without giving rise to any general phenomena. In most cases the local lesions present a course which, even when rapid, is generally progressive. In cases of phlegmon or erysipelas, as well as in those of pneumonia, it is possible by means of inspection or auscultation to follow the extension of the process. Sometimes, however, the local lesion develops almost instantly. This occurs in young subjects endowed with a nervous system react- ing quickly and energetically. Such, for instance, is observed in children in conditions described by clinicians as acute pulmonary con- gestion. The child is suddenly seized with fever, and auscultation practised immediately reveals an intense blowing murmur. On the following day ever3rthing is again all right; the fever has subsided, the murmur is no longer perceptible. These facts, which have been so well studied by Bergeron, Cadet de Gassicourt, and Hirne, must at the present day be considered as examples of veritable abortive pneumonias. Immediately upon its arrival the microbe gives rise to violent reactions, which often result in the instant arrest of its course. The excitation of the nervous system is expressed by a con- gestive fluxion which arrests the infection. In the same order of ideas, although their meaning is more difficult to understand, we may mention herpes, which is so frequently observed in infections, and urticaria, which appears especially in cases of digestive disorders. EVOLUTION OF DISEASES 365 Evidently the phenomena of fluxion are alone capable of making a sudden appearance; the other reactionary symptoms develop more slowly, and if at times they appear suddenly it is because their be- ginning has been effected in a gradual manner, and, having already advanced to a certain degree, they become manifest only when they abruptly provoke morbid reactions. There is often a lack of harmony between general and local mani- festations. In a certain number of cases the two orders of symptoms begin simultaneously and manifest the same mode of invasion; in others the disease is at first characterized by one or the other series of symptoms; in still other instances local reactions are progressive, while general manifestations are abrupt, and vice versa. There exist, therefore, a whole series of different modes of action of which clinical experience furnishes well-known examples. Stationary Period. — Since the time of Hippocrates it has been the custom to admit three periods or stages in the evolution of acute diseases: an invading period, a stationary period, and a period of decline. Jaumes has proposed another division. He admits but two periods — namely, one characterized by a morbid effort corresponding to the period in which the organism appears to be overwhelmed; and one occurring only in favourable cases — i. e., a period of improvement and restoration. In other words, the first period corresponds to the attack by the pathogenic cause, and the second to the curative effort of the organism. This division is quite in harmony with the present- day conception of disease. It would have been perfect if reaction really followed action, and if disease followed a regularly descending course after arriving at its height through a progressive aggravation. In reality the facts are more complex. As we have repeatedly stated, the defensive reactions begin at the same time as the offensive actions, and at times even before all appreciable symptoms. Consequently, the two classes of symptoms constantly intermingle, with the exception, however, that the pathogenic agent has the advantage in the begin- ning. The reactions of the invasion period indicate that the organism is defeated, or at least on the defensive. Then comes a period when the struggle assumes a serious character, and the two participants fully display their forces. This is the stationary period, which at times seems to remain unchanged, and at others to present a series of deviations depending upon the various vicissitudes of the struggle. This period is the most important from a nosological standpoint, since the characteristic symptoms of the disease are well developed; they are so grouped as to constitute a special type, which is easily defined and classified. It is at this time that a previously hesitating diagnosis may be made more certain. 366 STATIONARY PERIOD In studying the stationary period, the local symptoms and general phenomena must likewise be taken into consideration. When the local manifestations occupy the external parts, they may easily be studied. Such is the case with erysipelas, abscesses and phlegmons, cutaneous ulcerations, and gangrene. These also are quite easily recognised when they occupy a mucous membrane which can be readily explored, such as that of the mouth and phar3mx. In case a deeply seated organ is attacked, the study becomes more dif- ficult ; yet, according to the modifications manifested in the functions of the organ and the changes which may be perceived by means of physical examination, palpation, percussion, and auscultation, we can quite exactly determine and follow the evolution of the phenomena produced in the deeper parts of the economy. In certain instances even the minutest examination fails to reveal any organic alteration, because the symptoms are of a general char- acter. The latter consist in reactionary manifestations referable chiefly to the nervous system, the secretions, and thermogenesis. The nervous symptoms are those which have already been noted in treating of the invasion period — namely, headache, incapacity for work, a diminution of psychical acuity, delirium, and, exceptionally, convulsions. The secretions are for the most part diminished; the urine is scarce, the saliva is not abundant, and the tongue is dry. Finally, thermogenesis is also perverted, and there is usually a rise of both peripheral and central temperature. A comparison of local and general symptoms leads to the follow- ing conclusions : Sometimes the local and general phenomena follow a parallel course. They are aggravated or diminished simultaneously; they de- cline and disappear almost at the same time. Sometimes there is a decided discord between the two orders of manifestations. Thus, for instance, the local lesion may subside, while the general symptoms grow worse. In such cases there is generally some fresh complication. More frequently the reverse is the case, the general phenomena van- ish, whereas the local manifestations seem to remain stationary. This fact is particularly striking in pneumonia. From one day to the next a sudden defervescence occurs; the temperature, which had risen to 40° C, falls to 37° C. ; the secretions are re-established; the patient experiences a feeling of well-being which makes him realize that his sickness is over, and yet no improvement has taken place in the con- dition of the lung; on the contrary, the stethoscopic signs are the same as the day before. The same lack of parallelism is observed in erysipelas, but not constantly; the general phenomena subside, while the cutaneous lesion persists without any change. EVOLUTION OF DISEASES 367 Finally, in certain cases the discord is no longer real, as in the preceding examples, but only apparent. The local lesion seems to remain stationary, and yet the general phenomena are modified or aggravated. These indicate either a local change, which we are thus permitted to recognise and predict, or a new perturbation, perhaps a commencing complication. In order to recognise the nature, follow the evolution, establish the prognosis, and predict the possible accidents of a disease, we must at the same time note its local and general manifestations, and their harmony or discordance. Let us first consider the local phenomena. Five results are pos- sible : 1. The local lesion, which has begun during the period of invasion, is not modified during the stationary period, but follows a very simple course, increases gradually, reaches its height, and then, in favourable cases, declines. But no notable change in its character or aspect appears. Of numerous illustrations it will suffice to mention mumps, ery- sipelas, and gonorrhoea. We might add scarlet fever and measles, in which the eruption characterizing the stationary period extends pro- gressively to all parts of the skin, but always preserves an invariable aspect. 2. In other cases the local lesion is modified from day to day. As an example in which observation is easy, an abscess may be taken. At first induration is found, then the lesion undergoes softening, be- comes fluctuating, and opens exteriorly. A like course may be ob- served in cases of visceropathies. In simple bronchitis there is a period of crudity when expectoration is difficult and painful; then a period of coction, when the sputa become mucopurulent and are easily thrown out. Examination of the sputa, as well as auscultation, demonstrate the changes characterizing these two periods. By the same methods of exploration we can follow perfectly the evolution of a pneumonic focus: In the beginning there is pulmonary obstruction resulting from the exudations, and auscultation reveals crepitant rales ; next, a fibrinous exudation into the air cells takes place — this is the period of red hepatization, characterized by tubal breathing; finally, the exudation softens and auscultation reveals rales of resolution (rales de retour). 3. Instead of remaining localized, the local lesion extends and invades the neighbouring parts. Here erysipelas and pneumonia may again serve as examples. While often circumscribed, erysipelatous inflammation sometimes extends to a great part of the skin. At times it covers the entire 368 LOCAL PHENOMENA surface of the body. This is a particular clinical form justly de- scribed under the name ambulatory erysipelas. The same evolution may be observed in the lung, under which circumstances pneumonia is designated as migrating. In certain but fortunately very rare cases a local lesion grows both deeper and larger, causing considerable loss of substance. This is what constitutes phagedenism, observed mainly in the soft chancre, which lesion may destroy the penis, invade the scrotum and thighs, and follow a serpiginous, extensive course, the duration of which may be months or even years. 4. The local lesion sometimes progresses by successive stages. At a moment when the lesion seemed on the point of subsiding or had even disappeared, a renewal sometimes occurs in the region primarily attacked. This is observed especially in erysipelas. At times the renewal occurs in parts more or less distant from the region primarily affected — for example, the orchitis occurring in mumps, and endo- carditis, pericarditis, or meningitis of pneumonia. The pathogenic agent thus tends to colonize distant tissues or organs: it is, as it were, a relapse at a distance. 5. Finally, the local lesion may be modified by an additional infec- tion. Pathogenic microbes implanting themselves, for example, in a part already diseased, give rise to suppuration, and may even invade the economy. In gonorrhoea the gonococcus remains localized in the urethra; common bacteria, however, soon join it, and may subse- quently provoke very serious disturbances. Although the gonococcus may sometimes invade the organism, the so-called gonorrhoeal rheu- matism nearly always depends upon ordinary pyogenic bacteria. The process is one of attenuated purulent infection, to which the agent of gonorrhoea has merely opened the way. General phenomena usually follow a course parallel to that of local manifestations. During the stationary period they may remain quite unmodified. In pneumonia, for instance, the fever remains about 40° C. Dyspnoea, thirst, and headache remain about the same during the entire evolution. The same remarks are true of t5rphoid fever, although some differences are revealed by a more careful study. In some cases the general symptoms are modified several times, so that the stationary period permits of division into a certain number of secondary periods. In other instances the general symptoms keep pace with the local, as is observed in smallpox. Sometimes the changes do not seem to harmonize. Thus, in tu- bercular meningitis three periods, which apparently do not correspond to anatomical changes, have been described according to the general symptoms. After a phase characterized by violent headache, fever, EVOLUTION OP DISEASES 369 constipation, and vomiting, a marked remission occurs, which lasts nearly a week; the patient is believed to be convalescent, when the symptoms are renewed, and go from bad to worse, ending in death. In a certain number of infections the modifications in the general symptoms express the generalization of a primarily local microbic process. Such is the case with the malignant pustule. The lesion is at first characterized simply by a cutaneous eschar; thus, in certain eases, phenomena of general infection are subsequently produced, indi- cating the invasion of the economy by the pathogenic agent. Like- wise, in cases of septicsemia or pyaemia consecutive to local lesions, the changes occurring in the general symptoms reveal the invasion of the organism. Nosologists have divided the stationary period of diseases by tak- ing into account both the modifications occurring in the local symp- toms and the general manifestations. Undoubtedly, these divisions are not always perfect. Didactic descriptions are necessarily sche- matic and can not give an exact idea of the complexity of clinical phe- nomena. We have above referred to tubercular meningitis. Its evolu- tion in three phases, admitted by all the classical treatises, is, how- ever, quite rare. The phenomena very seldom, if ever, progress with such quasi-mathematical precision as has been attributed to them. The clinical types are, in reality, far more complex and variable than may be supposed from the classical descriptions. Notwithstanding their variability, general phenomena evolve ac- cording to four types. T3rpes have been divided into continued, re- mittent, intermittent, and irregular, mainly upon the basis of the precise data of medical thermometry. The continued type is represented by the cases in which the symp- toms, after having reached the stationary period, do not present any change from one day or one moment to another; the condition re- mains the same. The classical example is typhoid fever, which dis- ease is often called continued fever. However, on looking into the matter more closely, it may readily be recognised that the continuity is not perfect; a series of variations is constantly produced which have rightly led clinicians to look upon the so-called continued fevers as remittent fevers. Every morning the temperature is a few tenths of a degree lower than on the previous evening, and the general manifestations, although continuing grave, are slightly attenuated. These variations are nothing else than an exaggeration of normal phenomena. In fact, in health the temperature is modified at dif- ferent hours of the day ; it describes a regular curve, whose minimum is between 3 and 5 a. m., and maximum between 4 and 7 p. M. ; the difference between the two figures is, on an average, 0.8° C. In 370 LOCAL PHENOMENA typhoid fever, the morning temperature usually varies between 39.5" and 40° C. ; that of the evening, between 40° and 41° C, the difference being from half a degree to one and a half. But it may sometimes become more notable. Later on the remissions are accentuated, as is observed at the end of the disease. Quite frequently there will even be seen at this period great variations tending to bring the morning temperature to a normal. This is what is called the amphibolic stage. When the remissions become considerable the temperature at cer- tain moments returns to the normal figure. The fever is then called intermittent. The intermittent fevers are often divided into two great groups: the malarial intermittent fever and the symptomatic intermittent fevers. Paludal fever, or malaria, is intermittent because, it is said, the parasite which causes it — Laveran's hematozoon — periodically invades the blood of those affected; the symptoms then become manifest, and are characterized by the three classical stages of chills, fever, and sweats. The parasite then takes refuge in certain organs — in the spleen and in the marrow of bones — and then the febrile paroxysm subsides. The fever will reappear upon a new incursion of the para- site. This theory is doubtless too simple, since the parasites are often found in great numbers in the blood after the end of the parox- ysm. This pathogenesis has been easily admitted for the reason, perhaps, that it is difficult to formulate another, perhaps also by analogy with recurrent fever. In the latter case, the presence of spirilla in the blood exactly coincides with the development of the paroxysm. The symptomatic intermittent fevers differ from the malarial in that their paroxysms are less regular. Contrary to what occurs in malaria, the fever generally returns in the evening, is sometimes re- peatedly reproduced during the same day, and reappears at different hours on the day following. These paroxysms should always arouse the suspicion of a suppurating focus in the viscera. They are par- ticularly frequent in suppurative hepatitis, angiocholitis, urinary in- fections, and ulcerating endocarditis, and almost constant in purulent infection. Despite their intermittent course, they are connected with progressively growing lesions; they are intermittent, although the evolution is continuous. This discordance is difficult to explain. It may be supposed, how- ever, that the toxines liberated by the suppurating focus act only after a certain incubation — that there is produced a phenomenon similar to that occurring in cases in which an infection begins sud- denly. The paroxysm is the result of cumulative doses and the febrile EVOLUTION OF DISEASES 371 reaction is probably connected with elimination of noxious substances ; the symptoms reappear when a new accumulation is produced. Whatever may be the explanation, febrile intermission is only an exaggeration of physiological remission. All fevers are not freely intermittent, probably because each paroxysm begins before the pre- vious one is terminated; according to this hypothesis, remittent fevers should be considered as intermittent. In this way, it is very readily understood that on certain days very marked remissions might occur even in continuous fevers. This is frequently observed in typhoid fever, notably toward the fourteenth day, sometimes the six- teenth or the nineteenth. Clinical Forms. — The stationary period of infectious diseases, being the longest, and especially the best characterized, has served to differentiate clinical types. On the basis of their evolution, cyclical diseases may be admitted in which the duration is sufficiently defined and is determined by a regular succession of morbid phenomena. Pneumonia, typhoid fever, and eruptive fevers belong to this category. However, it should be remembered that the figures given by authorities are subject to numer- ous variations. The term of nine days assigned to pneumonia, and of three weeks to typhoid fever, represent averages which are seldom realized. Nevertheless, the term may be retained in contradistinction to noncyclical diseases, such as diphtheria or erysipelas, whose capricious course defies all efforts at averaging. Even in those diseases in which the stationary period is best deter- mined, very great variations may be observed. In certain cases the evolution is shortened, either because the disease assumes a subacute, speedy course, causing death very rapidly, or, on the contrary, because it follows an abortive course. Pneumonia is again a good illustration. This infection, produced by the classical pneumococcus, may kill in certain instances within a few hours. This happens in the aged, in diabetics, and in individuals suffering with previous diseases, particularly erysipelas. In this connection we may also mention the speedy types of scar- latina, smallpox, and cholera. Death may occur at the beginning of the stationary period, and even before the latter is clearly established. Pneumonia also furnishes the best example of an abortive infection. The disease begins suddenly, reaches the stationary period, and all at once defervescence becomes established toward the third or fourth day. Abortive typhoid fevers have also been described, and we may also admit the occurrence of abortive fevers — i. e., such as are cut short after a prodromic period. Thus, an individual who has been 3Y2 CLINICAL FORMS exposed to the contagion of smallpox is seized with all the premoni- tory symptoms of this disease ; then the symptoms disappear and the eruption is characterized by two small pustules. This is evidently an instance of an attack of smallpox deserving the name abortive. Not- withstanding the intensity of the symptoms of invasion, the disease is cut short. Cases of abortive erysipelas which stop suddenly after the period of invasion at the very beginning of the stationary period may also be admitted. It is useless to multiply examples. While these facts are already well known, we believe them to be far more frequent than is usually supposed. Many febrile paroxysms, transi- tory malaises, and sudden chills, which are followed by no special manifestations whatever, and which run their course in a day and sometimes in a few hours, are to be accounted for by an infection that is aborted. Consecutive to infections occurring during convalescence from eruptive fevers or erysipelas, we often see febrile paroxysms, which, it seems, are referable to no other cause. This is demonstrated by the fact that numerous transitions are observed between the ephem- eral fevers, which can in no wise be accounted for, and those which indicate a relapse or a complication. Lastly, the diseases aborting spontaneously should be placed parallel with those aborting in conse- quence of therapeutic intervention. Cases of this kind, formerly rare, will become more and more frequent as we become better acquainted with specific medicaments. The latter are sometimes represented by vegetable or mineral products. Such are the salts of quinine, which arrest the malarial infection; the salts of silver, which stop a begin- ning gonorrhoea; and especially the preparations of mercury, which suspend the evolution of syphilis. At present specific and abortive remedies are looked for in substances derived from immunized ani- mals. The results obtained by serotherapy inspire us with the hope that the time is not far distant when it will be possible to arrest the evolutions of a great number of infectious diseases. The acute infectious diseases, even when they follow a cyclic course and terminate within a well-determined time, may in some cases be prolonged beyond the usual limits. For instance, pneumonia, instead of lasting nine days, may not reach defervescence until toward the twelfth or even the fifteenth day. Likewise, typhoid and eruptive fevers are not infrequently prolonged in an unusual manner, although examination of the patient fails to explain the persistence of the morbid symptoms. There is, so to say, a torpidity of the organism which does not succeed in producing the special conditions capable of arresting the infection. In a great number of cases, however, prolongation of the disease is due to a particular course or to the influence of complications. EVOLUTION OF DISEASES 373 The evolution is prolonged as the result of successive invasions. At the moment when the infection is believed to be nearly terminated a new focus is produced. Pneumonia and typhoid fever may evolve in this manner, and although the new attack is generally of shorter duration than the first, the total duration is thereby considerably prolonged. This mode of evolution, while rare in the diseases above referred to, is the rule in certain infections, such as recurrent typhus and intermittent fever. Such is precisely the case with varicella, the duration of which is extremely variable on account of the variation presented by the course of successive renewals. In certain cases the renewal of morbid symptoms is preceded by an interval of recovery; then it is said that there is a recurrence. As in the case of relapse, recurrence also is generally less grave than the first attack; but this rule offers a great number of exceptions. Finally, morbid evolution may be prolonged by complications oc- curring during the stationary period or convalescence. xTew phenom- ena, mostly due to superadded infections, may thus lengthen the duration of a disease for a very long time. It is evident that nothing but hypotheses can be advanced as to the causes which intervene to abridge or prolong infections. Aside from those cases in which secondary complications are produced, it is not understood why the morbid action is cut short, and then reappears at the moment when defervescence Was about to set in, or even after the beginning of convalescence. The solution of these problems is intimately connected with the study of predisposition, immunity, and the mechanism of recovery. If, as is generally admitted, recovery is effected by virtue of chemical and dynamic modifications produced within the organism ; if it is dependent upon an increase of the germi- cidal power of the tissue fluids and upon the phagocytic activity of the cells, the duration of the disease will, of course, depend upon the rapidity of the organic changes — namely, upon the reactionary power of the organism. Eelapses, on the other hand, would be due to an insufficiency of reaction. This explanation, however, is inadequate. What we desire to know is the conditions which cause the economy to react promptly in one case, slowly in another, and incompletely in a third. The question is thus reduced to a problem of a much more general nature. We have seen that the various morbid reactions are in part dependent upon the nervous system, and in part due to the state of general nutrition. They vary notably from one subject to another, and this variability is in relation with the hereditary or personal antece- dents of the individual, with his special innate characteristics and idio- syncrasies ; in other words, with the different causes to which we have constantly referred to explain the development and course of diseases. 374 CLINICAL FORMS Eeactionary differences also explain the differences of termination. When reaction is energetic and timely, it succeeds in destroying the invading microbes; if slight or slow, it only arrests their progress and the process passes into a chronic condition; if too weak or too tardy, it fails to save the organism, and the disease terminates fatally. These considerations suffice to demonstrate that the same infec- tions disease may present varied symptoms and follow an extremely variable evolution. Supposing all conditions to be the same as far as the microbe is concerned, the influence of the organism makes itself constantly felt and contributes to modify the scene. Therefore a cer- tain number of clinical forms have been admitted. These divisions are evidently quite arbitrary. In order to establish them, the various cases encountered have been compared with an habitual average type, running its course without the intervention of any unusual influence. In this way clinical forms have been grouped under two heads : First, according as modifications depend upon some anomaly in the course, or in the morbid symptoms, or in localization; or, second, according as they are due to the condition of the subject. With some variation this division may be applied to all infections. In order to fix the ideas, let us consider the two diseases in which clinical types are the most numerous and the most varied — i. e., pneu- monia and typhoid fever. The two following tables will show how clinical forms may be classified; the terms sanctioned by usage are clear enough to make description unnecessary. Clinical Forms of Pneumonia 1. Divisions based on the Study of the Disease. 1. According to the course. Abortiye pneumonia. Speedily fatal pneumonia. {Double. With successive foci. Migrating. Infecting pneumonia. 2. According to the morbid elements or symptoms. Inflammatory pneumonia. Adynamic pneumonia. Ataxic pneumonia. Pneumonia with icterus. Bilious pneumonia. 3. According to localization. Pneumonia of the base. Pneumonia of the apex. Central pneumonia. Massive pneumonia. Pleuro-pneumonia. EVOLUTION OF DISEASES 375 II, Divisions based on the Condition op the Subject. 1. According to the age. Pneumonia of children. Pneumonia of the aged. 2. According to the previous state of health. Pneumonia of cachectics. Pneumonia of drinkers. Pneumonia of the obese. Pneumonia of diabetics. Pneumonia of bronchitics. Pneumonia of the tubercular. Pneumonia of those suffering with malaria, etc. 3. According to the coexistence of another infection. Pneumonia of typhoid fever. Pneumonia of erysipelas. Pneumonia of acute articular rheumatism, etc. Pneumonia of influenza. Clinical Forms of Typhoid Fever 1 Divisions based on the Study of the Disease. 1. According to the course. Abortive typhoid fever. Prolonged typhoid fever. Speedily fatal typhoid fever. Typhoid fever with relapses. 2. According to the morbid elements. Mucous typhoid fever. Ambulatory typhoid fever. Inflammatory typhoid fever. Bilious typhoid fever. Hemorrhagic typhoid fever. Ataxic typhoid fever. Adynamic typhoid fever. Putrid typhoid fever. Hyperpyretic typhoid fever. Sudoral typhoid fever. 3. According to the localizations. Nervous forms i^^.°i°g^^- ( Spinal. Thoracic form. Gastric form. Icteric form. Renal form. Cardiac form. Septicaemic form. 25 376 TERMINATION OF INFECTIOUS DISEASES II. Divisions based upon the Condition op the Subject. 1. According to the age. Typhoid fever of children. Typhoid fever of the aged. 2. According to the previous condition of health. Typhoid fever of cachetics. Typhoid fever of the obese. Typhoid fever of drinkers. Typhoid fever of the tubercular. 3. According to the coexistence of another infection. Typhoid malaria. Laryngo-typhus. Pneumo-typhus. Termin"ation of Infectiotjs Diseases We have repeatedly shown that the organism is provided with means of protection which prevent the penetration and multiplication of pathogenic germs. The latter may succeed in invading the econ- omy only when the vigilance of the cells is distracted for a moment and the humours are altered by some affection. Then the disease manifests itself. Modifications in the cellular nutrition are imme- diately produced, however, which transform the blood, the humours, and the tissues, and make of them culture media nonadapted for the pathogenic agent. Now, two results are possible. In some cases the changes are produced slowly and progressively; the organism grad- ually rids itself of the germs and neutralizes the action of the toxines which impregnate it. Defervescence is produced in a slow manner; the fever diminishes progressively, by lysis, and the various functions consume a more or less long time in returning to their normal condi- tion. It is therefore possible to follow the progress of recovery day after day. This is what takes place in typhoid fever. In other cases, on the contrary, the termination is abrupt and sudden, as in pneumonia. It is then said that a crisis has occurred. Crises. — From the earliest antiquity it has been noted that certain diseases may present sudden changes in their evolution. This is crisis, which supervenes when the peccant (corrupt) humour has undergone coction; Nature expels it from the body or causes its deposition in some part of the organism. The latter result was formerly considered fortunate or unfortunate, according as deposition occurred in an organ of little importance or indispensable to life. These ideas led Hippoc- rates to formulate the following definition: "A crisis in diseases is either an exacerbation, a decline, a metaptosis, another affection, or the end." EVOLUTION OF DISEASES 377 The crisis, however, did not occur at undetermined periods; it appeared on fixed days, called critical days, which corresponded to weeks or half weeks — that is to say, to the fourth, seventh, tenth, fourteenth, seventeenth, and twentieth days. The critical days were preceded by the indicating days, when an exacerbation of the symp- toms was usually observed. It may be added that Hippocrates did not regard the critical days as possessing an absolute value; the crisis might occur twenty-four hours sooner or later. Galen, on the con- trary, attributed to each day an absolute significance. He argued that acute diseases did not last more than forty days, and considered the crisis as a sudden reversion to health. The latter definition has prevailed. At the present day the name crisis is reserved for the ensemble of favourable changes occurring suddenly in morbid evolution. One of these changes is that of the temperature, which in the course of one night falls from 40° to 37° C. In some cases the ther- mal reduction is excessive. The thermometer marks 36° or 35° C, and this hypothermia sometimes occasions disquieting phenomena, especially in the aged; it is attended with collapse, and demands in- tervention for restoration of heat to the patient. With the fall of the fever the secretions are re-established; the skin becomes moist and the urine abundant. On the previous day the patient may have voided 500 to 600 grammes; after the crisis diuresis may reach 2, 3, and even 4 litres. But what is still more notable, perhaps, is the feeling of well-being experienced by the sub- ject. As the crisis usually occurs during the night, it is surprising to find the individual, who was left in a condition of great suffering on the previous evening, completely cured on the following morning. The local phenomena, however, have not changed. If the case be one of pneumonia, the physician finds the same stethoscopic signs as on the previous day; if a case of erysipelas, he observes that the cuta- neous lesions have not improved. Modifications which might lead the inexperienced to error may be observed in the circulatory apparatus. On the previous day the pulse may have been rapid and weak, but regular; at the mo- ment of crisis it becomes strong and slow, but at times irregular and unequal. This phenomenon is observed especially in children, and probably depends upon a nervous disturbance, which is of no grave significance. The sudden and profound changes occurring at the moment of crisis may occasion new nervous reactions — e. g., convulsions in chil- dren and delirium in adults. There are cases on record in which a paroxysm of delirium tremens developed at the moment of defer- 378 TERMINATION OF INFECTIOUS DISEASES vescence of a pneumonia. These disturbances, though sometimes alarming, are generally without gravity. Among other critical manifestations, transitory erythemata, out- breaks of urticaria and herpes, sometimes diarrhoea, a bilious attack, or epistaxis, may be mentioned. Special attention has been devoted to changes presented by the blood and urine. Dr. Hayem has described a hematic crisis in which the white cor- puscles, increased in number during the disease, return to their nor- mal number. The red corpuscles have been progressively diminished, and at the time of the crisis an activity on the part of the hemato- mas ts occurs, designed to increase the red globules. The urine has been the subject of numerous researches. During the disease its quantity progressively diminishes. At the moment of the crisis a veritable discharge occurs. The polyuria is very abun- dant. The urea, which may have been reduced to 12 or 15 grammes, rises to 30 or 40 ; the chlorides, which were represented by 1 or even 0.8 gramme, reach 10 and 12 grammes. The modifications in the amount of chlorides have been attributed to the diet. This opinion is inadmissible, for it is contradicted by the abundant discharge at the moment of recovery. It is also known that if chlorides or iodides are adminstered to pneumonia patients, these substances accumulate in the organism and are eliminated only at the time of crisis. Likewise, the phosphates and the sulphates increase when defervescence is pro- duced, but in less notable proportions. The same is also true with regard to those poisons which are nor- mally excreted by the urine, they being in great part retained in the organism during the disease. During the stationary period the tox- icity of the urine progressively diminishes; at the time of crisis it is considerably increased, and reaches, or even exceeds, the normal figure. It should not be concluded from this result that recovery is due to the sudden elimination or to the urotoxic discharge. On the contrary, the reverse is true: it is because the patient has recovered that crisis has appeared. This is proved by the fact that in certain cases the urinary crisis occurs twenty-four hours before, or, what is more demonstrative, after recovery. Thus the patient, being cured, is capable of rejecting the poisons which impregnate his organism, but to which he had already become insensible. As to the crisis, it is to be considered simply as an exag- geration of normal phenomena. It is established that in a healthy man the elimination of autogenous poisons is not effected in a con- tinuous manner: the urinary secretion varies from one day to an- other; it follows a tertian, less frequently a quartan type. Then, EVOLUTION OF DISEASES 379 even in a normal state of things, accumulations and discharges are constantly produced — that is to say, little crises. It is a particular example of a general law to which we have frequently referred. We have already shown that there is no uniform movement in nature, and that all vital acts are remittent. Starting from this physiological fact, we may regard crisis as a natural phenomenon or an exaggera- tion of the normal type. The infectious diseases ending by crisis are not very numerous. Besides pneumonia, which is the type of the kind, we may cite ery- sipelas, smallpox, and typhus fever; however, crisis is not so clear in all cases, nor is it of constant occurrence. There is a disease in which crisis occurs in a reverse direc- tion: that is, cholera. In the stationary period the temperature is below the normal; at the moment of recovery it rises above and sometimes reaches a figure quite notably above the normal. Thus, a febrile, reactionary period develops, sometimes attended by grave manifestations, which may impart to the patient a typhoid aspect. Convalescence. — When the morbid process seems to have been arrested and recovery obtained, the organism is not yet completely restored. There is still a last period termed convalescence. The appetite, which had been suppressed during the disease, reap- pears, and is often so marked that it is difficult to prevent the patient from overeating. The temperature often falls below the normal; the figures 36.5° and 36° C. are not infrequent, and may be observed for a week or more. Emaciation appears or increases, this being probably due to the great amount of waste which is eliminated by the different emunc- tories, notably through the respiratory apparatus and the kidneys. Then, at the end of a few days, the patient grows fat, his weight often exceeding that noted before the commencement of the disease, and at times he becomes slightly obese. The nervous system having been most affected during the sta- tionary period, therefore returns more slowly to its normal condition. During the first days following recovery, when all the organs are work- ing regularly, the nervous system is still disturbed. The individual is unable to keep on his feet or walk; if an abrupt movement is at- tempted, dizziness and palpitation are experienced. Now and then a febrile paroxysm occurs, as, for instance, when he happens to read a little too much, or on the occasion of a visit, an emotion, or an act of little importance, such as making his toilet; the thermometer then marks 38° or 38.5° C. These disturbances, which seem to de- pend simply upon a lack of equilibrium of the centres of thermal 380 CONVALESCENCE regulation, and not upon an additional infection, are transitory and in no wise disquieting. The nervous manifestations of convalescence are sometimes much more marked than would be expected in view of the comparatively innocent character of the disease. In this regard nothing is more instructive than influenza. Even after the slight forms which have lasted but a few days, convalescence is very tedious; weakness, asthenia, and incapacity for work may persist for weeks or months. Finally, some of the symptoms of the stationary period may still reappear. A convalescent from typhoid fever will easily have diar- rhoea ; a convalescent from a thoracic affection will, upon the slightest cause, cough and have pain in the side. Evidently the duration of convalescence varies according to the nature, type, and gravity of the disease, and also according to the age or previous condition of the subject. Aged individuals and those who are already weakened require more time to be re-established, and they may often have to go to the country or to a warm climate. Convalescence may be interrupted by a great number of accidents. Besides the nervous fevers already referred to, other causes may produce a rise of temperature up to 39° or 40° C. After a day or two the temperature again becomes normal. This is often a process of abortive relapse; the disease, not well extinguished, has recom- menced and has been arrested by means of timely medication or the natural defences of the organism. In other cases a septicaemia is superadded to the primary disease. Some authorities have even maintained that the relapses of typhoid fever should be considered as infections of intestinal origin — i. e., that the alterations of Foyer's patches, by lessening the means of defence, permit the invasion of the economy by the habitual microbes of the alimentary canal. Febrile paroxysms connected with cutaneous suppurations may also be observed; the alterations of the skin, like those just referred to in the intestine, permit the pus cocci to produce abscesses or boils. At times an infection is produced in other organs; pneumonia oc- curring during convalescence from any disease may be taken as an example. Lastly, in certain cases febrile paroxysms occur, which are ex- plained by the aggravation of an antecedent chronic infection. For example, in an individual who has suffered for a more or less con- siderable period with a torpid (slow) tuberculosis, and then contracts the measles, convalescence does not become duly established after this intercurrent infection; he remains weak and suffering; he has slight fever every night, and emaciates and loses strength; the pulmonary k EVOLUTION OF DISEASES 381 lesions extend, and finally they either cause death, or, after a certain time, they are arrested and resume their former slow course. Relapses and Recurrences. — Convalescence may also be inter- rupted by a relapse. In certain infectious diseases relapse is the rule. We refer to recurrent typhus, and to a particular form of infectious icterus, im- properly called WeiFs disease. Relapse is frequent in typhoid fever, influenza, and broncho-pneu- monia ; it is rare in uncomplicated pneumonia and exceptional in other diseases. In most cases it is caused by a fault of the physician or of the patient. Alimentation may have been too rapid or too abundant; the patient may have got up too soon, or exposed him- self to the cold, and especially to fatigue. It is relatively easy to treat a disease during the stationary period; but at the moment of convalescence the physician is often greatly embarrassed and requires much tact and experience. Relapse sometimes manifests itself in a slow and progressive man- ner; more often it appears suddenly, even in the case of typhoid fever. In this disease the temperature reaches 39° or 40° C. on the evening of the first day. In a general way, relapses are less grave and of shorter duration than the primary affection; but there are many exceptions to this rule, and a relapse may be more prolonged, graver, or even fatal. A distinction has justly been established between relapse and re- currence (recidive). Relapse means a new beginning of a disease without a new infection; recurrence is connected with a new infec- tion. In a good many cases the distinction is easy. When a person is attacked with typhoid fever or erysipelas after an interval of fifteen or twenty years, such is evidently a case of recurrence ; but when the symptoms reappear at an early period, interpretation becomes ex- tremely difficult. Some individuals, particularly women, have ery- sipelas every month. Is such a case an example of recurrence or of relapse? It is impossible to answer, since we do not know what period of time is required for the destruction of the germ. The present tendency is to increase the importance of relapses at the expense of recurrences, and to admit that the microbes remain inactive in the organs and tissues, but ever ready to assume the offensive upon the slightest occasional cause. Indeed, it has even been asserted that in most cases the recurrences of gonorrhoea are but relapses; in fact, the gonococcus persists during an almost indefinite period in the urethra which it has invaded for the first time. Erysipelas and pneumonia belong to the number of diseases which seem truly capable of frequent recidives. Recurrences of measles are 382 PASSAGE OF ACUTE INFECTIONS quite common; those of typhoid fever, smallpox, and scarlet fever are very rare. As to syphilis, recurrence is altogether exceptional; most of the cases cited as examples of a second chancre are accounted for by a confusion with tertiary lesions of the genitals, which sometimes simulate a primary lesion. Passage of Acute Infections to a Chronic Condition. — Although recovery is the normal termination of infectious diseases, there are certain cases in which the evolution is prolonged beyond the usual limits. The disease is then said to have become chronic. The duration of acute diseases has been arbitrarily fixed at forty days : beyond this term chronicity is supposed to be established. If the question be considered from a higher standpoint, it will be seen that an essential difference between the two processes is fur- nished by the study of the evolution. Acute disease is a morbid process in a state of modification; each day brings about a change which, though often but slightly marked, can nevertheless be recognised by a careful examination. It will then be noted that the organism is reacting — ^that is, struggling with all its forces to arrest and destroy the morbific cause. It is in revolt against the invader. In a chronic disease the organism submits to the yoke of the patho- genic agent and seems to have no other ambition than to live with it; it hardly tries to circumscribe its progress; it abandons itself, being incapable of continuing the battle. The reason the condition of the patient is not more quickly reduced is that the invader itself has become less active and aggressive. Thus a tacit agreement is made between the microbe and the organism, and the disease persists, undergoing only extremely slow changes. Therefore an acute disease is distinguished by a lively, often too energetic, reaction; a chronic disease is characterized by the absence, insufficiency, or slowness of reaction. At times, however, the organism may for a moment recover its energy. The result is acute attacks, often occurring without any appreciable cause, and at times as the result of exposure to cold, trau- matism, or an intercurrent infection. Under such conditions the pathogenic microbe makes a fresh attack, with the result that the organism shakes off its torpidity. This acute spell may be ill di- rected, undisciplined, and precipitate the morbid evolution and thus rapidly cause death. In other instances, after having given rise to painful symptoms, it will lead the organism to recovery. A rebellious gonorrhoea, for example, has been seen to disappear after a new acute attack. This is a cure of disease through aggravation of disease. EVOLUTION OF DISEASES 383 Medicine has attempted to imitate these natural procedures — for example, irritant local applications realize this indication. Koch's tuberculine does not act otherwise; it whips, so to say, the torpid evolution of chronic tuberculosis. An acute process may become chronic without any notable changes being produced : it stops at a given moment of its course. This may occur at the moment of aggravation as well as at the time of improve- ment of the disease. The violent manifestations subside, the reac- tions and pains cease, and in certain cases the symptoms are so slight that the patient believes himself cured. Illustrations abound; they are mostly drawn from cases of nonspecific infections, mainly inflam- mations of organs — e. g., enteritis, nephritis, and cystitis — ^which gradually pass into a chronic condition; also various suppurations, commonplace or specific; gonorrhoeal urethritis, for instance, is thus transformed and often persists during an entire lifetime, occasioning no disturbance, and unknown even to the patient. Finally, of the specific infections we must specially mention tuber- culosis, which, after an acute attack, may follow a slow evolution. In order to more closely study the evolution of chronic lesions, let us consider an abscess situated somewhat profoundly. In its de- velopment it produces various disturbances. Then, when it is opened to the exterior, the symptoms cease; suppuration, at first very abun- dant, diminishes progressively. An early recovery may be expected; but at a certain moment the improvement is arrested, and a fistula, giving issue to a sero-purulent liquid, is established. There is no longer any general or local reaction; without any apparent incon- venience the organism supports this lesion, which becomes chronic. However, at the moment when chronicity is established the discharge undergoes some modifications. It loses its freely purulent character; it becomes more serous, more mucous; at the same time, the microbes diminish in number and virulence. Failure to recover in such instances is often due to the presence of a foreign body, a splinter, or a sequestrum in the focus; or else there is diseased tissue at the bottom of the fistula. When it is pos- sible to intervene and to extirpate or remove this inflammatory thorn, the organism triumphs over the bacteria and the lesion heals. Thus foreign bodies, although absolutely harmless when they are aseptic, maintain an infection which would be cured in their absence; this is a remarkable example of pathogenic association. In cases of chronic infections, the microbe, although attenuated, is not absolutely inoffensive. It seems even that its feeble pathogenic potency is in great measure due to some protective power exerted by the wall of the morbid focus. Dr. Chauveau has shown that the 384 CHRONIC CONDITIONS pus of a seton which produces no disturbance is virulent; if a par- ticle of it be inoculated in another point of the economy, disturb- ances are caused. The pus was endured only in its old focus. In cases of chronic suppuration, fistulas may from time to time become occluded; the subjacent focus is then filled with pus and in- creases in volume; it becomes painful and gives rise to fever. After an artificial or natural opening, the lesion resumes its slow and chronic course. In other cases the fistula becomes closed; it appears to be healed, as no symptom is any longer apparent. For months or years the lesion gives rise to no disturbance whatever ; then the focus, which seemed extinguished, is again kindled, and a new attack is produced. Such a course is observed especially in osteomyelitis, where a seques- trum may provoke very tardy disturbances appearing at considerable intervals. The microbe had slumbered for years as an absolutely inoffen- sive guest; an occasional, often unnoticeable, cause has permitted it to regain a little virulence and give rise to inflammatory reactions. A similar evolution is sometimes observed after typhoid fever. This disease never passes into a chronic state, but the microbe that has provoked it may become localized at certain points, notably in the bone marrow, and thus call forth a slow inflammation which termi- nates, after several months, in a focus of osteomyelitis. Bacterio- logical examination demonstrates the presence of Eberth's bacillus therein. In his case the acute disease ends in a chronic process quite different from what it originally had been. We can find by no means less interesting examples in the history of ulcers. Under this name are designated losses of substance having no tendency toward reparation. Ulcers result from very varied lesions which, owing to peculiar conditions, have not been able to terminate in recovery. Let us consider, for example, the varicose ulcer. A slight infection, an abscess, a pustule, a simple abrasion, having induced an infection so mild that no symptom is expressed and the existence of which we admit simply by induction, is the starting point. Separation is not effected because the tissues are altered ; their nutrition is profoundly affected by the varicose condition of the veins ; the skin becomes hard, brownish, and sometimes is attacked with eczema. The little lesion sufficed to produce a chronic affection in the suffering tissue. The same explanation is applicable in ulcerating dermosynovitis. This is a trophic lesion provoked by an ordinary cause or a slight infection, and it develops and persists because nutrition is profoundly disturbed by the nervous lesions. This ulceration is observed espe- cially in ataxics. EVOLUTION OF DISEASES 385 The data of clinical experience are confirmed by demonstrating that section of sensory nerves hinders considerably the process of repair. For example, division of the sciatic nerve in a guinea pig is often followed by ulcerations in the foot operated upon. But if care be taken to protect the limb by means of a sort of plaster shoe, infec- tion is prevented and no nutritive disturbance appears. The same is true of ulcers of mucous membranes. A common- place lesion, in most cases of an infectious origin, may serve as a starting point for an ulcer of the esophagus, duodenum, and espe- cially the stomach. Ulcer of the stomach develops in hyperchlorhydric dyspeptics; the excess of acid hinders reparation. Filhene has given an experimental demonstration of this pathogenesis. Two rabbits received considerable doses of arsenic subcutaneously : in one of them kept as a control, gastric ulcerations developed ; in the other, to which bicarbonate of soda was administered to neutralize the gastric juice, no lesion was produced. Although the organism plays a very important part in the develop- ment of ulcers, we must recognise that the lesion is sometimes de- pendent upon the nature of the pathogenic agent, its degree of virulence, and the point where it is developed. The ulcerations of tuberculosis, glanders, and syphilis and the phagedenic lesions belong to this group ; the influence of the organism, without being absolutely nil, is in these cases considerably reduced. An acute lesion may pass into a chronic state under a form rela- tively favourable — namely, induration. In such instances the organism was capable of completely destroying the pathogenic agent, but the alterations produced were too profound to admit of perfect repara- tion. The tissue, instead of returning to its primary condition, is replaced by a newly formed fibrous production. This termination is observed in superficial lesions, in certain abscesses, and in adenopa- thies, but it is particularly important in deeply situated tissues and organs. In this manner cicatrices are produced which, when located in the mucous membranes, cause deformity and hinder their normal action. When the cicatrices occupy such passages as the esophagus or the urethra, they result in stricture; in the viscera, such as the heart, liver, or kidneys, they produce sclerosis. In these cases the chronic process differs completely from the acute. As we have shown with reference to scleroses, the process of repair remedies the first disturbances, but creates a hindrance to the regular activity of the organs. The chronic processes, the mechanism of which we have just indi- cated, undergo no modification or progress slowly, either toward re- covery or toward death. In both cases changes ending in one or 386 DEATH IN INFECTIONS the other of these two terminations are produced either in an insidi- ous manner, or else the chronic course is interrupted by an acute attack !which leads to recovery or death, as the case may be, or a third alternative leaves the organism in the same condition as before its occurrence. Death in Infections. — When an acute disease ends in death, the fatal termination may occur abruptly, in an unexpected manner, or slowly and progressively, preceded by more or less prolonged agony. If autopsy is performed, macroscopic or microscopic lesions are some- times found ; in other cases the post-mortem examination gives a nega- tive result. By taking into account the diverse results which may be obtained, the causes of death may be divided into three groups: (1) mechanical disorders or barriers; (2) lesions of an important organ; (3) general infection or intoxication. As a striking example of the mechanism of death ly a mechanical cause, we may mention diphtheritic laryngitis. The false membrane developing in the larynx hinders the passage of air and may cause death, partly mechanically, partly through the reflex spasm which it excites. Likewise, a phlegmon taking its origin in certain regions may, by its size or by the oedema surrounding it, mechanically induce a fatal termination. In these examples death evidently results from the obstacle created by the lesions, since if the false membrane be detached or the circula- tion of air be re-established through intubation or tracheotomy, or the phlegmon be opened, the disturbances disappear immediately. The local lesion which may thus endanger life is not, however, the work of a microbe, but is due to a reaction of the organism which seems to fight against itself. If we more closely investigate the succession of the phenomena, we understand that the organism has produced a false membrane or a purulent focus in order to prevent general infec- tion. The lesion thus created was designed to circumscribe the morbid process and to oppose the penetration of microbes or their toxines. However, the organism is not always capable of proportioning its effort to the work required. In a good many instances reaction exceeds the end. A microbe penetrating into the lung induces an acute pulmo- nary congestion : the vessels dilate in order to facilitate the escape of fluids and cells which will arrest the development of the parasite. But the reactionary phenomena are often too intense, and may give rise to grave symptoms. In other cases, the microbe reaches the sur- face of the lung and irritates the pleura, which then secretes a fluid, which is often so excessive in amount that evacuation of the exudate becomes necessary. Lastly, in certain cases reaction is not too strong; it is truly bene- EVOLUTION OF DISEASES 387 ficial, but it is produced in particularly delicate localities and on that account may become dangerous. Such, for example, are congestion, oedema, and abscess observed in the brain. Under these various conditions the organism has endeavoured to remedy the immediate disturbances, but it has mobilized too great a number of cells or given issue to an excessive quantity of liquid. Therefore, under such circumstances, the necessity of employing therapeutic measures to the organism itself with a view of moderating the morbid reaction and of endeavouring, for example, to check the active congestion, which threatens to give rise to asphyxia by reason of its intensity, is of the greatest importance. At other times, on the contrary, the organism must be aided in its efforts to accomplish that part of its work which it is unable to do alone. Puncture of a pleural collection or the evacuation of a cerebral abscess is not medication against nature, but a complementary method aiding the insufficiency of natural means. As, on the other hand, morbid reactions may endanger life by their excessive intensity, on the other their insufficiency may be a new cause of disorders. When a microbe develops, it gives rise to the local devel- opment of deadly substances which destroy the surrounding cells; the destroyed elements are liquefied and, when possible, thrown out. When the organism fails to remedy the imminent accidents by the various means at its disposal, notably through the accumulation of wander- ing cells, or if the leucocytes be killed as they arrive at the point of invasion, a more or less complete destruction of the affected tissue will result. Gradually extending, necrobiosis may reach a vessel, and, if the course of the process is rapid, a grave or fatal hemorrhage occurs before a clot is formed. In other cases an important cavity is opened; for instance, the wall of the intestine is perforated. In these various cases lesions which are apparently sufficient to account for death will be found at the autopsy. As a result of anatomico-pathological discoveries we have become so accustomed to attach an exaggerated importance to anatomical lesions that we are satisfied when the autopsy reveals a morbid focus in some important organ. Let us take, for example, the case of a child dead of measles. During life a murmur was found at the base of one lung, and, on opening the cadaver, a focus of broncho-pneu- monia is, in fact, discovered at that point. The mechanism of death in this instance appears to be easily understood. Yet, on a little reflection, it will be acknowledged that it is hardly possible to attrib- ute the fatal termination to a lesion so small as not to hinder hema- tosis to any great degree. The same reasoning is applicable to other organs, as well as to those cases in which multiple lesions are 388 DEATH IN INFECTIONS found. In acute miliary tuberculosis, when the tubercles have invaded the serous system only, why has the individual died? Pushing the question further, it must be asked. Why has he succumbed, even when the multiple granules have invaded the viscera? There generally re- mains sufficient intact parenchyma to assure the function of the organ. Without wishing to abuse examples, we may refer to cerebral soften- ing, which, even when limited, may occasion death, whereas it is pos- sible to experimentally remove the greater portion of the brain with- out endangering life. The anatomical lesion is a small matter, and it is not sufficient to explain everything. It is here that modern science intervenes and rightly proclaims the role of toxines secreted in the diseased organs and leads to the admission that death is due to poisoning. This interpretation is con- firmed by those cases in which no manifest lesions are revealed by post-mortem examination. Let us suppose an individual succumbing to anthrax. The blood is disintegrated, dark, and sticky, and the spleen is swollen and the other viscera congested. At times small visceral ecchymoses are met with, and that is all. This is evidently somewhat disappointing. How- ever, on examining a drop of the blood or a particle of the organs under the microscope, innumerable bacilli are observed, and thus some light is thrown on the problem. Here death is attributable to a gen- eral infection — Toussaint said it was due to an obstruction of the capillaries by the bacteria. However, this invasion and dissemina- tion of the foreign elements does not seem to be sufficient to explain the fatal termination. It is neither by crowding the vessels nor by abstraction of oxygen or of the materials necessary for cellular reno- vation that the bacteria have destroyed life. On the contrary, it is by the secretion of soluble substances that the function of the cells has been disturbed. This interpretation, which may seem contestable as regards anthrax, is the only one admissible in reference to those diseases whose patho- genic agent is localized at a certain point of the organism. In diph- theria, gaseous gangrene, and cholera the microbes do not invade the economy ; they remain localized in the skin or confined to the digestive canal. Death can not, therefore, be attributed to any other cause than the soluble substances engendered by the micro-organisms. It is not enough, however, to say that death is the result of an intoxication; we will endeavour to indicate the mechanism of a fatal termination a little more precisely. In certain cases lesions are found which of themselves would be sufficient to endanger life. For example, the autopsy reveals degen- EVOLUTION OF DISEASES 389 eration of the liver and kidneys, myocarditis, or hemorrhages of the suprarenal capsules; chemical analysis shows the diminution or even the absence of glycogen in the liver; and microscopical examination demonstrates cellular lesions in most of the organs. It may then be asked whether these multiform alterations have not played a part in bringing about the final result, and whether the auto-intoxication re- sulting from organic insufficiency has not been added to the microbic intoxication. This, however, would tend to again displace the problem, for it is at any rate to be recognised that the cellular lesions are in certain cases too limited to have exerted a marked influence. We are thus brought to again admit a toxic action. This action, however, is not immediate; the poisons do not kill rapidly, but a cer- tain length of time elapses between the moment of their introduction and the instant when the first responsive manifestations appear. In- stead of at once arresting the nutritive activity which essentially char- acterizes life, and microbic toxines disturb nutrition by adulterating the intercellular medium. Whether the poison itself modifies this me- dium, or whether the secondary products originating under the influ- ence of the toxine act as a ferment, is a matter of little importance. What is an important fact, however, and one to be kept well in mind, is that even when a fatal dose is at once introduced into a vein the animal succumbs only after the elapse of several hours. This means that a whole series of modifications in nutrition are produced through the influence of the toxine. We are thus led to consider not the total death, but the individual death of the parts of the organism — i. e., of the cells. It might be supposed that, under the influence of toxines, nutrition is equally per- verted in all parts of the organism; but such a conception is hardly admissible. The cells are disturbed according to a fairly determined order — those which perform the highest functions are affected first. Since the nerve cells occupy the highest position, experimentation in accordance with clinical facts shows that it is upon them that the deleterious action of toxines is in most cases exerted. The dynamic state of the nerve cells being thus modified, it is comprehensible that an occasional cause, by producing in them an abnormal excitation, may induce sudden or speedy death. Otherwise, the fatal termination supervenes gradually, as the result of a progressive weakening of me- tabolism. In order to admit these different conceptions without reservation, we should be exactly informed as to the functional state of the dif- ferent parts of the organism at the moment of death. Here is a most difficult question which has not as yet been the subject of experi- mental studies. 390 EVOLUTION OF NONINFECTIOUS DISEASES In brief, death as a result of infection is death from intoxication. The microbic poisons accumulate in the organism and hinder or pre- vent normal cellular life. It is possible that they act by forming com- binations with the cellular protoplasm. It is more probable, however, that they affect the cells by adulterating the intercellular medium. The result is a series of functional disturbances inducing death, and at the autopsy no lesion, or almost none, is found even under the micro- scope. If any lesions are met with they are too small to explain the fatal termination. If life is prolonged, functional disturbances induce anatomical modifications, and also they secondarily produce important cellular lesions which play an important part in the mechanism of deferred deaths. Here, however, the question is no longer one of infection, but of organic lesions progressing on their own account and deriving no particular character from their origin. We are thus led to say a few words with regard to the evolution of noninfectious diseases. Evolution of Noninfectious Diseases It is useless to dwell upon mechanical agents. They do not cause diseases, but they produce lesions only. Popular good sense has long recognised the distinction between wounded and diseased subjects. In the development of wounds we need only study their mode of reparation. Traumatism is sometimes a cause of disease, because it either excites nervous reactions or opens a door, sometimes to intoxi- cation, but generally to infection. It is not necessary to dwell upon these facts, which have already been discussed. We may also neglect to consider the physical agents, which, as a rule, simply produce lesions or some nervous reaction. The role played by them has already been pointed out. The history of chemical agents — ^namely, of intoxications — is more important. Let us first consider acute intoxications. In general, a certain time elapses between the moment when the poison is introduced into the organism and the instant when disturbances appear. This is the period of latency, which must not be designated as incubation, since there is no development of a pathogenic agent. Exceptionally, disturbances ensue immediately — for example, when prussic acid is ingested. The onset may be slow and progressive or abrupt and sudden, and is followed by a stationary period, which is generally of quite short duration. As an example we may mention alcoholic intoxication. Drunkenness appears some time after the ingestion of the alcoholic beverage, and its disappearance is rapid and complete. Such is not always the case, however. The absorption of a great amount of alco- EVOLUTION OF DISEASES 391 hol may be followed by visceral lesions which are of subsequent and independent development. If the liver is affected, an acute steatosis may be observed, which rapidly causes death, accompanied by mani- festations of grave icterus. Similar remarks are applicable to phosphorus or cantharides poisoning. In both of these instances hepatic or renal lesions occur and continue to develop long after all the toxic substance has been eliminated. At other times symptoms persist because the poison has facilitated the development of an infection. In mercurial poisoning, a stomatitis or an enteritis, the work of the microbes of the mouth or the intestine, may produce gangrenous and ulcerous lesions in the mucous mem:- branes altered by the mercury. In a similar manner the development of broncho-pneumonia consecutive to carbonic-oxide intoxication must be attributed to the intervention of microbes. Thus in all acute poisonings we must take into account both the primary and, as a rule, transitory effects produced by the poison, and their more or less deferred consequences, which are due either to vis- ceral lesions resulting from the poisoning or to secondary infection. Chronic intoxications are far more common and interesting. For years individuals absorb considerable quantities of poison without the least apparent derangement. During this long latent period the mor- bid phenomena develop insidiously; visceral lesions are produced, and then symptoms appear, either slowly, progressively, or even with an astonishingly abrupt intensity. The progressive development of morbid events is easily explained by the development and continuous aggravation of the lesions. The sudden and often unexpected appearance of the disturbances is refer- able to one of the following causes : sudden augmentation of the daily dose of the toxine, suppression of the toxine, or intervention of a new mechanical, physical, chemical, or animate pathogenic agent. The influence of an increase of the habitual dose is easily under- stood. A man who is in the habit of drinking to excess will have an attack of intoxication or delirium as a result of indulgence greater than usual. A fresco painter who tolerates his saturnism will have an attack of lead colic after breathing more of the poison than usual — for example, after having scraped a wall painted with white lead. At first sight it is still surprising to observe disturbances follow the suppression of the daily toxine. The fact is that the poison has become necessary to the regular performance of functions and has been made, as it were, a constituent part of the cellular protoplasm. In other words, it is an indispensable excitant, and if it is lacking dis- orders become manifest, which disappear as soon as it is again admin- 26 392 EVOLUTION OF NONINFECTIOUS DISEASES istered. Such is the case with the alcoholic and the morphine eater, who are often seized with disquieting symptoms when they are forced to abandon their pernicious habit. As soon, however, as they take a dose of their usual poison, all the disturbances vanish. An idea of the results of a total suppression may be obtained by a consideration of the daily life of an alcoholic. On awakening in the morning, his ideas are not quite clear, and his hands are agitated with a continuous trem- bling. As soon as he takes a drink, however, the symptoms disappear, intelligence again becomes quite bright and the trembling ceases. The poison has therefore become indispensable to the regular activity of the organs. The visceral lesions produced in the course of intoxications, like those developing in the course of infections, often remain latent for a very considerable period. They may give rise to disturbances on the occasion of some intercurrent cause which breaks the unstable state of equilibrium of the organism. For instance, an alcoholic individual, who seems to be in good health, suffers from a traumatism, a sunstroke, or an infectious dis- ease, when he is at once seized with delirium tremens. The sudden intervention of a new cause provokes the appearance of symptoms. The same is true of an individual affected with plumbism. Lead colic is an acute episode in the course of a chronic intoxication; it occurs, as a rule, as the result of some occasional cause, particularly of an excess in drinking. The development of visceral lesions is generally caused by intoxi- cations and infections. These lesions, as we have repeatedly stated, develop independently, deriving no particular character from the cause or causes from which they originate. The symptoms and evolution of a nephritis, a cirrhosis, or a cardi- opathy do not differ according to the agent which has occasioned them ; on the contrary, everything depends upon the nature and extent of the lesions. It is readily understood that a profound but localized alteration is far better borne than a superficial but diffused one. Likewise, symp- toms are less marked when the interstitial tissue is affected than when the glandular cells are attacked. It is true that the organs comprise a much greater number of cells than is necessary for the continuation of life. From 40 to 50 per cent of the glandular tissues may be sup- pressed with impunity; one third of the liver may be removed, one kidney extirpated, or one lung excised, without any great disturbance. With certain glands, even very important ones like the pancreas, a very small part suffices for the regular performance of their functions. These remarks perfectly explain the frequency of latent affections. EVOLUTION OF DISEASES 393 A visceral lesion may run its course silently for months or years without expressing itself by any symptom. The organic lesion will be discovered perchance. On auscultating the heart the physician may find an aortic insufficiency until then unsuspected, or, on examining the urine, he finds sugar or albumen, while no disorder whatever made him suspect the existence of diabetes or nephritis. Notwithstanding the absence of disorders, these lesions constitute a permanent danger, for sudden or unexpected death is often the con- sequence of such latent conditions. In certain cases symptoms appear progressively or abruptly, being excited by some intercurrent and often very slight cause. The organ- ism is in such a state of unstable equilibrium, however, that disturb- ances may appear on the slightest occasion. Thus, a hepatic cirrhosis may remain absolutely latent; then, in consequence of a cold, ascites rapidly develops, and from that moment all the manifestations of the affection are displayed. The symptoms produced in the course of a permanent affection are often transitory; they cease and subsequently reappear, although the lesion persists. We are thus led to say a few words in reference to intermittence in diseases. Without again referring at length to infections, we shall first recall the example of malaria. The paroxysms occur periodically, leaving the condition of health intact in the intervals. It is admitted in this in- stance that intermittence is explained by the life cycle of the parasite. However, in visceral suppurations the fever may also assume the same character. While the cause acts continuously, the organism acts only in an intermittent manner. The same fact is observed (and its inter- pretation then seems much easier) when there is excitation of a mu- cous membrane. Thus, in spasmodic laryngitis or croup, the glottic obstacle, though permanent, gives rise only to attacks of suffocation of a paroxysmal character. Although the lesion remains the same, and does not vary from one moment to another, it excites spasms only at intervals. Then, after an effort, perhaps as the result of exhaustion, the affection resumes a milder course. It may be remarked that physi- ology has prepared us to accept these results. For the production of a phenomenon, a series or a summation of excitations is often required ; reciprocally, the excitation persisting, the effect may cease. An ener- getic current applied to the pneumogastric nerve arrests the heart, but only for a moment, since, despite the persistence of the stimulant, the beating recommences. Similar phenomena are observed under a great number of cir- cumstances. Even traumatic lesions are not exceptions. The pain felt in old cicatrices on seasonal or barometric variations pre- 394 EVOLUTION OF NONINFECTIOUS DISEASES sents a periodicity which is explained by the influence of cosmic variations. The mechanism of periodicity in chronic affections is a subject of special interest. This mechanism may easily be explained by one of the following two processes, as the case may be: At times there is a slow accumulation of toxic substances and the paroxysm breaks out when the toxines become too abundant; at other times there is a cir- culatory hindrance, and nutrition, although sufficient in the state of rest, is unable to supply the needs of the organ during the period of activity. In the former case, the paroxysm may be looked upon as a sort of discharge calculated to neutralize, eliminate, or modify the toxic sub- stances. There is a growing tendency to attribute to auto-intoxication an important role in the genesis of paroxysmal manifestations oc- curring in the course of a neurosis. The fit of epilepsy has been ex- plained in this manner. Whatever may be the value of this hypothesis, it is undoubtedly true that the patient feels better after a crisis: he finds himself relieved by a sort of salutary discharge. The same remark may also be applied to the intermittent manifestations which occur in the course of diatheses. An asthmatic and particularly a gouty paroxysm are prepared by modifications of nutrition, which is subse- quently improved in a notable degree. The subject experiences a feel- ing of well-being. Then, little by little, the disturbances slowly and insidiously return, until they end in a new attack. The second mechanism above referred to is much better known. It is best exemplified by arteriosclerosis. In this affection, the arteries having lost their elasticity, circulation is unsatisfactory: as long as the organs are at rest, reparation is sufficient ; as soon, however, as they become active, disorders become apparent. In this manner a syndrome is produced which can be studied in animals as well as in man — i. e., intermittent claudication (limping). Whenever the subject walks for some time the insufficiency of arterial circulation hinders the activity of the muscles and gives rise to limping. What is easily observed in the limbs is equally produced in the vis- cera. According to the felicitous expression of Grasset, an intermit- tent claudication of the organs exists. Visceral disturbances become manifest as soon as a more active circulation becomes necessary. A good many causes may therefore give rise to this phenomenon. As a clear illustration, we may take sclerosis of the coronary arteries. Although the circulation has become very defective, no disturbance is produced; then, all of a sudden, a paroxysm of angina pectoris occurs which seems to appear spontaneously and without any apparent cause. In reality, it is due to some gastrointestinal, pulmonary, cardiac, or EVOLUTION OF DISEASES 395 nervous disorder. A too hearty meal, difficult digestion, exposure to wind, overexertion, a strong moral impression have demanded of the heart an increase in work. This organ, which accommodated itself to the ischasmia produced by the sclerosis of the coronaries as long as its activity was moderate, no longer receives a sufficient amount of blood under the new conditions. Therefore the first manifestation of a chronic, slow, and progressive process appears abruptly. At the end of a few minutes the symptoms subside, and the individual resumes the appearance of good health until the moment when a new attack occurs. In proportion as the attacks are repeated, however, the mi- nutest causes suffice to provoke their return. A time arrives when the attacks seem to be produced spontaneously; the occasional cause is too slight to be recognised. The same thing may be repeated with regard to many other mani- festations. The attacks of asystole, despite the persistence of the lesion, are also intermittent; they appear on the occasion of some in- termittent cause, which will become slighter in proportion as the accidents are aggravated, and, in the end, will pass unnoticed; the paroxysm will possess the appearances of spontaneity. The same remarks are applicable to other organs and to various apparatus — lung, liver, kidney, and the nervous system. Latent Diseases. — If the accessory cause which explains the de- velopment of periodical accidents is lacking, the disease may remain latent. Diseases, even those that are acute, are sometimes unexpressed by any disturbance. Among the infectious diseases, we shall only men- tion typhoid fever and pneumonia. There are cases of typhoid fever in which the symptoms are so feebly marked that the subject continues to attend to his business. This is the form which has been well studied under the name waTking typhoid fever. While generally innocent, this form does, however, occasionally expose the subject to terrible com- plications, and may end in rapid death by perforation of the diseased intestine. Pneumonia is quite frequently latent in the aged. !N'o reaction is produced; the individual gets up, leads the same existence as on the preceding days; then he suddenly becomes ill and succumbs in a few minutes. The autopsy shows gray hepatization of one of the lungs, and the observer is astonished that lesions so strongly marked should have developed without giving rise to the slightest symptom. Among latent affections we may cite a goodly number of cases of pericarditis, pleurisy, and even acute meningitis. Consecutively to an otitis or a sinusitis, diffuse suppurations may invade the meninges without any reaction being produced, not even slight headache. 396 METASTASIS Lastly, it must also be remembered that chronic affections of the organs, such as cirrhoses of the liver, nephrites, valvular lesions, and particularly aortic insufficiency, spinal and cerebral affections, gastric ulcer, and sometimes cancer, may remain latent for a great length of time, and they may subsequently produce rapid disturbances or even cause sudden death. They may finally give rise to no manifes- tation at all. They are revelations of the autopsy. The evolution of a disease may be modified by various superadded phenomena and by intercurrent complications. In certain instances the occurrence of a complication causes the primary phenomena to disappear. Nervous affections and parasitic diseases of the skin have been seen to stop for a time on the appearance of some acute infec- tion. Lastly, in certain instances, an existing manifestation sud- denly vanishes when a similar phenomenon develops at another point. This is known as metastasis. Metastasis. — Metastasis is the transportation of a morbid process from one point of the organism to another. In order for metastasis to exist, the transportation must be complete — viz., the primary lesion must disappear. According to this definition, the so-called metastatic abscesses are very improperly so named. In this case there is not a disappearance of the initial process, but a generalization of an infection. Nor are the cancer metastases to be admitted. When an epithelioma of the intestine is followed by the development of a similar neoplasm in the liver, it is a case of extension through embolism. Thus defined, metastases are quite rare. A few examples have been observed in infections — e. g., the urethral discharge often dis- appears when a gonorrhoeal orchitis supervenes. A better example is furnished by the history of rheumatism: when cerebral manifesta- tions appear, the swelling of the articulations diminishes and the pains often disappear with astonishing rapidity; there is a transpor- tation of the fluxion which leaves the articulations to invade the nerv- ous centres. In fact, the congestive and'fluxionary phenomena are the most easily displaced. The knowledge of these facts has led to an important therapeutic method — ^i. e., revulsion. When cupping is practised upon the thorax, pulmonary congestion diminishes; when an irritation is provoked in the intestine, the encephalonic or me- ningeal congestion is diverted. From this point of view calomel gives excellent results. By creating a new congestive process, it is possible to cause the older one to disappear — i. e., to provoke a metastasis. If we consider the diathetic affections, or, to speak more exactly, if we consider arthritism, we find well-known facts entering into this EVOLUTION OF DISEASES 397 group. Between certain morbid manifestations a perfect balance exists, and the ancient physicians have laid much stress upon the diseases which it is frequently dangerous to cure. Facts of this kind are to-day regarded as doubtful, perhaps on account of their being difficult of interpretation. It seems certain, however, that the disap- pearance of an eczema may be followed by an attack of asthma, and a very curious balance exists between certain skin diseases and various internal manifestations — e. g., hemicrania, enteritis, etc. Gout may also alternate with various diathetic disorders. Its study also furnishes an excellent illustration of metastasis. An indi- vidual is seized with a very painful paroxysm; the big toe, much swollen and red, causes intense suffering. In order to mitigate the pain, he plunges his foot in cold water ; relief is at first produced, but soon visceral symptoms appear, involving the heart, the brain, or the stomach — symptoms which are often very grave and sometimes fatal. It is then said that gout has retroceded or ascended. The idea of this misplacement may appear odd; but it must be recognised that to-day, just as in the past, no satisfactory explanation can be given. Several observations recorded as examples of retroceded gout are undoubtedly referable to gastritis or to degeneration of the myocardium, and espe- cially to uraemia. !N"evertheless a few facts remain that can not be thus explained. For want of a better explanation, we shall consider them as belonging to the group of metastases. Recovery. — Whatever may be the disease under consideration, re- covery may take place gradually or abruptly. In the latter case a true crisis is produced; the symptoms yield at once; the previously dis- turbed organic functions are re-established, or they may even be aug- mented and exceed physiological limits. Thus in a great number of diseases the urinary secretion diminishes. At the moment of recov- ery there occurs a urinary discharge similar to that which we have noted in infections : a transitory polyuria appears during one or sev- eral days. This urinary crisis is of very common occurrence after intoxications, painful affections, and in the course of affections of the organs — e. g., liver, kidney, and heart. The same variations may be produced in the temperature. If hyperpyrexia has existed during the disease there will be hypothermia at the time of recovery, and vice versa. In a great number of intoxi- cations, as in certain infections, such as cholera, for example, the grave events are accompanied by a rectal temperature as low as 35.5° or 36° C. Subsequently, at the time of recovery, a reaction is pro- duced and the thermometer reaches 39° or 40° C. In the case of a transitory disease or affection, recovery of health may seem complete and the cure perfect. 398 RECOVERY As regards chronic affections, the morbid symptoms may also decline, and, on a superficial examination, recovery may seem to be established and all the lesions repaired. In reality such is not the case. Every morbid manifestation lasting for some little time brings in its train irreparable lesions. The disorders cease because a series of modifications which assure compensation have been produced. There first occurs disappearance of altered elements, which are replaced by connective tissue — the cicatricial tissue which always comes to fill the vacant space created by the destruction of differentiated elements. The organism possesses such an overabundance of cells in its glands as well as in its most highly organized parts, such as the nervous cen- tres, that it does not feel the loss of a few of them. On the other hand, the healthy supplement the diseased parts, and compensating hypertrophies and hyperplasias are thus produced. This is a mechan- ism which we have studied at length in connection with morbid sym- pathies (page 328). The cardiac hypertrophy that assures the com- pensation of a valvular lesion or contributes to the re-establishment of the activity of a diseased organ, such as the kidney or lung; the hypertrophy of the bladder, which overcomes the difficulty of micturi- tion in cases of urethral stricture; the hyperplasia of the liver or kidney, which furnishes new elements to replace those which have been destroyed, for some time maintain an almost normal state of health. This re-establishment, however, is but apparent. Sooner or later a functional insufficiency appears, which brings fresh disorders in its train. Absolute cure is not possible save in traumatism. In nontrau- matic cases the functional disturbances may recede and disappear; the organism then seems to return to a state of health as perfect as before the disease. In reality, however, the pathogenic cause, whether toxic or infectious, has imposed a lasting modification upon the nutri- tion of the subject. This modification, which, as we have repeatedly stated, explains recovery, will carry the economy out of the physio- logical channel. So that after each morbid effect there still persist some changes which are often too small to be noticed, but which, if the pathogenic causes be repeated, may, by summation, result in more or less marked lesions, new disturbances, organic affections, or finally in death. Death. — Death may occur in two different ways : progressively, as is most frequently the case, or suddenly. Two varieties of sudden death are to be distinguished. At times the termination is foreseen. The physician can diagnosticate a disease or a lesion recognised to be capable of killing suddenly. For example, a person known to have EVOLUTION OF DISEASES 399 aortic insufficiency may live for ten, twenty, or thirty years without suffering at all from his lesion; but he is liable to succumb at any moment. Facts of this kind are not legally considered as cases of sudden death. In legal medicine this distinction is reserved for unforeseen death, attacking individuals in apparently good health; for it is dem- onstrated that a really healthy individual is not exposed to sudden death. Traumatism excepted, it may be affirmed that every individual succumbing suddenly was affected with a lesion which was until that moment latent. It is said, and constantly repeated, that sudden death is generally due to rupture of an aneurism, or to cerebral congestion. This is an error. According to the statistics of the Paris morgue, rupture of an aneurism is not encountered even in the proportion of 4 per 1,000. As regards cerebral congestion. Professor Brouardel declares he has never seen it in cases of sudden death. What is most frequently found is degeneration of the myocardium, aortic insufficiency, interstitial nephritis, gastric ulcer, and sometimes pleurisy or embolism. Finally, in some cases tuberculous meningitis, and especially suppurating meningitis induced by a purulent coryza or otitis, are observed. Since the time of Bichat, classical works repeat that death is effected through the lungs, heart, or brain. It is quite evident that death through the brain can no longer be admitted to-day; it should be said that death occurs rather through the medulla. Thus modified, the conception is still inexact. In fact, we must rise to a higher idea and look for the mechanism of death, not in an apparatus, but in a general disturbance, in some modification affecting the function of the cells. We are thus brought to consider death as connected with an arrest of cellular nutrition. In certain instances this arrest of nutrition may occur under the influence of violent excitation, as is the case in nervous shock. The exchanges between the morphological elements and the surrounding medium are suppressed; there is a retention of noxious products in the cells and lack of renovation of the humoral medium. In most cases death occurs because waste substances accumulate in the humours and arrest the nutritive exchanges. This is what nota- bly occurs when lesions exist in the liver and the kidneys. Hence, when death is spoken of as occurring through these organs, it is meant that there has been an auto-intoxication of the organism as the result of their disorders. Similarly, when there is an arrest of the heart — namely, syncope — or suppression of the pulmonary emunctory — ^namely, asphyxia — death results from a lack of organic depuration. 400 DEATH The blood during cardiac arrest no longer carries to the various cells the substances necessary for their nourishment, and is therefore unable to rid them of useless materials. In asphyxia the absorption of oxygen and the rejection of carbonic acid do not take place, and this also results in intoxication. Therefore, in thus attempting to penetrate the mechanism of death, we reach the conclusion that the fatal termination can not be ex- plained by the lesion or the suppression of an organ. Those who have upheld this hypothesis have considered the apparent phenomenon; they have given a formula applicable only to higher individuals ; they have proposed a restricted definition for a general manifestation. The suppression of a function can not characterize a process which is observed when that function no longer exists. Death, like life, can not be understood except when all series of beings are taken into consideration. Its definition is therefore to be looked for in the disturbances, not of an apparatus, but of all the cells. In other words, in the higher forms of life we must consider two orders of phenomena: (1) a suppression of functions which does not consti- tute death, but leads to it if the disturbance persists; and (2) an arrest of nutrition which indicates the true cessation of life. The suppression of cardiac pulsations, for instance, is not synonymous with death, for if they recommence, the individual revives. The same is true as regards suppression of the pulmonary function. Puncture of the medulla itself is not necessarily fatal, since artificial respira- tion may maintain life. All these lesions and disturbances only pre- pare the fatal termination. Now, with reference to nutrition, we have shown that cellular nutrition and the organs concerned therein should be considered sepa- rately. Cellular nutrition is the general phenomenon essentially char- acterizing life; its suppression characterizes death. If we consider the unicellular beings, we readily understand that nutrition will stop under two quite different conditions. Sometimes the cell will lose its aptitude to derive from the liquid medium wherein it lives the materials necessary for its incessant renovation, and to throw out those that have become useless or harmful. These conditions are realized under the influence of certain too violent excitations or of certain lesions produced by mechanical, physical, or chemical agents. At other times the medium itself becomes unfit for maintaining life, on account of the nutritive elements having been exhausted or the cellular wastes having accumulated. These extremely simple facts will permit us to explain the mechan- ism of death in higher beings. In fact, we find the same two con- ditions. EVOLUTION OF DISEASES 401 A shock or violent excitation may cause arrest of nutrition; but it is readily understood that the pathogenic cause can hardly act at once upon all the cells of the economy. This hypothesis, which might be maintained with regard to some poisons, is hardly probable. In most cases the arrest of general nutrition is produced through the nervous system. Let us take, for example, a violent traumatism. In the case of a unicellular being it inhibits directly the nutritive activ- ity of its protoplasm ; in the case of a higher organism it produces an excitation of the nervous terminations which gives rise by reflex action to the morbid state already studied at length under the name of nerv- ous shock. The mechanism is more complex in the latter case, but it is essentially the same. It also intervenes in internal traumatisms — for example, when a pulmonary embolism, a cerebral embolism, or hemorrhage cause sudden or speedy death. Toxic substances also kill by arresting cellular nutrition. Some- times they form stable combinations with the protoplasm; sometimes they seem to act by transmitting to it a sort of molecular vibration. In considering a unicellular being, it is easy to conceive the mechan- ism of death in both cases. In individuals of a higher rank, however, it would be necessary to admit that all the cells are simultaneously killed by the poison — a thing that can never be realized. Certain highly organized cells, notably the nerve cells, are the first to die. If the being succumbs, it is because disorders have been secondarily pro- duced in the humoral medium — i. e., in the plasma in which the cells are immersed. The phenomena thus become more complex, a fact that is due to the greater complexity of the organism. In order to understand the mechanism of death we must recall what has been stated in connection with nutrition. The higher beings are provided with an internal medium whose constitution must remain fixed and invariable. Numerous organs work to this end. If one of them should stop working, if others should be unable to take its place, death will be the consequence. Let us see the principal cases which may be encountered. 1. The materials of renovation are no longer furnished to the blood, because the subject is submitted to inanition, or because the digestive canal has become incapable of transforming or absorbing food; death ensues because the first act of nutrition — assimilation — no longer takes place. 2. The result is similar when the requisite amount of oxygen is not furnished to the cells, either because the red blood corpuscles are not sufficiently numerous, or else they are no longer able to fix this gas, as occurs in carbonic-oxide poisoning. 3. In case of arrest of the circulation, the suppression of cardiac 402 DEATH activity causes death because cellular renovation is no longer effected, and the blood, which serves at the same time as a way of excretion, ceases to throw out the useless substances. 4. The situation is quite similar when respiration is arrested ; the cells succumb because the gaseous exchanges are suppressed; oxygen no longer arrives and carbonic acid is no longer exhaled. 5. Lastly, the arrest of nutrition may result from lack of depura- tion consecutive to alterations of the emunctories. The products of disassimilation are no longer rejected; they saturate the medium and prevent diffusion of harmful substances out of the cell. The lesions of the liver, kidney, and highly vascular glands kill by this mechanism; they arrest nutrition by virtue of the auto-intoxication which they produce. In brief, if the proceedings called into play are multiple, the final result is always the same. In vegetables as well as in animals, in uni- cellular beings as well as in those placed at the top of the scale, death is always produced through the same mechanism. Therefore, modifying the usual formula, we shall say : Death is the result of an arrest of cellular nutrition, either because the proto- plasm becomes incapable of carrying out the double movement of assimilation and disassimilation, or because the medium in which the cells are immersed or in contact undergoes modifications rendering exchanges impossible. The arrest of nutrition is a general phenomenon applicable to all beings. In all it is due to either of the two mechanisms above indi- cated. In the higher organisms, however, it occurs under conditions more and more complex in proportion to the growing complexity of the apparatus concerned in assuring the activity of the protoplasm and the renovation of the organic medium. CHAPTER XXI EXAMINATION OF THE SICK General appearance of the patient— Posture— Facies— Corporeal deformities— Ex- amination of the integuments — Systematic examination of the various appa- ratus— Greneral rules for the examination of the circulatory and respiratory organs, the digestive canal, liver, spleen, pancreas, peritoneum, urinary and genital organs, and the nervous system. The examination of patients may be made in several ways. It is customary, however, to follow an almost identical course in all cases. The external appearance, the facies, and posture of the patient are first noted; at the same time some questions are asked him as to pain and other disturbances from which he may be suffering. The first impressions thus obtained give an idea of the nature of the dis- ease and serve as a guide to exploration. The hereditary and per- sonal antecedents and present symptoms of the patient must then successively be considered. As already stated, the first question asked of the patient is in- tended to locate the seat of his pain. In most instances the phenom- ena of pain lead us to an immediate recognition of the parts affected. Spontaneous pain and that which is excited by touch or movement, and which may therefore be located with greater precision, are of unquestionable semeiological value. It is well to remember, however, that the investigation of the phenomena of pain may also lead to error. For instance, an individual complains of pain in the stomach and frequent vomiting. Gastralgia is at once thought of, and the stomach is treated with negative result. Here failure to relieve the patient is due to the fact that the gastric symptoms were those of ataxia. At other times patients with some spinal disease complain merely of pains irradiating in the limbs or located in one or several of the joints; these pains are too hastily referred to rheumatism, and sodium salicylate or antip5rrine are prescribed without effect. In this connection the morbid sympathies which unite the heart and the lungs are pre-eminently instructive. Physicians are often I 403 404 GENERAL APPEARANCE OF PATIENTS consulted by patients complaining of palpitation of the heart. In fact, the pulse is found to be quick, beating from 100 to 120 per min- ute. Bromide is prescribed with no benefit, and digitalis causes aggra- vation of the symptoms. Here nonsuccess is due to the fact that these so-called cardiac patients are in reality pulmonary consump- tives; they are subjects of lung lesions which are unattended by any lung symptoms, but which could readily be discovered by means of auscultation. On the other hand, many young women complaining of slight but persistent cough, complicated at times by hemoptysis, are treated as consumptives, dosed with cod-liver oil and creosote, and re- peatedly cauterized at the apex of their thoraxes, and yet the respira- tory apparatus is intact or but secondarily disturbed. The initial lesion is seated in the heart : it is simply a case of mitral stenosis. These few examples sufficiently prove the necessity of always exam- ining all the organs in a systematic manner. This is the only means of avoiding such gross errors as have just been referred to. General Appeaeance of Patients Before entering upon a methodical examination of the organs, however, it is necessary to exactly observe the patient's attitude, facies, and general appearance. While ancient physicians knew nothing of percussion, auscultation, or bacteriology, and the methods of explora- tion employed by them were rudimentary, they have nevertheless left us certain precepts which it would be an error to ignore. At the present day too much is made of scientific procedures. Attitude, Decubitus. — In case an individual is so seriously affected as to be compelled to lie in bed, his posture must first be noted. In the first place, there is the horizontal posture upon the back. As a rule, this is the position assumed by individuals in suffering, and by those who are exhausted or have lost consciousness. The same position is taken by those attacked with hemiplegia, although some- what modified by the fact that the paralyzed side, being less strong than the other, shrinks, as it were, and the healthy side appears to be prominent. In a case of cerebral anaemia the head is low; in that of congestion the head is raised high and supported by pillows; the relief produced by this position is so considerable that even patients in a semicomatose state constantly ask to have their heads elevated. Another variety of horizontal decubitus is the lateral, which is fre- quently observed in cases of thoracic affections. When an individual has pain in the side not connected with any alteration of subjacent organs — in other words, when he suffers, for instance, from neuralgia, pleurodynia, or muscular rupture — he lies upon the affected side. The compression thus produced diminishes EXAMINATION OF THE SICK 405 the pain ; a feeling of relief is experienced by pressing the hand upon the affected part or by compressing it against the bed. The phenomena are more complex in cases of acute affections of the respiratory passages. At the outset the patient lies mostly upon the healthy side; later on he lies upon the diseased side, in order to breathe more freely with the intact half of the chest. In case of pleurisy it is altogether impossible for the patient to lie upon the healthy side, for the effusion, obeying the laws of gravity, compresses the mediastinum and presses against the intact side, thus preventing respiratory movements. In cardiac diseases the victims lie upon the right side. This is an exaggeration, as it were, of a normal phenomenon; even in good health it is more or less uncomfortable to lie upon the left side. At a more advanced stage the sufferer assumes an altogether peculiar position: he sits with his head and shoulders supported by pillows; the legs are dependent, while his arms are kept in a motionless posi- tion with a view to furnish a point of support to the auxiliary muscles of respiration. In case of abdominal superficial pain, the sufferer will likewise try to exert pressure upon the abdomen: sometimes he will lie ex- tended upon his back with the thighs and legs bent, the hands widely opened and pressing upon the abdomen ; at other times he will simply lie upon his abdomen. If the pain is very intense there will be agi- tation and frequent change of position. In some instances the de- cubitus is quite peculiar and might be called semilunar incurvation. The patient is rolled upon himself; the vertebral column describes a half circle, and the thighs are flexed upon the pelvis. This position is observed in cases of peritonitis, and in hepatic or renal colic. It is also well to be acquainted with the odd positions assumed by those suffering from gastric ulcers. At the time of a paroxysm the patient instinctively assumes a posture calculated to avoid contact of the food with the diseased walls. If the anterior surface is diseased, he lies upon his back ; if the posterior surface is the site of ulceration, he lies upon his abdomen ; he lies upon his right or left side according as the ulcer is situated upon the left or right side. The importance of these various attitudes is readily understood with reference to the diagnosis of the site occupied by the gastric lesion. Finally, there is another posture which is frequently observed in tubercular meningitis: the child lies upon one side, with the legs strongly flexed upon the thighs. The Fades of Patients. — Next to the posture, the facies of the patient must be noted. A great number of nervous or mental de- rangements impart to the face an altogether peculiar expression. In 406 THE FACIES OF PATIENTS some instances the peculiar appearance results from paralysis of cer- tain muscles — e. g., the immobility of the eyes in external ophthal- moplegia, the crying countenance in labio-glosso-laryngeal paralysis. In other cases the features remain motionless — e. g., in paralysis agi- tans; or the integument loses its property of contractility, as is ex- emplified by the marblelike countenance in sclerodermia and by the lunar facies of myxcedema subjects. In other instances parts become unduly developed, as occurs in acromegalia, or they become asym- metrical. Paralyses of the seventh pair, whether central or periph- eral, associated with or without hemiplegia; paralyses of the motor oculi, conjugate deviation of the head and eyes, glosso-labial hemi- spasm of hysterical subjects, the facial trophoneurosis of Komberg, all give rise to absolutely characteristic deformities. Likewise, in the course of various neuroses the facies offers some peculiar characters. The staring and ecstatic expression of hysterical patients, the stupefied aspect of an epileptic after an attack, the par- ticular countenance imparted by the exophthalmia of Graves's dis- ease, represent as many well-known examples. The expression of the physiognomy is of great importance in the diagnosis of cerebral diseases. According to the type of mental de- rangement, the countenance is calm or agitated, indifferent or pre- occupied, depressed or inspired. The contracted visage of the lype- maniac, the satisfied countenance of the general paralytic, and the wandering look and trembling lips of the alcoholic are also matters of common observation. We can not undertake to describe all the different appearances which may be observed in various diseases. We shall recall the ade- noidian facies, characterized by a stupid expression, transversely flat- tened nose, half-open mouth, and effaced naso-genian folds ; the facies of drinkers, characterized by a nose increased in size and covered with small veins; the mitral facies, with bluish lips, cyanosed cheeks, and puffed skin; the aortic facies, intensely pale; and the Brightic facies, swollen and whitish, etc. We must dwell somewhat longer upon the modifications, and par- ticularly the dyspnoea produced by thoracic diseases, and upon abdom- inal affections. Three types of dyspnoic facies have been distinguished. One is due to defective inspiration. For example, there may be in the larynx some trouble caused by a foreign body or a diphtheritic pseudo-mem- brane, in which case the patient remains sitting with the neck strained, eyes protruded, nostrils dilated, and the face very pale. In the young each inspiration produces a visible depression above the sternal notch and along the border of the false ribs: this is the EXAMINATION OF THE SICK 407 suprasternal and infrasternal retraction caused by the action of atmos- pheric pressure. In case of expiratory disturbance the appearance is entirely differ- ent. The face is flushed, puffed, and bluish; the cervical veins are much distended; the eyes are motionless, half closed, and tears flow from the eyelids. This is the asphyxial facies. The third type occurs in consumptives. Its characteristics are, as every one knows, emaciated figure, protruding and red cheeks, fine nose with a jerking respiration, difficult speech, and often extinguished voice. Of the abdominal facies several varieties are admitted. In the first place there is the facies grippe, which is met with in grave lesions, in peritonitis, intestinal occlusion, and at times in hepatic and renal colic. The striking feature is the considerable diminution in the size of the features; the face appears to be shrunken and diminished; the nose is thin, elongated; the muscular fibres have retracted, and this renders the osseous prominences more appreciable. The skin is pale and often covered with cold sweat ; the integument loses its tenderness and elasticity; hence, the folds made in it persist for quite some time. In children suffering from digestive disorders and marasmus the features are drawn, the furrows deepened, the neck hollow and ema- ciated. The facial expression recalls that of a little old man. A third type is represented by the cholera facies. The integument is violet, the nails dark, the lips blue, the eyes sunken in their orbits ; the extremities, nose, and lips feel cold to the touch, and even the breath is cold. This special type, realized to its highest degree in cholera, is encountered in a great number of other diseased condi- tions accompanied by choleriform manifestations; it may almost be designated as the facies of agony. Three more particular facies may be admitted: the syncopal, the apoplectic, and the agonal facies. Syncope is characterized by an abrupt arrest of the heart; the individual becomes completely pale, respiration is suspended and the pulse imperceptible. In case of apoplexy the patient is motionless and lies upon the back; all the functions are in abeyance; breathing and circulation alone persist. Even these, however, are profoundly modified; the breathing especially is noisy and often stertorous. Finally, when agony arrives, as it does in most acute or chronic dis- eases, the cerebral functions are gradually suspended; respiration is painful and slow, the skin retracts, the nose is tapering, the eyes are dull, half closed, and glassy. Then breathing is gradually ar- rested; after a few minutes of apncea it is resumed, but again stops; 27 408 CORPOREAL DEFORMITIES finally, a last inspiration takes place, and often the body is shaken by a slight spasm; the pupils suddenly dilate and the extremities are in complete relaxation. This is death. Corporeal Deformities. — In order to complete the study of the external habitus of the patient, corporeal deformities must be looked for, the existence of which is often of very great semeiological im- portance. The patient should be examined, when possible, both in the re- clining and upright position. The appearance of external forms may be noted in these two positions; moreover, it is well to instruct the patient to take a few steps, which may cause certain symptoms to become more manifest. Deformities may be general or partial. The general deformities are, as a rule, referable to alterations of the skeleton. Rickets and, less frequently, osteomalacia produce de- formities which may be very extensive. The appearance of a rachitic is a familiar one: the child's stature remains short, while the head is voluminous, with tardily closed fontanelles, the spine is incurved, the ribs are deviated so as to form two prominences, the pelvis is deformed, the limbs are curved, and the epiphyses too voluminous. Furthermore, it is well to know that even a partial lesion, provided it is profound, may cause secondary deformities modifying the entire architecture of the body. Such is the case with Pott's disease. Finally, general deformities may be produced by muscular atro- phies, provided the latter be extensive and involve most of the muscu- lar system. Partial deformities must be looked for successively in the head, trunk, abdomen, and limbs. In all regions deformities may depend upon some lesion of the skin or subcutaneous cellular tissue (derma- titis, cicatricial retractions, keloids, tumours, abscesses, oedema, etc.), or the vessels (aneurism, varices), or the muscles, skeleton, and, in the case of the head and trunk, of subjacent organs. In the head, deform- ities may affect the cranium ; they are referable to the epoch when the sutures, not having yet been effected, the lesions of the brain and me- ninges induce deformities of the skull, which moulds itself upon sub- jacent parts. It will suffice to mention hydrocephalus as an example. Of the main deformities affecting the face may be cited tropho- neurosis, the deviations due to paralyses or contractures of the mus- cles supplied by the seventh pair, fluxion and swelling of the parotids (parotiditis and mumps), and the protrusions caused by suppura- tion or tumours in more deeply seated parts, especially the sinuses of the face. Thoracic deformities, apart from those produced by rickets, are EXAMINATION OF THE SICK 409 due to affections of the lungs, and, less frequently, of tlie heart. At times they are bilateral and symmetrical, as in the case of pul- monary emphysema ; at other times fhey are limited to one half of the chest, as occurs in pleurisy, pneumothorax, pleuro-pulmonary cancer, and tumours of the mediastinum. The diseased side is expanded and remains so even during expiration, which thus exaggerates the differ- ences. In case of chronic pleurisy, retraction of the organized exudate consecutively produces flattening of the affected side. There are also partial protrusions due to the presence of aneurism, abscess, or empyema bulging exteriorly under the form of a large tumour, which sometimes presents pulsations (pulsatile empyema). Alterations of the heart are less frequently productive of deform- ities. In case of considerable hypertrophy or pericarditis with profuse effusion prominence of the praecordial region is observed. Likewise the deformities of the abdomen may be general or par- tial. The abdomen is distended and increased in size in case of ascites, tympanites, and acute or chronic peritonitis. In other in- stances a region presents an anomalous prominence — e. g., consider- able hypertrophies of the liver or spleen are expressed by a tumefac- tion of the hypochondrium, which is quite notable when the patient is standing. The lower abdominal organs very frequently give rise to deformities : a distended bladder, a uterus that is gravid or full of fibromata, and ovarian cysts are the most important causes. Examination of the external anatomy of the different members of the body, and particularly the extremities, should never be neg- lected. In fact, they may present numerous trophic disorders, many of which are of certain semeiological value. Some deformities are connected with nodular rheumatism, while others are due to chronic gout. There is a morbid state characterized by considerable hyper- trophy of the extremities — namely, acromegalia. Finally, there may be observed upon the third phalanges of the fingers the so-called nodes of Heberden; the so-called nodes of Bouchard upon the sec- ond phalanges, and connected with nutritional disturbances, partic- ularly with dilatation of the stomach ; the spatular fingers met with in children suffering from congenital cyanosis; the Hippocratic fingers, characteristic of tuberculosis; and the pneumic arthropathies of Marie, which occur when pulmonary respiration is greatly embar- rassed. The study of deformities of the hands will be completed by look- ing for a manifestation described by Landouzy under the name camp- todadylia. This state, which should not be confounded with retraction of the palmar aponeurosis, is observed in arthritics, and consists in the impossibility of fully extending the fingers, particularly the fifth. 410 EXAMINATION OF THE INTEGUMENTS Examination of the Integuments A rapid examination of the skin should follow that of the general appearance of the patient. The colour may be modified over the entire body or the greater part of it, or only over a certain region. In some instances the skin is pale and discoloured. It presents a peculiar white, waxy hue in anaemia; the mucous membranes of the lips, gums, eyes, and genital organs are also pale. At certain points, especially at the lines of the face, a bluish hue is observed, which is particularly pronounced in anaemia of young women and is known as chlorosis. The appearance is so characteristic that the diagnosis is made at a glance. It is well to remember, however, that certain symp- tomatic anaemias may assume the mask of chlorosis in young women, as is observed, for example, in certain cases of tuberculosis or syphilis, in the course of gastrointestinal disturbances and especially in un- complicated mitral stenosis. Chronic intoxications by carbonic oxide, or lead, give rise to some- what particular anaemic conditions. The same is true of repeated hemorrhages and, above all, metrorrhagias. One of the most typical forms is the anaemia of cancer subjects ; their colour is of an absolutely characteristic straw-yellow hue. This appearance, taken in conjunc- tion with the emaciation, permits the observer to confidently diagnos- ticate the existence of cancer. Of the other affections producing pale- ness it will suffice to mention pernicious anaemia, leucaemia, amyloid degeneration, and Bright's disease. Acute articular rheumatism de- serves special mention because of the intense paleness and profuse odorant sweats characterizing it. Pinally, paleness of the integument may result from vascular spasm; in this case, however, it is transitory. It occurs under the influence of emotion or of anger, during chills, and particularly in leipothymia and syncope. Congestion of the skin is of quite frequent occurrence, but, as a rule, it is local. In plethoric individuals the red colour is appreciable only on the face and at times in the hands. This condition is known as sanguineous temperament, which appears to be dependent upon a peculiar state of the circulation rather than upon a real augmenta- tion in the amount of blood. General or at least very extensive cutaneous congestions may occur in the course of a great variety of affections. Erythema is then said to exist. In its simplest expression erythema consists in redness which can be dispersed by pressure. In a great many instances, however, a further development of the phenomenon takes place: slight hemor- EXAMINATION OF THE SICK ; 411 rhages or exudations are produced which may simply infiltrate the skin, as in urticaria, or raise the epidermis and thus give rise to bullae (erythema multiforme). The redness characterizing eruptive fevers — measles and scarlatina — as well as the rashes occurring as epiphenomenon in the course of most varied infections, particularly at the beginning of smallpox, are nothing more than erythemata. In order to avoid grave error in interpretation, it must be remem- bered that in certain individuals, especially in women of nervous tem- perament, vasomotor disturbances are easily produced. These are gen- erally limited to the face and chest, and become apparent when the physician begins the examination of the patient. They are called pudic erythemata. Localized redness, especially in the face, may be observed; such, for example, is the redness of the cheeks in pneumonia. Examination of the integument may also reveal various altera- tions, some of which are of importance from the standpoint of general pathology, while others, on the other hand, enter into the group of skin diseases. Thus we may find hemorrhages (purpura, ecchymoses), inflammations (erysipelas, eczema), vesicular lesions (herpes) or bullae (varicella, pemphigus), pustular inflammations (acne, ecthyma, variola), etc. We can not, of course, dwell upon all these lesions, which should always be carefully noted. Apart from the red colour dependent upon active congestion, there is also a blue colour referable to passive congestion. When the latter hue is general, it indicates profound asphyxia — i. e., a very great dis- turbance of hematosis. This condition occurs in cardiac or pulmonary insufficiency, and in grave adynamic states, such, for instance, as the algid stage of cholera. In all these cases cyanosis is especially marked in the extremities, hands and feet, the face, and particularly in the lips. It will suffice to remember the appearance of a patient suffer- ing from cardiac disease during the period of asystole. Cyanosis is local when it is due to compression of a large vessel; it may then serve to diagnosticate an intrathoracic tumour. The skin may likewise present anomalous colours resulting from the deposition of yellow or brown pigment. Every one is familiar with the yellow hue of icterus, which first becomes apparent in the conjunctiva, where it must always be looked for, since this localization serves as a point of differential diagnosis from the yellowish hue common to conditions of anasmia, saturnism, malaria, and cancer, which at times recall the colour of icterus. When there is a deposit of brown pigment, the examination of the mucous membranes is also of great importance. There exists a special 412 EXAMINATION OF THE INTEGUMENTS affection connected with alterations of the suprarenal capsules and semilunar ganglia, designated as Addison's disease, and characterized by a brownish colour of the skin and by the presence of brown or slaty spots upon the mucous membrane of the mouth. This latter localiza- tion differentiates Addison's disease from other melanodermias, for example, from those observed in consumptives suffering from intes- tinal lesions, in individuals affected with malarial cachexia, in certain diabetics, etc. Examination of the integument must include a search for cicatrices. This exploration is sometimes of the first importance, since it may furnish a clew to antecedent pathological occurrences which are un- known to, forgotten, or denied by the patient himself. Of the cutane- ous cicatrices some are of traumatic origin and of little importance; others are referable to destructive affections of the skin or mucous membranes, such as acne, ecthyma, variola, tuberculosis, and, above all, syphilis. The syphilitic gummata are frequently seated upon the inner face of the tibia. These consist of round, sometimes confluent and polycyclical lesions; the central portion is colourless, white; the peripheral portion is formed by a brown circle. It is impossible to exaggerate the importance of this stigma which should lead to the institution of specific treatment, the only one capable of saving the patient. It is comprehensible that the smallest cicatrix presents a semeiological value of the highest importance in the case of an indi- vidual suffering from aphasia or apoplexy, or fallen into a state of helplessness. Other cicatrices also possessing a certain importance are repre- sented by vibices. The best known type is that observed in women who have been pregnant : the skin of the abdomen is covered with whitish stripes due to rupture of the elastic fibres. The same lesions occur whenever the skin is too much distended : they are found on the chest during and after a pleurisy; they are also observed in individuals who have rapidly grown; they are of frequent occurrence upon the outer side of the thighs in consequence of an attack of typhoid fever. After inspection of the skin palpation is practised, which furnishes information as to the elasticity, dryness, and temperature of the in- tegument. The skin loses its elasticity to such a degree in grave dis- eases, especially in affections of the alimentary canal, that it preserves for a moment the folds made on it. This phenomenon is very marked in enteritis of children, in intestinal occlusion, and in cholera. The skin is thickened and indurated in certain affections, such as ichthyosis, scleroderma, etc. It is dry in grave infections and in dia- betics; the return of moisture is a good sign, constituting one of the manifestations of defervescence. In other cases sweats are exagger- EXAMINATION OF THE SICK 413 ated, either all over the skin or in certain portions thereof, and they may be of an anomalous character. Coloured, sanguinolent, clammy, and odorant sweats have been recorded. In acute articular rheu- matism the body especially is covered with profuse sweats having a strong, almost characteristic odour. The odour of cutaneous perspira- tion is modified in a great number of morbid states — e. g., in gastro- intestinal dyspepsia, in urinary affections, and in infectious diseases, such as typhoid and typhus fever, cholera, etc. Palpation likewise furnishes important information in regard to temperature. In some instances it reveals a thermal rise limited to a certain region, and thus leads to the discovery of some local inflam- mation; in other cases it indicates a general modification. Practice enables one to readily appreciate the variations of cutaneous heat. It should be well known, however, that palpation does not always furnish exact information as to the systemic temperature. There may exist dissociation — viz., the temperature of the skin may at times fall considerably, while central temperature is above the normal. Such, for instance, is the case in the first stage of intermittent fever. Examination of the skin must be completed by that of its adnexa — i. e., of the nails and hair. The nails often present trophic disturbances. In the course of the most varied diseases they become thin to such a degree that, after the termination, a more or less profound transverse furrow is observed. In other instances they become brittle, and are striated longitudinally. In chronic tuberculosis they thicken, assume the incurvation of a bird's beak over the digital pulp, and, conjointly with the transversal enlarge- ment of the last phalanges, they contribute to impart to the finger that peculiar appearance which is designated as Hippocratic finger. - Analogous trophic disturbances are observed in the hair, which becomes dry, brittle, and easily falls out. Without speaking of affec- tions of the pilous system, we shall confine ourselves to a simple men- tion of the early baldness of arthritics, and the alopecia of syphilitics, which denudes the scalp in a diffused manner and not infrequently involves the eyebrows. Examination of the integument may often reveal alterations of the subcutaneous cellular tissue. QEdema, tumours, pseudo-lipomata, and tophi are recognised at a glance, and may guide the physician in his task of clinical analysis. The same is true of dilated veins, the presence of which indicate* the development of a collateral circulation and leads to the discovery of deep-seated disorders. Examination of the Lymphatic Glands. — Either at the beginning of or during an examination the state of the lymphatic glands must be inquired into. In certain instances these glands are so greatly enlarged 414 LYMPHATIC GLANDS as to form tumours readily appreciable at first glance. Tubercular, cancerous, and suppurative glands acquire a considerable volume. In the majority of cases, however, they are to be sought for by means of palpation. Particularly the glands of the neck, groins, and axillae must be explored, and less frequently the mastoid, the occipital, and the deep-seated glands, while those in the iliac fossa are readily dis- covered by palpation. The mesenteric, and especially the tracheo- bronchial ganglia, require a more delicate method of exploration, to which reference will be made in connection with examination of the abdomen and thorax. Ganglionic hypertrophy may be local or general. In the former case it involves a certain group of glands and indicates an inflamma- tory or other lesion of the corresponding organs. In the latter case, if the subjects are young children and the enlarged glands are numer- ous but not very voluminous, tuberculosis must be suspected; micro- polyadenitis is of great semeiological value. In adults, ganglionic hypertrophy is met with in a great number of acute or chronic infec- tions, notably in syphilis. Finally, more voluminous adenopathies may characterize a particular disease — viz., lymphadenitis. When an idea as to the state of the patient is formed by means of a rapid general examination, then all the organs and apparatus must be systematically passed in review. It makes no difference with what part of the body examination begins; the observer will generally be guided by the first information acquired. The disturbances first expe- rienced, the seat of pain, and the results of interrogation serve as guides. It is therefore well to begin with that apparatus which appears to be most affected. With a patient who complains of pain in the side, coughs, and breathes with difficulty, the chest is first examined; with another suffering from intestinal disorders, attention is first given to the abdomen; in still other instances, the nervous system is first re- viewed. Even when a diagnosis appears to have been perfectly deter- mined by the examination of one apparatus the rest of the organism must always be systematically explored. This is the only way to avoid gross errors. We shall therefore review the principal rules presiding over clin- ical examination. We shall indicate the usual procedures which can be utilized by the physician without the aid of any instrument. This method of exploration, which is, as a rule, sufficient to lead to diag- nosis, may, however, be completed by more delicate procedures; but the latter, requiring special knowledge and highly complicated instruments, do not admit of current use in daily practice. They will be briefly referred to in the next chapter. EXAMINATION OF THE SICK 415 Examination of the Circulatory Apparatus The physician may have already been guided to a diagnosis by the information furnished by the patient. Paroxysms of dyspnoea, par- ticularly of that dyspnoea designated as dyspnoea of effort; presence of a slight perimalleolar oedema in the evening ; palpitation, prsecordial pain, and a phenomenon of far greater importance — i. e., attacks of angina pectoris — are the disturbances which draw the physician's attention to the heart. The facies of the patient also guides the investigation. The special mode of lying, the bluish hue, and the throbbing of the jugular veins in a mitral patient have already been referred to. Examination of the circulatory apparatus must be conducted with a strict method. It is well to begin, not with the heart, but with the pulse. By means of palpation of the radial and the temporal arteries it must first be determined whether arteriosclerosis exists. The beat- ings which may involve certain arteries, especially their flexuous rami- fications, must be carefully noted. They can be made out by means of inspection of the vessels of the elbow joint, temple, and neck. Abrupt movements of extension produced at each cardiac systole are observed in arteriosclerotics and aortics, and are known as the dance of arteries. After this first inspection the pulse is felt and its frequency regis- tered. Its strength and fulness is determined, and whether it is regu- lar and equal. The pulse is irregular when its pulsations are not sepa- rated by equal intervals; it is said to be unequal when the successive beats do not possess the same intensity or volume. It must also be noted whether the pulse is full or compressible. In the former case the artery remains sufficiently open after beating; in the latter, it empties itself abruptly. A strong but compressible pulse immediately suggests an aortic insufficiency (Corrigan's pulse). It is possible to exaggerate these characters by raising the patient's arm; it is readily understood that the depression consecutive to the cardiac systole is thus made more apparent. In such cases the examination must be completed by a research of ^^ capillary pulsation," a name designating the alternation of redness and paleness visible in richly vascular parts of the body, such as the forehead — after friction is made in order to increase the influx of blood — the nails, and the palate. It is well, moreover, to feel the various arteries, especially those of the neck, in order to note the presence or absence of thrill, which is particularly frequent in cases of aortic insufficiency. Without dwelling on other peculiarities which may be presented by the pulse, we must mention dicrotism. This is the exaggeration of a 416 CIRCULATORY APPARATUS normal phenomenon — ^viz., the arterial pulsation is followed by a sec- ond slighter shock. Examination of the Heart. — After these first inquiries as to the state of the circulatory apparatus, examination of the heart is taken up. Inspection. — It is necessary for the patient to be in the reclining posture at the time of this examination. This rule admits of no ex- ception. He must lie upon his back, and the physician should place himself at his left side, and then take such a position as to bring his face down to the level of the patient's thoracic wall. Examin- ing the praecordial region in this position, he will clearly see, unless the subject be obese, under normal conditions, the apex beat, about 2 cen- timetres below the nipple. Under pathological conditions the im- pulse may be stronger or weaker, and it may even be imperceptible. The apex beat may be displaced downward and outward. The praecor- dial region may present a general vaulting or a limited pre-eminence, which may at times be very pronounced and even pulsating, as occurs in case of aneurism. In certain instances a more delicate phenomenon is observed — viz., the systolic retreat of the apex — indicating a peri- cardiac adhesion, and often attended by an undulating movement of the praecordial region. Palpation. — A second mode of examination is represented by pal- pation. The intensity and extent of the cardiac impulse and the ex- istence of thrilling can be made out by the hand flatly applied to the praecordial region. Then an exploration is made with one finger with a view of determining exactly the point at which the impulse takes place, as well as the point of the thrill, should any exist, and, finally, the sensitiveness of the organ. Peter has justly laid stress upon the importance of the pain which is produced by pressing upon the heart in cases of myocarditis or pericarditis. Palpation is mostly resorted to for determining the position of the apex beat. One finger is fixed at the point where the pulsation is felt, then with the other hand the intercostal spaces are counted. In this manner it is learned that, under normal conditions and in the reclining position, the apex beat is situ- ated at the fourth intercostal space. It is often said simply that it beats below the nipple. This point of comparison is very simple and convenient, but it is not precise, especially in women, whose mammary glands are often distended or hanging; variations are therefore too considerable to permit the use of this point of localization. Even in the normal state the situation of the apex beat varies with the position assumed by the patient. When he lies upon the left side, the beat is displaced 2 to 5 centimetres; when he lies upon the right side, the point of pulsation is not changed. In the standing EXAMINATION OF THE SICK 41Y position it is somewhat lowered and deviates outward. It is likewise important to know that in children the apex beat is located 2 or 3 cen- timetres outside of the nipple under normal conditions. After having determined the place where the shock is produced, its intensity should also be noted. In order to accomplish this, the ex- aminer must be familiar with the practice of palpation and have pre- served the memory of the tactile sensation obtained in normal indi- viduals of the same age and nearly the same degree of muscular and adipose development as the subject under examination. Palpation next informs us as to the cardiac rhythm — ^that is, as to the regularity and equality of the beats. When the beating is irregu- lar, it is well to examine simultaneously the heart and the radial artery. In fact, a curious discordance between the rhythm of the heart and that of the pulse is observed in some cases. False in- termittences are said to exist when no cardiac irregularity corre- sponds to the radial irregularity; in this instance there is simply cardiac inequality; the weakest beats are not transmitted to the periphery. If palpation is practised with sufficient care, information of the first importance is at times acquired for diagnosis. Indeed, it is pos- sible to thus perceive murmurs which are too often looked for by means of auscultation alone. When the murmur is vibrating, it is expressed by a purring tremor readily appreciable by palpation ; if the pulse be examined at the same time, it can easily be learned at what instant of the cardiac revolution this tremor is produced. It is even easier to determine its seat, and palpation renders good service in this regard as well, since the murmurs are propagated and auscultation always permits location of them as precisely as does palpation. Mitral stenosis especially may be diagnosticated without the aid of auscultation. By means of this same procedure certain other phenom- ena may also be perceived — for instance, pericardiac frictions and often galloping murmur. Percussion. — After palpation, percussion is practised, proceeding from the sonorous toward the nonsonorous parts. Two zones are thus delimited: a peripheral zone, which is dull, and corresponds to that portion of the heart which is covered by the lung; and an internal zone, triangular in shape and of absolute flatness. The first begins from the left border of the sternum, at the lower part of the second rib, and is limited by a curved line reaching the apex. The zone of flatness begins lower down at the level of the fourth rib, and termi- nates also at the apex. The flatness of the lower part of the heart is confounded with the flatness of the liver. In order to outline the right border of the heart, we must percuss below the right nipple; 418 CIRCULATORY APPARATUS when the upper limit of the liver is obtained, it must be united to the apex by a straight line. Then we must delimit, on the right side of the sternum, the dull zone which is produced by the prominence of the organ. Finally the aorta is percussed, which normally gives a dulness of 2 centimetres on the right side of the sternum. Cardiac flatness varies considerably under various pathological con- ditions. Without describing the phenomena that may be observed, we shall give simply a summary of the principal modifications. 1. Hypertrophy of the left ventricle : The apex is displaced down- ward and thrown outward. The line marking the upper limit of flat- ness is raised and passes above the nipple. 2. Hypertrophy of the right ventricle: The apex beat is pushed slightly outward; the line limiting the flatness passes a little above the nipple, and there is a notable zone of flatness on the right side of the sternum. 3. Pericardial effusion. a. If the fluid is not very abundant, it accumulates in the infero- external angle of the pericardium; flatness is found at a point below the apex beat. h. When the effusion amounts to about 400 grammes, the flatness takes a peculiar form, known as flatness in the shape of a coffee-ring cake {en brioche) ; at the upper part a quite characteristic notch is found (Sibson's notch). c. In cases of profuse effusions, flatness is triangular in shape, with the base down. The right side of the triangle is less oblique than the left. Auscultation. — The last and the most important mode of explora- tion is auscultation. As the physician must place himself at the left side of the patient, he will consequently auscultate with his right ear. It is better, however, to acquire the habit of auscultation with either ear. Moreover, it is well to feel the pulse of the subject while listen- ing to the pulsation of the heart, in order to readily determine the time of the cardiac revolution. Although it is not an absolute rule, it is preferable to begin aus- cultation with the base and explore successively the aortic orifice in the right second intercostal space, then the pulmonary orifice in the left third intercostal space, the mitral orifice at the apex beat, and finally the tricuspid orifice at the xiphoid appendix. Two sounds are heard under normal conditions. The first or the systolic corresponds to contraction of the ventricles; it is customary to represent it by a brief (^). Then comes the brief silence, and after this the second or diastolic sound, which coincides with the closure of the semilunar valves; this is represented by a long ( — ). EXAMINATION OP THE SICK 419 Filially, another period of silence is produced, that is the long silence, after which the movements are repeated. The object of listening to a heart is to determine the force of the impulse; the relationship between cardiac and arterial pulsations; the modifications of rhythm and pitch, and whether any pathological murmurs are superadded to or replacing a normal sound. In order to appreciate the force of pulsations, one must have lis- tened to a great number of healthy hearts. The ear preserves, as it were, the memory of the physiological sounds and perceives very ex- actly the changes which occur. It should be borne in mind that these modifications may vary from one orifice to another. Hence, an exaggeration of the second sound is quite frequently met with at the pulmonary orifice, indicating nothing more than some disturbance in the circulation of the lung. Diminution in the intensity of the cardiac sounds may be due to several causes. In some instances it depends simply upon the exag- gerated obesity of the subject; in others it is referable to weakness of the myocardium, and then it is the first sound that grows dull and finally disappears. This phenomenon, while very serious, is, however, of less gravity than weakness of the second sound. Lastly, the heart beats may grow weak and even become imperceptible as the result of effusion within the pericardium. In the latter case, when the fluid is not too abundant, it is possible to perceive the sounds through a stethoscope pressed well upon the chest when the patient is in the sit- ting posture with the body inclined a little forward. The disturbances of the cardiac rhythm may be divided into two groups : intermittence and arrhythmia. In case of intermittence the series of pulsations is from time to time interrupted by a more or less periodical suspension. The patient is not infrequently conscious of these arrests, and justly notices that suppression of a beat is followed by a systole of far greater energy. Arrhythmia is divided into regular and irregular. The irregular comprise: (1) The false steps — i.e., irregularities in the succession of heart beats. (2) Chronological perversions characterized by a too prolonged duration of some one of the heart beats or of one of the periods of silence. Regular arrhythmia includes (a) the cardiac higeminia and trigeminia — viz., the production of two or three beats one after another, followed by a sufficiently long pause; (b) the alternating pulse (Traube), characterized by one strong beat followed by a weak pulsation, whether bigeminia be present or not; (c) the coupled rhythm of the heart, when the cardiac revolutions are coupled, so to say, in strokes of two ; the first of the couple is strong, the second is so weak that it is not perceptible at the radial artery except when a 420 CIRCULATORY APPARATUS registering apparatus is employed; (d) lastly, under the name of alternating pulse, cases have been recorded by Dr. Bard in which a series of strong pulsations is followed by one of weak strokes. The cardiac rh3rfchm may also be modified by certain changes occur- ring in the relations or intensity of each heart beat. For example, the two sounds may become equal, then the duration of the two periods of silence, and the pitch as well as the intensity of the two beats be- come similar. In this event, the frequency being augmented at the same time, the ear perceives exactly the same rhythm as when a foetus is auscultated. Hence the name foetal rhythm justly given by Stokes to cases of this kind. This phenomenon, which is observed in acute myocarditis, possesses great semeiological importance and is of highly unfavourable prognostic significance. The rhythm may be modified as a result of the decomposition of one of the sounds. In most cases it is the second sound that is decom- posed. The result is a rhythm with a triple sound made up of one brief and two long sounds following each other very closely. This is the murmur of recall (bruit de rappel), which may be encountered in normal subjects; in this case, however, it is intermittent and transi- tory, and is due to the fact that the two sets of semilunar valves do not close simultaneously. This is what occurs in pathology when some disturbance of the pulmonary circulation modifies the play of the valves — e. g., in mitral stenosis. In some rare instances — ^not so rare, however, as most authorities believe — the rhythm with three sounds is due to the breaking up of the first sound. The author has frequently met with this rhythm in auscultating at the base of the xiphoid, but it has been impossible to determine its pathological significance. Auscultation frequently reveals an additional sound preceding the systole; this is the galloping murmur. The superadded sound consti- tutes a tactile rather than an auditory phenomenon; it depends upon an abrupt distention of the ventricle, whose elastic force has increased at the expense of the contractile power. It is therefore readily per- ceived by palpation, and it is thus possible to recognise that it pre- cedes the first sound and is independent of it. The galloping murmur is perceived in two different places. In most cases it is a galloping murmur of the left heart, and is heard a little inside of and above the apex beat, resulting from alteration of the myocardium. It is of very frequent occurrence in sclerosis of the heart, and generally accompanies interstitial nephritis. A second variet)^ far less frequent, is the galloping murmur of the right heart, which is heard over the xiphoid appendix and indicates gastrointes- tinal, oftener hepatic, disorders, particularly colic of lithiasis. EXAMINATION OF THE SICK 421 The modifications above referred to may easily be represented in a schematic manner: a) Ky O' ^y K^ v^ &) y^ \^ v^ \^ v^ c) \^ \^ K^ K^ K^ /) Legend Normal rhythm a Bigeminated rhythm h Murmur of recall c Decomposition of the first sound d Galloping murmur e Foetal rhythm / The rhythm may also be modified by additional murmurs originat- ing in the pericardium. These are frictions, the name of which is sufiicient to indicate the character. They have been compared to the murmur produced when paper is crumpled or to the creaking of new leather. They may accompany the two movements of the heart or one of the two periods of silence. The murmur is, as a rule, one of a to-and-fro character. When the friction occupies one of the periods of silence it produces a rhythm with three sounds, which must not be confounded with the galloping murmur. The blowing murmur is comparable to that produced when bellows are blown in making a fire (Laennec). The murmur is said to be systolic when it covers the first movement of the heart ; diastolic, when it accompanies the second; mesosystolic, when it occurs during the brief silence; presystolic, when it precedes the first sound; it then coincides with the contraction of the auricle, and therefore should be called auricular systolic. In case one has not yet become well accus- tomed to auscultation, it is better to feel the pulse while listening to the heart; the murmurs accompanying the radial pulsation are sys- tolic; those which precede it are presystolic; those that follow it are mesosystolic. The diastolic murmurs are readily recognised, since they accompany the second sound, and are, as a rule, gentle and aspiratory. The following table shows the relationship existing between the various movements of the cardiac revolution and the murmurs that are met with: 422 CIRCULATORY APPARATUS First Movement. Short Sn.ENCE. Second Movement. Long Silence. Ventricular systole. Shock of the apex. Radial pulse. Systolic blowing murmur. Mesosystolic blow- ing murmur. Closure of the semilunar valves. Diastole, auricular systole. Presystolic murmur. The first thing to do is to time and locate the murmur. In doing this the stethoscope is often of valuable service. When this is done, it is, at least theoretically, quite easy to draw conclusions. It will suffice to remember the physiological state of the heart at the moment the murmur is produced. During the systole the ventricles contract; if the seat of the murmur is at one of the auriculo-ventricular orifices, it is because the blood flows backward from the ventricle to the auricle; there is then insufficient closure, or, as is said, insufficiency or incompetency of one of the auriculo-ventricular valves. When the murmur is heard at one of the arterial orifices, it indicates that this orifice does not allow the blood to pass through it as easily as under normal conditions, this being due to diminution of its calibre. Stenosis is then said to exist. When the murmur is diastolic and coincides with the second sound, it means that the blood flows backward from the arteries into the ventricles; there is aortic insufficiency, and, exceptionally, insuf- ficiency in the pulmonary artery. The diastolic murmur heard at the apex has particular characters; it is a rolling rather than a blowing sound. It is produced by stricture of an auriculo-ventricular orifice, nearly always of the mitral. The significance of the presystolic mur- mur is the same. These varieties of murmurs may very readily be understood by examining the following table : ' Systolic 03 S ,.....! At the base To the right of the sternum. To the left of the sternum. At the apex At the xiphoid appendix To the right of Diastolic Presystolic. . j At the base the sternum. To the left of the sternum. At the apex At the xiphoid appendix, At the apex At the xiphoid appendix. Aortic stenosis. Stenosis of the pulmonary artery (quite rare). Mitral insuflBciency. Tricuspid insuflBciency. Aortic insufficiency. Pulmonary insufficiency (exceptional). Mitral stenosis. Tricuspid stenosis (rare). Mitral stenosis. Tricuspid stenosis (rare). EXAMINATION OF THE SICK 423 Without dwelling on the characters of murmurs, we shall only recall that the murmur of mitral insufficiency is often a whistling, sometimes a musical or piping one. That of aortic insufficiency is mild, soft, and blowing. That of mitral stenosis is rather analogous to rolling. Finally, a systolic, forcible, vibrating murmur is at times heard in the centre of the praecordial region, unattended by purring tremor; it means inocclusion of the intraventricular septum. In this case, and when there is stenosis of the pulmonary orifice, it is well to auscultate the back of the patient. Over the fourth dorsal vertebra a murmur is heard indicating the persistence of the arterial channel; it is due to a lesion of compensation occurring quite fre- quently in cases of congenital malformations of the heart. When a murmur is found, timed, and located, its propagation must then be determined. This is of considerable importance in definitely locating the murmurs, and especially for distinguishing those due to cardiac lesions from those produced independently of any alteration of the heart and which constitute nonorganic mur- murs. This distinction is not always easily made; it presents great interest, however, for the reason that organic murmurs are signs of grave lesions, while nonorganic have no prognostic value. Nonorganic murmurs are usually mesosystolic, exceptionally dias- tolic or rather mesodiastolic. They are soft, blowing, and superficial ; they easily vary from one moment to another; they are best heard at the end of inspiration, and disappear at the end of expiration. Tak- ing ground on this last character. Professor Potain ascribes to these murmurs a pulmonary origin. They are due to the fact that the systolic contraction imparts to the anterior border of the lung move- ments which cause the expulsion or the aspiration of a certain amount of air. According to this pathogenesis, it is comprehensible that these murmurs should be heard exclusively in those parts of the heart which are in contact with the lungs. In the mitral area the organic and the nonorganic murmurs occupy the apex. But whenever a murmur is heard either outward or inward from the apex or at the left border of the heart, it can be pronounced as nonorganic. Of course organic murmurs may be conducted into these regions, but the nonorganic or extracardiac murmurs alone are localized therein. In the aortic area murmurs are nearly always organic. In the pulmonary area they are sometimes organic and at other times nonorganic. The same is true along the left border of the sternum and at the ensiform cartilage, although in these last two areas nonorganic murmurs very seldom occur. Extracardiac murmurs are attenuated when the subject takes the standing posture ; then, in fact, the heart comes more directly in con- 28 424: CIRCULATORY APPARATUS tact with the thoracic wall. For the same reason they likewise disap- pear during an effort. If the patient can frequently be auscultated, daily modifications are observed, and even disappearances. It must also be borne in mind that nonorganic murmurs are incapable of propagation. This fact is of great consequence, since organic mur- murs present propagations which are very important to know. Mitral murmurs, for example, are conducted into the left axilla and are heard behind, especially in children, under the angle of the scapula. It is therefore necessary that these areas should always be included in the auscultatory examination. The murmurs of the pulmonary orifice are conducted toward the left clavicle; they suddenly stop before reaching this bone. Aortic murmurs are extended toward the right clavicle, which they reach and often go beyond, since they are still audible in the vessels of the neck. In a great number of instances the diastolic murmurs of the aortic orifice follow another direction. They are propagated along the sternum, from above downward, and are very clearly heard at the xiphoid appendix; in certain cases their maximum occupies the apex, in others the left portion of the sternum. Notwithstanding the vari- ability of localization, interpretation is easy. The murmur of aortic incompetency presents special characteristics and is attended by phe- nomena which do not permit of error. As already stated, it is a soft, blowing murmur, so peculiar that no other lesion can simulate it except at times some extracardiac murmur or friction. There are, however, manifestations accompanying the murmur which settle the diagnosis: these are a jerking pulse, called Corrigan's pulse, throb- bing or dance of the arteries, the intermittent double crural murmur, and capillary pulsation. In the way of practical conclusion it may be said that ausculta- tion at the classic foci is not sufficient ; the propagations of murmurs must also be looked for. In order to obtain positive information as to the nature and site of murmurs, the ear should be applied to spots far removed from the areas where they are produced. Extracardiac murmurs are produced and expire on the spot, while intracardiac mur- murs are diffuse. Before they can be declared to be organic, apex murmurs must be heard in the axilla, and even in the back ; and basic murmurs must be conducted through the vessels emanating from the affected orifice or along the sternum. In case a murmur should be diffuse and is heard at two orifices, it is often difficult to tell whether we have to deal with a single mur- mur or two different ones. Judgment should be based especially on the pitch. When a murmur is heard in one area and is propagated to another orifice, still preserving the same acoustic characters, al- EXAMINATION OF THE SICK 425 though weakened, it is possible to affirm with certainty that the lesion is single. When two differently timed murmurs are heard, it should not be hastily concluded that two lesions exist. For instance, a double aortic murmur — namely, a systolic followed by a diastolic murmur, does not necessarily mean a double aortic lesion — i. e., a stenosis with insuffi- ciency. In a great number of instances aortic incompetency is at- tended by a systolic murmur which simply depends upon the rough- ened condition of the orifice. Finally, when a diastolic blowing mur- mur is heard along with a presystolic murmur of the apex, it does not necessarily follow that there is aortic insufficiency with mitral stenosis. A simple aortic incompetency may give rise to both mur- murs. According to Flint, the presystolic murmur is due to the vibration of the mitral valves caused by the blood current. According to Keyt, it is produced at the beginning of systole. Examination of the Peripheral Vessels. — Examination of the cir- culatory apparatus is terminated by the study of the peripheral ves- sels. As already stated, the pulse must first of all be felt and flex- uosities of the arteries looked for. After exploration of the heart the condition of the vessels may again be studied, if there is reason for so doing. If aortic dilatation is suspected, palpation should be prac- tised above the clavicles in order to determine whether the sub- clavian arteries, particularly that of the right side, are not raised. The fingers should be pressed above the manubrium to discover whether the dilated aorta is not bulging there. The neck of the patient must next be examined to decide whether any arterial pulsa- tions, and especially venous pulsations, exist. In the case of tricuspid insufficiency, the blood regurgitates into the auricle and vena cava during ventricular systole. It thus imparts a series of pulsations to the brachiocephalic venous trunks; when the valves supplying these veins yield, the blood easily flows back into the jugulars. The latter then pulsate like arteries; this is venous pulse. By pressing the blood from below upward, it is easy to see that the lower portion again becomes full; this minor exploration thus enables the physi- cian to conclude as to the unquestionable presence of venous regur- gitation. Palpation may also reveal the existence of arterial thrill. In cases of aortic incompetency a thrill is found particularly in the carotids, at times so intense as to first suggest aneurism. Furthermore, auscultation of the arteries should not be over- looked. Arterial and venous sounds are to be sought for in the neck. Arterial murmurs may be due to propagation of some aortic murmur or to the presence of an aneurism of the carotid or aorta. Venous 426 RESPIRATORY APPARATUS murmurs are commonly nonorganic. The most important is that of chlorosis; it is a continuous murmur (bruit de diable) with systolic re-enforcement. When aortic incompetency is suspected, the stethoscope must also be applied to the femoral artery at the base of Scarpa's triangle. The ear there perceives a double murmur, which has been well studied by Purozier. In brief, the diagnosis of a heart lesion can only be made in a precise manner by taking into consideration a whole series of phe- nomena. Examination of the heart is not sufficient. This must be supplemented by examination of the vessels for the diagnosis and by that of various organs for the prognosis. We are thus led to speak of the other viscera. The respiratory apparatus will first be con- sidered. EXAMIN^ATIOIT OF THE ReSPIRATOEY APPARATUS Larynx. — Examination of the larynx can hardly be made without special instruments. It is possible, however, to acquire some infor- mation concerning the state of this organ by questioning the patient, and especially by interpreting certain functional derangements. The patient complains of pains during deglutition; he often suc- ceeds in locating them precisely : the trouble is not in the throat, but farther below, in the neck, and pressure upon the larynx gives rise to painful sensations, which serve to establish the diagnosis. Phona- tion is sometimes painful, and always disturbed; the voice does not possess its normal quality; it is hoarse, bitonal, or multitonal. At a more advanced stage the patient is unable to speak except in a whisper. The phenomena become complicated when the passage of air is hindered by various causes, such as partial destruction with secondary vegetating productions, cicatricial stricture, swelling of the mucous membrane or subjacent parts, as occurs in the oedema of the glottis, formation of pseudo-membranes in croup, and in the presence of a foreign body or a polypus. Under these conditions the obstruction of the air passage is expressed by a special facies and a series of manifes- tations of semeiological importance. Dyspnoea is experienced during inspiration; the air penetrates but slowly, often giving rise to a hissing murmur, and, particularly in young subjects, to a depression above the sternum, known as suprasternal retraction. At the same time, especially if the obstacle is very troublesome, each contraction of the diaphragm is attended by the formation of a furrow along the border of the false ribs; this is called infrastemal retraction. These phenomena, which are very striking in diphtheritic laryngitis. EXAMINATION OF THE SICK 427 indicate the necessity of operative intervention — tracheotomy or in- tubation. A relatively simple examination thus makes evident that the dyspnoea depends upon laryngeal alteration. In a great many in- stances the signs just described are the only ones to be considered. Laryngoscopic examination is useless and even dangerous in a patient suffering from asphyxia. Auscultation of the larynx, which reveals the so-called flag murmur in case of pseudo-membranes, is a proced- ure seldom resorted to. Beonchi and Lungs. — When the other parts of the respiratory apparatus are in question, attention is directed to their alterations by the various symptoms described by the patient. These are pain in the side, dyspnoea, cough, and expectoration. Subjective Symptoms. — The pain in the side is commonly referable to irritation of the intercostal nerve, produced by inflammation of the pleura. To enumerate the causes capable of giving rise to this in- flammation would be to cite all the affections which attack the pleura primarily or secondarily. The principal conditions are pleurisy, pneu- mothorax, inflammation of the peripheral parts of the lungs, whatever their nature, pneumonia, broncho-pneumonia, gangrene, embolism, or tuberculosis. The pain is spontaneous, and is aggravated by move- ment and cough; it is often exasperated by palpation. In certain in- stances it irradiates toward the hypochondrium and loins. When there is diaphragmatic pleurisy, pain is produced by pressure with the finger either over the course of the phrenic nerve, between the scalens, or along the left border of the sternum, or else at a point situated at the intersection of the prolongation of the sternal border and the tenth rib. This is the diaphragmatic button of Gueneau de Mussy. Dyspnoea is equally a subjective and an objective phenomenon. The patient complains of oppression, and the physician notes certain changes in the respiratory rhythm, to which reference will be made in treating of inspection. Cough is an abrupt contraction of the expiratory muscles attended by spasm of the constrictors of the glottis. It is a reflex phenomenon whose point of origin may be found in the most varied parts of the organism — e. g., the external auditory canal, the tonsils, the alimentary canal, the liver, and the spleen. In thoracic affections it presents cer- tain peculiar characters connected with its origin or the lesion exciting it. At times it is dry, as is observed in pleurisy and in the beginning of most pulmonary affections. It becomes moist as soon as bronchial hypersecretion is produced, and it is then accompanied by expectora- tion. Cough may occur in isolated efforts in ^^ spells.'^ In bronchial dilatation the patient on awakening rejects by long paroxysms of cough 428 EXPECTORATIONS purulent liquids accumulated during the night. In the beginning of tuberculosis cough appears in the morning, toward 5 a. m. In whoop- ing cough the paroxysmal character is most manifest. There then occur several series of coughing separated by a hissing inspiration, all ending in the expulsion of a viscous fluid. The name " whooplike " (coquelucJioid) has been given to a cough similar to whooping cough, but less hissing, and commonly connected with a hypertrophied con- dition of the tracheo-bronchial glands. Furthermore, according to its acoustic characters, cough may be sonorous, hoarse, or hissing. Although cough possesses no more than a restricted value from a semeiological standpoint, it acquires considerable importance by the products which it expels to the exterior. Expectorations must be care- fully studied. We shall first consider the results furnished by a simple examination with the unaided eye ; in most cases this is the only mode of exploration which can be resorted to, and we shall see that it gen- erally affords the physician sufficient information. Expectorations. — Sputa may be serous, mucoid, seropurulent or mucopurulent, or sanguinolent. Serous sputa, consisting of a frothy, aerated fluid, are quite rare; they are met with in asthmatif orm bronchitis of arthritics and in cases of so-called albuminous expectoration, which is sometimes ob- served in consequence of thoracentesis. Expectoration is tenacious and colourless in acute pulmonary con- gestion and splenopneumonia. Mucoid sputa, consisting of a transparent, glairy, colourless, aer- ated, and frothy fluid, expresses simply a bronchial hypersecretion; they are observed in bronchitis, at least in the beginning. In tuber- cular cases they sometimes contain small purulent particles, and, after a paroxysm of asthma, small dry, elastic, and granular masses. In plain (lobar) pneumonia the sputa are mucoid, but possess an absolutely characteristic appearance : they are viscous, thick, adhering to the vessel, and rusty in colour. Their semeiological importance is very great for the reason that in central pneumonia, auscultation revealing no disorder, they constitute the only certain sign of the disease. Mucopurulent expectoration is of very frequent occurrence. It is observed in the second stage of acute bronchitis, in chronic bronchitis, and in tuberculosis. In the last-named disease the sputa have a special appearance, on account of which they have been called nummular sputa. They are large round or oval flat masses swimming in a mucoid fluid and remaining clearly separated when placed in water. This very important expectoration is not, however, absolutely pathog- EXAMINATION OF THE SICK 429 nomonic; it is also found in bronchial dilatation, influenza, and measles. Mucopurulent expectoration may be coloured by the substances inhaled by the patient. Hence it is black in anthracosis and red in siderosis. Purulent sputa form at the bottom of receptacles a greenish-yellow mass having the appearance and odour of pus. They are encountered in the last stages of acute bronchitis, influenza, caseous pneumonia, and particularly in dilatation of the bronchi. In the morning the patient empties his bronchial cavities which were filled during the night. In certain instances a patient is seen to suddenly expel a consider- able amount of pus through the respiratory passages. This is desig- nated as vomique. Three causes may give rise to it. It sometimes results from a pulmonary abscess opening into the bronchi, in which case the pus is usually thin and reddish ; at other times it is due to the opening of a purulent pleurisy, at times occupying the great pleural cavity, but in most cases being confined to a limited spot. These are generally cases of metapneumonic and especially interlobular pleurisy ; the pus is quite copious, somewhat thick and greenish. Finally, a third variety, more difficult of diagnosis, is represented by those cases in which an abscess, formed in a neighbouring region, opens into the bronchi; suppurations of the liver, kidneys, and mediastinum, and abscess caused by congestion, are the most frequent agencies. Expectorations may also contain more or less organized produc- tions, such as pseudo-membranes proceeding from the larynx, at times from the trachea or bronchi, in some cases presenting a ramified ap- pearance, reproducing the ramifications of the respiratory passages. These productions are seldom met with in diphtheria, but more fre- quently in a type of chronic bronchitis which for this reason is desig- nated as pseudo-membranous. There may also be found membranes or detritus of hydatids, or miuute granules of a yellow colour, indicating an actinomycotic focus opening into the lungs. Finally, expectoration may contain variable quantities of blood, under which circumstances it is called hemoptysis. Of this two prin- cipal varieties are admitted. At times the blood is red, aerated, and frothy, as is the case in hemoptysis of bronchial origin; it is of fre- quent occurrence, and is the type encountered in tubercular subjects. At other times the blood comes from a pulmonary hemorrhage; an infarction, or, in other words, a pulmonary apoplexy, has taken place. These sputa, described since the time of Laennec as hemoptoic, are, unlike the preceding variety, dark, thick, viscous, and nonaerated; they adhere to the walls of the vessel containing them and exhale an 430 PHYSICAL SIGNS acrid odour. Tliis kind of expectoration is observed in cardiac pa- tients, particularly in mitral stenosis, in the course of infectious or chronic dyscrasias, such as Bright's disease, and as a result of em- bolism. Bronchial hemoptysis may be sufficiently profuse to cause death; it is not, however, prolonged after the occlusion of the vessel from which it issued. Pulmonary hemoptysis is less abundant, but it lasts several days in succession, since the lungs require a certain length of time to rid themselves of the blood infiltrating the parenchyma. Not unlike these two varieties is the expectoration having the ap- pearance of currant jelly ; it is met with in cases of pulmonary cancer. A last advice is to smell expectorations. Their odour possesses great semeiological importance, especially in cases of fetid bronchitis and pulmonary gangrene. The odour often leads to the diagnosis of a sphacelated focus. Examination of sputa may be completed by microscopical and bac- teriological researches, the principles of which will be referred to in connection with diagnosis. Physical Signs. — Inquiry into the physical signs is conducted in the same manner as in the case of the circulatory apparatus. The general appearance of the patient is first noted. The exact number of respira- tory movements per minute is registered, and it is often of interest to determine the relationship existing between the frequency of respira- tion and that of the pulse. Under normal conditions the respiration rate is 16 and that of pulse 80 per minute; that is, a ratio of 1.5. It is equally easy to make out the amplitude, form, and rhythm of respira- tion. The movements may be more or less profound than in health, they may also be unequal or irregular. In certain instances respiration presents peculiar rhythm, of which there are three notable types: Cheyne- Stokes respiration is especially observed in cerebral or me- ningeal lesions, particularly in tubercular meningitis, as well as in cer- tain auto-intoxications, such as uraemia. It is characterized by the following rhythm : The respiratory movements are at first rapid and superficial, then they become more and more profound; this is fol- lowed by a gradual diminution in the amplitude of the movements, which are finally arrested; there is apnoea for a few seconds and then breathing is again resumed, at first hardly perceptible, but becoming progressively fuller. These various phenomena thus follow each other in regular alternation. KussmauVs respiration occurs in diabetic coma. It is characterized by an abrupt and deep inspiration, followed by a pause, then by a, quick expiration and a new pause. EXAMINATION OF THE SICK 431 These two respiratory types are probably referable to disturbances of the medulla; at all events, they are independent of pulmonary lesions. With the expiratory dreathing of Bouchut we return to our subject. This peculiar type of respiration is met with in children suf- fering from broncho-pneumonia. It is, as it were, the reverse of the normal type. Breathing begins with a brisk expiration, followed im- mediately by an inspiration; repose takes place after inspiration in- stead of after expiration. As already stated, the mode of breathing and the important de- formities of the chest are noted by means of inspection. Previous dis- eases may have produced deformities which disturb the regular play of the lungs and thus favour alterations of this organ. Pott's disease and rickets often cause extensive deviations in the form of the thorax. In other instances the defective conformation results from occupa- tions which necessitate certain movements or certain attitudes. These facts are not without importance, but they act only as predispos- ing causes. Deformities connected with alterations of the respiratory apparatus may be general or partial. General deformities occur under two principal forms. In emphysema the lungs, having become too voluminous, give rise to dilatation of the thorax. The chest is rounded and, in advanced eases, is deservedly called "barrel-shaped." The sternum is pushed forward, the intercostal spaces are no longer visible, the supraclavicu- lar depressions disappear, the neck is shortened, and the head appears to be borne directly upon the shoulders. The consumptive's appearance is just the reverse of the preceding. The chest seems to be elongated, the eminences are more apparent than in health, the interspaces are more conspicuous, the scapulae are protruding, and the muscles atrophied. If a slight percussion is practised, fibrillary contractions (myoidema) appear beneath the skin covering the muscles, especially the pectoral muscles. The partial deformities of the chest consist in bulgings and re- tractions. In tumours of the mediastinum and in pleural effusions, one half of the thorax is increased in size; it sometimes assumes a rounded shape and imparts to the chest the appearance described as oblique oval. In order to well appreciate these deformities the following pro- cedure may be resorted to : One end of a string is held by a finger at the upper part of the sternum at equal distance from both clavicles; the lower end is then brought to the pubis. Under normal conditions the string divides the anterior part of the thorax into two equal halves ; it therefore traverses the middle of the sternum. In case of effusion 432 PHYSICAL SIGNS or tumour, the point of the sternum is deviated toward the diseased side, and the deviation to one side of the middle line measures the degree of deformity. Instead of bearing on one side of the chest, as in the example above described, the deformity may be local and express a more extended tumefaction. Such is notably the case with purulent pleurisies. The impulse of the heart is sometimes transmitted to this tumefaction, thus constituting the pulsatile empyema which may be mistaken for an aneurism. Certain functional derangements disturb the expansion of the thorax. As a result of intense pain or of some inflammatory lesion in the neighbourhood of the diaphragm, the breathing becomes far less deep upon one side than upon the other ; it may even be arrested on the affected side, resulting in manifest asymmetry during inspi- ration. Partial deformities may consist in retractions. In cases of chronic pleurisy the persisting adhesions give rise to retraction of the dis- eased side. Laennec has laid great stress on this type of alterations, of which he has given a figure that has become classical. These various alterations of the thorax sometimes produce skin lesions. When there is exaggerated expansion the skin cracks and presents vibices, which persist for an indefinite period and at times serve for retrospective diagnosis. Finally, examination of the integument may reveal oedema of the thoracic wall, an important phenomenon, for, in case of pleurisy, it is a sign pointing to the purulent character of the collection. Less frequently a subcutaneous emphysema is found due to the presence of gas bullae proceeding from some minor fissure in the respiratory ap- paratus. The results afforded by inspection should be completed by mensu- ration. It is possible to obtain important information by means of bimanual palpation. The patient being in the sitting posture, one hand is applied to the anterior part of the chest, the other to the pos- terior; in this manner the expansion is appreciated by the separation of the arms from each other. By examining alternately each half of the thorax and by seating one's self successively to the right and to the left of the patient, the deformities and expansion of each half may be determined with a little practice. A procedure which is as simple as but more exact than the pre- ceding consists in measuring each half of the chest with a centimetre measure, or even with a string. One end of the string being fixed at the spinous apophyses, the other end is brought to the middle of the sternum. In thus taking the measure, the modifications of EXAMINATION OF THE SICK 433 the thorax produced by breathing must, of course, be noted, and the degree of expansion at the end of inspiration and expiration registered. Palpation. — Palpation practised with the hand flatly applied to the thorax at times reveals friction and rales. When there is abundant pleural collection it is possible to feel with the hands the fluctuation in an intercostal space. Palpation may also appreciate the beating and reducibility of certain tumours. Palpation is particularly useful in recognising vocal fremitus. The patient is ordered to count aloud, and the physician, carrying his hands successively over all parts of the thorax, appreciates the intensity of vibrations, which may be increased, lessened, or absent. The changes are better noted when the two sides are compared. Increase in vocal fremitus indicates increased density of the pulmonary parenchyma; the phenomenon is therefore produced in case of compression, intense congestion, hepatization, and tubercular induration. Diminution of fremitus means that the parenchyma is rarefied, as occurs in emphy- sema, and especially that the lungs are abnormally separated from the chest wall; therefore fremitus is weak or altogether absent when the pleura is thickened, and 'particularly when there is liquid or gas in the sac. This research is one of great semeiological importance, for it serves to differentiate pneumonia from pleurisy and pneumothorax from a cavity. Percussion. — After palpation, percussion is practised. Care should be taken to percuss from the apex of the chest downward, first in front and then behind, one side and then the other, and, moreover, to compare the two sides in percussing the homologous parts. It must be remembered, however, that sonority is not the same everjrwhere, even under normal conditions. On the right side there is an area of hepatic flatness appreciable behind and still more so in front, where it begins at the fifth rib and becomes absolute below the sixth. The modifications of sound revealed by percussion consist in in- crease or diminution of sonority. In the former case tympanism is said to exist; in the latter, flatness. Tympanism may be general, unilateral, or partial. When general, it corresponds to a permanent distention of the air cells — viz., to em- physema. It is unilateral especially in pneumothorax. When partial, it indicates a limited pneumothorax, or that the subjacent portion of the lung is pushed away and compressed. Hence, in case of pleural effusion and at times even of pneumonia, a tympanitic sound is often heard beneath the clavicle, designated as Skodism, in honour of a Vienna physician, Skoda, who demonstrated it. Flatness may occupy a more or less extensive portion of one lung 434 PHYSICAL SIGNS or of both lungs. It varies in intensity. When it is fery slight, as occurs in certain cases of tuberculosis, dulness is said to exist. Flat- ness is very obvious in pneumonia and is absolute in pleurisy. Certain areas should be percussed with special care. These are the infraclavicular regions and the supraspinous fossae. Dulness at the apex is, in fact, of great semeiological importance, since it is one of the principal signs of pulmonary tuberculosis. A very careful percussion should be made over the roots of the bronchi in children. The ganglia located there, being often increased in size, give rise to flatness. Finally, in the anterior and lower part of the left side, there is a semilunar space known as Traube's space, presenting tyrapanitic reso- nance with high pitch, due to the presence of the stomach. This space becomes flat on percussion in cases of very copious pleural effusion. Care should always be taken to percuss during the two movements of breathing, directing the patient to open and close his mouth, and to sit down or stand up. In fact, it is readily understood that the tone should be more tympanitic during inspiration, for a greater amount of air is at this time present in the lungs. When the mouth is open, resonance increases; when it is closed, it diminishes. These modifications of resonance are supposed to possess diagnostic value in distinguishing a cavity from a pneumothorax ; but, in reality, the differences are not constant. In case of large cavities, the separate strokes of percussion below the clavicle elicit a peculiar sound, called cracked-pot sound (hruit de pot fele)y which results from sudden compression of the air. This phenomenon is produced only when the mouth is open; it disappears after several percussions, to reappear after a deep inspiration. It must also be remembered that the position of the patient modi- fies the results of percussion. The pitch is lower in the sitting than in the lying posture of the subject. All these somewhat dry details are indispensable, since in a great many instances the differences appreciated by percussion are minute and have no value except when exploration is performed under well- determined conditions. Auscultation. — Although percussion is very useful, auscultation affords information of greater certainty. Auscultation, like percussion, should also be made from above downward, and the corresponding regions of the two sides compared. The points to be noted are the intensity and tone of the respiration, the relative duration of its various cycles, and in certain instances the superadded murmurs. EXAMINATION OF THE SICK 436 The breathing may be more intense than normally ; then it is des- ignated as puerile, for respiration is more active in children than in adults. It may be hardly perceptible or not all over a more or less extensive region: this is respiratory silence (pleurisy with copious effusion, massive pneumonia). Modifications in pitch are very numerous. They are described as rude or harsh, humming or jerking, which terms sufficiently indicate their stethoscopic characters. Finally, the relative duration of the various respiratory phases may also have been modified; notably expiration may become longer than inspiration. These various modifications, though quite slight on the whole, acquire great importance in certain instances. Humming respiration, coinciding with exaggerated resonance on percussion, is a sure sign of emphysema. A jerking respiration with a prolonged expiration below the clavicle indicates incipient tuberculosis. Superadded murmurs are of far greater importance. They are resolvable into frictions, which take place in the pleura, and rales, which are produced in the trachea, bronchi, or lungs. It is not always an easy matter to distinguish frictions from rales. It is well to recall that frictions are more superficial and less regular, are generally heard at both phases of the breathing, and are not modi- fied by cough. Their intensity and pitch are variable. At times they are slight and mild, similar to the murmur produced by the crushing of tissue paper; on other occasions they are intense, recalling the noise made by new leather. Their presence justifies the physician in diagnosticating a dry pleurisy. Eales are resolvable into three groups: dry or sonorous rales, crepitant rales, and moist rales. Dry or sonorous rales are called rattling when they have a grave pitch, and sibilant when acute. They are frequently intermingled and may coexist with a variety of sonorous rales resembling the cluck- ing of the hen. They indicate bronchial inflammation or catarrh. The crepitant rale is similar to the noise produced by throwing a little salt into fire; it may more exactly be obtained by taking a lock of hair between the thumb and finger and twisting it before the ear. This sort of rale is heard during or rather at the end of inspira- tion, and is characteristic of pneumonia. Laennec described under the name of crepitant rale of resolution that sound which is audible at the third stage of pneumonia. It is clearly different from crepitant rale in that it is larger and moister and is commonly produced in both phases of the breathing. It is a subcrepitant rale. 436 PHYSICAL SIGNS Moist rales are divided, according to their size, into rales with gross bubbles, with bubbles of medium size, and with small bubbles. Rales with gross hubbies, or mucous rales, are met with in bronchitis, in bronchiectasis, and in chronic pulmonary congestion. Rales with bubbles of medium size, or subcrepitant rales, are heard when the inflam- matory process reaches the bronchi of middle calibre. Rales with fine bubbles signify capillary bronchitis, a focus of congestion, or incipient broncho-pneumonia. When located at the apex, they constitute a reli- able sign of tuberculosis. When bubbling rales are mixed with sono- rous or sibilant rales, a tempestuous murmur (bruit de tempete) is said to exist. Cavernous is called a bubbling rale which gives to the ear the sen- sation of resonance in a cavity. Unequal, irregular, dry, or moist murmurs are often heard at the apices, known as crachling. When dry, they are symptomatic of a be- ginning tuberculosis; when moist, they are connected with softening of the lesions. There is blowing when the respiratory murmur is replaced by a sound more or less analogous to that which is heard on auscultation over the trachea or the roots of the bronchi. This stethoscopic phe- nomenon is due to condensation of the pulmonary parenchyma, which transmits to the ear the murmur produced in the adjacent healthy parts. The blowing is called bronchial when it is similar to that heard on auscultation of the bronchi. It is said to be tubal when it has a slightly metallic character. These various murmurs, whose qualities are very variable, may be well fixed in the ears by the following prac- tice: The hands are united in the shape of an ear trumpet and through them the vowels a, e, o, or the diphthong ou, are pronounced in a low, blowing voice. By further narrowing the trumpet thus formed and pronouncing the vowel i, a different murmur is produced, which is analogous to the pleuritic blowing murmur. The pleuritic murmur is a tubal blowing murmur transmitted from the bronchi to the ear through the lung compressed by the pleural effusion. The interposition of a liquid layer modifies the quality of the sound; the murmur becomes soft, as if veiled or produced at a distance from the ear. It is not absolutely distinctive of pleurisy, since it also occurs in certain pulmonary congestions, particularly in Grancher's spleno-pneumonia. As to the bronchial murmur, it simply indicates increased density of the lung. It occurs under the most varied circumstances — e. g., pneumonia, broncho-pneumonia, pulmonary congestion, caseous masses, tumours, and sclerosis. A murmur may be due, not to the transmission of a normal sound. EXAMINATION OF THE SICK 437 but to the production of a superadded one in some dilated or exca- vated portion of the respiratory apparatus. When dilatation is not considerable, a murmur similar to bronchial murmur is still heard, as is the case in dilatation of the bronchi. When, however, there is a large excavation, the cavernous or, at a more advanced degree, the amphoric murmur is met with. The former of these may be produced by blowing through the hands widely separated, the latter by blowing into a bottle with a large neck. The cavernous or gurgling murmur is symptomatic of excavation, without, however, prejudging the pathological nature of the latter. It may be found in bronchial dilatation as well as in gangrene or abscess of the lungs, and by preference in tubercular cavities. It is often combined with moist rales which possess the same quality, and are designated, according to their size, as cavernular, or cavernous. When the rales are numerous and varied gurgling is said to exist. The amphoric murmur, which at times originates in a vast cavity, is encountered especially in pneumothorax. In conjunction with it an additional murmur is very often heard, analogous to that which would be produced by grains of sand falling into a metallic cup: this is Laennec's metallic tinlding, due to the resonance produced through the layer of air by the fine rales in the lungs. The metallic tinkling should not be confounded with Trousseau's brassy murmur (bruit d'aurain). In percussing with one coin upon another flatly placed upon the anterior wall of the chest, a metallic sound is heard by auscultation of the posterior wall, which sound appears to be pro- duced just under the listening ear. This is Trousseau's murmur of brass. Finally, as with air there is commonly associated a more or less considerable amount of liquid, it is possible, by shaking the pa- tient, to hear a hydro-aerial noise similar to that produced when a half -filled bottle is agitated : this is Hippocratic succussion. Lastly, the voice and the cough must be auscultated. The patient should be instructed to speak aloud while the physi- cian is auscultating. Sonorous syllables must by preference be pro- nounced. It is customary to tell him to count, beginning with 30, or to repeat the figure 33. The voice assumes the same quality as the murmur. Should a sharp and tremulous pleuritic murmur exist, the voice will also arrive at the ear with the same characters: this is egophony. This phenomenon is almost pathognomonic of pleurisy or of spleno-pneumonia ; it is often more clearly heard than the blowing murmur. In cases in which bronchial or cavernous murmur is pres- ent, the voice partakes of the bronchial or cavernous quality. Moreover, the whisper of the patient is in some instances per- ceived by auscultation as clearly as though the patient were speaking 438 THE DIGESTIVE CANAL into the ear: this is called aphonous pectoriloquy, which is mostly ob- served in serous pleurisy. Those above indicated are the principal physical signs to be looked for in cases of pulmonary affections. In order to diagnosticate well, one must consider all the phenomena observed, coordinate and group them, and also take into account not only their characters but their locations. For instance, localization at the apex is an important sign of tuberculosis. Furthermore, the mobility of certain phenom- ena should not be overlooked. The stethoscopic signs are apt to vary considerably from one moment to another in uncomplicated bron- chitis, particularly in pulmonary congestion, and at times in broncho- pneumonia. Not including emphysema and the rare lesions of the lungs, we can easily represent in tabular form (page 439) the diverse physical signs which enable the physician to make a differential diagnosis of thoracic diseases. It is of course to be remembered that the diag- nosis is not possible unless the subjective disturbances, expectoration, general phenomena, and especially the course of the events are duly taken into consideration along with the physical signs. EXAMIN^ATION" OF THE DIGESTIVE CaNAL Examination of the alimentary tract must be made from above downward, beginning with the lips, teeth, tongue, and throat. Very little can generally be learned from observation of the lips, and what little information is obtained is not connected with the condition of the digestive organs. It will suffice, therefore, to recall here the dry- ness of the lips in grave infections, the trembling observed in a great number of nervous diseases (the most remarkable type of which occurs in general paralysis), the eruptions, such as herpes, which are pro- duced in fevers, the bluish colour of cardiac patients, etc. Examination of the teeth is of greater interest. In children, the delayed appearance of the teeth is dependent upon nutritive derange- ments. Their erosions and notches are symptomatic of rickets and hereditary syphilis. In the case of syphilis a lesion of great semeio- logical bearing is frequently observed, consisting in a peculiar form of the upper incisors, to which reference is already made under the des- ignation of Hutchinson's tooth (page 228). Dental caries possesses considerable importance; it sometimes ex- plains digestive disturbances. Many dyspeptics have been cured by having their teeth taken care of, or by using artificial teeth. On the other hand, premature decay of the teeth is often referable to nutritive disorders. In diabetes, for example, the second lower molars are affected and their alteration serves as a guide to the diagnosis. Prema- EXAMINATION OF THE SICK 43d a 1 Very abundant pleurisy. Pleurisy with moderate effusion. Pulmonary congestion with pleural type (spleno- pneumonia). Pulmonary congestion with pneumonic type. Pneumonia. Broncho-pneumonia. Tuberculosis (first degree). •