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 ^LECTURES 
 
 ON 
 
 AUTO- INTOXICATION IN DISEASE? 
 
 OR 
 
 SELF-POISONING OF THE INDIVIDUAL 
 
 CH. BOUCHARD, 
 
 PROFESSOR or PATHOLOGY AND THERAPEUTICS, MEMBER or THE ACADEMY OF MEDICINE, 
 AND PHYSICIAN TO THE HOSPITALS, PARIS. 
 
 TRANSLATED, WITH A PREFACE, 
 
 THOMAS OLIVER, M.A., M.D., F.R.C.P., 
 
 PROFESSOR OF PHYSIOLOGY, UNIVERSITY or DURHAM ; PHYSICIAN TO THE ROYAL INFIRMARY, NEWCASTLE- 
 
 nPON-TYNE ; AND EXAMINER IN PHYSIOLOGY, CONJOINT BOARD OF ENGLAND. 
 
 PHILADELPHIA : 
 THE F. A. DAVIS COMPANY. 
 
 LONDON : 
 
 F. J. REBMAN. 
 
 1894.
 
 COPYRIGHT, 1894. 
 
 THE F. A. DAVIS COMPANY. 
 [Registered at Stationers' Hall, London, England.] 
 
 Philadelphia, Pa., U.S.A.: 
 
 The Medical Bulletin Printing House, 
 
 1916 Cherry Street.
 
 13 
 8 
 
 PREFACE. 
 
 IN placing this translation of Professor Bouchard's " Lectures 
 on Auto-Intoxication in Disease" before my medical brethren, 
 I feel that I am performing a service highly useful to the pro- 
 fession. No apology is required from me, unless it be for the 
 failures on my part to render fluently into English the meaning 
 of the French text. I have tried, as far as possible, to give a 
 literal and a readable translation. 
 
 Bouchard deals, in his " Auto-Intoxication," with subjects 
 of every -day interest to the medical practitioner. Man}' of the 
 facts therein alluded to can no longer be ignored. Putrefactive 
 processes in the intestinal canal and the development of phj-si- 
 ological and pathological alkaloids play an important part in 
 many diseased processes until latelj 7 unknown or misunder- 
 stood. These lectures may, therefore, be regarded as an inquiry 
 into the operation of poisons introduced from without or gen- 
 erated within the body of man, and the part they play in health 
 and disease. No subject commands a greater interest; none 
 demands more serious study. 
 
 Death frequently carries off in a few hours or days individuals 
 who are in the prime of life and in apparent good health, and at 
 whose post-mortem the most careful examination fails to reveal 
 alterations of structure such as can explain the fatal stroke. 
 Epidemics, not of a specific character, but traceable to poisoned 
 water or food, have unexpectedly appeared in certain neighbor- 
 hoods ; or members of a marriage party have died without much 
 warning, death being attributed, and very properly, to some 
 article of diet partaken of at the wedding-feast. These are the 
 cases that have aroused public opinion and awakened profes- 
 sional interest in a subject toward the elucidation of which the 
 pathological chemist has vied with the bacteriologist. 
 
 The investigations of Selmi, Brieger, Pasteur, Frankel, Han- 
 kin, Martin, and Bouchard, not to mention others, have shown 
 how disease may depend upon the presence in the system of sub- 
 
 (v) 
 
 ; / '
 
 yi PREFACE. 
 
 stances capable of combining with acids to form chemical salts, 
 and which correspond to inorganic and vegetable bases. It 
 was to these substances that the Italian toxicologist, Selmi, gave 
 the name of ptomaines, by which is meant chemical compounds 
 basic in character, and formed by the action of bacteria upon 
 organic matter. It is owing to these basic properties and their 
 resemblance to vegetable alkaloids that ptomaines are sometimes 
 spoken of as putrefactive or vegetable alkaloids, the term leuco- 
 maines, or animal alkaloids, being reserved for those basic sub- 
 stances resulting from tissue metabolism in the body. 
 
 Without discussing the question as to whether ptomaines 
 are poisonous or not, for Bouchard in these pages confines him- 
 self rather to the general action of animal poisons than to a 
 designation of them, it is sufficient to state that all ptomaines 
 are not poisonous. Some are quite inert. Brieger restricts the 
 term ptomaine to the non-poisonous basic products, whilst those 
 that are poisonous he calls " toxins." Ptomaines contain 
 nitrogen, and in this respect they resemble vegetable alkaloids. 
 Many of them contain oxygen, whilst in others this is awanting. 
 
 The one invariable circumstance surrounding the development 
 of ptomaines is the part played by bacteria. As ptomaines owe 
 their development to the activity of micro-organisms it must 
 follow that the alkaloid formed will depend upon the peculiar bac- 
 terium present, the nature of the material acted upon, the con- 
 ditions under which putrefaction goes on, and probably, too, upon 
 the health of the individual in whose body the putrefactive proc- 
 esses are taking place. It has frequently been demonstrated how 
 the nature of the soil alters the character of the micro-organisms 
 that have flourished upon it. Temperature exercises its own pecu- 
 liar influence. Some bacteria, too, require oxygen, whilst others 
 are capable of thriving apart from it. Thus it was that Pasteur 
 divided bacteria into two classes, the aerobic and the anaerobic. 
 When putrefaction occurs in the presence of air, the ptomaines 
 formed naturally differ from those produced under conditions 
 from which air is largely excluded. At all times they are ex- 
 tremely subtle. Occurring as transition products in the proc- 
 esses of putrefaction, ptomaines are to be regarded as " tem- 
 porary forms through which matter passes while it is being
 
 PREFACE. vii 
 
 transformed by the activity of bacteria from the organic to the 
 inorganic state " (Vaughan and Novy, " Ptomaines and Leuco- 
 maines"). The daily round of human life is a repetition of in- 
 tegrations and disintegrations, of processes of building up and 
 breaking down. Metabolism is taking place everywhere within 
 the human body, with the result that the complex molecules of 
 brain and- muscle in their catalysis pass through intermediate 
 stages, and are finally resolved into carbonic acid, water, and am- 
 monia. We do not know what part oxygen plays in putrefaction, 
 but the researches of Pasteur have shown how important is the 
 role pkiyed by myriads of micro-organisms. We are forced to 
 acknowledge the great impetus given to disintegrating processes 
 in organic matter by bacteria. In no part of the body is this 
 more true than in the intestine. At the present time it is a 
 debatable question as to how far even normal digestion may 
 not be aided by the multiplication of micro-organisms. Pas- 
 teur has isolated as many as seventeen microbes in the mouth. 
 Some of these dissolve albumen, gluten, and casein, whilst others 
 are capable of converting starch into glucose. Considering the 
 multiform changes that take place in the small intestine during 
 digestion, changes of a chemical, putrefactive, and fermentative 
 nature, there must be produced substances of a highly complex 
 nature alkaloids or ptomaines which, when absorbed into the 
 S} r stem, may seriously affect the vitality of the individual. We 
 are all, to some extent, protected against the injurious effects of 
 micro-organisms by the fact that the products secreted as the 
 result of microbal activity react upon the organisms themselves, 
 and thus limit their longevity. 
 
 It is the function of the gastro-intestinal juices, aided by the 
 movements of the stomach and intestine, to convert foods into 
 such soluble forms that they can be utilized by the econom}'. 
 Landois and Stirling show how undigested proteids and their 
 derivatives may be acted upon by fungi. " Many fission fungi 
 e.g., bacillus subtilis and the spirillum of cheese can produce a 
 peptonizing ferment ; so that a small amount of the peptonizing 
 done in the intestine may be due to microbes." This, though 
 not proved, has been rendered probable by the experiments of 
 Vignal. "From the normal intestinal mucus Babes has isolated
 
 Viii PREFACE. 
 
 five species of bacteria, whilst an enormous number of micro- 
 organisms exist in the large intestine and faeces. All these 
 organisms resist the action of the digestive fluids, save a few, 
 which are dissolved by the gastric juice. The researches of 
 Duclaux, Vignal, and others have shown that certain of these 
 micro-organisms secrete soluble ferments identical in their action 
 with the ferments of the digestive juices. Vignal states that cer- 
 tain of these organisms contribute to the dissolution of food in the 
 intestine. It is certain that they contribute to many processes 
 of fermentation and decomposition which go on in the intestine. 
 During fcetal life these organisms are wanting, but they are 
 numerous a few days after birth. In this connection we cannot 
 fail to remember that bacteria by their action can produce in albu- 
 minous fluids albumoses and peptones, and that the former bodies 
 are now regarded by bacteriologists as substances which play an 
 important role in many pathological processes " (Landois and 
 Stirling, " Physiology," page 344). 
 
 Bouchard, in his "Auto-Intoxication," clearly indicates to us 
 that man is constantly standing, as it were, on the brink of a 
 precipice ; he is continually on the threshold of disease. Every 
 moment of his life he runs the risk of being overpowered by 
 poisons generated within his system. Self-poisoning is only 
 prevented by the activity of his excretory organs, chiefly the 
 kidney, and by the watchfulness of the liver, which acts the part 
 of a sentinel to the materials brought to it by the portal vein 
 from the alimentary canal. Disease is not something altogether 
 apart from the individual. The patient and his disease are too 
 often found living under identical conditions. 
 
 Lauder Brunton, in his " Introduction to Modern Thera- 
 peutics," devotes considerable space to the discussion of this 
 all-important subject. Chemical investigation has shown how 
 disease depends upon the products of putrefaction and fermen- 
 tation, rather than upon the direct action of the microbes upon 
 the tissues. It is this fact which renders knowledge of the life- 
 history of bacteria so valuable to us ; for, long after the microbes 
 have been destroyed the enzymes, or ferments, which they formed 
 continue to act, and are not destroyed by a temperature which is 
 destructive to the organisms themselves.
 
 PREFACE. IX 
 
 Scarcely a month passes without a death being reported and 
 traceable to a meal of tainted meat. Dr. Stevenson, of Guy's 
 Hospital, has recently demonstrated the far-reaching and fatal 
 consequences of such a diet. I myself have reported lately in 
 the Lancet a case of acute peripheral neuritis, ending in rapid 
 death, and due in all probability to certain viands partaken of 
 at a particular banquet. The cooking of meat, already tainted 
 by the presence of microbes, whilst it is destructive to the organ- 
 isms, still allows the ferments they have formed to carrj-on their 
 work of decomposition. It is thus that the cold meat or beef- 
 steak pie which forms the material substratum of the Monday's 
 dinner, though eaten with impunity when hot on the previous 
 day, becomes a source of danger. Of this I had a striking illus- 
 tration a few years ago, in the industrial schools of this city, of 
 which I happen to be the honorary physician. A certain Sim- 
 day's dinner of roast beef had been enjoyed by all the inmates 
 of the school. On the following Tuesday morning there was 
 an epidemic of diarrhoea in the school such as had never been 
 witnessed before, there being upward of one hundred cases. 
 Several of the older lads were not slow to express the opinion 
 that their food had been drugged by materials taken from 
 the surgery. The case, however, was perfectly clear. Those 
 children who had not partaken of the slightly warmed-up cold 
 meat left over from the Sunday's dinner although placed under 
 the same dietetic conditions, except as regards that one par- 
 ticular meal alone escaped. It is to subjects such as these 
 that Bouchard draws special attention, and shows the efficacy of 
 intestinal antisepsis. 
 
 Setting aside the chapters on the " Toxicity of Urines," and 
 in which Professor Bouchard is, perhaps, seen to greatest advan- 
 tage, the lectures devoted to typhoid fever and cholera contain 
 suggestions of considerable value from a therapeutic point of 
 view. It is only lately we have come to recognize that, once the 
 dangers incidental to typhoid fever have been successfully over- 
 come, there are risks yet to be met ; in a word, auto-intoxication 
 from poisons generated within the intestinal canal. There are 
 few medical men who have not had some experience of the suc- 
 cess which has followed the administration of intestinal anti-
 
 X PREFACE. 
 
 septics in enteric fever. In my own consulting practice I have 
 used beta-naphthol with excellent results. I can recall one case 
 in particular, where a young gentleman, in the fifth week of en- 
 teric fever, was so prostrated and blanched by intestinal dis- 
 charges that he could not be turned in bed without fainting, with 
 an almost imperceptible pulse, a temperature of 105 to 106 F., 
 almost in extremis, and whose life I consider was saved by beta- 
 naphthol and other intestinal antiseptics. We know that naph- 
 thalin is sparingly soluble, and that it passes to a large extent 
 unchanged through the alimentary canal. No one denies to it, 
 however, the power of destroying the disagreeable odor of the 
 motions. Salol, or the salicylate of phenol, has also given ex- 
 cellent results. Having passed through the stomach undecom- 
 posed, it comes into contact with the pancreatic juice in the 
 duodenum, and is thereby split up into salicylic and carbolic 
 acids. The latter is set free where it is required, but, as Brunton 
 says, it has the disadvantage of being poisonous, and so betol or 
 salicylate of beta-naphthol is to be recommended instead. All 
 the substances belonging to the phenol class may be regarded as 
 antiseptics in the largest sense of the word. Outside the system 
 they readily arrest the development of germs, but within it their 
 action is not so definite. They are antiseptics so long as they 
 are not absorbed. Once this occurs, the antiseptic power of 
 the phenols is suspended. They then form non-antiseptic com- 
 pounds, Hoelscher in his experiments having shown that the 
 blood does not become sterile even after large doses of guaiacol. 
 A fairly large experience of the treatment of cei'tain diseases 
 in which the blood is poisoned e.g., puerperal fever, certain 
 forms of pneumonia, ulcerative endocarditis, etc. has led me to 
 place considerable reliance upon the efficacy of the phenols. 
 When absorbed they no longer exercise a direct action upon the 
 germs, but they exert another action, viz., a de-poisoning one. 
 Seifert and Hoelscher maintain that when the phenols are ab- 
 sorbed they induce a de-poisoning of the bod}- by combining 
 with and eliminating the toxic albumens produced by the action 
 of disease germs. Phenols are not found free in the blood. 
 They are eliminated in the urine as ethereal sulphates, in the 
 form of salts that have resulted from the oxidation of some com-
 
 pound of the phenols with albumen, and, to a large extent, with 
 toxic albumens, the result of the vital activity of germs. It is 
 believed that the compounds of toxic albumens and phenols 
 are non-toxic. The} 7 quickly undergo oxidation, hence the ap- 
 pearance of phenols in the urine as ethereal sulphates. Chemical 
 disintegration and recombinations undoubtedly occur, and to 
 these must be attributed, by the process of de-poisoning just 
 alluded to, the good results that follow the administration of 
 antiseptics in certain forms of blood-poisoning. Under all cir- 
 cumstances a rigid intestinal antisepsis cannot but be of the 
 greatest possible utility. 
 
 The salols pass through the stomach without undergoing 
 decomposition. In the small intestine salols and phenols are 
 split up into their antiseptic constituents : salol into salicylic and 
 carbolic acid, betol into salicylic acid and beta-naphthol, whilst 
 guaiacol carbonate the new remedy for phthisis decomposes 
 into guaiacol and carbonic acid. 
 
 I shall leave the reader to follow Dr. Bouchard in his criti- 
 cism of cholera and its relation to the comma bacillus. 
 
 The part played by auto-intoxication in mental diseases is 
 attracting attention. In the Medical Week, August 11, 1893, 
 there is a length}- report upon the subject as discussed, at the 
 French Congress of Psychological Medicine, by Drs. Re'gis, 
 Chevalier-Lavaure, and others. It has long been known that the 
 various fluids of the body undergo modifications in the insane. 
 Recent investigation has shown that the urine is much less toxic 
 than normal in cases of mania, while the lethal action of this 
 fluid is increased in melancholia. Maniacal urine gives rise to 
 excitement and convulsions when injected into an animal, while 
 the injection of urine from a case of melancholia is followed by 
 depression of spirits, restlessness, and stupor, a proof that 
 auto-intoxication is the cause and not the effect of the mental 
 condition. Besides, in the mental disorders that arise during 
 the course of such infectious diseases as typhoid and other 
 eruptive fevers, as well as in puerperal fever, there is little doubt 
 that these disturbances are due to the action of pathogenic 
 organisms, either directly or indirectly through the influence of 
 their toxins ; and according to the stage of the illness, so is the
 
 xii PREFACE. 
 
 character of the mental symptoms. One has only to mention 
 these facts to throw into bold relief the excellent results that 
 frequently follow the administration of antiseptics and excitants 
 to the emunctories. 
 
 This translation is given in the hope that English readers 
 may find in its pages much that is interesting from a pathological 
 point of view, and much that is valuable and suggestive from a 
 therapeutical. For mistakes attributable to myself I crave in- 
 dulgence ; for Americanisms in spelling I am in no way respon- 
 sible. As a translation, I am only too conscious that the work 
 is far from being perfect. If, however, the book serves a useful 
 end, I shall be fully repaid for the time and labor I have spent 
 upon it. 
 
 I cannot draw this preface to a close without thanking Pro- 
 fessor Bouchard for the freedom he has allowed me in translating 
 and publishing this work, and also of expressing my sense of 
 indebtedness to my friend and clinical clerk, Mr. Wm. Turnbull, 
 for his kindness in revising the proofs, and for the great help he 
 has afforded me in drawing out the index. 
 
 THOMAS OLIVER. 
 
 7 ELLISON PLACE, NEWCASTLK-UPON-TYNK, 
 January, 1894.
 
 CONTENTS. 
 
 LECTURE I. 
 
 PATHOGENIC PROCESSES IN THE MAIN, 1 
 
 LECTURE II. 
 
 PRODUCTION AND ELIMINATION OF POISONS BY THE ORGANISM, 14 
 
 LECTURE III. 
 
 PRELIMINARIES TO THE EXPERIMENTAL STUDY OF THE TOX- 
 
 ICITY OF THE PRODUCTS OF EMUNCTION, . . . .22 
 
 LECTURE IV. 
 
 ON THE TOXICITY OF URINES, 29 
 
 LECTURE V. 
 
 CAUSES OF THE TOXICITY OF URINE, 46 
 
 LECTURE VI. 
 
 TOXIC PRINCIPLES IN URINE THE PART THEY PLAY IN PRO- 
 DUCING UREMIA, 60 
 
 LECTURE VII. 
 
 ORIGIN OF THE TOXIC SUBSTANCES OF URINE TOXICITY OF 
 
 THE BLOOD AND TISSUES, 69 
 
 LECTURE VIII. 
 
 ORIGIN OF THE TOXIC SUBSTANCES OF URINE TOXICITY OF 
 
 THE FLUIDS AND OF THE CONTENTS OF THE INTESTINE 
 (BILE AND THE PRODUCTS OF PUTREFACTION), . . . 83 
 
 (xiii)
 
 XIV CONTENTS. 
 
 LECTURE IX. 
 
 ORIGIN OF THE TOXIC SUBSTANCES OF URINE TOXICITY OF 
 
 THE PRODUCTS OF PUTREFACTION AND OF THE F.&CES, . 90 
 
 LECTURE X. 
 
 INTESTINAL ANTISEPSIS, 97 
 
 LECTURE XI. 
 
 PATHOGENESIS OF UREMIA DISTINCTION BETWEEN THE SYMP- 
 TOMS OF THE PRE-UR^EMIC PERIOD OF NEPHRITIS AND THE 
 SYMPTOMS OF INTOXICATION, . . . . . .102 
 
 LECTURE XII. 
 
 PATHOGENESIS OF UREMIA DISCUSSION OF THE EXCLUSIVE 
 
 THEORIES, 108 
 
 LECTURE XIII. 
 
 PATHOGENESIS OF UREMIA DISCUSSION OF THE EXCLUSIVE 
 
 THEORIES, 114 
 
 LECTURE XIV. 
 
 PATHOGENESIS OF UREMIA THE PART PLAYED BY ORGANIC 
 SUBSTANCES AND MINERAL MATTERS IN UR^EMIC INTOXI- 
 CATION, 120 
 
 LECTURE XV. 
 
 THE THERAPEUTIC PATHOGENESIS OF URAEMIA, . . . 127 
 
 LECTURE XVI. 
 
 TRANSITORY OR ACUTE AUTO-INTOXICATION OF INTESTINAL 
 
 ORIGIN INTERNAL STRANGULATION AND CONSTIPATION, . 138 
 
 LECTURE XVII. 
 
 ACUTE OR TRANSITORY INTESTINAL AUTO-INTOXICATION GAS- 
 TRIC DISORDERS INDIGESTION POISONING BY TAINTED 
 
 MEATS, ... .146
 
 CONTENTS. XV 
 
 LECTURE XVIII. 
 
 CHRONIC GASTRO-INTESTINAL AUTO-INTOXICATIONS DILATA- 
 TION OP THE STOMACH, 154 
 
 LECTURE XIX. 
 
 DILATATION OF THE STOMACH ETIOLOGY, PATHOGENESIS, AND 
 
 THERAPEUSIS, 173 
 
 LECTURE XX. 
 
 AUTO-INTOXICATION OF INTESTINAL ORIGIN TYPHOID FEVER, . 187 
 
 LECTURE XXI. 
 
 PATHOGENIC THERAPEUSIS OF TYPHOID FEVER ANTISEPSIS OF 
 
 THE INTERNAL MEDIUM, 194 
 
 LECTURE XXII. 
 
 ON THE PATHOGENIC THERAPEUTICS OF TYPHOID FEVER THE 
 
 TREATMENT OF HIGH TEMPERATURE, .... 201 
 
 LECTURE XXIII. 
 
 PATHOGENIC THERAPEUTICS OF TYPHOID FEVER NEW MODE OF 
 
 BATHING IN FEVERS; DIETING OF FEVER PATIENTS, . 208 
 
 LECTURE XXIV. 
 
 AUTO-INTOXICATION BY BILE. PATHOGENESIS OF JAUNDICE, . 222 
 
 LECTURE XXV. 
 
 MALIGNANT JAUNDICE : AGGRAVATED JAUNDICE, . . . 229 
 
 LECTURE XXVI. 
 
 THE TOXIC NATURE OF PATHOLOGICAL URINES, . . . 236 
 
 LECTURE XXVII. 
 PYOCYANIC DISEASE, POISONING; ACCIDENTS IN DIABETES, . 243
 
 Xvi CONTENTS. 
 
 LECTURE XXVIII. 
 POISONING BY PATHOLOGICAL POISONS. CHOLERA, . . .249 
 
 LECTURE XXIX. 
 CHOLERA (CONTINUED), 257 
 
 LECTURE XXX. 
 CHOLERA (CONCLUSION), 265 
 
 LECTURE XXXI. 
 
 THE GENERAL TEIERAPEUTICS OF SELF-POISONING, . . . 273 
 
 LECTURE XXXII. 
 GENERAL RECAPITULATION, 280 
 
 INDEX, , 289
 
 LECTURES ON AUTO-INTOXICATION. 
 
 LECTURE I. 
 PATHOGENIC PROCESSES IN THE MAIN. 
 
 Preponderance of pathogenesis iu the preoccupations of contemporary medicine. 
 The four great pathogenic processes : primary elementary dystrophies ; nerve 
 reactions ; previous disturbances of nutrition ; infection. Influence of 
 earlier disturbances of nutrition upon the production of most of the chronic 
 and of many acute diseases. Definition of diathesis considered as a morbid 
 
 temperament. Infection. Living nature of contagious matter. Small 
 
 number of diseases for which parasiticism has been established with certainty. 
 Extreme probability of the hypothesis according to which all contagion 
 might be the function of a vegetable organism. The part which medicine 
 plays in the presence of the doctrine of micro-organisms. The abundance of 
 microbes around man and the relative infrequency of infection. Association 
 and combination of pathogenic processes. The powerlessness, as a rule, of 
 nervous reactions to determine by them alone disease. Morbid predis- 
 positions established by the arthritic and scrofulous diatheses. Disease 
 opportunity. Diathesis of short duration established by a nervous reaction, 
 which interferes for the time being with nutrition, and opens the portal to 
 Infection. Diathesis acquired. Diathesis hereditary. Interrupted accidents 
 
 in the course of diatheses. Bond between new discoveries and traditional 
 
 medical observation. The physician has a double duty : to contend with 
 
 microbes, and to fortify the organism against them. How disturbance 
 
 of nutrition may produce disease. Intoxication of the organism by in- 
 crease or retention of normal matter. Intoxication by the formation of 
 
 abnormal matter. The part intoxication plays iu the processes of infection. 
 
 Five hypotheses relative to the mode of action of pathogenic microbes. The 
 role of microbes iu the formation of certain poisons normal to the organism. 
 
 GENERAL PATHOLOGY. 
 
 WE are living in an age when it is proper to live and when 
 all are interested in medical matters. It is not that medicine 
 has, in ai^ sense of the word, revived, but that she has simply 
 changed her attitude of observation. 
 
 After having devoted herself during many long }-ears to the 
 verification of symptoms, to the research of anatomical lesions, 
 to the study of pathological physiology, she comes at last to 
 study the origin of disease. What is characteristic of these 
 modern days, so far as medicine is concerned, is the high place 
 we assign to the study of the origin of diseases. 
 
 1 0)
 
 2 LECTURES ON AUTO-INTOXICATION. 
 
 If the causes are innumerable, you know that the processes 
 following those which induce disease can be relegated to four 
 types. These four chief pathogenic processes are: (1) primary 
 elementary dystrophies, (2) nerve reactions, (3) disturbances 
 antecedent to nutrition, and (4) infection. 
 
 The first of these processes is the most simple, but it is the 
 least studied, and I may add that it is almost completely un- 
 known. It is that which arises from the vital activity of cells, 
 when it is directly brought under our notice by some cause, 
 physical, mechanical, or chemical; from the lightning-stroke to 
 the intoxications, or by the way of trauinatism. If one neglects 
 more than is necessary the study of that simple process, it is be- 
 cause very often it is complicated with effects of a local char- 
 acter, vascular or otherwise, which are the reflex result of ner- 
 vous requirements. 
 
 We have known for a very long time the important part 
 played by the nervous system as an intermediary in the produc- 
 tion of disease. Have we exaggerated it, or have we accorded 
 to the reflexes a pathogenic influence greater than that which 
 they have in reality ? When they are set in operation in a per- 
 son in good health they only rarely cause the development 
 of the malady properly called ; their role is often to bring 
 about fleeting indispositions or troubles, for a longer or shorter 
 period, to the extent of realizing predisposition or the morbid 
 opportunity. 
 
 You know that those pathogenic influences are peripheral or 
 central. It is in their action upon the cutaneous nerve-endings 
 that cold and moisture interpose as a cause of disease ; it is by 
 their direct action upon nerve-centres that disorders of the af- 
 fections, changes of disposition, mental fatigue, and so many 
 other psychical disturbances frequently bring about deteriorated 
 health. Generally speaking, it is only a condition accessory or 
 predisposing to the development of the disease ; it is rarely the 
 nearest or exclusive provocative cause. 
 
 The two other pathogenic processes of chief importance are 
 disturbances antecedent to nutrition and infection. Disturb- 
 ances of nutrition rule, in my opinion, the largest number of 
 chronic diseases, and explain the appearance of many illnesses
 
 PATHOGENIC PROCESSES IN THE MAIN. 3 
 
 of an acute character. I had devoted to this study the first 
 years of my profession, and I have returned to it when I 
 have tried to determine the exact domain of diathesis and the 
 processes by which we can undertake the cure of diathetic dis- 
 eases. My constant effort has been, and my duty will, perhaps, 
 be, to render to diatheses the part which is theirs by right in 
 the prejudices of medicine. To do that, I have been obliged to 
 disengage them from the mystic cloud which encircled them, and 
 I have rendered them physiologically intelligible when I have 
 said that diathesis is a permanent disturbance of nutrition, which 
 prepares, provokes, and maintains different diseases, as seen in 
 their location, their evolution, and pathological process. This 
 was to restore to diathesis its traditional signification ; it was to 
 consider it anew as a morbid temperament. 
 
 Infection is the last of the four pathogenic processes. We 
 find, again, traces of this notion very far back in the past, but it 
 has assumed form only within the last quarter of this century. 
 It is what we call, or it is what, now particularly, deserves to be 
 called, contagium vivum. 
 
 The interpretation of infection has provoked the warmest 
 discussions in our times. The brilliancy of certain recent dis- 
 coveries has been to fascinate and to dazzle. It has caused, 
 according to temperament, enthusiasm or sarcasm, infatuation 
 or dread. Infatuation or dread, these are two sentiments 
 which science repudiates. She will continue, in spite of resist- 
 ance, and in spite of the intemperate displays of an exaggerated 
 enthusiasm, to march, serenely and unmoved, toward truth. 
 
 At the present time the living nature of contagious material 
 is beyond all question. Ever since man has known contagion 
 he has been asking himself of what it might consist. Of all 
 hypotheses, not one has been verified, until the day in which it 
 has been demonstrated that in the body of an individual attacked 
 by a contagious disease there exist the lower vegetable organ- 
 isms, capable of implanting themselves and of multiplying in 
 the tissues of a healthy man, and of determining in him a disease 
 similar to the original. That is the final termination of all sys- 
 tems relative to contagion. 
 
 Demonstration 1ms not been made for all contagious diseases;
 
 4 LECTURES ON AUTO-INTOXICATION. 
 
 doubtless it is not even complete, save in a number more 
 limited than we maintain. Parasiticism is established with 
 absolute certainty in four diseases of man, charbon, glanders, 
 tuberculosis, and gaseous gangrene ; besides, proof is nearly 
 established in blennorrhagia and erysipelas. To these diseases of 
 men we may add several experimental septicaemias, the cholera 
 of fowls, swine fever, and symptomatic pustule. This is a small 
 number, and yet it is large if we consider that in those cases 
 alone where infection could be interpreted in a positive manner 
 the solution has been universally agreed upon. Contagion has 
 always been recognized as the function of a vegetable organism. 
 
 Have we the right to generalize, and can we say that it is 
 always due to the transfer of a vegetable from the contaminating 
 to the contaminated individual ; that in all these cases infection 
 is the result of the introduction into the economy and of the 
 multiplication of a vegetable parasite? No, absolutely ; yes, if 
 we are content to enunciate an extremely probable hypothe- 
 sis. We surely except nervous contagion, which results from 
 example. 
 
 In regard to diseases of a contaminating nature, every time 
 that we have found an explanation of contagion it has been that 
 which I have just given you ; no other has been verified, no 
 other is verifiable. 
 
 Let us admit, then, at least provisionally, that each contagious 
 disease is produced by a microbe. Let us wait until positive 
 proof shall be furnished for those in which the microbe has not 
 yet been demonstrated. We will accept without astonishment 
 the announcement of its discovery, and without uneasiness the 
 delays which might be caused by that demonstration. Let men 
 trained to the difficulties and to the refinements of microbio- 
 logical research give us this fulfillment of demonstration, and it 
 will be with thanks that we will praise every one of their discov- 
 eries. The role of the physician is not exclusively to seek the 
 infectious agent; but it ought to count with him. To speak of 
 microbe in the place of virus or of contagion is not to replace 
 one word by another ; it is to substitute positive knowledge for 
 ignorance or whim. It is, at the same time, to state this emi- 
 nently practical question : What are the conditions which render
 
 INFECTION IS PRECEDED BY DISORDERED NUTRITION. 5 
 
 possible the development of the microbe ? What are the con- 
 ditions which ma}' hinder its multiplication? 
 
 What renders possible the development of an infective dis- 
 ease is not the chance meeting of man and microbe. This meet- 
 ing is constant, but it is generally without result. Microbes, 
 even the most dangerous, assail us. They are spread around 
 us with the same prodigality that nature distributes develop- 
 ing matter, and yet growth is uncommon. Infectious disease, 
 too, is only an accident, because the infectious agent finds only 
 exceptional circumstances favorable, I do not say to its pene- 
 tration, but to its development and its multiplication. 
 
 The healthy man is not attractive to the microbe. Almost 
 constantly invaded by infectious agents, he reacts against them, 
 and in this contest keeps generally uppermost to such a point 
 that often the disease does not even become apparent. 
 
 It is not thus with him when his vitality is weakened ; then 
 his means of defence diminish. Just as we see rushes become 
 covered with soil where certain unusual circumstances are op- 
 posed to the natural flow of water, so certain microbes may in- 
 vade the human organism, whose health breaks down, whenever, 
 by the fact of disordered nutrition, the chemical constitution is 
 modified. 
 
 It is, therefore, a modification antecedent to nutrition which 
 renders infection possible. Disease is thus the result of two dif- 
 ferent processes, one of which can only act by means of the 
 other. In short, pathogenic processes are rarelj r isolated ; in the 
 great majority of cases they are associated and combined. 
 
 In regard to this complexity, you do not find it only where 
 there is question of contagion, but also where there is question 
 of the most simple form of disease, traumatism, for example. 
 In those primary and elementary forms of failure of nutrition 
 where the cause directly attacks certain cellular groups, where the 
 cells become detached from each other, crushed, soddened, 
 disease will scarcely ever be established by this unique disor- 
 der of a cellular group. Nearly always tranmatisn will dcirr- 
 mine the putting into operation of new pathogenic processes, 
 infection, and nerve reactions. Disorganization of cells allows 
 the entrance of infectious agents, and prepares in them the mat-
 
 6 LECTURES ON AUTO-INTOXICATION. 
 
 ter that they should destroy. Besides, the cause which is capable 
 of inducing alterations falls oftenest upon the nerve elements, and 
 through them, as an intermediary, provokes reflex disturbances. 
 Some manifest themselves in. the wounded part, where the irrita- 
 tion of blood, absorption, and nutrition cause work to be done 
 in an abnormal manner. Others reflect upon the whole economy ; 
 the heart contracts oftener, respiration is accelerated, and the 
 elaboration of material is found altered in all the cells of the body. 
 Urea and carbonic acid are produced in much greater quantity. 
 Nerve reaction has not only added certain peculiar features to 
 local manifestations, it has bound the whole organism to the 
 work which is going on in the wounded part. 
 
 Besides, nerve reactions nearly always borrow the co-opera- 
 tion of another pathogenic process. Every nerve excitation, 
 cold, shock, emotional or traumatic, may produce syncope, epis- 
 taxis, diarrhoea, and polyuria. These are not, then, diseases. 
 The real disease, when it is roused by nerve reaction, infers, 
 except in cases where the intensity of the stimulation is excessive 
 and those wherein the nervous system is abnormally excitable, 
 infers do I say it ? an essential deterioration of the organism. 
 
 In whom does a draught of cold determine a coryza or a 
 bronchitis ? In every one, will you say ? Perhaps ; but especially 
 in those whose health is habitually or actually altered. Amongst 
 the diathetic, especially arthritic or scrofulous, you will see 
 this fleeting nerve reaction produce in them lasting effects ; the 
 coryza is tenacious and the bronchitis is stubborn. Disease 
 will quickly follow upon nerve reaction, but it is the unavoid- 
 able deterioration of the organism which may hasten its explo- 
 sion, and which often renders it persistent and chronic. In the 
 non-diathetic man, for the present weakened or indisposed, dis- 
 ease resulting from nerve stimulation will be not less prepared 
 by disturbance of nutrition, although the disturbance is only 
 transitoiy, " it is the morbid opportunit}'," the brief diathesis 
 of the authors of last century. Men fatigued by overwork or 
 pleasure exposed to depressing influences are struck by con- 
 ditions, real and disease-developing, from insignificant nerve 
 excitations, which would have produced nothing in perfectly 
 healthy men.
 
 INFECTION POSSIBLE BY INFLUENCES UPON NERVOUS SYSTEM. 7 
 
 Very often disease induced by nerve reflex even disease 
 from cold is an infectious illness, and we have not onty in this 
 particular case a new example of the .association of the two dif- 
 ferent pathogenic processes, but we find here the association of a 
 third factor. In reality, nerve reaction could not have created 
 infection : it could act onlj'by rendering this infection possible; 
 by weakening the defence which the healthy organism naturally 
 opposes to microbes ; by modifying nutrition so as to develop a 
 chemical medium favorable to the cultivation of vegetable 
 organisms. The reaction of a disturbed nervous system induces 
 temporary disturbance of nutrition. This, in its turn, opens 
 the way to infection always at hand, to germs always present, 
 which, without doubt, have to fulfil in nature another part, but 
 which, destined to destroy dead matter, are also capable of 
 destroying living matter when they find it in a state of prepara- 
 tion. In this, perhaps, lies the pathogenic history of angina, of 
 pneumonia, and of rheumatism. 
 
 If nerve reaction, by corrupting for the moment nutrition, 
 can produce the morbid opportunit3 r , it may also modify nutrition 
 in a lasting manner, and develop diathesis, but it will be the 
 acquired diathesis. The acquired diathesis, once established, 
 may become hereditarily transmissible ; and if you go back to 
 its etiology, be it in the individual or in his ancestors, you will 
 easily recognize that it has hud for its origin the putting into 
 abnormal play of nerve reactions. Let a bad alimentary hygiene 
 cold and moisture, privation of air and light cause an infant 
 to be scrofulous, and let the permanence of the same causes 
 keep up in him this nutritive disorder, which we designate under 
 the name of scrofulous diathesis ; or let a young man, by 
 Ii3'gienic errors, by the abuse of the table, by protracted studies 
 at night, by venereal excesses, l>y nervous shocks, which may 
 be the consequence of complete derangement of mind, as also 
 of a jaded brain, develop this other nutritive disorder, which we 
 designate under the name of arthritism, in both of these each 
 cell will have a tainted nutrition, and will produce cells that 
 maintain the same nutritive t} r pe. And amongst these cells the 
 generative elements ovule or spermatozoon in their turn will 
 give birth to the cells of a new being, whose nutritive activity
 
 8 LECTURES ON AUTO-INTOXICATION. 
 
 will be similar to the individual that has begotten them. The 
 acquired diathesis has become hereditaiy ; it does not recognize 
 for its cause in the descendants the vice of their own nerve 
 reactions. In these, nevertheless, the diathetic state really 
 arises from nerve perturbations experienced by their ancestors. 
 There are certain historical families whose pathological gene- 
 alogy we even know, and where the reality of the origin of 
 these morbid states can be verified. 
 
 The diathetic nutritive disorder is more than a morbid 
 threatening ; it is disease in activity. But how is this disease 
 going to break out ? It is generally after, the operation of an 
 external cause which has induced nerve changes ; another 
 example of the necessary association of several pathogenic 
 processes. Here is an arthritic ; how will he be seized with an 
 attack of gout? Very often after a chill, a shock, emotional 
 or from injuiy. Disease thus called forth in the course of a 
 diathesis is an episode, a paroxysmal accident ; but this acci- 
 dent, this episode, may appear spontaneously, as the consequence 
 of the excess of the nutritive disorder which oftenest recognizes 
 as its determining cause nerve change. Some people persist in 
 not making this distinction, in not seeing in gout anything but 
 the gouty accession; so much so that gout would not be a 
 disease, but a succession of independent diseases. But what 
 explains and links the attacks together is precisely this diathetic 
 state, which I consider the result of a failure of nutrition. The 
 attack of gout, on the contrary, which is the paroxysmal acci- 
 dent in the course of a diathesis, is characterized by an accelera- 
 tion of nutrition, as I said a long time ago, and is repeated 
 to-day, as if it were a novelty : it is the curative attempt which 
 re-establishes the broken equilibrium. 
 
 If nerve shock is capable of thus inducing an attack of 
 gout in an arthritic it will never cause it in an individual whose 
 nutrition is not weakened. The nutritive derangement which 
 renders possible the pathogenic influence of nerve reactions fa- 
 vors also parasiticism. Is it not amongst arthritics that you see 
 developed by preference pityriasis versicolor? Is it not amongst 
 the scrofulous that you see erysipelas repeated witli a truly dis- 
 heartening frequency ? I have multiplied examples sufficiently
 
 SEARCH AFTER MICROBES. 9 
 
 to be able to say that, without any preliminary change in nutrition, 
 man is sheltered from infection. I have excepted syphilis, 
 against which he seems unprotected. It is because several 
 pathogenic conditions are necessary before disease can be pro- 
 duced that we generally resist harmful influences. The causes 
 of disease are innumerable ; but, in order to attack and conquer 
 us, the} 7 must be associated ; without this necessity they would, 
 without doubt, have annihilated the human species. 
 
 Thus, only to deal with infectious diseases, I am right, you 
 see, in telling you now that the physician ought not to allow 
 himself to be absorbed alone in the research after a microbe. He 
 ought to occupy himself with the infectious agent ; but he ought 
 also to retain a good deal of his anxiety for the study and research 
 of circumstances which disarm the organism against the invasion 
 of that agent. When the physician shall be in possession of 
 this double knowledge that man}' diseases are produced by mi- 
 crobes, and that these can only act by means of a deterioration 
 of the health, resulting from various pathogenic processes, he 
 will recognize that the new discoveries contain nothing sub- 
 versive, and that the lessons taught by ancient medical observa- 
 tions are not compromised; he will know that the part he has to 
 play is still the same to-day as it was twenty years ago, and that 
 whilst seeking the means of combating microbes he ought and 
 he will always be obliged to sustain the forces of the organism 
 and make good its defence, inspiring himself constantly with this 
 truth : before every illness there is a disturbance in life, for nu- 
 trition is life. What can bring about this disturbance, the first 
 step to be overcome before becoming ill ? It may bring about a 
 change in the production or distribution of the forces which lib- 
 erate certain substances elaborated by the living organism. It 
 may modify the matter itself, augment or diminish it, whilst 
 preserving the normal proportion, or it may bring about dispro- 
 portion of the constituent elements ; it may, in short, cause the 
 appearance of abnormal substances through perversion of the 
 changes associated with nutrition. From absolute increase of 
 normal matter, or the production of abnormal, intoxication may 
 be developed. 
 
 Substances the most essential to the constitution of the body
 
 10 LECTURES ON AUTO-INTOXICATION. 
 
 may become hurtful when they accumulate. If the subtraction 
 of water is dangerous, its excess is none the less so ; it changes 
 the conditions of osmosis ; it causes a swelling up of the cells, 
 and washes out their dialysable material ; it thus disturbs their 
 chemical constitution, and weakens or perverts their functional 
 activity. Mineral substances can, by their excess, equally deter- 
 mine accidents that are truly toxic, the salts of potassium par- 
 ticularly. The most important excrementitious material car- 
 bonic acid could not be retained in the organism a few minutes 
 without death being the consequence. The biliary acids also, if 
 they do not find a free escape outwardly, produce fatal poisoning. 
 All the soluble ferments elaborated by certain glands can exer- 
 cise a poisonous influence, either local or general. We find 
 even in certain secretions in saliva, for example products ex- 
 tremely toxic, and which are not ferments. This toxicity is 
 only partly due to alkaloids. Whatever opinion we may have 
 in regard to the origin of alkaloids, it is certain that we meet 
 with them in normal tissues, and it is possible that they may be 
 one of the results of this disassimilation of animal cells ; but it 
 is not demonstrated that these alkaloids of the normal tissues 
 are toxic. It is not thus, however, with the alkaloids of certain 
 products of secretion, of urine in particular. Without multi- 
 plying examples, you see that the augmentation of normal sub- 
 stances, either by increased formation or retention, can induce 
 quite a series of toxic accidents, some of which have already 
 been named, such as asphyxia, uraemia, uricsemia, cholsemia, 
 glycaemia. 
 
 Perverted nutrition leads up to the development of new sub- 
 stances which may become toxic. There are often formed in the 
 organism peptones, which do not originate in the intestinal tube, 
 but which are injurious in this sense, that, being dialysable, they 
 escape by the urine, and thus bring about an abnormal spolia- 
 tion of the organism. There are thus produced abnormal albu- 
 mens, which escape by the kidneys, and seem capable of destroy- 
 ing the nutrition of the renal epithelium and of inducing certain 
 nephrites. Disease also causes the appearance of abnormal 
 coloring matter or of substances transformable into coloring 
 matter, amongst which are found those that, in urines, take on
 
 ACTION OF MICROBES UPON THE TISSUES. 11 
 
 a red coloration under the influence of perchloride of iron. I 
 will mention leucin, tyrosin, and all the imperfect excre- 
 mentitious products which arise from insufficient elaboration 
 on the part of the liver, and many other toxic substances, of 
 which I know neither the names nor the constitution, but 
 whose presence in morbid urines I shall demonstrate to yon 
 physiologically. All these substances are capable of producing 
 forms of intoxication, amongst which I will mention eclampsia, 
 acholia, diabetic coma, and many other grave conditions, as also 
 numerous indispositions. 
 
 If intoxication is one of the accidents likely to arise from 
 disturbances of nutrition let us see what infection can do. We 
 have thought over many of the hypotheses bearing upon the 
 mode of action of microbes. But if the anatomy of these hurt- 
 ful agents is scarcely known their ph}-siology is still less known. 
 We have imagined that they act in five different ways. We 
 have ascribed to them a mechanical role, supposing that they 
 might cause obstruction in the vessels, more particular!}- those of 
 the lung and the kidney. The fact is perfectly demonstrated for 
 charbon and for the septicaemia of Charrin ; but the microbes 
 which live in the blood are rare almost the exception. It is 
 also admitted that they ma3 T induce traumatic changes, erode 
 and perforate cells. This is a hypothesis whose aid I called in 
 when I established the group of infectious nephrites. We really 
 find microbes in the organism, in urine, and we find a lesion 
 of the renal epithelium. It is admissible that they have broken 
 through this epithelial barrier, and that in their course through 
 it they have brought about its deterioration ; but in this there 
 is only probability. The history of the cholera of fowls proves 
 to us that they attack muscular fibre ; in certain catarrhs of the 
 bladder and vagina they penetrate in large numbers the epithe- 
 lial cells. I have demonstrated in blennorrhagia that the micro- 
 coccus of Neisser inhabits essentially the protoplasm of the 
 pavement cells of the urethra or of the conjunctiva, and that 
 the leucocytes are for it an accessory or secondary resting-place. 
 
 It is also said that microbes cause death by the anatomical 
 lesions which they develop. Assuredly there is amongst them 
 those which produce oedema, haemorrhage, suppuration, emphy-
 
 12 LECTURES ON AUTO-INTOXICATION. 
 
 sema, and gangrene ; but to say that they act because they pro- 
 duce these effects is to solve the problem by admitting as dem- 
 onstrated that which is still a matter of discussion ; the essen- 
 tial thing would be to know by what process they determine 
 such local lesions. 
 
 This fourth hypothesis has been enunciated : that the mi- 
 crobe, in order to nourish itself, consumes what is useful, the 
 subtraction of which is prejudicial to the organism. The ex- 
 ample of charbon has been quoted in support of this, and its 
 aerobic bacteridium takes hold of the oxygen to the detriment 
 of the blood-corpuscles. This ingenious hypothesis has not 
 even received the beginning of demonstration. 
 
 Lastty, infectious agents can produce something injurious, 
 can elaborate substances that are toxic. There, at least, and 
 there only, do we find a beginning of the proof. Indeed, we 
 know a good many bodies produced by the life of microbes. We 
 have studied in the fermentations which they induce in the flask, 
 carbonic acid, marsh-gas, hydrogen, even sulphuric acid, am- 
 monia, the ammonia compounds, the volatile fatty acids, many 
 complex alkaloids whose toxicity has been experimentally 
 demonstrated, indol, phenol, skatol, etc., all can poison, for 
 these bodies are toxic. They besides form soluble ferments, 
 which undoubtedly play a part in the production of local 
 lesions by breaking up in some way or other living cells. It is 
 therefore certain that intoxication in part arises from the harm- 
 ful action of microbes ; in all probability such is the part they 
 chiefly play. 
 
 It is not only in infectious diseases that we have to reckon 
 with the intoxication produced by them, it is also in the normal 
 state. Indeed, man, -in the condition of physiological life, is 
 inhabited, for a considerable length of his digestive tube, by 
 inferior vegetables. I have formerly shown you the toxicity of 
 intestinal matter; it is in part due to the poisonous products 
 elaborated by these microbes. A portion of these products is 
 absorbed, disease may prevent their elimination, and there arises 
 from this a poisoning. Intestinal fermentation increasing ab- 
 normally, the heap of toxic matter may become such that its 
 absorption produces intoxication in spite of the integrity of the
 
 VARIOUS MEANS BY WHICH TOXIC PRODUCTS ARE FORMED. 13 
 
 renal emunctory ; it is to this cause that many d}'speptic acci- 
 dents ought to be referred. Thus, in the normal as in the patho- 
 logical state, the organism is a receptacle and a laboratory of 
 poisons. 
 
 The object of the lectures which follow will be to find out 
 what part is played by self- intoxication in the production of 
 disease and morbid accidents.
 
 LECTURE II. 
 PRODUCTION AND ELIMINATION OP POISONS BY THE ORGANISM. 
 
 The healthy organism receives and forms poisons. Constant danger of auto- 
 intoxication. Means by which the organism manages to escape from it. 
 
 Origins of poisons in the healthy organism; alimentation, especially min- 
 eral substances ; the secretions (saliva, bile) ; digestion and intestinal 
 putrefactions ; disassimilation of the tissues. The blood is the ebbing and 
 
 flowing current of all the poisons. Demonstration of the presence of 
 
 poisons in the blood. Direct demonstration is still incomplete. Indirect 
 demonstration : we find in the urine, naturally or modified, the same poisons 
 as in the digestive canal and in the tissues ; they must, therefore, have trav- 
 ersed the blood. Opinions offered to explain the harmlessness of the 
 
 poisons of the digestive canal. Destruction or modification by dialysis in 
 passing through the intestinal mucous membrane, the epithelium, and the 
 capillaries (Stich). Hypothesis relating to the white cells. Protective part 
 played by the liver, which stops on their passage alkaloidal poisons coming 
 
 from the intestine (Heeger), and destroys them. Experiments of Schiflf. 
 
 Role of the emunctory organs in the expulsion of poisons. Intestinal 
 emunction : the putrid diarrhoea of anatomists ; salutary diarrhoeas. Illu- 
 sions relative to diarrhosa spoken of as supplementary to the renal emunction. 
 Cutaneous emunction : elimination of water ; perspiration favorable to 
 elimination of poisons. Elimination of volatile fatty acids : odors arising 
 from the skin when nutrition is deranged. Causes of the death of animals 
 
 which have been varnished. Pulmonary emunction, carbonic acid, water, 
 
 volatile fatty acids : fetidity of the breath in those who are constipated and 
 
 in hypochondriacs. Renal emunction : its preponderating influence. The 
 
 kidney can eliminate all toxic products except gas. Toxicity of urine : 
 danger of oliguria : critical polyuria at the decline of fevers. 
 
 I HAVE said that the organism, in its normal, as in its patho- 
 logical state, is a receptacle and a laboratory of poisons. 
 Amongst these some are .formed by the organism itself, others 
 by microbes, low forms of vegetables, which either are the 
 guests the normal inhabitants of the intestinal tube, or are 
 parasites at second hand, and disease producing. Man is in this 
 way constantly living under the chance of being poisoned ; he 
 is alwaj^s working toward his own destruction ; he makes con- 
 tinual attempts at suicide by intoxication. And yet this intoxi- 
 cation is not realized, for the organism possesses numerous 
 resources which enable him to escape the intoxication which is 
 (14)
 
 PRODUCTION AMD ELIMINATION OF POISONS BY THE ORGANISM. 15 
 
 always threatening. He throws off these toxic substances into a 
 special reservoir, from which they afterward pass outward; and, 
 besides, the blood constantly subtracts from the organs the 
 poisons as soon as the}' are formed in them. 
 
 I have shown in the first lecture how numerous are the toxic 
 substances contained in the organism. In the first rank are 
 placed the mineral substances introduced with our food ; then 
 come the products of physiological secretion, saliva and bile; 
 the products of digestion ; digestion, too, whilst it transforms 
 albuminoid substances into peptones, also gives birth to alka- 
 loidal poisons; and, lastly, toxic substances resulting from intes- 
 tinal putrefactions. Without doubt, the stools eliminate the 
 greatest part of these poisons which are expelled with them, 
 but, nevertheless, owing to the slow movement of the intestinal 
 contents, the mucous membrane absorbs a certain part of them. 
 We find in the close relationship of our tissues other poisons 
 which are the result of the life of cells. The}- pass out into 
 the extra-cellular fluids, along with which they pass into the 
 lymphatics and blood-vessels. It is, therefore, into the blood 
 that all the poisons are carried, the whole of those that are 
 made by the tissues, and part of those which are formed in the 
 digestive tube. Theoretically we cannot conceive how things 
 could be otherwise. But, evident even as this view of the sub- 
 ject appears, it must be demonstrated. Direct demonstration 
 of it has only been realized in a very incomplete manner. After 
 ligature of the colon, Planer found H 2 S in the blood of the 
 portal vein. Carter has there met with indigo in animals the 
 subjects of intestinal derangements. I have seen, like Gautier, 
 alkaloids not only in the tissues, but in the blood. Here is a 
 beginning of direct objective demonstration, but it is only yet a 
 resemblance. It is not a certainty. 
 
 On the 4th of December, 1884, we extracted, by means of 
 chloroform, alkaloids from 50 cubic centimetres of muscle of beef. 
 These alkaloids, soluble in chloroform, give precise reactions with 
 the following reagents : Tanret's solution, iodized iodine, phos- 
 l>ko-inolybdate of soda and tannin. September 3, 1884, a healthy 
 rabbit is killed, then cut up into pieces; it weighs thus minced,
 
 16 LECTURES ON AUTO-INTOXICATION. 
 
 without the abdominal viscera, 1012 grammes. It is digested in 
 2 litres of absolute alcohol, to which has been added water acidu- 
 lated with H 2 SO 4 , and this macerates for two days. We collect 
 the alcohol as it is filtered, and again unite it to the alcohol 
 which bathed the muscles of the animal, and which we obtain by 
 pressure. We have thus 1896 cubic centimetres. We evaporate 
 at 40 ; then the alcohol, reduced by one-third, is evaporated at 
 80 (we lose by accident one-third of this). In the watery 
 residue we find all the reactions usual to alkaloids. The precipi- 
 tates obtained are abundant with the following reagents : Tanret, 
 iodized iodine, phospho-molybdate of soda, ferric cyanide, double 
 iodide of potassium, and cadmium. This residue, made alkaline 
 by soda, is mixed well with ether. We decant the ether, which, 
 shaken up well with a little HC1 that has been added to it, is dis- 
 tilled. The residue is an ethereal extract. It is precipitated 
 fairly well, by means of the iodized iodine and molybdo-phos- 
 phate of soda reagent. 
 
 Indirect demonstration will be given if we find in the prod- 
 ucts of excretion those poisons which we have observed in 
 the tissues and in the intestinal canal; and, if it is proved that 
 these poisons are eliminated by organs in which they are not 
 formed, the logical conclusion will be that the blood is the 
 necessary medium between the seat of the formation of these 
 poisons and their place of elimination. But the poisons which 
 exist in the tissues and in the intestinal canal are also found 
 in the urine, either naturally or modified by oxidation or united 
 to nitrogenous or sulphur radicals : oxalic acid, in the state of 
 oxaluric acid ; phenic acid, in the state of compound sulpho- 
 phenic acid, or phenyl-sulphurous ; bodies of the aromatic 
 series, indol, scatol, cresol ; butyric acid, as in the stomach; 
 lactic acid, as in the stomach and first part of the intestine ; 
 acetic acid, as it is formed under certain pathological influences, 
 in considerable quantity in the whole length of the intestinal 
 canal. 
 
 We also find alkaloids in the urine : some show themselves 
 in a modified form, as quinine ; others naturally, and without 
 having undergone any previous alteration. Amongst these alka- 
 loids some are soluble in chloroform, others are insoluble in this 
 body, but soluble in ether ; both are found in the urine, with the
 
 REASON WHY TOXIC ACCIDENTS ARE INFREQUENT. 17 
 
 same characters as in the intestine. There is nothing in physiol- 
 ogy which warrants us in considering all these bodies as products 
 elaborated by the kidney ; it is the blood, therefore, which 
 carries them there. One of the first authors occupied in the 
 experimental investigation of these intoxications (Stichj thought 
 that the poisons of the intestinal canal must be neutralized, 
 destroyed, or undergo modifications which would deprive them 
 of their toxicity, consequent upon their passage through the 
 absorbent membranes of the intestinal canal, which played the 
 part of a dyalyser, through the epithelial cells and through the 
 walls of the capillaries. He is astonished to find so many 
 poisons in the intestinal canal and yet so few toxic accidents ; 
 and, considering that the poisons of the intestinal canal are 
 innocuous to the animal which has formed them, whilst the same 
 poisons become harmful to an animal of any other species into 
 which they have been introduced by the rectum or stomach, he 
 is led to think that each kind of animal has the power of destroy- 
 ing of itself the poisonous substances which it forms. This is 
 a view of the matter of which we have no demonstration. 
 
 According to Hoffmeister, the white globules play a part 
 in the transformation of peptones into albumen, since we no 
 longer find in the emunctories the peptones which we have 
 injected into the blood. We could, perhaps, apply this hypoth- 
 esis of Hoffmeister to the destruction of poisons, and say 
 that the toxic substances corning from the intestinal canal are 
 neutralized in the blood by the white globules. To explain 
 the harmlessness of the poisons of the intestinal canal, we have in 
 addition invoked the protective action of the liver. This organ 
 stops, arrests, as we know, certain portions of our food ; it 
 impedes the passage of grape-sugar and stores up glucose 
 under the form of glycogen. It plays also a protective part 
 in arresting alkaloidal substances. Heeger has injected into the 
 portal vein blood containing alkaloids (nicotine, strychnine, mor- 
 phine, quinine). The blood examined coming from the liver 
 contains less of these ; the substances injected have diminished 
 by one-fourth or one-half. Perhaps the liver places itself in 
 opposition to all the poisons of the organism, and robs it of 
 the blood which carries them. 
 
 2
 
 18 LECTURES ON AUTO-INTOXICATION. 
 
 Schiff has revived the question. He operates with nicotine. 
 The same dose of this substance which, introduced into a 
 peripheral vein, kills an animal, does not kill another animal of 
 the same weight if we inject it into a branch of the portal 
 vein. Schiff introduces a quantity of nicotine into the intestinal 
 canal of an uninjured animal, and it is not found to be intoxi- 
 cated by it. The same dose intoxicates the animal if we have 
 ligatured its portal vein, for then the toxic substance reaches 
 the general circulation by the accessories of the portal venous 
 system, without having passed through the liver, which would 
 have arrested it. 
 
 Fresh liver is triturated with nicotine. An infusion of this 
 is injected into an animal, and it does not kill it. The same 
 dose of nicotine ground up with an equal weight of renal or 
 muscular tissue kills it. The liver is not alone content in 
 arresting these poisons ; it destroys them. These facts have 
 been experimentally verified in my laboratory by C. H. Roger, 
 who, as regards this question of the protection of the organs 
 by the liver, has added to our knowledge many new facts, 
 which I shall have occasion to describe to you. But the alka- 
 loids are not the most poisonous substances of the organism. 
 This explanation is right as regards them, but is not applicable 
 to all ; it is necessary to add to it this other piece of information, 
 that man escapes intoxication by the intestinal, cutaneous, pul- 
 monary, and renal emunctions. 
 
 The part played b}' the intestinal emunctory in the elimina- 
 tion of certain poisonous substances is attested by the com- 
 monly fetid stools of persons who frequent the post-mortem 
 theatre. Their fetid character recalls the putrid odor of the 
 emanations from the cadavera. Sometimes this emunction is 
 defective ; for, if the largest part of the toxic material is thus 
 expelled, a part is absorbed ; there is a defective circle for cer- 
 tain molecules of poisons. We find in the intestine toxic sub- 
 stances arising from the disassimilation of matter, taurocholic 
 and glycocholic acids, or their derivatives, cholic and cholalic 
 acids, dyslysin, a b'ody formed by the liver, afterward trans- 
 formed in the intestine. We find these mineral salts formed 
 out of bile or secreted by the intestinal glands themselves. The
 
 IMPROBABILITY OF VICARIOUS FUNCTION. 19 
 
 intestine also contains gases which are not all formed there ; 
 there are individuals in whom, in a very short time, an excessive 
 tympanitis is developed. In such cases certain gases are 
 probably secreted by the digestive canal. I do not know what 
 they are, nor even whether they are analogous to those which 
 bring about fermentation. We find hydrocarbons, sure enough ; 
 nitrogen probabty ; perhaps carbonic acid, and even ox}-gen, 
 since certain aerobic microbes live in the intestine. To what 
 extent are these gases poisonous? It is difficult to reply to this 
 question. Those which produce hysterical tympanitis do not 
 appear to be poisonous. 
 
 From these facts follow certain applications that may be 
 made to pathology. Has it not been said now for a long time 
 past that there are " salutary diarrhoeas ? " People who have 
 lived for several years, the subjects of diarrhoea, and retain- 
 ing the appearance of perfect health, have seen their diarrhoea 
 and their health disappear at one and the same time. We may de- 
 rive from these facts some encouragement in inducing diarrhoea 
 in certain cases, without, however, raising exaggerated hopes 
 in any one, the subject of a supplementary diarrhoea, of his being 
 able to compensate the insufficienc}' by another emunctory. We 
 have spoken of the intestine acting vicariously for the kidney 
 by discharges of serum. For my part, I scarcely believe in 
 vicarious functions any more for the skin than for the intestine. 
 In increasing more actively the cutaneous and intestinal secre- 
 tions we remove a considerable quantity of water from the 
 organism, but not what ought to be eliminated dissolved in the 
 water. There is a certain quantity of material associated with 
 a determined quantity of water, according to the emunctory by 
 which the water is thrown out. If, for example, there is in the 
 blood 0.15 gramme of urea for 1000 grammes of water, the urine 
 carries away 15 grammes of urea for every 1000. The sweat 
 will only carry awa} r 0.15 gramme for every 1090, exactly the 
 proportion which is found not in the blood, but in the liquor 
 sauguinis. Then 1 kilogramme of water, which by the renal 
 channel would have carried away 15 grammes of urea, only 
 carries away 30 centigrammes by the skin and the intestine. 
 One emunctory can scarcely vicariate for another.
 
 20 LECTURES ON AUTO-INTOXICATION. 
 
 By the skin are eliminated water, salts in small quantity, 
 carbonic acid, and some volatile fatty acids. Copious perspira- 
 tions may be useful in certain intoxications, caused by poisons, 
 for instance, not because they eliminate the poisons themselves, 
 but probably because they expel from the organism the abnormal 
 products which it has formed under the influence of the poisons. 
 
 In many putrid intoxications amongst individuals who are 
 the subjects of deep-seated foul sores the odor of the skin recalls 
 that of their suppuration. What enables us to understand 
 the useful part played by the perspiration in the cure of these 
 morbid states is the odor which the skin takes under the influence 
 of certain disorders of nutrition. Amongst hypochondriacs 
 the alienated, living in absolute inactivit} r , and with defective 
 alimentation fatty acids are eliminated more abundantly by the 
 skin. From this arises the odor special to the places inhabited 
 by men forced to this kind of life, the odors of asylums, of 
 prisons, barracks, odors which differ one from the other. 
 When nutrition is deranged, by depressing influences acting 
 through the intermediary of the nervous system, we may be 
 warned of its being so by the odor. 
 
 There is in existence an experimental demonstration of the 
 part which the cutaneous emunctory plays in the elimination of 
 toxic substances. We know that the varnishing of the skin of 
 animals produces a marked fall in the heat of the body. Is this 
 the result of failure of the cutaneous respiration ? It is hardly 
 probable. Is it due to the action of the vaniish upon the nerve 
 terminations ? Why, this reflex action is much less than faradi- 
 zation, the application of cold or of heat ; besides, what these 
 forms of irritation of the tissues determine is albuminuria, not 
 haematuria, convulsions, and reduced temperature. What is 
 special to the varnishing is perhaps the retention of poisonous 
 substances which the skin ought to eliminate. 
 
 By the lungs are eliminated carbonic acid (1100 grammes in 
 twenty-four hours), water, ammonia sometimes, and often volatile 
 fatty acids, which explain the fetid character of the breath of 
 people the subjects of constipation and of hypochondriasis, and 
 which are the result of a depraved nutrition or of an incomplete 
 destruction of matter. By the lungs, too, are eliminated poi-
 
 KIDNEYS, THE MOST IMPORTANT ELIMINATING ORGANS. 21 
 
 sonous substances scarcely known, to which Du Bois-Reymond 
 has drawn attention, especially the volatile poisons accidentally 
 introduced into the digestive canal (alcohols, ethers, chloroform, 
 asa foetid a). 
 
 But of all the organs of elimination the most important is 
 the kidnej r . One cannot, as in the case of the intestine, reproach 
 it with being a defective emunctory, capable of re-absorbing a 
 part of the products which it eliminates. Absorption does not 
 take place in the urinary channels, at least in the normal con- 
 dition. If there is produced a desquamation of epithelium, 
 intoxication, it is true, shows itself; it is then a complex thing, 
 resulting not only from the re-absorption of substances which 
 the kidney ought normally to eliminate, but from poisonous sub- 
 stances which the decomposing urine forms in the urinary chan- 
 nels under the influence of ferments which are found there. 
 
 What, then, does the kidney eliminate? Everything save 
 gaseous material: in the first place, water; then two-thirds, at 
 least, of the solid matter, especially mineral matter, of which you 
 will not be slow in recognizing the eminently poisonous power; 
 many nitrogenous substances (urea, coloring and odoriferous 
 material). Certainly, all these substances are not poisonous, 
 but many of them are. What is certain is that urine, taken 
 altogether, is toxic. We have always regarded oliguria as a 
 troublesome thing ; whereas, on the contrary, at the declination 
 of fevers, a critical polyuria is nearly always useful, because it 
 expels poisonous substances formed by the economj* during the 
 illness. There may arise unpleasant symptoms, according to the 
 relative impermeability of the kidney for certain substances.
 
 LECTURE III. 
 
 PRELIMINARIES TO THE EXPERIMENTAL STUDY OP THE TOXICITY 
 OF THE PRODUCTS OF EMUNCTION. 
 
 Necessity of demonstrating experimentally that the retention of excrementitious 
 material may cause intoxication. Pulmonary, intestinal, and cutaneous 
 emunctories are inconvenient for this demonstration. Choice of the urinary 
 
 secretion for research upon the toxicity of the products of emunction. 
 
 Comparison of the various methods employed by the. experimenter for 
 introducing in to the organism substances the toxicity of which he wishes to 
 study. Introduction by the digestive canal and subcutaneous injection 
 inconvenient. Advantages of iutra-venous injection. Its- harmlessness ; 
 
 its facility. Uniformity of the results obtained. Study of the action 
 
 consequent upon the liquids employed to serve as excipieuts in the injection 
 of poisonous substances, water, alcohol, glycerin. 
 
 THERE exists, as we have said, in the organism an incessant 
 tendency to toxaemia from accumulation, and from which it es- 
 capes by various means, thanks to the part plaj'ed by the liver, 
 which forms an active barrier to poisons taken from the digestive 
 tube, but is insufficient -for those formed in the tissues, thanks 
 especially to the safeguard which is established through the 
 einuuctory apparatus. In order that intoxication may be 
 avoided, it is necessar3 T that the five emunctory offices should be 
 in a state of anatomical and functional integrity; that the blood, 
 the circulatory apparatus, and the nervous system should func- 
 tionate normally. Everything caught in the meshes of these 
 organs may cause intoxication. It seems, at least, that this 
 should be so ; but appearance may not be real : presumption is 
 not demonstration. 
 
 If I say that death nearly always arises from intoxication, 
 because, in nearly all diseases, it is asphyxia which puts a ter- 
 mination to all vital acts, and that asphyxia is an intoxica- 
 tion, I seem to be formulating a syllogism which is indisput- 
 able. Yet it is only a sophism, however, for asphyxia is a 
 (22)
 
 STUDY OP THE TOX1CITY OF THE PRODUCTS OF EMUNCTION. 2<J 
 
 complicated thing, and if intoxication from excess of carbonic 
 acid is one of its factors want of oxygen is another. There 
 is, then, no idea so reasonable as that which requires demon- 
 stration. Consequently, we ought to prove that the retention 
 of substances destined to be eliminated by the emunctories is 
 capable of producing intoxications in the doses in which these 
 substances are formed in the normal organism. The problem 
 to be solved is to seek for the measure of the activity of 
 the toxic substances which are eliminated in twenty-four hours 
 by all the emunctories combined, and what enables us to de- 
 termine this in a given time is the quantity of poison capable 
 of intoxicating a known weight of living matter. We cannot 
 set ourselves to solve this problem with any emunctory that we 
 choose. 
 
 Thus, amongst emunctories whose failure to functionate 
 can contribute to intoxication of the organism the lung is 
 be3'ond all dispute: without counting the other toxic substances 
 it eliminates, the carbonic acid which it exhales in twenty-four 
 hours would poison a man a great number of times. 
 
 The intestine does not offer a soil for useful experiments, for 
 we are powerless to make the distinction between toxic products 
 which are brought there by the secretions and those which are 
 formed therein. In regard to the skin, researches are embarrass- 
 ing, on account of the small quantity of products secreted and 
 of the difficulty which we have of collecting them. It is, there- 
 fore, from the urinary tract that we will seek for the demonstra- 
 tion of the toxicity of the products of emunction ; by it, is 
 reserved the speciality of eliminating toxic substances which are 
 not volatile, a deduction being allowed for that which is 
 destroyed in the liver and in the totality of the organism. 
 
 What methods are allowed to us for the introduction into the 
 organism of toxic substances ? Ingestion by the digestive canal 
 is an illusory method. We are obliged to dilute the toxic ma- 
 terials to make them acceptable. We introduce them into an 
 organ which is continually eliminating by the stools a part of 
 its contents. How can we know what quantit}' of that which 
 we have introduced has been absorbed? Besides, absorption 
 from the intestinal canal is very slow, and the organism has
 
 24 LECTURES ON AUTO-INTOXICATION. 
 
 time to protect itself by eliminating the poison. M. Morel- 
 Lavalle'e has communicated to the Clinical Society the following 
 fact : In a patient who had ingested 60 grammes of laudanum 
 from 2 o'clock in the morning to 8 o'clock in the morning, 
 washing out of the stomach removed 45 grammes of the poison. 
 In six hours one-fourth only of the poison had been absorbed. 
 When we proceed to the introduction of toxic substances by 
 means of the digestive canal we never can know if what has 
 been introduced has been absorbed, and we run the risk of 
 being forced to consider substances inoffensive whih are really 
 poisonous. 
 
 Injection by the subcutaneous cellular tissue is liable, in 
 great part, to be similarly criticised; elimination, it is true, will 
 only be made by the blood, but absorption is slow, whilst 
 emunction is rapid. It is, therefore, difficult to form an exact 
 appreciation of the quantity of the injected substance which is 
 contained in the blood at the precise moment at which such a 
 phenomenon shows itself. Besides, the injection produces by 
 itself certain disturbances which may cloak the action proper 
 to the injected substance. It is painful, and provokes nervous 
 reactions. It causes particularly albumin uria ; the injection of 
 4 cubic centimetres of water by the subcutaneous method in the 
 case of a rabbit induced this phenomenon. 
 
 There remains the intra-venous channel. The dangers which 
 were attributed to it at first are erroneous. It is almost as easy 
 and quick from the operative point of view as injection into the 
 cellular tissue; 'it is, besides, more searching, more inoffensive, 
 and less painful. Thanks to it, we can, in a period equal to a com- 
 plete revolution of the blood, distribute through the whole of 
 the organism a known quantity of poisonous material, and know 
 exactly what dose is contained in the blood at the moment in 
 which there bursts forth the first indication of toxicity. 
 
 I have made comparisons between injections of saccharified 
 urine into the intra-venous channels and subcutaneously. When 
 this is introduced directly into the blood glycosuria shows itself 
 three minutes after the beginning of the injection.
 
 STUDY OF THE TOXICITY OF THE PRODUCTS OP EMUNCTION. 25 
 
 INTRA-VENOUS INJECTION OF DIABETIC URINE. 
 
 On the llth of December, 1884, into a rabbit weighing 1645 
 grammes, we injected into the veins 133 cubic centimetres of 
 urine containing traces of albumen and 60 grammes of sugar to 
 the litre. The urine is filtered and neutralized. The quantity 
 of urine injected represents 4.85 grammes of sugar for each kilo- 
 gramme of the animal and 63.05 grammes for each kilogramme 
 of blood. At the 33d cubic centimetre, emission of urine already 
 rich in sugar. Toward the 71st cubic centimetre, fresh emission 
 of urine, richer in sugar than the first, and sufficiently albumin- 
 ous. At the end of the injection, third emission of urine, still 
 richer in sugar than the two preceding. The temperature, one 
 hour after, stood at 36.4 C. (97.5 F.). An hour and a half 
 after the injection the urine is found still to contain sugar. 
 
 December 12th. The urine contains a less quantity of sugar. 
 Temperature, 40 C. (104 F.). 
 
 December 13th. Trace of sugar; no albumen. 
 
 December 23d. The animal is quite well. 
 
 The same quantity introduced by the cellular tissue does not 
 produce glycosuria, because absorption is so slow that the blood 
 destroys the sugar as it is absorbed, without giving it time to 
 reach the kidney. 
 
 SUBCUTANEOUS INJECTION OF DIABETIC URINE. 
 
 Sixty -five cubic centimetres of the same urine are injected 
 into the cellular tissue of a rabbit weighing 1750 grammes, 
 about, therefore, 2.2 grammes of sugar for each kilogramme of 
 the animal. After the injection the urine of the rabbit does not 
 contain sugar ; it is albuminous. 
 
 December 12th. No sugar. Temperature, 40.1 C. (104.2 
 F.). In the evening the animal dies. At the autopsy, in the 
 region in which the injection was made, one sees neither suppu- 
 ration nor gangrene, but a reddish liquid, full of mobile organ- 
 isms, round, very small, which one also finds in the liver, and 
 which appear also to exist in the blood. 
 
 The intra-venous method is the less harmful, much as this may 
 appear paradoxical. One hundred grammes of fluid injected into 
 the blood are not followed by any accident. The same quantity
 
 26 LECTURES ON AUTO-INTOXICATION. 
 
 of this fluid, purified, or even previously raised to a temperature 
 of 100 degrees, if we inject it under the skin, causes the animal to 
 die from septic accidents. It is possible that some of the in- 
 fective agents derived from the intestinal tube or from without 
 cause the appearance of something in the cellular tissue, modified 
 by the presence of the injected fluid, which is capable of killing 
 the animal; whereas, on the contrary, when we inject into the 
 veins fluid even in appearance septic, a liquid rendered opales- 
 cent by the presence of bacteria, there may result from this no 
 accident, or albuminuria at the most. 
 
 INTRA-VENOUS INJECTION OF URINE RENDERED OPALESCENT BY 
 THE PRESENCE OF BACTERIA. 
 
 November 8, 1884. Urine of a patient the subject of arterio- 
 sclerosis. Quantity passed in twenty-four hours, 850 grammes. 
 This urine is albuminous ; it contains moving microbes, in the 
 form of rods, short and numerous enough. Neutralized, and 
 slightly alkalinized and filtered, it is injected into the veins of 
 a rabbit weighing 1580 grammes. The quantity injected is 135 
 cubic centimetres in eleven minutes, about 86 for each kilo- 
 gramme of the animal. The temperature of the rabbit before 
 the injection was 40 C. (104 F.). It lulls to 37.2 C. (99 F.) 
 immediately after. Myosis shows itself slowly : it only appears 
 toward the 80th cubic centimetre. There is emission of very 
 little urine. After the injection the animal remains lying on its 
 side ; its respiration is slow. The reflexes are hardly percep- 
 tible. At the end of twenty minutes the temperature is 37.8 C. 
 (100 F.) ; the animal is upon its paws. 
 
 It has lost 0.8 X 2.8 X 1580 calorics = 3539 calorics. 
 
 The urine has absorbed 12.2 X 0.135 calorics = 1647 calorics. 
 
 The rabbit, therefore, has made less by 1892 calorics. 
 
 November 10th. The animal has traces of albumen. 
 November 15th. It is quite well. 
 
 Perhaps bacteria are, after a time, neutralized by the oxygen 
 of the blood, especially if they are anaerobic bacteria, or if they 
 are the common bacteria which have not yet exercised their 
 influence except upon dead matter. We can inject thousands of
 
 INTRA-VENOUS INJECTION OP TOXIC MATERIAL. 21 
 
 millions of certain bacteria without the organism being the 
 least disturbed by it.* 
 
 The process of intra-venous injection is applicable to every- 
 thing that is soluble except oxygen. Nevertheless, it has been 
 proposed at the Academy of Sciences to make intra-venous in- 
 jections of oxygenized water. The splitting up of this, as I 
 have observed, would be immediate, and would end in gaseous 
 pulmonary embolism. At most, I have only seen experimental 
 injections utilized as a method of study, and not their appli- 
 cation to therapeutics. Intra-venous injections of medicines 
 into the bodies of men ought, according to the new order, only 
 to be employed in cases altogether exceptional, in cholera, for 
 example, or, as I have already once said, in a disease certain 
 to be speedily fatal, confirmed hydrophobia. 
 
 It remains for us, before proceeding with the injection of 
 toxic substances, to study how liquids behave physiologically 
 which serve for the dissolution of those substances. The 
 only excipients employed are water, alcohol, and glycerin. In 
 the rabbit, distilled water, at a temperature very notably below 
 that of the blood, only commences to show itself toxic when we 
 inject more than 90 cubic centimetres of it for each kilogramme 
 of the animal, say for 100 grammes of blood 117 of water. 
 Death ensues with 122 cubic centimetres for each kilogramme of 
 the animal ; that is, 157 grammes of water to 100 of blood. 
 Absolute alcohol is toxic beyond 0.6 cubic centimetre for eacli 
 
 * Watson Cheyne, in his " Lectures on Suppuration," delivered at the Royal Col- 
 lege of Surgeons, London, February, 1888, has shown how the disease which is experi- 
 mentally produced stands related to the number of micro-organisms injected. Taking 
 cultivations of proteus vulgaris, for example, he found that -fa cubic centimetre of 
 an undiluted cultivation was rapidly fatal when injected into a rabbit, the quantity 
 injected contained 250,000,000 of bacteria ; also, that 56,000,000 bacteria caused exten- 
 sive abscess, the animal dying in from six to eight weeks. Fewer than 18,000,000 
 seldom produced any effect. In diseases of this nature, however, many things have 
 to be considered, not only the quantity injected, but the virulence of the micro- 
 organisms and the susceptibility of the animal. Mice are peculiarly susceptible to 
 septicaemia; the injection of a single bacillus has induced death, whilst 4 cubic 
 centimetres of a jelly cultivation, and which contained myriads of bacilli, could be 
 injected into the ear of a rabbit without causing more than slight constitutional 
 disturbance and local redness with swelling, which lasted only a few days. In the 
 case of staphylococcns pyogenes aureus, Cheyne showed (Brit. Med. Journal, March 
 10, 1888) that it was necessary to inject 1.000,000,000 cocci into the muscles of rabbits 
 in order to cause a rapidly fatal result ; 250,000,000 produced simply a small circum- 
 scribed abscess. T. O.
 
 28 LECTURES ON AUTO-INTOXICATION. 
 
 kilogramme of the animal. The clot which it produces immedi- 
 ately redissolves in the blood coming from other veins, and there 
 arises no embolon from it. The more alcohol is diluted, the more 
 we can inject of it. The degree of dilution the most favorable 
 is 20 grammes for each 100 \>y volume, 20 cubic centimetres of 
 absolute alcohol for 80 cubic centimetres of water ; 1.45 cubic 
 centimetres of absolute alcohol carried to this degree of dilution 
 produce narcosis and comaj 3 cubic centimetres kill. For each 
 100 grammes of blood it is, then, necessary to take 2 cubic centi- 
 metres of alcohol to produce narcosis and 3.9 cubic centimetres 
 to bring about death. 
 
 Glycerin is less toxic than alcohol. We cannot employ pure 
 glycerin ; it produces viscid emboli. We must prefer dilu- 
 tion of it to 50 for each 100. We establish that 5 cubic centi- 
 metres of anhydrous glycerin for each kilogramme of the 
 animal produce muscular tremors, and that 14 cubic centimetres 
 induce death, with immediate cadaveric rigidity. We know, 
 then, for the future, that the substance whose toxic power we 
 wish to test by intra-venous injection ought not to be dissolved 
 in more than 90 cubic centimetres of water, in more than 1.45 
 cubic centimetres of alcohol, diluted in the proportion of 20 to 
 each 100, or 5 cubic centimetres of glycerin, diluted in the pro- 
 portion of 50 to 100 for each kilogramme of the animal.
 
 LECTURE IY. 
 
 ON THE TOXICITY OF URINES. 
 
 Admitted from all time by physicians, the toxicity of uriue has only recently 
 
 been demonstrated. Cl. Bernard and Frerichs have stated the question. 
 
 Isolated study of some of the toxic elements of certain urines: Gabriel Pou- 
 chet. Study of the toxicity of urine taken in its entirety negative conclu- 
 sion: Murou. Positive conclusion: Feltz and Ritter, Bocchi aud Schiifer. 
 
 Study of certain pathological urines: Lepine, Dupard, and Gudriu. My 
 
 owii experiments upon the toxicity of normal urine injected en masse by 
 intra-venous channel. Reply to certain objections raised against this method. 
 
 Choice of the rabbit as the animal to exhibit reactions. Physiological 
 
 phenomena consequent upon the intra-venous injection of normal urine, 
 myosis, accelerated respiration, torpor, polyuria, fall of temperature due to 
 diminished heat production ; survival or death, according to the dose injected. 
 Discussion upon the possible causes of death. Determination of the unity of 
 toxicity. Urotoxy. Urotoxic co-efficient. Toxicity of urines different 
 according to whether they have been secreted during the waking hours or 
 sleep. 
 
 WE have said that if the organism forms poisons and yet is 
 not poisoned, it is because the liver stops some of them and 
 that the rest are eliminated. The safeguard to the economy 
 resides in having an organ of arrest and in the emunctories. 
 We have admitted this idea hypothetically, but we have recog- 
 nized the necessity of verifying experimentally this view of the 
 matter, reasonable as it appears to us. From amongst possible 
 demonstrations we have chosen that which consists in prov- 
 ing that the emunctories really cast out externally toxic sub- 
 stances and that the excrementitious products are toxic. For 
 various reasons, which we need not recall, we have addressed 
 ourselves, in order to verify the toxicity of excrementitious 
 products, to those which the kidney eliminates, and we have 
 adopted the intra-venous injection as the experimental method. 
 
 Are urines toxic ? To this question we have at all times re- 
 plied in the affirmative, so much so that there is no necessity 
 to raise the question again. Upon this undebated point has 
 been built the thepry of uraemia. Urine is toxic : thus, when it 
 ceases to be secreted the organism is poisoned. We may say 
 
 (29)
 
 30 LECTURES ON AUTO-INTOXICATION. 
 
 that this is a true medical opinion of the matter ; but, true as it 
 appears to be, it claims demonstration. Cl. Bernard raised the 
 question ; Frerichs has followed it up. Physicians and physi- 
 ologists have, after these, emulously striven to find out what are 
 the substances to which urine owes its toxicity, ammonia, urea, 
 etc. In all these researches it is not of the urine itself that there 
 is question, but certain substances which we find in it or which 
 are developed in it in consequence of catalytic changes, car- 
 bonate of ammonia, for example. It is the study of certain toxic 
 substances of the urine which we have at length broached, and 
 not that of the toxicity of urine in kind. We have blamed the 
 coloring matter, odorous and volatile, and mineral matters, 
 potass in particular. They are, without doubt, toxic ; but they 
 constitute only a part of the toxicity of urines. 
 
 M. Gabriel Pouchet has found in normal urine alkaloids 
 chemically similar to the toxic alkaloids. In 1882 I extracted 
 from certain urines taken from patients the subjects of infectious 
 diseases alkaloids, with which I have been able to produce, ex- 
 perimentally, dilatation of the pupil, acceleration of the beats 
 of the heart, physiological effects which approach those of 
 atropine. But the question here was one of abnormal alkaloids, 
 or at least of alkaloids extracted from the urines of sick people. 
 It is by repeated attempts, made in various ways, that we 
 approach the solution of the problem. 
 
 The question, taken in its entirety, dates from 1868. Muron, 
 having made subcutaneous injections of urine, affirms the non- 
 toxicity of it ; but the method which he adopted ought to put 
 us into a state of mistrust ; we have seen why. MM. Feltz and 
 Ritter (in 1881) made intra-venous injections of urine just 
 as it is, and have concluded for the toxicitj 7 of urine. Bocchi 
 (at the end of 1882) repeated the experiments, and also con- 
 cluded that urine is toxic, considered as a whole. He has sub- 
 cutaneously injected normal urine into frogs, and has killed them ; 
 but amongst mammalia the rat and guinea-pig he has not 
 produced the toxic phenomena which he met with in the frog. 
 In April, 1883, Schiffer employed ethereal extracts of urine. 
 He killed frogs with the extract taken from 16 to 25 grammes of 
 urine, and rabbits with a quantity of extract which represents
 
 URINE NOT TOXIC FROM ITS ACIDITY ONLY. 31 
 
 1^ litres of urine; but if he has demonstrated the toxicity of 
 a product contained in urine, he has not elucidated the problem 
 of the toxicity of normal urine in man, for, according to these 
 experiments, it would be necessary, while the due proportions 
 were observed, that man should retain in his body a quantity of 
 urine equal to his own weight in order to be intoxicated by it. 
 The experiment of Schiffer only proves that urine contains 
 something which, in excessive dose, may become toxic. Very 
 interesting experiments, regarded from a physiological point of 
 view, were made in 1883 and 1884 by M. Dupard, under the 
 inspiration of M. Lupine, and afterward by MM. Lepine and 
 Guerin ; but as these experimenters only made use of pathologi- 
 cal urines, the results obtained do not demonstrate the toxicit}- 
 of normal urines. It is necessary to return to the method sug- 
 gested b}< Feltz and Hitter, the injection of normal urine just 
 as it is; that is what I have done, as these authors did in 1883 
 and 1884, by intra-venous channels. 
 
 It seems at first sight unlikely that one could introduce into 
 the vascular system urine as it is ; and, before everj'thing else, it 
 is necessary to reply to certain objections which cannot fail to 
 be raised against the legitimacy of this proceeding. And, first, 
 can we, without causing accidents, introduce into the blood a 
 considerable quantity of water, such as that which would serve 
 as a vehicle for the solid matter of the urine? We said in 
 the preceding lecture that we can inject without danger into 
 the blood up to 90 cubic centimetres of water for each kilo- 
 gramme of the animal. Can we inject urine as it is with an acid 
 reaction? Do we not run the risk of attributing to the action 
 of urine effects which would be sufficiently determined by the 
 introduction of a nornwllj r acid bod)' into an alkaline medium? 
 Theoretically we cannot afford to overlook this possible cause 
 of error, although there may be reason for us asking ourselves 
 if it concerns the theory of intoxication by retention in the 
 blood of urine not secreted, and if the acidity might not be 
 due to the action only of the renal secretion. We see neutral 
 salts which have become acid after having undergone dialysis ; 
 it is there a borrowed acid. In every case it would not be legiti- 
 mate to compare the effects of the retention of neutral urine
 
 32 LECTURES ON AUTO-INTOXICATION. 
 
 with the injection of acid urine. In fact, I have acknowledged 
 that the question of the reaction is a thing of indifference. At 
 first the urine is acid to a feeble degree ; it contains few free 
 acids; the acidity is chiefly due to acid salts. I have injected, 
 for the sake of comparison, and without obtaining differences in 
 the results, acid urines and the same urines exactly neutralized 
 by carbonate of soda. Yet, to be more cautious, I have, in all 
 my experiments, exactly neutralized the urines before injecting 
 them into the blood. It is a precaution which cannot diminish 
 the toxicity of urines, and which puts in the shade the objection 
 announced higher up. That admitted, we cannot inject into the 
 blood of an animal normal urine without determining physio- 
 logical phenomena and death with doses generally less and often 
 much inferior to those in which distilled water is toxic. 
 
 The phenomena which I am going to describe have been ob- 
 served exclusively in the rabbit. The rabbit is the best animal 
 to choose when there is question of injecting into the veins. The 
 posterior marginal vein on the dorsal part of the face, as it 
 spreads over the ear, easily allows of penetration taking place, 
 without preliminaiy removal of the skin, by means of a Pravaz 
 syringe. We can, even in the rabbit, penetrate directly into the 
 median artery of the ear. The choice of this animal singularly 
 diminishes the difficulties, and especially the slowness, of intra- 
 venous injections. The guinea-pig, which offers the same ad- 
 vantages, scarcely lends itself so well for experiments in the 
 laboratorjr, for there are economical necessities before which it 
 is necessary to bow. 
 
 The first phenomenon which follows the intra-venous injec- 
 tion of normal urine is contraction of the pupil. After the 
 injection of 10, 12, or 15 cubic centimetres of urine there 
 appears a myosis, which goes on gradually increasing until the 
 pupillary opening becomes pin-pointed. A little after the begin- 
 ning of the injection we notice acceleration of respiratory move- 
 ments, with a diminution of their range. Then the animal is 
 enfeebled, its movements become irregular and laborious ; somno- 
 lence now comes on. We remark, also, increase in the urinary 
 secretion and frequency of voiding the urine. Urine increases 
 more than any other material the urinary secretion. The diu-
 
 EFFECTS OF THE INTRA-VENOUS INJECTION OF URINE. 33 
 
 resis induced by the injection of distilled water is not to be 
 compared to that produced by the injection of normal urine. 
 At the same time, the temperature falls. This fall is constant, 
 it is true, after every intra-venous injection of liquid, but it is 
 much more considerable after the injection of urine. The 
 amount of heat lost by the animal is greater than that neces- 
 sary to raise to the temperature of the blood the quantity of 
 liquid injected. It is a thermic fall, which is dependent upon a 
 diminution of heat production. The temperature of the rabbit 
 falls from 39 C. (102.2 F.) or 37 C. (98.6 F.) to 32 C. 
 (89.6 F.); the hypothermia of itself in certain cases may ex- 
 plain the death. 
 
 We also notice a diminution of the palpebral and corneal re- 
 flexes ; often, too, exophthalmos. Death comes at last, without 
 convulsion or with moderate muscular tremors, with persistence 
 of the cardiac beats, and of contractility of the striated and unstri- 
 ated muscular fibre. The pupil remains contracted after death, 
 then it dilates again in some of the cases. If the smallest dose 
 of urine is injected, sufficient to produce coma, but not death, 
 the animal remains passive, with respiratory movements of 
 feeble range; chilled; with pupillary contraction; and with a 
 polyuria such that every two minutes an emission of urine takes 
 place. The superficial vessels are dilated ; the arteries beat with 
 such amplitude that their pulsations are easily felt up to the tip 
 of the ear. Then torpor diminishes, the fall of temperature is 
 arrested, heat production goes on again, and the pupil dilates. 
 At the end of half an hour return to health is definite, without 
 secondary phenomena. The animal may be kept under observa- 
 tion for weeks or months, without our being able to observe in 
 it any pathological accident. One fact to note is, that we 
 rarely set up albuminuria unless, for the most part, an albumi- 
 nuria which is very slight and very fleeting in the animals which 
 survive. On the contrary, after the injection of pathological 
 urines certain kinds, at least albuminuria is constant and 
 notable ; one may witness, too, luematuria. 
 
 What quantit}' of normal urine is necessary to produce 
 intoxication by intra-venous injection? This is a difficult ques- 
 tion to decide. The oscillation habitually takes place between
 
 34 LECTURES ON AUTO-INTOXICATION. 
 
 30 and 60 cubic centimetres for each kilogramme of the animal, 
 45 cubic centimetres, on an average. Pupillary contraction 
 often begins to show itself after the employment of 10 cubic 
 centimetres. The urine of a subject in whom abundant drinks 
 had produced a normal polyuria has been injected with im- 
 punity up to 97 cubic centimetres for each kilogramme of the 
 animal, a dose in which distilled water is already toxic. The 
 urine of this same individual, who was submitted to a chill 
 without becoming febrile, has killed with a dose of 12 cubic 
 centimetres for each kilogramme of the animal. The variations 
 of toxicity, already large in the limits of the normal state, 
 become still more considerable as we reach the border of the 
 pathological. 
 
 Pathological urines am not always more toxic than normal 
 urines ; they may be less ; they may differ from them in pro- 
 ducing other symptoms. Certain pathological urines determine, 
 with a dose of 10 cubic centimetres, convulsions, which we 
 hardly ever observe after the injection of normal urines. With 
 certain others it is necessary, in order to induce a phenomenon 
 of some kind or other, to inject as much urine, and even more, 
 than the dose in which distilled water causes death. Thus, dis- 
 ease sometimes augments, sometimes it diminishes the toxicity 
 of urine. Amongst certain albuminurias the innocuous nature 
 of the urine is a remarkable fact ; the kidney seems to have 
 separated from it the toxic substances, retaining them within 
 the organism. 
 
 When death follows an injection of urine, we may suppose 
 that it results from the mechanical action of the mass of urine 
 injected or from dilution of the blood. It is not so ; for we 
 can double and almost treble the mass of blood without inconve- 
 nience. Nor is death more to be attributed to the general hydra- 
 tion of the bodj r . If we reduce by evaporation the quantity of 
 urine lay one-half, only expelling the water from it, the toxicity 
 is doubly increased. The degree of concentration of a healthy 
 urine causes its toxicity to vary : a healthy man, but oliguric, is 
 more toxic than the polyuric, so far as regards an equal quan- 
 tity of urine, which proves that the urine does not kill by the 
 water, but by the substances which are in a state of solution
 
 ON THE TOXICITY OF URINES. 35 
 
 in the water. Whatever those substances may be, it is interest- 
 ing to know the degree of toxicity that they communicate to 
 urines ; that is to say, the toxic power of the matter which is 
 elaborated by a given weight of man and is eliminated in a 
 given time by his urine. 
 
 It has appeared to me necessary, for the clearness of later 
 explanations, to create a new name, and I excuse n^-self for 
 doing so. This neologism has for its object the denomination 
 of the unit, which will serve as a term of comparison in the 
 estimation of the variations of the toxicity of urine. I shall 
 call the unit of toxicit}' "urotoxy"; that is to say, the toxic 
 amount necessary to kill a kilogramme of living matter. This 
 unit we shall determine by experiment. I shall stucty thus the 
 urotoxic co-efficients; that is to say, the quantity of urotoxies 
 which 1 kilogramme of man can form in twenty-four hours. 
 
 A healthy man, weighing 60 kilogrammes, passes in twent}'- 
 four hours 1200 cubic centimetres of urine. If 50 cubic centi- 
 metres of this urine kill 1 kilogramme of animal, 1200 cubic 
 centimetres ought to kill 24 kilogrammes of the animal ; then 60 
 kilogrammes of man make and eliminate l>y the kidneys in twenty- 
 four hours what would kill 24 kilogrammes of animal. Thus, 
 1 kilogramme of man forms in twenty-four hours what would 
 kill 400 grammes of an animal. In order to kill 1 kilogramme 
 it is necessary to have 1 urotoxy. The urotoxic co-efficient of 
 this man of 60 kilogrammes is thus 0.4. This is almost the 
 normal co-efficient, which I have found to be, on an average, 
 0.464. 
 
 If 1 kilogramme of man forms in twenty-four hours what 
 is sufficient to kill 464 grammes of animal, he forms in twenty- 
 four hours almost one-half of what is necessary to kill himself. 
 On an average of two days and four hours man makes a mass of 
 urinary poison capable of intoxicating himself. There are varia- 
 tions in the normal state for the urotoxic co-efficient, but they 
 are limited. In the pathological state the urotoxic co-effick-nt 
 raivly exceeds 2 and rarely descends below 0.10. 
 
 The toxicity of normal urines varies according to numerous 
 circumstances, cerebral activity, muscular activity, sleep, diet- 
 ing, etc. The variations bear upon the intensity and upon the
 
 36 LECTURES ON AUTO-INTOXICATION. 
 
 quality of this toxicity. The urines of sleep, although more 
 dense, more rich in solid matter, are, in equal volumes, almost 
 always less toxic than the urines of the day. In an equal time 
 the urines secreted during sleep always contain an amount of 
 material less toxie than that secreted during the day. Man 
 elaborates during sleep from two to four times less poison than 
 during an equal time of cerebral activity. 
 
 TOXICITY OF THE URINES FORMED DURING THE DAY AND OP 
 THOSE FORMED DURING SLEEP. 
 
 September 15, 1885. We gather the urine of twenty-four 
 hours of a healthy adult man weighing 81 kilogrammes and 700 
 grammes. These urines are collected in three portions correspond- 
 ing to the periods of secretion, having in each a duration of eight 
 hours. The first portion commences from the moment of waking 
 quarter past 7 in the morning to quarter past 3 after mid- 
 day (morning period); the second portion from quarter past '3 
 to quarter past 11 at night (evening); the third portion from 
 quarter past 11 to quarter past 7 on the following morning 
 (sleep). 
 
 Urine of Eight' Hours the Morning Period. Quantity, 865 
 cubic centimetres ; density, 1027. This acid urine is exactly 
 neutralized by bicarbonate of soda, filtered, and injected into 
 a vein of the ear of a rabbit weighing 1750 grammes. The 
 rectal temperature of the rabbit before the operation was 
 39.6 C. (103.2 F.) ; owing to its not moving about, the 
 temperature fell at the beginning of the injection to 39.2 C. 
 (102.6 F.). Contraction of the pupil began when the animal 
 had received 25 cubic centimetres ; at 33 cubic centimetres, 
 emission of urine ; at 35 cubic centimetres, restlessness, re- 
 spiratory arrest, loss of palpebral and corneal reflexes ; death. 
 At this moment the temperature was at 39.3 C. (102.8 F.). 
 The heart still continued to beat for some little time. The 
 temperature of the urine injected was 26 C. (78.8 F.). The 
 animal was killed by the injection of 85 ^ >00 = 2( > cubic centi- 
 metres of urine for each kilogramme of the animal. 
 
 Urine of the Eight Hours Belonging to the Evening Period. 
 Quantity, 320 cubic centimetres; density, 1028; reaction, acid; 
 neutralized and filtered ; this urine is injected into the vein of 
 a rabbit weighing 1560 grammes. At the beginning of the 
 injection the rectal temperature of this rabbit was 40^C. (104 
 F.). At 3 cubic centimetres, quickened respiration; at 28
 
 TOXICITY OF URINES PASSED DURING THE DAY AND NIGHT. 37 
 
 cubic centimetres myosis commences, and is complete at 36 cubic 
 centimetres ; at 35 cubic centimetres, excessive movement ; at 39 
 cubic centimetres, convulsions, opisthotonos, death. The heart 
 continues to beat. The rectal temperature at the moment of 
 death is 39.8 C. (103.6 F.). The temperature of the urine 
 injected was 23 C. (73.4 F.). The animal was killed by the 
 injection of 39 ^ 00 = 25 cubic centimetres of urine for each kilo- 
 gramme of animal. 
 
 Urine of the Eight Hours of Sleep. Q.uantity, 220 cubic cen- 
 timetres; density, 1031; reaction, acid. This urine, neutral- 
 ized and filtered, was injected into a vein in the ear of a rabbit 
 weighing 1600 grammes. At the beginning of the injection the 
 rectal temperature was 40.2 C. (104.5 F.). After 6 cubic cen- 
 timetres had been injected there was quickened respiration. 
 At 21 cubic centimetres myosis had begun ; at 33 cubic centi- 
 metres, clonic convulsions; at 34 cubic centimetres, loss of 
 palpebral reflexes, exophthalmos, and momentaiy suspension of 
 respiration; at 46 cubic centimetres, very severe clonic convul- 
 sions ; then opisthotonos and death. The heart continued to beat. 
 The rectal temperature at the moment of death was 39.9 C. 
 (103.8 F.). The temperature of the urine injected was 23 C. 
 (73.4 F.). The animal was therefore killed by the injection of 
 ^ =28.75 cubic centimetres of urine for each kilogramme 
 of animal. 
 
 In equal volumes, the urines of the morning period, although 
 less dense, are more toxic than the urines of the evening period. 
 The totality of the urines of the morning period is represented 
 by \Y = 18.25 urotoxies. The totality of the urines of the 
 evening period represents 3 5 2 g = 12.8 urotoxies. The urines of the 
 sixteen hours of da}' represent, therefore, 31.05 urotoxies; or, 
 by the hour, 1.9406; or, by the hour and per kilogramme of man 
 who has furnished the urines, 0.02375. During one hour of wake- 
 fulness this man has therefore eliminated on an average per kilo- 
 gramme of his weight a quantity of urinary poison capable of 
 destroying 23.75 grammes of living tissue. In equal volumes, 
 the urines of sleep, although more dense, are less toxic than 
 the urines of wakefulness. The totality % of the urines of eight 
 hours of sleep represents 7.65217 urotoxies; or, by the hour, 
 0.956521 ; or, by the hour and per kilogramme of the man who' 
 bus farnished the urines, 0.0117 urotoxies. One kilogramme of 
 man, during one hour of sleep, eliminates, therefore, a quantity 
 of urinary poison capable of destroying 11.7 grammes of living 
 tissue. In sixteen hours of wakefulness this person has elimi- 
 nated per kilogramme what would kill 380 grammes of animal, 
 and in eight hours of sleep he has eliminated what would kill 93.6
 
 38 LECTURES ON AUTO-INTOXICATION. 
 
 grammes of animal. In the twenty-four hours (waking and 
 sleeping) he has thus eliminated a quantity of urinary poison 
 capable of destroying 437.6 grammes of animal. The urotoxic 
 co-efficient of this man was therefore 0.4736. From this we 
 conclude that, to kill 1 kilogramme of living matter, it would 
 have required for each kilogramme of this man two days, two 
 hours, and forty-three minutes. 
 
 On September 19, 1885, we gathered the urine of twenty-four 
 hours of a healthy adult man weighing 81 kilogrammes, 700 
 grammes. This urine had been received in two portions, 
 one corresponding to the sixteen hours of wakefulness and the 
 other corresponding to the eight hours of sleep. 
 
 Urine of Sixteen Hours of Wakefulness. Quantity, 700 cu- 
 bic centimetres ; density, 1028 ; urea, 24.4 grammes for every 
 1000, or 17.08 grammes for the whole of the wakeful period ; 
 reaction, slightly acid. This urine, neutralized and filtered, is 
 injected into a vein of the ear of a rabbit weighing 1720 grammes. 
 The rectal temperature at the beginning of the injection was 
 40.3 C. (104.6 F.). At the time that 23 cubic centimetres 
 of urine have been injected myosis commences ; the pupil is 
 pin-pointed at 33 cubic centimetres; at 36 cubic centimetres, 
 exorbitism, agitation ; at 43 cubic centimetres, respiratory pause ; 
 at 46 cubic centimetres, loss of e} r elid and corneal reflexes, 
 death without convulsions. The heart continued to beat. The 
 pupils continued pin-pointed after death. The rectal temperature 
 at the time of death was 39.5 C. (103.2 F.). The temperature 
 of the urine injected was 22 C. (71.6 F.). 
 
 This animal has, therefore, been killed by the injection of 
 26.74 cubic centimetres of urine for each kilogramme. 
 
 Urine of the Eight Hours of Sleep. Quantity, 225 cubic 
 centimetres; density, 1034; reaction, acid; urea, 27.2 grammes 
 for 1000, or, for the whole of the eight hours of sleep, 6.12 
 grammes. This urine, neutralized and filtered, is injected into a 
 vein on the ear of a rabbit weighing 1610 grammes. The rectal 
 temperature at the commencement of the injection was 40.2 C. 
 (104.4 F.). Myosis commences after 21 cubic centimetres had 
 been injected ; it was complete after 33 cubic centimetres; after 
 26 cubic centimetres, agitation ; at 46, clonic convulsions ; at 48, 
 strong convulsions whilst in opisthotonos ; death.- The heart 
 continued to beat but feebly, except the auricles, which contracted 
 with force. The pupils remained contracted after death. The 
 rectal temperature at the time of death was 39.7 C. (103.4 F.). 
 The temperature of the urine injected was 22 C. (71.6 F.). This 
 animal was, therefore,' destroyed by the injection of 4 -^~^= 29-81
 
 URINE MOST TOXIC IN EARLY PART OF THE DAY. 39 
 
 cubic centimetres of urine for each kilogramme. The urines of 
 the sixteen hours of the wakeful period represent ^g^j =26.178 
 urotoxies, or, by the hour, 1.G361 ; or, by the hour and per kilo- 
 gramme of man who has furnished this urine, 0.2002. A kilo- 
 gramme of man in one hour of the wakeful state eliminates, 
 therefore, what would kill 20.02 grammes of living material. 
 
 The urines of the eight hours of sleep represent J^ = 7.88336 
 urotoxies, or, by the hour, 0.98542, and, by the hour and for 
 each kilogramme of body-weight of the man who has furnished 
 the urine, 0.01206. A kilogramme of this man in one hour of 
 sleep eliminates, therefore, what would kill 12.06 grammes of 
 living tissue. There results from this that he eliminates what 
 would kill, in sixteen hours of the wakeful period, 320.32 
 grammes, and in eight hours of sleep, 96.48 grammes of animal. 
 Therefore, in twenty-four hours he eliminates what would kill 
 416.80 grammes of living- matter. The urotoxic co-efficient of 
 this man is beyond 0.4168. It would require for each kilo- 
 gramme of this man, in order to kill 1 kilogramme of living 
 matter, two days, nine hours, and thirty-five minutes. 
 
 During wakefulness the greatest toxicity belongs to the 
 first half of the day period. From a very health} 7 adult, I have 
 gathered separately the urines of the three periods of eight 
 hours, representing the whole supply of a day of twenty-four 
 hours, waking and sleeping. The first two periods from 7.15 A.M. 
 to 3.15 P.M., and from 3.15 to 11.15 P.M. represent the period of 
 wakefulness. The last period from 11.15 P.M. to 7.15 on the 
 following morning had been devoted to sleep. This man fur- 
 nished, per kilogramme and for eveiy hour, in the first period 
 (morning), what would kill 27.92 grammes of living tissue; in 
 the second period (evening) what would kill 19.58 grammes ; and 
 in the third period (sleep) what would kill 11.70 grammes. The 
 proportion of the urinary toxicity during these three periods of 
 the day has always been sensibly shown to be the same ; it may 
 be expressed respectively by the indices 7, 5, 3. A graphic 
 record will allow of the more easy penetration into the details 
 of this study. I represent a complete nycthdmere from 10 
 o'clock at night to 10 o'clock in the morning. The period of 
 sleep is shaded; it extends from 10 o'clock at night to 6 o'clock 
 on the following morning : it is thus eight hours. The period
 
 40 
 
 LECTURES ON AUTO-INTOXICATION. 
 
 of wakefulness is exactly divided into two equal parts of eight 
 hours. The one from 6 o'clock in the morning to 2 o'clock in 
 the afternoon represents the morning period of wakefulness ; 
 the other, from 2 o'clock in the afternoon to 10 o'clock at night, 
 represents the evening period. 
 
 The horizontal line measures the duration of the periods of 
 elimination. The area of the trapezes which rest upon this line 
 represents the quantity of poison eliminated in each period ; the 
 
 /\ 
 
 \ 
 
 \ 
 
 \ 
 
 \ 
 
 \ 
 
 \ 
 
 10 P.M. 
 
 6 A.M. 
 
 MID DAY 2P.M. 
 
 10 RNI. 
 
 vertical lines indicate by their length the intensity or the rapidity 
 of the toxic elimination for every instant of the day. We see 
 that the minimum of this elimination is at the moment when 
 man is asleep ; that it is then nine times less intense than the 
 eight hours previously, in the middle of the period of wakeful- 
 ness, and five times less than eight hours later on, at the end 
 of the period of sleep. We thus see that from the minimum to 
 the maximum, during the sixteen hours which represent sleep 
 and the morning period of wakefulness, the intensity of the
 
 URINE OP SLEEP ANTIDOTAL TO THAT PASSED DURING THE DAY. 41 
 
 toxic elimination is produced with a rapidity twice greater. 
 The urines of the day period do not only differ from the 
 urines of sleep by a toxicity twice greater, but the toxicity 
 of these two urines presents differences of a qualitative 
 character. The urines of sleep are always markedly con- 
 vulsive ; those of the day period are very little or not at all 
 convulsive, but they produce narcosis. It is at such a point 
 that we are asked if there is no possibility of accepting the old 
 toxic theoiy of sleep, that, according to which, the activity of 
 nerve-tissue is accompanied by the production of a substance 
 from disassimilation, whose action upon nerve-cells would be 
 soporific. If this theor}^ could be revived it would be necessary, 
 I believe, to expand it, and to attribute to the whole of the 
 economy the production of nai-cotic material. , What is certain 
 is, that during the day the body forms a substance which, when 
 accumulated, would induce sleep, and that during sleep it elabo- 
 rates, instead of this narcotic substance, a convulsive substance 
 which, when accumulated, could produce muscular twitchings 
 and induce waking. 
 
 The poisons of the day period and the poisons of sleep are 
 not only different as regards intensity and qualit}-, they are 
 antagonistic : the one is the antidote of the other. If we mix 
 the urines of the day period and those of the night proportion- 
 ately to their respective bulks, the toxicity of the mixture is not 
 a mean it is not necessarily intermediate between the toxicity 
 of the urines of the day and those of sleep ; it may be less 
 than the mean of those urines which were the least toxic. From 
 this we know that, in order to appreciate the whole of the toxic 
 matter formed by man, in order to determine his urotoxic 
 co-efficient, it is well not to attempt the toxicity of his urines 
 by employing a portion only of the mixture of the urines 
 passed in the twenty-four hours. It is necessaiy to determine 
 respective!}' the whole toxicity of the urines of the day period 
 and the whole toxicity of the urines of sleep, then to add the 
 two results. In determining alone the toxicit}- of the mixture 
 of the two urines we would get too small an index.
 
 42 LECTURES ON AUTO-INTOXICATION. 
 
 TOXICITY OF THE URINES OF THE DAY AND NIGHT MIXED. 
 
 We gathered the urine of twenty-four hours passed by a 
 young, healthy man, aged 28, weighing 69 kilogrammes. We 
 gathered separately the urine of nine hours of sleep from 10 
 o'clock at night to 7 o'clock in the morning and the urine of 
 fifteen hours of wakefulness, from 7 o'clock in the morning to 
 10 o'clock at night. 
 
 Urine of Sleep. Quantity, 450 cubic centimetres ; density, 
 1024. This urine, neutralized and filtered, was injected into a 
 vein on the ear of a rabbit weighing 1775 grammes. Death 
 supervened, after veiy slight convulsions, when 91 cubic centi- 
 metres had been injected. The animal had thus received for 
 each kilogramme 51.26 cubic centimetres of urine. 
 
 Urine of the Day Period. Quantity, 720 cubic centimetres ; 
 density, 1014. . This urine, neutralized and filtered, was injected 
 into a vein on the ear of a rabbit weighing 1725 grammes. 
 Death supervened, without convulsions, after 45 cubic centi- 
 metres. The animal had thus received 26.08 cubic centimetres 
 of urine for each kilogramme. 
 
 Urine of Twenty-Four Hours. We mixed one-third of the 
 urine of sleep (150 cubic centimetres^ and one-third of the 
 urine of the day period (240 cubic centimetres). This mix- 
 ture represented pretty accurately the mixture of the urine of 
 twenty-four hours. This urine, neutralized and filtered, was in- 
 jected into a vein in the ear of a rabbit weighing 1555 grammes. 
 Death supervened, without convulsions, after 73 cubic centi- 
 metres. The animal had thus received for each kilogramme 
 46.94 cubic centimetres. The urine of sleep represented 
 g^g =8.778 urotoxies. The urine passed during the day repre- 
 sented 2^g= 27.607 urotoxies. The urine of the twenty-four hours 
 represented, therefore, 8.778 -f 27.607 = 36.385 urotoxies ; but if 
 we wished to estimate this toxicity of the urine of the twent}'- 
 four hours by the experiment which shows the toxicity of the 
 mixture, we find that this toxicity would only be -^^=24.925 
 urotoxies. Thus, from the fact of their being mixed, the urines 
 of the day and of night lose about one-third of their toxicity. 
 From this we ought strongly to conclude that man eliminates 
 during sleep urine which is parti} 1 - antidotal to the urine of the 
 day, or vice versa. There would thus be, therefore, in the dif- 
 ferent conditions of nerve function, different elaborations of 
 material capable of giving rise to poisons antagonistic to each 
 other. From this experiment we can equally deduce that this 
 man was eliminating for each kilogramme of his own weight, 
 every hour during sleep, sufficient to kill 14.135 grammes of
 
 TOXICITY OF URINE REDUCED BY MUSCULAR EXERCISE. 43 
 
 living matter, and during the daj r 26.673 grammes ; that during 
 the period of twenty -four hours (day and night) he was eliminat- 
 ing sufficient urinary poison to kill 527 grammes of living 
 matter. His urotoxic co-efficient was therefore 0.527. To in- 
 toxicate his weight of living material he would require forty- 
 five hours and twenty-eight minutes. 
 
 The toxicity of the urine of sleep being only half of the 
 toxicity of the urine secreted during an equal period of the day, 
 we might think that the urine of repose ought to be less toxic 
 than the urine of muscular effort. But it is the contrary which 
 is true. One day of great muscular activity, spent in the open 
 air, in the country, diminishes the toxicity of the twenty -four 
 hours by one-third, and on that day the toxicity does not dimin- 
 ish only during the time devoted to muscular exercise. The 
 toxicity, which diminishes during work, remains less during 
 the repose which follows this work and during the sleep which 
 succeeds this day of muscular activity. This fact has, I think, 
 an important bearing, it shows that a large part of the toxicity 
 is not attributable to the mineral substances, which certainly are 
 not diminished by the fact of exercise, and that it depends upon 
 organic substances incompletely oxidized, whose toxicity dimin- 
 ishes in proportion as oxidation is more completely effected. 
 We urge upon all, without insisting upon it too much, the 
 interest which this experiment has from a therapeutical point 
 of view. 
 
 INFLUENCE OF EXERCISE UPON THE TOXICITY OF URINE. 
 
 We gathered the urine of the day and of sleep of a man of 
 81,700 kilogrammes, after a day of great bodily exercise, spent 
 in the open air. We have for the day urine 1070 cubic centi- 
 metres (density, 1020) and for the urine of sleep 243 cubic 
 centimetres (density, 1027). These urines are acid. The urines 
 of the day period were gathered on the llth of October, from 
 1.15 to 10.30 in the evening, and on the 12th of October, from 
 7 A.M. to 1.15 P.M. We have therefore the urine secreted during 
 fifteen and a half hours. The urines of sleep were received from 
 10.30 P.M. to 7 A.M., i.e., during eight and a half hours.
 
 44 LECTURES ON AUTO-INTOXICATION. 
 
 Into a rabbit weighing 1360 grammes we made an intra-venous 
 injection of the urine of the day period. Death supervened 
 after 72 cubic centimetres, preceded by some slight convulsive 
 movements. It had received, for each kilogramme of its own 
 weight, 52.94 cubic centimetres. The pupils were pin-pointed 
 at the moment of death. 
 
 Into a rabbit weighing 1360 grammes we injected the urine 
 of sleep. Death occurred after 66 cubic centimetres, after severe 
 convulsions and retroflexion of the body in the form of opis- 
 thotonos. It had received, for each kilogramme of its weight, 
 49.26 grammes. The pupils were pin-pointed. 
 
 Thus, during the fifteen hours and a half of the day period 
 1070 cubic centimetres of urine had been secreted. This urine 
 killed a kilogramme of rabbit with a dose of 52.94 cubic centi- 
 metres. Man during the day has therefore secreted what would 
 kill ^j 4 kilogrammes, and for each kilogramme of man and for 
 every hour 52 79 X$LJ x is.5 =0 - 01596 kilogrammes. Therefore, during 
 the day period 1 kilogramme of man secreted in one hour what 
 would kill 15.96 grammes of rabbit. During the fifteen and 
 one-half hours of the day 1 kilogramme of man secretes what 
 would kill 247.38 grammes of rabbit. 
 
 During eight and one-half hours of sleep 243 cubic centi- 
 metres of urine had been secreted. This urine killed 1 kilo- 
 gramme of rabbit with a dose of 49.26 cubic centimetres. Man, 
 during eight and one-half hours of sleep, killed J^~ kilogrammes, 
 and in one hour 492 g 4 ^ g --; and 1 kilogramme of man secreted dur- 
 ing one hour of sleep what would kill ^ex^sxsiT^ 7 ' 103 g rammes 
 of rabbit. In eight hours and thii'ty minutes of sleep 1 kilo- 
 gramme of man secreted what would kill 60.38 grammes of rab- 
 bit. In twenty-four hours (night and day) 1 kilogramme of man 
 secreted sufficient to kill 247.38 + 60.38 = 307.76 grammes of 
 rabbit. 
 
 The urotoxic co-efficient of this man is, in round figures, 
 0.308 : 1 kilogramme of man, in order to secrete what would 
 kill 1 kilogramme requires three days, five hours, and fifty-five 
 minutes. 
 
 In equal time the urines of the day period have a toxicity 
 more than double that of the urines of sleep. The exact rela- 
 tionship for the toxicity of sleep compared to the toxicity of the 
 wakeful period is 7.103 : 15.96 = 0.45. 
 
 On the whole, therefore, the urotoxic co-efficient of this man, 
 on a day of heavy muscular work in the open air, is 0.308. It 
 was, at two periods of repose, the 17th of September and the 
 19th of September, 0.474 and 0.417, or a mean of 0.445. The
 
 THE TOXICITY OF URINE. 45 
 
 relationship of the toxicity of the man who works to the toxicity 
 of the man in repose is as 0.308:0.445 = 0.692, or, in round 
 figures, 0.7. Muscular eifort in the open air has therefore sup- 
 pressed j\ of the toxicity. In this man twice, on the occasion 
 of sedentary work in town, the toxicity for each kilogramme 
 ami for every hour had been, during the day, 23.75 grammes and 
 20.62 grammes, a mean of 21.88 grammes, and during sleep 
 11.70 grammes and 12.06 grammes, a mean of 11.88 grammes. 
 By the fact of severe bodily exercise in the open air it became, 
 during the day, 15.96 grammes and during sleep 7.10 grammes. 
 The amount ^ = 0.720. The amount J = 0.597. 
 
 Muscular effort in the open air diminished thus from 27 for 
 every 100 the toxicity of the da}^, and its influence extended 
 also to the period of sleep which followed work, causing a loss 
 of 40 in the 100 to the toxicity of the urine of sleep. The 
 causes which influence urinary toxicity may therefore act during 
 the period of their application and also during a long period 
 of time after they have ceased to exist. It is for this reason, 
 doubtless, that the morning period is more toxic than that of 
 sleep and the period of sleep less toxic than that of the evening. 
 
 It is not sufficient to know that the urines have been rendered 
 toxic by the solid substances which they contain. What are 
 these substances? Amidst the different symptoms of urinary 
 intoxication, what symptoms belong to such and such a sub- 
 stance? Is there no substance whose toxicity is masked by its 
 union with those that are more toxic, these killing the animal 
 before the first may even have been manifested, and whose toxic 
 power would be shown if they acted separately ? Is there not, 
 in the pathological state, a diminution of normal toxic sub- 
 stances and an increase of other substances incapable normally 
 of intoxicating? There are many other questions also to which 
 we must endeavor to reply. 
 
 Before demonstrating the degree of the toxicity of urine 
 taken in the bulk there is only one resting-place for our re- 
 searches. It is necessary to dissect, so to speak, this mass, and 
 to operate upon it in portions, in order to know intimately the 
 degree of toxicity of each of the elements which compose it.
 
 LECTURE Y. 
 CAUSES OF THE TOXICITY OF URINE. 
 
 RSsumfi of the physiological phenomena produced by the iutra-venous injection 
 
 of normal urine. Definition of urotoxy and the urotoxic co-efficient. 
 
 Research as to the possible causes of the toxicity of urine. Modification of 
 
 the toxicity of urine by time, temperature, exposure to air, fermentation. 
 
 Examination of the constituent elements of urine from the point of view of 
 the part which they may play in its toxicity. Water. Volatile substances. 
 Urea : Intra-venous injection of urea. Experiments of MM. Grehant and 
 Quinquaud by subcutaneous injection. Insignificant toxicity of urea. Uric 
 acid : Intra-venous injection of uric acid. Feeble toxicity of uric acid. 
 Creatinine : Its toxicity nil (Rauke and Schiffer). Odorous substances. 
 Coloring matters. Intra-venous injection of colored urine and of urine 
 decolorized by means of carbon. Very important diminution of toxicity and 
 loss of the myotic power of the urine after decoloration. Alkaloids. Analy- 
 sis of the toxic properties of urine by the dichotomic study of the extracts. 
 Substances soluble in alcohol. Substances insoluble in alcohol. Unequal 
 toxicity and toxic modality different in the two extracts. Effects pro- 
 duced by the substances soluble in alcohol, somnolence, coma, diuresis, 
 salivation. Hypothesis relative to the appearance of this property, which is 
 
 not possessed by urine naturally. Effects of the substances insoluble in 
 
 alcohol. Convulsions, myosis, diminution of heat-production. Unequal 
 
 assimilation of the toxic power of urine to that of certain alkaloids. 
 
 Hypothesis bearing upon the explanation of the physiological effects proper 
 to urinary extracts. Urea is, perhaps, the cause of the diuresis. Loss of 
 the myotic power and considerable diminution of the curative property after 
 carbonization, which has left in the urinary extracts nothing else than 
 
 mineral matter. Insufficiency of soda to produce the toxicity of urine. 
 
 Toxic importance of potass, which partly contributes to the convulsive 
 power of urine. 
 
 HAVING introduced normal urine into the veins, I have been 
 able to demonstrate that its toxic action bears especially upon 
 the nervous system, since it paralyzes movement without 
 destroying the contractility of muscle, in so far as it allows the 
 heart to continue beating. Disorders of movement become, 
 at length, apparent in the pupil, which becomes pin-pointed. 
 Myosis persists up to death, without there being any lesion 
 of the muscles of the iris, since the pupil generally dilates after 
 death. The movements of the respirator}' muscles are quick- 
 ened, those of the locomotor muscles weakened. The loss of 
 (46)
 
 DEFINITION OF UROTOXIC CO-EFFICIENT. 47 
 
 the reflexes in the advanced phases of intoxication, somno- 
 lence, and coma still show that the brunt is borne by the ner- 
 vous system. It is in the same sense that the disturbances of 
 the secretory apparatus are to be considered, the frequent 
 emission of urine, the salivary hypersecretion, of which we shall 
 speak soon, and, lastly, the fall of the temperature by diminution 
 of heat-production. That is the first fact, and it is the funda- 
 mental one in the phenomena of intoxication. 
 
 Before going further, it is necessary to establish a standard 
 to estimate whether an individual forms in a given time more 
 toxic matter than another individual. I have adopted the term 
 urotoxy, toxic unit, or toxicity of urines. The toxic unit is 
 the quantity of toxic matter capable of killing one kilogramme 
 of living animal, hi order to study afterward the reports of 
 the various toxicities, I have established what the urotoxic 
 co-efficient is, of which a brief argument will explain the 
 necessity. 
 
 If to kill a kilogramme of rabbit 30 cubic centimetres of the 
 urine of Peter and 60 cubic centimetres of the urine of Paul are 
 necessary, we are first led to believe that the urine of Peter is the 
 more toxic. Yet, we are not altogether right in stating the con- 
 clusion thus : for if, in twenty-four hours, Paul has secreted twice 
 as much urine as Peter, the loxicit}- is equal in the two. I go fur- 
 ther : Two individuals eliminate in twenty -four hours the same 
 quantity of urine; they kill with the same dose a kilogramme 
 of rabbit ; it does not necessarily follow from this that they 
 have the same toxic power, for another cause of variation 111:1 y 
 intervene, the weight of the individuals; if one, weighing 
 less by a half than the other, makes the same quantity of toxic 
 material, he has evidently a toxic power double that of the 
 other. 
 
 We are thus led to define the co-efficient of toxicity as the 
 quantity of toxic matter which a unit of weight produces in a 
 unit of time. I will say, with greater precision, the urotoxic 
 co-efficient of an individual is the number of urotoxies formed 
 in twenty-four hours by a kilogramme of that individual. 
 
 These premises granted. \vc come now to seek among the 
 constituent elements of urine for those to which the toxicity of
 
 48 LECTURES ON AUTO-INTOXICATION. 
 
 urine is due. We discard at once the idea that the water is 
 toxic. It may be introduced with impunity into the blood in 
 doses much larger than that in which urine kills. Besides, evapo- 
 ration causes the urine to become more toxic. When, by evapo- 
 ration, we reduce to one-half of its volume a urine which kills 1 
 kilogramme of rabbit with a dose of 60 cubic centimetres, we 
 see that this urine thus concentrated kills with a dose of 30 cubic 
 centimetres. Toxicity depends, therefore, not on the water, but 
 upon the substances which it holds in solution. If evaporation 
 is made slowly, we notice an absolute increase of the toxicity, 
 and no longer an increase proportional to the degree of concen- 
 tration. This can only be explained by chemical changes 
 undergone by substances that are unstable, substances which 
 really do not belong to the group of minerals. This fact, the 
 increase of toxicity by evaporation, allows us also to conclude 
 that the other volatile substances contained in the urine are not 
 either the cause of its toxicity. 
 
 We increase the toxicity of urines by leaving them for a long 
 time to themselves, even if we protect them from fermentation. 
 Rise of temperature, exposure to air especially, length of 
 time in keeping, all modify their toxic power. Such a urine 
 which killed by coma becomes toxic with a smaller dose, but it 
 does so by inducing convulsions. If fermentation is set up in 
 it, the toxicity varies ; it may be increased or diminished ; it is 
 in every case changed by it. If there is produced within it car- 
 bonate of ammonia, we may have the special phenomena wit- 
 nessed in annnonsemia. 
 
 The increase of toxicity on keeping the urine already allows 
 us to assume that it is not the mineral substances which are the 
 sole cause of the toxicity, since they are not more abundant in 
 old urine, the potass, notably, remains in the same quantity. 
 
 Before going further, we may pass in review some hypotheses 
 which have been enunciated on this subject, viz., the causes of 
 the toxicity of urine. Formerly, for example, urea was consid- 
 ered the chief poisonous agent, after the teaching of Wilson. 
 The intra-venous injection of urea, which I have practiced a 
 great many times, enables me to say that we can certainly kill 
 with urea, as with many other bodies, by modifying the
 
 INTRA-VENOUS INJECTION OF UREA. 49 
 
 conditions of osmosis : by increasing in such proportions the 
 density of the blood and the liquids of the organism that we 
 ph3'sically hinder the functions of nutrition. But the solutions 
 of urea which have not this excessive density do not kill, or they 
 lead to death only if we have injected more than 122 cubic 
 centimetres of it for each kilogramme, a dose in which pure 
 water kills. 
 
 INTRA-VENOUS INJECTION OF UREA WITHOUT MORBID PHENOMENA. 
 
 October 16, 1884. Into a rabbit weighing 1690 grammes we 
 inject, in ten minutes, into a vein on its ear, 100 cubic centi- 
 metres of an aqueous solution, which contains exactly 4 grammes 
 of urea. The animal has thus received per kilogramme 2.366 
 grammes of urea, and, as this urea has been introduced into its 
 blood, that makes 30.758 grammes per kilogramme of blood, 
 about two hundred times the normal quantity (2.366 X 13 = 
 30.758). The temperature at the commencement was 39.7 C. 
 (103.4 F.) ; at the end of the experiment it was 38.8 C. (101.8 
 F.). No morbid phenomenon. 
 
 October 25th. The animal is well. 
 
 October 28th. It remains quite well. 
 
 The temperature of this animal has fallen in ten minutes nine- 
 tenths of a degree. The heat-capacity of the tissues being 0.8, the 
 animal has, therefore, lost 1690 X 0.8 X 0.9 = 1216.8 calorics. 
 On the other hand, water injected, which was, at the commence- 
 ment, of a temperature of 1 6 degrees, is heated to 22.8 degrees, 
 and consequently has absorbed 100 X 22.8 = 2280 calorics. 
 Water has, therefore, taken from the body of the animal a 
 quantity of heat more considerable than that which it lost in 
 falling from 39.7 degrees to 38.8 degrees. Consequently, the in- 
 jection has not produced refrigeration by impeding heat-produc- 
 tion ; on the contrary, there has been, during the period of the 
 injection, an increase of calorification, since the temperature of 
 the animal has remained higher than that which it would have 
 attained by the fact alone of the refrigeration due to the injection. 
 
 Fatal accidents supervene only after an injection containing 
 6.31 grammes of urea per each kilogramme of the animal, or 82 
 grammes per each kilogramme of blood ; a supposition that there 
 is ten times more urea than we have found in the blood of
 
 ' 50 LECTURES ON AUTO-INTOXICATION. 
 
 patients who have succumbed, as one would say, to intoxication 
 from this substance. It is not admissible that urea is the toxic 
 agent of urine. 
 
 INTRA-VENOUS INJECTION OF A VERY LARGE DOSE OF UREA DEATH. 
 
 October 25, 1884. We injected, in thirty-five minutes, into a 
 vein in the ear of a rabbit weighing 1790 grammes, 113 cubic 
 centimetres of an aqueous solution of urea at y 1 ^ let us say 11.3 
 grammes of urea ; or, for each kilogramme, 6.31 grammes ; 
 or, for the total mass of the blood (137 grammes), 11.3 grammes ; 
 or, for a kilogramme of blood, 82.03 grammes. A fter injecting 35 
 cubic centimetres, respiratory disturbances were the first to be 
 noticed ; respiration became slower. After 58 cubic centimetres, 
 slight convulsions and tremors renewed from time to time; 
 respiration was still further slowed. At the end of the injection 
 the animal was comatose ; it died ten minutes after stopping the 
 injection. At the autopsy we found the blood of a blackish- 
 brown color ; nothing in the lungs ; almost no urine in the blad- 
 der. The quantity of urea which had been introduced into the 
 blood was about five hundred times greater than that which the 
 blood contains in the natural state. We might ask if the accidents 
 were due to the toxicity of this solution or to its degree of con- 
 centration, which might have modified the physical conditions 
 of the blood-globules or of the cells of the tissues. 
 
 The experiments which I have just cited appear to disagree 
 with the recent researches of Grdhant and Quinquaud. Death 
 supervened, in their experiments, after injection of 6 grammes 
 of urea for each kilogramme of animal ; but the injection was 
 made into the cellular tissue. Now, the additional loading of 
 blood by urea could only have been produced if the whole dose 
 had penetrated, all at once, into the circulation, which is scarcely 
 possible by the subcutaneou's method. These experiments, inter- 
 esting from an experimental point of view, are without clinical 
 application. 
 
 Six and thirty -one hundredths grammes of urea are necessary 
 to kill 1 kilogramme of animal ; to kill a man of 60 kilogrammes 
 it would require, therefore, that his blood should retain more 
 than 380 grammes of it at one time. But 1 kilogramme of man
 
 IS URIC ACID TOXIC? 51 
 
 forming, in twenty-four hours, only 0.33 grammes of urea, or 20 
 grammes for each 60 kilogrammes, it would require, in order 
 that his death should be due to retention of urea, that he should 
 make nineteen times more of it ( 3 2 ^ = 19) in twenty-four hours, 
 and that he should not eliminate any of it during that time ; or 
 that, making the normal quantity, he should remain nineteen 
 days without eliminating any. 
 
 Some have incriminated uric acid as the cause of the toxicit y 
 of urine. But it is made in our bod} 7 in far too minute a 
 quantity (50 to 60 centigrammes in twenty-four hours), and the 
 gouty man can have hundreds of grammes of urate in his de- 
 posits without being intoxicated by it. Besides, I have been 
 able to inject experimentally into the blood 30 centigrammes 
 of uric acid for each kilogramme of animal without apparent 
 accident ; I have even been able to inject as much as 64 centi- 
 grammes of uric acid in solution in 160 cubic centimetres of 
 water, to which the necessary additional quantity of soda had 
 been added to produce its solution. 
 
 EXPERIMENT BEARING UPON THE TOX1CITY OF URIC ACID. 
 
 March 8, 1886. "We took 1 gramme of uric acid, which we 
 dissolved in 1 cubic centimetre of soda-lye and distilled water. 
 We obtained 250 cubic centimetres of liquid. We passed 
 through it a current of C0 2 until it caused visible alterations. 
 We redissolved with a trace of soda, and filtered. A rabbit, 
 1560 grammes. Injection into the auricular veins of 250 cubic 
 centimetres. The animal received 1 gramme of uric acid, or, 
 per kilogramme, 0.641 ; it received of the liquid 160.35 cubic cen- 
 timetres. It did not die. Removed, it was only sick. Urine 
 alkaline, muddy, containing blood. Heated, this urine became 
 slightly clear. Albumen was precipitated. We filtered it hot. 
 On cooling, it again became muddy, in a very notable manner, 
 and gave an abundant precipitate of basic unites. We filtered. 
 Into the limpid liquid \ve poured a little acetic acid. We had 
 again an abundant precipitate of acid n rates. The murexide 
 reaction was very distinct. One hour and three-quarters after- 
 ward very strong convulsions, which were repeated, until death, 
 two hours and twenty minutes after the commencement of the 
 experiment. Autopsy : numerous foci of pulmonary apoplexy. 
 Nothing in the other viscera.
 
 52 LECTURES ON AUTO-INTOXICATION. 
 
 The animal died slowly, and another experiment, performed 
 for comparison, in which I injected the same quantity of water 
 and soda without uric acid, has proved to me that death was 
 alone due to the excess of the vehicle. En resume, 1 kilo- 
 gramme of man forms, in twenty-four hours, 8 milligrammes of 
 uric acid. We are far from accounting for, by means of this 
 agent, the intoxication which 10 to 20 cubic centimetres of 
 urine produce. 
 
 CONTROL EXPERIMENT MADE WITH THE SAME QUANTITY OF SODA- 
 LYE WITHOUT URIC ACID. 
 
 March 10th. We made a solution of 1 cubic centimetre of 
 the same soda-lye which had served for the previous experiment 
 in a quantity of distilled water sufficient to make 250 cubic cen- 
 timetres. We passed through it a current of C0 2 until it was 
 neutralized, and we injected some of this into the veins of a 
 rabbit weighing 1460 grammes. It received 236 cubic centi- 
 metres of this solution, or 160 cubic centimetres of liquid per 
 kilogramme. The injection was made at 4 o'clock; it lasted 
 fifteen minutes. At 7.30 the urine was bloody, limpid, acid. 
 After coagulation of the albumen by heat, filtration, and cooling, 
 no precipitate was produced ; nor was there produced .any 
 greater precipitate, in this same filtered and cold liquid, when 
 we added acetic acid to it. Died during the night. The only 
 difference between this and the last experiment is, that the first 
 rabbit received uric acid, whilst the second received none at all. 
 The results being the same in the two cases, it is clear that 
 death ought to be attributed to this excessive quantity, viz., of 
 water, 160 cubic centimetres, injected per kilogramme of the 
 animal, and we know that distilled water produces death after 
 122 cubic centimetres. Therefore, with 64 centigrammes per 
 kilogramme, uric acid is not toxic. I add that we can never 
 introduce into the veins of an animal more uric acid than in the 
 first experiment, since this dose of uric acid would saturate a 
 quantity of water which, of itself alone, is toxic. 
 
 We could continue the demonstration for creatinine, but the 
 experiments, already old, of Ranke and Schiffer having estab- 
 lished that it is not toxic, enable us not to insist any more upon 
 it. Besides, we shall return, on another occasion, to this 
 experimental investigation.
 
 THE COLOR PRINCIPLES IN URINE. 53 
 
 I have given some attention to the part which coloring and 
 odoriferous substances may play in toxicity. Evaporation, 
 which drives off odoriferous materials, increasing the toxicity 
 of the urine, puts them sufficiently out of all causal influence. 
 
 Also, as regards the coloring principles, I have proceeded in 
 the following manner: I estimate the toxic power of a urine by 
 a natural injection. I decolorize it by carbon. I inject this 
 decolorized urine, and I ascertain that it has lost nearly one- 
 third of its toxicity. A quantity equal to that which killed 
 only produces accidents that are scarcely perceptible. It pro- 
 duces particularly nothing more than pupillary contraction. 
 
 INTRA-VENOUS INJECTION OF URINE, COLORED AND DECOLORIZED. 
 
 December 4, 1884. 1. We injected 65 cubic centimetres 
 of a mixture of urine, taken from two healthy men, filtered and 
 neutralized, into the auricular veins of a rabbit which weighed 
 1650 grammes, or 39 grammes for each kilogramme. 
 
 We soon produced a pupillary contraction, very marked, but 
 not pin-pointed. The animal, after the injection, was very much 
 depressed. The temperature, previously 39.2 C. (102.6 F.), 
 fell Jo 38.4 C. (101.2 F.), and then to 37.8 C. (100 F.). 
 
 2. We injected 102 cubic centimetres of the same urine, 
 after having decolorized it, into a rabbit weighing 1670 grammes, 
 or 64 grammes for each kilogramme. The pupil was not con- 
 tracted. The animal appeared, after the injection, much less 
 indisposed than that in the previous experiment. Temperature 
 before, 39.2 C. (102.6 F.) ; after it, 38.6 C. (101.5 F.). 
 
 We are, therefore, tempted to say that one of the toxic 
 agents of urine is a substance fixed by carbon, and, as the 
 coloring substances have this property, of attributing to them 
 one-third of the toxicity of urine; but the conclusion does not 
 follow, for, along with the coloring material, other substances 
 may be fixed in the carbon. 
 
 One-sixteenth of the potass is arrested by the carbon, 
 nearly the whole of the alkaloids. If decolorized urine, which 
 has lost one-sixteenth of its potass, has lost, at the same 
 time, one-third of its toxicity, then it follows that in the urine
 
 54 LECTURES ON AUTO-INTOXICATION. 
 
 there is something toxic besides the potass. And if the urine, 
 which has lost the whole of its alkaloids, still retains two- 
 thirds of its toxicity, then it follows that the toxicity does not 
 wholly reside in the alkaloids. When we exhaust the dry 
 residue of the urine by means of alcohol, we see that the alco- 
 holic extract, which really contains the greater part of the alka- 
 loids, is sensibly less toxic than the residue insoluble in alcohol, 
 which ought to contain only a few of the alkaloids. Carbon, 
 therefore, removes from urine the substance which causes con- 
 traction of the pupil, but not all its toxic principles. 
 
 Let us follow the analysis of the toxic properties of urine 
 by means of extracts and by adopting the dichotomic method. 
 We shall evaporate a measured quantity of urine whose toxicity 
 is known. The dry residue is washed, at different times, in 
 absolute alcohol, and then we evaporate to dryness the whole of 
 the alcoholic liquids. We thus obtain two extracts, the one 
 containing substances soluble in alcohol, the other substances 
 insoluble in alcohol. These two extracts having been dissolved 
 in water, we have two solutions, the one representing the sub- 
 stances of the urine which are soluble in alcohol, the other the 
 substances which are insoluble in alcohol. We gauge the tox- 
 icity of these two extracts. We establish the fact that both are 
 toxic, but in different ways. 
 
 INJECTION INTO THE VEINS OP A RABBIT OP THE AQUEOUS EXTRACT 
 OP NORMAL URINE INSOLUBLE IN ALCOHOL ; DEATH. 
 
 November 11, 1884. We take 200 cubic centimetres out of 
 the whole quantit} 1 " of 1300 centimetres of normal urine passed 
 in twenty-four hours. We evaporate to dryness upon the water 
 bath with chloride of calcium ; the residue has been washed in 
 absolute alcohol ; all the alcoholic liquids poured together, 
 filtered, have been distilled in the i*etort to dryness ; the residue 
 .is the extract soluble in alcohol. The residue of the washings in 
 alcohol taken up by the water represents the substances of the 
 urine insoluble in alcohol. This aqueous solution of the residue 
 insoluble in alcohol occupies a volume of 48 cubic centimetres. 
 It is introduced by intra-venous injection into a rabbit weighing 
 1610 grammes. 
 
 After the entrance of 12 cubic centimetres the animal is
 
 ALCOHOLIC EXTRACT OP NORMAL URINE. 55 
 
 seized with tonic convulsions accompanied by straightening of 
 the head. These convulsions rapidly disappear after we discon- 
 tinue the injections- 
 
 At the end of 42 cubic centimetres the animal is seized with 
 a violent tonic convulsion with opisthotonos, vibratory tremor, 
 and it dies. At no period did it present contraction of the 
 pupil except immediately after death. Temperature before in. 
 jection, 39.2 C. (102.6"F.) ; at the moment of death, 38.6 C. 
 (101.5 F.). Symptoms commenced on the entrance of 31 
 grammes of urine for each kilogramme, and death supervened 
 when we had injected the insoluble extract from 108 grammes 
 of urine. 
 
 INTRA- VENOUS INJECTIONS OF THE ALCOHOLIC EXTRACT OF NORMAL 
 URINE; DEATH. 
 
 November 11, 1884. Of 200 grammes of urine treated in 
 the same way as we have said in the previous experiment, we 
 take the extract which is soluble in alcohol. This extract, 
 containing 3.90 grammes of urea, is diluted with distilled water 
 in such a manner as to have a volume of 39 cubic centimetres. 
 Urea is found there to be one-tenth. We inject 33 cubic centi- 
 metres of this solution into the veins of a rabbit which weighs 
 1870 grammes. We see the pupil contract rapidly; after the 
 tenth centimetre it is markedly contracted. Starting from this 
 moment its diameter oscillates, but up to the end of the in- 
 jection it remains smaller than in the normal state. From this 
 point of view this result is exceptional ; as a rule, the pupil is 
 contracted more by the aqueous than by the alcoholic extract. 
 The animal has no convulsion, but it falls gradually into a state 
 of sleepiness ; remains unmoved ; lies upon its side ; its pupil 
 gradually dilates and becomes very large. During this coma- 
 tose period the rabbit salivates and urinates abundantly. The 
 initial temperature, which was 39.4 C. (102.9 F.), falls in a few 
 minutes (10 or more) to 38.8 C. (101.8 F.). 
 
 In this experiment, the contraction of the pupil was mani- 
 fested, under the influence of the soluble extract, from 27 
 grammes of urine for each kilogramme. The last symptoms 
 corresponded to the injection of the soluble extract, from 90 
 cubic centimetres of urine for each kilogramme. 
 
 November 12th. The animal died during the night. Nothing 
 special at the autopsy. 
 
 The toxicity varies according to the individuals who have
 
 56 LECTURES ON AUTO-INTOXICATION. 
 
 furnished the urines. The toxicity of each of the extracts is 
 less than that of the whole urine. The manner in which they 
 show their toxicity is different. Thus, the solution from the 
 dry extract of substances soluble in alcohol produces somno- 
 lence, deep coma, diuresis. It does not cause a marked dimi- 
 nution of heat-production (the small quantity of caloric lost is 
 only equivalent to the equalization of the temperature, which 
 takes place owing to the quantity of liquid necessary to inject 
 the extract) ; it does not cause nryosis, but a new symptom is 
 caused, viz., salivation, a salivation lasting three-fourths of an 
 hour, at least equal to that which is produced by jaborandi. 
 
 Here, then, is a fact, at first sight inexplicable. How can one 
 part of the urine itself produce what the aggregate cannot? 
 In order to salivate, it probably requires a measured quantity of 
 the sialogenous material soluble in alcohol, and 3 r et there exists 
 an insufficient quantity of this sialogenous matter in the total 
 quantity of urine to cause death. 
 
 Experimented upon in its turn alone, the extract of sub- 
 stances insoluble in alcohol produces myosis, like normal urine ; 
 also convulsions, which we never obtain with the extract of 
 substances soluble in alcohol, but which we obtain exceptionally 
 with the aggregate of urine. The convulsions are a phenome- 
 non of later development ; it requires a larger quantity of the 
 extract insoluble in alcohol to induce convulsions than to bring 
 about contraction of the pupil. We observe, too, in addition, 
 diminution of temperature; but we neither obtain coma, diuresis, 
 nor salivation. Thus, we are forced to admit that there is a 
 plurality of toxic substances in urine. The tendency which we 
 have to regard intoxication by means of urine as similar to that 
 produced by certain alkaloids is not justified. Muscarine, for 
 example, produces myosis and salivation, but we see these two 
 phenomena dissociated when we experiment separately with the 
 extract of substances soluble and with that of others insoluble 
 in alcohol. 
 
 We can still say that coma, diuresis, and salivation are not 
 produced by mineral substances, of Avhich a very small quantity 
 (some salts of potass) pass into the alcoholic washing ; that 
 the convulsions, myosis, and fall of temperature are not attrib-
 
 PRODUCTION OP MY08IS AND CONVULSIONS. 57 
 
 utable to the mass of organic substances which have been caught 
 in the washing with alcohol. Coma, which the soluble sub- 
 stances in alcohol produce, is never caused by urea. This causes, 
 before death, no other phenomenon than diuresis ; it does not 
 cause diminution of temperature, and does not kill, except as we 
 have seen it in enormous doses by preventing osmosis. That is 
 what I mean. As for replying to other questions, as to the part 
 which is played by such or such a body on the production of 
 each of the symptoms observed after the injection of extracts, 
 I cannot. 
 
 I do not know what is the substance which, passing with the 
 urea in the alcoholic wash, produces coma. 
 
 Diuresis belongs to normal urine, to the part of the extract 
 soluble in alcohol, as it does to urea, which, experimented upon 
 purely isolated, is certainly diuretic. I may therefore think 
 that it is the urea which is the cause of the diuresis. 
 
 Urea does not increase salivation. Blood which has a sial- 
 ogenous power greater than urine contains much less urea. I 
 do not know what is the substance which produces salivation. 
 I can only say that we find it in the blood, in the muscles, and 
 in the liver. 
 
 What is it that produces myosis and convulsions ? Is it the 
 mineral substances ? We are tempted to say that it is. Decol- 
 orized urine, however, which has lost little of its mineral sub- 
 stance no longer causes convulsions nor myosis. Experiment- 
 ally, after carbonization of the extract, the dissolved residue, 
 which no longer contains anything but mineral substances, does 
 not produce convulsions or myosis. Myosis is never produced ; 
 but if we inject more mineral material than the mass of urine 
 contains which has killed without convulsions, we may induce 
 death, and then it is always preceded by convulsions. 
 
 We might raise as an objection to this experiment that car- 
 bonization has caused to become volatile certain mineral salts, or 
 that it has changed their chemical condition. But carbonization 
 is not calcination ; besides, in experimenting with fixed bases, 
 soda and potass, we can appreciate the direct etfects of these 
 substances. 
 
 Soda is convulsion-producing. Neutralized by carbonic acid,
 
 58 LECTURES ON AUTO-INTOXICATION. 
 
 that is to say, under the form of bicarbonate of soda in dilute 
 solution, it induces haemorrhages, by rendering the blood more 
 fluid. As Magendie said, and as I established again experi- 
 mentally in 1869, severe convulsions appear with a dose of 1.20 
 grammes for each kilogramme of animal, and death at 2.50 
 grammes. But urine contains at the most 8 grammes of salts 
 of soda per litre, that is to say, 48 centigrammes for 60 cubic 
 centimetres of urine. Urine contains, therefore, scarcely half 
 of the soda capable of producing convulsions, and one-fourth 
 of that capable of inducing death. 
 
 Potass is infinitely more toxic. Bicarbonate of potass causes 
 death, with violent convulsions, in small doses of 5 centigrammes 
 for each kilogramme of animal, and convulsions come on after 
 a dose of 3 centigrammes. Potass is forty-four times more 
 toxic than soda; but if AYC find 2 grammes of salts of potass 
 per litre of urine, that is, 12 centigrammes for 60 cubic centi- 
 metres, it is not in the form of potassium bicarbonate, but as 
 chloride sulphate and other salts of potassium, which are less 
 toxic, and whose degree of toxicity we shall investigate later on. 
 We can, nevertheless, admit that for potass there is a limit as to 
 toxicity. If there arise an excess of it in the blood, even little, 
 convulsions and death may be the consequence of it. 
 
 When we inject a solution of mineral substances, obtained 
 not by carbonization but by calcination, we sometimes observe 
 this paradoxical result : in order to kill, it requires less of these 
 substances than there is in the quantity of normal urine, the 
 injection of which produces death. That explains, I think, how 
 calcination has transformed into carbonates a part of the alka- 
 line salts ; and, as regards the same quantity of soda or of 
 potass, the carbonates of these bases are two or three times 
 stronger than the chlorides, sulphates, or phosphates. 
 
 Ammonia is toxic, less than potass, but more than soda. 
 At 15 centigrammes per kilogramme, ammonia, regarded as an 
 anhydrous substance, and neutralized in water by means of car- 
 bonic acid, produces convulsions and then death. But normal 
 urine only contains doubtful quantities of ammonia. 
 
 In short, amongst the mineral matters, potass is the one 
 thing alone which, perhaps, makes itself felt in the toxic totality.
 
 POTASS A TOXIC ELEMENT. 59 
 
 I have finished telling you what I know of the part which 
 belongs to each of these substances in the toxicity of urines 
 which we suspect. I' have said what I know, but not what we 
 ought to know. Analj-sis and the isolation of various toxic 
 principles from the urine ought certainly in the future to be 
 carried further.
 
 LECTURE VI. 
 
 Toxic PRINCIPLES IN URINE THE PART THEY PLAY IN 
 PRODUCING UREMIA. 
 
 Recapitulation of the seven toxic substances found in normal urine. Diuretic 
 substance, which is in reality urea. Useful function of urea. Narcotic sub- 
 stance. Sialogenous substance, whose action is not shown after the injection 
 of normal urine, because it is found to be masked by more toxic substances. 
 Two substances which cause convulsions. Organic convulsive substance, 
 whose physiological action is habitually masked by its association with a 
 narcotic substance. Substance which contracts the pupil. Heat-reducing 
 substance, acting through diminished heat formation. Mineral convulsive 
 material : potass. Neutralization of its action by a substance which produces 
 narcosis. Analysis of the cause of death after double nephrectomy. Com- 
 parison of the clinical symptoms of uraemia and of the physiological proper- 
 ties of the toxic substances of urine. Coma or convulsions : causes of the 
 comatose form, convulsive or mixed. Dyspnoea. Myosis : importance of 
 this sign, from a diagnostic point of view, as regards uraemia. Salivation. 
 
 Hypothermia. Diminution of the urinary secretion when urea ceases 
 
 to be formed or is retained in the organism. Re-instatement of the urea. 
 Additional toxic substances of urine, salts of soda, alkaloids. 
 
 AFTER having concluded the physiological analysis of the 
 toxic principles of urine, if we recapitulate the substances which 
 we have disassociated we find there are seven of them. There 
 is, first, a diuretic substance, fixed, of organic nature, since it is 
 destroyed by heat. It is not fixed by carbon ; it is soluble in 
 alcohol, and we find it mixed in the alcoholic extract along with 
 other substances which have different properties. This sub- 
 stance possesses, besides the preceding characters, the property 
 which experimentation allows us to attribute to urea, that of 
 augmenting the quantity of urine. We have thus the right to 
 say that this diuretic substance contained in normal urine is no 
 other than urea. Urea in this way, although it is a product of 
 disassimilation, plays a useful role in the economy : it possesses 
 the property of forcing the renal barrier; of removing, whilst 
 making its own escape from the organism, both the water in 
 which it is itself dissolved and other toxic matters which are 
 united with it. Without doubt, urea is itself toxic. It is like 
 (60)
 
 TOXICITY OF UREA. 61 
 
 ever}* other substance, like water itself, which, introduced in 
 sufficient quantity into the organism, can kill. 
 
 But in what dose is urea toxic? An enormous dose? It is 
 necessary to fetter the functions of the organism ; to introduce 
 into the veins 5.5 grammes to 6.3 grammes of urea per kilo- 
 gramme of the weight of the animal. In the experiments in 
 which we have killed rabbits b}' the injection of urea we required 
 from 71.5 grammes to 82 grammes for 1000 grammes of blood. 
 There are, therefore, few bodies in the organism so feebly toxic 
 as urea, if we except albumen and the water which naturally 
 exists in the blood. Sugar is more toxic ; we can, experi- 
 mentally, scarcely introduce more than 5 grammes per kilo- 
 gramme, or 65 grammes per litre of blood. Yet, in order to kill 
 immediately by intra-venous injection of a sucrose liquid, we 
 must introduce almost 10 grammes per kilogramme of the rabbit, 
 or 130 grammes per kilogramme of blood. In pathological blood 
 there may be 8 grammes of sugar per kilogramme of blood ; but 
 in pathological blood urea has been found in quantity at least 
 equal. Amongst the mineral substances the most inoffensive 
 elements, even bicarbonate of soda, which we so readily pre- 
 scribe therapeuticall}', cannot be injected in a larger dose than 
 2.50 grammes per kilogramme of animal, 32 grammes per kilo- 
 gramme of blood. In order to kill 1 kilogramme of a rabbit 5 
 grammes of chloride of sodium are sufficient; 6 grammes of 
 phosphate of soda; 9 grammes of sulphate of soda. Urea has 
 almost the toxicity of the most inoffensive salts. 
 
 We might say that urea, by inducing renal secretion, is 
 eliminated quickly, and that this rapid elimination protects us 
 against its toxic influence. The reply to this objection is found in 
 nephrectoni}' followed by injection of urea, an experiment already 
 performed by Bernard. In one of my experiments of the intra- 
 venous injection of urea in the rabbit, the animal was dead after 
 the introduction of 6.31 grammes of urea per kilogramme. It 
 had not urinated during the experiment, and at the autopsy the 
 bladder was empty. Besides, however active the renal circulation 
 may be, the rapidity with which the quantity of urea that we in- 
 ject is found, as having entered into the circulation by our 
 method of intra-veiious injection, is such that the elimination
 
 62 LECTURES ON AUTO-INTOXICATION. 
 
 has not time to occur, and the physiological properties of urea 
 show themselves immediately. 
 
 We have afterward met with in the urine a substance truly 
 toxic. It is narcotic; it is fixed, of organic nature ; is not fixed by 
 carbon ; is soluble in alcohol, and is found in the alcoholic extract 
 with urea and other substances. Certainly it is not urea, since in 
 the experiments made with urea we do not see it produce narcosis. 
 This narcotic substance which the urine contains I cannot name 
 to you ; a chemical analysis of it has not been made. We can only 
 designate it by enumerating some of the physical, chemical, and 
 physiological characters which we have found belonging to it. 
 
 A third substance is sialogenous; it produces salivation. Its 
 presence in urine could not be suspected from the injection of 
 normal urine ; the total quantity of urine sufficient to kill does 
 not contain this sialogenous substance in sufficient quantity in 
 order to produce its physiological effect. We only see saliva- 
 tion appear after the injection of urine deprived of a part of 
 its toxic substances, of those which lead up to death too rapidly 
 without giving time for the sialogenous substance to show its 
 properties. This substance is stable, organic, not fixed by 
 carbon, soluble in alcohol like the preceding, but it is distinct 
 from urea as well as from the narcotic substance. It certainly 
 comes from the body like urea, for we find it in the blood, the 
 liver, and the muscles in a greater quantity than in urine, but 
 urea is only found in minimum quantity in the extracts of blood 
 and muscle. We do not yet know its name or its chemical 
 nature ; we are only on the threshold of discoveries which yet 
 remain to be made in the chemical analysis of urine ; we have 
 only succeeded so far in dividing urine into several parts, in 
 each of which one day we shall isolate those bodies of which we 
 are only able to suspect the presence. 
 
 We find in urine two substances endowed with the property of 
 causing convulsions: one is fixed, stable, organic, since it is de- 
 stroyed by carbonization, and yet it is retained by carbon ; it 
 is, therefore, not mineral ; it is insoluble in alcohol ; it might 
 belong to the group of coloring substances, from the manner in 
 which it behaves ; it is really an alkaloid, since it is insoluble in 
 alcohol either in the form of a salt or a base. This organic
 
 SUBSTANCES WHICH CAUSE CONVULSIONS AND MYOSIS. 63 
 
 matter which determines convulsions is found in less quantity in 
 the urine of the day period than is the narcotic material, but it 
 is of less physiological activity ; and if injections of normal 
 urine do not often produce convulsions, it is probablj' because 
 the narcotic substance kills the animal before the convulsive 
 substance can have exhibited its properties. In order to 
 produce convulsions it is necessary to remove first from the 
 urine the poison which kills rapidly. Of this convulsive sub- 
 stance we also do not know the name. Then there is a substance 
 which causes contraction of the pupil ; fixed, organic, attaching 
 itself to carbon ; non-mineral ; consequently it is comparable in 
 certain respects to the substance which induces convulsions. 
 We might suppose that it is mixed with it ; that is to say, that 
 one substance might be endowed with the two properties ; we 
 might also ask if it is not a coloring substance or an alkaloid. 
 A coloring substance ? It is possible. Alkaloid ? Probably not, 
 for the same reason that we have given when speaking of the 
 convulsive substance. It is not probable that it is mixed with 
 the preceding, for all normal urines contract the pupil, but it is 
 very few of them which induce convulsions. It would be 
 necessary to admit that the substance which convulses the 
 sphincter iridis is more energetic than that which brings on 
 general convulsions. 
 
 Urine produces pupillary contraction in small doses, from 
 10 cubic centimetres, and in general it causes death without con- 
 vulsion in doses of from 30 to 50 cubic centimetres. We ought, 
 with cpnvulsive urines, at 60 cubic centimetres to see imme- 
 diately happen contraction of the iris, whilst the phenomenon 
 shows itself slowly enough. The separation of these two physio- 
 logical effects shows that they belong to two different substances. 
 We cannot give, any more than for other toxic substances, the 
 name of that which causes contraction of the pupil. 
 
 We have met with in the urine a substance which reduces 
 heat. It lowers the temperature by diminishing heat-produc- 
 tion, and not only like every cold liquid, which, introduced into 
 the organism, subtracts from it a certain number of calorics in 
 order to put it into equilibrium with its own temperature ; for 
 when we inject a cold liquid into the circulation, we only pro-
 
 64 LECTURES ON AUTO-INTOXICATION. 
 
 duce a very slight fall of the temperature of the body ; in real- 
 ity, in this case, we stimulate calorification exactly as is done 
 by the external application of cold : the organism tends to 
 remake, by an acceleration of internal combustions, the calorics 
 which we have removed from it, and it restores really a part of 
 it. After the injections of urine, on the contrary, the animal is 
 colder, not only as after every injection of cold water, because 
 the organism puts itself into an equilibrium of temperature 
 with the liquid injected, but because the organism loses a part 
 of its heat-producing power. Each unit of weight of the body 
 forms in a given time fewer calorics than in the normal state. 
 
 The heat-lowering substance is fixed, organic. Ammonia 
 also possesses the property of reducing temperature ; but that 
 of which we speak fixes itself on carbon, and is not, therefore, 
 a mineral. It is insoluble in alcohol, like the preceding. It maj' 
 be a color-substance ; it is certainly not the same material as that 
 which produces convulsions, for we do not observe any propor- 
 tion between the hypotfaonoic effect and the convulsive, no 
 more than between these and the pupillary contraction. It is, 
 therefore, a substance with an individuality of its own. 
 
 In short, we find in urine another convulsive substance, 
 fixed, inorganic. It is, briefly, potass, whose toxic and convul- 
 sive properties we have known for a long time. Nevertheless, 
 we cannot attribute to it alone the convulsions which the in- 
 jections of urine produce, for, in order to inject potass in a 
 toxic dose, very much larger quantities of urine would require 
 to be injected. If we could get rid of, by means of carbon, 
 a convulsive substance which kills too rapidly, we might see 
 convulsions come on due to potass. If, in dealing with, the 
 extract which at one and the same time contains both the 
 convulsive organic substance and potass, we destroy, by means 
 of heat, the organic matter ; convulsions are still produced, 
 but there must be, occasionally, a double quantity of urine. 
 Alcohol, it is true, has removed a part of the potass ; some- 
 times, however, in order to kill in convulsions, it is sufficient 
 to inject the mineral substances taken from a quantity of urine 
 less than the normal quantity of urine which produces death 
 without convulsions. This paradoxical result, which I have
 
 TWO SUBSTANCES CAUSE CONVULSIONS. 65 
 
 already mentioned and attempted the interpretation of in the 
 last lecture, might also be explained by the antagonistic action 
 of certain organic substances which correct the convulsive action 
 of potass. 
 
 En resume, there are two substances in urine which induce 
 convulsions, one, organic, producing a rapid effect, which kills 
 before the convulsions caused by potass could have been 
 produced; the other, potass, a salt of which, viz., chloride of 
 potassium, is convulsive and toxic at 18 centigrammes for every 
 kilogramme of the animal. This neutralization of one toxic 
 substance through admixture with another is seen under many 
 circumstances. Atropine can neutralize the physiological action 
 of pilocarpine. In the injections of normal urine the convul- 
 sive properties of the salts of potass are neutralized by their 
 mixture with a substance which produces narcosis and coma. 
 Thus, nrines contain the antidotes to certain of their own 
 poisons. 
 
 When we destroy the extract of urine by heat, the convulsive 
 action of the residue is, perhaps, weakened by the volatilization 
 of a part of the potass. In every case, there is good cause 
 for taking into account potass in the toxic phenomena con- 
 sequent upon the retention of substances which ought to be 
 eliminated by the urine ; for the accumulation of potass may 
 go on more rapidly than that of other substances coming from 
 the organism. If, in consequence of failure in the elimination 
 of the substance in urine which reduces calorification, disas- 
 similation of the tissues diminishes, the potass which con- 
 tinues to be introduced into the organism b}' the food and drink 
 may be soon found to be in a predominating proportion, and 
 may induce convulsions, which is one of its properties. Thus, 
 with urea, the urine contains seven toxic substances. To be 
 exact, it would be necessary to say that everything in the urine 
 is toxic, evei-y thing contained therein, even water and soda, 
 but I say seven, including therein only the substances which are 
 toxic in doses in which normal urine is experimentally toxic. 
 In this analysis, long as it may seem, of the toxicity of urines, 
 it is still only^vn outline, which chemistry, without doubt, will 
 finish, by the aid of improved methods.
 
 66 LECTURES ON AUTO-INTOXICATION. 
 
 It is sufficient for us, for the moment, to have demonstrated 
 experimentally that urine removes poisons from the body ; that 
 the kidney plaj'S a useful role ; that it is a good emunctory ; 
 that its suppression would be fatalty hurtful to the economy, 
 an old opinion, which is sanctioned by the name of emunc- 
 tory. Is it the case, however, that suppression of the urinary 
 secretion is fatally dangerous? At first, proof appears to 
 arise from the fact that death invariably follows double ne- 
 phrectomy. We say that death is, then (in such), the result 
 of an auto-intoxication. But the argument is not indisputable. 
 There are many other modes of death besides nephrectomy. 
 Might it not be that death was afterward caused by the want 
 of elimination of water, or that the reflex paths of the renal 
 plexus, being irritated, produce, in consequence of changes 
 in the elaboration of the matter of the body, transformation of 
 certain organic compounds, like that of urea, into carbonate of 
 ammonia, or that new compounds were formed by reaction, and 
 in an indirect manner? To this, as an objection, it has been 
 replied that after nephrectomy we neither see produced anasarca 
 nor oedema of the brain ; that we do not find in the organism 
 more carbonate of ammonia ; that the reflexes could not of 
 themselves have done so, since we have suppressed, in certain 
 experiments, the track along which they have passed. What- 
 ever the worth of this argument may be, in order to clear away 
 the last point which separates us from certaint}', it is necessary 
 that we should find again in the symptoms of uraemia the physio- 
 logical characters proper to the toxic matters of the urine. Does 
 the clinical picture of uraemia supply this want ? (Edema may 
 be present, but it is rare. 
 
 We observe coma and convulsions, sometimes one, some- 
 times the other of these symptoms, probably because the 
 kidney does not offer the same resistance to all the substances 
 which pass through it. In interstitial and in parenchymatous 
 nephritis it does not always retain the same substances, salts, 
 extractives, etc. ; from these differences in its permeability for 
 such and such a toxic substance might well result the predomi- 
 nance of comatose or of convulsive uraemia, or one of a mixed 
 nature.
 
 UREMIA AND ITS MANIFESTATIONS. 67 
 
 Dyspnoea is present in uraemia, with diminution of the range 
 of respiratory movements. I may point to myosis as one of 
 the constant characters of uraemia. In the evolution of chol- 
 eraic phenomena we see in succession the intoxication proper to 
 cholera and unemic intoxication. When this latter arises myo- 
 sis appears. All those suffering from the anuria of cholera have 
 the pupil contracted. Myosis has already been pointed out by 
 Roberts as one of the signs of anuria. 
 
 Salivation has been observed by A. Robin in uraemia. A sub- 
 normal temperature has been regarded as one of the commonest 
 manifestations. What is awanting in the picture of uraemia, in 
 order that it may be identical with that which poisoning by means 
 of the toxic principles of urine produces ? There is only awanting 
 the abundance of the secretion induced by the great elimination 
 of urea, for it is urea which is diuretic. Urea upon a diseased 
 kidney can no longer exercise a beneficent influence. Besides, 
 when urea is no longer formed in the body, the kidney even 
 when normal ceases to show its functional activity. In hepatic 
 uraemia, when the liver no longer forms urea; although the kid- 
 ney remains normal, we often see the same symptoms arise as if 
 it had become impermeable. We are thus led to this unexpected 
 conclusion, that the substance urea, which has been for such a long 
 time the scare-crow of physicians, is especially injurious when it 
 is deficient. In the enumeration of the toxic substances of urine, 
 I have neglected some, either because they are really scarcel}' 
 toxic, like the salts of soda, or because they are only found in 
 the urine in very small quantity. Such are the urinary alkaloids 
 b}' which we have only recently tried to explain the toxic acci- 
 dents of diseases in general, but which, although numerous in 
 both the normal and pathological state, have not until now been 
 proved, from our point of view of the toxicity of normal urine. 
 They belong, without doubt, to the number of those indeter- 
 minate and unknown substances of which I have attempted to 
 give a physiological analysis. M. Gabriel Pouchet said in 1880 
 that they were toxic : he saw them produce, in animals, muscular 
 weakness, stupor, convulsions, then death, with the heart in 
 diastole. But he had operated with the ethereal extract of large 
 quantities of urine, and upon very small animals,
 
 68 LECTURES ON AUTO-INTOXICATION. 
 
 Confining ourselves to the limit of things applicable to 
 pathology, if, instead of attending to the frog, we operate upon 
 the rabbit, we find that the toxicity of these alkaloids is nil in 
 the doses in which they are extracted from quantities of urine 
 capable of bearing some comparison to man. The quantity of 
 urine which would be capable of killing a man does not give off 
 to the ether sufficient alkaloid to kill a rabbit. 
 
 I believe that I have not neglected, in this analysis of the 
 toxicity of urines, anything but which was worthy of neglect. 
 The alkaloids of the urine are interesting from the physiological 
 point of view of their origin, but they do not seem to have the 
 power of explaining by themselves alone the intoxication arising 
 from normal urines.
 
 LECTURE VII. 
 
 ORIGIN OF THE Toxic SUBSTANCES OF URINE TOXICITT OF 
 THE BLOOD AND TISSUES. 
 
 The blood is unceasingly traversed by a current containing toxic material which, 
 coming from the organs, is continually being eliminated by the emunctories ; 
 but blood ought never to contain at any time, in the normal state, more than 
 an infinitesimal quantity of poison. Estimation of the toxicity of blood by 
 experimentation and calculation. Toxicity of the liquor sanguinis. Com- 
 parative injections of blood into animals of the same and different species. 
 Injections of blood-serum, of distilled water, and of artificial serum. Increase 
 of the toxicity of blood by the destruction of globules, which disengage 
 
 potass. Toxicity of aqueous and alcoholic extracts of blood. Toxicity of 
 
 the tissues and organs ; difficulty of this research. Toxicity of the extract 
 
 of meat due to the presence of mineral salts, 'such as potass ; and to organic 
 substances, such as creatiuin. Intra-venous injections of extracts of muscle. 
 Aqueous extracts of muscle produce convulsions, with the exception of 
 myosis. The extract of muscle, deprived of the potass which it contains, 
 
 does not produce any accident. Toxicity of an extract of liver. Toxicity 
 
 of bile. Various explanations offered. The toxicity of biliary salts is less 
 than one would have believed It ; they probably act only indirectly in destroy- 
 ing anatomical elements and in setting at liberty mineral or organic products 
 derived from cellular disintegration. Cholesterin possesses only an insig- 
 nificant toxicity. The coloring matters ought to play a very important role 
 in the toxicity of bile, since it, when once decolorized, becomes much less 
 toxic. Toxicity of bilirubin. 
 
 WE must now deal with the problem of the origin of the 
 toxic substances which urine contains. Whence does urine 
 obtain its toxicit}' ? We have established the fact that the 
 orgnnism forms toxic products, and that the kidney eliminates 
 them. It is now for us to show whether, on the side of the kid- 
 ney, there is anything toxic in the blood and in the tissues. 
 A priori, it is physiologically inadmissible that normal blood 
 can be toxic. If it was, the animal could not live. We know 
 that urine may be toxic such as when found outside of the 
 organism in a reservoir from which it cannot be re-absorbed in 
 the natural state; but blood itself cannot be, circulating, as it 
 does, in vessels which are not opposed to its diffusion into the- 
 tissues. If blood is not toxic, it is because normal urine is, and 
 
 (69)
 
 70 LECTURES ON AUTO-INTOXTCATION. 
 
 is incessantly removing toxicity from it. The blood is con- 
 tinually being traversed by a current of toxic material. It is 
 true that the poison is never found in it but in harmless quan- 
 tities. There is less toxic matter in the blood than in the 
 organs. The anatomical elements form substances which, if 
 retained, would fetter their life, but these substances leave them, 
 little by little, in order to penetrate into the blood. The quan- 
 tity of toxic matter eliminated by the kidneys in twenty-four 
 hours is, without doubt, one-half of what is necessary to kill the 
 whole of the body, and the blood has really received that quan- 
 tity in twenty-four hours ; but the elimination is incessant, and 
 at every instant of the day the blood never contains at one time 
 more than an infinitely small fraction of poison. 
 
 The estimation of those fractions ma}' be made for units of 
 time ; that is to say, for a complete revolution of the blood, say 
 about forty-seven seconds, taking into account certain slower revo- 
 lutions which take place in certain departments of the vascular 
 system. A man of 65 kilogrammes expels in twenty-four hours 
 1350 cubic centimetres of urine, which kill 1 kilogramme of rabbit 
 with a dosage of 45 cubic centimetres. This man eliminates, 
 therefore, in twenty-four hours, by his urine, sufficient to kill 
 ~ = 30 kilogrammes of living matter. The whole quantity of 
 blood of this man is jg 5 kilogrammes. The five kilogrammes 
 of blood of this man are thus traversed in twenty-four hours by 
 a quantity of poison capable of killing 30 kilogrammes. 
 
 The number of complete circulatory revolutions is 1850 in 
 twenty-four hours. In each complete revolution the kidneys 
 remove from 5 kilogrammes of blood a quantity of poison capable 
 of killing J^, and from 1 kilogramme of blood 185 ^ X5 = 0.003243 
 kilogramme, or 3.243 grammes. If, during a complete revolu- 
 tion, each kilogramme of blood discharges a quantity of poison 
 capable of destroying 3.243 grammes of animal substance, in 
 the same time this mass of poison will be furnished to each 
 kilogramme of blood by the organism, the in-going being equal to 
 the out-going. It follows from this that the blood ought to con- 
 tain constantly , at the least, this quantity of poison. It ought even 
 to contain more, for the blood is, during each cardiac revolution, 
 only deprived of a fraction of its quantity of poison by the renal
 
 RAPIDITY OF ELIMINATION. 71 
 
 emunctory. It is probable that there is in the blood more toxic 
 material than this minimum portion which penetrates there, and 
 which leaves it during the forty-seven seconds of a complete 
 revolution, and that there is a reserve of toxic material circulating 
 with the blood. Analogy helps to show us that it is thus as it 
 ought to be, and it will enable us to appreciate hypothetically 
 the importance of this reserve. 
 
 A man of 65 kilogrammes eliminates in twenty-four hours, 
 by 1350 cubic centimetres of urine, 1300 grammes of water and 
 24 grammes of urea. In a complete circulatory revolution he 
 eliminates 1850 times less of each substance, that is, O.T gramme 
 of water and 0.01297 gramme of urea. These quantities of 
 water and of urea are given up by 5 kilogrammes of blood. 
 One kilogramme of blood gives, therefore, during one total revo- 
 lution, five times less, or 0.14 gramme of water and 0.002592 
 gramme of urea. But this kilogramme of blood only gives up 
 these quantities of material from its liquid part, from its 
 plasma, which only constitutes one-half of the mass of blood ; 
 and the 500 grammes of plasma in 1 kilogramme of blood con- 
 tain only 450 grammes of water and 0.16 gramme of urea. The 
 calculation made, the blood loses, during a complete revolution, 
 SST? P ai 't f water from its plasma and ^ part of urea from 
 its plasma, which proves, as I established in 1872, that urea is 
 eliminated by the kidney fift} r -two times quicker than the water 
 (=M). 
 
 If the rapidity of the elimination of the blood-poison was 
 equal to that of urea, 1 kilogramme of blood would contain 
 sixty-two times the quantity of poison which this kilogramme 
 of blood eliminates in a complete revolution ; and as this quan- 
 tity eliminated is capable of killing 3.243 grammes of living 
 matter, 1 kilogramme of blood ought to contain sufficient poison 
 to kill 3.243 X 62 = 201 grammes of living matter, which repre- 
 sents a minimum of toxicity. 
 
 If, on the contrary, the rapidity of the elimination of the 
 poison was equal to that of the water, the quantity of toxic 
 matter inclosed in 1 kilogramme of blood ought to be 3214 
 times the quantity eliminated by this kilogramme of blood 
 during a complete revolution. One kilogramme of blood would,
 
 72 LECTURES ON AUTO-INTOXICATION. 
 
 therefore, be capable of killing 3.243X3214=10,423 grammes 
 of living tissue. This result is not preposterous ; this maxi- 
 mum of toxicity would not be incompatible with life. With 
 such a toxicity of its blood the animal would poison itself, if 1 
 kilogramme of blood was distributed 'to 10 kilogrammes of 
 its body ; but, in reality, 1 kilogramme of blood is distributed 
 to 13 kilogrammes of the organism. It is, moreover, extremely 
 probable that the real toxicity of the blood is less, and that it 
 is comprised between these two extremes. 
 
 These hypothetical calculations only show us the extreme 
 limits of the possible toxicity of the blood. We can, fortu- 
 nately, approach the question from the experimental side. The 
 injection of the blood of an animal into the veins of another 
 animal can produce death without this death being attributable 
 to embolism and without the augmentation of the mass of 
 blood being incriminated. The injection of 25 cubic centi- 
 metres of blood per kilogramme of animal invariably causes 
 death. What proves that death in such is the result of an 
 intoxication is that the fatal dose varies according to the part 
 of the vascular apparatus from which this blood has been with- 
 drawn. If, instead of drawing it from the general venous 
 system, we draw it from the portal vein, 14 cubic centimetres 
 are sufficient to cause death, instead of 25, this blood being 
 charged with putrid and biliary poisons taken from the intestine, 
 and not having them as yet removed from it by the liver. But 
 a kilogramme of animal contains ^=77 grammes of blood. 
 After the injection of 25 grammes of blood, this kilogramme 
 would contain 102 grammes, and then the animal dies. We ma}' 
 therefore say that 102 grammes of blood are sufficient to kill 1 
 kilogramme of animal. In other words, 1 kilogramme of venous 
 blood retains, in the normal state, sufficient poison to kill 9804 
 grammes of living matter. 
 
 These conclusions would be strictly exact if the blood 
 injected came from an animal of the same species as that into 
 which we make the injection. But, in my experiments, it is the 
 blood of the dog which has been injected into the rabbit. I 
 have reasons for believing that the blood is more toxic for an 
 animal of another species than for an animal of the same species.
 
 EFFECTS OF INJECTION OF BLOOD. 73 
 
 In experimental studies bearing upon transfusion, we have 
 properly said that the blood of one species is poisonous to 
 another, but we have" not made the estimation of the degree of 
 this toxicity, and we have always gone away from this point 
 with a false view that the blood of an animal is not toxic for an 
 animal of the same species. Whilst the blood of the dog kills 
 a rabbit at the dose of 25 cubic centimetres per kilogramme, 
 I have known the blood of the dog injected into another dog to 
 the extent of 30 cubic centimetres only produce a fleeting- 
 indisposition, whilst in the rabbit, in order to cause death, it 
 is necessary to inject 126 cubic centimetres of blood of rabbit. 
 This amount is considerable. It is true that it was a question 
 6f the injection of arterial blood. Death supervened by con- 
 vulsions, with moderate pupillary contraction. The urine con- 
 tained only traces of albumen, none of blood, none of haemo- 
 globin. There were no haemorrhages into any organ, except 
 from embolic foci, numerous enough, but very small, of 
 pulmonary apoplexy, to which death could not be attributed, 
 the respiratory rhythm not having been modified before the 
 final convulsion, which was very short. In this experiment the 
 animal died when each kilogramme of its body was irrigated by 
 77 + 126 = 203 grammes of blood. From this we infer by cal- 
 culation that 1 kilogramme of rabbits' blood is capable of killing 
 4926 grammes of rabbit, in round numbers, 5 kilogrammes. 
 And we still further draw the inference, if you wish to refer to 
 calculations just recently made, that l>y the kidneys the poisons 
 of the blood should be eliminated twice more quickly than the 
 water, but twenty-six times slower than urea. This remark is 
 not without some interest. It shows that if the kidney cannot 
 be got to eliminate urea, it may succeed in expelling blood- 
 poisons, and that, in the case of auto-intoxication, the witli- 
 drawal of large quantities of serum, or merely of water, might 
 not be without some utility. One last conclusion to draw from 
 the experiment is that, in order that death may be produced by 
 auto-intoxication, it is sufficient that the amount of the poisons 
 of the blood should become two and one-half times greater than 
 the normal quantity. 
 
 I give you the different steps by which I have entered into
 
 74 LECTURES ON AUTO-INTOXICATION. 
 
 this study of the toxicity of blood, the l^pothesis, calculation, 
 and experiment. I have no difficulty in recognizing that more 
 recent experiments have obliged me to admit that blood has a 
 toxicity still less than that which seems should be inferred from 
 the preceding experiment. In blood, the plasma alone may be 
 toxic. The living cells retain within themselves the inert or 
 hurtful substances of which they are composed. In order that 
 these poisons may act, it is absolutely necessary that they should 
 be in solution ; it is necessary that they should dialyze from the 
 blood into the tissues ; it is necessary that they should be in the 
 liquid part, non-living, in the plasma. There has, therefore, 
 been good cause for experimenting upon the toxicity of the 
 blood-serum. I have extracted from ten rabbits, by arterial 
 bleeding, 600 grammes of blood. The clot, after having been in 
 an ice-box for twenty-four hours, has furnished to me 260 
 grammes of a limpid serum, scarcely tinged. This serum has 
 been filtered and then injected into the veins of a rabbit. The 
 animal died, after having received 125 cubic centimetres of 
 serum per kilogramme. Death was preceded by a distinct, but 
 not punctiform, contraction of the pupil, by exorbitism, by 
 dilatation of the superficial veins, and, in the last moments, by 
 the loss of ocular reflexes, b}- convulsions, and by a frothy, san- 
 guineous running from the nostrils. The lungs, voluminous but 
 pale, were dotted with patches of pulmonary apoplexy. There 
 were no haemorrhages at any other point in the body. The urine 
 contained neither blood nor albumen. The heart continued to 
 beat for a long time after death. 
 
 The serum constitutes about one-half of the mass of blood. 
 I have injected, in this experiment, the poison dissolved from 
 250 grammes of blood. The animal had already in its vessels, 
 before the injection, 77 grammes of blood. When it died, its 
 tissues had at their disposal, per kilogramme of its weight, the 
 poison of 327 grammes of blood ; from this I am obliged to 
 conclude that 1 kilogramme of blood is capable of killing about 
 3 kilogrammes of animal. 
 
 Was death, in this experiment, due to toxicity of the blood 
 alone? I would not dare* to say so. I am obliged to take some 
 cognizance of the apoplectic patch in the lung and of the san-
 
 IS BLOOD MORE TOXIC THAN WATER? 75 
 
 guinolent oozing from the nostrils, which suggest the idea of 
 plethoric haemorrhages, and which raise the question whether 
 the enormous increase in the mass of blood has not been the 
 cause of death. Remember, however, that the animal died, 
 after having received into its veins 125 cubic centimetres of 
 serum, like the animal in the preceding experiment, after 
 having received 126 cubic centimetres of defibrinated blood. Re- 
 member, too, that distilled water causes death when we intro- 
 duce into the vessels more than 122 cubic centimetres of it. 
 From this comparison you will be able to conclude that blood is 
 less toxic than pure water. It is ou\y apparently so, and, at the 
 same time, a misuse of language. Water is not toxic, properly 
 speaking, and a liquid which kills in a larger dose than water 
 may be toxic. Water does not kill by its chemical composition, 
 by toxicity ; nor does it kill ain* more by its mechanical action, 
 by plethora; it kills by its phj-sical action, by swelling out 
 the globules and dissolving out the haemoglobin. If you wish, 
 to know to what point it is requisite to increase the mass of 
 blood in order that death may follow, or what is the limit at which 
 plethora becomes fatal, it is necessaiy, as I have done, to inject 
 into the veins water, to which a salt very slightly toxic has been 
 .uldrd, and in such proportion that in this solution the globules 
 of the blood are not deformed, a solution of sea-salt, 7 parts in 
 1000, an artificial serum. Yet, with such a liquid, death comes 
 in the rabbit only when we have injected for each kilogramme 396 
 cubic centimetres of the solution, or when we have multiplied the 
 mass of the blood six times. In such it is really with plethora 
 that we have to deal ; death is the result of a mechanical effect, 
 for during life the veins are seen to be extremely distended, 
 injection becomes difficult and laborious, and the piston of the 
 syringe is constantly driven back by the excess of the intra- 
 venous tension. All the liquid injected remains in the circulatory 
 apparatus, for the urinary secretion is not increased ; we do not 
 find liquid either in the stomach, intestines, or serous cavities, 
 and there is no oedema in any part, but we detect a focus of 
 pulmonary apoplexy. There has not been any physical action, 
 for the blood-globules are neither deformed nor decolorized ; 
 there has not been any chemical or toxic action, for we have
 
 76 LECTURES ON AUTO-INTOXICATION. 
 
 only injected 2.772 grammes of sodium chloride, and to kill a 
 kilogramme of rabbit we require 5.31 grammes of this salt. 
 If in order to kill by plethora we must increase the mass of 
 blood six times, I have not even tripled it in my injections of 
 serum or of blood, I add that in these experiments death can- 
 not be explained by a physical action, as when there is question 
 of distilled water. I have introduced into the veins a liquid 
 which is the natural medium of the globules, in which they 
 neither become swollen nor retracted. I come therefore to my 
 first conclusion, death is apparently only explained by intoxi- 
 cation ; but, notwithstanding, I maintain a reserve, for it is not 
 poisoning which could have provoked pulmonary apoplexy ; 
 something must have been added to the intoxication. 
 
 To avoid this something, we would require to inject the 
 poison of the serum in a state of greater concentration, the 
 removal of the water, the removal, too, of albuminoids, which, I 
 suppose, cannot be the toxic substances ; at least, when we inject 
 blood from one species into an animal of the same species. 
 That is what I have done ; I have coagulated the albumen and 
 concentrated by freezing the liquid got by washing the coagu- 
 lum. In order to produce death, I have been obliged to inject 
 the extract from more than 400 grammes of serum representing 
 800 grammes of blood ; yet it was simply the extract from the 
 serum of horse injected into the rabbit. In this experiment, 
 1000 of blood would kill 1250 of living matter. Calculation has 
 forced us to admit that a kilogramme of blood would be capable 
 of killing at the least 201 grammes, and at the maximum 10,423 
 grammes of living matter experimentation has narrowed these 
 extreme limits. It shows us that a kilogramme of blood could 
 destroy at the least 1250 grammes, and at the greatest 3000 
 grammes of living matter. The true index, as yet undetermined, is 
 between these two extremes. Besides the plasma, blood contains 
 globules. Do these globules increase the toxicity of the blood ? 
 Experimental^-, no ; yet these globules contain toxic materials, 
 and even in large quantity; but they are materials belonging to 
 the constitution of the globules, and these are living. Blood is 
 only a tissue of mobile cells, which haA r e, like every cell, a frame- 
 work. What enters into the composition of this frame-work is
 
 CELLS IN THEIR DESTRUCTION LIBERATE POISONS. 77 
 
 inoffensive for the cell so long as it is living ; but each cell con- 
 tains potass, which it keeps combined with other substances, 
 mineral or organic. This potass cannot injure living cells except 
 when liberated by the destruction of other cells ; in these con- 
 ditions potass passes into the liquids and its toxicity may then 
 be shown. If we destroy the globules by boiling or by charring 
 and inject the aqueous solution of this into the blood of an 
 animal, we bring about convulsions and death. 
 
 Alcohol removes water from the globules, extractive matters, 
 fat, cholesterin, and the salts of potass. With the alcoholic 
 extracts of blood we induce muscular weakness, convulsions, 
 , and very rapidly salivation, as I pointed out apropos of a 
 toxic substance in urine. It is from the blood that the kidney 
 gets this substance, which causes salivation. With the alco- 
 holic extract of blood, narcosis is observed only under abnormal 
 circumstances. I have seen it produced in one case with the 
 blood of a uraemic patient who was not eliminating its toxic 
 substances, but with normal blood we do not induce narcosis. 
 Into the alcoholic extracts of blood there pass nitrogenous 
 bodies, both basic and neutral ; I cannot say to which of them 
 the physiological phenomena of which I speak are due. I con- 
 sider that the living globules are harmless, but that they furnish 
 toxic matter when they are destroyed. I can only incriminate 
 the potass liberated by this destruction. I cannot always 
 accuse the alkaloids found, in normal blood, by Gautier and 
 myself, for they are found in a still smaller quantity than that 
 which urines contain, and we have seen that they represent only 
 a minimum part of the toxicity of urine. 
 
 En resume, blood contains, as we know, a reserve quantity of 
 poison; a small quantity of this poison is incessantly eliminated 
 by the kidneys ; it receives from the tissues an equal quantity 
 of it ; it contains, therefore, in the normal state, alwa3*s a cer- 
 tain quantity. If elimination is prevented and the supply of it 
 continues, accumulation of toxic material produces intoxication. 
 We know what the quantity of toxic matter is that is introduced 
 into the blood and eliminated by the kidney in a circulatory 
 revolution, and we also know what quantity of living matter 
 might be killed by this amount of toxic material ; we can, then,
 
 78 LECTURES ON AUTO-INTOXICATION. 
 
 fix the time necessary for 1 kilogramme of blood to kill 1 kilo- 
 gramme of animal. This period is two days and four hours ; 
 that is a theoretical average. In reality the time necessary is 
 longer, because in uraemia there are produced functional derange- 
 ments of the intestinal tube which prevent it absorbing the 
 poisons which it contains, were it only the potass of alimentary 
 origin ; moreover, the formation of the poisons of disassimila- 
 tion is prevented by intoxication itself; vomiting, chill. The 
 poisons only act when dissolved in the plasma ; the globules are 
 not toxic whilst they remain alive. The materials constituting 
 these anatomical elements are retained therein by the force of 
 tension which resides in every living cell ; but in case of death or 
 rapid disintegration of the cell, freedom is given to all the sub- 
 stances which were part of its constitution, potass, creatin, 
 leucin, and other nitrogenous substances. The proteid matters 
 would themselves be incriminated if it is true that they can, by 
 undergoing certain modifications, pass into the condition of soluble 
 ferments ; the experiments of Alex. Schmidt would tend to make 
 this a supposition. In every case, in spite of the work of the 
 school of Dorpat, I do not believe that the intoxication pro- 
 duced by blood can be attributed to dissolved haemoglobin. 
 The result of the sudden or rapid destruction of blood-corpuscles 
 is the production of such phenomena as muscular debility, sali- 
 vation, convulsions, and death, but never narcosis, unless when 
 we operate with the blood of a person who is ursemic or is suf- 
 fering from choleraic anuria. Of those effects, some are due to 
 the mineral constituents ; from the potass, notably the convulsive 
 phenomena arise ; of the organic substances there is one which 
 is present in the alcoholic extract of blood and urine, liver and 
 muscle, and to which salivation is attributed. 
 
 After having studied the toxicity of the blood, it would be 
 desirable to get to know the toxicity of the tissues. But this is 
 a still more delicate research ; we cannot inject them as they are 
 into animals ; we can only inject their extracts, and these ex- 
 tracts, these products of the disintegration of tissues, are toxic. 
 The toxicity of the extract of flesh has been known for a long 
 time. This may be of some utility from an alimentary point of 
 view ; to a certainty it is toxic. Jf it does not poison, that is
 
 LIFE WITHOUT FREE OXYGEN. . 79 
 
 because it has been introduced only in small quantity into the 
 organism, and that it is being constantly eliminated ; besides, in 
 every aliment there are toxic substances, and every aliment 
 would become a poison if renal elimination was not the safe- 
 guard of the body. It is said that what is toxic in the extract 
 of meat besides the mineral salts, potass, are organic substances, 
 such as creatinin, which in meat is in the form of creatin. The 
 stimulating effects after muscular depression are attributable 
 to it. 
 
 With the aqueous extract of muscle, which contains mineral 
 and organic substances, we produce neither salivation nor nar- 
 cosis, but convulsions, and, exceptionally, contraction of the 
 pupil. In these phenomena of intoxication there is no place for 
 the action of alkaloids ; the alcoholic extract of muscle causes 
 the salivation. An alcoholic extract of liver causes an excessive 
 salivation; the extract from 117 grammes of liver determines 
 death in the rabbit. When we know the toxicity of an extract, 
 if we suppress the potass which it contains, we deprive it of its 
 power of producing convulsions. For this purpose it is suffi- 
 cient to precipitate it in the state of tartrate of potass. After 
 this operation the extract of 216 grammes of muscle, which 
 caused convulsions and death, produces no accident whatever. 
 Besides potass, there exist in the extracts of the tissues such 
 bodies as tyrosin, leucin, butyric and acetic acids; they play 
 their part in those phenomena of intoxication, during life, com- 
 parable to those which supervene after the absorption of the 
 poisons of putrefaction. 
 
 Here is a remark of Gautier : " By the side of aerobic life 
 there is anaerobic life, thanks to which the cell is able to live 
 for some time without oxygen. The anatomical elements are 
 still engaged in the phenomena of oxidation, but at this time 
 they are taking oxygen into the tissue itself. If we weigh the 
 respired oxygen, that mixed with the fluids drunk and in combi- 
 nation with the food, and on the other side the oxygen fixed in 
 the carbonic acid exhaled by the lungs, the skin, contained in the 
 dejections and combined in the excreta, we find absolute equality 
 on both sides. But the free oxygen has not been sufficient; the 
 respired oxygen does not explain the surplus of water and cur-
 
 80 . LECTURES ON AUTO-INTOXICATION. 
 
 bonic acid ; the oxidations, therefore, have been made with the 
 oxygen of the combinations ; one-third of life is supported by 
 oxidation without free oxygen." Nutrition is thus, on one side 
 at least, comparable to fermentation when air is excluded. 
 
 Let us return to the liver and to its particular emunctory 
 function. Bile plays, without doubt, a part in digestion, but it 
 is a constituent of the excreta, and it undergoes, in part, ab- 
 sorption. Does the part absorbed produce intoxication ? Schiff 
 has told us that we can find bile in the blood just come from 
 the intestine, but not in the general circulation. He has ad- 
 mitted that the bile is seized again by the liver, then secreted 
 anew, and again retaken without cessation. If this perpetual 
 circle is true, the liver would, therefore, act as a protector to 
 the general circulation, as regards bile and other poisons. That 
 is possible, but not emphatically demonstrated. In every case 
 the contrary is true in pathological conditions ; bile may im- 
 pregnate the blood and tissues. Even in the normal state, in the 
 dog, bile passes into the whole of the circulation ; in this animal 
 jaundice is physiological. 
 
 To return to man, may bile itself cause in him intoxication ? 
 For a long time we have suspected the toxicity of bile. Deidier, 
 in the last century, made intra-venous injections of bile from 
 those who died of the plague. In our own century, at different 
 times, there have been undertaken experiments to clear up this 
 question. Bouisson concluded that filtered bile is inoffensive ; 
 that, unfiltered, it kills. It can bring about, like all viscid 
 liquids, like pure glycerin, pulmonary embolisms. Von 
 Dusch, Frerichs, and Bamberger have injected large doses of it, 
 and have only rarely induced death. Vulpian has injected up to 
 250 grammes of it into a dog during several days, 96 grammes 
 in one day alone. He has omitted to mention the weight of the 
 dog. Supposing it to weigh 10 kilogrammes, the toxicity of the 
 bile would be 9 cubic centimetres per kilogramme of the animal, 
 that is to say, five or six times stronger than that of urine. 
 That is little, when we think of the fatal consequences which 
 are attributed to bile. I have established that the bile of 
 oxen, mixed in twice its volume of water and injected into 
 the veins of a rabbit, produces death in the dose of 4 to 6 cubic
 
 TOXICITY OF BILE. 81 
 
 centimetres of pure bile for each kilogramme of animal. I 
 have recognized, besides, that bile decolorized by carbon loses 
 two-thirds of its toxicity. 
 
 Of the toxicity of bile, numerous explanations have been 
 offered. The biliary salts have been declared toxic in almost 
 infinitesimal quantities ; they have been found in such small 
 quantity in the blood of those who have died from severe jaun- 
 dice and from poisoning by phosphorus. Injections of tauro- 
 cholate and glycocholate of soda, made by von Dusch, Huppert, 
 and Kuhne, have produced scarcely any effect whatever. And 
 yet the results obtained by Leyden upon the dog and frog have 
 'little in agreement with each other. Concurrently with M. 
 Tapret, I have determined that the biliary salts in an aqueous 
 solution of 2 per cent, kill 1 kilogramme of rabbit ; the cholate 
 of soda, in the dose of 54 centigrammes ; and choleate of soda, 
 in the dose of 46 centigrammes. 
 
 We might incriminate cholesterin, but we have only been 
 able to induce cholesteraemia experimentally, by processes too 
 defective to enable us to draw from them any conclusion. The 
 absurd quantities of cholesterin which have been introduced 
 into the blood have only been done through the medium of soap 
 and water, or of potass, which would kill of themselves. At 
 any rate, amongst old people, the atheromatous abscesses which 
 we find widely open in the aorta contain sometimes several 
 grammes of cholesterin without there being any poisoning from 
 them. The coloring substances ought to be suspected by us as 
 toxic agents, since bile, once decolorized, is much less toxic. 
 Equally with M. Tapret, I have shown that bilirubin kills in 
 the dose of 5 centigrammes per kilogramme. 
 
 As for the biliary salts, they do not kill by direct intoxica- 
 tion alone. We can see under the microscope the harm which 
 they do. They dissolve and break up the blood-globules, and 
 also other cells, striated muscular fibres, and the cells of the 
 liver. They therefore cause anatomical lesions, and intoxication 
 arises from the setting free of toxic substances which enter into 
 the composition of the cellular elements. This intoxication 
 develops but slowly. 
 
 People intoxicated by bile are, therefore, in the condition of
 
 82 LECTURES ON AUTO-INTOXICATION. 
 
 animals into whom we have injected aqueous or alcoholic extracts 
 of the tissues. Amongst patients, so long as there is functional 
 activity of the kidney, all goes on well ; but if not, then they 
 die intoxicated by the potass and by other products of cellular 
 destruction. But it is not a primary intoxication ; it is 
 secondary, and is caused by the mineral or organic products, 
 and from the breaking up of the anatomical elements. 
 
 Amongst jaundiced people, we indeed observe a rapid dimi- 
 nution of the weight of the body. In acute yellow atrophy of 
 the liver, it seems that the muscles diminish in size. Besides, 
 if the kidney functionates well in jaundiced people, their urine 
 is very toxic, but not in the same manner as normal urine. This 
 does not determine convulsions ; jaundiced urine is convulsive, 
 and not narcotic. In small doses, even absolutely decolorized, 
 it remains toxic ; but it does not owe this property to the con- 
 vulsive material of normal urine, since this remains fixed in the 
 carbon. The convulsive property comes to it probably from the 
 potass, for bile produces nothing similar to it. Thus, jaundiced 
 urines owe their toxicity chiefly to the waste products of cellular 
 disintegration, and especially to the mineral products. We are 
 now beginning to foresee what intoxication may be in the 
 economy.
 
 LECTURE VIII. 
 
 ORIGIN OF THE Toxic SUBSTANCES OF URINE TOXICITT OF THE 
 
 FLUIDS AND OF THE CONTENTS OF THE INTESTINE (BlLE AND THE 
 
 PRODUCTS OF PUTREFACTION). 
 
 Toxicity of the fluids. It is due to the disassimilation or destruction of cells. 
 
 Products of disassimilation turned into the intestine by the liver. Toxic 
 
 power of bile compared with that of urine. Dangers of absorption or reten- 
 tion of bile. How the organism protects itself against the toxicity of bile. 
 Precipitation of a part of the biliary elements in the intestine and metamor- 
 phoses having for their object the insolubility of other elements ; toxicity of 
 jaundiced urines ; diminution of the toxic power of jaundiced urine brought 
 
 ' about by decolorizing. Putrefaction in the intestine caused by microbes 
 
 which are found normally therein. Role of the hydrochloric acid of the 
 
 gastric juice which neutralizes the activity of these microbes. Are putrid 
 
 substances toxic? Opinion of Haller. Experiments of Gaspard, Pamnn, 
 Bergmann, Billroth. Koch's argument. 
 
 IF animal juices are scarcely toxic, although they contain 
 more poison than the quantity which they give up to the emunc- 
 tories, the cells enclose poisonous substances which they retain 
 because these substances are part of their constitution, and which, 
 freed by the death of the cells, cause the fluids to become toxic. 
 
 These toxic matters are substances organized and mineral. 
 PotMss occupies the first rank among them; in the normal state 
 it is a constituent of the anatomical elements, but not of the 
 llnids. In the economy of the living animal a measured quan- 
 tit} r of toxic substance exists in a state of combination in the 
 cellular elements, and it is only by an abnormal modification of 
 these elements that we see their poisons come into the lluids. 
 The fluids contain notably only the exact quantity of potass 
 which they carry to the tissues or to the emunctories; the 
 potass, therefore, is only on its transit in these fluids. 
 
 The mineral and organic poisons are, therefore, in general, 
 poisons of disassimilation ; but in the organs whose disassimi- 
 lation produces poisons there are those which liberate a part of 
 the material of which they are composed, immediately it is free, 
 into particular canals, which conduct it to the exterior, e.g., the 
 glands of the skin, the liver. 
 
 (83)
 
 84 LECTURES ON AUTO-INTOXICATION. 
 
 Bile escapes direct absorption by the blood, but not all con- 
 tact with it, since at the surface of the intestine it is in contact 
 with the mesenteric capillaries ; only the liver is still there to 
 seize it anew and to throw it out again into the intestine. 
 
 Would bile be dangerous to the blood ? Assuredly ; its tox- 
 icity is less than is believed, but it is still considerable. 
 
 In an experiment of Vulpiau we see that 10 grammes of bile 
 per kilogramme of animal constitute a poisonous dose. We even 
 see it kill with 4, 5, or 6 grammes one kilogramme of animal. Bile 
 is, therefore, at least five times (occasionally ten times) more 
 toxic than urine. The small size of the gall-bladder and the small 
 quantity of bile which we find in it post-mortem would lead us 
 to believe that this secretion is of little importance. We change 
 that opinion when we know the quantity of bile secreted in 
 twent3 r -four hours. According to Beaunis, we may value at 
 about 1 kilogramme the quantity of bile produced in twenty- 
 four hours in man. From observation in cases of biliary fistulae, 
 Ran'ke found a mean of 14 grammes of bile per kilogramme of 
 living weight for twenty-four hours. Von Wittich has obtained 
 from such in a woman, in twenty-four hours, 528 cubic centi- 
 metres ; and in a woman equally suffering from fistula of the gall- 
 bladder, with complete obliteration of the gall-duct, I have seen 
 the daily quantity of the bile reach 800 grammes. Thus, if, in 
 equal time, the urine eliminates half of that which would kill a 
 man, bile eliminates thrice the quantity. The total quantity of 
 bile is six times more toxic than the totality of urine. 
 
 COMPARISON BETWEEN THE TOXICITY OF BILE AND 
 THAT OF URINE. 
 
 A man of 65-70 kilogrammes eliminates in twenty-four hours 
 1350 cubic centimetres of urine on an average, or about 20 
 grammes of urine per kilogramme. This urine can kill an 
 animal of 1 kilogramme after a dose of 45 cubic centimetres. 
 Man, for each kilogramme of his body-weight, eliminates, there- 
 fore, in twenty-four hours, by his urine, sufficient to kill 10U ^X20_. 
 444 grammes of living matter. A man of 37 kilogrammes elim- 
 inates in twenty-four hours 652 cubic centimetres of bile ; that 
 is, 13.45 cubic centimetres per kilogramme. This bile can kill
 
 TOXICITT OF BILE AND THAT OF URINE. 85 
 
 an animal of 1 kilogramme at the doge" of 5 cubic centimetres. 
 Man, for each kilogramme of his body-weight, eliminates, there- 
 fore, in twenty-four hours, by bile, sufficient to kill -J^~ = 2690 
 grammes of living matter. From what precedes we may con- 
 clude (1) that 1 kilogramme of living matter being killed by 
 5 cubic centimetres of bile and by 45 cubic centimetres of urine, 
 bile is nine times more toxic than urine ; (2) that the quantity 
 of bile secreted in twenty-four hours by 1 kilogramme of man 
 being capable of killing 2690 grammes of living matter, whilst 
 the quantity of urine secreted by 1 kilogramme of man in 
 twenty-four hours is capable of killing only 444 grammes of 
 living matter, the toxic activity of the hepatic secretion is six 
 times greater than the toxic activity of the renal secretion. 
 ^-==6. If all the bile which the liver secretes passed directly 
 into the blood, man would be poisoned by his own bile in eight 
 hours fift3'-five minutes. If all the urine that the kidneys 
 secreted passed directly into the blood, man would be poisoned 
 by his own urine in two days, six hours, and thirty -two minutes. 
 
 We see the danger which results either from any impediment 
 placed in the way of the elimination of bile or from its absorp- 
 tion. Fortunately, more than one-half is eliminated in twenty - 
 four hours by the digestive canal ; the water of the faeces repre- 
 sents the water of 400 grammes of bile. Besides, the other half 
 of the bile is not absorbed, for if it was eliminated by the urine the 
 toxicity of urine would be much more considerable, We would be 
 obliged to admit that the urine of twenty-four hours was capable 
 of killing the whole individual, or even twice the individual ; but 
 experiment has shown us that urine has not this toxicity. 
 
 What becomes, then, of this half of the bile which is not 
 thrown out by the digestive canal ? Does the liver destro}- it? 
 Do the tissues change it? These two hj'potheses are possible, 
 but not demonstrated. 
 
 What is demonstrated is, that in the intestine a portion of 
 the bile ceases to be absorbable. The coloring matter and the 
 biliary suits are metamorphosed, precipitated or rendered insol- 
 uble. Yet, in certain morbid conditions, bile may be absorbed 
 in the liver itself, at the margin of the hepatic cells. In these 
 cases, if the kidneys remain permeable, it becomes a menace to
 
 86 LECTURES ON AUTO-INTOXICATION. 
 
 intoxication ; if they have ceased to be so, poisoning is the 
 result. If the kidney has remained permeable, and no general 
 accidents have arisen, the urine becomes toxic, not to the indi- 
 vidual himself, but to the animals upon which we experiment. 
 Certain jaundiced urines are toxic at the rate of 13 cubic centi- 
 metres per kilogramme ; these urines owe, without doubt, a great 
 part of their toxicity to the presence of coloring matters, since, 
 once decolorized, they may be injected in double or triple the 
 quantity ; but the destruction of the blood-globules and hepatic 
 cells, the products of increased disassimilation, which the 
 rapid diminution in weight amongst jaundiced people bears 
 witness to, and especially the potass, contribute to rendering 
 jaundiced urines very toxic. 
 
 INTRA- VENOUS INJECTION OF A HIGHLY-JAUNDICED URINE. 
 
 March 11, 18S5. Into a rabbit weighing 1650 grammes we 
 injected 22 cubic centimetres of a very pronounced jaundiced 
 urine, coming from a patient in the Saint Landry Ward (Hopital 
 Lariboisiere), who was passing 900 grammes of it in twenty-four 
 hours. After the sixth cubic centimetre, agitation. At the 
 ninth cubic centimetre, pupil in great part contracted. At the 
 fifteenth cubic centimetre, pupil pin-point; spasms; hurried 
 respiration. At the twentieth cubic centimeti'e, screams ; 
 spasms. At the twenty-second cubic centimetre, death, the 
 heart still beating. The animal received 13 cubic centimetres 
 per kilogramme. 
 
 INJECTION OF THE SAME URINE DECOLORIZED, IN NEARLY 
 TRIPLE QUANTITY. 
 
 We completely decolorized, by means of animal charcoal, a 
 portion of the urine which served for the preceding experiment. 
 We injected into the veins of the ear of a rabbit weighing 1680 
 grammes 50 cubic centimetres of this urine. The injection was 
 driven in pretty rapidly. At the twenty-seventh cubic centi- 
 metre, slight tonic shaking, stronger at the forty-first cubic 
 centimetre. At the forty-eighth cubic centimetre, spasms, not 
 ceasing even at the fiftieth cubic centimetre. At this moment 
 tonic convulsions, with opisthotonos. Respiration, which had 
 become rapid after the twenty-fifth cubic centimetre, stopped ; 
 but the animal returned to life. At no moment had the pupil 
 been contracted. The rabbit had received SO cubic centimetres
 
 PUTREFACTIVE INTOXICATION. 87 
 
 per kilogramme. On the 12tli of March the rabbit had diarrhoea 
 and much albumen in its urine. On the 14th of March it was 
 quite well. 
 
 INTRA-VENOUS INJECTION OP JAUNDICED URINE. 
 
 March 14, 1885. Forty -five cubic centimetres of urine from 
 the same patient whose urine had served for the preceding 
 experiments were injected into a rabbit weighing 1450 grammes. 
 Spasms commenced after 12 cubic centimetres. At 20 cubic 
 centimetres the pupil began to contract. At 42 cubic centi- 
 metres it was ptinctiform. Spasms began and death came after 
 45 cubic centimetres, or 31 cubic centimetres per kilogramme. 
 
 INJECTION OF NEARLY DOUBLE QUANTITY OF SAME 
 DECOLORIZED URINE. 
 
 Into a rabbit weighing 1300 grammes we injected 70 cubic 
 centimetres of the preceding urine, decolorized by means of 
 carbon. Spasm came on after 68 cubic centimetres. The pupil 
 was not contracted. Death came after the seventieth cubic 
 centimetre. That was 54 cubic centimetres per kilogramme. 
 
 If bile is toxic directly and indirectly, the intestine is already 
 far as bile is concerned a source of intoxication, in as 
 feeble a proportion as we please, but still really so. From there 
 pass onward into the blood, in addition, other materials which 
 are eliminated by the urine, mineral salts (e.gr., potass) intro- 
 duced by the food, and other toxic substances of alimentary 
 origin. Nevertheless, this is only a minimum portion of the 
 poisons which the blood may derive from the intestinal canal. 
 
 There is a third source of intoxication for the blood ; it is 
 putrefaction : not only that which arises from the imperfect 
 metamorphosis of digested matter, but that which the presence 
 of micro-organisms in the intestinal tube incessantly maintains. 
 In the digestive canal the conditions most favorable for the 
 elaboration of poisons are realized. Therein are found nitrog- 
 enous substances, already peptonized ; and peptones are, as you 
 know, excellent culture-media for microbes. They are in asso- 
 ciation with a notable quantity of water in a tube at a constant 
 temperature of 37 degrees. The digestive canal is constantly
 
 88 LECTURES ON AUTO-INTOXICATION. 
 
 open exteriorly. Besides, the foods taken carry in with them 
 putrefactive agents ; respiration allows of the deposition of 
 dust in the pharynx, which, with each movement of degluti- 
 tion, is caught by the saliva, along with the micro-organisms 
 which it conceals. The conditions favorable for the mainte- 
 nance of putrefaction are so numerous that we ask whether 
 digestion can ever go on normally. Fortunately, the organism 
 secretes in the stomach, on the introduction of food, a juice 
 which is opposed to all fermentation. Experimentally, we know 
 that 1.10 grammes of anhydrous hydrochloric acid per litre pre- 
 vents all fermentation ; but the gastric juice contains more. We 
 find therein, per litre, up to 3.30 grammes, and even 5 grammes, 
 of hydrochloric acid, estimated as the fuming acid of commerce. 
 
 But infectious agents have not been destroyed by the gastric 
 juice in the stomach ; they have only been neutralized ; they 
 have only passed into a state of latent vitality. The action of 
 organized ferments re-commences when the foods have passed 
 through the pylorus. The acid of the gastric juice finds itself 
 at this moment neutralized by the alkalies of the intestine, 
 whose contents, if not alkaline or neutral, are in every case only 
 feebly acid by a commencement of acetic fermentation. 
 
 We have regarded the bile as capable of prolonging the 
 arrest of fermentations ; but bile is capable of undergoing fer- 
 mentation itself, or of putrefying. It can, therefore, only feebly 
 oppose fermentation in the small intestine. At any rate, it can 
 have no influence upon those which are actively carried on in 
 the large intestine. 
 
 Thus do we find the small intestine, on the one hand, and the 
 large intestine particularly, on the other, capaple of passing 
 products of putrefaction into the blood. But, are the putrid 
 substances toxic? Haller believes they are not. Gaspard, in 
 1822, established the fact that putrid substances are toxic, and 
 that they are actually more so than substances arising from 
 disassimilation. He injected into the veins of animals liquid 
 arising from putrefaction of blood or of meat. He induced 
 faintness, diarrhoea, and vomitings ; hyperaemia of mucous mem- 
 branes; then death; and at the autopsy ecchymoses of the 
 digestive canal were seen ; also of the cellular tissues, those
 
 PUTREFACTIVE INTOXICATION. 89 
 
 of the muscles and of the heart; swelling of the spleen and 
 the mesenteric glands ; congestion of the lungs, phenomena 
 all of which were verified by those who have since repeated 
 Gaspard's experiments. 
 
 Magendie has studied intoxication by gases from the basins 
 of water-closets, he had previous knowledge of the morbid 
 influence of putrid emanations. 
 
 The experiments of Gaspard have been regarded as correct 
 by Panum, Bergmann, and Billroth. It yet remains to be known 
 whether the facts observed by Gaspard arose from intoxication 
 or infection. So far as he is concerned, he could not distinguish 
 putrefaction from infection, not having any knowledge of infec- 
 tious agents. He injected into the blood of animals the prod- 
 ucts of the life of inferior organisms, and at the same time these 
 organisms themselves. At one and the same time, therefore, he 
 caused intoxication and infection. 
 
 Panum tried to solve this difficulty. By boiling at 100 C. 
 he destroj'ed the organisms themselves before injecting the prod- 
 ucts of putrefaction, and he, too, observed the same phenomena. 
 
 Koch has, besides, furnished another argument. If it is a 
 question of intoxication, the effects produced ought to be imme- 
 diate and proportional to the quantity of putrid matter injected. 
 If it is one of infection a period of incubation is necessarj*, 
 and the quantit} r ought not to seriously influence the accidents 
 which follow. Experiment, however, shows that in those cases 
 the accidents happen immediately after the injection of the 
 putrid material. If we inject small quantities of it, we have 
 accidents less grave than from large quantities. 
 
 Thus, the absence of incubation and the proportional ratio of 
 accidents to the quantity of poison decide the question of their 
 nature ; they are truly of the order of intoxications. It 
 remains, now, to isolate the toxic substances produced by the 
 lower organisms.
 
 LECTURE IX. 
 
 ORIGIN OF THE Toxic SUBSTANCES OF URINE TOXICITY OF THE 
 PRODUCTS OF PUTREFACTION AND OF THE FAECES. 
 
 Toxicity of the products of putrefaction in general. The accidents which they 
 determine belong to the order of intoxications. Attempts to isolate the 
 various products of putrefaction. Panum, Hemmer. The sepsine of Berg- 
 maun and Schmiedeberg. Multiplicity of the alkaloids of putrefaction. 
 
 Zulzer and Sonnensteiu, Selmi, A. Gautier, Brouardel, and Boutmy. 
 
 Variability of the products of putrefaction, according to temperature. Dim- 
 inution of the toxicity of putrid substances owing to filtration through char- 
 coal. Enumeration of the toxic substances which putrefaction causes in 
 
 vitro, acetic acid, butyric, valeric, sulphuric, ammonia, leucin, tyrosin, 
 
 indol, skatol, cresol, phenol, hydrocarbons, etc. All these bodies exist 
 
 also in the putrefactions induced in the interior of the digestive canal. They 
 
 contribute to rendering the faeces toxic. Demonstration of the toxicity of 
 
 faeces. Stich. My researches upon the alkaloids of faeces ; their multi- 
 plicity and their chemical characters. Intra-veuous injections of the extracts 
 of faeces. Aqueous and alcoholic extract. Extract of fasces deprived of their 
 mineral substances. Resume of the sources of toxicity. 
 
 IT is proved that putrefaction gives birth to poisons whose 
 effects are revealed in the putrid fever of Gaspard. We have 
 wondered if death, in the cases which he observed, was really 
 the result of intoxication. It is not explained by embolism, for 
 we find neither the clinical character nor the lesions of such. 
 Was it, then, a question of infection? Putrefaction, including, 
 as it does, infectious agents and their products, we introduce all 
 at once when we make injections of putrid substances. The 
 results obtained are capable of being attributed to infectious 
 accidents just as much as to toxic phenomena. The disease 
 may be explained by multiplication in the blood of micro-organ- 
 isms acting in accordance with one of the five methods which 
 are proper to them. To this objection the experiment of Panum 
 replies, for he only injected putrid matter after having heated it 
 to 100 degrees ; and he, also, observed the same phenomena as 
 Gaspard. 
 
 Hiller introduced into the blood filtered putrid matter no 
 (90)
 
 TOXICITY OF PRODUCTS OF PUTREFACTION. 91 
 
 longer containing any figured corpuscle visible under the micro- 
 scope ; he observed the same phenomena. Besides, I have 
 recalled to you the theoretical argument of Koch, if it was a 
 question of infection, a period of incubation would be necessary 
 in order that pathogenic organisms might have time to multiply 
 in the circulation. The microbes which are the most rapid in 
 their development require twenty minutes in order that one 
 of them can give birth to two others. Besides, one microbe 
 alone being quite sufficient theoretically to bring about infectious 
 disease, a most minute quantity ought to be sufficient to produce 
 the most severe accidents. We only know that the pl^siologi- 
 eal effects are, in these cases, proportional to the mass of toxic 
 matter introduced into the organism. 
 
 The toxicity of the products of putrefaction, taken generally, 
 being once established, we ought to try to isolate each one 
 of them. Panum, in 1856, made the first attempt at isolation. 
 He evaporated to dryness putrid matter; exhausted, by alcohol, 
 the dry residue; evaporated, by boiling, the alcohol from the 
 alcoholic solution, and had thus two extracts, the alcoholic 
 extract and the residue, insoluble in alcohol, which would be the 
 aqueous extract. Redissolving in water the two extracts, he 
 studied comparatively the effects which each one might produce 
 upon the living organism. He established thus the fact that 
 the alcoholic extract is very feebly toxic ; it represented one- 
 fifth of the total toxicity. The substances insoluble in alcohol 
 represent, consequently, the four-fifths of that toxicity. 
 
 Ten 3'ears later Heminer showed that putrid poison is in- 
 soluble in alcohol. 
 
 In 1868 Bergmann and Schmiedeberg made researches upon 
 the chemical character of the substances which cause putrid 
 material to be toxic. They obtained a crystallizable bod}-, com- 
 parable chemically to vegetable alkaloids, combining with acids 
 to form crystallizable salts, and producing the same physiologi- 
 cal effects as the injection of putrid matter. They have, there- 
 fore, considered it proper to ascribe to this body a role in the 
 production of toxic accidents. This sepsine, as they called it, 
 has been incriminated, since then, by surgeons, as the cause of 
 certain complications of wounds (pyaemia, etc.). But already
 
 92 LECTURES ON AUTO-INTOXICATION. 
 
 the experimenters of whom I have spoken had recognized, by 
 the side of this sepsine, other bodies having a different toxicity. 
 
 In 1869 Zulzer and Sonnenstein had signaled out the presence 
 of alkaloids in the products of putrefaction, having chemical 
 reactions comparable to those of atropine, having the property 
 of dilating the pupil and of accelerating the heart, alkaloids 
 which also exist (as I showed in 1882) in the extracts of the 
 urine of patients attacked with typhoid fever. 
 
 In 1871 Selmi again extensively resumed the study of the 
 question of the very numerous alkaloids of putrefaction, as well 
 as Gautier in 1872, Brouardel and Boutmy in 1880, devoting 
 their time to the study of the alkaloids of the cadaver. 
 
 The result of all these researches is that numerous alkaloids, 
 variously toxic, are developed in the course of the putrefaction 
 of organized substances. A putrid mass, taken en bloc, has a 
 very variable toxicity. Its toxicity increases more and more 
 in proportion as putrefaction advances. After the first products 
 of the transformation of organized matter are destroyed, the 
 toxicity, Avhich has been at length increasing in it, afterward 
 diminishes, and becomes annihilated at the end of a certain time. 
 Putrefaction by heat develops a more intense toxicit}' ; by cold, 
 it is not only slower, but modified also in its intensity, as the 
 following experiment proves. 
 
 As certain toxic organic substances lose a part of their tox- 
 icity after having been filtered through charcoal, I have caused 
 putrid substances to be filtered. These lose a large part of their 
 toxicity by this means. 
 
 INTRA-VENOUS INJECTION OP AN AQUEOUS EXTRACT OF MUSCLE 
 PUTREFIED IN THE COLD. 
 
 April 30, 1885. We macerated, in the cold, 500 grammes of 
 muscle in 500 grammes of water for twenty-four hours. We 
 pressed it; we obtained 502 cubic centimetres of a distinctly 
 colored liquid, and filtered it. We injected into a rabbit weigh- 
 ing 1850 grammes 50 cubic centimetres of this liquid, or 27 
 cubic centimetres per kilogramme. We observed a medium my- 
 osis and great depression. The liquid was not sufficient to allow 
 of a larger injection.
 
 TOXICITY OF PRODUCTS OP PUTREFACTION. 93 
 
 INTRA-VENOUS INJECTION OF AN AQUEOUS EXTRACT OF MUSCLE 
 PUTREFIED BY HEAT. 
 
 M:iy 5, 1885. 1. We macerated 1200 grammes of muscle in 
 1200 grammes of water, in a stove, for two days. The liquid, 
 strongly colored red, was filtered. Into a rabbit weighing 1720 
 grammes we injected 40 cubic centimetres of this liquid. Death 
 supervened, with dyspnoea and convulsions, but with little my- 
 osis, after a dose of 23.25 cubic centimetres per kilogramme. 
 
 2. We decolorized, by means of charcoal, a certain quantity 
 of this same liquid. Into a rabbit of 1480 grammes we injected 
 100 cubic centimetres. Death supervened, with slight convul- 
 sions and myosis. The animal received 67.56 cubic centimetres 
 per kilogramme. 
 
 The pupillary contraction which the injection of normal urine 
 causes is also produced by the injection of putrid material, 
 even though it has been filtered through charcoal. The toxicity 
 of these substances is, therefore, due to another substance than 
 that which exists in normal urine, since this, filtered through 
 charcoal, loses its power of causing contraction of the pupil. 
 
 These researches are still only on the surface, so to speak. We 
 have, at length, seen putrid intoxication in its entirety ; we have 
 afterward studied certain isolated parts of it. The alkaloids 
 have been studied with some care ; but the toxicity of putre- 
 factive products is due to other causes than alkaloids. There is 
 3 r et another series of toxic substances which putrefaction causes. 
 
 The acids, acetic, butyric, valeric, sulphuric, ammonia 
 and the ammonia compounds, leucin, leuceine, tyrosin, indol, 
 skatol, cresol, phenol, and the hydrocarbons are all toxic. All 
 may and do contribute, in their part, to the toxicity of putrid 
 substances, taken en bloc. 
 
 All that has just been said of putrefaction in vitro is appli- 
 cable to putrefaction in the digestive tracts ; for the digestive canal 
 is a veritable putrefactive apparatus. Moisture, heat, and the 
 germs coining from the atmosphere concur in producing putre- 
 faction as soon as the hydrochloric acid or the bile has disap- 
 p( :i red or become changed in its nature. The alimentary residues 
 which have not been digested and the peptones not yet absorbed 
 are transformed, without any alteration, into infectious agents.
 
 94 LECTURES ON AUTO-INTOXICATION. 
 
 Theoretically, in the second and, particularly, in the third parts 
 of the intestine, there ought to occur the same phenomena, and 
 the same bodies should develop which chemistry has revealed in 
 experimental putrefaction. In fact, we find in faecal matter the 
 alkaloids of putrefaction (as I have shown, in 1882). They may 
 develop there even under the influence of a ferment which is not 
 organized, trypsine. Since 1881 Tanret has seen that ether and 
 soda carry into the peptones some substances having the char- 
 acters of alkaloids, and which, in spite of certain analogies in 
 chemical reaction, differ already from peptones by their solubility 
 in ether. In 1883 Brieger demonstrated that alkaloids are devel- 
 oped during the act of peptonization. Faecal matter contains also 
 excretine, whose presence and toxicity Marcet has drawn atten- 
 tion to. Strong as was the presumption in favor of the toxicity 
 of faecal substances, it was yet necessaiy to demonstrate it briefly. 
 
 In 1853 Stich showed that faecal matter is toxic, but not to 
 the individual who has produced it ; because this experimenter 
 introduced into the intestine of one animal the faecal matter of 
 another. In reality, faecal matter is toxic, in a general way, to 
 living cells. If we seek for those elements to which the toxicity 
 of faecal matter is due, we have only the embarrassment of choice. 
 I will insist upon the alkaloids whose existence I demonstrated 
 in September, 1882. I made extracts by means of chloroform 
 and by ether, after having rendered faecal matter alkaline. 
 
 I arrived at this conclusion, that faecal matter contains various 
 alkaloidal substances, some soluble in ether and insoluble in chlo- 
 roform, others insoluble in ether and soluble in chloroform. All 
 have the characters of alkaloids, behaving like them under the 
 iodo-iodurated reagent, double iodide of mercury and potassium, 
 phospho-molybdate of soda, tungstate of soda, and tannin. I 
 have isolated them in notable quantities, but insufficient to pro- 
 duce intoxication. I believe, therefore, that putrefaction plays 
 a part in the toxicity of faecal substances, but less than is sup- 
 posed. I have practiced intra-venous injection with the extracts 
 of faecal matter. 
 
 The aqueous extract is toxic. It produces depression and 
 diarrhoea, phenomena the precursors of death. But it is chiefly 
 the alcoholic extract which is energetically toxic in small doses.
 
 TOXICITY OF FAECAL MATTER. 95 
 
 I have seen the alcoholic extract from 1 7 grammes of faecal mat- 
 ter kill, having induced severe convulsions. Now, man forms, 
 in twenty -four hours, 400 grammes of faecal matter. We can 
 seek for that substance to whose presence is due this toxicity 
 of the faeces. The extract of faecal matter, when it is deprived 
 of its mineral substances, salts of potass, and ammonia, when 
 it has been reduced to dryness, taken up again with absolute 
 alcohol, treated by an alcoholic solution of tartaric acid, filtered, 
 neutralized by sodium carbonate, evaporated, taken up again by 
 alcohol, dried anew, and taken up by water, only kills in doses 
 infinitely larger. It is no longer the extract from 39 gi-ammes 
 of faecal matter that we must inject to induce toxic and fatal 
 accidents, but the extract of 298 grammes. 
 
 INTR A- VENOUS INJECTION OF EXTRACT OF F.SCAL MATTER AND OF 
 THE SAME EXTRACT DEPRIVED OF MINERAL SUBSTANCES. 
 
 April 28th. We collected on April 23d 600 cubic centimetres 
 of faecal matter, which we exhausted with 1 litre of absolute alco- 
 hol. The alcohol was filtered and distilled. The residue was taken 
 up by 225 cubic centimetres of absolute alcohol. We afterward 
 divided the liquid into two parts, one of 150 cubic centimetres, 
 representing 400 grammes of faecal matter; the other, 75 cubic 
 centimetres, representing 200 grammes of faecal matter. A. The 
 second part (200 grammes) was distilled and taken up by water. 
 After filtration we obtained 90 cubic centimetres of liquid, of 
 which 1 cubic centimetre represented 2.22 grammes of fecal 
 matter. Into a rabbit of 1850 grammes we injected 33 cubic 
 centimetres of this liquid. At this moment convulsions, death. 
 That is, 17.8 cubic centimetres per kilogramme, or the ex- 
 tract of 39.5 grammes of faecal matter. B. The first part (400 
 grammes) was distilled and taken up by absolute alcohol. We 
 precipitated the potass and ammonia by tartaric acid. We also 
 neutralized, after filtration by sodium bicarbonate, filtered, evap- 
 orated, and took up by absolute alcohol. Again we filtered, 
 evaporated, and took up by distilled water, and then filtered. 
 We obtained 35 cubic centimetres of liquid, of which 1 cubic 
 centimetre represented 13.4 grammes of faecal matter. Into a 
 rabbit of 1340 grammes we injected, by an intra-venous channel, 
 35 cubic centimetres. No phenomena were observable. The 
 rabbit received 400 grammes of faecal matter, or the extract of 
 
 id 4UU g 
 
 offeecal 
 
 298 grammes offeecal matter per kilogramme.
 
 96 LECTURES ON AUTO-INTOXICATION. 
 
 We may, therefore, consider the following as contributing to 
 the toxicity of the fseces : on the one hand, potass and ammonia 
 chiefly ; on the other, something which is soluble in alcohol, and 
 which is neither potass nor ammonia ; then bile, and, lastly, the 
 residues of putrefaction. 
 
 To sum up : the aqueous extract of putrid matter is very 
 toxic, that of faecal matter is slightly so ; the alcoholic extract 
 of putrid matter is not very toxic, that of faecal matter is 
 decidedly so. 
 
 If we class toxic products together, we place in the first line 
 mineral substances, chiefly potass, alimentary products, or 
 those furnished by disassimilation ; in the second line the prod- 
 ucts of intestinal putrefaction, amongst which ammonia occu- 
 pies an elevated position ; in the third line the organic products 
 of disassimilation, and therein is included a small quantity of bile, 
 which may be re-absorbed by the intestinal mucous membrane. 
 
 Thus we recognize all the sources of the toxic materials of 
 the economy, the tissues, secreting organs, foods, putrefactions. 
 
 The toxic products coming from these four seats of origin, 
 introduced into the blood, give to it that slight degree of tox- 
 icity which we have been able to estimate. The blood imposes 
 this toxicity upon the products of secretion, and especially upon 
 the renal emunctory. After having demonstrated that the urine 
 is toxic, I showed that it cannot be otherwise. The blood is 
 not, to any extent, habitually toxic, because urine is strongly 
 so ; if this were no longer toxic the blood would become toxic, 
 since poisons are always being introduced into it, proceeding 
 from disassimilation, from foods, the products of intestinal 
 putrefaction, and the products of secretion. 
 
 We never observe accidents the outcome of intoxication 
 with normal kidne}^ ; if the kidneys are diseased the individual 
 dies. To all cases of death arising from suppression of the 
 renal function we apply the term uraemia. But what we already 
 know enables us to foresee that a complexity of phenomena is 
 hidden under this name.
 
 LECTURE X. 
 
 INTESTINAL ANTISEPSIS. 
 
 Resume of the causes of the toxicity of the contents of the digestive canal. Potass 
 
 and ammonia, bile, putrid substances. Poisons absorbed in the intestine 
 
 must traverse the blood, since they are found in the urine. Parallelism 
 between the toxicity of urine and that of material contained in the intes- 
 tine. We can diminish the toxicity of urine by inducing disinfection and 
 antisepsis of the digestive canal. Influence of charcoal taken in a suffi- 
 cient quantity upon diminution of the toxicity of urine. On intestinal 
 
 antisepsis. Conditions which a medicament ought to fulfill when destined 
 to briug about intestinal antisepsis. Salicylate of bismuth, salts of mer- 
 cury, iodoform, naphthalin. Their advantages and inconveniences. Method 
 
 of administering naphthalin. Charcoal fixes the coloring matter and the 
 
 toxic products of bile. Naphthalin is opposed to intestinal fermentation. 
 
 THE organism contains poisons the origins of which we know, 
 viz., the destruction of cells, disassiniilation, secretion, ingestion, 
 and putrefaction. 
 
 The digestive canal contains three orders of these poisons : 
 those which come from the ingesta, bile, and putrid material. 
 Its contents, therefore, should be toxic. Experimentation has 
 demonstrated that they are toxic from the potass and ammonia, 
 toxic from the bile and putrid material. 
 
 There are, therefore, poisons in one part of the organism 
 from which absorption is continually taking place. Can this 
 absorption produce intoxication ? We cannot demonstrate ex- 
 perimentally that the poison enters the blood, but we can demon- 
 strate that it leaves it. It is, therefore, necessary to see whether 
 the toxicity of the urine is in keeping with the toxicity of the 
 digestive tube, and as to whether their variations are parallel. 
 
 In 1882, whilst demonstrating the alkaloids found in normal 
 feecal matter, I considered those as the source of nearly all the 
 alkaloids of the economy. I have been able in one instance 
 to estimate their quantity as 15 milligrammes per kilogramme 
 of faecal matter. I noticed that each time these alkaloiclal sub- 
 stances increase in the fneces they increase in the urine, although 
 always smaller in quantity. I noticed, too, that the parallelism 
 is preserved not only from a quantitative point of view, but also 
 
 7 (97)
 
 98 LECTURES ON AUTO-INTOXICATION. 
 
 as regards their nature. Just as there has been a predominance, 
 in the digestive canal, of alkaloids soluble in ether or those 
 which are soluble in chloroform, so have I seen predominate, in 
 like manner, one or the other in the urine. 
 
 I am less inclined, to-day, to add so much -importance to 
 these toxic products. We can arrive at the same opinion by 
 taking toxic substances in their totality. 
 
 We may suppress a part of the toxic matter of urine by 
 fixing that of the intestine by means of charcoal, which retains 
 the coloring substances and the alkaloids. This is to induce 
 not antisepsis, but disinfection of faecal matter. 
 
 The extract of 200 grainmes of fsecal matter, in the case of 
 patients by whom we have caused to be ingested the required 
 quantity of charcoal, is inoffensive to those animals into which 
 we have injected it, whilst we killed with the extract of 17 
 grammes, of fsecal matter not disinfected, per kilogramme. This 
 intestinal disinfection by charcoal diminishes also the toxicity of 
 urine by from one-half to two-thirds. If we wished to push the 
 inquiry further, it would be necessary to produce antisepsis by 
 preventing even the putrefaction which is produced in the 
 intestinal canal. 
 
 It is a long time since we have produced antisepsis without 
 knowing it, just in the same way as M. Jourdain* made prose. 
 By giving calomel, or the black sulphide, we diminish, without 
 knowing it, putrefaction. Many physicians have done so con- 
 sciously, supposing that substances with a putrid odor would be 
 offensive to the elements with which they are in contact. 
 
 We have employed chlorine internally, and pure iodine, ex- 
 cellent antiseptics, the sulphites, hyposulphites, phenic acid, 
 creasote (Pecholier), and boracic acid. We have obtained 
 nothing by these means save, perhaps, with the sulphites (Sem- 
 mola, Pauli) and the sulphide of carbon (Dujardin-Beaumetz). 
 
 A reproach which at the outset we can theoretically raise 
 in regard to all of these substances, with the exception, perhaps, 
 of the last one, is, that they are soluble and absorbable. In the 
 long journey from the mouth to the intestine the antiseptic 
 agent loses some of its power. One other inconvenience which 
 
 * This refers to " Le Bourgeois Gentilhoinme " of Moliere.
 
 INTESTINAL ANTISEPSIS. 99 
 
 might arise from absorption of the antiseptic agent is, that, when 
 introduced into the blood in a sufficiently large quantity, it 
 might exercise therein a toxic influence. 
 
 The conditions which a substance should fulfill when des- 
 tined to bring about intestinal antisepsis are, that it should 
 not be absorbable, and yet should be capable of being given in 
 doses efficaciously antiseptic without inducing by itself any 
 toxic influence upon the organism. We must, therefore, use 
 insoluble antiseptics. 
 
 Salicylate of bismuth and iodoform, extolled by Vulpian ; 
 naphthalin (Rossbach) ; calomel, which is changed into bichloride 
 in the stomach and black sulphide in the intestine ; black sul- 
 phide employed alone (Serres, Becquerel), these have each in 
 their turn enjoyed considerable favor. A portion of these 
 agents is always absorbed. 
 
 Thus, with salicylate of bismuth the faecal matter is black- 
 ened owing to the sulphide of bismuth, and the urine contains 
 salicylic acid. 
 
 With iodoform, which I have employed for a long time now, 
 we find a little iodine in the urine, and the stools contain free 
 iodoform. 
 
 When we administer naphthalin the stools contain it. This 
 body, hitherto considered insoluble in water, is absorbed to the 
 extent of some centigrammes for every 5 grammes we have 
 given. The urine rapidly takes on a brownish-black coloration, 
 different from that of carbolic acid, which is tinted black, and 
 from creasote, which is of a greenish black. 
 
 Acetic acid, in small quantity, modifies the substance which 
 results from the passage of naphthalin into the urine. Under 
 its influence a rosy tint appears, which acetic acid does not pro- 
 duce in normal urine. We can estimate in the urine a body of 
 a compound-sulphur character, resulting from the combination 
 of naphthol and sulphur, a naphtho-sulphurous acid, which may 
 be arranged as naphtho-sulphite of soda. This union can only 
 have occurred by sulphur having been borrowed from the organ- 
 ism ; that is to say, by destroying albumen or nitrogenous matter. 
 But this quantity of sulphur is insignificant, as I have been able 
 to ascertain by the aid of M. Rosenstichl. From the whole of
 
 100 LECTURES ON AUTO-INTOXICATION. 
 
 the urine passed by a woman who had taken for ten days 5 
 grammes of naphthalin we were only able to remove 0.03 centi- 
 gramme of naphtho-sulphite of soda per litre. 
 
 For ten years I have made use of charcoal in large doses, 
 and, thanks to it, have obtained a diminution of the toxicity of 
 urine and of fsecal matter without preventing fermentation. 
 Since then I have added iodoform to charcoal, which neutral- 
 izes putrid ferments, according to the formula : Charcoal, 100 
 grammes ; iodoform, 1 gramme. 
 
 Following Rossbach, I experimented with naphthalin to 
 solve the question of the seat of the infectious agent in cholera; 
 then in typhoid fever, gastric fullness, putrid diarrhoeas ; finally, 
 in the healthy individual, without injury to the latter. 
 
 I give the formula : Five grammes of naphthalin, mixed 
 with an equal quantity of sugar, made aromatic with 1 or 2 
 drops of bergamot, divided into twenty powders, one of which 
 is to be taken every hour. 
 
 Fsecal matter at length loses its odor, unless it is simply 
 masked by that of naphthalin. But a second and greater 
 advantage is, that fsecal matter loses, to a great extent, its tox- 
 icity, the putrefactions within the intestinal tube being com- 
 pletely suppressed. 
 
 In the case of a man the subject of gastric trouble, 35 to 40 
 cubic centimetres of urine induced death for every kilogramme 
 of animal. After disinfection of the faeces by naphthalin, 90 to 
 100 cubic centimetres of urine were harmless. This harmless- 
 ness of the urine lasted as long as the antisepsis of the digestive 
 canal. Antisepsis suppressed, the urine became toxic again. 
 
 With charcoal I was less enlightened upon the cause of the 
 inoffeusiveness of the urine, since it fixed the coloring matter 
 of the biliary secretion. By means of naphthalin I only sup- 
 press fermentation. We would also require to suppress the 
 bile ; but as, in the case of people in whom bile ceases to flow 
 into the intestine, it passes into the blood, the problem cannot be 
 solved. We would require to have an individual the subject of 
 biliary fistula, and suppress in him alimentation. All causes of 
 toxicity removed, whatever will remain of a toxic character in 
 the organism would be attributable to the poisons of disassimi- 
 lation. Here is research for the future.
 
 INTESTINAL ANTISEPSIS. 101 
 
 To sum up : I have succeeded in demonstrating that not 
 only are there poisons in the intestine, but that the}' are a con- 
 stant menace of intoxication to the organism. After having 
 explained the sources of toxic substances, I have shown their 
 passage through the organism, their elimination by the urine, 
 and the sewage-wave ladened with toxicity coming from other 
 sources. If urine is not formed, there may result from this fact 
 intoxication, which will often be of intestinal origin. That is 
 why, in place of uraemia, I have proposed to call it stercoraemia 
 or coprsemia. 
 
 If I have written at such length upon plrysiological data, 
 it is because they were indispensable before undertaking the 
 analysis of pathological facts.
 
 LECTURE XL 
 
 PATHOGENESIS OF URJEMIA DISTINCTION BETWEEN THE SYMPTOMS 
 OF THE PRE-UR.&MIC PERIOD OF NEPHRITIS AND THE SYMPTOMS 
 OF INTOXICATION. 
 
 The knowledge of the action of the toxic substances contained in the urine does 
 not explain all the symptoms of nephritis. It only explains those of the 
 period of intoxication, when the organism produces more poison in twenty- 
 four hours than the kidneys can eliminate in the same time. A normal 
 kidney can eliminate more toxic material than it does in an ordinary way. 
 
 Examination of the various accidents which we observe in diseases of the 
 
 kidney before the uraemic period, albuminuria, cachexia from hypo-albu- 
 minosis. Dropsy. Vascular and cardiac troubles; their effect upon the 
 digestive canal and the nutrition of the skin. Haemorrhages. Eye troubles. 
 Spurious serous phlegmasias. All accidents precipitated may come on when 
 
 the urine is still normal as regards quantity and density. When the renal 
 
 impermeability has become excessive, the period of intoxication is announced 
 by one or several of the seven poisons which normal urine contains, variously 
 associated. There would, therefore, be not one, but several uraemias. Clin- 
 ical investigation has, for some time past, established various symptomatic 
 forms, and the five theories actually in existence, which are proposed in order 
 to explain the pathogenesis of uraemia, contain, all of them, an element of 
 truth. 
 
 WE know the various groups of toxic substances which, in 
 the normal state, enter into the blood and are eliminated by the 
 kidney. By lesions of the kidney allowing of the accumulation 
 of toxic products in the organism, it is apparent that we can 
 now clearly interpret the accidents which are produced in people 
 who are the subjects of disease of the kidney. We must not 
 delude ourselves, however; the pli3 T siological knowledge which 
 we have acquired only throws light upon some of the accidents 
 which complicate diseases of the kidnej^. 
 
 Amongst the symptoms of nephritis, many do not belong to 
 the domain of intoxication. Besides, every disturbance of the 
 renal function is not capable of determining a sufficient accumu- 
 lation of toxic substances in the econonry, and for sj'inptoms to 
 show it. In order that intoxication may be invoked, it is not 
 sufficient that the kidney should be diseased. It is necessary 
 that its permeability should be diminished to a degree such that 
 (102)
 
 PATHOGENESIS OP UREMIA. 103 
 
 it can no longer eliminate, in twenty-four hours, the quantity of 
 poison which the organism forms in twenty-four hours. Now, 
 it is certain that the kidney can, in the normal state, eliminate 
 infinitely more toxic material than it generally does. Let us 
 consider what a normal kidney can do. Instead of the 1200 to 
 1500 grammes of urine which it secretes ordinarily in twenty- 
 four hours, a normal kidney can secrete as much as 25 litres of 
 urine, and more. Instead of 20 to 30 grammes, it can eliminate 
 120 grammes of urea, and more, as in a large number of cases 
 of diabetes insipidus. Instead of 55 centigrammes of uric 
 acid, which the kidney eliminates in the normal state, it can, in 
 cirrhosis and in leukaemia, eliminate 8 grammes of it, and more, 
 in twenty-four hours. It can, in addition, eliminate other ab- 
 normal substances, up to 140 grammes of sugar per litre. Add 
 to this the fat existing in the form of granules, and not dis- 
 solved (chyluria). The kidney also eliminates substances which 
 it ought to retain, peptones and albumen. 
 
 It requires the kidney to be considerably diseased, for, owing 
 to its permeability, it is sufficient alone to eliminate the poison 
 formed by the organism, in proportion to its production. Below 
 this rate commences intoxication ; but before this arises we see 
 abnormal phenomena appear, and, first of all, albuminuria. 
 
 Albuminuria is the accident of bad repute in diseases of the 
 kidney, that to which we attach extreme importance, behind 
 which we find O3dema and all the rapidly developed or slowly 
 evolved accidents of Bright's disease, and which we regard as 
 causing exhaustion. Yet it is often a few centigrammes at the 
 most, a few grammes of albumen which the patient eliminates 
 each da}'. Such a slight spoliation is not capable of causing de- 
 terioration of the system. A woman who is nursing loses, with- 
 out any injury, 40 to 50 grammes of albumen or other proteid 
 matter by the lacteal secretion, and yet the system is not weak- 
 ened thereby. Her safeguard is the integrity of her appetite 
 and digestion. She loses albuminoid matter under one form and 
 recuperates it under another. But, in the same way as in the 
 nurse, insufficient alimentation and vomiting may diminish the 
 proteids ; and if the renal disease is accompanied by fever or 
 other phenomena which prevent nutrition and reparation, intense
 
 104 LECTURES ON AUTO-INTOXICATION. 
 
 albimiinuria becomes a cause of exhaustion, like abundant leucor- 
 rhoea, dysentery, suppurations, and frequently-tapped ascites. 
 An elimination of albumen in considerable quantity may cause 
 impoverishment of the blood. There are large albuminurias, 
 from 8 to 12 grammes in twenty-four hours. This last limit is 
 seldom exceeded ; we mention as very rare that of 16 grammes. 
 I have seen a patient lose 19 grammes daily of albumen, reck- 
 oned as dry albumen ; it was in a case of amyloid degeneration 
 of the kidneys, liver, spleen, and stomach. In these cases we 
 understand that a rapid cachexia is produced, by hypo-albumosis, 
 when the nephritis is accompanied by functional alterations or 
 lesions of the digestive canal. 
 
 There are patients in whom the density of the serum falls 
 from 1030 to 1013, consequent upon the absolute want in the 
 blood-plasma of proteid matter, and of a relative hydrsemia. 
 There is produced a correlative increase of water, relative 
 hydrsemia, and, besides, often enough, an absolute hydrsemia, 
 because there has been retention of water. 
 
 The extreme cases belong chiefly to amyloid nephritis, be- 
 cause in such the liver, spleen, stomach, and intestine are dis- 
 eased. All the organs whose function it is to transform the 
 peptones of digestion into serum-albumen have undergone de- 
 terioration at the same time as the kidney. When such a 
 large number of organs is diseased we can scarcely regard 
 all the accidents which happen as due to renal impermea- 
 bility. We cannot say that there is uraemia, nor even kidney 
 disease ; there is a general disease of the organs concerned in 
 assimilation. 
 
 Hydrsemia is not always caused by the retention of water ; 
 it may be produced by diminution in the amount of solid 
 matter. On the other hand, hydrsemia may be prevented by 
 attacks of vomiting, diarrhoea, anasarca, in spite of oliguria; 
 then comes thirst, a frequent accident, which introduces as 
 much water as the accessory emunctories can remove. There is 
 then a collection of conditions extremely complex, and all 
 foreign to intoxication ; therefore we do not pretend to explain 
 by intoxication most of the accidents of nephritis. 
 
 As a consequence of hypo-albumosis there appear oedemas,
 
 PATHOGENESIS OP UREMIA. 105 
 
 anasarca, and serous accumulations in the large cavities. Accord- 
 ing to Bartels, the hypothesis of Bright, which regards hydrse- 
 mia as favorable to the diffusion of serum, would not be suffi- 
 cient. Bartels believes that there is a hydrsemic plethora. He 
 calls to his aid the oliguria which generally accompanies oedema. 
 And yet in absolute anuria, such as is produced in the obstruc- 
 tion of the two ureters by calculi, anasarca is exceptional. I do 
 not know how oedema is produced in albnminuria, but the 
 hypothesis of Bartels seems to me to be inadmissible. 
 
 In a goodly number of cases we must take into consideration 
 both vascular and cardiac disturbance, but in interstitial nephri- 
 tis, in which cardiac lesion is the rule, we find little oedema, and 
 in amyloid degeneration, where the heart is normal, dropsy is 
 extreme. Yet some have thought that the hypertrophy of the 
 heart was compensatory to the renal impermeability ; at any 
 rate, it may be said that the heart is a dangerous auxiliary, 
 for grave accidents may result from this so-called providential 
 lrypertroph} r . 
 
 We see in certain cases lesions of the kidney, heart, and 
 vessels develop simultaneously ; all the vascular system is seized, 
 from the central organ of the circulation up to the finest extrem- 
 ities; and if the kidney can suffer from such a delicate symptom 
 as albuminuria, we have no right to disregard, on that account, 
 the sufferings of other organs. We know bow modifications of 
 the cardio-vascular S3 r stem bring about secretoiy disturbance in 
 the digestive canal, a dryness and a condition of prurigo of the 
 skin, which may be the consequence of a nutritive affection of 
 the terminations of the nerves in the skin. As the result of 
 vascular lesions we also observe hemorrhages, epistaxis, htem- 
 atemesis, entorrhagias, cerebral haemorrhage, and purpura. 
 
 All this is not allied to uraemia ; it is all beyond intoxica- 
 tion, and shows itself when the urine has still a normal density 
 or is raised, and when its quantity is increased, normal, or 
 slightly diminished. 
 
 All the foregoing accidents being eliminated, we ask what 
 remains to cause intoxication? It will be quite legitimate to 
 attribute to it one part only of the phenomena which might 
 supervene when the impermeability of the kidney is such that
 
 106 LECTURES ON AUTO-INTOXICATION. 
 
 it can no longer eliminate the toxic substances produced by the 
 organism in proportion to their formation. 
 
 Testing the urinary toxicity would -give us sufficient infor- 
 mation on this point, but it is a method little practiced, and at the 
 bedside we are in the habit of making estimations upon the total 
 quantity of urine eliminated in twenty-four hours and upon its 
 specific gravity. If the quantity and density remain normal we 
 have the right to say, from these facts, that the kidneys func- 
 tionate normallj 7 . If both are diminished, there is a danger of 
 intoxication. 
 
 We must not, in this estimation, take for our type the quan- 
 tity of urine secreted by a health)' man ; a sick man ingests 
 and destroys little. The numbers e.g., of 1350 cubic centi- 
 metres as the quantity and 1019 as the density are too high for 
 a patient ; they are only normal in a man who is walking about 
 and eating well. Lastly, the quantity and the density may 
 balance each other in a certain measure. 
 
 However it may be, all the accidents of nephritis of which 
 we have hitherto spoken are produced during a period in which 
 the urine is still normal in quantity and density. Retinitis, amau- 
 rosis, inflammation of serous membranes, and phlegmons appear 
 at a period already advanced. And yet there is nothing to show 
 that the retinites are uraemic accidents of the same nature as the 
 respiratory disturbances, or coma and convulsions. I admit 
 that, in individuals who retain their toxic products, all the cells 
 of the organism have a weakened vitality, only bordering upon 
 inflammation which has not resolved. But these incomplete 
 phlegmasias, cadema of glottis, hnemorrhagic and purulent peri- 
 carditis, are, at any rate, only accidents further removed and 
 indirectly due to intoxication. They denote simply a cachectic 
 state, of which poverty of blood and insufficient alimentation 
 are the principal factors. 
 
 Yet, after having eliminated from the category of uraemia 
 all these symptoms, all the accidents that we have just reviewed, 
 we come to others which, in the advanced periods of chronic 
 nephritis or in the course of acute nephritis, directly flow from 
 renal imperfection which has become excessive. Beyond that 
 we enter into the domain of intoxication.
 
 PATHOGENESIS OF URJEMIA. 107 
 
 We find ourselves in the presence of an intoxication which 
 may be due to one of the seven poisons, which analysis of the 
 products of toxicity has revealed to us, or to several amongst 
 them, associated two by two, three by three, or to all the seven 
 together ; finally, water (the elimination of which may be pre- 
 vented) may play a part in the morbid accidents. It appears 
 impossible that there should be one form of uraemia only. 
 Already clinically there have been described for a long time 
 different symptomatic forms. Perhaps there is a place in patho- 
 genesis for the five following theories, which include (1) cere- 
 bral oedema (Traube) ; (2) urea (Wilson) ; (3) ammonia 
 (Frerich) ; (4) extractive matters (Schottin), and, notably, 
 oxalic acid (Bence-Jones), urochrome (Thudicum), and (5) 
 potass (Feltz and Hitter).
 
 LECTURE XII. 
 
 PATHOGENESIS OP URAEMIA DISCUSSION OP THE EXCLUSIVE 
 THEORIES. 
 
 The uraemic period of nephritis is characterized by the appearance of chronic 
 or paroxysmal nervous accidents, cephalalgia, dyspnoea of the Cheyne- 
 Stokes type, convulsions, coma, associated or not with disturbances of 
 calorification and with other symptoms of the pre-uraemic period; for 
 
 example, cedemas. Clinical observation has established several modes of 
 
 grouping of symptoms of the uraemic phase whilst seeking to relate them to 
 
 certain anatomo-pathological forms. Every inventor of a pathogenic 
 
 theory has appealed to bedside observation for a justification of his opinion. 
 
 Traube incriminated, as the cause of uraemic accidents, the cerebral 
 
 oedema which might result from hydraemic plethora. His opinion is awant- 
 ing in anatomo-pathological proofs, and rests rather upon inadmissible 
 
 physiological arguments. Wilson invoked excess of urea in the blood. 
 
 Urea cannot explain accidents in the quantity in which it exists in the blood 
 of uraemics. Injection of urea into the stomach, into the cellular tissue, 
 into the veins after nephrectomy. 
 
 I HAVE shown that many of the accidents called ursemic 
 happen at a period of nephritis in which the retention of toxic 
 products is inadmissible. As long as the urine is of sufficient 
 quantity and has a density high enough, there is no intoxica- 
 tion. The question of uraemia can only be argued from acci- 
 dents happening at a time beyond that in which imperfection of 
 the kidney has become excessive, such as when it eliminates 
 no longer, in twent3 7 -four hours, the toxic products introduced 
 into the organism or formed by it during this length of time. 
 Then we may see a series of chronic or paroxysmal nervous 
 accidents happen, characterized by pain in the head, dyspnoea 
 of the Cheyne-Stokes type, vomiting, diarrhoea, convulsions, 
 and coma, at the same time as a certain number of accidents of 
 the preparatory period persist. We still find cedemas, which 
 increase or diminish ; alterations of temperature ; sometimes 
 hypothermia, which may fail and give way to hyperthermia. 
 
 The nervous accidents may be isolated or associated ; and 
 already, from this point of view, as from that of the co-exist- 
 ence of unusual symptoms, the presence or absence of low tem- 
 perature, cases of uraemia, observed clinically, seem so different 
 (108)
 
 DISCUSSION OF EXCLUSIVE THEORIES. 109 
 
 the one from the other that we must think of the existence of 
 various and mixed pathogenic conditions. Very likely we have 
 to do not with one intoxication only, but with numerous causes, 
 which may be isolated or associated ; so that if one explanation 
 holds for one case it does not necessarily hold for others, and 
 a false theory in one case may not be so in others. If we wish 
 to include the whole pathogenic study of uraemia, we must be 
 persuaded that we cannot offer one explanation alone of all the 
 nervous accidents which may appear in the course of disease of the 
 kidne} r . Besides, clinical observation has endeavored to group a 
 certain number of particular cases, according to their symptom- 
 atic resemblances, by calling to its aid pathological anatomy. 
 
 There exists a symptomatic form, characterized by early 
 dropsy of the anterior surface, developed a long time ago or 
 just a short time previously. We have seen oedema increasing, 
 the urine becoming less abundant, its density increasing (a 
 greater quantity of solid matter being found in each unit by 
 weight), or remaining the same. The patient has neither diar- 
 rhoea, vomiting, nor any other flux capable of carrying away 
 water, and there is oliguria ; there is, therefore, retention of 
 water in the organism. The other normal secretions continue ; 
 the tongue is moist. We in vain seek for the presence of ammo- 
 nia in the expired air. In these cases are found reunited all the 
 conditions of hydraemia or of hydraemic plethora. The urine 
 continuing to carry away the total quantity of solid matter which 
 ought to be eliminated by the kidneys, it is impossible to ex- 
 plain, by the theory of intoxication, the accidents which arise. 
 There is, on the contrary, an undoubted accumulation of water 
 in the organism. Thus, the idea has arisen that the accidents 
 called uraemic are due to an accumulation of water. 
 
 Traube has actually thought that the consequence of l^drae- 
 mia was a tendency to the production of oedema, and, notably, 
 to cerebral oedema. Coindet and Odier have seen there suf- 
 ficient conditions to explain the development of a ventricular 
 dropsy. According to their manner of viewing the subject, 
 interstitial oedema or ventricular drops} 7 , by compressing the en- 
 cephalon within and without, diminishes the space left free for 
 the blood ; hence cerebral anaemia involving the production of
 
 110 LECTURES ON AUTO-INTOXICATION. 
 
 comatose conditions when the anaemia is especially marked at the 
 level of the convolutions, or convulsions if it predominate in 
 the mesencephalon. 
 
 If we wished to furnish, like Traube, a general explanation 
 of the facts reputed to be ursemic, his theory would be false ; and 
 it is so in effect, as he has formulated it. Indeed, in the large 
 majority of cases followed up by an autopsy cerebral oedema, 
 ventricular dropsy, and cerebral anaemia are wanting. And not 
 only has evaporation not demonstrated the existence of a larger 
 proportion of water in the tissues of the brain than normally, 
 but in place of anaemia it is easy to establish congestion pushed 
 to the point of extreme fullness of blood-vessels and to ecchy- 
 moses. These are the cases that disprove his theory. But, 
 besides, this must hold good for all cases or its falsity is not 
 demonstrated ; otherwise, it remains a pure hypothesis which 
 does not rest upon any foundation of direct observation. It is 
 untrue even as a theory, for a certain number of physiological 
 arguments invoked by Traube are inadmissible. 
 
 In a large number of cases we see ursemic accidents produced 
 in patients who are eliminating water in excess ; their urine is 
 more than the normal in quantity, and they have evacuations 
 from the stomach and intestines. 
 
 Hydraemia should have, as an effect, osdcma ; but it would 
 be necessary to demonstrate experimentally this relationship, 
 for neither experimental pathology nor clinical observation 
 confirms it. 
 
 Double calculous obstruction, suddenly developed, produces 
 uraemic accidents, at the end of a recognized time, without 
 inducing oedema. Thus is found broken one of the links in 
 the chain of reasoning of Traube. 
 
 Richardson has injected into the peritoneum of a dog a 
 quantity of water equivalent to one-fifth of the weight of the 
 animal. He has produced everj'thing but intoxication. He 
 has caused death by septicaemia, rendering possible, thanks to 
 the modifications which the injection had suddenly brought 
 about in the tissues, the escape of some infectious agent from 
 the digestive tube or from without, and which has become 
 capable of producing septicaemia.
 
 DISCUSSION OF EXCLUSIVE THEORIES. Ill 
 
 But, in what disease of the kidneys do we flnd in the body 
 such an accumulation of water? 
 
 Falck has injected the same quantity of water into the veins ; 
 he has seen convulsive accidents and death ; but these, we might 
 say, from the point of view of experimental pathology, are mon- 
 strous operations which are not at all comparable to pathological 
 facts. It is the exaggeration of a legitimate demonstration. 
 
 We may inject water into the blood in considerable quantity. 
 Death results from this injection when we have introduced into 
 the blood 122 grammes of water per kilogramme of animal, in 
 which case the density of the serum of the blood falls to 1007 ; 
 but the density of the serum of the blood in those the subjects 
 of uraemia falls seldom, if ever, below 1016. In the experiment 
 of Richardson and Falck the blood is nothing more than a 
 diluted blood. There come no longer into the capillaries any- 
 thing but swollen globules, deprived of haemoglobin and inactive. 
 How can we compare this excessive hy^lraemia with the moderate 
 retention of water in the blood which may exist in pathological 
 cases ? In absolute anuria uraemic accidents burst forth some- 
 times before the fifty-sixth hour, when a man has not as yet accu- 
 mulated more than 35 grammes of water per kilogramme of his 
 weight. But we know that injections of water only begin to be 
 injurious after 90 grammes per kilogramme. 
 
 It has not only been shown that the viscera may be invaded 
 by oedema. Bartels has proved, at any rate, that pulmonary 
 oedema does not exist in those suffering from uraemia. 
 
 Let us accept, however, if you please, cerebral oedema. I 
 am ready for all. concessions. But then it will be no longer a 
 question of intoxication. If this oedema has nothing to do with 
 the retention of solid matter it enters into the category of the 
 phenomena which we have previously eliminated from the list of 
 uraemia ; they are part of the mechanical accidents of nephritis, 
 and are improperly included amongst chemical accidents. 
 
 But, are there any chemical and toxic accidents in Bright's 
 disease? 
 
 We can furnish proof j'es, direct proof of this. Uraemic 
 patients are those whose urine has lost its toxicity. We have 
 seen renal elimination diminish in quantity and the density of
 
 112 . LECTURES ON AUTO-INTOXICATION. 
 
 urine fall, and we have been forced to believe that, the whole of the 
 solid substances 110 longer being eliminated, the individual was 
 going to become intoxicated. But on the day in which nervous 
 accidents called ursemic appear the urine ceases to be toxic. 
 The whole of the urine of twenty-four hours from a ursemic 
 patient cannot kill a rabbit, nor does it exceed the toxicity of 
 distilled water. And yet, whilst with 120 cubic centimetres of 
 distilled water per kilogramme of animal, used as an intra-venous 
 injection, you are in danger of inducing death, with this same 
 dose of certain urines taken from ursemic subjects you will deter- 
 mine no phenomenon, not even the pupillary contraction caused 
 by normal urine. 
 
 There yet remains to be known what is or what are the poisons 
 which determine the toxic and chemical accidents of ursemia. Let 
 us return for a moment to hypotheses. In the first line is placed 
 the old hypothesis of Wilson, which has recently been revived, 
 and according to which the accidents called ursemic would be 
 caused by the accumulation of urea in the blood. It is no longer 
 sufficient to say that the urine of those suffering from ursemia con- 
 tains less urea. It has been shown that there was in the blood as 
 much as thirty-two times more urea than in the normal state ; that 
 in the muscles there was as much as 1.20 grammes instead of 
 simply traces of it. I have met with it, amongst those suffer- 
 ing from choleraic anuria, in the tissues where it is not formed 
 normally. The theory, therefore, would be legitimate save for 
 its demonstration. 
 
 Gallois has injected into the stomach, Treitz into the veins, 
 and Richardson into the cellular tissue, large doses of urea. 
 Grehant and Quinquaud have likewise injected it into the cellu- 
 lar tissue. These last observers have seen toxic accidents. 
 Treitz, who had made injections into the veins, has not observed 
 anything. Hammond practices nephrectomy and then makes an 
 injection of urea, the animal dies. The experiment of Ham- 
 mond is repeated by Frerichs, Oppler, and Petroff, and these 
 conclude that after nephrectomy the animals, into which they 
 injected urea, do not die more quickly. This contradiction was 
 so singular that Feltz and Hitter have repeated the experiment. 
 They have at length induced death as speedily in healthy
 
 DISCUSSION OF EXCLUSIVE THEORIES. 113 
 
 animals as in those upon whom they had performed nephrec- 
 tomy. They employed urea which they had sent from Ger- 
 many, so as to have it purer. The verification made, it con- 
 tained sulphate and chloride of ammonia. Hitter began to 
 prepare pure urea himself, and, setting out from the day in 
 which he made injections with this urea, he no longer deter- 
 mined accidents. Such is, perhaps, the explanation of the 
 contradiction between various experimenters. 
 
 As for myself, relying upon my own experiments, I say that 
 urea, in the quantity in which we meet with it in the organism, 
 in pathological states, cannot be invoked to explain the acci- 
 dents called ursemic. 
 
 In order to kill a man it would require the quantity of urea 
 which he makes in sixteen days. But, in double calculous 
 obstruction, suddenly developed, uraemic accidents appear 
 sometimes at the end of the second day or at the commence- 
 ment of the third at the time that man has not yet made the 
 eighth part of that amount of urea which is necessary in order 
 to cause death. But during that time, as we know, he has been 
 able to accumulate sufficient of other toxic substances to bring 
 about intoxication. Clinical observation is here, therefore, com- 
 pletely in accordance with experimentation in denying to urea 
 the power of producing the intoxication called uraemic.
 
 LECTURE XIII. 
 
 PATHOGENESIS OF URAEMIA DISCUSSION OP THE EXCLUSIVE 
 THEORIES. 
 
 Theory of ammoncemia (Frerichs). Is the carbonate of ammonia resulting 
 from the breaking up of urea in the blood the cause ? Is urea transformed 
 into carbonate of ammonia in the digestive canal ? (Bernard and Grandeau, 
 Treitz, Jaksch.) Objection to the theory of ammonsemia as the absolute 
 
 explanation of ursemic accidents. Theory which incriminates extractive 
 
 substances; that of Schottin, Scherer, Oppler, Chalvet. Creatincemia of 
 Jaccoud. Examination of the possible action of each of the extractive sub- 
 stances, uric acid, hippuric acid, creatin, creatinin, leucin, tyrosin, taurin, 
 xanthin, hypoxanthin, guanin. Theory which invokes the coloring sub- 
 stance, urochrome (Thudicum). Element of truth which it contains. 
 
 THE clinical fact of which we are going to seek the explana- 
 tion is this : The co-existence of nervous disturbances, called 
 ursemic, with a diminution of the solid matter contained in the 
 urine of twent} r -four hours, a diminution proved by the volu- 
 metric examination of the whole of the urine of twenty-four 
 hours and the examination of its densit3 r . 
 
 I have shown that this diminution of solid matter of the 
 urine had for its corollary the retention of toxic material, since 
 I have proved the harmlessness of the urine passed by uraemic 
 subjects. 
 
 After this, whilst reviewing the various hypotheses which 
 have been built upon the nature of the poison or poisons, the 
 retention of which produces uraemic accidents, I have combated 
 the theory which recognizes this poison in urea; not that I deny 
 the toxicity of urea (I admit that of distilled water), but because 
 I am certain that urea cannot be toxic in the dose in which it 
 exists in the blood of unemic patients. 
 
 Urea being thus dethroned, we can conceive how, incapable 
 as it is of causing injury by itself, it may become harmful after 
 having undergone transformation. Frerichs has advanced the 
 theory that the carbonate of ammonia resulting from the disinte- 
 gration of urea is the pathogenetic poison of uraemia ; such is the 
 (114)
 
 UREMIA NOT DUE TO AMMONIA. 115 
 
 theory of ammonsemia. As was said when discussing oedema, 
 some have twisted the clinical aspect, in order to give a symptom- 
 atic entirety which would appear to be in accordance with theory. 
 It has been said that a particular form of uraemia shows itself 
 in those suffering from albnminuria without oedema, but having 
 diarrhoea and vomiting and with dry tongue. Then supervene 
 severe eclamptic accidents. The urine is scanty, and of little 
 density. Some may have found ammonia in the blood, and 
 the ammoniacal exhalation of the breath has been sometimes 
 established. Here, then, is a theory which stands well simply 
 as a theor}'. Yet let us see, for a little, some of the details. 
 One thing alone is convincing in this picture, the diminution 
 in the quantity and densit}' of the urine. But the retention of 
 ammonia is insufficient to explain this diminution of the density. 
 The presence of ammonia in the urine, although it is denied 
 still by many authors, is really and simply a trace, especially 
 at certain hours of the day. When I was physician at the 
 Bicetre, eight years ago, I established the presence of ammonia 
 in the urine after meals composed of roasted meat, that is, 
 alimentary ammonia ; otherwise, these ammonurias consequent 
 upon meals are feeble. 
 
 The presence of ammonia in the expired air belongs to a 
 large number of pathological and even normal cases ; it is suf- 
 ficient that there may have been diyness of the throat and of 
 the mouth, owing to diminution of the secretions. 
 
 We have met with ammonia in the blood of some who were 
 the subjects of uraemia, but normal^ we find traces of it in the 
 blood ; there is constantly some of it in the blood of cadavera. 
 There is nothing, therefore, to authorize the incrimination of the 
 transformation of urea into carbonate of ammonia. Besides, if 
 urea is transformed into carbonate of ammonia, it is not by the 
 phenomenon of retention, it is by a fact of faulty nutrition. 
 
 But if nothing authorize the admission of this transforma- 
 tion as the cause of unemia, here is what authorizes its rejec- 
 tion. When we inject urea into the blood, it is eliminated in its 
 entirety in twenty-four hours, without the ammonia of the urine 
 being increased (Feltz and Ritter). The amount of urea found 
 in the urine exceeds but slightly that of the injected urea ;
 
 116 LECTURES ON AUTO-INTOXICATION. 
 
 besides, normal urea, owing to its diuretic action and by its 
 bathing the tissues better, leads to the elimination of an excess of 
 urea; but we do not find ammonia in the urine, or not more than 
 in the normal state. Therefore, the theory of Frerichs is wrong. 
 
 Bernard and Grandeau, Treitz, and Jaksch have thought that 
 urea may be transformed into carbonate of ammonia, not in the 
 blood, but in the digestive canal, after having passed through 
 the intestinal wall. But the renal path is the natural channel 
 of elimination, and so elective is it for urea that it is all but 
 impossible that it should take any other. Urea is eliminated fifty 
 times more quickly by the kidney than by any other emunctory. 
 If 1 kilogramme of blood contains 16 centigrammes of urea, 1 
 kilogramme of urine contains 16 grammes. But it is the plasma 
 of the blood which delivers the urea, and 1 kilogramme of plasma 
 contains 32 centigrammes of urea, fifty times less than the urine 
 contains. Urea, as I have said, passes through the kidney in 
 the ratio of 52, while water is as 1. As regards the other organs 
 of elimination, on the contrary, through the wall of the 
 stomach, for example, the filtration of urea is just the same as 
 for water. The liquid secretion contains urea and water in the 
 same proportion as the plasma of blood. 
 
 Blood cannot, therefore, carry to the stomach and intestine 
 sufficient urea for its transformation to explain intoxication. 
 In 1872 and 1873 I have shown this fact, apropos of hysterical 
 vomiting, attributed wrongly to ischuria or anuria. 
 
 As for invoking the disintegration of urea, in order to 
 explain the presence of ammonia in the digestive canal, it is 
 quite useless. There is enough of it normally, without the inter- 
 vention of urea. Can we say that ammonia may not play some 
 other part in uraeinic accidents ? I only say that ammonaemia is 
 not an explanation applicable to the whole of the facts of 
 uraemia, and that neither in the intestine nor in the blood can 
 urea produce ammonia in sufficient quantity to bring about 
 intoxication. 
 
 Nevertheless, ammonaemia may be produced in cases of abso- 
 lute retention by the kidney. Ammonia is toxic, in moderate 
 doses, like potass ; it produces convulsions and a great fall of 
 temperature. This symptom, which ammoniacal intoxication
 
 UR2EMIA AND THE PRESENCE OF EXTRACTIVES. 117 
 
 produces in the highest degree, is only an accident contingent 
 to certain uraemias. It may be, therefore, that ammonia belongs 
 to the number of toxic substances the accumulation of which 
 in the economy causes accidents, but it is not demonstrated that 
 the uraemic accident can be explained by the presence of am- 
 monia in the blood. We reject ammonaemia as the absolute 
 explanation, whilst admitting that it may be the key to certain 
 peculiarities, to some of the special symptoms of uraemia, and 
 that it may particularly arise in cases where intestinal fermenta- 
 tion is increased. Hypothermia is produced by normal urine, 
 but this, once it is filtered through charcoal, loses this property. 
 Urinary ammonia passes through the filter whilst the substance 
 which determines hypothermia is fixed on the charcoal. The 
 hypothermia of certain uraemias is not, therefore, capable of 
 being attributed to ammonia. 
 
 There exists in urine a group of bodies which are not all 
 named, and which are confounded under the title of extractive 
 substances. By degrees we recognize the chemical characters of 
 some of them, so much so that the unknown part of the 
 extract becomes gradually less and less. For a long time, now, 
 have these extractive substances been incriminated by Scherer, 
 Schottin, Oppler, Perls, and Chalvet. In this way has the 
 theory of poisoning by extractive substances originated which 
 Jaccoud has formulated, under the name of creatinaemia, with- 
 out accusing more particularly creatin, except in symbolizing, 
 under this category, the toxic action of all the group. 
 
 Clinical observation, which has pretended to give support to 
 the different theories, brings to this its array of -observations; 
 but, if we examine the facts cited as bearing upon poisoning by 
 extractive substances, for example, those of Chalvet, who has 
 demonstrated in these cases the increase of extractive matters 
 in the blood, we do not see such or such a clinical symptom 
 predominate. It is the picture of uraemia complete in all its 
 forms, with the exception of this form of supposed uraemia in 
 which the urine contains in twenty-four hours a quantity of 
 solids equal or superior to the normal. 
 
 In the cases in which Chalvet and those who share his 
 opinion have spoken, we see the amount of the extractives, of
 
 118 LECTURES ON AUTO-INTOXICATION. 
 
 urea, and coloring matter diminish in the urine ; in the blood 
 extractives increase whilst the toxicity of the urine diminishes, 
 as I have shown. That is true uraemia. .Well, let us see what may 
 be, from the point of view of the production of toxic accidents, 
 the action of each of the organic substances taken from this 
 group of extractives : 
 
 Uric acid is not toxic in the dose of 0.64 gramme per kilo- 
 gramme of the animal. Hippuric acid, according to Challon, 
 Feltz, and Hitter, can only become toxic in the quantities formed 
 by the animal in ten to twelve days. I have injected into the 
 veins of the rabbit hippuric acid, dissolved in water by the help 
 of a little soda, in the dose of 4.59 grammes per kilogramme of 
 animal, without inducing the slightest toxic phenomena. This 
 inoffensive amount represents nearly the whole quantity which the 
 animal would have required one hundred days to make. Creatin 
 undoubtedly increases in the blood of individuals who succumb 
 to uraemia (Scherer, Schottin, Hoppe, Oppler). Is the toxicity 
 due to it? Challan finds it toxic, Testut not toxic. Feltz and 
 Ritter have not been able to kill an animal by injecting into it all 
 at once the quantity of creatin which it excretes in seventeen 
 days. Creatin may, therefore, be incriminated still less than urea ; 
 for, if urea can kill when it is injected abruptly into the veins of 
 an animal in the quantity which it would have formed in sixteen 
 days, we do not determine in it, according to my experience, any 
 appreciable toxic accident, by injecting into it the quantity of 
 creatin which it would have formed in seventy-two days. Crea- 
 tinin, which exists in the blood in such small quantity that it 
 appears doubtful to many physiologists, is formed in the kidney 
 by transformation of creatin. Could it be taken up again by 
 the blood, in case of obstruction to the renal excretion ? Feltz 
 and Ritter have proved that the creatinin excreted in six days 
 does not kill, but that death may be caused by the quantity 
 which is excreted in thirteen days. It can, therefore, induce 
 intoxication, if it exist in the blood in sufficient quantity. But 
 it is an energetic base, capable of producing accidents by virtue 
 of its excess of alkalinity. It can only be employed in the 
 form of salts. The chloride of creatinin is hardly injurious ; 
 the quantity of creatinin excreted during ten days, and injected,
 
 UREMIA AND THE TOXICITY OP COLORING SUBSTANCES. 119 
 
 in the form of crcatinin chloride, by .111 intra-venous channel, 
 does not hasten death by one minute, in the case of a dog, after 
 nephrectoiny. Death has been induced on the third day, as 
 ordinarily (Feltz and Hitter). 
 
 Leucin: All that water can dissolve of it produces no acci- 
 dent (Feltz and Hitter). The quantity of tyrosin excreted in 
 three days by sick men is not followed by any toxic effect. 
 Taurin, in the dose of 0.5 gramme per kilogramme of animal, is 
 without effect. Xanthin, hypoxanthin, and guanin do not pro- 
 duce any result either. 
 
 The coloring substances have been incriminated ~by Thudi- 
 cum, on account of the feeble coloration of the urine of those 
 suffering from uraemia. We have seen already that normal 
 urine loses the one-half of its toxicity by decoloration ; decolor- 
 ized bile is also less toxic. The coloring matters are, therefore, 
 suspected by me from their toxicity point of view ; but does not 
 filtration by charcoal remove from the urine any other thing 
 than the coloring substances ? I am not right in saying that the 
 coloring substances are the true the principal cause of the 
 toxicity of urine. Nevertheless, they belong to the group of 
 those organic substances to which we ought to attribute nearly 
 the one-half of this toxicity. I have tried to estimate the 
 degree of toxicity of one of the coloring substances of the 
 urine, viz., nrobiliu. Thrice I have made, in the case of a 
 rabbit, an intra-venous injection of this substance ; thrice the 
 experiment has failed, from want of sufficient quantity of ma- 
 terial. I can only say that, if bilirubin kills, after a dose of 5 
 centigrammes per kilogramme, urobilin, in a dose of 15 centi- 
 grammes, does not kill at all.
 
 LECTURE XIV. 
 
 PATHOGENESIS OP URAEMIA THE PART PLAYED BY ORGANIC 
 SUBSTANCES AND MINERAL MATTERS IN UR^EMIC INTOXICATION. 
 
 Urea represents one-seventh or one-eighth of the total toxicity of urine ; ammo- 
 nia contributes to it a part scarcely appreciable. We can accord to the 
 coloring substances, and others fixeil by charcoal, two-fifths of the toxicity ; 
 but the sum of all the organic matter represents only two-thirds of the total 
 
 toxicity. The .difference is, therefore, made up by the mineral matters. 
 
 Exaggerated statements of Feltz and Ritter, who consider them the sole 
 
 cause of uraemia. -Analysis of the action of various mineral matters. 
 
 Earthy salts ; alkaline salts. Small importance of the salts of soda. Im- 
 portance of the salts of potass (chloride of potassium ; phosphate, sul- 
 phate, and phenylsulphate of potass). Physiological antagonism between 
 
 narcotizing substances and those of an organic and mineral nature, which 
 cause convulsions. The predominance of coma or convulsions in uraemia 
 depends upon the retention of convulsion-causing or narcotizing substances. 
 Uraemia is a mixed form of poisoning, and due to many causes. 
 
 IN recapitulating the bodies in which we recognize a certain 
 toxic power, we find urea, which would represent one-seventh or 
 one-eighth of the total toxicity of urine; ammonia, which is 
 toxic, but in a fraction which escapes us ; those substances which 
 behave in the manner of coloring matters, being, like them, fixed 
 by charcoal, and to which we ascribe two-fifths of the toxicity. 
 Each one of these bodies induces intoxication, and may play its 
 own part ; but the sum of all these organic substances only rep- 
 resents two-thirds of the whole toxicity of the urine. What 
 is, then, the difference necessary to complete this totality ? There 
 remains to us the mineral substances which, according to Feltz 
 and Ritter, would be the exclusive cause of the toxicity. There 
 is evidently fallacy in the statement of these authors, who 
 have made such remarkable researches. They refuse to take any 
 notice of partial or fragmentary intoxications ; they do not wish 
 to admit as a toxic agent anything but one substance alone. 
 This is the vulnerable point of their work. 
 
 These experimenters, who deny that all the toxic action is due 
 to the organic substances, have yet recognized their toxicity ; but 
 they do not take any account of these organic substances, because 
 (120)
 
 UREMIA AND MINERAL SUBSTANCES. 121 
 
 l>y them alone they have not been able to produce death, not 
 having carried the injection sufficiently far, and in strong-enough 
 doses. In the case of an animal dying within three days after 
 nephrectomy, they have said that the cause of death could only 
 be the substance which kills in a quantity equal to that which is 
 normally excreted in three days. Now, since by the extract of the 
 organic substances of the urine of three days the} r have not been 
 able to produce death, they deny to the organic substances every 
 toxic action, without wishing to admit that their partial toxicity 
 could be regarded as an explanation of the complete toxicity. 
 
 Let us see, however, with MM. Feltz and Hitter, what the 
 mineral substances can do ? These are vei\y numerous, but a large 
 number of them can be left out of consideration, on account of 
 their insignificant weight. A man of 75 kilogrammes eliminates 
 in twenty-four hours 1350 grammes of urine, the densit}' of which 
 is 1019. This urine contains 59 grammes of solid matter, which 
 is decomposed into 43 grammes of organic matter and 16 
 grammes of mineral. These last are composed of 2 grammes of 
 earthy salts (salts of lime and magnesia), 4 grammes of salts of 
 potass, and 10 grammes of salts of soda, including in these 
 weights the acids of the bases. If we state these as being the 
 figures for the composition of a litre of urine, we have : 
 
 finlkl mittpr 44 PTimTnps S Organic, 32 grammes. ( Earthy salts, 1.50 grammes, 
 lid matter, grammes, j Mineral) 12 grailimes . ) Salts of potass, 3.00 grammes. 
 
 ( Salts of soda, 7.50 grammes. 
 
 The whole of the earthy salts do not come out well in experi- 
 ment, on account of the difficulty which there is in maintaining 
 them dissolved in the blood-plasma by intra-venous injection. I 
 cannot, therefore, say anything about them. Besides, they are 
 in small quantity in the mineral mass. The alkaline salts, on 
 the contrary, are verj' soluble. They are of large quantity, and 
 deserve our attention. 
 
 The salts of soda seem the more important on account of 
 their weight. In reality they have only a feeble toxicit}-. Chlo- 
 ride of sodium kills 1 kilogramme of animal, in the dose of 5.17 
 grammes; but chloride of sodium is the most toxic of the salts 
 of soda of the urine. The soda of the urine of twent3'-fotir 
 hours would kill, at the outside, 2 kilogrammes, whilst this 
 quantity of urine kills 30.
 
 122 LECTURES ON AUTO-INTOXICATION. 
 
 It is otherwise with the salts of potass. They are occa- 
 sionally present in large quantity, 3 milligrammes per cubic 
 centimetre of urine. Forty to sixty cubic centimetres of urine 
 being toxic (the mean 45), the quantity of urine which kills one 
 kilogramme of animal would contain nearly 13 or 14 centi- 
 grammes of salts of potass. This would be nearly a suffi- 
 cient quantity if all the salts of potass were represented by 
 chloride of potassium ; but there are the phosphate, sulphate, 
 and phenylsulphate of potass, which do not have the same 
 toxicit}^. The chloride of potassium is the most toxic ; it kills 
 in the proportion of 18 centigrammes per kilogramme of animal. 
 But the phosphate of potass only determines toxic accidents 
 after a dose of 26 centigrammes. With the phenylsulphate we 
 have seen toxic accidents, but not death. These differences of 
 toxicity explain to us that the mixture of the salts of potass 
 gives a less toxicity than the chloride of potassium. 
 
 Like Feltz and Hitter, I have destroyed the organic matter 
 of urine and dissolved the mineral substances, and I have noticed 
 that frequently, contrary to their statements, the salts of potass 
 contained in 50 cubic centimetres of urine do not induce any 
 accident, but that accidents arise if -we take the salts of potass 
 contained in a double quantity of urine. In order to kill, there 
 is required sometimes a qantity of potass double that which the 
 usual quantity of urine causing death contains. Besides, this 
 quantity of potass kills in quite another way, with convulsions ; 
 whilst normal urine, taken during the height of the day, does 
 not induce convulsions. In death by potass the heart is arrested ; 
 it continues to beat, however, when it is urine which has caused 
 the poisoning. A normal, decolorized urine which still contains 
 nearly all its potass does not kill, even when we increase the dose 
 by one-half, and then it kills without convulsions ; in spite of 
 the larger dose, the action of potass remains obscured. 
 
 We have already spoken of these toxic associations which 
 exist in urine. The convulsive substance insoluble in alcohol, 
 when added to that which is soluble in alcohol, does not give 
 rise to convulsions. It is the result of a physiological antago- 
 nism. A substance which determines convulsions is neutralized 
 by another organic substance which produces narcosis, and this
 
 INFLUENCE OF POTASS. 123 
 
 association of the two hinders the appearance of convulsions. 
 There is an antagonism between the narcotic substances soluble 
 in alcohol and the convulsive substances which are insoluble; 
 a possible antagonism, too, between the first and potass. The 
 equilibrium resulting from the antagonism between these various 
 substances may be broken by increasing either the potass or the 
 convulsive organic substance. There are pathological urines 
 which, though decolorized, retain their convulsive power; this 
 is perhaps due to the potass. Convulsive urines are especially 
 febrile urines, since there is suppression of alimentation and an 
 increase of cellular destruction. 
 
 The diminution of alimentation does not introduce more 
 potass into the economy ; it diminishes the totality of the min- 
 eral salts. But the increase of disassimilation augments certain 
 nitrogenous substances, and particularly potass, by destroying 
 the mineral frame-work of the cells. Also, whereas potass only 
 represents one-fourth of the whole mass of the mineral sub- 
 stances, we find potass present in quantity at least equal to the 
 soda. If urine become scant} 7 , if, instead of 1000 grammes, 
 the secretion falls to 500, admitting the specific gravity to be 
 equal or higher even than the normal, the quantity of mineral 
 matter which it carries away may be equal to the normal, per 
 litre, but not for the twenty-four hours ; the emunction falls to 
 one-half or two-thirds of that which it ought to be ; there is 
 produced in the organism an accumulation of mineral substances, 
 particularly potass. This may then become a cause of intoxica- 
 tion ; for the substances which are antagonistic to it in the nor- 
 mal state no longer suffice to neutralize its convulsive action. 
 We know that, amongst ursemic phenomena, there may be, in 
 certain conditions, a predominance of the action of potass, which 
 may represent two-thirds of the toxicitj 7 , instead of one-third. 
 
 The study of the accidents which arise from intoxication by 
 potass leads up to the denial to it of the role of its being the sole 
 cause of uraemia. There are summed up in this word convul- 
 sions and death in opisthotonos ; but we observe neither con- 
 traction of the pupil, diuresis, low temperature due to dimin- 
 ished calorification, nor salivation. All the salts of potass kill 
 with stoppage of the heart, which urine does not.
 
 124 
 
 LECTURES ON AUTOINTOXICATION. 
 
 Thus I admit that potass is toxic, but not that urines are 
 rendered toxic by it alone. If we seek in clinical facts some 
 reasons for or against the exclusive pathogenic role of potass, 
 we find in uraemia reasons to reject the affirmation. First, we 
 must show that in those suffering from uraemia there is an accu- 
 mulation of potass ; but observers who have believed that they 
 have found this in excess have estimated their dosage upon the 
 total quantity of blood. Now, what is toxic in the blood can 
 only be what is in solution in the plasma; what is held as a 
 constituent part of the living cell by force of tension cannot 
 take any part in toxic actions. There is in serum only traces 
 of potass. In the researches, otherwise insignificant and con- 
 tradictory, which have been made upon the variations of potass, 
 we have taken notice of the serum and of the globules, which 
 are so richly provided with it and so strong in their affinity for 
 it. Suppose even that there is an accumulation of potass in the 
 blood-plasma ; it would not explain the unemia, in which there 
 are only convulsions ; it would not explain the subjective symp- 
 toms which precede those or accompany them, narcosis ; ursemic 
 coma; pupillary contraction, which is a prominent phenomenon 
 in uraemia (a circumstance impressed upon me during the course 
 of the last cholera epidemic). All these symptoms intoxication 
 by the whole of the substances of the urine explains, but not 
 by potass. We can appreciate the relative toxicitj" of the prin- 
 cipal mineral substances of the urine from the following table, 
 which I have taken from experiments made in common with M. 
 Tapret : 
 
 NAME OF SUBSTANCE. 
 
 Index of 
 Solution. 
 
 Quantity of Substance 
 Necessary to Kill One 
 Kilogramme of Animal. 
 
 Chloride of potassium, 
 
 
 
 Sulphate of potass, . . . . 
 
 
 
 Phosphate of potass, ... . . 
 
 
 0.263 gramme 
 
 Chloride of sodium 
 
 ttV 
 
 
 Sulphate of soda, 
 Phosphate of soda, 
 
 ? 
 
 9.00 grammes. 
 
 Chloride of magnesium, .... 
 
 ? 
 
 
 Sulphate of magnesia 
 
 
 
 Chloride of calcium, . 
 
 
 , gramme. 
 
 
 
 '
 
 ORGANIC SUBSTANCES AND MINERAL MATTERS. 125 
 
 If we apply these facts to the results of the analyses of urine 
 of man, we arrive, by means of calculations, of which I shall 
 spare you the details, at the following results : 
 
 One kilogramme of man eliminating in twenty-four hours a 
 quantity of urine capable of killing 461 grammes of animal, the 
 proportional part of the mineral matter in this toxicity may be 
 indicated as follows : potass kills 217 grammes ; soda, 30 
 grammes ; calcium, 10 grammes ; magnesia, 7 grammes. The 
 whole of the mineral matter kills 264 grammes. On the other 
 side, urea kills 63 grammes. There remains to be destroyed 134 
 grammes. We know from other experiments that normal urine 
 leaves behind in charcoal one-third of its toxicity ; that charcoal, 
 consequently, retains matter which must be capable of killing 
 154 grammes. Amongst these substances fixed in charcoal 
 there is one-sixteenth of the total potass ; this fraction of potass 
 would kill 14 grammes. The organic substances capable of 
 being fixed by charcoal would therefore be capable of killing 
 140 grammes. This figure passes by 6 be3'ond the 134 grammes 
 which remain to produce intoxication. That is due to errors 
 inherent in all these estimates; the cause of it maybe in the 
 charcoal being able to fix a part of the urea or some mineral 
 matter other than potass ; it may finally be explained by the 
 urine containing poisona which are antagonistic, a fact which 
 we have placed beyond doubt. 
 
 We may say that 1 kilogramme of man eliminates in twenty- 
 four hours organic matter, capable of being fixed by charcoal, 
 which is able to destroy at least 134 grammes of animal. These 
 substances (coloring, extractives, or alkaloids) represent 30 
 per cent, of the total toxicity. It is to these substances, still 
 undetermined, that hereafter the effort of chemistry should be 
 directed. We know of them only what physiology has taught 
 us, the one contracts the pupil, another is convulsive, and the 
 third lowers the temperature. Chemistry will also have to iso- 
 late, in the alcoholic extract, the narcotic substance and the sali- 
 vating, which is perhaps toxic. I have thought that the alkaloids 
 will only explain a very small portion of these 30 per cent, of the 
 toxicity attributable to undetermined bodies. 
 
 In any case, we have come to this conclusion : It is that the
 
 126 LECTURES ON AUTO-INTOXICATION. 
 
 whole of the mineral substances reckon, at the most, as 57 per 
 cent, of the urinary toxicity, and that potass explains, at the 
 most, 47 per cent, of this toxicity. Thus, uraemia comprises vari- 
 ous and multiple intoxications, to which are attributable various 
 symptoms. It is a mixed poisoning, not by urine (as one calls 
 it by misapplication of words), but by what should have become 
 urine ; for the accidents from the retention of urinary substances 
 are not those from the re-absorption of urine. The sources of 
 uraemia are: disassimilation, a certain number of secretions, 
 alimentation, especially the alimentary mineral substances, 
 and, lastly, intestinal putrefactions. The knowledge of these 
 origins of uraemia furnishes, as we shall see, valuable indications 
 from the point of view of treatment.
 
 LECTURE XV. 
 
 THE THERAPEUTIC PATHOGENESIS OP URAEMIA. 
 
 Resumt of the pathogenesis of uraemia considered as a complex intoxication and 
 due to poisons resulting from disassimilation, furnished by alimentation, the 
 
 biliary secretions, and intestinal putrefactions. The renal emunction, 
 
 having become insufficient, may be supplemented by other apparatus, the 
 skin and lung ? Baths of hot and dry air ; vapor baths. Sudorific medica- 
 ments. These methods have the fault of diminishing the renal secretion. 
 
 Means destined to arouse the renal function, either by reducing congestion of 
 the kidneys (revulsives, cupping, sinapisms) or by accelerating ,reflexly the 
 renal circulation (utility of dry cutaneous friction). Action of medicaments 
 called diuretics (caffeine, digitalis). Indications, counter-indications, and 
 management of digitalis in nephritis. Cold injections as a diuretic ; cool 
 
 drinks. Urea as a diuretic medicine. Can we supplement the kidney by 
 
 utilizing, as an emunctory, the mucous membranes of the digestive canal ? 
 Vomitings : their inconveniences. Purgatives : the dehydration of the tissues 
 
 which they produce may become dangerous. Of bleeding : it removes 
 
 from the blood one-sixteenth of the extractive material which the urine 
 ought to throw out. A bleeding of 32 grammes removes as much poison as 
 280 grammes of diarrhoeic liquid, and as 100 litres of perspiration. Utility 
 of bleeding supported by clinical experience. Its formal indication in 
 acute curable nephritis. Its employment owing to its being the best and a 
 
 rapid expedient in the terminal uraemia of chronic nephritis. Antidotes 
 
 to uraemic poisons. Inhalations of chloroform. Action of chloral. Bromide 
 of sodium. Traditional and pathogenic therapeutics. Milk regimen to 
 diminish biliary secretion and to prevent putrescible intestinal residues. 
 Charcoal as the means for fixing the coloring matter of the bile. Interdic- 
 tion of roast meat, aliments rich in extractive and mineral matter, soup. 
 Diet composed of milk, white of egg, cheese, boiled meat. Disinfection and 
 intestinal antisepsis with iodoformized charcoal and naphthalin. Agree- 
 ment between the means which experiment has ratified and those which are 
 the outcome of a study of pathogenesis. 
 
 I REGARD unemia, then, as a complex poison, to which, in 
 unequal proportions, all the poisons introduced normally into 
 the organism or found therein physiologically contribute, when 
 the quantity of poison formed or introduced in twenty-four hours 
 can no longer be eliminated in the same time by the kidneys, 
 which have become scarcely sufficiently permeable. This view, 
 the legitimacy of which, I think, I have experimentally demon- 
 strated to you, differs, to a certainty, from the old doctrines and 
 
 (12T)
 
 128 LECTURES ON AUTO-INTOXICATION. 
 
 even from those which still prevail to-day, since each one of them 
 endeavors to attribute to the action of one substance alone all the 
 accidents called uraemic. Between the best of these opinions that 
 which, self-recommended by the name of Schottin, incriminates 
 the whole group of extractive substances, an opinion which M. 
 Jaccoud designates under the theory of creatinsemia and that 
 which I have proposed there is still this difference, viz, that 
 Schottin and the partisans of his theory have only regarded as 
 toxic agents the substances which originate from disassimila- 
 tioii ; but to me this is only one of the sources of the produc- 
 tion of the toxic bodies, and it is necessary to add to them the 
 poisons furnished by the biliary secretion, alimentation, and 
 intestinal putrefactions. 
 
 The pathogenetic theory which I admit is, then, more com- 
 prehensive than its predecessors. Uraemia is to me, I repeat, 
 intoxication by all the poisons which, normally introduced into 
 or found in the organism, ought to have been eliminated by the 
 renal path, and are prevented from being so owing to the im- 
 permeability of the kidneys. 
 
 Such a conception has led to therapeutic views which appear 
 to me not to be deprived of interest. But before approaching 
 them I ought to treat the question of the possible supplanting 
 of the kidney by other eliminating organs. We have really,, 
 for a long time, thought, in cases where the renal apparatus 
 fails, to accomplish its depurative acts, of causing it to be sup- 
 planted by other organs, such as the skin and lungs. Thus 
 we have given to those suffering from uraemia baths of hot and 
 dry air; we have proposed by this means to introduce, at 
 each inspiration, a certain quantity of dry air, which, expelled 
 during expiration ladened with moisture, removes in this way 
 water from the organism. We have also tried to induce depri- 
 vation of water from the economy by increasing the perspira- 
 tion, either by administering vapor baths or by the employment 
 of sudorific medicines, such as jaborandi. In all these cases 
 we certainly remove something from the blood, but not, unfor- 
 tunately, that which is toxic. We, perhaps, remove from the 
 economy certain toxic substances which ought normally to 
 depart by the skin, but not those which the kidney is charged
 
 THE THERAPEUTIC PATHOGENESIS OF UREMIA. 129 
 
 with the duty of eliminating. What we specially remove from 
 the organism by this means is water. The inevitable result is 
 diminution of the quantity of urine ; and it is difficult for me to 
 admit that this diminution of urine is a useful result in the case 
 of patients whose urine is already diminished, both as regards 
 quantity and specific gravity. 
 
 The question might be more logical!}' raised when it is pro- 
 posed to increase the secretion of urine by various means. Some- 
 times we have attempted to diminish the congestive state of the 
 kidney, either in acute diseases or in cases of congestive exacer- 
 bations arising in the course of chronic affections of this organ, 
 b} T means of revulsives (wet or dry cupping, leeches, sinapisms). 
 Sometimes we are obliged to stimulate the nervous sj-stem by 
 irritating its cutaneous branches by friction, in order to obtain, 
 in a reflex manner, a quickening of the renal circulation and, 
 consequently, an increased secretory activity of the kidney. I 
 am convinced that, in manj' cases, cutaneous friction increases 
 urinary secretion. We have demanded the same result for cer- 
 tain medicines, caffeine and digitalis especially, means differing 
 from the preceding, since they are applied to the central nervous 
 system. Apropos of digitalis, I cannot refuse to tell }-ou that 
 this medicine ought not to be indifferently emplo3 r ed at all pe- 
 riods in diseases of the kidney. When the function of the kid- 
 ney is impeded it is prudent to use only with extreme caution 
 certain medicines. When the impermeability of the kidney has 
 become such that it ceases to have the power of eliminating 
 toxic substances formed by the organism, there is then retained 
 the medicinal substances ; the kidney is as impermeable for 
 therapeutic poisons as for natural poisons, and the emplo3'ment 
 of toxic medicines, in similar cases, has no other effect than to 
 bring about an association of medicinal intoxication with a 
 ursemic. 
 
 Digitalis succeeds, however, in certain cases of Bright's dis- 
 ease, in increasing the quantity of urine, but it is chiefly so when 
 there are cardiac disorders associated with disease of the kidney, 
 and when this organ has not become very impermeable; at a 
 period more advanced we ought to dread the action of digitalis. 
 I do not say that it is absolutely necessary to renounce it, but
 
 130 LECTURES ON AUTO-INTOXICATION. 
 
 it is necessary to watch the administration of it very carefully. 
 Prudence, moreover, does not consist in using small doses only ; 
 we must employ, on the contrary, sufficiently large doses, doses 
 which run the risk of being toxic, without which we would not 
 obtain any result ; but these doses ought to be sufficiently small 
 so that we may have time to immediately suppress the adminis- 
 tration of the drug if there appear signs of intolerance, nausea, 
 or vomiting. It goes without saying that digitalis is inapplicable 
 in that form of uraemia which is characterized clinically by 
 gastro-intestinal accidents. 
 
 There are yet other means of increasing the quantity of urine. 
 We may propose the displacement of a part of the mass of blood, 
 which is in relative stagnation in certain parts of the vascular 
 system, and to throw it into the main circulation, in order to 
 increase the pressure within the vessels of the kidney. Between 
 the arterial capillaries of the abdomen and the liver is found 
 quite a considerable mass of blood accumulated in the portal 
 system and in the hepatic and splenic parenchyma; we may 
 throw that reserve, nearly stagnant, into motion in the general 
 circulation ; we may empty, in a word, the portal system, in 
 order to augment the general arterial tension and, in conse- 
 quence, set the renal function agoing. This result may be ob- 
 tained by the introduction of cold water into the abdomen, by 
 the employment of cold injections. I have seen, in certain cases, 
 a grave anuria disappear by the use of cold injections ; it is 
 therefore a means we ought not to neglect. We may carry in 
 cool drinks, which, besides the stimulation which they impress 
 upon the contractility of the abdominal vessels, will induce ab- 
 sorption of a certain quantity of water, in order still to increase 
 diuresis. Amongst the liquids which it is usual to prescribe, 
 milk is one of the most powerful medicaments which we can op- 
 pose to uraemic accidents, and not only to albuminuria. Its 
 advantages are numerous, as we shall see. 
 
 We can also utilize as a medicament a body which has been 
 considered, until to-day, a poison, and which is capable, more 
 than any other, of encouraging the secretion of urine. I am 
 now speaking of urea, to which we certainly cannot attribute 
 the accidents of uraemia, and which, on its own side, even com-
 
 UREA AS A DIURETIC. 131 
 
 bats them by forcing the renal barrier. In animals, urea has 
 been experimentally demonstrated to be a diuretic. In a healthy 
 man, ingested by the gastric mucous membrane, it has not ap- 
 peared to increase the quantit} r of urine. It would therefore 
 remain to be determined whether, in a sick person, by subcu- 
 taneous injections of urea, we could succeed in increasing the 
 urinary secretion. I have undertaken in animals, and more 
 lately in men, experiments bearing upon this point. In a patient 
 with Bright's disease, the subject of a cardiac affection, I have 
 once seen the subcutaneous injection of urea induce a diuresis 
 of 7 litres in twentj'-four hours ; but I ought to say that in the 
 renewed relapses of oliguria in this same patient the injection 
 of urea has failed, as has also, at other times, the administration 
 of digitalis, which some weeks previously had abundantly 
 induced diuresis. 
 
 I have established that the skin and the lung cannot vicari- 
 ously aid the kidney which has become incapable of accomplish- 
 ing its task of elimination. But, have other emunctories the 
 power? Or, at least, can we not utilize as emunctories large 
 mucous surfaces, such as that of the digestive canal, the stom- 
 ach, and intestine? 
 
 For a long time we have combated uraemia by inducing vomit- 
 ing. We have sought to imitate what occurs in certain cases of 
 uraemia in which vomiting is frequent ; it is therefore proposed to 
 provoke a secretion of extractive matter from the surface of the 
 stomach. It is not shown that the vomiting notably increases 
 the gastric secretion. It 1ms, on the contrary, two evident 
 inconveniences : it produces two effects, lowering of arterial 
 tension and, in consequence, diminution of renal secretion ; and 
 increase of the cutaneous secretion, which further diminishes 
 the renal secretion. Besides, some have quickly given up this 
 practice, and have had recourse to the intestine, in which the}' 
 have provoked l^-persecretion by drastic purgatives. Purgatives 
 have been employed for a very long time, in accordance with 
 theoretical views. It is upon the theoiy of Wilson that phy- 
 sicians have relied, who have wished, by means of purgatives, 
 to remove urea from the blood ; but the intestinal secretion has 
 no elective action upon urea ; it only removes urea from the
 
 132 LECTURES ON AUTO-INTOXICATION. 
 
 blood ill the proportion in which it is found in the blood-plasma. 
 If the serum of blood contains, per litre, 32 centigrammes of 
 urea, the liquid which exudes into the intestine under the influ- 
 ence of purgatives contains exactly 32 centigrammes of urea 
 per litre. 
 
 On the other hand, if we remove one litre of water from the 
 blood by the intestinal tract, it is simply a litre of water less 
 that will pass away by the renal path ; but this litre of water, 
 eliminated as urine, could have removed fifty times more urea. 
 In addition, we know that the theory of Wilson is wrong, and 
 that urea is not the cause of the uraemic accidents. 
 
 Let us see what is the composition of the substances elimi- 
 nated by purgatives, only considered as poisonous. Purgatives 
 remove from the blood, in the first place, water ; they dehydrate 
 the blood and, consequent!}', the tissues; this dehydration, per- 
 haps, causes a diminution of cedemas and effusions into serous 
 cavities; this will remove, perhaps, water from the cells and, 
 along with this water, a portion of toxic material. But there 
 will only result from this a favorable effect if we immediately 
 restore to the tissues the water which we have just removed; 
 otherwise, we shall have only displaced the poison by making it 
 pass from the cells into the plasma ; after dehydration it is 
 necessary to bring about immediate hydration. This is a dan- 
 gerous game ; we are never sure of being able to graduate at 
 will these alternatives of subtraction and restitution of water 
 from the blood an,d tissues. 
 
 Nevertheless, I do not wish to- proscribe a method in favor 
 of which clinical experience seems to have decided for a long 
 time past. Diarrhoea does not remove urea from the blood, but 
 it removes poisons from it. In an adult, in good health, I have, 
 for six consecutive days, measured the urinary toxicity, in 
 periods of four hours. The curve of the toxicity is reproduced 
 each day, regularly and always at the same time. But I have 
 established a disturbance coincident with a diarrhoea. During 
 the four hours coincident with this diarrhoea, urinary toxicity 
 had undergone notable diminution. I have thought that the 
 poisons which were then awanting in the urine had been carried 
 away by the intestinal fluid.
 
 BLEEDING IN UREMIA. 133 
 
 We have until now only discussed means that are injurious 
 or uncertain. What is thought of bleeding? What happens 
 when we remove blood from a uraemic ? In removing 32 grammes 
 of blood you remove from it 50 centigrammes of extractive sub- 
 stances ; the daily elimination by urine is 8 grammes ; you, there- 
 fore, in this way, remove one-sixteenth of the extractive sub- 
 stances which the urine ought to carry away. This result is 
 not insignificant ; for, if the kidney ought to remove in one 
 hour these 50 centigrammes of extractives, and if the convulsive 
 or comatose accidents resulting from this non-elimination can 
 kill the patient during this hour, the bleeding which you induce 
 may save the life of the patient, by removing, for the moment, 
 from him, the excess of toxic material which causes the develop- 
 ment of fatal accidents. 
 
 In an\ r case, it is certain that we remove from the economy 
 more extractives b}- bleeding than by any other channel, the 
 renal tract excepted ; for a bleeding of 32 grammes removes 
 from it as much as 280 grammes of a liquid diarrhoea does, or as 
 100 litres of perspiration. Besides, it is not only 32 grammes 
 of blood the quantity drawn by two leeches which we have 
 removed in similar cases. Abercrombie, Marshall Hall, Ra}'er, 
 and many others in addition, have employed copious bleedings 
 for uraemic accidents, and the}* have seen patients cured who 
 were assuredly threatened by death. It is chiefly in acute cura- 
 ble nephritis, such as scarlatinal nephritis, that bleeding finds its 
 formal indication, and if uraemic accidents arise; for, in these 
 cases, the renal malady only demands cure when the patient 
 does not succumb to the fleeting attack of uraemia. In these 
 cases, therefore, it is obligator}- to practice bleeding, not only 
 because it is theoretically legitimate, but because, practically, it 
 has been shown to be useful. 
 
 On the contrary, in chronic diseases of the kidney, the 
 utility of bleeding is doubtful. We cannot incessantly go on 
 bleeding a patient with uraemia whose kidney is definitively and 
 irrevocably diseased ; we should only hasten death by impov- 
 erishing his blood. There is scarcely, therefore, cause for prac- 
 ticing bleeding in the terminal uraemia of chronic nephritis, 
 except once, viz., at that moment when accidents threaten inline-
 
 134 LECTURES ON AUTO-INTOXICATION. 
 
 diate death, and when there is no other hope than of delaying 
 for a little the fatal termination. Since, in the majority of cases, 
 we cannot derive great benefit from bleeding, we have thought 
 of employing antidotes capable of opposing their physiological 
 effects to those of the poisons which have induced the uraemic 
 attacks. 
 
 Inhalations of chloroform have been successful, especially in 
 this particular intoxication, which singularly resembles uraemia, 
 viz., in the eclampsia of lying-in women. The evidence of their 
 utility has not been so great in the uraemia of nephritis. In 
 every case they find their application only in the convulsive form, 
 and, of course, we cannot think of them for the comatose form. 
 It is also for the convulsive variety that the action ol chloral 
 should be reserved, of which we do not otherwise know what is 
 its exact value in these cases. Bromide of potassium, which has 
 also been proposed, ought to be rejected at once ; for it can of 
 itself determine intoxication by the potass which it contains. 
 If we wish to treat uraemic convulsive accidents by bromide 
 preparations we should use bromide of sodium ; but never 
 should we employ, in uraemia, any salt of potassium, no more 
 the bromide of potassium than the nitrate. Under other condi- 
 tions we would replace them with advantage by the bromide and 
 nitrate of sodium, which are just as active therapeutically and 
 forty times less toxic. 
 
 That is, therefore, the therapeutic programme for uraemia, 
 such as our predecessors have bequeathed to us. Amongst all 
 these means, what of worth remains? Certain diuretic agents, 
 first, such things as milk, and bleeding for certain cases. 
 Yet perhaps something else might be done for these uraemic 
 accidents by applying the pathogenic therapeutics which I have 
 been trying to put in favor during the six years that I have 
 lectured. There are, perhaps, therapeutical indications to be de- 
 rived from the knowledge we possess of the sources of the accu- 
 mulation of toxic substances in the econonry, disassimilation, 
 the secretion of the liver, alimentation, and intestinal putrefac- 
 tions. Let us see if we cannot act upon one or other of these 
 sources of intoxication, so as to exhaust or diminish them. 
 
 Can we delay disassimilation ? Is there any indication for
 
 THE THERAPEUTIC PATHOGENESIS OP UREMIA. 135 
 
 administering those substances which have the reputation of 
 diminishing the exchanges of nutrition, and which have been 
 called the medicines that save the wear and tear, e.g., arsenic and 
 valerian ? It would be quite useless. Disease itself has produced 
 this arrest of disassimilation. The accumulation of toxic sub- 
 stances has checked the condition of osmosis ; an equilibrium of 
 tension has been established between the fluids, intra-and extra- 
 cellular ; the circulation of matter through the cell no longer goes 
 on, except imperfectly; combustible substances and the heat-pro- 
 ducing agent, oxygen, no longer enter, but with difficulty, into the 
 conflict, so little that we see the temperature fall, an evident 
 proof of a check given to nutrition. The temperature, taken in 
 the rectum, may fall to 30 degrees. The disease itself has gone 
 be} r ond the point wished for in our calculations. It is useless, 
 then, to think of impeding further oxidation, whose insufficiency 
 may, by itself alone, become fatal. I go farther : those things 
 which are especially toxic are the products of life without oxygen. 
 Increase the free oxygen, and you will only moderately increase 
 disassimilation, but the products of this disassimilation will be 
 much less toxic. I have seen exposure in compressed air diminish 
 by more than one-half urinary toxicit}'. It is, therefore, rational 
 to adopt the practice of Jaccoud, who speaks highly of the inhala- 
 tions of oxygen in the treatment of uraemia. 
 
 What can we do to combat that source of poison which is 
 resident in the biliary secretion? We can first diminish the 
 quantity of bile secreted. A means used empirically, and which 
 is excellent, is milk, when it is well digested, for if it is not 
 absorbed it purges and increases the biliary secretion. But 
 when the digestion of milk is perfect constipation is established, 
 and the dry and hard faecal residue which it leaves contains 
 almost no biliary pigment. We can also expel bile, when it has 
 been formed, by washing it out by the help of certain neutral 
 salts, whose action is limited to making it force its way rapidly 
 through the intestinal contents as far as the anus. You will 
 avoid, in every case, the potass purgatives, soluble cream of 
 tartar and the salt of Seignette. But in bile the greatest part 
 of its toxicity rests in the coloring matter. We have proof that 
 decolorized bile is much less toxic. We have the means of
 
 136 LECTURES ON AUTO-INTOXICATION. 
 
 decolorizing bile in the digestive canal by administering char- 
 coal in sufficient quantity. 
 
 We can diminish the toxicity which is resident in food- 
 sources by diminishing, from this point of view, chiefly their 
 mineral substances, e.g., potass, which contributes a very im- 
 portant share in the production of intoxication. We will 
 choose, for ursemic subjects, food that is quickly digested and 
 absorbed, and which will also have the advantage of not handing 
 over to the agents of intestinal putrefaction undigested and 
 easily putrescible material. We will search for foods not rich in 
 extractives and in potass. We will, then, avoid meat and, as we 
 have done, empirically, for a long time, we will choose milk, which 
 is slightly rich in potass, and which has proved itself satisfac- 
 torily, from so many points of view, in the treatment of uraemia. 
 We will add to this the white of egg, and, in case of need, cheese 
 which no longer contains the soluble mineral matter of milk 
 and boiled meat ; but we will interdict soup. 
 
 Finally, a very important indication is to prevent intoxication 
 caused by the products of intestinal putrefaction. We ought to 
 endeavor, first, to admit only a small quantity of putrescible 
 matter into the digestive canal, so that the digestive residue 
 may form solid masses, presenting at the point of contact with 
 the absorbing mucous membrane only surfaces that are hard and 
 not extensive. The past}' residues incessantly mashed by the 
 intestines, on the contrary, successively allow of the absorption 
 of the poison contained in their superficial and deep layers. 
 Milk-food, when it is well tolerated, which is the rule when milk 
 is ingested in small quantities and well broken up, produces the 
 desirable result ; that is to say, faecal matter scanty and solid. 
 Thus, from whatever point of view we regard it, milk is opposed 
 to all sources of intoxication. 
 
 We can still fix the toxic products of intestinal putrefaction 
 so as to prevent their absorption. Charcoal gives us the means 
 of doing so. We may even oppose putrefaction itself by induc- 
 ing intestinal antisepsis. We possess, in the association of 
 iodoform in charcoal, and in naphthalin, means which theoret- 
 ically permit us to practice this thoroughly. Salicylate of bismuth 
 may be employed for the same end, and, if we were afraid of the
 
 BENEFICIAL INFLUENCE OF INTESTINAL ANTISEPSIS. 1ST 
 
 passage and accumulation in the blood of the small quantity of 
 salicylic acid absorbed, we might substitute for it the subnitrate. 
 In fact, my colleague, Dr. Tapret, has applied this theoret- 
 ical idea to the treatment of uraemia, and he has thrice seen 
 ursemic accidents disappear when intestinal antisepsis had been 
 induced. I, myself, have seen in one case, formidable ursemic 
 d3-spncea disappear within twenty-four hours after the adminis- 
 tration of naphthalin. The patient, who was diabetic, succumbed 
 later on to gangrene, but, to a certainty, he would have been 
 dead more quickly from his uraemia. These are only four cases, 
 but they are encouraging, especially when we think of the 
 small number of therapeutic means at our disposal for treating 
 uraemia. 
 
 Thus, to resume, diuretics (and, in the first place, milk: 
 milk as food), intestinal antisepsis, bleeding for accidents imme- 
 diately threatening, and, finally, inhalations of oxygen, that is 
 the treatment which experience has confirmed. It is also that 
 which arises naturally from the conception of the disease, which 
 we have admitted.
 
 LECTURE XYI. 
 
 TRANSITORY OR ACUTE AUTO-!NTOXICATION OP INTESTINAL 
 ORIGIN INTERNAL STRANGULATION AND CONSTIPATION. 
 
 Increase of the quantity of poison contained in the digestive canal when there is 
 an augmentation of the activity of normal fermentation. Symptoms and 
 
 signs of the increase of acid fermentation and of putrid fermentation. 
 
 Parallel relation between the increase of intestinal fermentation and increased 
 toxicity of urine. Poisons which are found in the intestines and which pass 
 into the urine. Phenol, indol, and indican ; cresol. Substance which gives a 
 claret color to urine after the addition of perchloride of iron, but which is not 
 
 acetone. How the organism is protected against poisons derived from the 
 
 intestines. Part played by the liver from the point of view of the arrest and 
 destruction of putrid poisons. Experiments of Schiff and of G. H. Roger. 
 
 Utility of hardening the intestinal contents. Role of auto-intoxication 
 
 of faecal origin, in internal strangulation and the morbid states called intes- 
 tinal septicaemia (Humbert). The two periods of constipation : constipation 
 with retention of liquid faecal matter causes symptoms of intoxication, and 
 hardening of the substances renders the second period of constipation less 
 harmful. 
 
 WE know that tbe poisons contained in the intestines, also 
 those which come from food, from bile, or putrefaction, enter, on 
 the one hand, into the complex intoxication called uraemia. We 
 can, therefore, understand how, if the quantity of poison increase 
 in the intestines, an intoxication becomes possible ; at the same 
 time, that disassimilation does 'not hand over to the blood a 
 larger amount of toxic material even when the kidney remains 
 permeable. 
 
 To-day we are going to study intoxication by re-absorption 
 of substances contained in the digestive canal, without the 
 presence of other pathological states. Experiment has proved 
 to us that the toxicity of the intestinal contents is mixed, and 
 has revealed to us its various sources. These sources, let us 
 recall them : 
 
 1. Foods even the most inoffensive in appearance and the 
 flesh of muscle are toxic, particularly, on account of the mineral 
 matter and" potass principally. We have shown this by injecting 
 aqueous decoction and the alcoholic extract of meat. 
 (138)
 
 AUTO-INTOXICATION OP INTESTINAL ORIGIN. 139 
 
 2. Bile contains poison. The eight hundred or one thousand 
 grammes of bile which are turned each day into the intestines 
 of an adult of average weight are toxic on account of the color- 
 ing matters principally, e.g., bilirubin, and also other substances: 
 some known, such as the biliary salts, others unknown. 
 
 3. Putrefactions which develop in the alimentary residues 
 engender poison. The extract of 2.5 grammes of putrefied meat 
 is sufficient to kill. 
 
 4. Finally, we have learned that faecal matter is toxic ; that 
 this toxicity is due chiefly to potass and ammonia; and, on the 
 other hand, and this represents about one-fifth of the total tox- 
 icity, to the union of organic principles, in which are included 
 alkaloidal substances. 
 
 Thus, the paths are prepared for the study of intoxication 
 of intestinal origin, since we know that, in normal conditions 
 even, there is material for intoxicating, and as to what proportion 
 each of the poisons shut up in the intestines bears to the 
 toxicity of the whole. 
 
 We shall now see how, under normal conditions, the contents 
 of the intestines may become more toxic, and how, even with a 
 kidney functionally free, if the production of toxic material is 
 accidentally more abundant, it may yet accumulate in the blood 
 in a proportion capable of causing S3 r mptoms of intoxication to 
 arise. When fermentation has become more active in the whole 
 length of the digestive tube, we see produced a succession of 
 phenomena truly characteristic. The unusual development of 
 gas determines abdominal meteorism and tympanites, which may 
 be from the stomach or intestines, or it may be at once carried 
 to the stomach or intestines. The disengagement of gas reveals 
 itself by eructations, preceded by burning sensations in the 
 stomach, or accompanied by pyrosis in the oesophagus and 
 ph.'irynx. It may induce acid vomiting, the acidit}- of which is 
 most frequently due to acetic acid v rarely, h} r drocbloric. The 
 acidity of the mouth may cause changes in the teeth. The con- 
 tents of the intestines, which have become abnormally acid, may 
 not only provoke diarrhoea, by irritating the mucous membrane, 
 but irritate also the skin outside the rectum, as witness the 
 erythema of the bu.ttocks in the acid dyspepsias of infants. An
 
 140 LECTURES ON AUTO-INTOXICATION. 
 
 acid reaction is substituted for the normal of the intestinal 
 contents. We notice changes in the color of the stools : bile is 
 expelled, with a green color. The production of sulphuretted 
 hydrogen is diminished. Certain substances, administered with 
 the view of arresting the diarrhoea, such as bismuth, give no 
 longer to the stools a black color, for there is no longer formed 
 sulphide of bismuth. These are the external signs which indi- 
 cate, even to the naked eye, the production of acid fermentation 
 in the digestive canal. 
 
 When fermentation of a putrid character predominates, there 
 is produced rather an excessive disengagement of 'sulphuretted 
 hydrogen, ammonia, and sulphate of ammonia, which reveal 
 themselves to our senses by the odor of the gas expelled. 
 
 Parallel to these objective phenomena there exist those of a 
 subjective character, amongst which the most ordinary are fatigue, 
 depression, headache, buzzing in the ear and deafness, disturbances 
 of sight, and vertigo. With a kidney acting well things may not 
 go farther ; but, if the renal emunction is insufficient, we ma} 7 
 see developed a fraction of urasmic intoxication through simple 
 exaggeration of intestinal fermentation. If, for example, abun- 
 dant vomiting has caused oliguria, we may have coldness estab- 
 lished, paralysis of the vessels of the skin, cramps, convulsions, 
 coma, paralyses, death even, whilst the kidney itself may not be 
 really diseased. It will be sufficient for the development of such 
 accidents that the quantity of toxic material introduced into the 
 blood should exceed the activity of the kidneys charged with 
 the function of eliminating it. 
 
 From proof of the preceding facts, we can already con- 
 clude that the quantity of urine passed is very important in the 
 intoxication of intestinal origin; that variations of urinary 
 toxicity may be, in similar cases, the measure of the degree of 
 intoxication ; and that we should find, under the influence of 
 intestinal fermentation, an increase in the toxicity of the urine. 
 I have known that in a large number of diseases it is thus. If I 
 suppress intestinal fermentation, I cause the toxicity of urine 
 to diminish ; I cause it to diminish, but not to disappear, since 
 I only suppress one of the natural sources of its toxicity. I 
 can diminish the toxicity of urine either by neutralizing the
 
 INTESTINAL SOURCE OP CERTAIN POISONS. 141 
 
 products of putrefaction, by the aid of charcoal, which prevents 
 their absorption, or by preventing putrefaction itself, through 
 causing intestinal antisepsis, by means of iodoform and naph- 
 thalin. I have thus proved the reality of the passage of a larger 
 quantity of toxic material from the intestines to the kidnej' in 
 cases where there has been an increase in intestinal fermentation. 
 
 This proof had already been given formerly by chemistry. In 
 my experiments of 1882, in which I only occupied myself with 
 one class of toxic agents, alkaloids, I had shown that they 
 increase in a parallel manner in the faeces and in the urine. I 
 had concluded that the organism is, from this fact, under the 
 risk of a constant menace of intoxication. Other observers had 
 preceded me in this path. Stadeler, in 1848, had found phenol 
 in the urine, without drawing any conclusion from it. In 1877, 
 Baumann found phenol in faecal matter; we must really admit 
 that this passes from the digestive tube into the urine. In 1826, 
 Tiedemann and Gmelin discovered in the duodenum a substance 
 which gave a red color with chlorinated water, indol. Bracon- 
 not, without noticing in his discovery any relationship with 
 the preceding, has shown in the urine the existence of a certain 
 substance of a different color, cyanurine, which is indican 
 derived from indol. In 1872, Jaffe made a subcutaneous injec- 
 tion of indol, and he saw that indican appeared or increased in 
 the urine. The indol, therefore, which is formed in the faeces is 
 the cause of the urinary indican. 
 
 These early experiments are the source of all that have been 
 made since then. A very convincing experiment is that of 
 Senator. He seeks for indican in the urine of the newly-born, 
 and he does not find it ; he analyzes the meconium, and does 
 not find indol therein. Nothing is better shown to-day than the 
 parallel relation between the increase of indican in the urine and 
 indol in the faeces. That is to say, variations of urinary imlk-an 
 according to the activity of intestinal fermentation. Aloysius 
 Martin established that in every disease of the intestinal tube 
 there was an increase of urinary indican. Hassal found a 
 large proportion of it in the urine of people suffering from 
 cholera; Gubler, in typhoid fever and cholera. One of Gnbler's 
 pupils A. Robin studied its variations in typhoid fever.
 
 142 LECTURES ON AUTO-INTOXICATION. 
 
 Carter and Jaffe have shown that urinary indican increases in 
 consequence of the retention of faecal matter in intestinal 
 obstruction and in internal strangulation. Senator showed the 
 same fact in certain kinds of constipation ; in these the alvine 
 secretions are maintained in a liquid or semi-solid state. 
 
 Analogous researches have been made for other substances 
 by Salkowsky, for phenol and cresol. We see them increase 
 like indican in the urine, in certain forms of diarrhoea, and in 
 intestinal obstruction. I will say the same of a substance, not 
 defined chemically, revealed in the urine by a claret coloration 
 induced by the addition of perchloride of iron to it. It has 
 been observed by Senator, Riess, and Litten, not only in aceton- 
 semia or sugary diabetes, in pernicious anaemia or leucocy- 
 thsemia, but in grave dyspeptic states, in certain cases of carci- 
 noma of the stomach, all cases in which anomalous fermenta- 
 tion is produced in the digestive tube. I have also seen, often 
 enough, this coloration of urine in the grave forms of dilatation 
 of the stomach, in cancer of the stomach, and in typhoid fever. 
 This material is assuredly not acetone ; it is analogous to it 
 only by this reaction when brought into contact with perchloride 
 of iron. It was absent in certain diabetics whose breath, more- 
 over, had the odor of acetone. I believe, with the authors 
 named above, that it is frequently found related to increase of 
 fermentation in the digestive canal. 
 
 All these substances, known or suspected, are only some of 
 the products of intestinal putrefaction, but they show very well 
 the parallelism between the entrance of putrid matter into the 
 blood and its increase in the urine. We know, therefore, that 
 if these putrid substances are formed in excess, there may result 
 from them an intoxication even without the kidney being dis- 
 eased. Nevertheless, as all these substances exist normally in 
 the digestive canal, we may ask whether the organism has no 
 other protection against them than the kidney. It is possible 
 that the liver may give this protection, and that the experiments 
 of Schiff relative to the alkaloids may be of a more general sig- 
 nificance. This hypothesis may rest upon some experiments 
 recently performed in my laboratory by G. H. Roger. 
 
 The alcoholic extract of rotten meat is twice less toxic when
 
 SENTINEL ACTION OF LIVER. 143 
 
 we inject it into the portal vein than when introduced into the 
 general circulation. Extracts of the intestinal contents of the 
 rabbit and the dog kill, by a smaller dose, frogs deprived of their 
 liver, than healthy frogs, or those in which we have tied the 
 afferent vessels of the kidneys. It appears, therefore, to be 
 certain that the liver arrests or transforms toxic substances 
 which originate in the intestinal canal. This conception again 
 has been verified experimentally : blood drawn from the portal 
 vein of the dog kills a rabbit in a dose of from 13 to 14 cubic 
 centimetres per kilogramme, whereas it is necessary to use 23 
 cubic centimetres of blood removed from the liver. 
 
 These recent experiments seem to lend support to a hypothe- 
 sis put forward by Schiff now a long time ago. You know that, 
 in consequence of an abrupt ligature of the portal vein, the 
 animal falls into a state of somnolence and dies in one or two 
 hours, if it is a dog ; in thirty or fort} 7 minutes, if the experi- 
 ment has been performed upon a rabbit. Schiff supposes that 
 the death is due to an intoxication consequent upon the reten- 
 tion of a poison which the liver was charged with the function 
 of destroj'ing. This poison would originate during disassimila- 
 tion, and Schiff considers that he has demonstrated its existence 
 by the following experiment : He removes the liver from a frog, 
 the animal bearing the operation well ; that is, without immedi- 
 ate death. He injects into it blood removed from a healthy 
 dog ; the frog does not die. He ties the portal vein of this dog, 
 which falls into somnolence and dies. He takes some blood 
 from this dog and injects it into the frog ; this becomes, in its 
 turn, somnolent, and dies, at the end of from half an hour to an 
 hour. 
 
 The experiment has been repeated in my laboratory by M. 
 Roger; he has injected into rabbits the blood of a dog, before and 
 after ligature of the portal vein. In these two cases the toxicity 
 has been the same, viz., 25 cubic centimetres per kilogramme. 
 This result completely opposed to that of Schiff does not 
 cause me, in any way, to repudiate the idea that the liver arrests 
 and is constantly transforming toxic products ; the comparative 
 toxicity of the portal and hepatic blood demonstrates it. Only, 
 in the experiment of Schiff, poisoning has no time to be pro-
 
 144 LECTURES ON AUTO-INTOXICATION. 
 
 duced ; the animal appears to succumb, as Claude Bernard has 
 said, to an intestinal hyperaemia and consequent cerebral 
 anaemia. In order to study auto-intoxication, after suppressing 
 the function of the liver, it will be necessaiy to join together 
 the portal vein and the renal. The experiment made by Holni- 
 kew, from another point of view, has allowed the animal to live 
 from eight to ten hours. 
 
 I think that we may, therefore, conclude that the liver is an 
 organ of protection to the economy ; that it arrests more or 
 less of the toxic material in general, not the whole, since a part 
 passes into the urine. The liver is certainly not the only agent 
 which acts the part of protector to the organism against poisons. 
 There may yet be made to intervene, as an auxiliary agent of 
 protection, rapidity of intestinal expulsion by the stools, hard- 
 ening of the intestinal contents, which, transformed into a hard, 
 faecal bolus, becomes almost inoffensive, because it no longer 
 allows of absorption. 
 
 After having admitted this hypothetical and theoretical 
 mechanism of intoxication by poisons of intestinal origin, let 
 us see if there exist, really and clinically, such intoxications. 
 On this point I shall borrow from the teaching laid down in the 
 work of M. Humbert, who has used the word intestinal septi- 
 caemia in the sense of intoxication. I find therein startling 
 examples of intoxication in some of the phenomena which are 
 produced in the course of surgical affections causing intestinal 
 obstruction. In the first place, mechanical phenomena are 
 demonstrated by the arrest of matter, pain complained of above 
 the obstacle, and abdominal distension. Then reflex actions : 
 vomiting which cannot be attributed to intoxication, fall of 
 arterial tension, frequency of the pulse, perspiration, etc. All 
 these reflexes are often arrested at the end of one or two days, 
 and during these two days vomiting ceases. Then appears a 
 new phase, characterized by prostration and collapse, a par- 
 ticular pallor of the skin, not pale, owing to spasm of vessels, 
 but earthy-looking, from being impregnated with coloring 
 matter; coldness, and muscular cramps. Humbert asks whether 
 a part of this complicated clinical picture should not be attrib- 
 uted to intoxication. We must certainly reply to him in the
 
 AUTO-INTOXICATION OF INTESTINAL ORIGIN. 145 
 
 affirmative. Why this period of respite? It is inexplicable on 
 the theory of reflexes. It finds, on the contrary, an explanation 
 in intoxication. Examination of the aforementioned facts does 
 not offer to us, doubtless, a true demonstration, but it forces us to 
 consider. It is not uncommon to observe cases of strangulated 
 hernia in which accidents continue when the intestinal strangu- 
 lation has been relieved, because putrid material is freely spread 
 throughout the whole length of the digestive tube, which 
 absorbs it. 
 
 An objection often made to the hypothesis of intoxication 
 of faecal origin is the fact that constipation is compatible with 
 health. If this hypothesis were true, say some, intoxication 
 would be realized to the full in constipated people. I reply 
 that constipation ought to be regarded as a protection against 
 intoxication. It supposes that all that is absorbable has been 
 absorbed, the aqueous part with what was held in solution. 
 In constipation there is, at first, a preliminary phase, in which 
 appears a threatening of intoxication, but, in the second place, 
 intoxication is no longer in operation. 
 
 Besides, are constipated people healthy ? They have head- 
 ache, migraine, and vertigo. Hypochondriacs, whose suffer- 
 ings are chiefly subjective, are constipated. They experience a 
 number of nervous disorders of sensibility, buzzing in the ears 
 and psychical troubles. All the insane are constipated, and alien- 
 ists endeavor specially to guard against constipation. I do not 
 say, of course, that psychical troubles are caused by constipation. 
 I only say that they are, in a certain sense, exaggerated by it. 
 I say that the nervous system is maintained in a condition of 
 hurtful disposition by constipation, and that we render a service 
 to patients attacked by cerebral troubles when we cause to dis- 
 appear, at the same time as constipation, the unhealthy disposition 
 of the nervous system. 
 
 Thus we see, in the two examples of septicremia of Humbert, 
 and of constipation, the maximum and the minimum of accidents 
 attributable to the intoxication of intestinal origin.
 
 LECTURE XVII. 
 
 ACUTE OR TRANSITORY INTESTINAL AUTOINTOXICATION GASTRIC 
 DISORDERS INDIGESTION POISONING BY TAINTED MEATS. 
 
 Explanation of the symptoms of gastric disorder from retention of toxic material 
 in the stomach. Washing out of the stomach in certain forms of intestinal 
 obstruction. Indications for emptying the intestines in surgery and obstet- 
 rics. Indigestion, with excessive production of toxic matter in the digest- 
 ive canal. Presence of sulphuric acid in the intestines and emunctories in 
 a case of grave indigestion (Senator). Case of indigestion with enormous 
 
 quantity of alkaloids in the intestines and urine. Poisoning by tainted 
 
 meats : old sausages. The epidemic at Andelflngen. Why these morbid 
 states are intoxications and not infections. 
 
 I HAVE just shown you, in internal strangulation and m con- 
 stipation, the two extremes, the maximum and the minimum of 
 intoxication of intestinal origin. In the morbid state still 
 badly known which we call acute dyspepsia things are, at 
 their origin, obscure and complex. We do not know what is 
 the primary cause of gastric fullness, but we do know that 
 there exists in this affection, at a given moment, a diminution 
 of the secretions ; of the saliva, whence the clammy state of the 
 mouth; of the gastric juice, whose peptogenetic power is weak- 
 ened ; of the intestinal glands, which causes constipation. The 
 appetite is diminished, and that is very advantageous, since the 
 digestive power is less, and also because the taking of food in as 
 large a quantity as under ordinary conditions would transfer to 
 parasitic ferments more putrescible material. In these condi- 
 tions of imperfect digestive secretions I see the possibility of a 
 development of anomalous fermentations. It is certain that the 
 subjective troubles felt by patients cannot be explained by an 
 insufficient alimentation of so short a duration. On the con- 
 trary, the production of putrid fermentations explains the bitter- 
 ness felt in the mouth, headache, and depression. If I have not, 
 therefore, any information as to the primary cause of the dis- 
 ease, I have reasons for supposing that one part ought to be 
 attributed to intoxication in the pathogenesis of some of the 
 accidents. 
 
 (146)
 
 WASHING OUT OF STOMACH. . Ht 
 
 In certain individuals habitually the subjects of diarrhoea, 
 who have, nevertheless, during each day, only one liquid and 
 fetid stool, we observe nearly always headache, vertigo, and some 
 shivering. They in general experience bitterness in the mouth ; 
 their breath and their skin have a disagreeable odor. But all 
 these inconveniences may disappear for a time by evacuating the 
 contents of the large intestine. The individual who awakens 
 with a sensation of lassitude ma}' be deprived of it l>y a simple 
 injection. What I say to you in regard to this does not consti- 
 tute a demonstration, but it is more a reason for adding to the 
 probabilities in favor of the part played by intoxication in the 
 genesis of troublesome, though attenuated, nervous symptoms, 
 apart from any completely-established disease. 
 
 We may see more severe symptoms yield after simple evacua- 
 tion of the contents of the digestive canal. Washing out of the 
 stomach is not a curative means, properly speaking; but it 
 removes certain forms of malaise, headache, and migraine. In 
 certain patients, the subjects of dilatation of the stomach, lavage 
 causes not only the disappearance of pain, pyrosis, and heart-burn, 
 but all the other accidents called reflex. Assuredly, washing 
 out does not cure dilatation of the stomach, but it is in certain 
 cases necessary, and it renders considerable service in weaken- 
 ing the most painful symptoms, services which are manifest, 
 but, unfortunately, also transitory. In my clinique was :i woman 
 whose stomach was dilated. She suffered from constant supra- 
 orbital headache. Washing out was always immediately followed 
 by a disappearance of this headache. 
 
 When the stomach retains substances more toxic, which 
 happens, for example, in intestinal obstruction, washing out has 
 a utility no less observable. Senator had formulated this indi- 
 cation. M. Chaiitemcsse was able to verily the reality of this 
 in a patient, in my service, attacked with an intestinal obstruc- 
 tion from an unknown cause. Faecal vomiting bore witm-ss t. 
 the accumulation of toxic material in the stomach, and would 
 explain the general symptoms which accompany intestinal ob- 
 struction : the small pulse, coldness, owing to paralysis of the 
 cutaneous vessels, etc. Four litres of a horribly fetid liquid 
 were evacuated by means of the cesophagcal tube, and we saw
 
 148 LECTURES ON AUTO-INTOXICATION. 
 
 the disappearance of symptoms of peritonism, which so closely 
 resemble intoxication. A new accumulation of faecal matter 
 was followed by a return of the grave symptoms, which evacu- 
 ation of the contents of the stomach again caused to disap- 
 pear and cured the individual. He was cured not by lavage, 
 but thanks to the lavage, which gave him respite by arresting 
 intoxication and in giving to him, I presume, time for the 
 strangulation to free itself. There are, therefore, cases in which 
 toxic accidents caused by the reflux of putrid material into the 
 stomach have disappeared, thanks to lavage. 
 
 There are other circumstances in which we might suppose that 
 stagnation of intestinal material causes fever. After laparotomy 
 the- fever cannot be explained, in many of the cases, by a septic 
 condition of the peritoneum, and we see it disappear after get- 
 ting rid of constipation (Kiistner). Accoucheurs know quite 
 well how certain febrile incidents which supervene in the course 
 of parturition disappear after alvine evacuation, either sponta- 
 neous or induced by light purgatives. This hurtful influence of 
 the stagnation of matter in the intestines after operations ex- 
 plains old traditions forgotten in surgical practice. It was the 
 rule in olclen times to prepare those about to be operated upon 
 by administering to them in succession an emetic one day, then 
 on the following day a purgative, and that in two or three 
 takings. We no longer push to the same extent to-day this 
 preventive line of therapeutics ; but, the operation concluded, 
 unless it be one upon the abdomen, we can, with advantage, it 
 would appear, and upon the evidence of M. Verneuil, induce 
 intestinal evacuation. These, then, are clinical facts which agree 
 with theoiy. 
 
 There are cases in which we have been able to demonstrate 
 that the grave accidents of a true indigestion were of a toxic 
 order. Senator has seen in one of his friends a fact of this kind, 
 in whom intoxication resulted from sulphuretted hydrogen pro- 
 duced in the intestines of the patient. There had been vomiting 
 and eructations, giving off, as well as the gases emitted by the 
 anus, the odor of rotten eggs. The symptoms consisted of 
 fainting, anxiety, and clouding of the intellect. But the poison 
 could be detected in the emunctories ; the emitted gases black-
 
 INTESTINAL AUTO-INTOXICATION. 149 
 
 ened paper impregnated with acetate of lead ; the stools, the 
 urine also, contained sulphuretted hydrogen. We could, there- 
 fore, notice in these cases certain symptoms which contribute in 
 part to the classical picture of poisoning by H 2 S, as in certain 
 dyspepsias. We have demonstrated the presence of this poison 
 in the intestines, and then in the urine ; it is, therefore, certain 
 that it had traversed the blood. 
 
 In some people special foods, without being either toxic or 
 putrid, induce regularly an indigestion and grave phenomena. 
 In similar cases, if there is intoxication, it is the result not of 
 the food, but of the non-digestion ; the digestive juices cease to 
 transform food which the stomach does not care to receive ; 
 the nervous system produces disorders of secretion ; the gastric 
 juice stops flowing into the stomach, or else the HC1 is absent 
 from it at the moment of the conflict of the food with the 
 microbes. But the HC1 not only serves the purpose of swelling 
 and of l)3'drating the alimentary mass, it ought to protect it 
 against parasitic ferments. These being no longer- neutralized, 
 anomalous fermentations are produced in the stomach and in 
 the intestines ; the toxic products of these fermentations are re- 
 absorbed. There arises from this an intoxication, which is not 
 serious, fortunately, because the renal function protects the 
 organism. 
 
 In 1882 I made known the following observation: A man 
 could not take fish, cooked the day before and eaten cold. One 
 day, when he had partaken of this, which his nervous system did 
 not accept, digestion was arrested, and he experienced the 
 ordinary symptoms of an indigestion, at first stomachal and 
 then intestinal. Diarrhoea Listed not only until the last particles 
 of the ingested food were eliminated, but well beyond that even. 
 It was accompanied by prostration and anguish. But the first 
 accidents only appeared after a veritable incubation of eight 
 hours, during which, without doubt, microbes had formed the 
 amount of poison which caused so prolonged an intoxication; 
 and, in order that there should be formed such an abundance of 
 the poison, it was necessary that there should have been an 
 undoubted multiplication of normal bacteria in the digestive 
 canal. In fact, I have been able to estimate the quantity of
 
 150 LECTURES ON AUTO-INTOXICATION. 
 
 microbes, in these cases, as one-third of the faecal mass. There 
 was an increase of the intestinal alkaloids, since from 12 grammes 
 of faecal matter I was able to remove sufficient alkaloids to esti- 
 mate the proportion of it as 15 milligrammes per kilogramme 
 of faecal matter. In the urine was also found a quantity of 
 alkaloids fifty times greater than the normal amount. 
 
 That is a case, therefore, in which, without there having been 
 an introduction of meat in a state of fermentation into the 
 digestive canal, and without our being able to establish particular 
 microbes, there was produced, by the multiplication alone of 
 normal bacteria, a considerable increase of one, at least, of the 
 toxic substances which the intestine ordinarily receives. I know 
 of the circumstance of three people who were simultaneously 
 seized by accidents of the same kind. Breakfasting together, 
 they had eaten fish, with a certain distaste, about 10 or 11 in 
 the forenoon. At 7 o'clock at night one of the three felt indis- 
 posed ; the other two sat down at table, but found themselves 
 attacked, at the time of dessert, by identical symptoms. It was 
 a question of an illness consisting of vertigo, prostration, 
 vomiting, and diarrhoea. These symptoms were not the result 
 of an intoxication, since they only appeared after an incubation 
 of eight hours. The diarrhoea was not that which supervenes in 
 indigestion and which ceases immediately after the elimination 
 of food not digested ; it continued, night and day, during eight 
 days, with from eight to fifteen evacuations daity. The patients 
 remained, all this time, in a semi-sleepy condition. The three 
 people are now cured, and for all of them the duration of the 
 illness was the same. This disease might be attributed, quite 
 legitimately, to a putrefaction which had taken place in the 
 digestive canal, and to a reproduction of putrid agents which 
 had formed poisons. 
 
 We must recognize in these facts something analogous to 
 poisoning by sausages, known for a century and a half, since 
 1735. Facts are plentiful. Muller, in 1869, had collected 263 
 observations. Some have sought for the toxic material in the 
 residue of meat. This research had remained, without any 
 result, until Hoppe-Seyler discovered the existence of an al- 
 kaloid, but without demonstrating its toxicity. Brouarclel and
 
 TAINTED MEATS AND SAUSAGES. 151 
 
 Botmy, more fortunate, have demonstrated the toxicity of an 
 alkaloid which was contained both in the viscera of a woman 
 who died, after having eaten some preserved goose, and in what 
 was left of this goose. This alkaloid presented analogies with 
 conicine, but also differences. 
 
 It is certain that true intoxication may result from the eating 
 of tainted meats. Gaspard and Panum have shown that the 
 putrefaction of meat develops a poison capable of inducing 
 accidents both serious and fatal. But in these cases the symp- 
 toms are quickly developed; thej ? commence half an hour after 
 the ingestion of tainted meat. Besides, in a general wajr, we 
 do not eat meat actually putrefied and alreadj 7 ' capable of intoxi- 
 cating by itself. We ingest meat which is only beginning to 
 putrefy, in the depths of which microbes are at work determin- 
 ing a fermentative process, which goes on, under conditions par- 
 ticularly favorable, when the tainted food has found its way into 
 the digestive tube. The accidents which result from it are 
 slowly developed ; they only light up eight to eighteen hours 
 after the ingestion of suspected foods. In this period of incu- 
 bation no sj'mptom reveals the explosion which is preparing; 
 but, once the poison is formed, toxic accidents are quickly 
 developed. 
 
 Krautzer has related a case of intoxication by sausages. 
 Four people had treated themselves to Wtirtemberg sausages 
 scarcely sufficiently cooked, for people with delicate tastes 
 prefer particularly sausages the superficial part of which alone 
 has been influenced by the fire. Out of these four people, one 
 remained free from any symptom, the other three were taken ill, 
 and one of them died. After an incubation period of eighteen 
 hours, the symptoms experienced were almost identical in in- 
 tensity ; they consisted in disturbances of sight strabismus, 
 diplopia, ptosis, pupillary dilatation and paralytic phenomena. 
 Injections of pilocarpine which were made did not induce perspira- 
 tion. Thus, there is a form of intoxication caused by a poison 
 which dilates the pupil and hinders the secretion of sweat, which, 
 consequently, is not awanting in analogy to atropine. And yet, 
 amongst the putrid alkaloids, there is one which is endowed with 
 analogous properties, which I had formerly extracted from the
 
 152 LECTURES ON AUTO-INTOXICATION. 
 
 faecal matter of patients the subjects of typhoid fever, a disease 
 in the course of which intestinal putrefactions are very intense. 
 
 We have just witnessed a small epidemic in a family. We 
 have also seen epidemics of a similar nature visit with severity 
 a whole locality. The unwholesome flesh of an animal is given 
 out for consumption in a village, at the time of a fete, which 
 draws a great many people there. The incubation of accidents 
 having been long amongst the first consumers, the tainted meat 
 continues to be distributed amongst the people who have come 
 from neighboring villages. These, returned each to his own 
 house, are seized with identical troubles, and quite a series of 
 small epidemics is developed, having for its origin the infection 
 caused by the unwholesome meat consumed in the village where 
 the fete had taken place. 
 
 Twelve years ago I broke the lance with Lebert in the inter- 
 pretation of the epidemic at Andelfingen. In the little town in 
 Switzerland, a large number of deaths resulted from an intoxi- 
 cation due to diseased meat. And yet there was always a slow 
 incubation and a long duration, which eliminated the idea of 
 intoxication. There was question rather of a disease which de- 
 veloped gradually in the individual, and continued after the com- 
 plete elimination of the tainted food. In similar cases the sub- 
 stances although healthy after ingestion putrefied in their turn. 
 
 Some have thought that this disease was trichinosis or typhoid 
 fever. Griesinger was party to this last opinion. Lebert, on the 
 contrary, was inclined to regard it as an intoxication from tainted 
 meat. Having had the documents in hand, I insist upon the long 
 duration of the incubation which was observed in the patients. 
 It has been shown since that there could not be any question of 
 trichinosis. At the autopsy of some of the people who had 
 been at that time ill, and had recovered, made a long time after- 
 ward, no calcified cysts were found in their muscles. If one 
 allies himself with the opinion of Lebert, he can only accept the 
 unwholesome meat as having caused the intoxications; the 
 accidents can only be explained by the mechanism of infection. 
 Why had certain individuals no sign of illness, in spite of the 
 fact that they consumed the same meat as those who became ill 
 or died? It is probable that they had eaten the parts of the
 
 AUTO-INTOXICATION AND INFECTION. 153 
 
 tainted meat that were the best cooked, the external parts, 
 where the action of heat had in part neutralized the poison. 
 
 Thus, in the famity epidemic of which I have just spoken, 
 out of four people who ate the same sausage, one remained free 
 from accident. This fortunate individual was the apprentice, and 
 to whom the masters had given the crust of the sausage, a part 
 much less prized by them than the central, but in which microbes 
 must have been destroyed by the action of heat. The infection 
 in the cases which I have just examined is not an infection with- 
 out any relation to intoxication, for there is no question of a 
 general infection, but of a surface infection. Without doubt, 
 there is at once induced an increase, more or less rapid and 
 enormous, of the quantity of infectious agents introduced into 
 the digestive canal ; but, secondaril}' to infection, there is, in all 
 probability, produced an intoxication. There are infectious 
 maladies in which microbes inhabit the blood ; they can subtract 
 oxj'gen from the blood-cells or from emboli in the small vessels. 
 There are other infectious diseases where microbes are present 
 in certain tissues, and induce therein anatomical lesions. In all 
 these cases the symptoms and death are easily explained. But 
 there are other infectious diseases where microbes,, only exist 
 upon a mucous surface, where they do not penetrate, and do 
 not alter the limiting membrane. How, in these cases of sur- 
 face infection, are we to explain the general symptoms and 
 death, if it be not by intoxication ? The danger as regards the 
 organism can only arise from the absorption b}' it of the toxic 
 products secreted by the infectious agents. The small microbes 
 form poisons like many large mushrooms. 
 
 There are cases in which infection no longer operates in an 
 acute transitory manner, but during several months and years; 
 it is the result of habitual putrefactions, of which the digestive 
 tube is the seat, in many of the chronic diseases which affect it, 
 and which are opposed alike to good digestion as to the healthy 
 elaboration of material. This is seen in cancer of the stomach, 
 in certain chronic dyspepsias, and in dilatation of the stomach. 
 Thus, besides the inconveniences which, from a nutrition point 
 of view, flow from imperfect digestion and insufficient alimenta- 
 tion, we see symptoms and alterations arise which bear witness 
 to the chronic deterioration of the organism by intoxication.
 
 LECTURE XVIII. 
 
 CHRONIC G ASTRO-INTESTINAL AUTO-INTOXICATIONS DILATATION 
 OP THE STOMACH. 
 
 Chronic auto-intoxication, having as the point of its origin the digestive canal, is 
 observed in chronic diarrhoea, cancer of the stomach or of the intestine, and 
 in chronic dyspepsia. Dilatation of the stomach may be taken as the type of 
 
 the morbid states which produce chronic auto-intoxication. Incredulity 
 
 of a part of the medical public as regards the subject of dilatation of the 
 stomach. Its frequency demonstrated by clinical statistics. Why it lias 
 been until pow unknown. It can only be revealed by physical signs. Insuf- 
 ficiency of percussion as the means of diagnosis of dilatation. Value of the 
 
 splashing sound as a means of delimitation of the stomach. Consequences 
 
 of gastric dilatation. Direct symptoms on the side of the gastric tube and 
 
 its annexes. Gastritis. Gastro-intestinal dyspepsia. Hepatic congestion. 
 Ectopia of the right kidney : floating or mobile kidney only exists in women 
 and military men ; it is induced by repeated congestion of the liver in people 
 the base of whose chest is made to undergo habitual constriction. Acci- 
 dents remote and at a distance. Disorders of innervation : sensibility to 
 cold. Disorders of the senses and intelligence. Disorders of general nutri- 
 tion and of the emunctories. Skin affections. Catarrh of mucous mem- 
 branes. Albuminuria and peptonuria. Inflammation of certain tissues and 
 
 of phlebitis. Alterations of the osseous tissues : deformity of the 
 
 phalango-phalangeal articulations of the fingers. Its semeiological value; 
 possible relation between dilatation of the stomach, rachitis, and osteomala- 
 
 cia. How can we explain the reaction of dilatation of the stomach upon 
 
 the whole of the organism ? Beau had already taught how dyspepsias pro- 
 duce an impression upon the nervous system. .Dyspeptic coma. General 
 
 accidents of dilatation of the stomach are no more surprising than those of 
 nephritis. Functional dignity and importance of the digestive canal in the 
 relative positions of the organs. Why the train of symptoms in dilatation 
 of the stomach should not be confounded with arthritism ; it constitutes, at 
 
 the most, minor arthritis. Clinical types of dilatation of the stomach: 
 
 latent forms, dyspeptic, hepatic, neurotic, cardiac, asthmatic, renal, cutane- 
 ous, rheumatic, acute or chronic consumptive. -Diseases of debility in- 
 
 which dilatation of the stomach is induced : chlorosis, tuberculosis. 
 
 Dilatation of the stomach is the result of an acquired diathesis. 
 
 THE facts enumerated in the preceding lecture do not all 
 
 constitute a strict demonstration of intoxication, they onl}' 
 
 cause it to be presumed. Nevertheless, there are some of them 
 
 which cany conviction, that of Senator, for example, in which 
 
 (154)
 
 TOXINS OP INTESTINAL ORIGIN. 155 
 
 one poison only sulphuretted hj'drogen was found in the 
 intestine and in all the excreted products : that which is personal 
 to me, and in which I have found alkaloids in enormous quan- 
 tity in the urine, as well as in the intestine. 
 
 Secondary intoxication can alone explain the fatal accidents 
 consecutive to surface infection ; for, if we understand the 
 mechanism of death in diseases where the infectious agent is 
 spread out in the whole of the organism, in the blood, or in the 
 principal viscera, how could life be arrested by a disease in 
 which the infectious agent rests on the surface of the mucous 
 membrane of the digestive tube, if that infectious agent does 
 not forniva poison which, being absorbed, diffuses itself through 
 the whole economy so as to impregnate the cellular elements or 
 to energetically impress the nervous system ? 
 
 There are, besides, cases in which some have been able to 
 isolate and define chemically toxic bodies ; Brouardel and 
 Boutin} 7 have done so. There are others where the symptoms 
 observed bear a remarkable analogy to certain well-known forms 
 of poisoning. Lepine and Daniel Molliere saw a case of intes- 
 tinal obstruction followed \>y accidents simulating intoxication 
 by atropine, with scarlatinal redness, mydriaSM, and acceleration 
 of the pulse. 
 
 We are now going to approach chronic intoxications having 
 as their point of origin the intestinal tube. They may be ob- 
 served in chronic diarrhea, in cancer of the stomach or intestine, 
 in chronic dyspepsia, and, above all, in dilatation of the stomach. 
 
 A year ago, I brought forward the statistical analysis of 220 
 cases of dilatation of the stomach which I had personally ob- 
 served. I could bring forward to-day nearly 400 cases, of which 
 274 have been seen by me outside of the hospital, and the others 
 in my service. When I announced to 3-011, last year, my virws 
 upon the consequences of dilatation of the stomach, I had not 
 met opponents by word alone. But at the Medical Societ}* of 
 the Hospitals, in the press, and in conversations with confreres, 
 I have found incredulity and jesting, which in our country 
 always welcome a new announcement. I believe that my oppo- 
 nents have passed bej'ond the question ; that they cannot judge 
 otherwise, because they were in want of facts to control my
 
 156 LECTURES ON AUTO-INTOXICATION. 
 
 way of viewing it. I do not know whether my opponents have 
 subsequently made the control Of that which I had advanced ; 
 but I have done it. Some may sa}', it is true, that my control 
 ought to be held only as a suspicion. And yet, if I am not mis- 
 taken, it seems to me that the denials, which were universal, are 
 fewer and less noisy ; they may carry with them divergence of 
 opinion as to the frequency of such a fatal concomitant, or bf 
 disease itself, but people no longer deny the existence of it. 
 
 I have said that dilatation of the stomach was neither an 
 anatomical curiosity nor a rarity ; that, whilst very frequent in 
 the sick, it is relatively uncommon in the healthy; and I have 
 mj^self asked the question whether people who, in appearance, 
 are not ill, but still have the physical signs of dilatation of the 
 stomach, are truly healthy? I have said that, generally speak- 
 ing, gastric dilatation had existed for a long time before the' 
 commencement of the disease with which we find it associated, 
 and that there is a cause for considering, in a very large number 
 of patients, besides the principal disease by which they are 
 designated, the other, dilatation of the stomach, which has the 
 appearance of being an accessory, and which has, perhaps, pre- 
 pared the way for invasion of the first. 
 
 Why has dilatation of the stomach been so little known for 
 such along time past, and yet so frequent? Because it cannot 
 be recognized save by establishing its physical signs ; but often- 
 est, on examination of the patient, the symptoms of which they 
 complain are not of the nature*to lead us to search for it. 
 
 Indeed, I can affirm, from an analysis of the facts, that 
 dilatation of the stomach may exist without inducing anomalous 
 sensations, without dyspeptic or gastralgie symptoms, in two- 
 thirds of the cases. It is a disease which does not announce 
 itself; we know that it passes unperceived. 
 
 The physical signs which permit of the recognition of dila- 
 tation of the stomach can be furnished by different methods of 
 clinical examination. Percussion is difficult and delicate to 
 practice, sometimes insufficient, and is rendered false in its 
 results, owing to tympanites of the colon. Succussion furnishes 
 no certain sign; it may bring out the noise of fluid in a normal 
 stomach, and yet it cannot reveal the extent of the dilatation.
 
 DILATED STOMACH AND ITS DETECTION. 15 f 
 
 I Lave pointed out as the best sign the sound of splashing, 
 already drawn attention to by Chomel. But it is necessary, in 
 order that it should have the whole of its semeiotic value, that 
 there should not have been recently the ingestion of any con- 
 siderable quantity of food capable of producing mechanically a 
 fleeting distension ; it is necessary that splashing should be 
 detected in a person who is fasting. If 3-011 do not hear it at 
 the first stroke, 3 r ou must not affirm that the stomach is not 
 dilated. It may be flattened and fall flabbily behind the abdom- 
 inal wall, like an apron ; but if you introduce one-third of a 
 glass of water into a dilated stomach, you will immediately hear 
 splashing over a region much greater in extent than in the 
 normal state. In the healthy man this phenomenon is never 
 perceptible fifteen hours after a meal. I still admit, through 
 courtesy, that it is necessary to perceive the splashing below the 
 middle of a line drawn from the umbilicus to the point nearest 
 to the border of the left costal arch. But, in reality, this line is 
 of little importance. Every stomach which is not retracted 
 when it is empty is a dilated stomach. Dilatation is not disten- 
 sion. A dilated stomach is a stretched stomach the cavity of 
 which is apparent only when it is empty, because, though its 
 walls then touch each other, it is no longer capable of diminishing 
 its own size by retraction. 
 
 It is not enough to know only that the stomach is dilated ; it 
 is necessary to know, in a precise manner, the dimensions of 
 this dilated stomach, to know its extreme limit below and its 
 extreme limit to the right of the median line, to pursue the 
 search after splashing until it disappears from above downward 
 and from left to right, and to establish thus its limits by the 
 determination of the two lines, traced upon the limits of the 
 zone where we observe splashing, one of these lines being 
 horizontal, the other vertical, parallel to the median line and 
 situated to the right of this line. 
 
 Is it possible, as some have said, to confound stomachal with 
 intestinal splashing? No; this is heard lower down. Besides, 
 we proceed to seek it from above downward, and from left to 
 right. In addition, it is easy to establish that the arrival of 
 water in the stomach is immediately followed by the noise
 
 158 LECTURES ON AUTO-INTOXICATION. 
 
 (bruit) of splashing ; water has not had sufficient time to reach 
 the colon. I still insist upon the necessity of assuring one's self 
 of the constancy of the phenomenon, which, sought for under 
 the same conditions, ought always to be perceived at the same 
 points. 
 
 If the demonstration can be considered as clinically accom- 
 plished, it is also anatomically. We can cause chopping to 
 appear in the cadaver, and we delimit the dimensions of the 
 area where it is heard ; we open the abdominal wall, and we can 
 convince ourselves that these are indeed the limits of the 
 stomach ; afterward, we sew up the wall, and anew we observe 
 chopping within the same limits. 
 
 Be certain that we do not often give ourselves the trouble of 
 seeking for dilatation of the stomach in the exact conditions 
 which I have indicated, and still less of measuring it. Yet we 
 ought to be able to know exactly the number of centimetres 
 which a stomach measures. If there truly exist marked dilata- 
 tion of the stomach, such as I have indicated; if there are 
 stomachs which, during several years, reach almost to the pubis, 
 as we have been able to verify them at the autopsy, it appears 
 a priori impossible that such an anomaly could exist without 
 disturbance of health. Assuredly, one can have a large stomach 
 and not experience dyspeptic troubles, but he is the victim of 
 disturbances in the elaboration of food. Men whose stomach 
 is dilated complain of their indisposition as being of very slow 
 development ; they are, nevertheless, ill for a long time before 
 becoming patients. Their diseases are, therefore, diseases of 
 debility, because the alimentary material, incompletely digested 
 and undergoing putrid fermentation, is no longer sufficient for 
 their nutrition. They are the victims of an insufficient alimenta- 
 tion both because the imperfection of digestion reduces the 
 value of assimilable material and because putrid fermentation 
 destroys another part of this ; for the hydrochloric acid of the 
 gastric juice, being too diluted, is no longer capable of oft'ering 
 opposition to the anomalous fermentative actions induced by 
 the figured ferments. 
 
 We notice, then, in individuals who present the physical signs 
 of dilatation of the stomach : 1. Pulmonary phthisis. 2. Chlorosis
 
 SYMPTOMS OF DILATED STOMACH. 159 
 
 (both of which accompany gastric dilatation, the first in two- 
 thirds of the cases, the second in four-fifths). 3. Nervous or hypo- 
 chondriac S3 r tnptoins. We see men without energy, who present 
 themselves at the hospital because they can no longer work, on 
 account of phj r sieal and mental debility ; we regard them often 
 as idlers, if not as hypochondriacs; we make an error in diag- 
 nosis. 4. Lastly, other symptoms, so varied and so numerous 
 that their mention at first provokes incredulity. 
 
 I shall not return to the details which I gave last }-ear upon 
 this subject. I ought, nevertheless, to make again a brief men- 
 tion of them. We meet, amongst patients whose stomach is 
 dilated, symptoms directly connected with the digestive tube. 
 The appetite is in general preserved ; it may be augmented. The 
 most of those who are the subjects of dilatation eat largely. 
 Ingestiou is not at all painful. But, at the end of two, three, or 
 four hours, the stomach is blown out, eructations are produced, 
 inodorous at first, then musty, sometimes fetid ; a sensation of 
 heaviness or of heat at the epigastrium ; pyrosis ; regurgitations, 
 whose acid odor demonstrates the reality of the anomalous fer- 
 mentations which are going on in the stomach, for the hydro- 
 chloric acid has no acid odor. This is due to acetic acid. The 
 faeces are generally doughy, stinking, acid ; although soft, they 
 are expelled slowly, and with pain. Their acidity is due, we 
 can assure ourselves, to the predominance of acetic acid. 
 
 The consequence of this development of acid in the whole- 
 length of the digestive tube is an inflammatory condition. We 
 notice catarrh of the stomach, ulcerative gastritis, to which 
 patients often succumb after twentj'-five years of bad stomach ; 
 these are the false cancers, as they are called, or malignant gas- 
 tritis without tumor. The large intestine is inflamed ; around 
 the Hecal matter are seen glairy secretions and sometimes blood 
 (membranous enteritis). 
 
 Besides the phenomena of gastro-intestinal dyspepsia, there 
 exists hepatic congestion. We find, amongst people with dil:iU-d 
 stomach, a swollen liver, often indolent; sometimes there exi>ts 
 an aching in the right hypochomlriuin ; sometimes jaundice, 
 without colorless stools. This congestion of the liver is of 
 short duration, and is modified vi-ry rapidly ; it may appear and
 
 160 LECTURES ON AUTO-INTOXICATION. 
 
 disappear in two or three days ; it sometimes, too, passes unno- 
 ticed. Of the 274 cases which I have observed outside the 
 hospital, I have found it thirteen times in 100 ; that is to say, in 
 one-eighth of the cases. 
 
 The knowledge of this tendency to hepatic congestion is 
 not without interest, from the point of view of the explanation 
 of the recurring jaundice of infants. It also explains, perhaps, 
 the ectopia of the right kidney, which I have always seen co- 
 incide with a dilatation of the stomach, but I can only believe 
 that this coincidence is accidental. It was made, in 1875, by 
 Bartels. This observer has an opinion different from mine as to 
 the bond which unites these two facts, ectopia of the kidney 
 and dilatation of the stomach. Bartels believes in the primary 
 displacement of the kidney. The kidney, says he, falls upon the 
 horizontal portal portion of the duodenum and opposes mechani- 
 cally the departure of food from the stomach, which thus 
 dilates. But if the kidney is displaced primarily, why is it 
 always the right kidney ? I say that the right kidney is 
 dislocated, because it is the liver which pushes it out of its 
 place. We do not find ectopia of the right kidne}' in all people 
 whose stomach is dilated, but only in those whose thorax is the 
 seat of a habitual constriction at its base, in women and military 
 men. Bartels has recognized this fact. The corset and the 
 abdominal band prevent the liver, when it increases in volume, 
 from passing in front of the kidney. Thus, if, ten or fifteen 
 times a year, there are produced sudden developments of hepatic 
 congestion, we can easily understand how the kidney, pressed 
 against, little by little, is displaced consecutively to the gradual 
 elongation of its vascular attachments. We observe, in all the 
 cases of dilatation of the stomach, luxation of the kidney four- 
 teen times out of 100. If we consider sex, the frequency is 28 
 per cent, in women and 3 per cent, only in men. Thus, if in 
 women more than one-fourth of the dilatations are attributable 
 to luxation of the kidney, dilatation of the stomach ought to be 
 in men sensibly less frequent than in women. Yet experience 
 shows that dilatation of the stomach is at least as frequent in 
 men as in women. 
 
 Dilatation of the stomach, on account of the anomalous fer-
 
 NERVOUS SYMPTOMS IN DILATATION OF THE STOMACII. 161 
 
 mentations which are the consequence of it, is accompanied, 
 besides, by distant disturbances, many of which form part of the 
 classical series of dyspepsias and are considered of the nature 
 of reflex. These are first the nervous symptoms of dyspeptics 
 (dyspepsia is accompanied by dilatation of the stomach in seven- 
 eighths of the cases). 
 
 Those who are ill are depressed in the morning, on awaken- 
 ing; at the end of half an hour they have often recovered their 
 alacrity. They complain of a painful circle around their head, 
 of headache, of feeling very depressed, an uneasy disposition ; 
 sensibility to cold, insomnia, vertigo, which belong to the history 
 of all diseases of the stomach ; obscuration of sight, hemiopia, 
 diplopia, weakness of the right internal muscle of the eye, 
 hallucinations of sight ; partial and fleeting dropsy of the 
 limbs, of an arm or a leg ; contracture of the extremities of 
 the hands, as pointed out by Kussmaul, Dnjardin-Beaumetz, 
 Hanot, and Hayem, and of which I have recently met with an 
 example. I have seen a patient who, at 2 o'clock in the morn- 
 ing, awoke in a start, and in a state of grief, with a contrac- 
 ture of the hands, a contracture which extended up to the arms 
 and the shoulders ; this condition lasted for five weeks. I de- 
 tected in her a dilatation of the stomach, and prescribed the ap- 
 propriate treatment ; on the following night she had not the crisis, 
 nor had she it on the subsequent evenings, so long as she observed 
 the regimen. One day she failed to do so ; the same evening con- 
 tracture of the hands re-appeared. It has entirely disappeared 
 since, thanks to the continued observance of a better hygiene. 
 
 I have noticed, too, transitory aphasia, and once fatal syn- 
 cope, disturbances of vascular innervation, a sensation as if two 
 or three fingers were dead, palpitation, flushing of the face two 
 or three hours after meals, false angina of the breast, nocturnal 
 perspirations (limited to the head, neck, and thorax). I would 
 also mention, following Chantemessc and Le Noir, bilateral inter- 
 costal neuralgia. 
 
 All these phenomena may be, strictly speaking, regarded as 
 reflex. But there are others which arise from the abnormal 
 metamorphosis of matter. And, as for these, how ara they to 
 be explained if not by intoxication ? 
 
 11
 
 162 LECTURES ON AUTO-INTOXICATION. 
 
 Besides the nervous symptoms which are rightly or wrongly 
 considered reflex, I have detected, in people whose stomach is 
 dilated, symptoms on the side of the general nutrition and dis- 
 turbance of the emunctories. 
 
 I have said that they are, in general, patients who are chilly ; 
 they have, nevertheless, free perspirations, night and day, and 
 after the least exercise, a walk on foot upon even ground, or 
 after having ascended two flights of stairs. These perspirations 
 have a heavy or musty odor, as of mouldy bread, according to 
 the statement of some of the patients. 
 
 We notice amongst them eczema thirteen times out of one 
 hundred, pityriasis in front of the sternum or of the head, 
 pityriasis versicolor. 
 
 Urticaria is not uncommon amongst those suffering from 
 dilatation. But urticaria, although it does not pass for a dis- 
 ease of intoxication, and although it is not frequently noticed 
 in the course of infectious diseases, yet it has arisen, in some 
 unexplained way, during indigestion and gastric embarrassment. 
 We have seen it follow the ingestion of mussels, certain stale 
 fish, and various shell-fish. Are not these all toxic causes ? Urti- 
 caria has often been observed after puncture of hydatid cyst 
 of the liver; it has been attributed, in similar cases, to the intro- 
 duction of a part of the fluid of the cyst into the peritoneum 
 and to its subsequent entrance into the lymphatic channels ; it 
 would be, even there, a kind of intoxication. It is not correct 
 that some should put as the cause of it exclusively the action of 
 the peritoneum. Whilst chef de clinique, I have seen a young 
 girl, the subject of a hydatid cyst, upon whom Behier had ad- 
 vised a large opening of the liver to be made by means of suc- 
 cessive cauterizations, after the manner of Recamier ; in order to 
 bring about adhesion with the abdominal wall, he had, by means 
 of Canquoin paste, produced a kind of tunnel into the hepatic 
 tissue. He reached a cyst of a size so small that he thought 
 that there were multiple cysts and that he would have to resort 
 to puncture, to be made in the depths of the tunnel. There 
 only flowed out a few spoonfuls of a liquid clearly hydatid, in 
 which booklets were detected by the microscope. He pushes 
 .the treatment farther, and there is seen to escape a jet of red
 
 SKIN ERUPTIONS AND DILATATION OP THE STOMACH. 163 
 
 blood, come from a branch of the portal vein. And yet, the 
 only accident after this was a general eruption of urticaria. 
 It is evident that penetration of the liquid of the cyst, took 
 place- directly into the blood, and that there was here clearly a 
 case of toxic urticaria without any intermeddling of the peri- 
 toneum. 
 
 Besides, I think that urticaria is often of a toxic nature, like 
 other congestive eruptions with vesicles on the skin ; quinine 
 eruptions, which may assume the erythematous form ; scarlatinal 
 or papular, like a variety of the erythema due to copaiva, or 
 like the exanthem of belladonna. 
 
 Amongst certain young girls, we see acne on the temples on 
 the parts about the chin coincide frequently with dilatation of 
 the stomach, as well as acne rosacea, with scarlet redness of the 
 nose and cheeks, which -develop about two hours after meals, 
 and which, for a long time past, have been considered as indica- 
 tions of a bad stomach. Are not these cutaneous manifestations 
 of toxic origin, like those which often follow the ingestion of 
 chloral ? 
 
 I suppose that, as the result of the ingestion of these various 
 medicaments, the cutaneous vasomotors are impressed by the 
 direct action of the poison, or their disturbance is the result of 
 a reflex of the nervous system. Yet, Avhen it is a question of 
 morbid secretions, like acne and eczema, it is difficult to admit 
 the interference of the nervous system. Would it not be more 
 advisable to incriminate the elimination of fatty volatile acids? 
 Whatever may otherwise be the interpretation, the empirical 
 fact of the linking on of dilatation of the stomach to a large 
 number of cutaneous manifestations remains certain ; it is, 
 therefore, a series of links and not an accidental association. 
 For a pathogenic explanation I propose to you, for the time 
 being, intoxication. 
 
 The mucous membranes, like the cutaneous coverings, serve 
 for the elimination of gaseous matters and volatile fatty acids 
 arising from abnormal fermentation which has taken place in the 
 stomach. The odor of the breath is a witness to their elimination 
 by the respiratory mucous membrane. Besides, people who are 
 the subjects of dilatation of the stomach catch cold easily, cougU
 
 164 LECTURES ON AUTO-INTOXICATION. 
 
 habitually ; their bronchi secrete mucous sputa which are with 
 difficulty detached, and lead up to dyspnoea and rhouchi. I 
 have (bund sibilant, noisy, recurrent bronchitis ten times in 
 every one hundred of my actual statistics (instead of 15 per cent, 
 in my statistics of last year) ; dyspnoeic respiration of paroxysmal 
 character, recalling the advent of asthma, four or five times in 
 every one hundred. I have also noticed recurring coryza and 
 frequent sneezing in the morning. These, also, I suspect, we 
 must rather consider the result of the elimination of toxic sub- 
 stances than a reflex act. 
 
 On the part of the kidneys, there exist important disturb- 
 ances. Without speaking of ectopia, upon which I need not re- 
 turn, and whose mechanism is quite peculiar, albumiuuria is 
 extremely frequent, not only as a trace, but in measurably large 
 quantities, in the form of a retractile coagulurn when the action 
 of heat is made to follow that of coagulating reagents. I have 
 established it seventeen times in one hundred cases in my most 
 recent statistics (I had said 13 per cent, for one hundred last 
 year). When the condition of the stomach has been relieved 
 albuminuria diminishes, or even disappears, to return, however, 
 on the least indiscretion of diet. It follows in a line parallel 
 to that of the disease. 
 
 Can we consider the albuminuria as dyscrasic and arising from 
 a vitiation of the general nutrition ? Is it the consequence of irri- 
 tation, or of inflammation of the renal tissue by toxic substances 
 which it is eliminating? I do not undertake the solution of 
 these questions. 
 
 Albuminuria is variable as regards its intensity and its per- 
 sistence ; it is most frequently curable. In certain cases it lasts 
 for a long time, being the sign of a renal lesion. M. Tapret had 
 pointed out the bruit de galop in a case in which albuminuria 
 appeared to be associated with the existence of a dilatation of the 
 stomach ; the albuminuria having disappeared, the heart ceased to 
 beat in accordance with the albuminuric rhythm ; later on, it is 
 true, cardiac troubles had returned. I have observed several 
 analogous cases. 
 
 Peptonuria is frequent in dilatation ; I believe I was the first 
 to draw attention to it. Whilst in the normal state, peptone
 
 AFFECTION OF TEIE BOOT TISSUES. 165 
 
 cannot be discovered in the blood, either because it has been 
 transformed into albumen in its passage through the walls of the 
 intestine, or the liver has changed it, or the white blood-cells 
 have laid hold of it. In certain people, the subjects of dilated 
 stomach, it passes into and remains in the blood, and is dialyzed 
 afterward in its passage through the kidneys. 
 
 Let us now put upon record the modifications of general 
 nutrition in people whose stomach is dilated. As a goodly 
 number of the organs suffer, it is, therefore, not surprising that 
 one should have to note loss of power, diminution of physical 
 and moral energy, emaciation in the advanced phases, but often, 
 also, lax obesity with pallor, abundant deposit of unites in the 
 urine, increase of acidity of the urine, and the appearance of a 
 red-wine coloration on the addition of perchloride of iron. 
 
 Inflammation may seize certain of the tissues ; we notice 
 phlebitis. I have, twice out of one hundred times, noticed 
 spontaneous phlebitis, and I have insisted upon the importance 
 of this point, which no longer permits us to accord to sponta- 
 neous phlebitis coming on in the course of a chronic d3 r spepsia 
 the signification which Trousseau assigned to it. Purpura, 
 which indicates fragilit}' and bad nutrition of the vessels, is met 
 with two or three times in every one hundred. 
 
 In short, I ought to recall the existence of modifications of 
 the bony tissue in the neighborhood of certain articulations. I 
 have insisted upon the frequency of nodosities on the phalan^o- 
 phalangeal articulations of the fingers; they are formed by 
 enlargement of the bases of the second phalanx ; in some 
 rare cases upon the anterior part of the base are seated two 
 lateral nodules, as we see them in the rheumatic nodules of 
 Heberden, which are always found at the third articulation. 
 We often see the four fingers of the two hands present, simul- 
 taneously, these deformities. Nearly always the patients are 
 astonished when we call their attention to these ; the}' consider 
 that they have always had them. Sometimes, however, the 
 parents know the date, approximately, of their appearance, after 
 an absence from home, such as, for instance, their return from 
 college. In some people, pains are felt in the joints which have 
 become deformed.
 
 166 LECTURES ON AUTO-INTOXICATION. 
 
 Sometimes other joints may be deformed. I have noticed, at 
 the metacarpo-phaiangeal articulation of the thumb, a swelling and 
 pain. In cases much more rare, I have noticed pain and swelling 
 at the level of the wrist; we sometimes observe painful swellings 
 of other joints, and, in particular, of the internal extremity of 
 the clavicle. Out of the whole of the observations, I have 
 noticed joint deformities twenty-five times in every one hundred, 
 and in men, taken apart, thirty-two, times in one hundred. They 
 are susceptible of improvement, or of lessening if the stomach 
 improve. I have seen oscillations running pai'allel with this 
 condition. 
 
 What can be the meaning of these nodosities? 
 
 Some have said, in opposition to me, that they were the effect 
 of rheumatism, just as dj'spepsia is. But, really, there is no 
 choice in this of rheumatic deformation. Chronic partial rheu- 
 matism affects the knee and the hip ; the nodosities of Heberden 
 are seated at the third articulation of the fingers. Asthenic 
 primary gout and deforming rheumatism seize the wrists and 
 the phalango-phalangeal articulations at once, and only sec- 
 ondarily the second articulations. Why do we not see, in 
 dilatation of the stomach, other joints seized, the knees and 
 metacarpo-phaiangeal? Otherwise, the subarticular signs of 
 rheumatism are awanting in those who, having dilatation of the 
 stomach, are, at the same time, the bearers of nodosities on the 
 fingers ; it is only by a begging of the question that we attribute 
 them to arthritism. 
 
 In any case, I maintain the reality of the following empirical 
 fact : When you find people whose fingers present, at the level 
 of the second articulation, the nodosities of which I have spoken, 
 you will nearly always notice in them the physical signs of dil- 
 atation of the stomach. 
 
 We may see nodosities situated also at the second joint of tlie 
 big toes ; one is rarely led to seek for them in consultation, but, 
 seeking them, I have found them in some cases. 
 
 Not only may other joints be affected, but the osseous tissue 
 itself may suffer, even in the continuity of the long bones. Thus 
 may sometimes be explained rachitis and osteomalacia. If in the 
 child, rachitis, as M. Comby has said, may be one of the con-
 
 DYSPEPTIC COMA. 167 
 
 sequences of dilatation of the stomach, it has appeared to me in 
 several cases that osteomalacia, in the adult, may receive a 
 similar interpretation. 
 
 En resume, it seems to follow, from the existence of so 
 man}' organic and functional troubles in people the subjects of 
 dilatation of the stomach, that there is created in the organism 
 a special aptitude for the tissues to become inflamed, and for 
 perversions of nutrition to arise, from which result fragility of 
 some part of the tissues and changes in the form of others. 
 
 What has occasioned surprise among many physicians, when I 
 have pretended to establish a relationship of cause and effect 
 between dilatation of the stomach and the other symptoms 
 which are associated with it, is the variety of these symptoms, 
 which a simple change of form of that viscus is incapable of 
 explaining to them. Numerous, however, are the local diseases 
 which take their hold upon the organism. 
 
 For a long time past, since Beau and before him, we have known 
 how dyspepsias cause an impression upon the nervous system, the 
 feelings, movements, nerves of the vascular system, and ideation ; 
 we have admitted that certain nervous symptoms, contracture 
 of the extremities, may be induced by gastro-intestinal trouble. 
 Whatever the disease of the stomach may be, certain functional 
 disturbances are sufficient to cause the development of dyspeptic 
 coma, which, symptomatically, is identical with diabetic coma. 
 
 This coma has been seen in cancer, chronic ulcerative gas- 
 tritis, and I have seen it in dilatation of the stomach. Jacksch 
 and Senator have properly described it. There is, at first, agi- 
 tated movement, jactitation ; then comes a gradual somnoles- 
 cence, rapidly changing into coma. We notice a singular 
 form of dyspnoea, twenty or thirty respirations only per min- 
 ute, but constituted by a deep and laborious inspiration, with 
 great movement of the larynx and a moaning, panting expira- 
 tion. The temperature is normal; the pulse small, frequent, and 
 compressible. The odor of the breath recalls that of chloroform ; 
 probably it is due to the same substance as that which is exhalrd 
 in the breath of diabetics, since we find it in urine with the 
 same chemical reaction. It has, besides, been also noticed in 
 leucocytluemia and pernicious anu-mia.
 
 168 LECTURES ON AUTO-INTOXICATION. 
 
 Is it astonishing, therefore, that severe nervous symptoms 
 should be caused by a simple dilatation of the stomach ? 
 
 What occurs in the chronic gastroenteritis of infants due to 
 a defective or premature alimentation ? At first there appears 
 green, acid diarrhoea, which excoriates the buttocks; then arise 
 subsequent phenomena, fever, cutaneous eruptions (erythema- 
 tous, eczematous, and pustular), and, lastly, the peculiar nodosi- 
 ties of rachitis. These are, really, alterations of the bony tissue, 
 induced by a primary disease of the stomach. 
 
 It has been accepted, but not without difficulty, that, the 
 kidney being diseased, there may result from it general disturb- 
 ances, dropsies, nervous accidents, headache, pruritus, deaf- 
 ness, amaurosis, dyspnoea from functional trouble of the heart, 
 but, also, modifications in the structure of the heart ; hypertrophy 
 of the left ventricle with, as a stethoscophic sign, reduplication 
 of the first sound. It has been thoroughly acknowledged, be- 
 cause each fact was presented in an isolated and successive man- 
 ner, that all these conditions, so varied, arise from disease of 
 the kidney. I believe that, in the same manner with regard to 
 dilatation of the stomach, we will come to recognize the fact that 
 the accidents so varied which accompany it are really subordi- 
 nated to it. 
 
 If I am of this opinion, it is because I represent to myself 
 the kidney as an organ with a functional dignity inferior to 
 that of the digestive canal ; it eliminates matter without alter- 
 ing it; and j'et, what disturbances its diseases cause in the 
 organism ! 
 
 What can it be, therefore, which passes when the stomach is 
 at fault, the functional derangement of which disturbs the whole 
 intestine ? How is it possible for its derangement not to affect 
 the whole organism ? Think of the physiological importance of 
 the digestive tube. It introduces into the organism all the solid 
 and liquid material, all except oxygen, and, before introducing 
 the material, it must elaborate it. It has, therefore, not only to 
 play the part of an emunctory, but its functional derangement 
 must vitiate part of the emunctory apparatus and the cells of 
 all the organism. 
 
 Some people are willing to admit the reality of the symp-
 
 AFFECTIONS OF JOINTS. 169 
 
 toraatic grouping which I have indicated, but they do not con- 
 sider that all the associated symptoms may be subordinated to 
 the stomach; there would be links established between them and 
 it, but no subordination. As in certain cases of dilatation we 
 find re-united several symptoms which recall arthritism, nodosi- 
 ties of joints, migraine, neuralgias, sibilant bronchitis, eczema, 
 :md as arthritism determines dyspepsia accompanied by a cer- 
 tain degree of laxity of the stomach, we are forced to rely upon 
 this coincidence, so as to say that dilatation of the stomach is 
 only one of the consequences of arthritism, like the other 
 symptoms of which I have just spoken. 
 
 But this assemblage of symptoms of an arthritic nature is 
 only the small coin, as it were, of arthritisra ! They are dis- 
 orders which may arise outside of the arthritism ; they are not 
 the grand, fundamental signs of the diathesis; it is, so to speak, 
 arthritis minor. We have in this enumeration met with neither 
 diabetes nor gout. These are two diseases which are not met 
 with outside of arthritism ; on the contrary, dilatation of the 
 stomach is rare amongst diabetics and the gouty. The} 7 may, 
 nevertheless, arise in such by way of d}-spepsia, should they be 
 dyspeptic, and yet great eaters ; for they accumulate one meal 
 upon the preceding one not digested ; they thus take meals 
 irregularl} r , and in too great quantity. I do not say that arthri- 
 tism is not concerned as a predisponent in the pathogenesis of 
 certain dilatations of the stomach. But there is another influ- 
 ence, the direct heredity of this organic disposition. We very 
 often see a mother and her four children the subjects of dilata- 
 tion. Is it because they live in common and in the same manner, 
 and undergo the same hygienic trials ? No ; it is that there are 
 families in whom the stomachs have a congenital tendency to 
 undergo dilatation. 
 
 In a ward in the hospital, out of ten patients taken at ran- 
 dom, you will find three with dilatation. This frequency of 
 dilatation in the class of people attending hospital, and which is 
 less predisposed to arthritism, agrees little with the opinion 
 which would see in dilatation of the stomach an affection of an 
 arthritic nature. It is true that, in our time, men of the work- 
 ing class have borrowed from the governing classes a certain
 
 170 LECTURES ON AUTO-INTOXICATION. 
 
 number of their faults and vices of Irygiene. But I have little 
 hope in convincing the generation to which I belong. When 
 one has taken up a certain line of study he does not care to 
 leave it to undertake another. I address myself, therefore, 
 chiefly to those who are now receiving their education, and I 
 ask them to affirm my statements. It is not by immediate dis- 
 cussion that one can settle such questions, but only by facts. 
 And yet, amongst those who attack my manner of viewing them, 
 how many of them are there who have ever thought of seeking for 
 dilatation of the stomach amongst all patients ? Amongst those 
 who may wish to do so, how many of them know how to do it? 
 And, amongst those who can seek for the existence of a dilata- 
 tion, how few are preoccupied with the greatness of the 
 question? If we now examine under what appearances dilata- 
 tion of the stomach is presented to us, we are led to recognize 
 several clinical types of it. 
 
 There exists a latent form ; it is the most frequent, since it 
 constitutes two-thirds of the cases. No abnormal sensation is 
 complained of by the patient ; no functional trouble is revealed 
 on his being interrogated. Only a careful examination of all 
 the organs can alone enable us to recognize the physical signs 
 of dilatation of the stomach. In the dyspeptic form, the 
 patient complains of pains, of slowness of digestion, and often 
 of constipation. The hepatic form is constituted by congestion 
 of the liver, which shows itself by increased size in the volume of 
 this organ and sensation of weight in the right hypochondrium. 
 It is sometimes accompanied by jaundice, and frequently appears 
 in young subjects, which is, perhaps, the explanation of the 
 chronic jaundice of infancy. 
 
 There exists a form which simulates biliary lithiasis ; pseudo- 
 gastralgic pains, which are often really gastralgic, show them- 
 selves slowly, when intestinal digestion commences. Owing to 
 the hydrochloric acid being deficient, acetic acid is produced in 
 excess, and irritates the mucosa of the intestinal tract. We 
 should include movable kidney rather in the renal form, although 
 it depends upon repeated congestions of the liver. 
 
 To the neurosal type belong vertigoes, depression in the 
 mornings, migraine, vascular spasms of the fingers, spinal irrita-
 
 ORGANS AFFECTED. 171 
 
 tion, cerebro-cardiac neurosis, hj'pochondriasis, contractures of 
 the extremities. 
 
 The cardiac form includes palpitations, breathlessness, beat- 
 ing in the temples, redness of the face, cardiac anguish, and 
 false angina pectoris. 
 
 The asthmatic form, or bronchitic, is that in which coryza is 
 frequent; in which glutinous expectoration, occluding the 
 bronchial tubes, provokes laborious cough with sibilant sounds, 
 which disappear when the patient has succeeded in expelling 
 it. 
 
 The renal form it is very important to recognize. When we 
 have established in a person an albuminuria which is not the 
 transitory albuminuria of fever, and when we are undecided be- 
 tween the hypothesis of a lesion of the kidney and that of a car- 
 diac affection, it is necessary to think that this albuminuria may 
 be of dyspeptic and stomach origin, since seventeen times in 
 every one hundred albuminuria co-exists with dilated stomach. 
 Simultaneously, the same accidents may exist as those which 
 are under the dependence of other albuminurias, cardiac hyper- 
 trophy, for example. 
 
 Under the name of the cutaneous form we may include 
 urticaria, acne rosacea, and certain circumscribed eczemas, etc. 
 
 The rheumatismal form, although the word may be defective, 
 is characterized by the predominance of joint manifestations, 
 which at once attract the attention, and which are often wrongly 
 looked upon as chronic rheumatism. To this form phlebitis is, 
 perhaps, attached. I have seen this amongst medical men who 
 had dilatation of the stomach and who considered themselves 
 the subjects of rheumatismal phlebitis. 
 
 Lastly, there is occasion to admit an acute or chronic con- 
 sumptive type. In the acute consumptive type the patient has 
 always suffered in his stomach for ten or fifteen years, then he 
 rapidly feels himself thoroughly exhausted, and soon after he is 
 no longer able to leave his room, not even his bed. The phy- 
 sician, finding no organic lesion, calls the case one of nervous 
 fever. To the chronic consumptive type belongs the case of so 
 many patients who in the hospitals pass either for idlers or 
 hypochondriacs.
 
 H2 LECTURES ON AUTO-INTOXICATION. 
 
 We could multiply these types, but around these ten ma}' be 
 grouped all the other sjnnptoms. We must still remember the 
 fact that dilatation of the stomach renders the economy more 
 vulnerable, and opens the door to diseases of debility. Chlorosis 
 amongst young girls and pulmonary phthisis are often induced 
 by dilatation of the stomach. This latter exists in two-thirds 
 of the tubercular, and, if we have sought for it early enough, we 
 can convince ourselves that the physical signs of dilatation 
 have sometimes for long preceded the first symptoms that may 
 be regarded as the premonitions of tuberculosis. 
 
 I am, therefore, fully of the opinion that dilatation of the 
 stomach is the outcome of a veritable acquired diathesis, a 
 morbid disposition due to a disturbance of the general nutrition. 
 Do we not see it, for example, induce alterations in the skeleton 
 in the same way as that to which we attribute the production of 
 rachitis? If it is true that in rickets it may be the formation 
 of lactic acid in excess which hinders the calcification of the 
 bones, in patients attacked with dilatation of the stomach the 
 formation in the digestive tube and the absorption of acetic acid 
 in excessive quantity perhaps explain the nodosities on the 
 fingers. I have even seen osteomalacia produced ; at least, the 
 bones were painful at the level of the ribs, joints, femur, and 
 pelvis. I have seen the pain increase by standing so as to render 
 walking impossible.
 
 LECTURE XIX. 
 
 DILATATION OF THE STOMACH ETIOLOGY, PATHOOENESIS, AND 
 THERAPEUSIS. 
 
 Causes of dilatation of the stomach. Hygienic causes : excessive, permanent, 
 or too frequent distension of the stomach, In consequence of bad alimentary 
 hygiene. Pathological causes : catarrhal or interstitial inflammations ; me- 
 chanical obstacles to the evacuation of the contents of the stomach. Physio- 
 logical causes : insufficient iunervation ; congenital or acquired debility of 
 the muscular tunic ; reciprocal relations between typhoid fever and dilatation 
 of the stomach ; predisposition of those suffering from dilatation to contract 
 
 typhoid fever. Therapeutics based upon the knowledge of causes. General 
 
 stimulants. Alimentary hygiene. Regularity and infrequency of meals. Sub- 
 stantial alimentation in small volume. Choice of foods. The unsuitableness 
 of alcoholic drinks and of everything which keeps up excessive fermentation 
 in the stomach. Why insufficiently-baked bread is not easily digested. Re- 
 cent researches upon the fermentation of bread. Necessity for reducing 
 
 the quantity of drink. How the dietary which I propose for dilatation of 
 the stomach is not simply the dry regimen proposed by Chomel for dyspep- 
 sia due to the use of liquids. Milk food as the preparatory regimen in the 
 
 cure of dilatation. Mixed regimen of eggs and milk. Regimen of infre- 
 quent and complete meals. Nutritive enemata. Antiseptic medica- 
 tion as an auxiliary to the dietetic regimen : chloroform-water, hydrochloric 
 lemonade. Indications for washing out the stomach. Treatment of pyrosis 
 
 and of ulcerative gastritis. Advantageous result of the above-mentioned 
 
 regimen : rapid disappearance of the most disturbing and most painful 
 symptoms. Necessity for lengthened continuation of treatment, in order 
 to arrive at a complete cure, which is not always possible. 
 
 IN order to place before you again, in a few words, all the 
 knowledge we have accumulated upon intoxication of intestinal 
 origin, I recall to you that, after having demonstrated their reality, 
 I have shown 3-011 how intoxication may be the result of normal 
 fermentation, if the kidney is diseased, and how, with a healthy 
 kidney, intoxication may be produced by abnormal fermentation. 
 Afterward, I have proved to you that intoxication of intestinal 
 origin, from abnormal fermentation, may show itself in either 
 the acute or chronic state. The time has now come for consid- 
 ering the therapeutics of this intoxication. I ought already to 
 have dealt with, in a summary manner, intestinal antisepsis, 
 
 (173)
 
 174 LECTURES ON AUTO-INTOXICATION. 
 
 having been almost of necessity led to it, in order to interpret 
 ursemia and to study its therapeutics. I am now led to undertake 
 this question, whilst studying the treatment of intoxication 
 from chronic dyspepsia ; that is to say, chiefly from dilatation of 
 the stomach. But all the treatment of chronic intoxication 
 of digestive origin does not lie in intestinal antisepsis. It is 
 not sufficient to neutralize or to delay fermentations. Without 
 neglecting the employment of charcoal, which fixes the products 
 of putrefaction, of iodoforrn, and of naphthalin, which prevent 
 these from developing, it is necessary to address ourselves to 
 the physiological actions of the organism, in order to correct 
 the functional disturbances of the digestive canal. 
 
 We ought, if we can, to act upon the disease which leads to 
 fermentation in the digestive canal by referring to its causes, or 
 to what is predominant in chronic dyspepsias, that is, dilatation 
 of the stomach. In eight cases of dyspepsia we find seven 
 times an exaggerated distension of the stomach with an impos- 
 sibility of retraction. The causes of this excessive, permanent 
 distension are numerous. Some arise from faulty alimentary 
 hygiene. Excessive distension, too often repeated and pro- 
 longed, leads up, more or less rapidly, to a forced condition of 
 stomach. Individuals who eat too much or drink too often 
 dilate their stomach, but other hygienic errors lead to the same 
 result. To eat too quickly, when we come to table with an 
 excessive appetite, due to irregularity in our meals, is hurtful, 
 for a very fine mechanical division of food is indispensable for 
 its digestion. Irregularity of meals has also for its conse- 
 quence the leaving of only too short an interval between certain 
 meals. A meal is then introduced into the stomach, which still 
 contains part of the preceding one. These are all bad hygienic 
 habits, which mechanically engender dilatation of the stomach. 
 Other causes may also be in operation, such as bad teeth, which 
 prevent good mastication. 
 
 We can remedy all these causes in the premonitory period, 
 but when the stomach is thus forced, what then ? You will be 
 able to advise a certain number of palliative measures, which 
 will only bring to the patient a minimum of help, if you do not 
 seek in the minute analysis of the elements of the morbid state
 
 PYLORIC OBSTRUCTION AND MUSCULAR DEBILITY. 175 
 
 those which therapeutics could attack with the greatest chances 
 of success. 
 
 Mechanical distension sometimes follows from pathological 
 causes, from an antecedent dyspepsia having determined 
 habitually too long location of food in the stomach ; from a 
 chronic catarrh of the mucous membrane, preventing physio- 
 logical secretion ; cancerous or cicatricial constrictions of the 
 pylorus. The puckered cicatrix of a cured ulcer of the pylorus 
 may progressively lead up, in quite a mechanical manner, to 
 distension of the stomach, where digestion, nevertheless, is 
 normal in operation. "We may attribute a large share in the 
 pathogenesis to debility of the muscular wall. General nervous 
 debility that state of irritable debility and neurasthenia which 
 exists amongst hysterical people and in ataxies causes varia- 
 tions in the energy of the central nervous sj-stem, whence there 
 results distension ; but this is rarely permanent. We notice, too, 
 an intermittent distension in exophthalmic goitre, in convales- 
 cence from serious affections, after grief, prolonged indisposition, 
 sad mental preoccupation. All these distensions have not }-et 
 become dilatation, but may end in it. It is also necessary to 
 take cognizance of the radical debility of such and such a tissue 
 in certain people, in consequence of which, in the pathogenesis 
 of dilatation of the stomach, there is occasion given for the 
 influence of heredit}'. It is certain that in the same famil}'- dila- 
 tation of the stomach exists amongst several individuals, without 
 our being able to call to our aid, in order to explain it, a group 
 of hygienic defects. It may be said of the stomach, as of the 
 scrotum, which is habitually retracted in certain people, that there 
 is a weak condition in some, owing to a natural muscular debility. 
 
 Lastly, debility of the muscular wall of the stomach may be 
 the result of a morbid degeneration. The study of degenera- 
 tions of the muscular wall has been made in the intestine by 
 Blaschko, Sasaky, Nothnagel, and Schleimpflug. They have seen 
 atrophy to be the result of fatty degeneration of the muscular 
 tunic itself, consecutive to inflammatory affections of the mucous 
 membrane, to intemperance, or to habitual alcoholic intoxica- 
 tion, to lesions of the intestinal and central nervous system, 
 and, lastly, to infectious diseases.
 
 176 LECTURES ON AUTO-INTOXICATION. 
 
 These causes are probably attributable to debility of the 
 gastric muscular wall. After typhoid fever it is developed ; 
 oftener it arises at the beginning and even before the commence- 
 ment of the disease. It is not rare that t} r phoid fever is devel- 
 oped in people whose stomach has already been dilated. I have 
 seen, in the course of these two last years, twelve cases of 
 typhoid fever in my practice at the hospital ; that is to say, 
 coming on in patients under treatment for another illness, twelve 
 times was there question of patients the subject of dilatation of 
 the stomach. We might ask the question, whether dilatation 
 had not prepared the way for the introduction of the infectious 
 agent ? I content myself, for the moment, by an empirical 
 statement of the fact. The largest number of patients whom we 
 treat in the hospitals for typhoid fever carry nodosities on the 
 second articulations, which prove that dilatation was the 
 primary. 
 
 If these, therefore, are the varied causes which may., take 
 part in dilatation of the stomach, what resources may their 
 knowledge furnish us with for their therapeutics ? Nothing of 
 consequence, save two things. If there exist habitually a con- 
 dition of primary dyspepsia, aggravated recently, it will be 
 advisable to combat this dyspeptic state, in order to allow 
 the stomach to become retracted. If the nervous system should 
 increase the retractility of what remains of healthy muscular 
 fibres, general stimulants can indirectly give advantageous 
 results ; they will not cure, but they will aid in the cure. We 
 may stimulate directly the nerve terminations in the gastric wall 
 by simple bitters and astringent bitters. We may give attention 
 to the general nervous system in its cutaneous and peripheral 
 expansions ; we may prescribe dry or aromatic friction, change 
 of air, high altitudes, sea-air. It is necessary to remove all 
 care, preoccupation, and to procure distraction by traveling 
 and pleasurable occupation. Distraction is particularly neces- 
 sary during meals, which it is well to take in pleasant company. 
 These are small measures, but their utility is beyond question. 
 We might derive benefit from the cold or hot douche, or the 
 shower bath, with ordinary water, or that containing sulphur or 
 saline material. We need not ask how a cutaneous douche
 
 PRINCIPLES OF ALIMENTARY HYGIENE. 177 
 
 revives the stomach ; it is simply a question of improving function. 
 With a bad tool a workman may do pretty good work. Sulphur- 
 ous and saline baths, sea-baths, cold baths, and baths of Plom- 
 bieres may be useful. I can scarcely believe in the favorable 
 influence of electricity, in spite of the results of which some 
 have made a great noise. They publish at first the successful 
 cases, and they forget to mention the others. Inhalations of 
 oxygen sometimes answer well ; these improve the appetite and 
 stimulate digestion. 
 
 Lastly and chiefly, we must pay attention to alimentary 
 hygiene. This includes the whole of the means which cause 
 digestion to be rapid, and which thus prevent a protracted stay 
 of food in the stomach. We may put it in the following axiom : 
 it is necessary that the stomach should be distended the least pos- 
 sible, least often, and for the shortest time possible. We must first 
 masticate well; consequently, certain buccal preparations are 
 sometimes necessary. We must eat slowly, and without mental 
 worry. It is necessary to abstain altogether from work immedi- 
 ately after meals. Fatiguing work is bad, even if it is physical 
 work ; what is useful is no longer repose, but muscular activity 
 in the open air, without it being pushed to the extent of fatigue. 
 
 There must be neither eating nor drinking between meals. 
 The meals must be widely separated from each other. To eat 
 once a day is impossible. If we only make two meals, should 
 these be separated b} r twelve hours? No ; the needs of the 
 organism are much less during the period given up to repose. 
 We must allow nine hours between the two meals as the interval 
 by day, and fifteen hours as the interval by night. This infre- 
 quency of meals is sometimes sufficient to cause heartburn to 
 disappear and the sensations of heat, and to arrest the emacia- 
 tion of patients who should moderate their appetite in order to 
 prevent their pains. As a rule, we must allow to patients three 
 meals per diem, with an interval of eight hours between the two 
 principal ones and four hours between the first and second. 
 We must make exception for growing children. The hours 
 should be, for example, 7.30 and 11.30 in the forenoon, and 7.30 
 in the evening. In the cases where this interval is not sufficient 
 for the digestion of the preceding meal to be completed, it will
 
 178 LECTURES ON AUTO-INTOXICATION. 
 
 be necessary to proceed with the artificial evacuation of the 
 stomach. 
 
 The meals ought not to be copious, but substantial. It is 
 advisable to suppress all that is unnecessary and made with 
 
 water, consequently, liquid foods. Yet it is necessary to 
 
 give sufficient, and even a little more, because the organism 
 may be obliged to eliminate an excess of solid material l>y the 
 urine, which can only be done by the help of a determined 
 quantity of water. We must never expose ourselves to the 
 attempt to reach the limit on this side of which urinary depura- 
 tion might be prevented. We would not allow liquids at other 
 than meal-times ; 375 grammes of drink at each meal, or three- 
 fourths of a litre in twenty-four hours, ought, in a general way, 
 to be sufficient. 
 
 As digestion requires that the foods should be not only 
 softened, but penetrated by the gastric juice, they must not be 
 fatty. The stomach is not called upon to digest fat, but the 
 latter might prevent the stomach from digesting what it ought, 
 by preventing the hydrochloric acid of the gastric juice from 
 softening, penetrating, and hydrating meat and other alimentary 
 substances. It is better still to have the fat emulsionized, as in 
 milk. The food ought to be as much divided as possible ; we 
 must, therefore, prescribe food easy of mastication, not hard 
 food, but cold or very well cooked meat and boiled fish. It is 
 necessaiyto avoid, as much as possible, everj'thing that may have 
 a tendency to undergo fermentation, alcohol, which furnishes 
 acetic acid, acid substances, and certain parts of bread. Wine 
 is certainly unfavorable, especially red wine, and, above all, pure 
 red wine. But pure water is distasteful to certain people, and, 
 as they no longer have any appetite, they lose weight if they are 
 submitted to this regimen. In order to give the least amount of 
 alcohol possible, we must advise to be added to wtiter one-fourth 
 of white wine, one-third of beer, or a teaspoonful of brandy. 
 
 Bread is generally badly borne by dyspeptics, but rice, 
 barley, oatmeal, and unfermented pastes are allowed. As re- 
 gards bread, we may allow only the crust or grated crumb. 
 The reason for this restriction is this : Baking, having inter- 
 rupted the fermentation of the dough, has not stopped it alto-
 
 FERMENTATION AND THE PROCESS OF BAKING. 179 
 
 gether; consequently, this fermentation re-appears when moisture 
 and temperature are again favorable to it. In thoroughly-baked 
 bread fermentation is,'on the contrary, entirely stopped. What, 
 then, is this fermentation of bread ? The idea generally adopted 
 on the subject is that which was clearly defined by Graham. In 
 the presence of cereal! n (diastase) starch is broken up into 
 maltose and dextrin. Maltose, under the influence of saccharo- 
 myces minor, forms two sugars, dextrose and Isevulose. The 
 two sugars, un'der the influence of the saccharom3 T ces, ferment, 
 producing alcohol and carbonic acid, which cause the bread to 
 rise. 
 
 M. Duclaux, who has accepted this theory in principle, denies, 
 moreover, the existence of alcohol in this fermentation. The 
 question has been taken up again by M. Chicandart. The result 
 of his researches is that, in dough in process of fermentation, we 
 do not find either soluble starch or dextrin. The first part, 
 therefore, of the theory of Graham falls. We do not find in it 
 more sugar than in flour. We do not find alcohol either, but 
 in the fermented dough there exist acetic and butyric .'ic-ids, 
 supposing we only employ gluten without starch, and lactic 
 acid with pure gluten. We also find leucin, ty rosin, phenol ; 
 that is to say, the products of the fermentation of a nitrogenous 
 substance. 
 
 What undergoes fermentation in dough is, therefore, the glu- 
 ten, which gives birth to the products of acetic fermentation in 
 the presence of a bacterium, the bacillus glutinis. But this 
 resists the temperature to which the centre of the crumb is 
 found to be carried during cooking ; and it may, therefore, carry 
 on in the stomach acetic fermentation. By the knowledge of 
 these facts is explained the usefulness of un fermented and grated 
 bread in the feeding of dyspeptics. 
 
 After having laid down the general rules for a dietary which 
 has for its aim the attainment successively of functional ameli- 
 oration, then the anatomical restoration of a digestive canal 
 deteriorated by dilatation of the stomach, I proceed to state 
 precisely the concrete formula of the regimen. 
 
 I remind you that meals ought to be takt'ii :it iv.irular hours; 
 that, if it is possible to obtain consent from patients for only
 
 180 LECTURES ON AUTO-INTOXICATION. 
 
 two meals in twenty-four hours, these ought to be separated by 
 an interval of nine hours ; but that, as during the greater part 
 of the time three meals are necessary, the intervals ought to be 
 four hours between 'the first and second and eight hours between 
 the second and third. Thus, the first meal will be taken, for 
 example, at 7.30 in the morning, the second at 11.30, and the 
 third at 7.30 in the evening. 
 
 The patients ought to take nothing between meals, and 
 should strongty resist any impulses of hunger or thirst, when 
 even this resistance would cause them suffering, and in spite of 
 the momentary relief which satisfaction of these desires would 
 appear to give them. We will frequently secure from patients 
 this difficult resignation when we have clearly made them under- 
 stand the necessity, and when we have dazzled them with the 
 hope of a definite and absolute cure. Meals should be taken 
 slowly, and mastication should be slow enough to reduce the 
 aliments into pulp. 
 
 It is necessary to insist upon the prohibition of liquid ali- 
 ments which dilute the gastric juice, and of fats which remove 
 from the action of this juice the solid alimentary substances, and 
 to insist, also, upon the advisability of eating only a little bread. 
 
 The early breakfast should not be abundant : an egg, cooked 
 fruits, or marmalade, neither bread nor drinks. At the second 
 meal there should be cold meats (well cooked), hot meats (but 
 broiled in preference to underdone roasts), meat-soups, boiled 
 fish, eggs lightly cooked, eggs prepared in milk, milk in some 
 way solidified, paste (e.g., vermicelli) ; rice prepared in milk, or 
 in soup, or with the juice of meat; vegetable-soups (considered, 
 wrongly, as increasing flatulent dyspepsia), cheese, comp6tes of 
 fruit. Of fresh fruits these only will be allowed : strawberries, 
 peaches, and grapes. I do not know why the}' are better digested 
 than other fruits by dyspeptics, but I indicate the fact to you as 
 the result of experience. Other fruits should only be allowed 
 cooked. 
 
 The important advice as regards drinks is resumed in the 
 instruction not to drink at the first meal nor between meals, and 
 not to drink at any of the two principal meals more than a glass 
 and a half, each glass containing 250 grammes ( litre). In the
 
 EATING AND DRINKING: INDICATIONS TO BE FULFILLED. 181 
 
 summer-time, for patients who perspire profusety, we would 
 moderate, somewhat, the rule, in order to make some compensa- 
 tion for the loss of liquid. Drink should be, by preference, pure 
 water; alcohol ought to be avoided, because it gives rise to 
 acetic acid. But, our habits being repugnant to the use of pure 
 water, we would advise the addition to the water of one-third 
 beer or one-fourth of white wine ; we would reject red wine, 
 which contains too much alcohol and tannin, also the infusion 
 of tea. 
 
 It has been wrongly stated that the regimen, thus formulated, 
 was the dry regimen already laid down by Chomel. But the 
 whole regimen, according to Chomel, was limited to the sup- 
 pression of liquids. Mine proposes to satisfy three indications; 
 to obtain these gastric distension should be slight, infrequent, 
 and of short duration. 
 
 In order to bring about the first, I am willing to give sufficient 
 alimentation in the smallest volume possible. I moderate the 
 employment of water, both because it occupies space and dilutes 
 the gastric juice. Chomel has seen dyspepsia from liquids 
 which is real and which may coincide with certain cases of dila- 
 tation of the stomach, but not with all; the dyspepsia of liquids 
 is not dilatation of the stomach. 
 
 The second indication requires that the meals should be 
 infrequent. 
 
 The third is fulfilled by the emplo3 r ment of solid foods, easy 
 to digest and very finely divided, in order that the surface of 
 digestion may be increased. I exclude aliments easily trans- 
 formable into acetic acid ; that is why I reduce alcohol to a 
 minimum ; and I suppress bread, which I only allow transformed 
 into crust or toasted. 
 
 This regimen, such as I have just formulated, presupposes 
 that there is still great digestive power. In a certain mnulu'r 
 of cases, neither meat nor farinaceous vegetables are digested. 
 What is to be chosen, then, the dry regimen? No; but milk 
 diet, on condition of instituting it according to the precepts 
 laid down by Cruveilhier for the treatment of ulcer of the 
 stomach, in frequent doses and in small quantities, in order that 
 its digestion may be rapid and complete. Milk diet is a prepar-
 
 182 LECTURES ON AUTO-INTOXICATION. 
 
 atory regimen. We should begin with the quantity strictly 
 necessary to prevent deterioration of the organism, 1 table- 
 spoonful every two hours, if it is advisable; then 1 litre daily 
 in ten equal doses; that is to say, 100 grammes every two 
 hours, from 6 or 7 o'clock in the morning to 10 or 11 o'clock 
 at night, nine doses in the day ; one during the night. By 
 increasing progressively each dose, we reach 2 litres in the 
 twenty -four hours, which are sufficient for the sustenance of any 
 man. Lastly, 2^ litres, in ten doses of 250 grammes, should not 
 be exceeded. And then we should proceed, by insensible transi- 
 tion, to mixed diet. We add, first, a } r elk of an egg to one of the 
 cups of milk, then to several, which brings us up to ten yelks 
 of eggs. At this period we would replace, at 10 o'clock in the 
 morning, the cup of milk by rice-soup, barley, oats, oatmeal, or 
 paste, but suppressing the cup at midday, in order to allow the 
 stomach four hours to digest the soup. In the evening the 
 same substitution should be made at 6 o'clock. After a week 
 of these two light meals, suppressing four cupfuls of milk, we 
 can then add a whole egg to the soup ; then fish or cold fowl at 
 the morning meal, and at that of the evening clear soup of 
 potatoes. From this time onward we may boldly approach the 
 diet of two complete meals in the twenty-four hours ; then we 
 may alternately add, if necessary, the small, supplementary meal 
 of the morning. 
 
 Sometimes from the first it may be necessary to maintain the 
 patient a little more, if his weakness is excessive, or to beguile 
 his thirst. We may have recourse to alimentary drinks or to 
 nutritive enemata. We may employ aqueous solutions of pep- 
 tones, properly prepared, which we now find procurable in 
 France, and which have nothing in common with the products 
 falsely sold for a long time under this designation. Or shall we 
 be obliged to have recourse to alimentary powders (to meat 
 powder), which have been of signal service in certain diseases 
 in which it was necessary to maintain nutrition ? I do not think 
 so. They have, doubtless, the advantage of being very finely 
 divided, but they remain difficult of digestion, because they nau- 
 seate. We cannot dispense with the part which the nervous 
 system plays in the cure of the diseases of the stomach ; the
 
 HOW TO PREVENT FERMENTATION IN THE STOMACH. 183 
 
 patient who swallows with dislike does not digest. It would be 
 better, in case of need, to allow any fine pulp of cooked meat. 
 
 In order to prevent the excessive fermentation which dilata- 
 tion of the stomach favors, we should have recourse to the anti- 
 septic method. Many antiseptics are at our disposal. Creasote 
 (which has been employed for more than thirt} r }'cars, in acid 
 dyspepsias particularly), iodoform, and naphthalin fail, very 
 often, because they spoil the appetite; salicylic acid, in a suf- 
 ficient dose to be truly antiseptic, induces nervous derange- 
 ments ; salicylate of bismuth, less soluble, is also less active. 
 Chloroform-water is better; oxygenized water is good ; but what 
 is better still is hydrochloric acid, which prevents anomalous 
 fermentations and aids physiological digestion. No fermenta- 
 tion is possible in a liquid which contains for every 1000 parts 
 1.10 grammes of anhydrous hydrochloric acid, equivalent to 3.30 
 grammes of the fuming hydrochloric acid of commerce. The 
 liquor which I employ is a solution with this formula : 
 
 Fuming hydrochloric acid, pure, . . 4 grammes. 
 Water, 1000 grammes. 
 
 It is, generally speaking, neither disagreeable nor irritating. 
 It is a little painful to some patients, cancerous particularly, or 
 those who have ulcerations lying upon the great curvature. We 
 may give it at one meal, only in the dose of a few mouthfuls dur- 
 ing the course of the meal, or a glassful at the end of it. We 
 may give as much as 750 grammes of the solution apart from 
 the meals. When digestion is not terminated three or four 
 hours after the meal, we must come to the aid of the stomach 
 by replacing its exhausted secretions. As a help, I ought to 
 speak of the practice of washing-out, so much in vogue for the 
 last few years. It has given satisfaction on the old erroneous 
 idea that fluids which have accumulated in the stomach ought to 
 be removed. The real service which it renders is, to free the 
 stomach of the remains of previous digestions not attacked by 
 the gastric juice and undergoing putrefaction. 
 
 Washing out the stomach does not cure dilatation, it can 
 only relieve some of its consequences ; and as for its advantages, 
 these are accompanied by certain inconveniences, e.0.,the dim-
 
 184 LECTURES ON AUTO-INTOXICATION. 
 
 inution of the appetite and of digestion, and, in consequence, 
 increase of emaciation. Nevertheless, it is a necessary method 
 under certain circumstances. We ought to lay it down as a 
 principle that we should never introduce an additional meal into 
 the stomach when the previous one has not been digested. Five 
 hours after ingestion the presence of food in the stomach is 
 pathological, and from the sixth hour onward there will occur 
 in this alimentary mass anomalous fermentation. Beyond the 
 seventh hour the alimentary residue will undergo exclusively 
 acid or putrid fermentation. When, therefore, rational signs or 
 exploratory catheterization shall have established stagnation of 
 the alimentary residue in the stomach, there will be formal 
 reasons for evacuating it. Then we can leave the stomach to 
 rest for two hours, to recover itself, so to speak. Patients 
 undergoing lavage ought to have only two meals per diem. At 
 the same time you should make antisepsis; but, in order to 
 attain this end, no liquid is necessary. We cannot introduce 
 hydrochloric acid into an empty stomach, especially as, in these 
 cases of putrid stagnation, there exists already upon the greater 
 curvature punctated haemorrhages and ulceration of the mucous 
 membrane. But there is no inconvenience whatever in intro- 
 ducing iodoform (in pill), creasote, or nitrate of silver, which 
 may be useful in overcoming pyrosis. This extremely painful 
 symptom yields too, generally speaking, after a few days of 
 regimen, without the employment of medicines. 
 
 When pain is such that, in spite of the stoicism which you 
 would like to inspire in your patient, it is necessary to intervene 
 to give him immediate relief, we can neutralize the corrosive 
 acids which cause such great pain by means of sodium bicarbo- 
 nate, prepared chalk, calcined magnesia, charcoal, to all of 
 which may be added a small quantity of opium or combined 
 with chloroform-water, which relieves pain and checks fermenta- 
 tion ; finally, cocaine may render some service in diminishing 
 the sensibility of the mucous membrane. When ulceration of 
 the stomach supervenes, the therapeutic indications are those 
 laid down by Cruveilhier. The patient is then in a grave con- 
 dition, having reached a very advanced stage of the illness. 
 
 In making an abstract of the cases in which patients come
 
 GASTRIC DILATATION AND ITS PROSPECTS OP CURE. 185 
 
 to you only in the last stages of their illness, you will derive 
 great benefit always from the dietetic and therapeutic rules 
 which I have just laid down. You will sometimes see patients 
 who have suffered for ten years lose their suffering at the end 
 of two days, and declare themselves cured at the end of three 
 weeks. Remember that this is not even an apparent cure, and 
 that all the symptoms will re-appear on the day following that 
 on which the regimen has been abandoned. 
 
 At the end of what time, then, can we hope for a cure? In 
 the case of certain stomachs, dilated from the period of infancy, 
 cure will never be realized ; but, thanks to the permanence of 
 the treatment, we can overcome the anatomical imperfection of 
 the organ. The largest number of patients can, nevertheless, 
 be cured, but not in less than two years ; and these cures are 
 easily broken. Long before the cure of the gastric symptoms 
 you will, fortunately, have the satisfaction of seeing disappear 
 the superadded diseases, unless phthisis is part of the morbid 
 process and the mushroom bacillus has developed upon the 
 waste which the organism has supplied to it. There are nervous 
 symptoms which may yield at the end of a few hours, even cer- 
 tain sibilant rales of bronchitis, which arise from intoxication, 
 and are due to gastric fermentation ; certain anginal cardiac 
 symptoms (dyspnoeal), and the cutaneous, and especially renal, 
 manifestations. Albuminuria rapidly improves and totally dis- 
 appears, at the same time that it is accompanied by cardiac re- 
 duplication. The alterations in the joints, caused and main- 
 tained by the excess of acetic fermentations, may even retrocede. 
 
 The possibility of obtaining similar results is a reason, in 
 my opinion, for insisting upon the indications to be fulfilled and 
 the rules to be followed in the treatment of chronic intoxication 
 of a digestive origin, the type of which is dilatation of the 
 stomach.* 
 
 * Since these lectures were delivered, M. P. le Gendre has studied more par- 
 ticularly certain points in the history of dilatation of the stomach, and he has pub- 
 lished the result of his researches in an inaugural thesis, "Dilatation of the Ktonmch 
 and Typhoid Fever. Scmeiological Value of the Nodosities of Bouchard." 
 
 M. le Gendre has commenced by fixing the mean capacity of the stomach of the 
 adult, estimated in cubic centimetres of water, basing his remarks upon an examina- 
 tion of sixty stomachs of cadavera taken hap-hazard ; he believed that he might con- 
 clude that this average was less than 1300 cubic centimetres. But in twelve cases, in
 
 186 LECTURES ON AUTO-INTOXICATION. 
 
 which he had made the autopsy upon subjects in whom dilatation had been diagnosed 
 during life by "splashing" as the method adopted for diagnosis, the stomach had a 
 cubic capacity of from 1450 to 3600 cubic centimetres. 
 
 M. le Gendre has described very minutely, from a morphological and anatomical 
 point of view, the knotty condition of the phalango-phalangeal joints of the fingers, 
 the semeiological value of which I have made known. In what refers to those who 
 are the subjects of dilatation, and are predisposed to contract typhoid fever, I am 
 reminded that, in nineteen cases of this disease which have come under my care 
 within the last two and a half years, the contagion had exerted itself nearly always 
 upon patients attacked with dilatation of the stomach ; it had even attacked four 
 authentic cases of relapse of typhoid fever, facts certainly very rare concerning 
 the subjects of dilatation. He draws attention to the relative frequency with which 
 we meet with taenia and the lumbrici in individuals whose stomach is imperfectly 
 fulfilling its functions ; which shows that the digestive canal of the subjects of dila- 
 tation is particularly favorable for the lodgment of disease-producing parasites, large 
 or small. 
 
 M. le Gendre finally insists upon the very peculiar frequency with which we 
 observe, in those the subjects of dilatation, certain morbid conditions badly classed 
 in nosology, afebrile or febrile gastric obstruction, continued febricula, synocha ; 
 choleriforni, gastro-intestinal catarrh, many of which are, perhaps, attenuated forms 
 of typhoid fever.
 
 LECTURE XX. 
 
 AUTO-lNTOXICATION OF INTESTINAL ORIGIN TYPHOID FEVER. 
 
 Part played by auto-intoxication in typhoid fever. Typhoid fever is caused by 
 an infective agent. History of the research after the pathogenic agent of 
 enteric fever. State of the question. My own researches. The infective 
 nature of typhoid fever, although not absolutely demonstrated, is probably 
 
 absolute. Besides the general infection of the economy by the pathogenic 
 
 agent, the intestinal ulce rations are a cause of intoxication, either by 
 increasing normal fermentations or by the induction of anomalous fermenta- 
 tive processes. Role of secondary infections arising from the migration 
 
 of common infective agents outside of the intestine, and of superadded 
 infections, by penetration into the debilitated economy of special pathogenic 
 
 agents : parotiditis, erysipelas, gaseous gangrene, furuncle, anthrax. Role 
 
 of increased temperature from the point of view of therapeutic indication of 
 the part played by inanition. Therapeusis of the accidents of auto-intoxi- 
 cation of intestinal origin ; disinfection of faecal material by charcoal. Anti- 
 sepsis of the intestine by iodoform and naphthalin. Part played by purga- 
 tives. Influence of intestinal antisepsis seen in the diminution of mortality. 
 
 THE stucty of intoxication of intestinal origin does not appear 
 to lead naturally to a digression upon typhoid fever. This is an 
 infectious disease, and not a toxic one, and j-et, -when we come 
 to study its therapeutics, it is necessary to deal with intoxica- 
 tion. In t3 r phoid fever, in short, there come into play not only 
 the minor vegetable organisms which, by one means or another, 
 produce all the disorders which an infective agent can cause. 
 By the side of infection there is evolved a secondary process, 
 an accessory one, which is subordinate to intoxication. Well, 
 then, were it only for this alone, therapeutics ought to concern 
 itself with intoxication in typhoid fever. The primary cause of 
 abdominal typhus is certainly regarded as an infective agent, 
 and this enters by the intestinal canal ; all that we know of its 
 mode of transmission authorizes us to believe this. But the 
 infective agent only exists trausitionally in the digestive tube; 
 that is not its habitat. The place where it is developed is the 
 lymphatic system, the closed follicles, Peyer's glands, mesen- 
 teric glands, and spleen. It may be eliminated by the intestine, 
 landing there at the moment of necrosis of Peyer's patches, and 
 be carried away by alvine discharges. 
 
 (187)
 
 188 LECTURES ON AUTO-INTOXICATION. 
 
 The organism which may be the infective agent of enteric 
 fever has been known for a long time, since 1811, by Reckling- 
 hausen ; then by Klein, Sokolof, Browitz, and Fischl, in 1878. 
 I have myself found it, in 1879, and I communicated, in 1880, my 
 researches. I have found it in all the pathological liquids, with 
 the exception of sudamina. It is a rod possessed of the power 
 of changing its form frequently, a bacillus one day, disposed, 
 later on, in the form of beads, then as isolated micrococci. We 
 find it, at the autopsy, in certain organs, the kidneys, spleen, 
 and glands. During life, I have found it in the urine; this 
 fact was a novelty at that period ; it led me to form the concep- 
 tion of infectious nephrites. I have said that, detected in the 
 'blood and urine, the microbe leaves its habitat to be eliminated 
 by the renal emunctory. This fact has been confirmed since 
 by Letzerich, who saw one form of the microbe, the coccus ; 
 then by Eberth, who saw it in the form of a rod ; and, finally, 
 by Klebs, Meyer, Friedlander, and Gaffky. But does this fact, 
 although agreed upon, prove that the microbe is the pathogenic 
 agent of typhoid fever? Certainly not ; it is necessaiy that we 
 should have proved its presence in all individuals ; that we should 
 have isolated it by successive cultures, which deprive it, by 
 degrees, of all that has been borrowed lay it from the patient or 
 the cadaver ; and that in inoculating its descendants into animals 
 we reproduce in them the disease with all its characteristics. 
 Besides, we cannot raise objections to the method that the 
 organism, even isolated and cultivated, has not caused the 
 disease. Negative results do not prove that this organism may 
 not be the pathogenic microbe. Do we know that there exists 
 an animal species liable to contract typhoid fever? 
 
 In every case the result of inoculations have been alwaj-s 
 negative; the cultures made from all the humors, with the 
 exception of sudamina, have been successful. I have inoculated 
 them into the rabbit, serpent, cat, dog, and pig, and I have 
 introduced them by the digestive canal, by subcutaneous 
 methods, and intra-venous injection. I have inoculated quanti- 
 ties of the culture fluid which are far from being weak, and 
 which certainly contain milliards of bacteria. 
 
 I have readily produced in the pig a feverish illness, with
 
 TYPHOID FEVER AND MICRO-ORGANISMS. 189 
 
 evening rise of temperature, and in which the thermometric 
 curve is broken up into a series of ascending oscillations a 
 stadium or plateau and a line of descending oscillations. Re- 
 covery took place in the two pigs operated upon. Had they had 
 a bastard typhoid fever? In these cases I ought to have commu- 
 nicated to them immunity for the future. Yet fresh intra-venous 
 injections of typhoid cultures have caused in them renewed 
 pyrexia similar to the first. Typhoid fever being a disease 
 which creates immunity, the anatomical lesions which are char- 
 acteristic of it in man, not having been established in other 
 inoculated pigs which have not recovered, I am forced to admit 
 that the disease which I have communicated to these animals is 
 not typhoid fever. Things remain, therefore, at the point in 
 which they were before these experiments, and I have no right 
 to teach that typhoid fever is a parasitic disease, like anthrax or 
 glanders. 
 
 Thus we have had, so far as the subject of the infectious 
 nature of typhoid fever is concerned, only probabilities. An 
 important argument is that typhoid fever is transmissible, con- 
 tagious. As a general rule, we do find a relationship between 
 cases. A patient who has come to a district becomes a centre 
 from which radiate other patients, who scatter the disease in the 
 healthy localities. Transmission especially occurs, as we know, 
 by the dejecta, and mediately through the drinking-water which 
 the dejecta have impregnated. Thus it is that, calculating upon 
 clinical and etiological facts, and not upon microscopic, we 
 have come to regard typhoid fever as the result of the introduc- 
 tion of a parasitic agent into the organism. But, besides 
 general infection, the disease induces local effects. The most 
 remarkable are the intestinal lesions, consisting in ulceration and 
 in gangrene of certain parts of the intestine, then in excessive 
 putrefactions, which are in this way developed, showing them- 
 selves by meteorism and a fetid diarrhoea. I do not say that 
 these putrefactions arise from the presence of a pathogenic 
 organism, but we have reason to believe that it operates upon 
 the normal excessive fermentations in the intestine, besides the 
 anomalous fermentative processes of which the organs are the 
 seat.
 
 190 LECTURES ON AUTO-INTOXICATION. 
 
 If the fecal matter of a man in health is toxic, in typhoid 
 fever the unusual intensity of normal putrefaction may easily 
 add something to the infection, and we may conceive how, from 
 such a source, there must be some notice taken of intoxication 
 in the treatment. We -must deal, too, with the secondary infec- 
 tions arising from the migration of ordinary infectious agents 
 from the intestine and from the surface of intestinal wounds into 
 the blood and the tissues, where their multiplication is favored 
 by want of resistance of the latter. It is probably these common 
 infectious agents, on the move, which cause certain forms of 
 abscess, furunculosis, anthrax, and externally ordinary eschars ; 
 in parts of the body which are not subjected to pressure, 
 certain spontaneous forms of gangrene arise, perhaps from the 
 action of common infective agents upon the tissues, where their 
 influence for harm is no longer counter-balanced by the activity 
 of the circulation and nervous system. 
 
 We sometimes see, in the course of typhoid fever, certain 
 infective processes superadded, such as parotiditis. Inflamma- 
 tion of the parotid is produced by ordinary infective agents, 
 which are introduced by the excretory salivary ducts; and this 
 occurs as much by other glands, e.gr., by the kidney when it is 
 no longer in function, and when the bladder is the seat of in- 
 flammation (miliary abscess ; surgical kidney). 
 
 Erysipelas is frequent in the advanced periods of typhoid 
 fever. We may even see it cause gaseous gangrene. In certain 
 cases the eschars from the decubitus of the patient are the point 
 of departure of an emphysema which extends some distance. I 
 have seen a case in which gaseous gangrene has been the cause of 
 death. It is not simply enough to conceive of typhoid fever as the 
 result of a general infection by putrid intoxication derived from 
 the digestive tube, or of secondary infection, and of superadded 
 infection ; we must consider it along with one of its necessary 
 effects, the fever. It is impossible to build up a systematic 
 treatment upon one pathogenic view onh r . Doubtless, if we 
 could at once destroy the pathogenic agent, this great blow 
 would be decisive and would put an end to the fever, as also to 
 all the fatal accidents. But, since we cannot attain this end, we 
 must, I repeat, reckon with the fever, and, if this becomes of 
 itself dangerous, try to reduce it.
 
 ANOMALOUS SYMPTOMS IN TYPHOID FEVEE. 191 
 
 We are here in the presence of a continued fever, which is, 
 without intermission, destroying the patient for weeks, which is 
 higher than 39 C. (102.2 F.), which brings about unusual meta- 
 morphoses in living matter, depriving it of oxygen ; induces 
 modifications which are subversive of nutrition and perversive 
 of disassimilation. This excessive temperature produces effects 
 which are harmful to muscular fibre and the nervous system. 
 Sometimes the patients die simply from the persistent hvper- 
 thermia. The physician has not, therefore, only to deal with 
 the cause of the disease. When he cannot suppress that, he 
 ought to struggle in succession against all the effects arising 
 from this cause. 
 
 During the long course of this fever, inanition is extreme. 
 The patient, taking no combustible material from the outer 
 world, lives upon his own tissues. He finds that it is impossible 
 for him to digest. We cannot, therefore, nourish him like 
 another person ; still, we should try, by ingenious means, to 
 introduce into his organism combustible material, and not allow 
 him to destroy his own tissues. 
 
 As many as are the indications to be fulfilled in the treat- 
 ment of typhoid fever, just as many are the difficulties to be 
 overcome. We must, so to speak, lay siege to the disease and 
 attack it at all points where it appears vulnerable. Yet I have 
 only laid down general indications ; there are still special 
 indications for such and such a disease, such and such a 
 particular accident. 
 
 I now come to the therapeusis of the accidents of intoxica- 
 tion of intestinal origin. In the last ten years I have been 
 giving charcoal to neutralize a part of the toxic products. More 
 recently, I have completed this method by the addition of means 
 to prevent the fermentations which develop toxic products. I 
 will tell you some results which I have obtained in these two 
 phases of my practice : 
 
 With charcoal I have deodorized and discolored completely 
 faecal matter; I diminished their toxicit}', and the alkaloids 
 found are no longer but in insignificant quantity in the filtered 
 liquid. These first effects some have denied. It has been said, 
 in one of the learned societies, that charcoal was not an anti-
 
 192 LECTURES ON AUTO-INTOXICATION. 
 
 septic substance, without it being known for what reason I was 
 employing it. Besides, it has been stated, too, that charcoal does 
 not succeed in disinfecting ; yet we have had proof of all that 
 I have said, by giving 2 grammes of charcoal in medicated 
 cachets. As for myself, who gave 100 grammes daily, spoonfuls 
 by the mouth every two hours, I have obtained liquid stools, 
 black, odorless, and not resembling fascal matter. Such matter 
 has not only optical and olfactory properties which are less dis- 
 agreeable, but intra-venous injections show that they are much 
 less toxic ; their toxicity is found reduced by four-fifths. Not 
 only is the matter contained in the intestine less toxic, but a 
 consequence easj r of demonstration is that the individual is not 
 poisoned, for the toxicity of his urine is found considerably 
 diminished. The urine remains toxic owing to the products of 
 alimentation or of disassimilation, but they are no longer convul- 
 sive. We must employ from 90 to 120 cubic centimetres of 
 urine in order to kill 1 kilogramme of animal. 
 
 Owing to the disinfection of the stools, we also obtain 
 other beneficial results. The patients have no longer the earthy 
 complexion, but a clear skin, white and red; the intestinal dis- 
 tension diminishes; the tongue remains moist; eschars are 
 extremely rare. 
 
 Finally, statistics resting upon more than 300 cases have 
 shown that the mortality had fallen to 15 per cent., instead of 20 
 to 25 per cent. In these statistics I include all the cases, with- 
 out exception, which have come under my hospital care : the 
 patients who have not been submitted to this treatment, those 
 who have come with an intestinal perforation, or have succumbed 
 to slow complications. I would be perfectly right in deducting 
 all these patients, in order to judge of the value of the treatment 
 by itself; but I have not done so in order to establish a compari- 
 son with other methods. I take the total mortality, en bloc, of 
 the hospitals of Paris. 
 
 For the last two years I have added, to disinfection, intestinal 
 antisepsis. After numerous attempts, after having employed 
 creasotelike Pecholier, salicylic acid, and mercurial preparations, 
 I have returned to the true principles of intestinal antisepsis by- 
 applying substances capable of acting throughout the whole
 
 MEANS EMPLOYED TO INDUCE INTESTINAL ASEPSIS. 193 
 
 length of the digestive canal; that is, insoluble substances, the 
 stilicylate of bismuth, iodoform, naphthalin. I have onl} 7 em- 
 ployed pheuic acid to wash out the large intestine, morning and 
 evening. I have caused to be given a carbolic enema of 1 in 1000, 
 except in the case of infants, where this sometimes causes a 
 collapse rather disquieting in appearance ; in the adult, even, one 
 has seen perspiration, faintness, almost coma. With the doses 
 to which I have alluded, these accidents are very rare; they 
 may be such as to cause a little fear, but they are not grave. 
 
 I cause to be taken daily by my typhoid patients 1 gramme 
 of iodoform, finely powdered and representing a surface of 60 
 square metres. I obtain, by this method, as the fecal matters 
 are deodorized and discolored, a diminution of the alkaloids 
 which the filtered liquid contains, a diminution of the toxicity 
 of the fsecal matter, the almost complete disappearance of the 
 agents of putrefaction. Microbes are no longer found in the 
 alvine secretions, save in very minute quantity. The tongue of 
 the patient is never diy. 
 
 The mortality in the same hospital, in the same quarter, with 
 the same physician, has fallen to 10 per cent., an index at once 
 consoling. The partisans of the cold-bath treatment are proud 
 enough with this index of 10 per cent., but I have reached it 
 without baths. 
 
 I have taken care to add to the preceding methods a purga- 
 tive every three days, a glassful of Seidlitz water, and I never 
 abandon the treatment without subsequently causing a clearing 
 out of the intestine by a purgative. Otherwise, there may be 
 produced in the large intestine a hard accumulation, capable of 
 causing alarming obstruction, with faecal vomiting. This pur- 
 gative is castor-oil, administered to the patient in a small dose, 
 whilst he is in a bath. 
 
 Such, then, are the principles of the antiseptic method 
 applied to the digestive tube of patients attacked with typhoid 
 fever. For one year I combined naphthalin with iodoform; the 
 time has not yet arrived for me to be able to judge of the value 
 of this new method of medicinal treatment.
 
 LECTURE XXI. 
 
 PATHOGENIC THERAPEUSIS OF TYPHOID FEVER ANTISEPSIS OP THE 
 INTERNAL MEDIUM. 
 
 Is general antiseptic medication theoretically admissible ? Can we destroy in- 
 fectious agents in the economy ? Antisepsis of the internal medium. Refu- 
 tation of objections. Substances capable of preventing the multiplica- 
 tion of infectious agents that are vegetable are not necessarily fatal to 
 animal cells : the aspergillus, for example. The antiseptic action of 
 medicaments is not paralleled by their toxic power. Therapeutic and anti- 
 septic equivalents. Antisepsis is proposed not so much in order to de- 
 stroy microbes as to prevent their reproduction. A simple change of the 
 medium is sufficient to cause large vegetables to become sterile. Expe- 
 rience has demonstrated the utility of employing antiseptic medicaments. 
 Specific medicaments are all antiseptic. Mercury. Quinine. Salicylic 
 acid. Phenic acid. The largest number of medicaments called antipyretics 
 act, perhaps, only as antiseptics. Attempts at producing general anti- 
 sepsis in typhoid fever. Mercury may, perhaps, shorten the duration of 
 typhoid fever. Its inconveniences as the exclusive method. 
 
 I CONTINUE the study of the therapeutic indications in 
 typhoid fever. Beyond internal antisepsis, of which I have 
 shown to you by statistics the incontestable advantages, is there 
 not something to do from the point of view of real general anti- 
 sepsis? Is there a therapeusis rigidly pathogenic of typhoid 
 infection? This disease may serve as an example to us more 
 than any other in order that we may judge of certain questions 
 of general therapeusis. Apropos of it, we may study the prin- 
 ciples of the antiseptic method, of the antipyretic method, and 
 the rules which should regulate the feeding of patients in 
 infectious febrile diseases. 
 
 I am anxious to declare that I do not substitute the anti- 
 septic method for the antipyretic in the treatment of typhoid 
 fever, and that I have not the desire to suppress all that has 
 been done in the way of antipyretic medication, in order to 
 attempt to substitute, for real and serviceable results, that which 
 is still hypothetical and irregular in its effects. 
 
 But if it is good to attack hyperthermia, which is a source 
 of continual danger in fevers, it is permissible to attack it in its 
 (194)
 
 ANTISEPSIS OF THE INTERNAL MEDIUM. 195 
 
 origin ; and in those maladies whose cause is the penetration of 
 vegetable organisms into the system, does it not become us to 
 seek for that which we ourselves can oppose to their presence 
 and multiplication? Can we, definitely, in infectious diseases, 
 effectually attack the infective agent? 
 
 Some have denied that this is possible. And yet the ques- 
 tion has been settled in the affirmative by surgery. We can no 
 longer discuss here the possibility of suppressing septic agents. 
 We are now dealing with infection of free or unbroken surfaces, 
 on which infectious agents multiply; on which are accumulated 
 toxic substances, infective agents which may proceed to form 
 colonies in various organs, and poisons which may cause else- 
 where secondary functional derangement. It is, besides, through 
 the imitation of that which surgeons have obtained that I have 
 demonstrated the possibility of effecting intestinal antisepsis. 
 In medicine, we can still quote the example of certain diph- 
 therias which remain for a time infectious on the surface, and to 
 which antisepsis of the surface is applicable. 
 
 When we are dealing with patients in whom the infection is 
 no longer on the surface, but one of general infection, things are 
 presented, it is true, under another light. Sometimes it is the 
 blood which may be the natural habitat of the infectious agents, 
 as in anthrax and relapsing fever. Sometimes the pathogenic 
 agents are localized in the tissues. In every case, one must 
 succeed in impregnating the whole organism with the antiseptic 
 agent. 
 
 But do we not injure, at the same time, the animal cells? 
 This objection, which appeals to sense, has been from the first 
 the principal reason why the opponents of antiseptic medication 
 have never supported it. It has been formulated in a startling 
 manner when it has been said, " We aim at the microbe and we 
 strike the patient." Nevertheless, this masterly expression, for 
 which I entertain respectful esteem, is, at the bottom, only a 
 sophism. We can answer, actually, that what is hurtful to one 
 vegetable cell is not always hurtful to another cell of an animal 
 nature. Thus, is there not a whole series of pathogenic agents 
 which are killed by a substance indispensable to the animal, viz., 
 oxygen (they are, unfortunately, not the most numerous) ? We
 
 196 LECTURES ON AUTO-INTOXICATION. 
 
 cannot, therefore, say that what will kill the microbe will neces- 
 sarily destroy the patient. We can, besides, support the argu- 
 ment by the experiment of Raulin, who has shown that silver, in 
 an almost infinitesimal dose, is opposed to the development of 
 the aspergillus. Here, then, is a substance fatal to certain 
 vegetable cells in a dose not at all hurtful to animal cells. On 
 the contraiy, certain inferior vegtables live preferably in media 
 poisonous to the animal (solutions of quinine, arsenic, and anti- 
 mony in doses fatal to man). We must, therefore, separate off 
 antiseptic substances so as to state precisely those which are 
 very hurtful to vegetable cells, and yet innocent so far as the 
 elementaiy tissues of the animal are concerned. 
 
 The antiseptic action of medicaments does not proceed in a 
 parallel manner with their toxic power. Bert was wrong in 
 identifying the nerve cell with the cell of the ferment. To 
 say that what is hurtful to a vegetable cell ought to injure, a for- 
 tiori, a nerve cell, is only true for certain cases and in certain 
 conditions. Aniline is toxic and antiseptic. Phenic acid is 
 equally toxic and antiseptic. But is there an} r parallelism be- 
 tween their toxicity and their antiseptic power? Aniline is five 
 times less antiseptic than phenic acid, but four times more toxic 
 for animal cells. 
 
 Can we compare, from the same points of view, phenic acid with 
 mercury? With the same toxic power, phenic acid is six times 
 less antiseptic than the salts of mercury. The choice of these 
 second substances is imposed upon us, therefore, when we wish 
 to obtain maximum action against microbes and the least against 
 the animal elements. 
 
 Amongst mercurial salts, all have not an antiseptic action 
 proportionate to their toxicity. The biniodide, eminently anti- 
 septic, is less toxic than an equal weight of the bichloride. 
 
 The iodides of potassium and sodium are moderately anti- 
 septic. To prevent the fermentation of a litre of soup, we must 
 add to it 48 grammes of iodide of potassium or 50 grammes of 
 iodide of sodium. The action that is hurtful to the ferment is 
 then sensibly the same for these two bodies, but the iodide of 
 sodium is forty times less hurtful to the animal than iodide of 
 potassium.
 
 ANTISEPSIS TO PREVENT REPRODUCTION OP MICROBES. 197 
 
 It is advisable, therefore, to compare therapeutic equivalents 
 of medicaments and their antiseptic equivalents. We can also 
 derive benefit from the combination of different antiseptic sub- 
 stances. If we wish to administer, simultaneously, two or three 
 antiseptics, it seems that we must in order not to run the 
 risk of causing intoxication not give any one of these bodies 
 in more than one-half or one-third of the dose which is the 
 limit of their toxicity. I have observed that we can go beyond 
 these fractions. In choosing antiseptics and in associating 
 them, we can double the antiseptic power and only increase 
 by one-third their toxic activity. Such a vegetable organism is 
 not otherwise influenced by an antiseptic agent which kills other 
 vegetables. There is room, therefore, for fresh experiments ; but 
 it is advisable to follow these therapeutic attempts, relying at first 
 upon the experimental method amongst animals. 
 
 I have tried to make experiments with antiseptics upon the 
 infective agent of typhoid fever, or at least upon its assumed 
 pathogenic agent whose culture is easy in the neutral soup made 
 from beef; its sensibility is greater to the action of biniodide of 
 mercurv than is that of the bacterium of fermenting soup, a 
 long bacterium whose sensibility is as 2, that of the typhogenetic 
 agent being 3. Finally, as a last argument, it is said in objection 
 that we cannot kill pathogenic bacteria without destroying the 
 cells of the patient. But what we propose is not so much to 
 bring about death of the microbes in the depths of the organism 
 as to prevent their multiplication. It is one thing to destroy an 
 individual and another to render him sterile. I borrow a con- 
 vincing example from botany. A palm-tree from Biskra, which 
 covers itself with fruits destined to ripen when it grows to the 
 limit it would have attained in the desert, can live quite well in 
 the greenhouses of the museum, but it will never develop within 
 them fruit capable of reproducing itself; it will not even bear 
 fruit in Algeria. Thus, a simple modification of the medium, 
 whilst leaving to vegetable organisms their vital integrity ami 
 all their energy, can render them incapable of multiplication. 
 The liquid of a malignant-pustule culture inoculated into sheep 
 belonging to Beauce will cause death in all of them, but if sheep 
 of the same breed are taken to Algeria, and are inoculated with the
 
 198 LECTURES ON AUTO-INTOXICATION. 
 
 same culture, nineteen inoculations out of twenty will remain 
 sterile. What is true with regard to large vegetables is also true 
 of the smaller. If we pass to the application of this idea of re- 
 production, it is perfectly immaterial whether man is rendered 
 incapable of multiplying cells during his illness ; but if we 
 can prevent the cells of his parasite from being multiplied, the 
 disease ceases, for it is not caused only by the presence and 
 development of the ferment, but by its multiplication. Let us 
 propose to ourselves only to oppose the latter, and let us merely 
 try to impede the activity of this multiplication. 
 
 En r&sume, general antisepsis is theoretically admissible, and 
 we have no right to refuse its admission by an a priori exception. 
 What it requires now is not argument; facts are necessary to 
 establish, and that thoroughly, the employment of antiseptics 
 which have impeded the course of certain infectious diseases. 
 
 Well, has experience not already produced an opinion ? Is 
 syphilis cured by the antiplastic virtue of mercury ? We can 
 scarcely maintain that to-day. In intermittent fever, is it as an 
 antithermic that sulphate of quinine brings about a cure ; and 
 in rheumatism, salicylic acid? 
 
 Quinine brings about a reduction of temperature in an im- 
 portant and useful manner in three diseases only, intermittent 
 fever, typhoid fever, and one of the forms of puerperal fever. 
 In a healthy man it increases it l>y some tenths of a degree; it 
 does not reduce it in other febrile diseases. In fibrinous lob:vr 
 pneumonia 3 to 4 grammes of quinine produce quinism without 
 reducing the temperature more than one-half a degree. In the 
 subject of pleurisy the effect is not more marked. In erysipe- 
 las you do not reduce the temperature even with large doses 
 of quinine. In the diseases in which quinine acts, it is only by 
 acting in opposition to the infective agent that it causes a 
 cessation of the fever which is the consequence of it. 
 
 It is not so with phenic acid. Plienic acid reduces tempera- 
 ture by its physiological properties ; by its action on animal 
 cells it diminishes calorification and also acts upon the vegetable 
 cells of infectious organisms. 
 
 An enema containing 48 grammes of crystallized phenic acid 
 was administered to two of my patients, at intervals of two
 
 SPECIFIC MEDICAMENTS ALL ANTISEPTIC. 199 
 
 minutes between each injection. The mistake was made by 
 attendants who were new to the work. The first patient uttered 
 loud cries while the solution was being administered to the 
 second. The nurse, being alarmed, ran for the house-surgeon, 
 who ordered the bowels to be immediately washed out with 15 
 litres of water. The patients were already in a state of coma, 
 in which they remained for several hours, their temperature being 
 35 C. (95 F.). One of them had a temperature of 40 C. 
 (104 F.) before this accident, the other was convalescent; the 
 first rose to 41.8 C. (107.4 F.) in the evening, and in the same 
 time the other reached exactly the same temperature ; the one 
 that had a temperature of 40 C. (104 F.) was apyretic the next 
 day with a temperature of 37 C. (98.6 F.), and remained con- 
 valescent; the disease was destroyed, but the patient was nearly 
 killed as well. This is also true of alcohol ; I observed it in the 
 case of a young woman who had caught tj'phoid fever in Rome. 
 She was having injections of 1 in 1000 of phenic acid. The 
 Sister of Mercy, by mistake, one day administered an enema 
 with alcohol at 80 C. (176 F.). Her malady had reached the 
 ninth day ; the first lenticular red spots were appearing. Her 
 temperature fell to 35 C. (95 F.) ; she was delirious and totally 
 blind. When the temperature once returned to 37 C. (98.6 F.), 
 it remained at this point for four days. The maladj" resumed 
 its course ; the microbes had merely been dormant ; they required 
 a certain time to reproduce the pyretic symptoms. 
 
 Almost all the drugs that reduce fever in typhoid fever are 
 antiseptic. All those that are reputed specifics or nro generally 
 considered useful are antiseptic : chlorine, iodine, sulphurous acid, 
 the sulphites and hyposulphites, the mercurials, essence of tere- 
 binthine, creasote, thymic acid,benzoic acid, salicylic acid, boric 
 acid, iodoform, quinine, resorcin, kairin, antipyrin, thallin. I 
 think, therefore, that experience confirms the general opinion 
 as to their usefulness, and that, practically as well as theoreti- 
 cally, a favorable effect may be obtained in the course of in- 
 fectious diseases by the employment of the above-named 
 substances. Of these, one especially lias been considered a spe- 
 cific, viz., mercury. It is long since calomel has been admin- 
 istered in large doses, or the black sulphide. Mercurial friction
 
 200 LECTURES ON AUTO-INTOXICATION. 
 
 was used by Serres, and by Becquerel, until salivation and ulcer- 
 ation of the mouth were produced. Since that time calomel 
 has been recognized as a valuable agent in German}- and Eng- 
 land, and in France by M. Salet, of Saint-Germain. He recom- 
 mends a method which consists in administering 1 centigramme 
 of calomel every hour until salivation ensues. At this juncture 
 the illness takes a turn one way or another. 
 
 This mode of treatment being supported by a considerable 
 number of facts, I determined to verify the results. I gave thirty- 
 two patients who were suffering from typhoid fever 40 centi- 
 grammes of calomel a day, in doses of 2 centigrammes every 
 hour, until mercurial salivation was produced.* In almost every 
 case this took place in from five to seven days. All the patients 
 that experienced this salivation recovered. The mean duration 
 of the malady was twenty one days, a short period, twenty-five 
 days being the usual duration. The mortality was low ; two out of 
 thirty-two died, or 6 per cent. Certainly, the number of cases was 
 too small to enable us to arrive at any definite conclusions. I 
 may merety mention that those who died were those who had taken 
 the least mercury, and were consequently not sufficiently under 
 its influence. The recoveries in less than twenty -one days were 
 twice more numerous than by the other method. 
 
 But I did not continue this treatment, although the patients 
 recovered more quickly, and seemed to recover more com- 
 pletely, as it has the disadvantages of causing a long period of 
 convalescence, great debility, and anaemia. Certain accidents, 
 too, seemed to me more frequent : epistaxis ; intestinal haemor- 
 rhage ; dysenteric, sanguinolent, and mucous stools. Other 
 patients suffered from later complications, pneumonia twelve 
 days after recovery from the original malady and a vegetative 
 endocarditis. However, although I rejected this method as an 
 exclusive mode of treatment, I thought it might be used with 
 advantage if the system were less completely impregnated with 
 the drug. I adopted it, therefore, at the commencement of the 
 illness only, and associated it with other therapeutic agents, 
 under the form of a mixed system of treatment, which I shall 
 describe in detail hereafter. 
 
 * 40 centigrammes equal 6.2 grains ; 2 centigrammes equal 0.31 grain.
 
 LECTURE XXII. 
 
 ON THE PATHOGENIC THERAPEUTICS OF TYPHOID FEVER THE 
 TREATMENT OP HIGH TEMPERATURE. 
 
 The use of calomel in minute doses as a general antiseptic agent. Conse- 
 quences of excessive temperature in infectious diseases. The effects of high 
 temperature obtained by experiment. The effects of high temperature as 
 
 regards denutrition. Excessive temperature indicates the gravity of the 
 
 disease, but does not cause it. It is, however, advisable to endeavor to 
 
 reduce it. Methods of lowering it. Sources of abnormal heat. Causes of 
 
 the rise of temperature in febrile maladies. The effects of antitherrriic 
 
 drugs and modes of treatment. 
 
 I HAVE described under four headings the therapeutics of 
 typhoid fever: the general antiseptic treatment, the intestinal 
 antiseptic treatment, the antipyretic medicinal treatment,, and 
 the dietetics of food and drink. 
 
 I have described at some length, in speaking of chronic 
 intoxications of intestinal origin, how I proceed with the intes- 
 tinal antiseptic treatment ; in my last lecture I gave my reasons 
 for rejecting the general antiseptic treatment by the exclusive 
 use of mercurial salts, at the same time admitting the specific 
 action of mercury. Thus, I employ part of the general anti- 
 septic method in combination with other modes of treatment. 
 
 I use calomel in minute doses at the outset, and until the 
 commencement of the second week. I administer each day 
 40 centigrammes of calomel, divided into 20 doses which a re- 
 taken every hour, without either trying to produce or obtaining 
 salivation. This treatment is continued for four consecutive 
 days. Generally speaking, it has seemed to me that the thermic 
 curve was modified, and that sometimes after the second day the 
 fever began to abate, varj'ing, at the end of four days, liciwcrn 
 39 C. (102.2 F.) and 40 C. (104 F.),at a period when in the 
 ordinary course of the malady the temperature would either be 
 rising or remaining stationary. I do not wish to produce and I 
 never obtain salivation. 
 
 I will now proceed to discuss those antipyretic or antithermic 
 drugs that are in great favor at the present day. There is a 
 
 (201)
 
 202 LECTURES ON AUTO-INTOXICATION. 
 
 certain school of medicine that sees nothing in fevers but fever; 
 with doctors of this class the thermometer is the source of all 
 therapeutic and prognostic indications ; they see improvement 
 only in lowering of the temperature. No clinical practitioner 
 can accept such a doctrine, and the audacity of the assertions 
 of the school in question has given rise to a reaction in the con- 
 trary direction, in Germany as well as in France. Thus we now 
 see the current of medical opinion take a new course. It is 
 now urged that fever may do some good, and that it should be 
 treated with respect, a theory that has long been unheard of in 
 the medical world. This is a return to the Hippocratic and tra- 
 ditional doctrine, which I have supported as regards diseases of 
 nutrition. 
 
 I have dwelt upon the theory that there are fevers which, at 
 certain times, re-establish equilibrium in exhausted nutrition by 
 bringing about interstitial metamorphoses. This is evident in 
 gout. But is it also true of infectious diseases? Can fever 
 help the system to free itself from the infectious organism ? We 
 know that certain microbes cannot live beyond certain tempera- 
 tures which do not kill a human being. The bacteria of malig- 
 nant pustule, which cannot live in a temperature higher than 
 40 C. (104 F.), have no effect on birds, their normal tem- 
 perature being above that point. Pasteur has shown that it is 
 necessary to cool a fowl, in order to render it able to contract 
 this disease. This experimental argument is brought forward to 
 show that the elevation of the temperature of the body in fever 
 creates a.plrysical medium that is unfavorable to the infectious 
 organism. 
 
 Nevertheless, the whole school of which I have already 
 spoken sees in pyretic maladies no other danger than that which 
 results from elevation of temperature. Liebermeister says ex- 
 pressly that the danger in fevers lies, above all, in excessive 
 elevation of temperature. He brings forward as an argument 
 the coagulation and decomposition, at 44 C. (111.2 F.), of the 
 lecithine which enters into the composition of the nervous ele- 
 ments and of the corpuscles of the blood. At 42 C. (107.6 F.), 
 at 43 C. (109.4 F.), and even at 41 C. (105.8 F.), the nerve 
 cells show abnormal excitability in the animal experimented upon.
 
 EFFECTS OF HIGH TEMPERATURE. 203 
 
 We note muscular agitation, acceleration in the beating of the 
 heart, and of the respiratory movements. The phenomena of 
 osmosis are modified by thermic elevation. Water is retained in 
 the cells. The tissues of those suffering from fever are richer 
 in water than when they are in their normal state. All this is, 
 unfortunately, true. But these are not the only phenomena to 
 be considered in cases of fever, and, moreover, the elevation of 
 temperature in illness does not reach 44 C. (111.2 F.),or even 
 43 C. (109.4 F.), unless it is, exceptionally, at the moment of 
 death or a little while after it. 
 
 Naunyn and Rosenthal have studied the effects of excessive 
 elevation of temperature obtained artificially. At 44 C. (111.2 
 F.), the cardiac muscle, like the other striated muscles, remains 
 contracted, and death ensues; but the same experimenters were 
 able to keep rabbits alive for weeks ranging between 41 C. 
 (105.8 F.) and 43 C. (109.4 F.), without any ill effects being 
 observed. 
 
 It is the same with fatty degeneration of the viscera, which 
 I studied in 1867, making experiments in elevation of tempera- 
 ture upon a dog. I caused the animal to raise its temperature 
 itself, simply by preventing it from losing the greater part of its 
 heat. It lived in an atmosphere saturated with moisture, and 
 heated to a degree very little below its own temperature. Thus 
 the loss of caloric, by contact and by evaporation, was sup- 
 pressed ; the animal, continuing to produce caloric, accumulated 
 it. The effects obtained thus, by the gradual elevation of tem- 
 perature, are increased action of the heart (300 beats) and of 
 respiration (80 to 90). The animal died, at 44 C. (111.2 F.), 
 at the end of about four hours. Independently of hemorrhages 
 under the pleura and the pericardium, we observed, four hours 
 after the commencement of the elevation of temperature, fatty 
 degeneration of the cardiac muscle and of the hepatic cells. I 
 was led to think that the excessive elevation of temperature was 
 the cause of the fatty degeneration, but Naunyn and Rosenthal 
 found that no similar effect was prodiicc'd in animals at the 
 excessive temperatures observed in man when suffering from 
 disease. 
 
 On the other hand, elevation of temperature does not seem
 
 204 LECTURES ON AUTO-INTOXICATION. 
 
 to increase nutritive metamorphoses ; the waste of nitrogenous 
 tissue is much the same when animals are subjected to elevation 
 of temperature as when they are in a normal condition. (Sima- 
 nowsky.) Speaking from a clinical point of view, there is in a 
 patient no parallel, notwithstanding the assertions of Hirtz, 
 between the excretions of urea and the elevation of temperature. 
 It cannot be said that high temperature appreciably increases 
 disassimilation. Charvot had already been struck, when he 
 was studying the elimination of urea in typhoid fever, at the 
 slight elimination that took place during the hyperthermic 
 period, whereas it increased during the abatement of the disease, 
 and still more during the period of convalescence. I pursued 
 this question further, studying the variations in the weight of 
 the body in typhoid cases. In these cases all the combustions 
 supposed to be necessaiy for the production of excessive eleva- 
 tion of temperature are compensated for, the diminution in 
 weight being quite insignificant, whereas, when they enter upon 
 convalescence, the diminution in weight is rapid, and attains its 
 maximum after apyrexia, when food is administered to the 
 patients. Excessive elevation of temperature is, therefore, not 
 a source of danger from the point of view of anatomical lesions 
 or from the point of view of denutrition. We may say, there- 
 fore, that it indicates the gravity of the disease, but d*oes not 
 cause it. Elevation of temperature announces, but does not 
 constitute, the danger. It is even an established fact that 
 the accelerated action of the heart which accompanies eleva- 
 tion of temperature cannot produce exhaustion of the heart ; 
 the functional incapability through excess of work is a myth, 
 for the mechanical work effected b}' the heart is less when the 
 contractions are so rapid (200 to 300 pulsations). The relaxa- 
 tion of the capillaries and the diminution of the arterial and 
 venous tension relieve the heart, and, from the point of view of 
 fatigue, the lessening of the resistance is not counterbalanced 
 by the multiplication of the cardiac contractions. 
 
 However, these considerations do not alter the fact that 
 methods of lowering the temperature are useful in certain cases, 
 or that when we have succeeded in lowering the temperature we 
 note an improvement in the symptoms and an amelioration in
 
 SOURCES OF ABNORMAL HEAT. 205 
 
 the general condition of the patient. Although the complica- 
 tions experienced by a patient whose temperature is 40 C. (104 
 F.) or 41 C. (105.8 F.) do not seem to result from the elevation 
 of temperature, nevertheless drugs or modes of treatment that 
 lower this excessive temperature cause some of these compli- 
 cations to disappear. This is seen to be the case, at least, with 
 typhoid fever and certain cases of scarlatina or cerebral rheu- 
 matism, for, except in these three diseases, it is not certain that 
 antipyretic treatment is really useful. How, then, shall we deal 
 with excessive elevation of temperature? By acting upon the 
 causes which produce normal heat or abnormal heat ? We cannot 
 choose indiscriminately between these two methods. We may 
 reduce the sources of normal temperature by bleeding, by ab- 
 stractions of serum, or by the administration of poisons producing 
 the same effect (veratrine and tartrate of antimony). These 
 methods, long in use, are now almost entirely abandoned. 
 
 But what are the sources of abnormal heat ? We do not know 
 yet, we can only surmise. They must be very different accord- 
 ing to different diseases. Are they normal processes carried to 
 excess, or are they abnormal processes that raise the tempera- 
 ture to fever height ? It has been suggested that there are mi- 
 crobes which burn side by side with normal organisms and raise 
 the temperature in the body as in test-tubes. This is merely a 
 hypothesis, supported by analogies, but not by experiment. 
 
 Another hypothesis is that of the retention of heat. It has 
 been said that tissue wastes more quickly in fevers. This is true 
 in certain diseases; in acute atrophy of the liver, for instance; 
 but it is not true in typhoid fever. Chalvet, twenty years ago, 
 observed, after Traiibe, that in a fever patient the heat radiation 
 is less than in a healthy person. A squaiv decimetre of his 
 skin loses a smaller number of calories than a square decimetre 
 of the skin of a person in normal health. It is possible that a 
 diminution in the abstraction of caloric results from this. 
 
 The rapid diminution of the corpuscles of blood in pyretic 
 diseases has been brought forward as showing a more rapid de- 
 struction of matter. Bockmann replies that the moment the 
 temperature becomes normal again, the corpuscles suddenly 
 reappear. They remain suspended in some part of the body
 
 206 LECTURES ON AUTO-INTOXICATION. 
 
 during the fever. Bockraaun and Naunyn admit that they 
 are temporarily withdrawn from the general circulation. This 
 would account for the great increase in volume of the spleen. 
 Hu'ter has observed, in septic and pyaemic disorders, globular 
 stagnations in certain parts of the capillary blood-vessels ; this 
 fact may be mentioned as corroborating the theory of a tempo- 
 rary abstraction of some of the corpuscles. 
 
 Winternitz has quite recently revived the opinion that the 
 retention of heat is the cause of fever. Marey also attributed 
 fever to a defective distribution of caloric. If, therefore, certain 
 fevers ma}^ be caused by the retention of caloric, it may be 
 suggested that the radiation of the latter should be increased. 
 Riess, experimenting upon animals suffering from infectious dis- 
 eases, lowers their temperatures artificially until they become 
 normal ; but the diseases continue and death ensues. The danger, 
 therefore, does not lie wholly in the excessive elevation of 
 temperature. 
 
 Nevertheless, I repeat that clinical experience shows that the 
 antithermic treatment is advantageous. How then does it act ? 
 Let us endeavor, as far as possible, to know what we are doing 
 when we employ antithermic agents ; those that have been used 
 successfully are quinine, salicylic acid, antipyrin, kairin, thallin, 
 and, above all, hydro-therapeutic treatment. 
 
 Murri has succeeded in showing that all these methods raise 
 the temperature of the skin, and, consequently, bring the heat 
 to the surface of the body, thus favoring the lowering of the 
 central temperature. Moreover, they do not act upon a fever 
 patient in the same way as upon a person in health. Quinine 
 does not lower normal temperature; yet it can, in typhoid fever, 
 cause the temperature to fall three degrees in a few hours. In 
 a healthy person it raises it one or two tenths of a degree, but 
 it increases the flow of blood to the skin. This is true in a 
 higher degree of salicj^lic acid, which favors perspiration ; like 
 the cold-bath treatment, which at first physically abstracts a few 
 degrees of heat, but afterward favors the relaxation of the 
 cutaneous capillaries, the congestion and heating of the skin ; 
 then the cooling, at the surface of the body, of a larger quantity 
 of blood from the central organs.
 
 EFFECTS OF ANTITHERMIC TREATMENT. 207 
 
 Theoretically, the cold-buth treatment increases combustion, 
 and should therefore increase calorification ; this is true in the 
 case of a healthy man, who then produces more heat than 
 under normal conditions. But, in the fever patient, this treat- 
 ment retards calorification. In typhoid fever, according to Ssis- 
 setzky, the patient does not give off any more carbonic acid and 
 does not excrete any more urea when he is subjected to refriger- 
 ation. Taking into account the uncertainties of theory, we are 
 justified in concluding that the causes of fever are various ; 
 that it depends sometimes on an increase of the normal calorifi- 
 cation, sometimes on the life of the infectious organisms, and 
 sometimes on the retention of the normal heat. In any case we 
 may safely say that the antithermic method is not without its 
 uses in typhoid fever ; that in this disease quinine is useful ; that 
 it answers to certain indications and realizes certain effects ; that 
 it is the same with cold baths ; but that in other disorders 
 pneumonia, pleurisy, etc. this antithermic treatment does net 
 offer the same advantages.
 
 LECTURE XXIII. 
 
 PATHOGENIC THERAPEUTICS OF TYPHOID FEVER NEW MODE OF 
 BATHING IN FEVERS; DIETING OF FEVER PATIENTS. 
 
 Uncertainties regarding the nature of fever. Probable multiplicity of the patho- 
 genic sources of fever. Impossibility of counteracting it by pathogenic 
 therapeutics. Antipyretic modes of treatment acquired by empiricism. 
 Antithermic drugs. Inconvenience of phenic acid and antipyrin. Utility of 
 quinine. My method of administering quinine in typhoid fever. Hydro- 
 therapeutic modes of treatment: lotions, wrappings, baths. The methods 
 of Brand, Liebermeister, Ziemssen, Riess. Their advantages and disadvan- 
 tages. My method : tepid baths, gradually cooled, but remaining tepid. 
 Details of their administration. Their advantages. The dieting of pa- 
 tients in typhoid fever and other long fevers. Didactic summary of my 
 
 treatment of typhoid fever. Statistical results. 
 
 BEFORE entering upon the practical side of the antipyretic 
 method, it would be expected that we should discuss the doc- 
 trines concerning the nature of fever. But, in examining pyre- 
 tological doctrines, we are met at every point by contradictions, 
 and I see that I am reduced to the confession, so humiliating to a 
 professor of general pathology, that I do not know what fever is. 
 
 Galen was not troubled with these uncertainties. To him 
 febris was color prseter naturam. This is a definite and concise 
 assertion, and the resume, as it were, of a description of the 
 morbid state. But now science demands further particulars, 
 and wishes to know the origin of this morbid condition, and 
 what is the source of fever. 
 
 It is not certain that there is one pathogenic source of fever. 
 I think, myself, there are several pyretogenetic processes. We 
 may raise the temperature of a body in various ways, by com- 
 bustion, radiation, friction, condensation, etc. ; in the same way 
 the temperature of the bodies of animals may be raised abnor- 
 mally under very varying conditions. 
 
 Fever may be the result of an increased combustion or an 
 increased dehydration, or it may be produced by the liberation 
 of the heat produced by the life of infectious germs, or by a 
 diminution in the losses of the body, or by resolution of the 
 forces of tension. 
 (208)
 
 THEORY OF FEVER. 209 
 
 In the living organism forces exist that are developed by the 
 metamorphosis of the matter in the cells, and which do not act 
 externally, either by motion or by heat. Life is a sort of un- 
 stable equilibrium that is maintained by the forces of tension. 
 These oppose the freedom of the chemical and physical actions, 
 where opposite electrical actions meet, the acids and alkalies. 
 J. Ranke proved, long ago, that the nucleus of a living cell 
 is electro-positive, whereas its envelope is electro-negative. 
 Why do not these opposing kinds of electricity combine to 
 bring about a condition of electrical neutrality, unless it is 
 because they are prevented by the opposing forces of tension ? 
 If death occur, neutralization is immediate. 
 
 It is the same with the nerves as regards the electrical con- 
 dition of the axis-cylinder and of the envelope ; the former is acid, 
 the latter alkaline, during life ; upon death, neutralization ensues. 
 The combustion being the same, if the tension is diminished, 
 part of the force will become apparent under the form of heat. 
 Is this theory regarding fever applicable to certain forms of 
 pyrexia ? I do not know. We can only form h} r potheses on 
 this subject. Remember what I said about uraemia. We have 
 found poisons, but not the poison of unemia. As regards fever, 
 there may exist not one single explanation, but various patho- 
 genic conditions. I have, moreover, called attention only to 
 those processes for which experimental or clinical data can be 
 furnished. 
 
 In short, fever is with us as with Galen, elevation of tem- 
 perature arising from causes that may strangely vary. Now, 
 from a therapeutic point of view, not being sure what fever is, 
 we are compelled to give up the idea of drawing up a system of 
 pathogenic therapeutics for its treatment. 
 
 We are thus obliged to return to empiricism, which is not 
 sufficient to satisfy us, but which can give us information result- 
 ing from the long accumulation of individual facts. Let us, 
 therefore, enter the domain of empirical observations. 
 
 We know, empirically, that certain modes of treatment lower 
 the temperature and bring about an improved state of affairs. 
 Thus, in the first place, quinine has evidently a beneficial action 
 on typhoid fever and some other forms of pj'rexia, intermittent
 
 210 LECTURES ON AUTO-INTOXICATION. 
 
 fever, and in one form of infection of women in childbed ; its 
 action is undoubtedly favorable, but it is only temporary. 
 
 Phenic acid has a certain antipyretic action, but perhaps not 
 a favorable one ; autipyrin has also this action, but its influence 
 is unfavorable. When the temperature is at 40 * or 41 C., a suf- 
 ficient dose of quinine produces a fall of from 1 to 3 degrees, which 
 may last for twenty-four hours. At the same time, we note also 
 the disappearance or diminution of the nervous troubles that 
 were attendant upon the high temperature ; the patient is evi- 
 dently better, and accidents which might soon cause death may 
 thus be averted. It would, therefore, on first thoughts, seem 
 advisable to prolong indefinitely this favorable effect. Vogt 
 twenty years ago, and Joft'roy recently at the Hotel-Dieu, have 
 tried the continuous administration of quinine. I also wished to 
 see what results could be obtained by this means. I was soon 
 obliged to abandon the experiment. With 2 grammes of quinine 
 we get a fall of 1, 2, or 3 degrees ; but in the evening of the next 
 day the temperature rises again, and by the morning of the fol- 
 lowing day the fever has reached its original height. Should 
 quinine, therefore, be administered in the evening as a prevent- 
 ive ? But the second dose does not produce the same effects. 
 Three days at least must elapse before the quinine regains its 
 power. It is an intermittent remedy. It has been asserted that 
 if given continuously the temperature varies between 39 and 
 40 C., instead of between 40 and 41 C. Is this advantage suf- 
 ficient? As for myself, I never give a second dose of quinine 
 until after an interval of sevent3'-two hours. I only give it then 
 if the temperature taken in the morning in the rectum exceeds 
 40 C., or if that taken in the evening exceeds 41 C. The 
 doses that I have adopted are 2 grammes during the first and 
 second periods of seven days ; 1^ grammes in the third period ; 
 1 gramme in the fourth and after. I never give less than this ; 
 ^ gramme would be of no use. It is well to know that from 
 the eighth to the eleventh day we often obtain only a slight 
 lowering with doses that are generally efficacious either before 
 that time or after. This is almost necessarily the effect produced 
 
 * 40 C. equal 104 F. To convert degrees Centigrade into Fahrenheit multiply 
 by 9, divide by 5, and add 32 to the result.
 
 SUDDEN DEATH IN FEVER ATTRIBUTED TO QUININE. 211 
 
 by quinine; it aims only at an accident, viz., the excessive ele- 
 vation of temperature. 
 
 As for other remedies that are reputed to be antithermic, 
 phenic acid, resorcin, antipyrin, thallin, you cannot depend upon 
 them. In regard to antipyrin, the lowering that it produces is 
 rarely accompanied by an improved general condition, for it 
 causes at the same time a lowering of nervous activity. The only 
 objection to quinine, setting aside the buzzing in the ears, which, 
 however, affects fever patients less than persons in health, is the 
 accusation urged against it that it is liable to cause sudden death. 
 During ten years, out of five hundred cases, I have only found 
 sudden death occur seven times with patients who were taking 
 quinine. Four of these deaths happened in the same week ; and 
 in several hospitals, at the same time, similar cases came under my 
 notice. But chemical analysis showed that the drug administered 
 to the patient under the name of quinine was really not quinine. 
 It was a compound little known, in which cinchonine predomi- 
 nated. If we set aside these cases, therefore, there remains three 
 cases of sudden death out of five hundred cases of typhoid fever, 
 a proportion which does not exceed the ordinary percentage 
 of sudden death in this malady. The post-mortem examination 
 showed that in the patients that had died suddenly the heart 
 was contracted and absolutely empty of blood. Now, the toxi- 
 cology of quinine teaches us that when death is caused by this 
 drug the heart is found to be dilated and gorged with blood. 
 Moreover, since that time, I have not had a case of sudden death. 
 
 In short, then, I consider that by administering quinine to 
 typhoid patients, according to the rules already stated, we obtain, 
 as well as a diminution of temperature, an improved condition 
 generally. But I must add that in most other forms of pyicxia 
 this treatment has failed. In pneumonia, pleurisy, and erysipelas, 
 we obtain, as a rule, neither a full of temperature nor an im- 
 proved general condition. 
 
 Abstraction of heat is the only non-medicinal means of 
 lowering the temperature of fever patients. Many methods of 
 abstracting heat in fever patients have been tried. Since the 
 time of Sydenham and Currie, cold air has been used, currents 
 of air between open windows, and cold water in various ways.
 
 212 LECTURES ON AUTO-INTOXICATION. 
 
 The continuous sprinkling of the patient is, perhaps, the 
 most painful process. A cold shower-bath also produces a dis- 
 agreeable nervous action. Bathing with cold water gives an 
 unpleasant shock, and the abstraction of heat by these two 
 methods is very slight. Wrapping in a wet sheet is painful for 
 some moments. 
 
 Local applications, such as a bladder of ice on the abdomen, 
 produce, at first, a vascular spasm, and then stasis in the vessels ; 
 the skin is chilled and the cellular tissue also ; necrosis may set 
 in, but the body, as a whole, is not cooled. 
 
 The circulation of cold water by means of the ingenious con- 
 trivances of Dumontpallier and Clement produce a real refriger- 
 ation, but these processes are little used as yet, and I am not, 
 therefore, in a position to express an opinion as to their merit. 
 
 Enemata of cold or iced water certainly cool the rectum, 
 but they do not produce a general reduction of temperature. 
 
 It now remains for us to speak of the method which is gen- 
 erally preferred, the ordinary bath, in which the temperature 
 of the water is lower than that of the body of the patient. 
 
 The cold bath may be given according to the method of Brand 
 or Liebermeister. According to Brand, when the temperature 
 exceeds 38.5 C., a bath of low temperature is given eight 
 times a day, for from ten to fifteen minutes. 
 
 Liebermeister leaves the patient in the bath throughout the 
 whole course of the illness ; the duration is the same, and he 
 gives twelve baths a day. The temperature may be 15 C., 
 but this has been abandoned ; from 18 to 20 C. is the general 
 rule ; it may be even 25 C. Care must be taken to apply cold 
 water to the head first. 
 
 The patient is left in the bath until the cold chill is complete, 
 and he is often taken out in an alarming state. Our feelings 
 must be well under control if we are to carry out this treatment 
 rigorously in face of the sufferings of the patients. It is worth 
 mentioning that if we cause them great suffering we can almost 
 guarantee their recovery. But is there no treatment that is as 
 efficacious without being so inhuman ? 
 
 The cruelty of cold baths has led to tepid baths being sub- 
 stituted for them. There is the tepid bath at a disagreeably low
 
 FEVER-TREATMENT BY BATHS. 213 
 
 temperature, viz., 28 C., which might as well be called a cold 
 bath ; for to a man whose temperature is 40 C. the sensation is 
 the same at 28 C. as at 25 or 20 C. 
 
 Ziemssen has proposed a tepid bath, gradually cooled. The 
 temperature, at first, is 35 C., and to a fever patient even this 
 gives a very unpleasant sensation of cold. Then the tempera- 
 ture of the bath is rapidly lowered, so that in ten minutes it 
 fulls to 25 C. The patient remains in this cold bath for from 
 ten to fifteen minutes, until the teeth begin to chatter, as in the 
 methods of Brand and Liebermeister. This is the cold bath 
 preceded by a short phase of bearable temperature. But this 
 method does not do away with the sudden nervous shock. 
 
 I will also mention Riess's continuous bath, which lasts 
 twenty-four hours a day at a temperature of 34 C. The tem- 
 perature is moderated b}- this method, which may be useful. 
 The mortality would be 6 per cent., according to Riess, but 
 his statistics are only derived from forty-eight cases. This 
 continuous tepid bath becomes rapidly unbearable, and the 
 patients prefer the cold baths according to Brand's method. 
 
 I will now describe my own method, which I have been trying 
 for more than a year. My object was to develop a bath in which 
 the patient might lose heat without anj' nervous shock or spasm 
 of the cutaneous vessels. What we wish to arrive at is not 
 merely abstraction of heat by contiguity or conductivity. On 
 the contrary, what we require is that the blood should come from 
 the centre of the body to the surface to be cooled. 
 
 The temperature of the bath, at first, is two degrees below the 
 central temperature, 38 C., for instance, if the temperature of 
 the patient is 40 C. The patient can bear this well and experi- 
 ences no shock. The water is gradually cooled at the rate of 
 one-tenth degree per minute, or one degree in ten minutes, until 
 it is lowered to 30 C., but it is never cooled beyond this point. 
 The time necessary for this cooling is an hour and a half if the 
 temperature of the patient is 40 C.,or an hour and ten minute-; 
 if it is 38 C. 
 
 No feeling of nervous shock and no peripheral vascular spasm 
 occur during this long period. The pulse is not constricted. 
 At about 33 C. the patient finds his bath cool ; at 32 C. he finds
 
 214 LECTURES Otf AUTO-INTOXICATION. 
 
 it cold, but even at 30 C. he continues to speak and talk, show- 
 ing a wonderful mental condition. He has nothing of the typhus 
 stupor about him. The lowering of temperature realized is much 
 more considerable than with the cold bath. 
 
 I give the bath eight times a day, like Brand. Certain pa- 
 tients can thus pass half the day in the water. The lowering of 
 the temperature is more lasting than with the cold bath, and 
 sudden rises of temperature are much less considerable. 
 
 By plunging a patient into a bath which is only two degrees 
 below his own temperature, I do not provoke the reflex vascular 
 spasm that prevents the blood from coming to the skin to be 
 cooled. The lowering of the temperature of the water is effected 
 insensibly, and never transforms the bath into a cold one. 
 
 * What are the effects that result from baths administered ac- 
 cording to the mode that I recommend ? An almost constant 
 lowering of the central temperature, a refrigeration which varies 
 according to the stage of the disease and the hour of the day. 
 The -cooling is, on an average, five-tenths of a degree; it may 
 sometimes amount to three degrees. I speak from an experience 
 supported by the results of six thousand baths. Some excep- 
 tions should be mentioned. For instance, in certain patients the 
 temperature is not reduced ; we even observe a rise of tempera- 
 ture of one- to five- tenths of a degree. This anomaly is seen in 
 certain very nervous women, and in certain men toward the end 
 of the treatment, when the repetition of the baths has ended by 
 developing in them an insurmountable repugnance and keen irri- 
 tation. 
 
 The elevation of temperature which takes place after the bath 
 is slow; it is never a sudden rise. 
 
 It is to be remarked that we succeed better in cooling the 
 patient in proportion as his temperature is higher, so long as 
 his temperature remains between 37 and 40 C. ; but, on the 
 contrary, with patients whose temperature is excessive, above 
 40 and 41 C., the cooling is slighter in proportion as the tem- 
 perature is higher. The lowering is less between 41 and 42 C. 
 than between 40 and 41 C. Below 38 C., also, cooling is diffi- 
 cult ; a man in health is scarcely cooled at all in a tepid bath. 
 
 The differences in the lowering of the temperature in the baths
 
 EFFECTS OF BATHS. 215 
 
 vary also according to the periods of the disease. In that stage 
 where excessive temperature is the leading feature, and at the 
 commencement, it is more difficult to cool the patients ; the aver- 
 age fall is five-tenths ; later on it is six-tenths ; and in the fourth 
 week, seven-tenths. 
 
 There are also variations according to the time of day. The 
 temperature of a typhoid patient rises from 7 o'clock in the 
 morning to 3 o'clock in the afternoon ; then a diminution 
 takes place, and after that another rise, the maximum of which 
 is reached about midnight. From midnight to 7 o'clock it 
 abates again, and the patient loses the excess of temperature 
 that he had gained during the day. It is between midnight and 
 6 o'clock in the morning that the most important diminutions 
 of temperature are obtained after the bath ; a fall of three degrees 
 is often observed toward morning. 
 
 Do the patients derive any other benefits from the baths be- 
 sides the physical abstraction of heat ? Without doubt they do. 
 In the first place the lowering of temperature resulting from the 
 bath is accompanied by an improved general condition, as with 
 quinine ; whereas with the diminution of heat obtained by means 
 of antip3 - rin the general condition remains the same or grows 
 worse. 
 
 Other advantages also are obtained. When delirium sets in 
 at the commencement, it abates after, at the most, three days of 
 the treatment. There is no more of the real typhus stupor. The 
 patients that are treated by the baths do not cease to understand 
 what is said to them and to answer questions. 
 
 According to Skinner, one of my pupils who has written a 
 very good thesis on the study of my system of baths, we find 
 that the patients always take great interest in the variations of 
 their temperature, and discuss among themselves during the bath 
 the number of tenths of a degree noted before and after. 
 
 The tongue remains moist, and if dry at the beginning of the 
 treatment, this dryness disappears after a few baths. The teeth 
 are not discolored. The complexion has not tlint e:irtliy pallor 
 that denotes the thorough poisoning of the system. It is wliito 
 and often even pink in those patients that have a fine skin. 
 
 Lastly, the need of sleep manifests itself M l't r r.-u-h lmtli,and
 
 216 LECTURES ON AUTO-INTOXICATION. 
 
 the patients enjoy sleep at night, an unusual thing with typhoid 
 patients. For this last reason I do not give baths from 2 to 6 
 o'clock in the morning, for fear of disturbing this night-sleep, 
 which is precious. Only in order to give the eight baths in the 
 twent3 r -four hours, the intervals between them should be a little 
 shorter from 3 o'clock to midnight. Amongst the advantages of 
 the baths I may mention the rarity of eschars. 
 
 But all these results are obtained from tepid baths in typhoid 
 fever only. We have said that cold baths could be employed in 
 pneumonia, erysipelas, and pleurisy. I tried in these diseases 
 cold baths and tepid baths systematically cooled. I did not in 
 these cases observe the salutary effects which are so evident in 
 typhoid fever. 
 
 Thus I do not think that this can be called a general anti- 
 thermic method. Perhaps, however, it would be applicable to 
 certain hyperthermic forms of scarlatina and cerebral rheuma- 
 tism. I cannot speak from personal experience on this point. 
 I have, however, observed remarkable results from it in measles. 
 
 Are there no disadvantages attendant upon this system of 
 tepid baths gradually cooled ? 
 
 We cannot attribute to them pulmonary congestion, which is 
 neither more frequent nor more marked than with other modes 
 of treatment, and which, on the contrary, veiy often decreases 
 during the baths. Neither pneumonia, pleurisy, nor any other 
 grave visceral lesion has been reported as resulting from the 
 baths. But when the epidermis at last becomes puffy and 
 macerated at the palms of the hands and the soles of the feet, 
 we often find, in the case of workmen, or in cases where the 
 epidermis is very thick, that whitlows and accumulations of pns 
 close to the nails form under the skin. Besides this inflam- 
 matory complication, it is not unusual to find, after a few baths, 
 a rather painful glandular swelling in the axilla, but never real 
 adenitis. The hands and feet must be watched so as to let out 
 the pus as soon as it is observed, or we shall find that extensive 
 inflammation of the lymphatics will soon ensue. However, these 
 are accidents of minor importance. 
 
 I discontinue the use of the baths in the event of intestinal 
 hasmorrhage or pulmonary hepatization. When, in a female
 
 OBJECTIONS TO MILK. 217 
 
 patient, the menstrual period occurs during the course of typhoid 
 fever, I do not generally find it necessarj' to interrupt the baths. 
 
 I now come to an important point in the therapeutics of 
 grave pyretic diseases, the question of diet. 
 
 In these disorders, and especially in typhoid fever, the secre- 
 tions of the digestive tube are dried up or perverted. It seems, 
 therefore, a priori impossible to feed the patients, and natural 
 to condemn all attempts at alimentation. 
 
 Milk, which is so easy to digest, and which from its fatty 
 nature and its sugar seems so well adapted to keep up the strength 
 of fever patients, and make up for the waste by combustion, is 
 not without its drawbacks. It raises the temperature, and the 
 urinary secretion is lessened. Those who are in favor of a milk 
 regimen order a large quantity to be given in typhoid fever so 
 as to increase the urinarj^ secretion. Now, when I give milk 
 in any considerable quantity, I notice that it causes, through 
 indigestion, an aggravation of the patient's condition. I there- 
 fore maintain that all food should be rigorouslj- withheld. But 
 I give water in abundance, and water containing substances that 
 are slightly nutritive and capable of introducing into the system 
 certain mineral elements, under the form of meat extract, broth, 
 and cereal extract. This latter was considered useful in fever 
 cases two thousand years ago. The ptisan of Hippocrates was a 
 decoction of bade}'; strained ptisan was prescribed at the begin- 
 ning of fevers, and ptisan that was not strained at the end. I 
 give my patients an extract of meat and barley which contains 
 mineral elements that are calculated to repair the losses resulting 
 from the disassimilation of mineral material in the cells. I en- 
 deavor to prevent the waste of mineral matter, as it plnys tlu> 
 part of middle-man in organic changes. Chloride of sodium is 
 indispensable for the phenomena of osmosis ; phosphates are the 
 mediums between the bases and the acids. 
 
 To this regimen I add vegetable acids, in the form of lemon- 
 juice, which introduces potass, and which is combustible. 
 
 Lastly, I administer substances that nre both plastic and 
 combustible, peptones. I give 50 grammes * per day, ivi-kiming 
 the dry peptone. These peptones, which are chemicall}' pure 
 
 I.e., a little more than 1% ounces of dry peptone.
 
 218 LECTURES ON AUTO-INTOXICATtOtf. 
 
 and prepared honestly, and are very different from certain prod- 
 ucts sold under the same name in commerce, are, as we have 
 said, plastic combustible substances calculated to make up for 
 the waste of nitrogenous matter in the body. 
 
 In the regimen of our typhoid patient another substance that 
 figures as a combustible agent is fat in a form that can be ab- 
 sorbed, i.e., glycerin formed outside of the system ; for we know 
 that glycerin is one of the products of the division of fatty sub- 
 stances in the duodenum. The patient absorbs every day 200 
 grammes of glycerin, and }'et is not purged. I only allow wine 
 in very small quantities. 
 
 This is the whole of my system of dietetics. Thanks to it, 
 only a very slight loss of weight is observed during the period 
 of fever. The loss of weight is sometimes nil; it varies gen- 
 erally between 100 and 300 grammes a day up to the end of this 
 period, as far as the fifteenth day ; later on, at the moment of 
 the crisis, and when convalescence is established, the loss may 
 amount to 1 kilogramme per day for three to five days ; but, 
 from the third day after alimentation is resumed, the weight of 
 the patient increases again. Several principles of this dietary 
 are applicable to the intense fever of certain chronic maladies. 
 In the acute p} r rexia of very short duration, as in pneumonia, 
 the necessity for alimentation is not so urgent. 
 
 I will now sum up briefly and didactically the rules for the 
 treatment of typhoid fever as I have just described it. These 
 rules may be classed under four main headings : the general 
 antiseptic treatment, the intestinal antiseptic treatment, the 
 antithermic treatment, and the regimen to be observed. 
 
 As soon as the diagnosis is made or suspected, I prescribe: 
 
 (a) A purgative, to be repeated regularly every three days 
 (15 grammes of sulphate of magnesia). 
 
 (6) Forty centigrammes* of calomel per day, in 20 doses of 
 2 centigrammes (one every hour), are administered for four con- 
 secutive days. This constitutes the general antiseptic treatment. 
 
 (c) The intestinal antiseptic treatment consists in mixing 
 100 grammes of powdered vegetable charcoal with 1 gramme of 
 iodoform and 5 grammes of naphthalin. The whole is mixed 
 
 * 40 centigrammes equal 6.2 grains.
 
 SYSTEMATIC TREATMENT OF FEVEB. 21 9 
 
 with 200 grammes of glycerin and with the 50 grammes of pep- 
 tone that form the basis of nourishment. This mixture forms 
 a black, semi-liquid paste, which is taken in twenty-four hours 
 in doses of a tablespoon ful every two hours in a third of a glass 
 of water. I wash out the bowels regularly ever}' morning and 
 evening by means of an injection containing 1 part in 1000 of 
 phenic acid, each injection consisting of 50 centigrammes of 
 phenic acid to 500 grammes of water. 
 
 (d) Fjrom the first day the patient takes eight baths a day 
 until he is completely cured, when the temperature varies between 
 37 and 38 C. The baths are resumed if the temperature exceed 
 37.5 C. I reserve quinine for cases in which, notwithstanding 
 the baths, the temperature remains too high. The doses are 
 2 grammes during the first two periods of seven days, l grammes 
 during the third period, and 1 gramme during the fourth and fifth. 
 These quantities are administered in large doses 50 centi- 
 grammes every half-hour. But I do not return to quinine until 
 after an interval of three days. The signal for the employment 
 of quinine is a temperature in the rectum of 40 C. in the morn- 
 ing or 41 C. in the evening. Often the baths dispense with the 
 nse of quinine and constitute in themselves a sufficient system 
 of antithermic treatment. 
 
 (e) The diet comprises : broth cooked with barley and ad- 
 ministered freely (l litres to 2 litres a day) ; glycerin (asso- 
 ciated, as I have said, with charcoal, iodoform, and naphtlialin, 
 and also with peptones) ; lemonade made from lemons, with the 
 addition of a little wine. This is certainly a complicated sj-stem 
 of therapeutics ; it cannot be otherwise, as the indications to be 
 fulfilled are complex. 
 
 This systematic treatment, te it understood, does not exclude 
 the treatment of certain accidents ; for instance, excessive or 
 prolonged delirium by opium, pcritonitic complications l>y nic:ms 
 of ice or Neapolitan ointment. I have only discussed those 
 symptoms that are common to all patients; for if, as has been 
 said, we are to study the patients and not the disease, it is no 
 less true that all patients show in their illnesses general featmv* 
 without which they would not have the disease at nil. Why 
 should I be reproached for employing a systematic mode of
 
 220 LECTURES ON AUTO-INTOXICATION. 
 
 treatment? Is it not as natural to contend systematically with 
 excessive temperature, infection, and self-poisoning, as it is to 
 feed one's self systematically every day ? When I discontinued 
 the baths for some reason in the course of the illness, the tem- 
 perature in the patients went up again to 40 and 41 C., and 
 sometimes they died. 
 
 What results have I obtained from my method ? 
 
 Formerly the mortality from typhoid fever, in the cases that 
 came under my notice, was 25 per cent. When I succeeded in 
 neutralizing the intestinal poisons, it fell to 15 per cent., then to 
 10 per cent., when I obtained a successful intestinal antiseptic 
 treatment. It has fallen to 7 per cent, since I instituted the 
 complete system of treatment, which was in April, 1884. 
 
 This is a better result than Liebermeister has obtained by 
 cold baths. And I reckon the total mortality, including patients 
 that arrive at the hospital at a very advanced stage of the fever, 
 without having been treated at all, having, as I found in one 
 case, a temperature of 42.6 C., and those who are brought to 
 us already attacked with peritonitis through perforation ; I in- 
 clude deaths that may be attributed to later complications, cases 
 in which the treatment has been suddenly discontinued for some 
 cause or other, and those cases in which the method has not 
 been strictly carried out. Thus, in the beginning, when it was 
 not possible for me to arrange for baths at night, in the case of 
 one patient, the temperature, which had fallen during the day 
 under the influence of the baths, rose in the night to 42 C., 
 and the third night he died. 
 
 The number of patients that have been subjected to the com- 
 plete treatment is now one hundred and twent} r -nine,* out of 
 which there have been nine deaths, showing a mortality of 7 
 
 *At the date of this publication (November, 1886) the number of cases of 
 typhoid fever treated by M. Bouchard's staff at the Lariboisiere Hospital since 
 April 1, 1884, is two hundred and twenty-six, out of which there have been thirty-one 
 deaths, or a mortality of 11.7 per cent. Is this increased rate of mortality to be at- 
 tributed to a chance accumulation of critical cases, or to a modification introduced 
 into the treatment, salicylate of bismuth having been substituted for the charcoal, and 
 the peptones having been suppressed against his will, during a considerable period ? 
 But in any case 11.7 per cent, is low as compared with the general mortality in this 
 hospital. The Lariboisiere Hospital has been open a third of a century, and during 
 that time the average mortality in typhoid fever has been 21 per cent. It is still 18 
 per cent, for the last six years.
 
 IMPROVED MORTALITY STATISTICS. 221 
 
 per cent. The mean duration of the illness has been nineteen 
 days. The frequent relapses which attack 20 per cent, of the 
 patients have fallen to 10 per cent, in the last period. In fact, 
 we have every reason to congratulate ourselves on these results ; 
 and I am convinced that we have obtained them by attacking 
 the malady wherever we find it vulnerable, in its primordial 
 cause infection, as in its necessary effects poisoning, fever, 
 and inanition.
 
 LECTURE XXIY. 
 
 AUTO-INTOXICATION BY BILE. PATHOGENESIS OF JAUNDICE. 
 
 The elements constituting bile. Experimental studies of the toxic nature of 
 bilirubiu and the biliary salts. How the greater number of the elements of 
 bile become inert by precipitation in the digestive tube. The role of the 
 liver as a protecting agent against the part that might be re-absorbed. 
 When bile passes into the blood, the white connective tissues, by fixing 
 the bilirubiu, prevent it from injuring the other elements. The urine then 
 draws it off little by little. The biliary salts are gradually eliminated by 
 the urine. The sudden injection of a considerable quantity of bile into 
 the blood kills animals without producing jaundice. The slow injection of 
 the same quantity of bile causes jaundice and does not kill. Influence of 
 biliary retention on the hepatic cells and on nutrition. 
 
 BEFORE concluding the study of intoxication by the natural 
 poisons of the system, I will discuss poisoning by bile, or jaun- 
 dice. This is a question that I have already touched upon in- 
 cidentally when, in speaking of uraemia, I had occasion to quote 
 some of the data relating to the poisonous nature of bile. When 
 once it is spread over the surface of the intestines, bile is found 
 to be under very different conditions than when it is in the liver. 
 The re-absorption of bile takes place, no doubt, with some in- 
 tensity in the duodenum, but it is principally inoffensive matter 
 that is re-absorbed, and, moreover, if the noxious portion of the 
 bile is re-absorbed in any considerable quantity, it is again stopped 
 by the liver and rejected into the intestines. In order, there- 
 fore, to study fully the toxic effects of bile, we must examine it 
 in the liver at the moment of its secretion. 
 
 Bile is very abundant, being almost equal in quantity to the 
 urine ; its secretion is over 800 cubic centimetres in twenty-four 
 hours; and it may even amount to 1200 and 1300 cubic centi- 
 metres. It is a diffusible liquid, passing b}' means of exosmosis 
 into the blood; it is rich in solid substances (from 10 to 15 per 
 cent.) all capable of dialysis. Bile does not contain albumen ; 
 but mucin is found in it, and this gives it its viscosity ; it also 
 contains cholesterin, which is erroneously considered poisonous, 
 as we find considerable quantities in atheromatous abscesses of 
 (222)
 
 POISONOUS QUALITIES OF BILIARY DERIVATIVES. 223 
 
 the aorta ; olein, margarin ; coloring matter, important from a 
 toxic point of view ; the biliary salts and the alkaline soaps, by 
 means of which the cholesterin is held in solution. 
 
 Of the various coloring substances, bilirubin is the only one 
 that we need discuss; the others bilifulvin, biliverdin, bili- 
 fuscin, biliprasin, and bilihumin are merely derivatives of bili- 
 rubin. Bilirubin is soluble in water and in chloroform ; it 
 gives rise to Gmelin's reaction when treated with nitric acid. 
 This coloring matter is generally precipitated suddenly in the 
 intestines, on contact with the acid cli3 r me, which renders it 
 insoluble and prevents it from being re-absorbed. We must 
 take into account the biliary salts whose base is sodium, which 
 is a non-poisonous base. The glycocholic and taurocholic acids 
 of Lehman n, still known as cholic and choleic acids, are very 
 unstable. Under the influence of potass and heat they generate 
 cholalic acid, and, besides this, the first-named gives off glyco- 
 col, and the second taurin. The biliary acids are also trans- 
 formed, under the influence of sulphuric acid, into choloidic acid 
 and into glycocol or taurin, a reaction which, upon contact 
 with certain digestive juices, is effected in the intestines as in 
 the test-tube. Finally, the cholalic and choloidic acids take the 
 form, in the intestines, of an insoluble substance, viz., dystysin, 
 which is no longer injurious. 
 
 The coloring matter and the biliary acids, which are both 
 poisonous, becoming thus insoluble in the intestines, we need 
 not wonder that, notwithstanding the quantity of bile poured 
 into the intestines and the intensit}' of its re-absorption, no 
 poisoning takes place, even when the kidney is only slightly 
 permeable. But these transformations are neither immediate 
 nor constant. In certain persons we find, even near the anus, 
 bilirubin still intact, and biliary acids that have not undergone 
 transformation, owing to the rapidity and intensity of the con- 
 tractions of the intestines. 
 
 Even in a normal state of health a certain quantity of the 
 toxic matter may be re-absorbed in the duodenum. But the 
 liver, as Schiff has shown, arrests these poisonous substances 
 and restores them to the intestines or transforms them into 
 harmless matter.
 
 224 LECTURES ON AUTO-INTOXICATION. 
 
 In any case, the reality of the toxic nature of bile, which 
 has long been believed in by the medical world, has recently 
 been experimentally established. According to my experi- 
 ments, from 4 to 6 cubic centimetres of bile are required to kill 
 in convulsions a living animal weighing 1 kilogramme, and, since 
 the daily secretion of bile is about 1000 cubic centimetres, we 
 must conclude that during every twenty-four hours a man 
 makes, by the activity of his liver alone, an enormous quantity 
 of poison, enough to kill, in twenty-four hours, three men of his 
 own weight, 1 kilogramme producing enough to kill more than 
 2800 grammes of living matter. Man forms, in eight hours, 
 enough poison to kill himself simply by his hepatic secretion. 
 Now, in twenty-four hours the urine does not eliminate half the 
 quantity necessary to poison a man ; the urine of two days and 
 four hours would be required in order to do this. The volume 
 being equal, bile is nine times as poisonous as urine ; in an equal 
 period of time the biliary secretion represents a degree of toxic 
 power six times as great as the urinary secretion. I have 
 shown that bile decolorized by carbon has one-third of the toxic 
 properties of bile in its natural condition. 
 
 This leads us to suspect the toxic nature of bilirubin. We 
 M. Tap ret and myself have demonstrated it by an intra-venous 
 injection of this substance dissolved in water by means of a 
 little soda. Bilirubin kills rabbits in a dose of 5 centigrammes 
 per kilogramme. We found, moreover, that each of the biliary 
 salts is only one-tenth part as poisonous as bilirubin. 
 
 The urine does not carry away the whole of the poisonous 
 matter secreted by the liver, therefore the greater part of this 
 substance must be neutralized in some part of the body. Even 
 if the urine owed the whole of its poisonous nature to bile, the 
 latter would have had to lose five-sixths of its toxic properties 
 in some other way. 
 
 This neutralization is effected in the intestines, in the liver, 
 in the tissues, and in the blood. 
 
 Schiff thinks that bile does not poison us, because the liver 
 take.s it back and rejects it, to take it back and reject it again, 
 and that each time a smaller and smaller portion is absorbed. 
 The true protection seems to me to be the precipitation of the
 
 PROTECTIVE ROLE OF THE TISSUES IN JAUNDICE. 225 
 
 poisonous elements of the bile, i.e., the coloring matter and the 
 salts, which, when once precipitated, escape from absorption. 
 
 I think, also, that the tissues play a certain protective r61e : 
 they consume and transform the minute portions of bile which, 
 having been absorbed, have penetrated into the general circula- 
 tion ; they fix the bilirubin. The blood consumes the biliary 
 acids. 
 
 Is it the same when the bile is re-absorbed into the liver 
 itself? When, in consequence of an osmotic change, the bile 
 passes from the biliary cell into the blood-vessels, the flow of 
 bile extends to the general circulation, and is no longer confined 
 to one region ; the protection of the intestines and the liver is 
 suppressed. It is the bile in its entirety that passes from the 
 liver into the blood, and not the part which is unimportant, 
 from a toxic point of view which was re-absorbed in the intes- 
 tines. 
 
 The coloring matter and biliary acids will circulate through- 
 out the body. A part will escape through the kidneys, but the 
 greater part goes to impregnate the tissues, the anatomical ele- 
 ments, the normal and pathological humors. The skin, the con- 
 nective tissue, the hepatic cells, the muscular fibres, the vitreous 
 bod} r , all the epithelial cells, the sj-novial fluid, and the serous 
 cavities are penetrated with bile. Upon examination, the ana- 
 tomical elements give two reactions : that of Gmelin for the pig- 
 ment and of Pettenkofer for the acids. This is what is asserted 
 by clinical and pathological anatomy, but the appearance of these 
 gross manifestations of the passage of bile into the blood is 
 not immediate ; emotional jaundice, if it exist, is a rare excep- 
 tion. When we are quite sure of the precise moment of the 
 stoppage of the bile, as in hepatic colic, in which it is indicated 
 by pain, we may easily see that it is often twentj'-four hours, or 
 even more, before the icteric tint shows itself in certain mucous 
 secretions and in certain parts of the skin. The urine is colored 
 more quickly. How is it that so -long a time elapses before the 
 tint shows itself upon the person himself? This fact seems to 
 contradict the data furnished by experiment. 
 
 I make an intra-venous injection of bile and kill the animal 
 in a few minutes, without the skin having taken the jaundiced
 
 226 LECTURES ON AUTO-INTOXICATION. 
 
 tinge or the urine having been colored. This is an experimental 
 fact that contradicts clinical experience. It has even been 
 asserted that the intra-veuous injection of bile cannot produce 
 jaundice.* Feltz and Ritter never succeeded in obtaining it. 
 
 Vulpian injected 250 cubic centimetres of bile into a dog 
 slowly, the injection lasting three days ; the animal became 
 icteric. It is true that dogs are often icteric normally. Never- 
 theless, in Yulpian's experiment the tissues and organs were 
 tinged with bile, and the jaundice was certainly very pronounced. 
 
 It is because bile is so poisonous that a sudden injection of 
 bile does not produce jaundice ; death ensues before the tissues 
 have had time to become colored. When, instead of bile, a 
 solution of bilirubin only is injected, the five centigrammes of 
 bilirubin that are sufficient to kill one kilogramme of living 
 animal matter are also sufficient to cause intense jaundice during 
 the few minutes that elapse between the commencement of the 
 injection and death. When the bile is suddenly introduced into 
 the circulation, the coloring matter does not tinge the tissues. 
 A piece of white silk, quickly plunged into icteric urine and 
 washed immediately, is scarcely colored ; in this urine still more 
 diluted it is colored in proportion to the duration of its immer- 
 sion, and the urine is discolored. When the animal is suddenly 
 poisoned, we must consider the quantity of soluble poison that 
 can, at a given moment, produce an impression on the nerve- 
 cells, also the time necessary for the fixation of the pigment on 
 the white tendinous and aponeurotic fibres, etc., in order to color 
 them. In order to color a tissue, time is necessary, rather than 
 concentration of bile. 
 
 Once freed from its coloring matter, bile loses part of its 
 toxic property ; thus, when bile is injected, if the injection is 
 sufficiently slow, the white fibres, by fixing the bilirubin, pro- 
 tect the nerve-cells. During this time, the biliary salts escape 
 by way of the kidneys or are consumed in the blood. We may 
 
 * Vaughan Harley has shown (Brit. Med. Jour., Aug., 1892) that in jaundice, 
 contrary to the hitherto-entertained pathological doctrine, the bile which stains the 
 skin and discolors the urine is not absorbed into the general circulation by the blood- 
 capillaries, but solely by the lymphatic system of vessels, and that it does not reach 
 the general circulation by the hepatic veins, but by the thoracic duct. Where the 
 thoracic duct has been ligatured no bile is found in the urine or blood. A similar 
 view is held by Foster, in Text-book of Physiology, p. 440. T. O.
 
 RENAL PERMEABILITY THE SAFEGUARD IN JAUNDICE. 227 
 
 thus, both experimentally and clinically, obtain icteric colora- 
 tion without poisoning, if the injection or re-absorption be 
 slow. 
 
 Clinically speaking, if all the bile secreted in eight hours 
 were introduced suddenly into the blood, we should see fatal 
 nervous effects produced immediately. But as elimination is 
 incessantly being effected through the kidneys, and as the 
 fibres of the connective tissue are being incessantly colored, 
 whilst the blood re-absorbs only gradually, nervous accidents 
 are thus averted. The tissues serve to. protect the organism 
 against certain poisons. Experience shows us that the most 
 intense form of jaundice, viz., black jaundice, does not kill, pre- 
 cisely because the coloring matter, which is ten times more 
 poisonous than the biliary salts, becomes fixed. 
 
 Thus, in addition to the protection afforded by the liver and 
 intestines, the system finds a protection against biliary poisoning 
 owing to tissues which, as regards functional importance, occupy 
 the lowest rank among the anatomical elements, drawing off 
 from the blood the greater portion of the coloring matter, in 
 order to absorb it themselves. Lastly, the kidneys also take 
 part in the elimination of the biliary acids ; we find, in the urine 
 of those suffering from jaundice, sulphur incompletel}- oxidized, 
 or in the form of sulphur compounds; this sulphur is derived 
 from the taurin, and should be eliminated by the intestines. 
 
 Notwithstanding this elimination through the kidneys, part 
 of the biliary salts, passing through the system, affects the blood- 
 corpuscles, the hepatic cells, the muscular fibre, the epithelial 
 elements, and according as the kidne} 7 performs more or less 
 perfectly its work of elimination it causes more or less rapid 
 destruction of these elements. Sometimes only disassimilation 
 is merely hastened, and emaciation is then rapid. Sometimes 
 disassimilation is so rapid that the oxygen that is available 
 ceases to be available for combustion ; fatty degeneration then 
 results from the persistence of one of the products of the 
 disintegration of the nitrogenous matter. 
 
 Moreover, the retention of the biliary acids acts upon the 
 hepatic cell, which itself undergoes fatty degeneration. Then a 
 new effect is produced, the functional consequence of acute
 
 228 LECTURES ON AUTO-INTOXICATION. 
 
 atrophy of the liver, viz., suppression of the final processes of 
 disassimilation. 
 
 The substances disassimilated no longer undergo all the met- 
 amorphoses to which the}' are normally subjected in the liver. 
 The matter that is decomposed no longer takes the form of ex- 
 crement ; the albuminoid substances remain colloid, instead of 
 being crystalloid and therefore dialysable. Urea, which is an 
 eminently diuretic substance, diminishes ; the result is a diminu- 
 tion of renal activity. Now, this is a new danger, a fresh obstacle 
 to elimination. Often also the kidney is affected on its own 
 account by the cause that has produced jaundice, an infectious 
 malady, for example. But this has to do with quite another kind 
 of poisoning. The liver no longer makes bile, and yet it is not 
 acholia that kills the patient. The poisoning is due to all the 
 causes that are poisoning the system when the kidneys no longer 
 act, and also to those substances that are ordinarily transformed 
 by the liver into excrementitious mattei*. 
 
 The greatest danger in jaundice is renal impermeability. On 
 the other hand, severe cases of jaundice may be cured if the 
 kidneys remain permeable.
 
 LECTURE XXV. 
 MALIGNANT JAUNDICE : AGGRAVATED JAUNDICE. 
 
 Importance of the functional and anatomical soundness of the kidneys from the 
 point of view of the cure of jaundice. The various causes that often render 
 the kidneys unhealthy in jaundice. Consequences of the tissues being im- 
 pregnated with bile. The diminution and then the suppression of the hepatic 
 functions : the influence of the stoppage of the functions of the liver on 
 assimilation and disassimilation. Accumulation in the blood of the waste 
 products of nutrition incompletely transformed and unfit for excretion. To 
 auto-intoxication by natural poisons succeeds poisoning by anomalous 
 
 poisons. The relation of the various accidents attendant upon aggravated 
 
 jaundice : cholaemia, acholia, uraemia. The extremely poisonous nature 
 
 of the urine of patients suffering from jaundice, so long as the kidneys are 
 permeable. Importance of polyuria in the prognosis of jaundice. Distinc- 
 tion between the aggravated forms of jaundice and the particular malady 
 called malignant jaundice, or acute yellow atrophy of the liver, which is, 
 perhaps, caused by an infective agent, and may be developed without 
 jaundice. 
 
 FROM what I said in the preceding lecture on the subject of 
 the causes of the poisoning in jaundice, I showed that there are 
 two poisons in bile, the biliar}- salts, which have alwa3*s been 
 recognized as poisons, and a substance which, up to the present, 
 has not been appreciated, from a toxic point of view, viz., the 
 coloring matter. This is, I think, anew revelation in pathology. 
 I wish also to call particular attention to the fact that, although 
 in jaundice a considerable quantity of poison enters into the 
 system, nevertheless, in the great majority of cases, this intro- 
 duction of poison is not followed by death, as the organism is 
 doubly protected. 
 
 In the first place, the kidneys cany off part of the pigment 
 and the biliary acids and their derivatives ; therefore the urine 
 becomes poisonous, and I have found that jaundiced urine kills 
 in the proportion of ten and even seven cubic centimetres per 
 kilogramme of the animal. On the other hand, the fibres of 
 the connective tissue fix the most important of the poisons of 
 bile, the coloring matter. The tissues, by becoming colored, with- 
 draw from the circulation, in increasing proportion, this poison, 
 
 (229)
 
 230 LECTURES ON AUTO-INTOXICATlOtf. 
 
 and exercise gradually a sort of condensing power. Neverthe- 
 less, notwithstanding this double protection, we observe, even in 
 mild cases of jaundice, as the first signs of poisoning, slowing 
 of the pulse, pruritus, nasal haemorrhages, and rapid emaciation. 
 If the kidneys become less permeable, the conditions of poison- 
 ing increase. Now, the kidneys often act insufficiently in jaun- 
 dice, frequently through a cause that is independent of and 
 anterior to the jaundice itself. Nephritis may supervene and 
 aggravate the malady, resulting often from the same cause that 
 has produced the jaundice, an infective agent. The liver also 
 may become disordered, like the spleen and the kidnej^s, owing 
 to infectious agencies having reached it. Lastty, the impermea- 
 bility of the kidneys may be the consequence of the jaundice 
 itself altering the epithelial cells. The consequence of the im- 
 permeability of the kidney is the retention of the coloring mat- 
 ter and of the biliary salts. The biliary impregnation of the 
 red corpuscles, the hepatic cells, muscular fibre, epithelial cells, 
 and the vascular membranes causes destructive modifications in 
 all these elements. 
 
 Disassimilation is more rapid or is affected by anomalous 
 processes. The destruction of the cellular elements takes place 
 either totally or by fatty degeneration. We note a diminution 
 in the number of corpuscles, which are swollen and spherical. 
 The serum contains haemoglobin in solution, not modified. The 
 heart, which is altered in its structure, loses some of its energy ; 
 its beats are at first slower, and then feebler and more frequent. 
 
 Then atrophy of the liver may set in. Atrophy of the liver 
 is characteristic of one form of jaundice, but does not belong 
 exclusively to it, and it may occur even in cases which pass 
 from the benign to the grave form. We note at first a gradual 
 diminution, and finally suppression, of the hepatic function, 
 which consists in transforming the materials of disassimilation, 
 as well as those of assimilation. 
 
 We must not forget that the liver has a double function. On 
 the one hand, it has to develop the matter absorbed from the intes- 
 tines sugar, for instance in order to form glycogen ; if this 
 work cease, the organism is deprived of a substance that is 
 indispensable to it. On the other hand, the liver has to com-
 
 CONSEQUENCES OP SUPPRESSED HEPATIC FUNCTION. 231 
 
 plete the development of the materials produced \>y disassimila- 
 tion ; before they pass inta the excretory passages, colloids 
 should be converted into crystalloid dialyzable material. 
 
 Thus, when atrophy of the liver sets in, the repair of the waste 
 of tissue is interfered with, and there is an accumulation of the 
 matter produced by disassimilation, which has not been able to 
 pass into the state for being excreted. The proteid substances 
 no longer reach the state of urea; therefore, the urea diminishes. 
 Now, this is the most important physiological diuretic, forcing 
 the water to pass away through the kidneys and to carry off at 
 the same time the other solid excrementitious matter. 
 
 While these modifications are taking place in the natural 
 chemistry of the liver parallel chemical modifications of the 
 blood are also going on. An accumulation of leucin, tyrosin, 
 xanthin, and hypoxanthin is produced in the blood and in the 
 tissues. These same substances consequently appear in the 
 urine ; and besides other substances, the greater number of 
 which are little known, we find in the urine imperfectly-formed 
 albumens, which have not the normal point of coagulation by 
 heat, and which act differently when treated by chemical reagents. 
 The kidney is not constructed for the elimination of these 
 bodies, but, nevertheless, they force their way through the renal 
 barrier. 
 
 The biliary function, also, of a liver which is being destroyed 
 by jaundice is soon diminished or suppressed. The liver be- 
 comes incapable of forming the pigment and the biliary acids, so 
 that the jaundice itself may diminish, and even disappear; the 
 biliary pigment decreases in the urine, and at a given moment, 
 in patients that were at first poisoned by bile, biliary poisoning 
 is suppressed. We no longer find in the urine biliary acids 
 or compounds of sulphur, or the incompletely-oxidized sulphur 
 derived from them. 
 
 When we administer to a patient suffering from acute atropl^y 
 of the liver a substance which, tinder normal conditions, should 
 undergo certain metamorphoses in the liver, substances which, 
 like naphthalin, fix the sulphur radicals, we find that the 
 elaboration of this body say, 1 naphthalin is not accomplished 
 according to the normal processes. Instead of being eliminated
 
 232 LECTURES ON AUTO-INTOXICATION. 
 
 in the form of naphthyl-sulphite of soda, it is found in cholera 
 patients, for instance in the urine, in a form which is as yet 
 undefined, notwithstanding M. Rosenstiehl's researches ; it gives 
 rise to a particular coloring matter, of a purple-violet tint, 
 similar to that of permanganate of potash. I have observed this 
 coloration, which is due to an anomaly in the elaboration of the 
 naphthalin, in acute atrophy of the liver and in .two cases of 
 typhoid fever. Thus, when the liver is destroyed, disassim- 
 ilated substances are defectively elaborated ; the chemistry of 
 malignant jaundice confirms this, and this particular case of the 
 anomalous elaboration of naphthalin in acute atrophy of the 
 liver and cholera furnishes a still better demonstration. 
 
 Besides the disorders resulting from the suppression of the 
 hepatic functions in malignant jaundice the kidneys, if not already 
 disordered, soon become so. In the same way that lead, silver, 
 mercury, and cantharides, when being eliminated, cause true 
 toxic nephritis, so do the biliary poison and the poisons fabri- 
 cated in a secondary manner, by imperfect disassimilation, during 
 their elimination, produce renal changes. This is, then, a fresh 
 hindrance to renal ejection, and a new cause of the retention of 
 poisons in the system. Lastly, the vessels also become affected ; 
 extravasations are produced, and in some cases, which cannot be 
 called exceptional, renal haemorrhage still further increases the 
 impermeability of the kidneys. Thus, while the chances of 
 biliary poisoning diminish, causes of secondary poisoning appear, 
 which continually increase in consequence of the renal imperme- 
 ability, the anomalous elaboration of the liver, and the alteration 
 of all the cells of the body. 
 
 Auto-intoxication by natural poisons is succeeded by self- 
 poisoning by other morbid poisons. If objections are raised to 
 this singular complexity of the phenomena, if I am blamed for 
 substituting for the too simple and natural idea of the patho- 
 genesis of the serious accidents attendant upon jaundice, owing 
 to the action of the biliary salts, that of the train of processes 
 which take place one after the other in natural sequence, I shall 
 answer that not a single link in this chain can be shown to be 
 false, and that the truth of each separate detail can be established. 
 Only the degree of their subordination is left in doubt.
 
 RENAL PERMEABILITY THE SAFEGUARD IN JAUNDICE. 233 
 
 Now, with regard to jaundice that has become serious, we 
 are obliged to appeal to this succession of the various processes. 
 I cannot affirm positively that such and such a succession is the 
 absolute order of facts, but I firmly believe that they all play an 
 important part, and I am inclined to believe that the order of 
 complications is as follows : Biliary poisoning (cholaemia) ; cell- 
 degeneration, particularly alteration of the hepatic cells; atrophy 
 of the liver and suppression of its functions (acholia), renal 
 changes from various causes, ending in renal inadequacy; Lastly, 
 self-poisoning, of a mixed nature, through acholia, i.e., through 
 the retention of anomalous toxic products; and through uraemia, 
 i.e., through the non-elimination of the normal toxic products, 
 which should be carried off by the urine. 
 
 This uraemic element cannot alwaj-s be compared with ordi- 
 nary uraemia ; it cannot be uraemia from an alimentary cause, 
 the patients being scarcely nourished at all ; nor can it be poison- 
 ing from re-absorption of bile, since the latter ceases to be 
 secreted ; the putrefactions of intestinal origin certainty con- 
 tribute to it as one cause, but it is principal!}* a poisoning by 
 the normal or abnormal refuse throwli off by intense disassimila- 
 tion, setting free potass, which is quite capable of poisoning 
 and of causing convulsions in a large number of cases, and also 
 organic matter incompletely elaborated. Thus, the greatest 
 danger in severe jaundice is the impermeability of the kidnej-s. 
 If the kidneys remain permeable, the patients discharge urine 
 that is intensely poisonous, and which has a great tendency to 
 cause convulsions. This urine, even when decolorized by carbon, 
 retains its convulsive power; it is sufficiently powerful to kill 
 animals in opisthotonos, as if they were poisoned by the potass 
 that has been sent in excess into the blood through the exag- 
 gerated disassimilation of the tissues. If the kidneys are no 
 longer permeable, the urine will no longer have this convulsive 
 power, but the patient will be poisoned and have the con- 
 vulsions. 
 
 As long as renal impermeability is not manifested, the prog- 
 nosis may be reserved in severe attacks of jaundice, and complete 
 recovery is possible. In certain cases, after having observed 
 the hepatic dullness diminish every day, we then see it return by
 
 234 LECTURES ON AUTO-INTOXICATION. 
 
 degrees to its original limits, showing that the liver has regained 
 its volume in the space of a few weeks or a few days. I have 
 personally remarked two instances of this kind. The severe 
 jaundice was not then complicated by renal lesions ; the polyuria 
 remained constant, and from three to four litres of urine were 
 secreted daily. Is all that I have said applicable to the partic- 
 ular malady which Rokitansky has called acute } r ellow atrophy 
 of the liver? to the form of severe jaundice described by Ozanam ? 
 to the typhoid jaundice of Lebert? to the essential hsemorrhagic 
 jaundice of Monneret, or the essentially-grave jaundice of Genou- 
 ville ? I do not think so. What I have said applies to simple 
 attacks of jaundice that have become severe ; moreover, these 
 are perhaps the most common class. 
 
 According to Frerichs, the primordial cause is atrophy of 
 the liver, which, by vitiating the elaboration of the various 
 kinds of matter, produces all the other complications. Other 
 hypotheses have been proposed. We need not discuss jaundice 
 proceeding from the suppression of the hepatic function, no 
 more than jaundice from polycholia or from too great activity 
 of the hepatic function, the jaundice in these cases being only 
 slight, of short duration, or absent. At least, there have been 
 as many theories formed about severe jaundice as about uraemia. 
 
 Buhl's theory is, that severe jaundice is the result of 
 cerebral oedema ; that, elimination of water by the bile being 
 suppressed, hydraemia ensues, and then cerebral oedema. Can 
 we admit that the 800 or 1200 grammes of water in the quantity 
 of bile formed daily can produce such effects when we know that, 
 normally, the intestines re-absorb half or two-thirds of this 
 water? 
 
 Uraemia alone is to be considered the cause, according to 
 another opinion. I have taken it into account, as you know, but 
 we can only trace its terminal complications. There onty, then, 
 remains acholia, the suppression of the part played by the liver 
 in disassimilation ; this is French's theory, and I believe it to 
 be the correct one. 
 
 But what can produce the atrophy of the liver? Everything 
 tends to show that it is the consequence of a general infective 
 malady, not only because infectious agents have been found in
 
 ACUTE ATROPHY OP THE LIVER, AN INFECTIVE PROCESS. 235 
 
 the fluids and the tissues, but because at the same time we find 
 fever, purpura, a polymorphous erythema, scarlatiniform, cir- 
 cinate, and globular eruptions on the skin, the pharynx, and the 
 palate, and because an acute nephritis exists, with parallel 
 determinations to the various viscera. 
 
 Jaundice does not necessarily supervene in acute yellow 
 atrophy of the liver, but it may form a connecting link between 
 the destruction of the hepatic cells and .the appearance of a 
 nephritis, which adds to the symptomatic list its own contingent 
 of accidents traceable to uraemia. The study of severe jaundice 
 thus serves as an introduction to the study of poisoning by 
 anomalous products.
 
 LECTURE XXYI. 
 THE Toxic NATURE OF PATHOLOGICAL URINES. 
 
 Causes of death in infectious diseases. Examination of the poisons in the tissues 
 of animals that have died from infection. The toxic nature of the urine in 
 tetanus. Special characteristics of the toxicity of the urine in fevers ; con- 
 vulsive properties. The part played by poisoning in the ataxo-adynarnic 
 accidents of fevers and in the death-struggle. 
 
 WE know that in the course of infectious diseases there exists 
 a perversion of the nutritive processes, more particularly in the 
 function of the liver-cells. Under the influence of the disease 
 we note the appearance in the urine of anomalous material, the 
 products of imperfect disassimilation, colloid substances, and 
 modified albumens. We find drugs undergo unusual trans- 
 formations, naphthalin, for instance, being eliminated without 
 having entered into combination with sulphur. Some of these 
 anomalous products may be poisonous, but this is only a matter 
 of conjecture, requiring demonstration. This task is not an easy 
 one, and often ends in a negative or doubtful -result. 
 
 I have long endeavored to find the substance which causes 
 death in infectious diseases. If, in certain cases, death may be 
 attributed to the withdrawal of oxygen from the blood, as in 
 charbon ; to capillary obstructions hi the more important organs ; 
 to septic foci being established by the infectious agents passing 
 out of the vessels, the explanation, in the majority of cases, lies 
 in poisoning. I have found hardly any trace of those poisonous 
 substances that are well known, especially in infections of diges- 
 tive origin, surface infections. I found that the alkaloids were 
 increased, but that they could only account for a very small part of 
 the auto-intoxication. I have searched for this poison in gaseous 
 gangrene. Charrin has also endeavored to find it while studying 
 the form of septicaemia that will in future bear his name. 
 
 Extracts were taken from all the organs of five animals that 
 had died of septicaemia. These extracts were injected into 
 healthy animals and produced poisoning, but with extracts from 
 (236)
 
 ANIMAL ALKALOIDS IN HEALTH AND DISEASE. 237 
 
 the organs of healthy animals we also obtain poisoning. Does 
 not the destruction of the anatomical elements allow substances 
 to become free that are held in the living cells by the forces of 
 tension ? The normal poisons have thus prevented the discovery 
 of the anomalous poison. Amongst the substances that may be 
 suspected we have particularly studied the alkaloids. We have 
 extracted alkaloids from the bodies of animals that have died 
 of infectious diseases ; but we also find alkaloids in the tissues 
 of healthy animals, although, perhaps, in smaller quantities. 
 However, the quantity of alkaloids extracted from the bodies of 
 five animals that had died of septicaemia was not sufficient to 
 produce poisoning. We have not, therefore, succeeded in finding 
 the morbid poison that kills in infectious diseases, but these 
 negative results do not alter the fact that we must admit the 
 existence of such a poison in these cases. How, for instance, 
 can we explain the fact that gaseous gangrene, which is so emi- 
 nently infectious, but which only produces local anatomical 
 injury, without embolism or any inflammatory process, can 
 cause death, if it is not that, simultaneously with the production 
 of oedema, a poison is fabricated which kills the higher elements 
 of the system ? This is mere hypothesis, it will be said. Yes, 
 but hypothesis that is almost necessary. 
 
 Not having been able to select one single poisonous substance 
 that could really be considered capable of producing the effects 
 referred to, I endeavored to study the poisonous element as a 
 whole, taking all the poisonous substances in the eliminating 
 liquid, the urine. By proceeding in this manner, I arrived 
 at results that seemed to me to be convincing. 
 
 A patient attacked with tetanus passed no urine for two 
 days. M. Labbe collected the urine when it re-appeared. On 
 being injected into the veins of an animal, it produ< .<! mild 
 tremors after the sixth cubic centimetre ; myosis appeared ; the 
 pupils were punctiform at ten cubic centimetres. From t\v-lvr 
 cubic centimetres there were violent tonic spasms and convul- 
 sions up to the thirty-fourth cubic centimetre; death thru m- 
 sued from opisthotonos. Is not this almost a complete repro- 
 duction of the symptoms of tetanus? We then thought that 
 the urine contained a convulsive poison, which was the cause
 
 238 LECTURES ON AUTO-INTOXICATION. 
 
 of the tetanic convulsions. We were half inclined to see in 
 this the confirmation of the infectious nature of tetanus. This 
 theory was very tempting. But when we studied the toxic 
 properties of the urine in pneumonia in six cases, we found 
 at once that it is more poisonous than normal urine ; it is 
 capable of killing in the proportion of nineteen cubic centi- 
 metres per kilogramme of the animal, as a minimum, the average 
 proportion being thirty-eight cubic centimetres. We observe in 
 the animal the ordinary signs of poisoning by normal urine, 
 myosts and lowering of temperature ; but, besides these symp- 
 toms, we get tonic convulsions absolutely similar to those pro- 
 duced by the urine of a patient suffering from tetanus, spasms 
 with lasting muscular rigidity, and, finally, death from opisthoto- 
 nos. The urine of patients suffering from pulmonary spleniza- 
 tion killed animals, when injected in quantities of twenty-two cubic 
 centimetres, with the same convulsions. In typhoid fever, at its 
 commencement, before intestinal antiseptic action has yet been 
 effected, I have seen the urine produce only those toxic phe- 
 nomena that belong to normal urine, no convulsions, very little 
 pupillary contraction, narcosis ; death ensues at fifty, sixty, and 
 seventy cubic centimetres. 
 
 In lead poisoning, sixty-six cubic centimetres of urine per 
 kilogramme have produced death without convulsions. In leu- 
 cocythaemia the urine has caused death in convulsions at fifteen 
 cubic centimetres. The urines of those suffering from jaundice 
 cause death with convulsions ; the fatal result might in this case 
 be attributed to the substances of biliary origin, the acids, or the 
 coloring matter ; but I have reason to think that death is due to 
 another cause. The urine of albuminuric patients not suffering 
 from uraemia causes death at fifty-four cubic centimetres without 
 convulsions. The urine of those attacked with uraemia is no 
 longer poisonous. 
 
 From all these experiments it follows that in certain chronic 
 diseases the toxic nature of the urine is the same as when it is 
 in a normal condition, and that the symptoms are the same as 
 those produced by normal urine ; but in the greater number of 
 pathological urines, and in that of all feverish diseases, we find an 
 increase in the normal degree of toxicity, and also new toxic
 
 CONVULSIVE PROPERTY OF FEBRILE URINES. 239 
 
 properties, especially the power of producing convulsions. The 
 urine of fever patients has all the characteristics of normal 
 urine, with less somnolence and with the addition of convulsions. 
 The convulsive tendency is no doubt present in normal urine, 
 but as long as the convulsive poison and the narcotic poison are 
 in conjunction the latter annihilates the former. It is possible 
 that normal urine might be capable of producing convulsions if 
 the narcotic poison were withdrawn. Thus, the injection of the 
 urine of those suffering from disease produced neither the repe- 
 tition of the symptoms of the disease nor 4he reproduction of 
 the disease itself. Nevertheless, I once found that the urine of 
 a patient suffering from phthisis produced tuberculosis. Lan- 
 douzy quotes a similar case, and Toussaint also. Before that 
 occurred, he had observed the reproduction of charbon by inoc- 
 ulation with the urine, and Charrin succeeded in reproducing his 
 septicaemia by the same means. But we reproduce, by the injec- 
 tion of urine, those infectious diseases that can be transmitted to 
 animals, and in which the infectious agents are eliminated through 
 the kidneys. What I thought to obtain by the injection of these 
 pathological urines was not the transmission of the disease, but 
 the reproduction of some predominating symptom. I did obtain 
 an anomalous symptom, but this was produced indiscriminately 
 by the urine of tetanus and that of pneumonia. In the case of 
 diseases that are not infectious, or those in which the microbes 
 are not eliminated through the kidneys, how can we explain the 
 greater toxicity of the urine and that special convulsive property 
 which we find is common to nearly all febrile or consumptive 
 diseases ? 
 
 Has the disease, by perverting nutrition, generated poisonous 
 substances? In pneumonia, is some alkaloid, or other poison 
 formed ? This question is at present unsolvable. Moreover, if 
 we admit that special toxic substances are formed by the disease, 
 how can we explain the fact that all diseases shall produce the 
 same convulsive poison? Another hypothesis is that the patho- 
 logical urines owe their toxic nature to certain normal poisons 
 produced in superabundant quantities. Several substances pro- 
 duced by normal disassimilation may cause convulsions. If 
 alimentation is suppressed in feverish diseases, disassimilation is
 
 240 LECTURES ON AUTO-INTOXICATION. 
 
 increased. The weight of the body sometimes diminishes several 
 kilogrammes in twenty -four hours. Now, the destruction of the 
 tissues sets free potass, a substance that causes convulsions. In 
 typhoid fever the urine, which is only slightly toxic at first, when 
 matter is being slowly destroyed and the weight of the patient 
 is scarcely diminished, becomes decidedly poisonous at the period 
 of convalescence, when rapid emaciation takes place. This is 
 one argument in favor of the hypothesis in question. 
 
 The coloring matter is increased in the urine of fever patients ; 
 for instance, from six to sixty and eighty in twenty -four hours. 
 Now, highly-colored urine causes contraction of the pupil and 
 convulsions; on being decolorized by charcoal, they lose their 
 convulsive property. However, the convulsive power of certain 
 pathological urines does not disappear from them under discolor- 
 ation, which proves that, in these cases, the convulsions are due, 
 to'a large extent, at least to potass, and not exclusively to convul- 
 sive organic matter. Is it not a striking fact that febrile urine, 
 in which the coloring matter is from ten to twenty times as abun- 
 dant as in normal urine, becomes so intensely convulsive ? We 
 also note in fever a diminution in the salts of alimentary 
 origin, chloride of sodium, for instance. Potass, on the other 
 hand, is doubled or trebled. In short, then, what fever does is 
 to pour in excess, into the blood and the urine, potass and color- 
 ing matter, or at least toxic substances which are habitually asso- 
 ciated with coloring matter. Now, potass and coloring matter 
 are powerfully convulsive ; I am, therefore, inclined to think that 
 the urine, in acute diseases, owes its toxicity not to a special 
 poison, but to certain normal poisons in excessive quantities. 
 Febrile urine produces the same phenomena as normal urine, 
 only more quickly, myosis, polyuria, lowering of temperature. 
 Somnolence appears very tardily ; the effect of the narcotic sub- 
 stance is diminished, it being overpowered by the convulsive 
 poison. The latter, when produced in excess, quickly manifests 
 its power, which, under normal conditions, is concealed by the 
 narcotic poison. 
 
 How is it that these substances, which render the urine 
 poisonous, do not poison the patient? Precisely because the 
 urine is poisonous, i.e., because it carries off the poison. But
 
 POISONS ARE ELIMINATED BY THE URINE. 241 
 
 if the kidneys begin to work defectively, complications appear 
 convulsions, the final ataxo-adynamic phenomena of every dis- 
 ease which may result not only in secondary nephritis, but also 
 in an insufficiency of urine during the death-agony. The death- 
 struggle is a form of poisoning, as all the signs observed in the 
 dying testify, from the pupillary contraction which appears at 
 first to the final convulsion and the last throe.
 
 LECTURE XXVII. 
 
 PYOCYANIC DISEASE. POISONING ACCIDENTS IN DIABETES. 
 
 Do pathological poisons really exist ? Pyocyanic disease. The researches of 
 
 M. Charrin. Can sugar become a poisoning agent in diabetic subjects? 
 
 Dehydration is the cause of nearly all the accidents of diabetes. Aceto- 
 naemia. Diabetic coma. 
 
 HAVING been led by theory to seek for one poisonous substance 
 in disease, I have found, in the organism of patients, substances 
 which may be poisonous, but they occur in such proportions that 
 it is impossible to attribute the poisoning to them under ordinary 
 conditions. Seeking for a morbid poison I have only been able 
 to find the normal one. 
 
 In pyretic diseases, or those of a rapidly -consumptive nature, 
 I have found that the coloring matter produced in excess, and 
 potass, liberated by the too rapid destruction of cells, both having 
 Convulsing properties, may cause poisoning if the kidney 
 become impermeable, whether it is attacked with nephritis or 
 whether its action is suspended as in febrile or agonic oliguria. 
 During the last phases of disease, we may observe the appear- 
 ance of the signs of poisoning that are characteristic of coloring 
 matter and potass. 
 
 Under these circumstances the poisoning has certainly been 
 prepared indirectly by the disease, but there has been no special 
 poison fabricated by it. The fact of knowing that the lungs no 
 longer act, or that the temperature is too high, when we see 
 ataxo-adynamic accidents set in, does not give us the right to 
 speak of pneumonic poison, tetanic poison, and so on. We see 
 simply a phase of uraemic poisoning, with this distinction, that 
 the poisoning is produced by exaggerated disassimilation, and 
 that it is retained in the blood through the inadequate action of 
 the kiclne3 7 s.> 
 
 This does not mean that there are not in certain maladies 
 true morbid poisons, engendered by the normal life of microbes 
 or the diseased life of human cells. But the difficulty is to 
 collect and isolate these poisons. 
 (242)
 
 BLUE PUS. 243 
 
 If this subject could be studied like the pathogenic agent 
 of blue pus, it could perhaps be more easily explained. Blue 
 pus is characterized by two things, a body having the chemical 
 characteristics of the alkaloids, and which has long been recog- 
 nized, viz., pyocyanine ; and a microbe, a mobile bacillus, which 
 produces this substance, and which is mentioned by Gessard. 
 The microbe is easily recognized, since the blue color of the sub- 
 stance that it fabricates betrays it wherever it is met with. The 
 blue is completely fixed by chloroform ; afterward, in the pres- 
 ence of acidulated water, the chloroform is discolored and the 
 water takes a roseate tinge. By this reaction we can always 
 recognize this organism, which develops rapidly and resists the 
 action of all the other ferments. 
 
 Taking advantage of this characteristic, M. Charrin has made 
 experiments in inoculation and injection with liquid cultures. 
 Clinical surgery has shown that blue pus, when brought into 
 contact with a wound, does not produce infectious accidents ; 
 but, it may be asked, what would happen if it forced its way 
 through the barrier of the tissues? This hypothesis has been 
 answered by the injection into the veins of pure "culture 
 liquids" containing both the microbe and pyoc3'anine. The 
 subcutaneous injection seems harmless, hut an animal that is 
 subjected to an intra-venous injection of 1 or 2 cubic centimetres 
 of liquid, prepared in this way, becomes feverish and tvuses to 
 eat ; it may be attacked with intense albuminuria and diarrhoea ; 
 it becomes emaciated and ill. We must mention that a certain 
 number of rabbits prove refractory, and that often considerable 
 doses are required in order to succeed. Is this malady of an 
 infectious nature? We know that microbes are cliininatnl 
 by the urine and faecal matter. But are they still alive? 
 Yes ; since we observe, simultaneously with their presence, the 
 reaction of pyocyanine in the liquids impregnated with these 
 substances. 
 
 We may push the question still further, and, by treating the 
 bacillus and the chemical substance separately, we may endeavor 
 to ascertain their respective roles in the mechanism of the dis- 
 ease. We withdraw the microbes from the liquids in which 
 they have been cultivated, employing for this purpose either
 
 244 LECTURES ON AUTO-INTOXICATION. 
 
 heat and filtration or filtration by means of the tested Chamber- 
 land cylinders; * we find in the filtered liquids all the reactions of 
 pyocyanine, and we can, moreover, make sure by cultivation that 
 these liquids no longer contain any microbes. If, under these 
 conditions, we inject into the veins of a rabbit the filtered 
 liquid, which is rich in pyocyanine, we find that the toxicity of 
 this liquid is comparatively slight, whether we inject successive 
 quantities for several days, or whether we inject at once 60 
 cubic centimetres of the liquid. The animals, upon receiving 
 these injections, which are made antiseptically, show only transi- 
 tory effects, and in some cases can be cured ; whereas, when the 
 same liquids, containing microbes, are injected in the same 
 animals, these animals, as I have said, become diseased and 
 generally die. We are thus led to think that in the development 
 of this experimental disease, while taking into account the action 
 of the chemical substance, we must also consider the material 
 lesions, nephritis, enteritis, etc., which seem to be created by 
 the microbe itself. To speak of nephritis only, for instance, we 
 do not always produce it in a lasting form, by injecting into 
 a rabbit, in a certain quantity, crystallized pj-ocyanine, or a 
 liquid containing pyocyanine deprived of microbes ; whereas, 
 when we inject a liquid culture containing microbes, if the animal 
 survive a certain number of days, nephritis is established perma- 
 nently, and microbes are found in the blood, the kidneys, and 
 the urine. "Under these conditions the blood, the kidneys, or the 
 urine, on being treated, show the presence of pyocyanine. It 
 is, therefore, from these experiments, probable that the microbe, 
 besides its possible chemical action, produces a traumatic effect 
 on the kidneys and causes a nephritis, which then acts on its 
 own account, and places the animal in the position of a patient 
 attacked with Bright's disease, f 
 
 * See Wilson's Hygiene, page 232. 
 
 t The results indicated were obtained by experiments on the rabbit ; we are not 
 speaking of those that can be obtained upon other animals, the guinea-pig, for 
 instance, and by varying the modes of introduction. The results in these cases 
 may be different, and this is not surprising, since the conditions of the experiment 
 are changed. M. Charrin is of opinion that fresh reservations should be made as 
 regards the role of the chemical substance. Recent experiments have shown him 
 that the pyocyanine bacillus could live under certain conditions without gener- 
 ating pyocyanine itself. It is, therefore, possible that in the animal a body is formed 
 which is more or less like pyocyaiiine, but possesses a different degree of toxicity 
 and acts differently.
 
 CONSEQUENCES OF EXCESS OF SUGAR IN THE BLOOD. 245 
 
 We must now endeavor to find out whether the poisons are 
 produced in consequence of a disordered state of the general 
 nutrition. 
 
 As regards sugar, the formation of which is considered by 
 certain physicians as the result of a disordered state of nutrition 
 of the liver, can we look upon it as a poison ? Not in my opinion. 
 Sugar is not essentially poisonous ; it only becomes injurious by 
 its quantity. If it is not consumed, transformed, or destroyed 
 by the organs, it becomes a poison like carbonate of soda, which, 
 in excess, may become poisonous although it forms an integral 
 part of the blood. As long as the blood contains only one in a 
 thousand of sugar, the system is not appreciably affected ; but 
 above 3 per 1000 (Bernard) or 5 per 1000 (Pavy) the effects 
 of poisoning ensue, and a special pathological condition is 
 established. 
 
 One of the first symptoms of excess of sugar in the blood is 
 glycosuria, which does not exist when there is only 1 per 1000 
 of sugar in the blood. When this proportion is increased, the 
 hyperglycaemia deranges the quantity of the urine. In fact, 
 when sugar is eliminated, it carries awa}^ its equivalent of 
 water of diffusion, which is in the proportion of 7 parts of 
 water to 1 of sugar. Under normal conditions, the blood does 
 not allow itself to be dehydrated ; when it gives up a portion 
 of its water, it recovers it immediately by drawing it from 
 the plasmas and the elements of the tissues. The blood cannot 
 have less than its normal percentage of water; in order to 
 supply the renal secretion, it must be incessantly receiving 
 water, which is either conveyed to it by drinking, or which it 
 draws from the tissues and especially from the plasmas, which 
 represent in weight a third of the economy. If the water 
 obtained by drinking and the water from the plasmas fail to 
 keep up the required supply, under any other circumstances than 
 the case of hyperglycoemia the renal secretion could be dimin- 
 ished or suppressed. But as long as there is in the blood water 
 and sugar in excess, there is produced a glycosuria accompanied 
 by the water of diffusion due to the sugar; when the glycaemia 
 is intense, the sugar, which must necessarily be supplied with 
 its equivalent of water of diffusion, dehydrates more and more
 
 246 LECTURES ON AUTO-INTOXICATION. 
 
 the plasmas and the tissues. One of the primary effects of poison- 
 ing by sugar is, therefore, the extraction of water from the system. 
 Then a modification is produced in the phenomena of osmosis ; 
 the sugar, having rendered the blood more dense, becomes a fresh 
 medium for the elements of the system, and is thus another cause 
 of the abstraction of water from the plasmas. We find the sensa- 
 tion of thirst appear. A diminution ensues in the aptitude of 
 the water to leave the blood ; the , pulmonary exhalation dimin- 
 ishes as well as the cutaneous exhalation. 
 
 Under normal conditions one-third of the total quantit}^ of 
 water that passes out of the system is eliminated by the lungs 
 and the skin. In a diabetic subject, according to Burger, these 
 emunctories only eliminate one-twelfth. 
 
 Among the consequences of this dehydration of the tissues, 
 we must note diabetic cataract, which has been demonstrated 
 by an ingenious experiment performed by M. Lecorche. This is 
 the explanation that is generally admitted ; but in reality the 
 crystalline opacity which is produced experimentally by de- 
 hydrating the body by means of sugar or salt is not cataract ; 
 it disappears when the tissues have regained their normal per- 
 centage of water. Diabetic cataract, on the contrary, is per- 
 manent, and we not infrequently see it developed in patients 
 that are suffering from oedema, in which case there is no question 
 of dehydration. 
 
 As the results of the derangemeut of the nutritive processes, 
 we note the appearance of anomalous products of disassimilation, 
 anomalous albumens, so frequent in diabetic subjects, and the 
 increase of extractives or urea ; these features are not the 
 unfailing rule, but they are accidents that might be explained 
 by hyperglycsemia. 
 
 The dehydration of the tissues, when it exists onty in a mod- 
 erate degree, provokes certain functional disturbances, which, in 
 the nerve-elements, take the form of an exaggerated excitability 
 and rapid fatigue, and, in the muscular elements, are manifested 
 by cramp, as in cholera. A higher degree of dehydration is 
 attended by nervous accidents of great gravity, in which cate- 
 gory we may perhaps include diabetic coma. 
 
 When we were discussing typhoid fever and dyspepsias, we
 
 COLOR-TEST OP URINE IN ACETON^EMtA. 247 
 
 mentioned a particular alteration of the fluids, in consequence 
 of which the breath exhales an odor similar to that of chloroform 
 or rennet-apples, and also a particular chemical reaction of the 
 urine. It has been suggested that this odor of the breath and 
 this reaction of the urine may belong to acetone. 
 
 In certain urines a few drops of perchloride of iron will give 
 a claret-colored tint, or the shade produced may be darker, even 
 violet. The reddish-brown tinge is very frequent under various 
 morbid conditions; this is due to substances the nature of which 
 has not been chemically defined ; acetone gives a wine-red color, 
 but this tint may be produced by other substances. This 
 reaction is met with in certain forms of dyspepsia, in t3'phoid 
 fever, scarlatina, leucocythaeinia, and in pernicious ancemia ; it is 
 very frequent in diabetes. Nevertheless, in many diabetic sub- 
 jects, we may observe for years the chloroform ic odor of the 
 breath, without ever detecting it in the urine, and still rarer 
 in this disease is the reaction of perchloride of iron. If a salt 
 due to the combination of diacetic ethyl with soda resulted from 
 the transformation of the acetone, we should obtain the colora- 
 tion without the odor ; otherwise we get the chloroformic odor 
 in the urine without the coloration. In short, in nearly all 
 cases of diabetic coma, perhaps in all, we find the color-reaction 
 of the urine and the odor of the breath. It is therefore proba- 
 ble that in these cases poisoning exists similar to that of 
 severe dyspepsia. I know nothing of the pathogenic condi- 
 tions of those forms of poisoning termed acetonaemic. The 
 clinical fact having been observed by Brieger, at the clinic of 
 Frerichs, under various pathological conditions ; by Senator, by 
 Jaksch in carcinoma of the stomach and in severe forms of dys- 
 pepsia, and by myself in typhoid fever and in a very great num- 
 ber of cases of dilatation of the stomach, it seems to me pr ! ta- 
 ble that the cause of it is some morbid substance elaborated in 
 the intestines. These accidents can be reproduced in every 
 feature experimentally, as has been shown l>y tin- experiments of 
 M. de Gennes. 
 
 However this may be, we note in certain diseases, not neces- 
 sarily infectious, a body, or a series of bodies, which, on being 
 eliminated by the urine, give a red coloration upon the addition
 
 248 LECTURES ON AUTO-INTOXICATION. 
 
 of perchloride of iron. These bodies are the result of the defec- 
 tive elaboration of matter by the human organism ; they are 
 anomalous substances, not engendered by microbes. Amongst 
 these substances are acetone, diacetic ether, and oxybutyric 
 acid, which are poisonous ; thus we find in this class some true 
 morbid poisons. In diabetes this reaction of the urine and the 
 odor of the breath may serve as a basis of diagnostic and prog- 
 nostic indication. 
 
 Two years ago the odor of the breath enabled me to form 
 the diagnosis in a case in which a child had been suddenly 
 attacked with comatose symptoms. It was not known that the 
 child was ill when he was brought home from school in a state 
 of complete coma. The skin was dry, and there was no patellar 
 tendon reflex. Guided by the odor of the breath and the 
 absence of the reflex, I expected to find sugar in the urine ; but, 
 as the child passed no urine, I had those parts of his clothing 
 washed that were likely to be stained with urine ; in the infusion 
 thus procured I obtained the reaction of sugar, and was thus 
 enabled to pronounce the attack to be diabetic coma, which 
 ended in death in a few hours.
 
 LECTURE XXVIII. 
 
 POISONING BY PATHOLOGICAL POISONS. CHOLERA. 
 
 Former opinions as to the causes and the nature of cholera. Influence of the 
 prevailing pathogenic theories on the choice of prophylactic modes of 
 treatment. Mode of propagation of cholera. Importance of the transmis- 
 sion by water. Other possible modes of contagion. Attempts to discover 
 the agent of infection. The French Commission in Egypt. The researches 
 and opinions of Koch. The value of the comma bacillus. Studies of the 
 trausmissibility of cholera to animals. 
 
 IN studying diseases caused by poisoning I am naturally led 
 to speak of cholera and to sum up the knowledge that we pos- 
 sess of its nature. All that has been said with regard to the 
 etiology of the plagues of antiquity and of the Middle Ages has 
 been repeated in modern times with regard to cholera. It was 
 at first attributed to the wickedness of man and the anger of 
 God; to this religious view succeeded the idea of poisoning by 
 means of witchcraft, a theory to which were attached corollaries 
 of certain practices that were reputed to be prophylactic. Wells 
 and springs were believed to be poisoned. Certain persons, and 
 especially doctors, were accused of being the promoters of direct 
 poisoning. These absurd accusations were made in Paris in 1832 
 and in Naples in 1884. In the past, Jews and doctors were often 
 associated together in public denunciations relating to pestilen- 
 tial diseases. They were suspected of poisoning food. Travel- 
 ers generally were also suspected, not only those who were 
 infected, but all foreigners; a foreigner was looked upon as a 
 deadly enemy. Previous to the pestilence being attributed to 
 water, the air and the clouds had been made responsible for it ; 
 there was a time when a certain cloud hovering over a town was 
 reputed to be pestilential in virtue of some peculiar reflection or 
 some unusual tint. These ideas were prevalent in the fourteenth 
 and fifteenth centuries, and we have actually seen them revived in 
 the second half of the nineteenth century ! Naturally the pro- 
 phylactic measures proposed were in harmon}' with these etiolog- 
 ical chimeras. It was necessary to avert the divine wrath by 
 
 (249)
 
 250 LECTURES ON AUTO-INTOXICATION. 
 
 expiatory deeds, by penances and fastings imposed on evil-doers. 
 Believers in the efficacy of pilgrimages and processions are to be 
 found, even at the present day, in all classes of society. 
 
 People were more practical during the Black Plague ; they 
 appointed sentinels to guard the wells. In Paris also, in 1865 
 and in 1873, 1 noticed that the casks of the water-carriers on the 
 Quai St. Bernard were guarded by the police. Was this a con- 
 cession to popular prejudices on the part of the authorities, or 
 did the authorities share these prejudices? Sentinels were also 
 placed at the gates of towns, the portcullis was lowered and the 
 drawbridge raised. In our own times sanitary cordons have been 
 drawn up round uninfected towns in the south and travelers 
 have been received with gunshot. 
 
 Yet- a calm examination of facts has shown that cholera is a 
 disease that is endemic in certain countries ; for centuries it has 
 been prevalent on the Delta of the Ganges. Thence it spreads ; 
 it follows a caravan and marks the route from the Ganges to 
 Mecca, where it attacks the Mussulmans, Hindoos, etc., assembled 
 together; on its return it rages amongst all the caravans, some- 
 times completely destroying them, or it advances with them as 
 far as Hedjaz and Persia ; it then continues its migration through 
 Russia to Western Europe. Its progress has also been traced 
 from Hedjaz into Egypt, to Alexandria, where it forms a fresh 
 centre, thus menacing Europe from two sides. We know that its 
 migrations are determined by commerce and by routes followed 
 by the great human currents, seas, rivers, roads, and railways. 
 
 What strikes us in the history of cholera, when we hear of 
 its having appeared almost simultaneously at several points, is 
 that it is always a sea-coast town that is first attacked. It never 
 appears first in an inland district. 
 
 With regard to this, it has been asserted that, in a certain 
 number of instances, a port has been infected without any patient 
 suffering from cholera having disembarked there. But even if 
 the infection is not conveyed by those who have been attacked, 
 the ship itself has been contaminated or brings infected linen. 
 The corpses of those that have succumbed to the disease may 
 have been thrown into the sea, but the discharges and the linen 
 impregnated with them have remained on board. In these cases
 
 DISSEMINATION OP CHOLERA. 251 
 
 the linen has never been disinfected; the truth has not been 
 told as regards this matter. We can see how much importance 
 may be attached to the official statements relating to the disin- 
 fection of suspected ships or cargoes by the pretense of disinfec- 
 tion that we witnessed during the last epidemic. The authorities 
 did right not to insist upon the disinfection of the people them- 
 selves ; I am not so sure that they were justified in not ordering 
 the thorough disinfection of clothes, linen, and bedding after 
 landing ; it was then too late. But at the lazaretto how did 
 they act? They did not even demand that the people entering 
 the lazaretto should take a bath. 
 
 Since that time a great outcry has been raised against us by 
 the public and the press, and public authorities have been shaken 
 in the confidence they had placed in doctors, and begun to ask 
 themselves whether the latter had ever deserved this confidence. 
 
 Often still, when we follow the dissemination of cholera 
 through France, we can trace it to linen that has not been disin- 
 fected. On studying the history of a great number of local epi- 
 demics, we find that laundresses have been attacked first. The 
 dissemination of cholera has also been attributed to water. It 
 is probable that several centres have been created by this agency. 
 It is almost an established fact that, in towns, the districts that 
 have escaped have been those which could not come into contact 
 with the discharges of those attacked, conveyed through the 
 medium of water; on the other hand, our canal of the Ourcq, 
 with its array of boats, was one of the most powerful agents of 
 transmission at an}^ rate, in the last epidemic ; and the districts 
 first attacked were a part of the Faubourg Saint Antoine and the 
 Rue Sainte-Marguerite, those to which the water of the Ourcq 
 was brought by direct canalization. 
 
 In hospitals where water is economized, where infected and 
 nnfiltered water might be used for culinary nnd i>li:inu:iriMitir:il 
 purposes, at La Charite* and at Lariboisiere, cases occurred* 
 within the building before any cholera patient from the town 
 had been brought to the hospital. To the same cause mny IT 
 attributed the disastrous infection of the Asylum for Old People, 
 in the Rue de Bretenil. As regards the other centres of infection, 
 it is impossible to explain their origin categorically, on account
 
 252 LECTURES ON AUTO-INTOXICATION. 
 
 of the mixing of the water of the Dhuys and the Vanne with 
 that of the Ourcq, in consequence of the anastomoses which are 
 the great fault of our system of canalization, and which cause an 
 ebb and flow from one stream to the other. 
 
 With regard to the spreading of infection by water we cannot 
 believe that there is any truth in the assertion that the infection 
 may be conveyed up the river, along the Rhone for instance, 
 from Marseilles to Avignon ; no one, on reflection, can admit 
 that the germs could be carried against the stream. 
 
 The link that is missing in the chain of evidence of contagion 
 is direct contagion. But if measles, small-pox, and scarlatina 
 are spread chiefly in this way, we can understand that with typhoid 
 fever and cholera the infection is conveyed not through the 
 body itself, but through what comes from the body. We must 
 also take into account the vegetables that grow close to the earth 
 and that are eaten raw, and various modes of contamination by 
 drinking. We have naturally been led to consider cholera as a 
 disease that is indirect^ contagious, like typhoid fever ; it was 
 natural, therefore, to look for the agent of contagion in cholera. 
 The pathogenic study must be entered upon from a parasitic 
 point of view, and, in fact, the first reports of the discovery of 
 organisms said to be infectious date from 1848. These first 
 reports have no scientific value, but they serve to show the spirit 
 in which the investigations have been carried on since that time. 
 
 Virchow in 1848 and Hallier in 1867 found frequently para- 
 sitic organisms, but in liquids where microbes constantly exist. 
 Regular, systematic investigations did not commence until the 
 European commissions were sent to Alexandria, in 1883; these 
 researches were instituted by the French Commission, which in- 
 cluded among its members Messrs. Straus, Roux, Nocard, and 
 Thuillier, and by the German Commission of R. Koch. The 
 great secrecy observed by the French Commission was fully justi- 
 fied. At first, it is true, the telegraph told too much ; but when 
 the members of the Commission spoke themselves, they expressed 
 their doubts at the right time. They had found traces of an 
 organism in the blood, but they added that this differed singu- 
 larly from the various ferments known, not being colored by the 
 ordinary processes and not being susceptible of cultivation.
 
 CHOLERA AND THE COMMA BACILLUS. 253 
 
 Koch has also, on the other hand, discovered an organism in 
 the form of a comma, which cannot be classed under any of the 
 five groups of ordinary parasitic intestinal microbes. These 
 comma-shaped organisms appeared to him to be on the surface 
 or in the interior of the intestine of cholera patients, and they 
 are sometimes in such quantities as to constitute nearly the 
 whole of the excretions. Koch has seen them in the choleraic 
 discharges, on the cells whilst desquamation is going on, or 
 between them and penetrating into the interior of the intestinal 
 glands and into the superficial parts of the mucous membrane ; 
 but he has neve* found them anywhere else, having searched for 
 them vainty in the ganglia, the kidne3's, the spleen, the blood, 
 and the lymph, and yet he has already asserted that these organ- 
 isms' are the pathogenic agents. The comma bacillus is a short, 
 slender, moving body, which fixes certain stains like other patho- 
 genic organisms. The examination of this germ presents no 
 difficulty. It is slightly curved ; its dimensions are as follow : 
 length, from 1^/K to 2|^; breadth, from 0.6ft to 0.7/M. These 
 comma microbes maybe found linked together by twos or threes, 
 so as to form a little chain ; they may be curved in opposite di- 
 rections or in the same direction, so as to appear in the form of 
 an S, or of part of a circle, or they may assume a spirillar form. 
 Such is the statement of Koch, which rests solely on the empiri- 
 cal fact of his having found, on the surface of the intestine, an 
 organism which is not present under ordinary conditions, and 
 which is very abundant in cholera. But it has yet to be ex- 
 plained how this organism causes the disease. Koch says that, 
 after it has left the intestine, he can continue its germination 
 on any moist surface, on the surface of food, and on the soil 
 when the temperature is not too low and when the atmosphere 
 is damp. The question then arises as to how a district is ever 
 freed from it. The fact that a lake contained any of these organ- 
 isms would be sufficient to render it permanently infected, and 
 Koch actually discovered in India a lake the waters of which 
 contained these comma bacilli, which he was able to cultivate; 
 in this way there would be a perpetual interchange of infectious 
 germs between the earth and man. This explanation is simple ; 
 in fact, it is too simple to be admitted. If it were true, how is
 
 254 LECTURES ON AUTO-INTOXICATION. 
 
 it that in Paris and in Germany, where the cultivation of chol- 
 era germs has been studied unceasingly, the various labora- 
 tories have not been infected? How is it that the disease has 
 not broken out amongst the experimentalists ? 
 
 In order to distinguish the bacillus which he has found in 
 those attacked with cholera, Koch has endeavored to find cer- 
 tain special characteristics a different action on gelatin, and a 
 particular configuration in the zone of liquefaction which 
 would reveal the nature of the bacillus. This characteristic, 
 however, is not wholly convincing. 
 
 It must be remarked that the same organism has been found 
 in cases of sporadic cholera by Finckler, of Bonn ; it was, per- 
 haps, somewhat larger than Koch's bacillus. Thus, in two dis- 
 eases which resemble each other in their symptoms to such a 
 degree that the most learned physicians do not express a decided 
 opinion as to the nature of the accidents attendant upon them 
 until after the extension and propagation of the disease, we 
 find microbes exactly similar in form. Against the pathogenic 
 value to be attached to the comma microbes it has been urged 
 that, as they exist only in the intestine, they could not so 
 rapidly cause such serious general disorders. But it may be 
 that these organisms engender a toxic substance, which, when 
 once absorbed, affects all the cells of the sj-stem. 
 
 Other investigators M. Emmerich at Vienna, and M. Doyen 
 here think, moreover, that they have found pathogenic mi- 
 crobes in some of the viscera. M. Emmerich, who states that 
 he has seen them, did not recognize amongst them the comma 
 bacillus. M. Doyen, not having absolutely detected them in 
 sections, draws conclusions from sterilized cultures made with 
 portions of the liver and kidneys, in which the existence of the 
 microbe was not shown by the microscope ; these cultures had 
 reproduced the comma bacillus. 
 
 All this consists merely of hypothesis. I am ready to grant 
 that the comma bacillus may be a microbe that is peculiar to 
 cholera, although it has been found in the saliva of people not 
 suffering from that disease. But what conclusions can be drawn 
 from the discovery of this microbe? It has been cultivated, 
 but these cultivations have not succeeded in reproducing the
 
 FAILURE TO PRODUCE CHOLERA EXPERIMENTALLY. 255 
 
 disease. Is it likely that the result, which could not be obtained 
 even from the discharges of the patients themselves, could be 
 obtained from the supposed agent of infection of cholera, culti- 
 vated and isolated, when not an atom of the organism of the 
 person attacked with the disease had been removed with it? 
 Since 1865 and 1866 attempts have been made to produce cholera 
 experimentally with the perspiration, the vomit, and the dis- 
 charges of cholera patients. The experimentalists have suc- 
 ceeded in killing animals, probably by communicating to them 
 certain forms of septiceemia, but not by reproducing cholera ; and 
 yet the}' hope to succeed by the introduction of the great-grand- 
 nephews of microbes that have been taken from material that 
 will not of itself produce cholera ! 
 
 It was thought that the failure of the experiment was due 
 to a defective method of introducing the pathogenic organisms 
 into the intestine, because they did not avert the protecting 
 influence of the gastric juice, the acidity of which would pre- 
 vent the development of the microbes. Now, since 1832, it has 
 been erroneously asserted that the choleraic discharge is always 
 neutral or alkaline ; I have found it to be acid. The acidity of 
 the intestinal liquid was slight, but was still present at the 
 moment of death. This fact contradicts the theory of the sup- 
 posed protective influence that would be exercised by the gastric 
 juice. Moreover, if animals do not take cholera when choleraic 
 matter is introduced into their stomachs, how is it that the dis- 
 ease is conveyed through the gastric channel in the case of men, 
 who also have an acid gastric juice ? Certainly they have it no 
 longer when they are suffering from cholera, but they had it up 
 to that time. 
 
 When we introduce the agents, that are supposed to generate 
 cholera, directly into the duodenum, the action of the bile 
 being suppressed by means of a ligature round the bile-duct 
 (Nicati and Rietsch), accidents are produced which resemble 
 those of cholera ; and as it is found, at the post-mortem exam- 
 ination of cholera patients, that the gall-bladder is distended, 
 and that there is no bile in the intestine, the development of 
 cholera in man is attributed to the suppression of the biliary 
 secretion. Bat it is because the patient has cholera that we
 
 256 LECTURES ON AUTO-INTOXICATION. 
 
 find in him the biliary secretion suppressed. After examining 
 all the theories that have been expressed and all the experiments 
 that have been made, I arrive at the conclusion that the proof 
 of the transmissibility of cholera to animals is still wanting ; 
 they have been caused to die sometimes from peritonitis, from 
 septicaemia, or from poisoning, but not from cholera.
 
 LECTURE XXIX. 
 
 CHOLERA (CONTINUED). 
 
 Objections to the pathogenic value of the comma bacillus. Introduction of the 
 microbe by the hypodermic method ; M. Ferran's inoculations. Experi- 
 mental researches relating to the value of the comma bacillus. Intestinal 
 antiseptic treatment does not prevent choleraic accidents. Search after a 
 poison in the discharges of cholera patients, in their tissues and their secre- 
 tions. The intra-venous injection of the urine of cholera patients into animals 
 reproduces most of the symptoms of cholera. 
 
 IN the critical examination which I have made of the pathog- 
 eny of cholera I have examined the claims of Koch's bacillus, 
 and I have found various objections calculated to lessen the 
 confidence that might be felt with regard to its importance. 
 The only argument of any weight in favor of Koch's opinion is 
 the presence, in the second part of the intestines of those attacked 
 with cholera, of special organisms not found in the intestines of 
 healthy people, nor in those of patients suffering from other dis- 
 eases ; it is, in fact, the presence of these organisms from the 
 very commencement of the choleraic attacks, often in consider- 
 able quantity and sometimes to the exclusion of all other 
 microbes, in the alimentary canal. With the exception of this 
 empirical fact, which only leads to a hypothesis, all the argu- 
 ments brought forward are misleading. 
 
 The demonstration to be desired was to obtain the suspected 
 organism in a state of purity, and by its introduction into a 
 healthy body to reproduce cholera. It was thought that this 
 experiment could only be tried on animals. Now, animals do 
 not contract this disease. They have always, both spontaneously 
 and experimentally, resisted the influence of choleraic discharges 
 introduced directly into their bodies. Could it, then, be expected 
 that cholera would be communicated to them by means of the 
 cultivated germs? It seemed highly improbable; but, neverthe- 
 less, attempts have been made to realize this result by distorting 
 nature, so to speak. 
 
 (257)
 
 258 LECTURES ON AUTO-INTOXICATION. 
 
 Experimentalists endeavored to get rid of whatever might 
 protect the animal against the action of the cholera germ, viz., 
 the gastric juice, the bile, and the intestinal movements. They 
 rendered the gastric juice alkaline, they conveyed the organism 
 supposed to be pathogenic directly into the duodenum, and 
 they introduced into the peritoneum as much as 5 grammes of 
 tincture of opium per kilogramme of the animal. The results 
 obtained were various. Sometimes death ensued, but more often 
 the animal survived. When death occurred, it was generally 
 from peritonitis or septicaemia. No results calculated to con- 
 vince us of the truth of the theory were obtained ; only Messrs. 
 Nicati, Rietsch, Koch, Ferran, and Van Ermengen are convinced. 
 Others, even M. Cornil, who still holds that the comma bacillus 
 is really the cholera bacillus, make formal reservations with 
 regard to the subject of the experimental reproduction of 
 cholera. 
 
 These results, which I consider negative, do not, however, 
 prove that Koch's bacillus is not pathogenic. They only prove 
 that animals, which are, as we know, refractory to the action of 
 choleraic matter, also resist the cultivated descendants of the 
 microbes which it contains. But is it the same with man ? He 
 contracts cholera spontaneously. Is he, then, attacked with 
 symptoms of cholera when the comma bacillus is developed in 
 his system ? We cannot quote any experiment of importance in 
 answer to this question. We may mention the experiments of 
 Bochefontaine, who swallowed pills containing choleraic dis- 
 charge : he experienced nausea and even vomiting. He inoc- 
 ulated himself in the cellular tissue with the liquid in which the 
 germs were cultivated : inflammatory swellings resulted, but 
 there was no sign of the general symptoms of cholera. The first 
 experiment must not be considered absolutely convincing. The 
 bacilli might be absent from the matter introduced into the 
 system, or they might be in a very small quantity, or the mode 
 of administration might have neutralized them. The second 
 method cannot be appealed to, as cholera is not contracted by 
 hypodermic inoculation. All that we know goes to prove that 
 the infectious agent is introduced through the digestive channels. 
 
 This mode of inoculation has been repeated by M. Ferran.
 
 INOCULATION OF CHOLERA. FERRAN. 259 
 
 He obtained the local phenomena experienced by Bochefontaine, 
 local septic action in the tissues, rarely terminating in suppu- 
 ration. I do not know what value may be attached to these 
 inoculations from a prophylactic point of view.* But I can see 
 already objections to his methods of procedure. In any case, as 
 far as man is concerned, the facts obtained by experiment do 
 not enable us either to admit or deny the theories of Koch with 
 regard to his bacillus ; but, experimental proofs being wanting, 
 observation may, in a roundabout fashion, lead us to certain 
 conclusions. 
 
 Before the period when I had to treat cholera patients in the 
 last epidemic I had for a long time reflected on what course I 
 should adopt if cholera did break out. I had seen that the 
 results of physiological treatment were absolutely nil, with the 
 exception of intra-venous injections. On the other hand, I knew 
 the uselessness of all empirical modes of treatment. Opium, 
 alcohol, etc., have given the same statistical results. I was thus 
 justified in making an experiment in pathogenic therapeutics 
 at the time when a new doctrine gave us the hope of defending 
 the patient against the parasitic germ that was supposed to 
 menace his life. 
 
 * At the time this lecture was delivered wo had no definite information to enable 
 us to form an opinion on the experiments of Ferran. It could only be said that the 
 principle of his method, if there was any principle in it, had not been proved so far 
 as cholera was concerned. The attempt to create a sort of immunity from a disease 
 by simply changing the mode of introduction of a microbe is a principle that was 
 known before M. Ferran's time. Messrs. Arloing, Cornevin, and Thomas were the 
 first to demonstrate it, in their splendid experiments on symptomatic charbon. But 
 what is true of one pathogenic agent of disease may be false as regards another, and 
 we should therefore, in this case as in all others, guard against hasty generalizations. 
 Unfortunately, the importance of the results announced by M. Ferran is considerably 
 diminished by the report of the French Commission, composed of Messrs. Brouardel, 
 Charrin, and Albarran. This report shows us that M. Ferran was not able, or, at all 
 events, not willing, to give proofs of what he had advanced, both as regards the 
 morphology of the comma bacillus and the effects obtained from it upon animals. 
 The phenomena observed in persons inoculated in no way resemble those of a slight 
 attack of cholera, as the Spanish physician asserted ; their blood never contains any 
 of the bacilli. Moreover, M. Ferran refuses to explain the composition and prepara- 
 tion of his lymph, or, if he gives an explanation, he abandons it a few days after for 
 another. Lastly, the statistics that ho publishes, although numerous, are far froa 
 being unassailable. In short, the scientific value of M. Ferran's method has not yet 
 been proved. This is the verdict pronounced by the French Commission, and we 
 must own that tins verdict has boon in no way weakened by the later reports of the 
 other Commissions (Belgian, American, Italian, and Spanish) that were sont to 
 Valencia for the same purpose.
 
 260 LECTURES ON AUTO-INTOXICATION. 
 
 Accepting, therefore, the theory of Koch provisionally, 
 everything seemed to indicate that antiseptic treatment adapted 
 to cholera was the path to follow. If we were dealing with an 
 agent of infection that was scattered through the blood and the 
 tissues, all idea of antiseptic treatment would have had to be 
 given up. But we had before us a doctrine that asserted, authori- 
 tatively, arguments that were capable of misleading. I therefore 
 applied the doctrine of Koch to the therapeutics of cholera in all 
 sincerity and good faith. It may be summed up thus : Cholera 
 is produced by a poison formed by organisms in the intestinal 
 canal; it is an infection of an accessible surface. We were 
 able to destroy by antiseptics other microbes in the alimentary 
 canal. Therefore, if Koch was right, it was necessary to intro- 
 duce into the alimentary canal a substance capable of destroying 
 life in all the microbes, a non-absorbable and, consequently, an 
 insoluble substance. I was led to proceed in cholera as in 
 typhoid fever. I employed iodoform in such a state of division 
 that the dose employed represented a surface of sixty square 
 metres; I gave 1 gramme a day in conjunction with 5 grammes 
 of naphthalin, a substance that is almost insoluble. I have had 
 a mortality of 66 per cent., i.e., equal to that of the other hos- 
 pitals. This is not a very gratifying result, but we may learn 
 something from it. 
 
 What objection can be raised to the accuracy of the following 
 proposition ? " If the pathogenic organism exists in no other part 
 of the system, and if we have succeeded in destroying it in the 
 intestines, choleraic accidents ought not to be produced." In the 
 first place, it may be urged that Koch's microbe is not influenced 
 by iodoform or by naphthalin. This resistance would be sur- 
 prising on the part of an organism that is more vulnerable than 
 most of the known microbes, since it is killed by heat and desic- 
 cation. Moreover, I may mention an experiment made by M. 
 Chantemesse, who checked the germination of the bacilli by 
 introducing into the substance about to be used for their cultiva- 
 tion a small quantity of the preparation administered to the 
 patients. 
 
 It may also be said that the treatment was instituted too 
 late, the morbid poison being already formed and absorbed. I
 
 CHOLERA NOT THE RESULT OF INTESTINAL INFECTION. 261 
 
 answer \>y facts. A certain number of the patients subjected to 
 the antiseptic treatment recovered. I continued to give them 
 iodoform and naphthalin ; several of them had a relapse. Now, 
 these had ceased to be influenced by the poison absorbed at first. 
 A fresh germination must, therefore, have taken place in the 
 system of infectious agents that had remained in some part of 
 the organism, but not in the alimentary canal, the latter having 
 remained aseptic. I conclude from this that the germination of 
 the pathogenic agent of cholera does not take place in the 
 intestines. 
 
 While I was attending the cholera patients, I also attended 
 typhoid patients in other wards. The latter having been sub- 
 jected rigorously to iodoform and naphthalin, their intestines 
 were aseptic, and yet two of them took the cholera in the course 
 of the typhoid fever, and their evacuations consisted of black 
 matter having only the odor of naphthalin. We have, therefore, 
 two series of facts proving that cholera cannot be a surface 
 infection seated exclusively in the intestinal cavity. The ali- 
 mentary canal is, in all likelihood, the channel through which the 
 infectious agent enters, this entrance being probably effected 
 through the stomach rather than through the intestines ; but it 
 is not in the alimentary canal that the multiplication of this 
 organism takes place. 
 
 If Koch's theory is undermined, it is only in one of its 
 claims. I do not say that the bacillus is not the pathogenic 
 agent, but I think that, if it is, it must exist elsewhere than 
 where Koch has seen it. Other investigators believe that they 
 have succeeded in staining it, and in finding it in various organs; 
 they have obtained cultures with fragments of the viscera. 
 Whether the infectious germ in cholera is Koch's bacillus or any 
 other, one must exist ; and we should not be justified in denying 
 its existence simply because we have not seen it. The microbe 
 of hydrophobia, which we cultivate in animals and which we can 
 attenuate or intensify, has not yet been discovered. We may, 
 therefore, proceed, notwithstanding the absence of direct demon- 
 stration concerning its nature, and admit, in the interest of both 
 prophylaxis and therapeutics, that cholera is an infectious disease. 
 But, granting that there must be a certain pathogenic agent in
 
 262 LECTURES ON AUTO-INTOXICATION. 
 
 cholera, let us ask ourselves if this agent does not produce some 
 substance, and if it does not kill by causing a kind of poisoning. 
 This idea, which I formulated in 1879, speaking of infectious 
 diseases generally, has been taken up by Klebs and Koch, in 
 connection with cholera. It would be necessary to show that 
 there exists in the bodies of those attacked with cholera, or in 
 their excretions, a particular toxic substance, capable of repro- 
 ducing in other living beings symptoms similar to those of 
 cholera. 
 
 M. Gabriel Pouchet has discovered the existence of an alka- 
 loid in the discharges of cholera patients, and M. Hayem also 
 mentions one. It would have been more satisfactory if they had 
 stated whether these were particular alkaloids distinguished from 
 those which are found normally in the faecal matter of both the 
 sick and the healthy. 
 
 Even before these discoveries, on September 20, 1884, in the 
 case of a rag-picker suffering from cholera, one of that little group 
 of individual cases that formed the local epidemic of Saint-Ouen, 
 the forerunner of the true Parisian epidemic, I found, in an 
 extract of 575 cubic centimetres of intestinal matter, a consider- 
 able quantity of an alkaloidal substance, a quantity which cer- 
 tainly exceeded the proportion of alkaloids generally contained 
 in faecal matter. This alkaloidal substance differed from the 
 other intestinal alkaloids in one of its chemical characteristics. 
 If, like them, it was precipitated by the iodo-ioduretted reagent, 
 by the iodides of mercury and of potassium, by the phospho- 
 molybdate of soda, by tungstate of soda, it did not present the 
 reaction with tannin. During the epidemic of November, 1884, 
 I found this alkaloid again with the same characteristic. I also 
 saw it crystallized in the form of long and extremely fine 
 needles ; but I was not able to experiment upon its physiological 
 characteristics, not having been able to obtain a sufficient quan- 
 tity of it. For this reason, I thought it best to leave the report 
 of these observations among my laboratory notes. 
 
 Another question arises as regards this alkaloid. Supposing 
 it to be a substance peculiar to cholera patients, might it not have 
 been produced in some other way than by the action of parasitic 
 organisms? I know that in cholera patients matter is formed
 
 SYMPTOMS PRODUCED BY INJECTION OF CHOLERAIC URINE. 263 
 
 differently from that in other people, whether ill or in good health. 
 Speaking of this, I may mention a peculiarity in connection with 
 naphthalin. All my patients were treated with this substance. 
 In some it underwent normal metamorphoses. In others it 
 underwent unusual metamorphoses, which I have also remarked 
 in acute yellow atroph} r of the liver and in two cases of typhoid 
 fever. In these latter cases, the urine, instead of retaining the 
 somewhat dirty, blackish-brown tint which it assumes in people 
 that have been subjected to naphthalin, assumed spontaneously, 
 at the moment of emission, a deep-violet color, like that of a 
 solution of permanganate of potass. It was not the pink tint 
 that is generally obtained by means of acetic acid in the urine 
 of patients who were being treated with naphthalin. The violet 
 matter in choleraic urine is soluble in ether, whereas that 
 which appears upon the addition of acetic acid in the urine of 
 other patients treated with naphthalin will not dissolve in ether. 
 This anomalous fact is probably owing to certain changes in the 
 liver. Other substances besides naphthalin might, therefore, be 
 as irregularly transformed, and certain anomalous substances 
 found in the passages or in the alimentary canal of cholera 
 patients may have been generated in the liver or in the system 
 without the intervention of microbes. There are, besides, in 
 cholera patients, special toxic substances, which cause death in a 
 different manner to the normal poisons of the system. There is 
 a choleraic poison which is shown by the special toxicity of the 
 urine of cholera patients. The experimental injections of the 
 urine of cholera patients rarely produce in animals the symptoms 
 of poisoning by normal urine. 
 
 Myosis is generally defective. Instead of appearing at the 
 tenth cubic centimetre, it comes later or is absent altogether. 
 But one sign is very soon observed, which is not produced by 
 injections of any other kind of urine, cyanosis, which is shown 
 on the inner surface of the ear in the rabbit ; then muscular 
 cramps, which in no way resemble the convulsions produced by 
 other kinds of urine, being spasms which begin long after the 
 commencement of the injection and continue for half an hour 
 after it has ceased. They consist of a slow and protracted 
 stretching of the hind-limbs, followed by four or five spasms at
 
 264 LECTURES ON AUTO-INTOXICATION. 
 
 the end of a minute and a half, another rigid extension of the 
 limbs, and fresh spasms ; eight, ten, or fifteen similar contrac- 
 tions may take place, and then quietness is restored. 
 
 Cooling of the surface is more marked after the injection of 
 choleraic urine than with normal urine. Albuminuria appears at 
 the commencement and is intense, whereas it is rare and does not 
 appear till late with normal urine. After the injection of normal 
 urine the animal is restored to health ; after the injection of chol- 
 eraic urine it is seized with pea-soupy diarrhoea, the motions being 
 pale or reddish, without any trace of bile. The albuminuria goes 
 on increasing; then, after a day and a half, anuria sets in, the 
 refrigeration continues and is more marked, and the animals die, 
 with a rectal temperature of 33 or 34 C. On the bodies being 
 examined, the intestine is found to be congested and filled with 
 pea-soupy, diarrhoeic matter, constituted mainly by the intes- 
 tinal desquamation, resembling choleraic diarrhoea so much that 
 it might be mistaken for it, except that no bacilli are found. 
 Either the urine injected was infectious, or we had obtained a 
 form of poisoning similar to that determined by the infectious 
 agent in cholera when it has produced the toxic matter.
 
 LECTURE XXX. 
 
 CHOLERA (CONCLUSION). 
 
 A special poison exists in the urines of cholera patients. The symptoms of the 
 animals into which they are injected cannot be explained by infection. Effects 
 produced on animals by the substances soluble and insoluble in alcohol and 
 contained in choleraic urine. The poison which causes the choleraic symp- 
 toms in animals is soluble in alcohol anjd is organic. The second period in 
 cholera is the result of a fresh intoxication occasioned by the normal poisons, 
 from which the kidneys no longer free the system : it is uraemia. Myosis in 
 cholera patients that are anuric. This terminal uraemia in cholera diflers 
 from ordinary uraemia, as several of the sources of the ursemic poisons are 
 suppressed. 
 
 THE history of the progress of cholera compels us to look 
 upon it as an infectious disease. But it is doubtful whether 
 Koch's pathogenic agent is the true one. Admitting, from 
 analogy, that there is an infectious agent peculiar to cholera, we 
 must ask ourselves whether the microbe is responsible for all the 
 ill effects observed, or whether, amongst the symptoms of the 
 illness, there may not be toxsemic accidents attributable to a 
 substance formed by the system itself, or by the microbe. 
 
 I believe that this poison really exists, and the study of the 
 toxic nature of the urine in cholera patients has led me to think 
 that it is eliminated by the urine. The toxicity of choleraic 
 urine presents special characteristics. Besides the properties 
 which it has in common with normal urine (pupillary contraction, 
 weakening of the muscles, certain respiratory disturbances, fall 
 of temperature, and diuresis) choleraic urine produces, in the 
 animals into which it is injected by the intra-venous method, 
 very marked cyanosis on the inner surface of the ear, a much 
 greater fall of temperature, lasting until death takes place ; 
 cramps, which I have never observed with injections of other 
 kinds of urine, and which are very different from opisthotonos 
 and convulsions, cramps which consist of a long, slow exten- 
 sion of the limbs, which is repeated at short intervals for half an 
 hour ; diarrhoeic evacuations, which may occur with certain nor- 
 
 (265)
 
 266 LECTURES ON AUTO-INTOXICATION. 
 
 mal or pathological urines as with distilled water, but in this last 
 case only with enormous quantities of urine, whereas a very small 
 quantity of choleraic urine produces motions of a whitish, yellow- 
 ish, grayish, or reddish color, the coloring being due to epi- 
 thelial desquamation of the small intestine and to the retention 
 of bile in the gall-bladder. 
 
 Albuminuria, which is rare and very slight with normal 
 urine, is in this case always considerable or intense, lasting 
 throughout the experimentally-produced disease. This albu-' 
 minuria may be succeeded at the last by complete anuria. At 
 length death ensues, not during the injection, but after an inter- 
 val of from twelve hours to four days ; whereas, with animals 
 whose death is caused by the injection of other normal or patho- 
 logical urine, death occurs always during the injection. With 
 choleraic urine nearly all animals die ; in those that survive we 
 may follow the development of the disease. The thermometer 
 indicates the gradual return of heat production ; the appetite 
 does not return for some time, the albuminuria diminishes, and 
 complete recovery is not effected until after about six days. 
 
 In what light are we to consider these accidents ? Are we 
 dealing with a case of infection or of experimental poisoning ? I 
 have answered some of the suppositions that might be made. To 
 account for infection, the infectious agent must have been in the 
 urine of the patient ; discharges containing bacteria must have 
 come from the kidneys. Now, we do not find any microbes in 
 the urine of cholera patients, either by direct examination or 
 after coloration. It is true that, in several diseases which are 
 evidently virulent, we cannot find microbes (hydrophobia, for 
 instance), or we can only demonstrate their existence by improved 
 methods of coloration (as in tuberculosis or leprosy). Thus, 
 there are microbes which remain invisible to us; the cholera 
 germ is perhaps one that calls for a special technical treatment 
 in order to be discovered. 
 
 We might have tried to obtain cultures with the urine of 
 cholera patients. I have not tried this, as I was only able to 
 obtain the urine of female patients; and in their urine one is 
 always liable to meet with some of those agents of infection which 
 germinate readily on the external genitals, the conditions of
 
 INJECTIONS OF CHOLERAIC URINE. 267 
 
 temperature and moisture being very favorable to their develop- 
 ment. But these means were not required in order to settle the 
 question. If the disease that we communicated to animals by 
 intra-venous injections of choleraic urine had taken the course 
 of an infectious disease, we should have to acknowledge the 
 existence of a phase of incubation which was altogether absent. 
 We saw all the symptoms appear immediately after the introduc- 
 tion of the urine and continue their course without any interrup- 
 tion. This total absence of incubation is a decisive argument. 
 Moreover, if the disease that we produced was of an infectious 
 nature, the quantity of urine injected would be of little impor- 
 tance ; the infectious germs, by their multiplication, would always 
 produce the same symptoms, whatever the quantity of choleraic 
 urine introduced into the system. Now, this was not the case : 
 we always observed an exact proportion between the quantity of 
 urine injected and the gravity of the disease. 
 
 Two animals survived, having been subjected to an injection 
 of only 12 cubic centimetres. All of those that died received 
 more than 17 cubic centimetres, and some as much as 90 cubic 
 centimetres. From the two reasons given above, I conclude that 
 the experimentalty-produced disease resulting from injections of 
 choleraic urine is of a toxic nature. 
 
 I evaporated all the water from some choleraic urine and 
 obtained, by the processes that I employ with normal urine, two 
 extracts, one containing the substances that are soluble in 
 alcohol, the other those that are insoluble in alcohol. I poisoned 
 some animals with these two extracts, but the results observed 
 were not the same in both cases. After the injection of the alco- 
 holic extract of normal urine we observe salivation, coma, and 
 death, if the quantity injected is sufficient ; if not, the animal is 
 restored to health in less than half an hour. 
 
 With the alcoholic extract of choleraic urine we rarely obtain 
 salivation ; we sometimes get somnolence, but the animals do 
 not recover. They have albuminuria and diarrhoea, and die 
 within two days. These last accidents albuminuria, colorless 
 diarrhoea, and death in two days are the same as those pro- 
 duced by the injection of choleraic urine itself. But I did not 
 obtain cyanosis and cramps with the alcoholic extract alone.
 
 268 LECTURES ON AUTO-INTOXICATION. 
 
 With the aqueous extract containing the substances that are 
 insoluble in alcohol I observed, as with normal urine, myosis and, 
 when the quantity was sufficient, convulsions, but these last in 
 no way resembled the spasms produced by the urine of cholera 
 patients. Lastly, in order to produce death, larger quantities 
 of the aqueous extract were required than of the choleraic urine 
 itself. When death occurred, it was always immediate, never 
 delayed. I never observed either albuminuria or diarrhoea, and 
 all the animals that survived were restored to health after this 
 short toxic illness of half an hour's duration. 
 
 Thus, there exists in choleraic urine something which is 
 carried off by alcohol, and which is different from the substances 
 generally found in urine, something which can be separated 
 from the other parts ; in short, a special morbid poison. Amongst 
 the toxic accidents caused by the alcoholic extract of choleraic 
 urine we note the absence of cramps. Are we mistaken in 
 attributing them to the cholera poison? Besides the special 
 features belonging to cholera poisoning, might not the cramps 
 be caused by the substance that gives the urine its convulsive 
 property, viz., potass ? But choleraic urine produces cramps at 
 17 cubic centimetres per kilogramme of the animal. I evaporated 
 400 cubic centimetres of choleraic urine ; the extract was reduced 
 to ashes and the residuum washed in distilled water, which 
 carries off all the potass. Now, the whole of the aqueous liquid 
 obtained was injected little by little, without producing any 
 toxic phenomena or convulsions. 
 
 Thus, there is in choleraic urine a poison which is a soluble 
 organic substance, and which I call the choleraic poison. I 
 cannot either name or define this poison chemically ; I only know 
 it by its physiological properties. I do not know whether it is 
 formed by the diseased organism carrying on the work of elab- 
 oration defectively, or by microbes, whether it is produced by 
 the patient himself, or by the vegetable parasites that have 
 caused the disease. 
 
 I cultivated in my laboratory Koch's comma bacillus. I had 
 at my disposal a considerable quantity of pure culture-liquid, 
 and I endeavored to solve the two following questions: 1. 
 Does the comma bacillus determine in the liquid the formation
 
 CULTURES OF THE COMMA BACILLUS ARE NON-TOXIC. 269 
 
 of a toxic substance ? 2. Does the comma bacillus really possess 
 a special pathogenic property, i.e., does inoculation with it 
 produce in animals the appearance of cholera ? 
 
 In order to answer the first question, I made several experi- 
 ments. I inoculated by the subcutaneous method some guinea- 
 pigs, weighing on an average 550 grammes, with from 3.8 to 35 
 cubic centimetres of the undiluted liquid in which comma bacilli 
 had been cultivated. These animals experienced no morbid 
 symptoms. In the second instance I introduced under the skin 
 of another guinea-pig, weighing 575 grammes, 20 cubic centi- 
 metres of the liquid heated to 63 C. Neither at the time of 
 the inoculation nor after it did the animal seem affected in any 
 appreciable degree. Proceeding with the solution of this first 
 question that I had asked myself, and wishing to employ the 
 intra-venous method, I experimented on the rabbit. I injected 
 into the veins of the ear of a rabbit, weighing 1800 grammes, 79 
 cubic centimetres of the culture-fluid, which had neither been 
 heated nor filtered from the bacilli, that is, 43 cubic centimetres 
 per kilogramme. At the moment of the experiment the only 
 effect shown by the animal was accelerated respiration, especially 
 at the end of the injection. It died twenty-four hours afterward. 
 The post-mortem examination showed pulmonary congestion, 
 slight diarrhoea, somewhat intense albuminuria, the absence of 
 comma bacilli in the excrement, and the presence of some of 
 these bacilli in the kidneys, to which the blood, having received, 
 had conveyed them. Altogether, the symptoms observed, and 
 especially the interval of time that elapsed between the injection 
 and death, suggested infection, and not poisoning. Lastly, an- 
 other rabbit, weighing 1990 grammes, received in the veins of 
 the ear in five minutes 92 cubic centimetres of the liquid, which 
 had been heated and filtered from the bacilli, or 46 cubic centi- 
 metres per kilogramme. The temperature fell eight-tenths at the 
 moment of the experiment, but the animal showed no other sign 
 of disturbance, and it afterward continued in good health. These 
 experiments, which I describe briefly, enable me to dispense 
 with long arguments. They fully justify me in giving a negative 
 answer to the first question : the liquids in which the comma 
 bacilli are cultivated contain no substance of a toxic nature.
 
 270 LECTURES ON AUTO-INTOXICATION. 
 
 In order to answer the second question, as to whether the 
 comma bacillus is capable of producing cholera in animals, I 
 experimented, like Koch, on guinea-pigs. Like Koch, I intro- 
 duced into the stomach of my guinea-pigs 11 cubic centimetres 
 of the liquid, after having first, according to the German scien- 
 tist's method, alkalized the stomach by means of 5 cubic centi- 
 metres of a 5-per-cent. solution of carbonate of soda, and arrested 
 all motion in the intestine by the intra-peritoneal injection of 3 
 cubic centimetres of tincture of opium. I must own that the 
 results I obtained were the same as those obtained by Koch 
 himself. My guinea-pigs soon died. After death I found that 
 the stomach was in most cases dilated, that the small intestine 
 contained, more or less abundantly, diarrhoeic matter, and that 
 there were comma bacilli, in varying quantities, to be observed 
 in this material. But I also instituted other experiments : with 
 some other guinea-pigs I alkalized the stomach and checked the 
 action of the intestine exactly according to Koch's method and 
 as I had done in the experiment just described. But in this 
 second experiment, instead of using the same kind of liquid as 
 before, I introduced into some of the guinea-pigs 11 cubic centi- 
 metres of an old charbon culture-fluid and into others 11 cubic 
 centimetres of liquid that had been turned acid by exposure to 
 the air, or some old pyocyanic culture-fluid. Well, the animals 
 died almost as rapidly as those that had received the comma 
 bacilli, presenting almost the same symptoms, except that the 
 diarrhoea was less abundant. These last results singularly de- 
 tract from the value of the first series of experiments; and, 
 without denying that the comma bacillus has any pathogenic 
 property, we are, in my opinion, justified in asserting that this 
 pathogenic property has not yet been clearly demonstrated. 
 
 If, then, judging by its analogy to other infectious diseases, 
 and by the history of its migrations and of its localized centres, 
 I am led to admit that cholera is caused by infection, I am also 
 justified in saying that, side by side with the infection, there ex- 
 ists in the pathogeny of cholera a secondary poisoning conse- 
 quent upon infection. I think that the symptoms which are 
 considered characteristic of cholera, and which enable us to form 
 the diagnosis, are the results of this poisoning. It is to this
 
 THE URAEMIA OF CHOLERA. 2tl 
 
 cause that we must attribute cyanosis, refrigeration, respiratory 
 disturbance, hiccough, the peculiar form of diarrhoea, intestinal 
 desquamation, cramps, dehydration of the tissues, albuminuria, 
 and anuria. These are the symptoms of cholera poisoning, and 
 I may add to the list the preservation of consciousness and the 
 absence of pupillary contraction. 
 
 But soon a second poisoning supervenes, which is associated 
 with the first or alternates with it ; it takes the clinical form of 
 mental torpor, loss of consciousness, somnolence, and coma. The 
 respiratory rhythm changes ; it becomes that of uraemia, or what 
 is known as the Cheyne-Stokes respiration. The temperature is 
 affected, sometimes rising and sometimes remaining low. At the 
 same time the pupils contract and become punctiform. 
 
 Is not this series of symptoms very different from that of the 
 earlier period ; and does it not, therefore, spring from another 
 kind of poisoning? We observe all these symptoms when 
 anuria and myosis appear, and they are all to be found in the 
 clinical picture of uraemia. Among authors I have not found 
 any indication bearing upon this fact. I was myself ignorant of 
 it until the day when this coincidence between the suppression 
 of the urinary secretion and the appearance of those symptoms, 
 the existence of which I knew to be in uraemia, stood clearly out 
 before me. 
 
 This uraemia of the second phase of cholera is not the ordi- 
 nary uraemic intoxication by poisons produced from four sources ; 
 we cannot in this case attribute it to alimentation, or to intes- 
 tinal putrefactions, or to biliary re-absorption, since there is no 
 jaundice at the time, and the absorption cannot be effected by 
 the intestine. The poison in this case comes from disassimilation. 
 
 This uraemic period has long been designated the period of 
 reaction, the external temperature being higher, i.e., equilibrium 
 being established between the rectal and peripheral temperatures, 
 a singular reaction, in which torpor appears instead of spasms, 
 and in which we can only see inertia of the whole nervous system I 
 It is a perversion of the meaning of the word to apply such a 
 name to this phase of the disease. It has also been termed the 
 typhoid phase, and the period of typhoid reaction, a designation 
 that is certainly less open to criticism, for in the condition of
 
 272 LECTURES ON AUTO-INTOXICATION. 
 
 the patients there is certainly something that reminds us of 
 typhoid fever. But the pathogenic conditions are not abso- 
 lutely the same. In cholera patients whose intestines are sub- 
 jected to antiseptic treatment there is no intestinal putrefaction ; 
 they experience poisoning by disassimilation only. It was 
 therefore asserted that this phase of cholera must be considered 
 a uraemic period. There was no need to wait for pupillary con- 
 traction in order to detect signs of uraemia ; the blood and the 
 tissues were analyzed, and extractive matter and urea were found 
 accumulated in them in considerable quantities (1 gramme 20 
 centigrammes and 1 gramme 30 centigrammes of urea per kilo- 
 gramme of muscular tissue). This period can be foreseen when 
 anuria sets in ; after pupillary contraction it can be affirmed. 
 In all patients seized with anuria myosis occurs ; I have observed 
 it in every case ; this is a clinical fact which, in my opinion, is of 
 some importance. 
 
 If we do not find in the uraemia following cholera all the 
 symptoms usually observed in ordinary uraemic poisoning, it is. 
 because several of the sources of the uraemic poisons are sup- 
 pressed. Disassimilation may supply the narcotic poison as 
 well as the convulsive poison. When potass is sent into the 
 blood in excess it causes convulsive uraemia ; but if convulsive 
 uraemia is not generally observed in the uraemic phase of cholera, 
 we can understand why not. The rapid and premature dehydra- 
 tion has drawn off with the water all the potass of the fluids 
 and a portion of that in the anatomical elements ; thus, when 
 the period of excessive destruction of matter arrives, potass and 
 mineral substances are not so superabundant in the blood as 
 organic and extractive substances. In a case that I have already 
 quoted, there was so little potass that an extract of 400 grammes 
 of the patient's urine did not cause convulsions in an animal. 
 We see that cholera furnishes us with an example of double 
 self-poisoning : first, by an anomalous product (this is cholera 
 poisoning, properly so called); second, by normal products 
 (this is a variety of uraemic poisoning). Moreover, the study 
 of cholera corroborates the theory that anomalous substances 
 may exist in some diseases, and that morbid poisons are not a 
 dream.
 
 LECTURE XXXI. 
 THE GENERAL THERAPEUTICS OF SELF-POISONING. 
 
 The course to be pursued is to prevent the poisons being formed ; to oppose their 
 penetration into the system ; if they have been absorbed, to try to destroy 
 them or to stimulate the action of the liver, which is a physiological destroyer 
 of poisons ; lastly, to encourage the elimination of poisons by the skin, the 
 
 lungs, the intestines, and the kidneys. Sudorifics, purgatives, diuretics, 
 
 bleeding, inhalations of compressed air and oxygen ; intra-venous injections 
 of antiseptic remedies. 
 
 Is it possible to make any therapeutic application of the 
 knowledge that we have acquired with regard to the pathogeny 
 of self-poisoning? The first course to take is to prevent the 
 poison being formed. When once it is formed, we must endeavor 
 to oppose its penetration into the S3 r stem by preventing its 
 absorption. This can be realized in certain cases ; certain toxic 
 substances are naturally precipitated in the intestines, and others 
 may be fixed by charcoal, which retains them physically. If the 
 poison has been absorbed, we must endeavor to destroy it. We 
 have found that the liver has the power of arresting poisons ; it 
 withdraws them from the intestine and eliminates or -destroys 
 them. We should therefore stimulate its action by certain thera- 
 peutic treatment. Lastly, if the poison has escaped the action 
 of the liver it should be eliminated by the skin, the lungs, the 
 intestines, and the kidneys. 
 
 If all these attempts should fail, we must have recourse to 
 certain antidotes which tend to counteract the physiological 
 effects of the poisons that menace the system. We have a 
 striking example of the antagonistic properties of poisons in 
 atropine and pilocarpine. This side of the question has so far 
 merely been sketched out. We have, however, indicated, from a 
 pathogenic point of view, the existence of poisons that are allied or 
 opposed to one another; in poisoning by substances in the urine, 
 I have shown how the action of the narcotic material prevents 
 that of the convulsive poisons. The knowledge of these facts 
 shows us, at any rate, that we should not give up the contest. In 
 
 is (273)
 
 274 LECTURES ON AUTO-INTOXICATION. 
 
 any case, we must never neglect, in auto-intoxication, to keep up 
 the strength of the patient, so that he may have time to eliminate 
 the poison. Sometimes we only require to keep him alive a few 
 minutes more in order to save him ; we cannot supply him with 
 radical force, but what he requires is active force. Thus we are 
 led to administer not tonics, but stimulants, which may awaken 
 some force remaining latent. 
 
 The therapeutic treatment is effected, to a certain extent, by 
 nature, or a portion of it is carried out by our organs ; in 
 uraemia, one of the sources of poisoning is already lessened, dis- 
 assimilation being checked by the disease itself in uraemic and 
 other patients attacked with self-poisoning. Poisoning by 
 substances of alimentary origin may be diminished. If potass 
 really kills, the diminution of solid ingesta diminishes the poison- 
 ing ; now, these patients still drink, but no longer eat. They must 
 not take broths which contain the mineral elements of meat. The 
 poisons of the secretions are opposed to each other, both naturally 
 and physiologically. The system itself exercises prophylactic 
 action. The bile which is not eliminated by the intestine is pre- 
 cipitated. Of the poisons which it contains, one, which is emi- 
 nently poisonous, the coloring matter, is precipitated when 
 brought into contact with acid chyme ; the other the biliary salts 
 is transformed and brought to the condition of dyslysin. In 
 this way man lives, thanks to the therapeutics which the system 
 exercises incessantly upon itself. 
 
 The substances which are generated in the intestine by putre- 
 faction, and which are neither precipitated nor eliminated, pass 
 on into the blood ; but a natural effort to stop them is made by 
 the liver, which partly prevents them from penetrating into the 
 general circulation. From this point of view, there is a great 
 difference between poisoning through the digestive channels and 
 that which is effected by intra-venous or subcutaneous processes. 
 I know a patient who takes daily 20 grammes of laudanum 
 without ill effects. Is this because the poison is eliminated 
 through the urine ? If so, this should be poisonous. But it is 
 not ; it kills only in the proportion of 64 cubic centimetres per 
 kilogramme. I might conclude that the poisons of the opium 
 have been destroyed, but in stating this conclusion I must make
 
 ELIMINATION OF POISONS. 275 
 
 the most express reservations, for a rabbit shows itself almost as 
 refractory to intoxication by opium as to poisoning by belladonna. 
 In my opinion, the reason why this patient has not been 
 poisoned is because I have introduced the poison through the 
 intestine. I must remind you of the facts observed by Schiff 
 with regard to the protective function of the liver, facts which 
 Messrs. Charrin and Roger have recently verified hi my labora- 
 tory. But still the true protecting agent of the system is the 
 kidney. 
 
 If I have once more returned to the many physiological 
 actions which tend to neutralize and expel poisons, it is in 
 order to show more clearly how therapeutic treatment may com- 
 plete the task of deliverance commenced by the system. As far 
 as the alimentary canal is concerned, I have shown that we can 
 expel the contents of the intestine, precipitate with charcoal and 
 fix certain poisons, and even suppress the formation of poison- 
 ous matter by instituting intestinal antiseptic treatment. 
 
 I have mentioned bleeding, which can curry oil' in one opera- 
 tion, by the abstraction of 32 grammes of blood, more poisonous 
 matter, it is said, than 100 litres of perspiration. I have sketchi-d 
 out the physiological compensations for the action of poisons that 
 can be obtained by the help of chloroform, chloral, bromide (of 
 sodium), diffusible stimulants, alcohol, and injections of ether. 
 
 In most diseases the morbid poison is a natural one, and 
 the ataxic or adynamic accidents of pyretic diseases are the con- 
 sequence of febrile oliguria ; these are auto-intoxications resulting 
 from more intense disassimilation, or from more rapid cell-de- 
 struction, which sets at liberty imperfectly-oxidized nitrogenous 
 matter and an excess of potass. We should, therefore, by 
 stimulating the renal discharge, hasten the elimination of this 
 excess of poison that has been sent into the circulation. 
 
 In cases which are certainly more rare, but the number of 
 which will be increased perhaps when we shall hnvr prm-li-rUnl 
 further into the secrets of the pathogenic processes, in cases 
 where a morbid poison is really formed by perversion of tin- nu- 
 tritive functions, we must endeavor to prevent the formation of 
 this poison. If it is formed in the tissues, will this be possible ? 
 It has always, up to now, been said that we cannot act upon
 
 276 LECTURES ON AUTO-INTOXICATION. 
 
 poisons which have impregnated the system. But, in the first 
 place, without speaking of poisons of interstitial origin, there 
 are those which may be formed on accessible surfaces. Already, 
 in some cases, we are able to effect a rapid cure of the suppura- 
 tion in abscesses, fistulae, and empyemata. 
 
 We know how to encourage the elimination of the poison, 
 and to prevent its continuation by drainage, washing, and the 
 attitude in which the patient is placed. We draw off mechan- 
 ically the putrid products, and contend against putrefaction 
 in the accessible natural cavities, the vagina, the uterus, and 
 the intestines. In such cases, antiseptic remedies bring about 
 an improvement at once: a sudden fall of temperature, a dimi- 
 nution in the dryness of the mouth, and alterations of the car- 
 diac rhythm. In diseases caused by eating bad food, in severe 
 putrid diarrhoea, provided that the treatment is instituted 
 before the occurrence of secondary accidents and the establish- 
 ment of metastatic centres, we can really effect a cure ; but, if 
 we have not succeeded in preventing the formation of poisons, 
 we cannot depend upon the protection of the liver, unless it is 
 interposed between the source of the poisons and the other 
 organs. This condition only exists in poisoning of intestinal 
 origin. It is true that a portion of the poisons absorbed will 
 pass back into the liver with the blood of the general circula- 
 tion, but this will only be a very small fraction instead of the 
 whole. 
 
 I very much doubt whether we shall ever know that the 
 function of the liver can be stimulated by medicinal treatment, 
 and whether the employment of purgatives, in intoxications that 
 are not produced through the intestines, can thus be justified. 
 In toxaemia from intestinal poisons, the utility of purgatives 
 is explained in quite another way ; they expel the poison 
 mechanically. 
 
 What can we do against poisons in the circulation ? Endeavor 
 to eliminate them. In all ages the course adopted has been to 
 increase the action of the various emunctories of the body. 
 To provoke perspiration was the alpha and omega of the thera- 
 peutic treatment of antiquity. Hot or warm drinks, wrapping 
 in hot linen or wet sheets, the administration of Dover's powder
 
 DIAPHORESIS AND BLEEDING. 277 
 
 have all been employed with the object of acting upon the hu- 
 mors. I am inclined to think that the result of perspiration is 
 not beneficial, since perspiration lessens the urine, which carries 
 out of the system so many toxic products. If in former times 
 it was thought advisable to provoke "perspiration, it was not used 
 so much in cases of poisoning in order to eliminate the poison 
 as in cases in which a dynamic action, such as the dilatation of 
 the cutaneous capillaries, might relieve the centres ; and when in 
 our own times we have thought it advisable to produce copious 
 perspiration with pilocarpine, we have not found the general 
 condition improved. It is true that perspiration may help to 
 eliminate certain toxic substances, but the true depuration of 
 the system is accomplished chiefly through the kidneys. It is 
 the kidneys that enable the body to be thoroughly cleansed, and 
 this is effected by increasing the renal secretions by cold drinks 
 and cold bathing. 
 
 When in typhoid patients the quantity of urine rises from 
 500 grammes to several litres and the result is an improvement, 
 it is very probable that this is owing to the expulsion of toxic 
 matter through the urinary passages. Lastly, we must not 
 omit the intestinal outlet, which may be acted upon by judicious 
 drastic treatment. 
 
 Bleeding is of use only in toxaemia attended with anuria and 
 serious impermeability of the kidneys. Perhaps it is possible to 
 do something more to destroy the poison or prevent its formation. 
 I have told you in what proportions compressed air diminishes 
 urinary toxicity. This may be explained in two ways : either 
 disassimilation, taking place in presence of a greater proi>ortion 
 of oxygen, gives rise to more completely oxidized products, 
 which are less toxic, or the corpuscles, having more oxygen at 
 their disposal, destroy in the blood a greater mass of poison. 
 Hence the utility, which is, perhaps, somewhat theoretical, of 
 compressed air or inhalations of oxygen. 
 
 If these methods fail, we can only have recourse to antidotes 
 the properties of which we have learned empirically ; in ataxo- 
 adynamic fevers, opium, musk, and sometimes chloral, which can 
 neutralize certain poisonous effects ; diffusible stimulants, al- 
 cohol, coffee, injections of ether. Even if the morbid poison is
 
 2t8 LECTURES ON AUTO-INTOXICATION. 
 
 formed by microbes within the organs, we are not justified in 
 saying that it is impossible to oppose its development. At any 
 rate, I have attempted this impossibility. In my trials of gen- 
 eral antiseptic treatment, I had to turn my attention to sub- 
 stances capable of arresting life in the infectious agents and 
 rendering the activity of the microbes less intense. I had to 
 adopt the intra-venous mode of injection for these substances ; for 
 the absorption is so slow by the subcutaneous or intestinal method, 
 and the elimination through the emunctories so rapid, that the 
 antiseptic agent would not have time to impregnate the whole 
 system. Observe that in all that I am saying there is nothing 
 that should at present be applied to the therapeutic treatment of 
 man; but I am justified in seeking, by experiments on animals, 
 the solution of problems which so deeply concern the future of 
 medicine. In order to try general antiseptic treatment by the 
 intra-venous method, it was necessary to attack first those dis- 
 eases in which the microbe exists exclusively in the blood. The 
 objection will perhaps be raised that the pathogenic agents of 
 infectious maladies do not, as a rule, inhabit the blood ; this 
 would, however, be to forget recurrent fever, charbon, or malig- 
 nant pustule. But, to speak only of the infectious diseases of 
 animals, if my attempts failed when directed against Charrin's 
 septicaemia, I obtained some encouraging results when treating 
 bacteridian charbon. 
 
 Last year I made out a list of some of the substances that 
 may be utilized for general antiseptic treatment. Of these I will 
 only discuss mercury. For my experiments I chose the bin- 
 iodide of mercury, the most antiseptic, but not the most toxic 
 of the salts of mercury. The therapeutic equivalent of the iodide 
 of mercury is 2 milligrammes. If we exceed this quantity we 
 jwovoke protracted albuminuria. This quantity is dissolved by 
 means of an equal quantity of iodide of sodium in from 5 to 12 
 cubic centimetres of water. 
 
 I will now give the resume of the trials of general antiseptic 
 treatment that I made with iodine and mercury. The greater 
 number of the animals attacked with bacteridian charbon that I 
 treated with injections of biniodide of mercury died. Never- 
 theless, when we effected the inoculation of the bacteria not
 
 GENERAL ANTISEPSIS. 279 
 
 under the skin, but in the blood in the veins, these animals lived 
 longer by several hours, even a day longer. Moreover, when the 
 animals died we no longer found any bacteria in their blood, nor 
 in cultivations of their organs, and the inoculations made with 
 their blood were negative. Why, then, did they die ? No doubt 
 because they were not able to bear the double attack of the ex- 
 perimental disease and the treatment ; but they no longer had 
 charbon. At length, after a series of failures, one animal recov- 
 ered, and this animal, on being re-inoculated twelve days after, 
 did not contract charbon. This is certainly only one fact, but I 
 may say that it is full of promise, and this single fact enables us 
 to believe that general antiseptic treatment is not merely a vain 
 dream, or a therapeutic chimera.
 
 LECTURE XXXII. 
 
 GENERAL RECAPITULATION. 
 
 HAVING arrived at the end of this study of the part played 
 by auto-intoxication in disease, it will be to our advantage to take 
 a rapid survey of the knowledge that we have acquired, and we 
 will therefore devote the last of these lectures to this recapit- 
 ulation. 
 
 We found, in the first place, -that disease may spring from 
 four main sources. Man, as we have said, contains in himself 
 the cause of many diseases. His life may not be normal, or, 
 to express the same idea in other words, his nutrition may be 
 defective. This impaired nutrition may have been inherited, 
 or he may be the victim of acquired nutritive disorders. Thus, 
 disease may arise from derangement of the nutritive functions. 
 The human organism may be disordered through external causes, 
 mechanical, physical, or chemical. To give an example of each 
 of these causes, we may mention bodily injuries, burns, and 
 poisoning. These causes reach the cells directly and provoke 
 their immediate reaction. I must own that this pathogenic 
 process rarely remains in a condition of simplicity, and that 
 often it is rendered more complex by nervous reflex action or by 
 infection. External causes, in fact, may also exercise an indi- 
 rect influence upon us through the medium of the nervous 
 system; it is through this fresh pathogenic process that the 
 diseases are developed which I have called diseases induced 
 through nervous reactions. Lastly, our bodies may be attacked 
 by parasites and become diseased through infection. 
 
 Poisoning, at its inception, comes under one of these great 
 pathogenic groups; but the other processes the preliminary 
 disorders of the nutritive functions, as well as nerve-reactions and 
 infection may also act in a secondary manner by intoxication. 
 When nutrition is lessened, as in obesity and gout, for in- 
 stance, we frequently observe certain nerve-troubles, apathy, 
 dejection, inaptitude for work, and headache, and we generally 
 (280)
 
 HOW ATJTO-INTOXICATION IS PRODUCED. 281 
 
 note in the renal, cutaneous, or pulmonary excretions some 
 incompletely-oxidized products of disassimilation, oxalic acid 
 and the volatile fatty acids. It is admitted, not without an 
 appearance of reason, that these bodies, which are all toxic, are 
 not foreign to the production of these nerve-symptoms. They 
 are the very first signs of poisoning due to the previous derange- 
 ment of nutrition. The same injurious substances, causing 
 similar nervous disorders, may, in people who are in good 
 general health, be produced superabundantly or destroyed insuf- 
 ficiently, owing to excesses, late hours, mental anxiet}-, or to the 
 influence of dampness, cold, or living in places that are badly 
 ventilated and badly lighted ; all of which causes affect the body 
 only by first acting upon either the central or peripheral nervous 
 system. This is another example of the first signs of poisoning 
 due to a pathogenic nerve- reaction. Amongst the substances 
 formed by certain microbes there are some which, even in small 
 quantities, are eminently poisonous. From such substances 
 certain microbes develop putrefactions, which may become the 
 pathogenic agents of certain forms of septicaemia. If, then, 
 the disease is not complicated by injury to important organs; if 
 the microbes do not exist in the blood, the nerve-centres, the 
 lungs, the liver, the kidneys, or the heart ; if they only exist sup- 
 pose it is a case of septicaemia in the cellular tissue of the region 
 contaminated, it is quite natural to attribute the general symp- 
 toms to the absorption of the poisonous matter formed by these 
 microbes, and we can hardly understand that these general 
 symptoms could have any other origin. There are, then, to all 
 appearances, certain cases in which infection leads in a secondary 
 manner to intoxication. Thus, man is poisoned not only when 
 he swallows a poisonous substance or when he breathes :i im-philic 
 gas, but also when he is attacked by certain diseases. Wh.-n 
 the poison is produced by some external cause, or when it is 
 formed in the system by a perversion of the nutritive functions 
 or by the secretion of a microbe, it must be considered an anom- 
 alous substance, either as regards its nature or its quantity. 
 But normal poisons exist. 
 
 The healthy man, as I have said, is both a receptacle and a 
 laboratory of poisons. In fact, he receives them in his food, he
 
 282 LECTURES ON AUTO-INTOXICATION. 
 
 creates them by disassirailation, and he forms them in his 
 secretions. The human body is the theatre of the toxic elab- 
 orations carried on by the normal microbes which constantly 
 inhabit the alimentary canal. And yet man is not poisoned. 
 He is defended in various ways against poisoning. In the first 
 place, his liver protects him, by arresting on their way, before 
 they pass into the general circulation, the poisons brought from 
 the intestine by the portal vein, in order to neutralize them 
 or throw them back into the intestine. Then the excretory sys- 
 tem expels the poisons which are in circulation. This is not a 
 purely theoretical view. I have demonstrated it experimentally, 
 taking the natural product of an excretion and studying its 
 toxicity by injecting it into the veins of an animal. 
 
 The traditional idea that normal urine is poisonous had been 
 rejected by Huron; its truth was only established in 1880, by 
 Feltz and Ritter. But they only observed the fact of the tox- 
 icity of the urine ; they did not pursue in detail the study of the 
 characteristics of the poisoning which results from the introduc- 
 tion of the urine into the veins. I have studied this subject, 
 determining not only the quality, but the intensity, of the urinary 
 toxicity. 
 
 I found first what mass of living matter can be killed by the 
 poisons which each kilogramme of the body of a healthy man 
 supplies in twenty-four hours to the renal secretion. I thus 
 possessed a standard which enabled me to study the variations 
 of intensity in the urinary toxicity, under certain physiological 
 conditions and under various pathological circumstances. 
 
 By varying the experiments I showed that there was not 
 one particular urinary poison, but that the urine contains many 
 poisons. Having by the h'elp of charcoal acted upon urine with 
 alcohol so as to separate its many constituents, I succeeded 
 in disassociating the various elements of its toxicity, and in 
 showing that it contains at least seven toxic substances: a 
 diuretic substance (urea); a narcotic substance; a substance 
 that produces salivation; one that contracts the pupil ; one that 
 lowers the temperature; two convulsive substances, one of an 
 organic nature, the other a mineral (potass). 
 
 It is because all these substances are carried away through the
 
 HOW AUTO-INTOXICATION IS PREVENTED. 283 
 
 urine that the urine is poisonous, and that man escapes. All 
 these poisons come from the blood ; and yet the blood is not 
 poisonous, for it is continually freeing itself from those that 
 flow into it, either by transferring them to the excretory 
 system or to the various organs, or by consuming them when 
 they are brought into contact with the corpuscles. I have just 
 said that the blood is not poisonous ; this assertion must not be 
 taken literally. As poisons are continually passing through it 
 on their way to the excretory system, the blood must necessarily 
 contain toxic matter at each moment. The blood, then, has 
 really a toxicity, which may be very slight ; the question is, can 
 this degree of toxicity be disregarded? To conclude that the 
 blood is not poisonous, from the fact that man lives with it dif- 
 fused over all his organs, is simply nonsense. The only state- 
 ment that we can permit ourselves to make, a priori, is that 
 the blood is not sufficiently toxic for a quantity amounting to 
 1 kilogramme to be able to kill or even seriously injure 13 kilo- 
 grammes of living matter. The toxicity of the blood is no 
 doubt considerably below this estimate ; but I have shown you 
 by several experiments that this toxicity really exists, and I 
 have fixed the somewhat narrow limits within which it is con- 
 fined. I have been led to the conclusion that a kilogramme of 
 living blood contains in its plasma, and only in its plasma, 
 enough poison to kill more than 1250 grammes of living matter, 
 and that a man would die toxsemic if his blood came to con- 
 tain ten times as much poison as it does in its normal con- 
 dition. But if the plasma of the blood is only sligtly toxic, its 
 cells contain poison, like all the cells of the body, and these toxic 
 constituents of each cell can only be set at liberty by disassimi- 
 lation or by the destruction of the cell itself. Amongst these 
 substances there are some which are toxic. These poisons, which 
 are contained in abundance in the cells of all the tissues, are 
 of two kinds ; there are organic substances resulting from disas- 
 simijation and secretion, and mineral substances, at the head of 
 which we must place potass. 
 
 Amongst the products of secretion, bile, which flows peri- 
 odically into the alimentary canal, contains poison ; it derives 
 its toxicity much more from its coloring matter than from the
 
 284 LECTURES ON AUTO-INTOXICATION. 
 
 biliary salts. But, normally, the bile that is secreted is not very 
 dangerous ; its coloring matter and its salts are, for the most 
 part, precipitated in the alimentary canal. 
 
 The alimentary canal, however, is an important source of 
 poisons ; it contains, in addition to the potass supplied by 
 various foods and the bile, the products of intestinal putrefaction. 
 I had to take up this question of intoxication by putrid products 
 from the points of view of many different experimentalists, 
 Gaspard, Panum, Hemmer, Bergmann and Schmiedeberg, Ziilzer 
 and Sonnenstein, Selrni, Gautier, Brouardel and Boutmy. Then 
 I studied intestinal putrefaction ; I showed that alkaloids exist 
 in faecal matter, that these alkaloids are of several kind.s, and 
 that when those of one kind predominate in the intestines we 
 also find them predominate in the urine. I established, accord- 
 ing to Stich, the toxic ity of faecal matter. I analyzed the 
 elements of this toxicity, and showed that it is due mainly to 
 potass and ammonia, but that, when freed from these two ele- 
 ments, faecal matter still retains a certain degree of toxicity 
 which must not be overlooked. I have shown that intestinal 
 antiseptic treatment, which causes the alkaloids to disappear 
 from faecal matter and urine, diminishes the toxicity of both. 
 
 Knowing the normal poisons and the various sources from 
 which they spring, I was able to study a form of poison due to 
 their retention, viz., uraemia. But I took care to distinguish 
 it from the non-poisonous symptoms that arise in diseases of the 
 kidneys, albumin uria, haemorrhage, cardiac and arterial injuries, 
 and oedema, including cerebral oedema. Thus, as you know, I 
 only admit as ursemic symptoms those that are toxic. I have, 
 moreover, furnished the only convincing proof of the reality of 
 toxic uraemia by showing that the urine of ursemic patients is 
 not poisonous. 
 
 The urine of uraemic patients is not toxic, owing to the fact 
 that all the poisonous substances normally eliminated by the 
 urine are retained in the system of those suffering from this 
 disease. But is all that is thus retained poisonous ? If only a 
 part is poisonous, which part is it? It is not urea. It is not 
 the mass of extractive matter ; it is not potass exclusively. The 
 toxicity cannot be explained by any one of these bodies singly.
 
 POISONING OF THE INDIVIDUAL BY FOOD. 285 
 
 Each of them contributes a different share to the general tox- 
 icity, the coloring matter three-tenths, the extractive matter 
 one- to two- tenths, and potass and other mineral substances 
 four- to five- tenths. The knowledge of the multiplicity of the 
 toxic agents enables us to understand, according to the one 
 which predominates, the many clinical features that uraemic 
 poisoning may assume, particularly the convulsive and the 
 comatose forms. It explains the appearance of certain special 
 symptoms, such as low temperature and pupillary contraction. 
 
 I think I have succeeded in showing you, gentlemen, that 
 these pathogenic observations not only satisfy scientific curiosity, 
 but that they have for corollaries practical applications ; and 
 that, in a word, they are far from being unimportant from a 
 therapeutic point of view. 
 
 After having studied the form of intoxication resulting from 
 the retention of the normal poisons, I commenced the study of 
 the morbid conditions caused by the exaggeration of their 
 formation, for example, gastric disorders, constipation, and 
 intestinal obstruction. I traced the history of various intoxi- 
 cations by poisons of intestinal origin, such as toxaemia from 
 bad sausages ; I quoted a case of Senator's, in which the cause 
 of the malady was hydrosulphuric acid, a case of poisoning 
 from fish, which I observed personally, and in which the ill 
 effects were attributable to the formation of an excessive quantity 
 of alkaloids ; I called your attention to a case of poisoning 
 from some preserved goose, in which Brouardel and Boutmy 
 discovered a poisonous alkaloid. I showed you that all these 
 cases are, in reality, within the domain of infection before they 
 end in intoxication. In all these cases, in short, we find, between 
 the consumption of the tainted food and the appearance of toxic 
 symptoms, rather a long period of incubation. It seems to me 
 that the poison elaborated by the microbes in the tainted food 
 was too small in quantity to cause poisoning, but that the 
 microbes, continuing to multiply with greater rapidity in the 
 alimentary canal, amounted in a few hours to a prodigious 
 number, and that then the toxic matter elaborated by them 
 formed a mass of sufficient importance to produce poisoning. 
 Here, again, incubation obliges us to admit infection ; but the
 
 286 LECTURES ON AUTO-INTOXICATION. 
 
 infectious agents form a poison, and the infection ends in 
 poisoning. But the most common condition in which we find in- 
 toxication occurring through the excessive formation of poisons 
 in the alimentary canal is, as I have told you, dilatation of the 
 stomach, which, independently of the digestive and nervous 
 troubles always recognized as being attendant upon the various 
 forms of dyspepsia, seem to me to cause many other disorders. 
 It engenders, especially, a habitually chronic albuminuria, which 
 may become permanent, but which remains curable for a long 
 time, and which is rapidly cured if, suspecting its cause, we take 
 the trouble to seek it out, and if, having discovered it, we know 
 how to contend against it. It is by provoking anomalous gas- 
 tric fermentation, by rendering excessive intestinal fermen- 
 tation, by preparing poisons, and especially acetic acid, that 
 dilatation of the stomach vitiates the nutrition of the osseous 
 tissue and produces a peculiar deformity of certain joints, a 
 kind of nodose rheumatism, osteomalacia, and, perhaps, rachi- 
 tis. There are other diseases of degeneration which spring from 
 disorders of the nutritive functions caused by dilatation of 
 the stomach ; I will merely mention those in which this patho- 
 genic influence is most manifestly shown, chlorosis and pulmo- 
 nary phthisis. 
 
 I showed the part played, even in infectious diseases, by 
 certain secondary intoxications, and I was thus led to expound 
 to you my views as to the treatment of typhoid fever, the car- 
 dinal points of which are, in my opinion, intestinal antiseptic 
 treatment, general antiseptic treatment, antithermic treatment, 
 consisting of tepid baths, gradually cooled, and a certain sys- 
 tem of dietetics. I was thus enabled to formulate, with regard 
 to typhoid fever, certain general rules that might be applied to 
 other acute diseases. 
 
 I showed you the share contributed by poisoning in jaundice. 
 This poisoning is twofold. The bile, contrary to what was sup- 
 posed, is poisonous mainly in its coloring matter. What saves 
 the system from the toxic power of this coloring matter is the 
 urine, which is continually eliminating a portion of it; and also 
 the cellular tissue and the fibrous tissues, the white fibres of 
 which retain within themselves the excess of coloring matter
 
 RENAL ACTIVITY PREVENTS AUTO-INTOXICATION. 287 
 
 that is not eliminated, and which, if it remained in circulation, 
 would seriously affect the working of the nerve-cells. On the 
 other hand, the biliary salts increase disassimilation, destroy 
 muscle-cells and blood-corpuscles, and thus set free organic and 
 mineral poisons, particularly potass. 
 
 Now, in many of the diseases that produce jaundice the liver, 
 whose normal function is to protect the system against the intes- 
 tinal poisons, is diseased or checked in its working. It ceases 
 to exercise its protective influence; it also ceases to form urea, 
 and urea is the best diuretic. It is this substance which, by 
 forcing the renal barrier, carries away "the other toxic material. 
 Thus, complete poisoning takes place, the successive phases of 
 which are cholaemia, acholia, and uraemia. In fact, in jaundice, 
 the true safeguard against poisoning is the kidnej'. As long as 
 it acts, the patient's urine is very toxic ; not owing to the 
 bile which it contains, but from the matter produced by ex- 
 aggerated disassimilation. If the kidneys perform their work 
 of depuration insufficiently, the urine ceases to be toxic, but 
 the patient is poisoned through the retention of the normal 
 poisons. 
 
 We have seen that the normal poisons are not alone the 
 cause of all intoxication. I showed you, in acute yellow atrophy 
 of the liver, an example of anomalous substances produced by 
 the vitiated elaboration of matter by the system. I allude to 
 certain unusual albumens, to the unusual transformation of 
 medicaments, such as naphthalin, which ceases in the case of 
 atrophy of the liver to pass from the system in the form of 
 naphthylsulphite of soda. Amongst these anomalous substum-rs 
 there are some which are toxic. 
 
 I will remind you that, in glycosuric patients, besides the 
 symptoms arising from incomplete destruction of the sugar 
 formed by the system, the latter may generate a substance 
 which, in the urine of patients attacked with diabetic coma, 
 takes a claret-colored tinge when brought into contact with per- 
 chloride of iron. This substance does not exist only in diabetic 
 subjects; it has been found in dyspeptic coma, in certain cases 
 of cancer of the stomach, pernicious ansemia, leucocythffiinia, 
 and I have observed it in dilatation of the stomach and in
 
 288 LECTURES ON AUTO-INTOXICATION. 
 
 typhoid fever. It has been experimentally established, as you 
 know, that this substance is toxic. Unlike the greater number 
 of auto-intoxications that we have met with up to the present, 
 what we call acetonsemia is self-poisoning by an anomalous 
 poison, a truly morbid one. 
 
 In cholera an anomalous elaboration of matter also exists, as 
 shown by the violet coloration observed, even at the time of 
 emission, in the urine of certain cholera patients that have been 
 treated with naphthalin. But cholera is an example of complex 
 poisoning. I told you that there exists in those attacked with 
 cholera a primitive poison, the essence of which is unknown, 
 which is produced either by the system under the influence of 
 pathogenic microbes, or by these microbes themselves. The 
 existence of this poison is shown, in my opinion, by the special 
 toxicity of the urine of cholera patients, which, on being injected 
 into rabbits, produces in them the choleraic syndrome, the 
 appearance of cholera, but not cholera itself. But I also told you 
 that besides the symptoms caused by choleraic poisoning those 
 suffering from cholera underwent, at a certain stage of the dis- 
 ease, a secondary intoxication through the retention of the 
 normal poisons, and I indicated myosis as the clinical criterion 
 of the appearance of this uraemic poisoning. 
 
 I concluded the series of these lectures with therapeutic ap- 
 plications, with regard to intoxications in general, deduced from 
 pathogenic knowledge. The treatment of self-poisoning derives 
 several of its features from the antiseptic method. It was nat- 
 ural, therefore, to see what result might legitimately be expected 
 from general antiseptic treatment. 
 
 In conclusion, I gave you certain reasons and quoted certain 
 experiments, of a nature to lead us to hope that in the future 
 general antiseptic treatment may produce good results. 
 
 And now, gentlemen, having taken a rapid retrospective 
 glance at the ground we have gone over together, I think I am 
 justified in making this assertion : When I have hazarded certain 
 hypotheses, I have never disguised from you the fact that they 
 were hypotheses; on the other hand, whenever I have made 
 positive affirmations, they have been supported by experimental 
 demonstration.
 
 INDEX. 
 
 Acetonaemia, 247, 248 
 Acetone, in urine, 142, 247 
 
 tests for, 142, 247 
 Acholia, abnormal metabolism a cause 
 
 of, 11 
 
 in jaundice, 228, 233. 234 
 Acid, acetic, in dough, 179 
 
 in intestine, 16 
 
 in muscle-extract, 79 
 
 in putrefactive products, 16, 93 
 
 in tissues, 16, 79 
 
 in urine, 16 
 
 phalangeal nodes due to, 172 
 Acid bile, 140 
 
 Acid, boracic, an antiseptic, 98 
 butyric, in dough, 179 
 
 in intestine, 16 
 
 in muscle-extract, 79 
 
 in putrefactive products, 16, 93 
 
 in tissues, 16, 79 
 
 in urine, 16 
 carbolic, an antipyretic, 198, 210, 211 
 
 an antiseptic, 98. 196 
 
 and mercury, 196 
 
 in dough, 179 
 
 in faeces, 141 
 
 in intestine, 16, 141, 142 
 
 in putrefactive products, 16, 93 
 
 in tissues, 16 
 
 in typhoid, 193, 219 
 
 in urine, 16, 141, 142 
 
 micro-organisms produce, 12 
 
 toxic power of, 196 
 cholic, in intestine, 18, 223 
 cholalic, in intestine. 18, 223 
 diarrhoea, 139. 140, 168 
 dyspepsia, 139, 140 
 faeces of dilated stomach. 159 
 glycocholic, in intestine, 18, 223 
 hippuric, toxic power of, 118 
 
 unemia due to, 118 
 
 hydrochloric, an antiseptic, 88, 149, 158, 
 183, 184 
 
 functions of, 149 
 
 in dilated stomach, 183, 184 
 lactic, in intestine, 16 
 
 in t issues, 16 
 
 in urine, 16 
 odor of breath. 159 
 oxalic, in Intestine, 16 
 
 in tissue, 16 
 
 in urine, 16 
 
 lira-Una due to, 107 
 
 stools. LM, iin. uj 
 
 sulphuric, micro-organisms produce, 12 
 
 a putrefactive product. '.'.! 
 taurooholio. in intestine, 18, 228 
 uric, ride Uric acid 
 valeric, in putrefactive products, !:{ 
 vomiting, 139 
 Acids, bile excretion of, 227 
 
 fatty, micro-organisms produce, 12 
 
 in dough, 179 
 
 in intestine, 16, 18, 141, 142, 223 
 
 Acids, in muscle-extract, 79 
 
 in putrefactive products, 16, 98 
 
 in tissues, 16 
 
 in urine, 16, 141, 142 
 
 toxic power of, 31, 32 
 
 vegetable, in typhoid, 217 
 Acne, in dilated stomach, 163 
 
 rosacea, in dilated stomach, 163, 171 
 Acquired diathesis, 7, 8 
 Acute atrophy of liver, circulatory system 
 
 haemorrhages in, 232 
 
 jaundice in, 235 
 
 kidneys in, 232 
 
 metabolism in, 232 
 
 naphthalinin.231,232,263 
 
 renal system in, 232 
 
 urine of, 232 
 Advantages of the intra-venous method of 
 
 study, 24 
 
 Ague, quinine in, 198, 209 
 Albumen, and peptones, 10, 17, 104, 164, 165 
 
 nephritis due to, 10 
 
 white blood-cells from, 17 
 Albuminuria, exhaustion due to, 104 
 
 hydrseiniadue to. 104 
 
 in Bright's disease, 103, 104 
 
 in diabetes, 246 
 
 in dilated stomach, 164, 171. 185 
 
 in intra-venous injections, 25, 26, 83, 61, 
 73, 87, 248, 264, 266, 267 
 
 in jaundice, 231 
 
 in lardaeeous disease, 104 
 
 in subcutaneous injections, 24 
 
 ffidema in, 105 
 Alcohol, intra-venous injections of, 27, 28 
 
 toxic power of, 28 
 
 Alcoholic extract, intra \ emm- injections 
 of. 65-57, 77-79, 91, 6, 142, 148, 267. 
 
 of blood, 77, 78 
 
 ,,1 choleraic in inc. 267, 268 
 
 ,.: i 
 
 of liver, 79 
 
 of muscle, 79, 112. 148 
 
 of putrefactive product*. 9L.M, MS, Ml 
 
 of n line, .Y.-.-.7. I..'.. LW, 288 
 the narcolic of, 56, 125 
 
 the Bialagoirae of, .A 78, 125 
 
 Aleoi.oi, -m. dilated -t..inach due to. 175 
 Alimentary method ot producing artificial 
 
 toxemia, 23,24 
 
 system, in dilated stomach, 159 
 
 ' in dx-pcp-i... I" 1 ' Hi'. lUi. 117 
 lie Inline-, lit.. 117 
 
 in Intestinal ..i.-nneti..,,. in 
 
 In intra v. noii* inji 
 
 66,77 
 in 111:1-1111:1. 108, 109 
 
 in the. 88, 93, 97.101 
 in :i-n,i.i. r-V I 
 Alkaloid, sepsii.. 
 Alkaloi.K in Mood. i:,. 17.77 
 
 in faces, 94, 97, 98, 139, 141, 1,50, 262 
 
 (80)
 
 290 
 
 Alkaloids, in intestine, 97, 98, 155 
 
 in putrefactive products, 91-93 
 
 in tissues, 15, 237 
 
 in urine, 10, 16, 30, 55, 67, 68, 77, 92, 97, 
 98, 125, 141, 150, 155 
 
 intestinal poisons due to,' 139 
 
 micro-organisms produce, 12 
 
 mydriatic, 92 
 
 of cholera, 262 
 
 tests for, 15, 16, 94, 262 
 
 the total toxic power of, 125 
 
 toxic power of, vide Toxic power 
 
 trypsin develops, 94 
 Amaurosis, in Bright's disease, 106 
 Ammonaemia, 48, 107, 115-117 
 
 convulsions in, 116 
 
 temperature in, 117 
 Ammonia, an antipyretic, 64, 116, 117 
 
 in blood, 115 
 
 in faeces, 96, 139 
 
 in intestine, 140 
 
 in putrefactive products, 93, 96, 140 
 
 in urine, 115 
 
 micro-organisms produce, 12 
 
 toxic power of, 58, 96, 97, 116, 117, 120 
 
 uraemia due to, 107, 115-117 
 Anaemia, pernicious, odor of breath in, 
 167, 247 
 
 urine of, 142, 247 
 
 urochromes of, 142 
 
 Angina, false, in dilated stomach, 161, 171 
 Anhidrosis. in toxaemia, 151 
 Anilin, antiseptic power of, 
 : of, 1! 
 
 of urine, 
 
 bat 
 lim 
 
 toxic power of, 196 
 Antagonism of the toxic 
 41-13, 62, 63, 122. 
 Antidotes, in uraemia, 134, 13 
 Antipyretic, ammonia as an, 64, 116, 117 
 
 antipyrin as an, 199, 206, 210, 211, 215 
 
 carbolic as an, 198, 210, 211 
 
 quinine as an, 198. 199, 206, 209-211, 219 
 
 the, of urine. 63, 64, 117, 125 
 
 treatment, 205-217 
 
 aths in, 205, 206, 212-216 
 mits of, 205, 216 
 Antiseptics, anilin, 196 
 
 bile, 88, 93 
 
 boracic acid, 98 
 
 calomel, 98, 99, 199, 200, 218 
 
 carbolic acid, 98, 196 
 
 charcoal, ^98, 100, 136, 174, 184, 191, 192, 
 
 combined, the more effective, 197 
 creasote, 98 
 
 formulae for use of, 100, 218, 219 
 general, discussed, 194-199 
 hydrochloric acid, 88, 149, 158, 183, 184 
 in dilated stomach, 174, 183, 184 
 in typhoid. Idl-l'i::. 198-200, 218, 219 
 intestinal, 98-100, 136, 137, 191-193, 199, 
 
 iodoform, 99, 100, 136, 141, 174, 183, 184, 
 193, 199, 218, 219 
 
 , 100, 136, 141, 174, 183, 193, 
 
 potassium iodide, 196 
 sodium iodide, 196 
 toxic power of, 99, 196, 197 
 uraemia, 136, 137 
 
 Anuria, choleraic, 78, 112, 271, 272 
 enemata in, 130 
 myosis in, 67, 272 
 obstructive, 105, 110, 111, 113 
 ocular symptoms in, 67, 272. 
 
 Anuria, treatment of, 130, 277 
 
 urea of, 112 
 
 venesection in, 277 
 Aphasia, in dilated stomach, 161 
 Arthritic diathesis, 6-S 
 Arthritis in dilated stomach, 165, 166 
 Artificial toxaemia, methods of producing, 
 
 Ascites, exhaustion due to, 104 
 Asphyxia, death by, 22 
 
 normal substances a cause of, 10 
 
 toxic origin of, 22, 23 
 Asthma, in dilated stomach, 164, 171 
 Asthmatic type in dilated stomach, 171 
 Ataxia, dilated stomach in, 175 
 
 Bacillus glutinis. 179 
 
 of cholera, 252-255, 257, 258, 260, 261, 
 
 268,269 
 of typhoid, 188, 189 
 
 injections of, 188, 189 
 pyocyaneus, 243, 244 
 
 injections of, 243 
 
 tests for, 243 
 
 Baths, in dilated stomach, 176, 177 
 in measles, 216 
 hi pneumonia, 216 
 in rheumatism, 216 
 in scarlatina, 216 
 in typhoid, 207, 212-217, 219, 220 
 in uraemia, 128 
 inflammations due to, 216 
 limits of, 216, 217 
 methods of use of, 212-214 
 the results of, 214-216 
 Bile, acid, 140 
 
 acids, disease due to, 10 
 
 excretion of, 227 
 
 in intestine, 18, 223 
 
 amount secreted per diem, 84, 139, 222 
 an antiseptic, 88, 93 
 and urine, toxic power of, 80, 84, 85, 
 
 224 
 
 blood arrests, 224, 225 
 charcoal acts on, 81, 135, 136, 224 
 composition of, 222, 223 
 excretion of, 85, 227, 229 
 in urine, 229 
 
 intestinal toxaemia due to. 138, 139 
 intra-venous injections of, 80, 81, 225, 
 
 liver arrests, 80, 84, 222-224, 227 
 
 minerals, toxic power of, 82 83, 86 
 
 of dyspepsia, 140 
 
 pigment, vide Bilirubin 
 
 poisons in, 139 
 
 potass in, 82, 83, 86 
 
 salts, tests for, 225 
 
 toxic power of, 81, 224, 227, 229 
 
 suppression of, 231 
 
 tests for, 223, 225 
 
 tissues arrest, 224-227, 229, 230 
 
 total toxic power of, 224 
 
 toxaemia, 222-235 
 
 toxic power of, vide Toxic power 
 Bilirubin and bile-salts, toxic power of, 
 224,227 
 
 in intestine, 223 
 
 intra-venous injections of, 224, 226 
 
 properties of, 223 
 
 tests for, 223, 225 
 
 tissues arrest, 225, 227 
 
 toxic power of, vide Toxic power 
 Blood, alcoholic extract of, 77, 78.
 
 INDEX. 
 
 291 
 
 Blood, alkaloids in the, 15, 17, 77 
 
 ammonia in, 115 
 
 amount of poisons in, necessary to pro- 
 duce death, 73 
 
 cells, from albumen, 17, 165 
 destroy poisons, 17 
 liberate poisons, 78-78 
 
 extract, iutra-venous injections of, 77, 
 
 78 
 toxic power of, 77, 78 
 
 in diarrhoea, 104 
 
 indigo in, 15 
 
 intoxication of the t 87 
 
 intra-venous injections of, 73, 143 
 
 leucin in, 231 
 
 micro-organisms in, 188 
 
 minerals in, 87 
 
 of Bright's disease, 104, 105 
 
 of cholera, 78 
 
 of diabetes, 245, 246 
 
 of jaundice, 230, 231 
 
 of lardaceous disease, 104 
 
 of p> rexia, 205, 206 
 
 of typhoid, 188 
 
 of uraemia, 78, 112,116 
 
 peptones in, 17, 165 
 
 poisons in the, vide Poisons 
 
 portal, 15, 17, 72, 143 
 
 potassium in, 124 
 
 putrefactive products in, 88, 89 
 
 sugar in, 245 
 
 sulphuretted bydromnte. 15, 149 
 
 the sialagogue of, 57, it, 78 
 
 the three sources of intoxication of, 
 K7,88 
 
 toxic power of, 69-78, 143 
 
 tyrosin in, 231 
 
 urea in, 112, 116 
 
 xanthin in, 2IU 
 
 Bread, the fermentation of. 1<9 
 Breath, odor of, in coma, Itf7, 247 
 
 in diabetes, 167, 247, 248 
 
 in dilat.-.l stomach, 15!, 163, 167, 247 
 
 in dyspepsia. 1-17, 217 
 
 in l.'-uksi-miii, I7.-JI7 
 
 in pernicious amuuiia, 167, .247 
 
 in tvphoid. 247 
 Bright-; disease, albuiuinuria in, 103, 104 
 
 anianrosis in, 106 
 
 l)l.XKl of, 101. 111'. 
 
 cerebral haemorrhage in, lOo 
 circulatory system m, 105, 106 
 coma m. 106 
 convulsions in, 106 
 cutaneous system in, lOa 
 entorrhagia in, 105 
 
 C|>M:i\i.- in. KIT, 
 
 ha;inateincsis in, 105 
 
 ha-moriha^o in. Ht"), 106 
 
 hyha-mia m. I 
 
 inflammation* in, 106 
 
 nervon.- -\>tem in. 106 
 
 ocular symptom- in, 108 
 
 cedema in, 105, 108 
 
 pericarditis in, 106 
 
 prarico in, liio 
 
 puipuni in. lu-i 
 
 retinitis in, 1U6 
 
 symptoms in, 103-106 
 Bronchitis, in diluted stomach. 164, 1<1 
 Bulimia, in dilated >tom;irh, 158 
 Butyric acid, vide Arid. l.t\ i ic 
 
 Caffeiue, in uraemia, 129 
 
 Calomel, an antiseptic, 98. 99, 199, 200, 218 
 
 in typhoid, 200, 201, 218 
 
 disadvantages of, 200 
 Canquoin paste, a caustic, 162 
 Carbolic acid, vide Acid, carbolic 
 
 eneraata in typhoid. 193, 219 
 Carcinoma, gastric, coma in, 167 
 
 dilated stomach due to, 175 
 toxaemia due to, 155 
 Cardiac type of dilated stomach, 171 
 Cardialgia, in dilated stomach, 159 
 
 in dyspepsia, 139 
 
 Cerebral haemorrhage, in Bright's disease, 
 105 
 
 oedema, in jaundice, 234 
 
 hi uraemia. 107, 109-111 
 Charcoal acts on bile. 81, 135, 136, 224 
 
 on faeces, 98, 100, 192 
 
 on putrefactive products, 92, 136, 141 
 
 on urine, 54, 57, 98, 100. 125. 192 
 Charcoal, an antiseptic, 98, 100, 136, 174, 184, 
 191, 192, 218, 219 
 
 formulae for us.- of. 100, 218, 219 
 
 in typhoid, 191, 192, 218, 219 
 
 in uraemia, 136, 137 
 
 Chemistry of putrefactive products. 91, 92 
 Chevne-Stokes respirations, inchoi. 
 
 in uraemia, 108 
 Chloral, in nra-mia, 134 
 Chloroform, in dilated stomach, 183, 184 
 
 in ma-mi. i. 134 
 
 Chlorosis, in dilated stomach, 158, 172 
 Cholaemia. in jaundice, 233 
 
 normal substances a cause of, 10 
 Cholalic acid, in intestine, IN. '^3 
 Cholera, alkaloids of, 262 
 
 anuriaof, 78. 111!. 157 1. '. 
 bacillus of, 252-255, 257, 
 
 - 
 
 258, 280, 281, 388, 
 
 blood of. 78 
 
 In \ ne-stokes respirations in, 271 
 
 etiology of. -Jl> 
 
 experimental, 255-259 
 
 la ., M of, 282 
 ioilolorm m. IN* i. "Jill 
 mv*i- in. I". 1_M. -7I. 'jr.' 
 naphtlialin in. .' 
 
 nervous svst.-m in. i~. l-'l. 271, 272 
 patholo 
 
 renal system in, '-Tl 
 respiratory syst, m in. '.Tl 
 sNinpiomsln, 7. f.'l. 271, 372 
 triiipciatun- in, -Tl 
 treatment of. 260, 261 
 uraemia in. 'J71 
 nrnif of, 112,141.268 
 Choleraic urine, extract* of .aW. 9M 
 mtra-yeiioiis Injection of, 26B ml 
 
 , 
 
 ( lio|i--ti-nn, t..\i, power of, 81. 221 
 Cli.-lic aci.l. i" intc-tin. 
 Circulat..rv -\~trm. m MaM >eilow atro- 
 
 phy of liver 
 in Bright's disease, 106, 108 
 
 'sie7.2IS.246 , 
 in dilated stomach, 158, 101, 165, 167, 
 
 171. 172 
 
 in <l\~]><M>sia, 140 
 to Ifiterfnia obvtraotiom, i4, 1S5 
 
 il.illt.-Mil.kll. 
 
 in intra-venoua injectiooa, 38, 86-88, M, 
 in jau'ii'iUm, 1 280, 282, 284, 285
 
 292 
 
 INDEX. 
 
 Circulatory system, in pyrexia, 203, 204 
 
 in typhoid, 200 
 Clinical types, the ten, of dilated stomach, 
 
 Coma abnormal metabolism a cause of, 11 
 
 diabetic, 167, 246-248 
 
 dyspnoea in, 167 
 
 in Bright' s disease, 106 
 
 in dilated stomach, 167 
 
 in dyspepsia, 140, 167 
 
 in gastric carcinoma, 167 
 
 in gastric ulcer, 167 
 
 in intra-venous injections, 32, 47, 55-57, 
 77 
 
 in toxaemia, 140 
 
 in uraemia, 66, 106, 108 
 
 ligature of portal vein a cause of, 143 
 
 odor of breath in, 167, 247 
 
 pulse in, 167 
 
 respirations in, 67, 167 
 
 temperature in, 108, 167 
 
 the breath in, 167 
 
 urine of, 247 
 Constipation, headache in, 145 
 
 in dyspepsia, 146 
 
 in hypochondriasis, 145 
 
 in insanity, 145 
 
 migraine in, 145 
 
 nervous system in, 145 
 
 toxaemia in, 145 
 
 urine of, 142 
 
 vertigo in, 145 
 Consumptive type of dilated stomach, 171, 
 
 Convulsions, and myosis, 57, 63 
 in ammonaemia, 116 
 in Bright' s disease, 106 
 in dyspepsia, 140 
 in emaciation, 240 
 
 in intra-venous Injections, 34, 37, 38, 51, 
 55-57, 74, 77, 79, 86, 87, 93, 95, 233, 
 237-240 
 
 in jaundice, 233 
 in typhoid, 240 
 in uraemia, 66, 106, 108 
 Convulsive, of urine, the inorganic, 64, 65, 
 
 125,239 
 
 the organic, 62, 63, 65, 125. 239 
 potassa, 58, 64, 65, 78, 79, 82, 95, 122, 123, 
 
 urine of 'jaundice, 82, 86, 87, 233, 238 
 of pyrexia, 123, 238-240 
 of sleep, 37, 41 
 Copraemia, 101 
 
 Coryza, in dilated stomach, 164, 171 
 Cramps, in dyspepsia, 140 
 
 in intestinal obstruction, 144 
 in intra-venous injections, 264, 265 
 Creatin, toxic power of, 79, 118 
 
 uraemia due to, 118, 119 
 Creatinaemia, 117, 128 
 Cresol, in putrefactive products, 93 
 
 in urine, 16, 142 
 Cupping, in uraemia, 129 
 Cutaneous eruptions, toxic origin of, 162, 
 
 163 
 
 system, excretion by, 18-20, 23, 131 
 in Blight's disease, 105 
 in diabetes, 246 
 in diarrhoea, 139, 168 
 in dilated stomach, 161-163, 171 
 in dyspepsia, 139, 140. 147 
 in gastric fullness, 147 
 in gastro-enteritis, 168 
 
 Cutaneous system, in intestinal obstruc- 
 tion, 144, 155 
 
 in intestinal toxaemia, 140, 144, 151 
 in intra-venous injections, 263 
 in jaundice, 230, 235 
 in typhoid, 192, 215 
 in uraemia, 131 
 type of dilated stomach, 171 
 Jyanosis, in intra-venous injections, 263 
 
 Deafness, in dyspepsia, 140 
 Death, amount of poison necessary to pro- 
 duce, 73 
 
 by potassium, 123 
 
 by quinine, 211 
 
 in infectious diseases, 236, 237 
 Debility, dilated stomach due to, 175 
 Definition, of diathesis, 3 
 
 of uraemia, 96 
 
 of urotoxic co-efficient, 35, 47 
 Diabetes, acetonaemia in, 247, 248 
 
 albuminuria in, 246 
 
 blood of, 245, 246 
 
 breath in. 167, 247, 248 
 
 cataract in, 246 
 
 circulatory system in, 167, 245, 246 
 
 coma of, 167, 246-248 
 
 cutaneous system in, 246 
 
 metabolism in, 246 
 
 nervous system in, 167, 246, 247 
 
 ocular changes in, 246 
 
 odor of breath in, 167, 247, 248 
 
 renal system in, 245, 247 
 
 respiratory system in, 167, 246 
 
 symptoms in, 167, 246-248 
 
 urea of, 246 
 
 urine of, 142, 245-248 
 
 urochromes of, 142, 247, 248 
 Diaphoretics, in uraemia, 128 
 Diarrhoea, acid, 139. 140, 168 
 
 erythema in, 139, 168 
 
 in dyspepsia, 139, 140 
 
 in intra-venous injections, 87, 88, 94, 
 
 in typhoid, 
 
 in uraemia, 108, , _.. 
 
 nerve-reactions a cause of, 6 
 
 salutary, 19 
 
 toxaemia due to, 155 
 
 toxic power of urine diminished by, 132 
 
 urine of, 132, 142 
 Diathesis, acquired, 7, 8 
 
 arthritic, 6-8 
 
 definition of, 3 
 
 in dilated stomach, 165, 166. 169 
 Diet, improper, dilated stomach due to, 174 
 
 in dilated stomach, 177-182 
 
 in typhoid, 217-219 
 
 in uraemia, 136, 137 
 
 toxic power of the urine varies with, 
 
 Digitalis, in uraemia, its dangers and uses, 
 
 129, 130 
 Disease, abnormal metabolism a cause of, 
 
 9-11 
 
 albumens a cause of, 10 
 Bright's, vide Briglit's disease 
 excess of minerals a cause of, 10 
 
 of water a cause of, 10 
 four pathogenic processes in, 2-12 
 infectious, dilated stomach a cause of, 
 
 176 
 
 dilated stomach due to, 175, 176 
 lardaceous, 104
 
 INDEX. 
 
 293 
 
 Disease micro-organisms, a cause of, 4, 5, 9 
 in urine of, 188 
 
 nerve-reactions, a cause of, 2-8, 66, 163 
 
 normal substances, a cause of, 10, 11 
 
 odor of sweat indicates, 20 
 
 pathogenic processes in, 2-13 
 
 peptones, a cause of, 10 
 
 secretions, a cause of, 10 
 
 sweat indicates, 20 
 
 the causes of, must be combined, 9 
 
 urochromes of, 141, 142, 232, 247, 248 
 Diseases, causing exhaustion, 104 
 
 due to abnormal metabolism, 10, 11 
 
 skin, in dilated stomach, 162, 163 
 Diuretic, the, of urine, 60, 61 
 
 urea as a, 57, 60, 61, 67, 116, 130, 131, 228, 
 
 231 
 
 Diuretics, in uraemia, 129-131 
 Dysentery, a cause of exhaustion, 104 
 Dyslysin. in intestine, 18, 223 
 Dvspcpsia, acid, 139, 140 
 
 acul diarrhcea in, 139, 140 
 vomiting in, 139 
 
 alimentary system in, 139, 140, 146, 147 
 
 breath in, 147, 247 
 
 cardialgia in, 139 
 
 circulatory system in, 140 
 
 coma in, 140, 167 
 
 constipation in. 146 
 
 convulsions in, 140 
 
 cramps in, 140 
 
 cutaneous system in, 139, 140, 147 
 
 deafness in, 140 
 
 diarrhoea in, 139, 140 
 
 dilated stomach due to, 161, 174, 175 
 
 erythema in, 139 
 
 faeces in, 139, 140 
 
 fatigue in, 140 
 
 headache in, 140, 147 
 
 intestinal antiseptics in. 111 
 
 intestinal gases of, 140, 148, 149 
 
 lavage in, 147, 148 
 
 nervous system in, 140. 147 
 
 ocular symptoms in, 140 
 
 paralyses in. 140 
 
 pyrona in, 139 
 
 renal system in. 140 
 
 secretions of. 139, 146, 147 
 
 sulphuretted hydrogen in, the intes- 
 tines of. ] ill. 1 K. ] |(l. l.V, 
 
 symptoms of, 139, 140, HO, 147 
 
 taste in, 137 
 
 teeth in, 119 
 
 toxemia in, 140, 148, 149, 155 
 
 treatment of, 147, 148 
 
 uni'iiiio symptoms in. 140 
 
 u rine of, 140-142, l'4i. '-M7 
 
 iirorhroiiie- of, 141, 142, 247 
 
 vertigo in. 140, 147 
 
 vision disturbed in, 140 
 
 vomiting of, 139 
 
 Dyspeptic type of dilated stomach, 170 
 Dyspnoea, in coma, 167 
 
 in dilated stomach, 164 
 
 in uraemia, 67, 108 
 
 Eclampsia, abnormal metabolism a cause 
 
 of, 11 
 Eczema, in dilated stomach, 162, 163, 171 
 
 in gastro-enteritia, 168 
 Emaciation, convulsion* in. 240 
 
 in dilated Stomach, 165 
 
 in jaundice, 82, 230 
 
 in typhoid, 191, 204, 218, 240 
 
 Emetics, in uraemia, 131 
 Enemata, in anuria, 130 
 
 in dilated stomach, 182 
 
 in typhoid, 193, 219 
 
 in uraemia, 130 
 Enteritis, in dilated stomach, 159 
 
 gastro-, of children, 168 
 Entorrhagia, in Bright's disease. 105 
 Epistaxis, in Brighfs disease, 105 
 
 in jaundice, 230 
 
 in nerve-reactions, 6 
 
 in typhoid, 190 
 Erysipelas, in typhoid, 190 
 Erythema, in diarrhcea, 139, 168 
 
 in dilated stomach, 163 
 
 in dyspepsia, 139 
 
 in gastro-enteritis, 168 
 
 in intestinal toxaemia, 155 
 
 in jaundice, 235 
 Etiology, of cholera, 249-252 
 
 of dilated stomach. 169. 174-176 
 
 of typhoid, 176, 189 
 
 of uraemia, 109 
 Evening, the urine of, 36-40 
 Excretion, of albumen, 103 
 
 of bile, 85, 227. 229 
 
 of bile-acids, 227 
 
 of fats, 103 
 
 by the kidneys, vide Kidneys 
 
 of peptones, 103 
 
 of poisons, vide Poisons 
 
 of sugar, 103 
 
 of urea, 71, 103. 116, 204, 207 
 
 of uric acid, 103 
 
 of urine, 103. 125 
 Excretory power of kidneys, 103 
 Exercise, urine of, 43-45 
 Exhaustion, causes of, 103, 104 
 Exophthalmic goitre, dilated stomach in, 
 
 175 
 Exophthalmos, in intra-venous injections, 
 
 33.37.38,74 
 Extractives, in fa-ces. 111 
 
 in putrefactive products, 93 
 
 micro-organisms produce. 1'J 
 
 toxic power of, 1I7-11U. Iti', 
 
 uremia due to, 107, 117-119, 125 
 Extracts, acids in. 7!> 
 
 alcoholic. 55-37. 77-79, 91, 94-06, 125, 142, 
 143. 27. 268 
 
 in typhoid. "JIT 
 
 intr.i venous injections of, 54 
 
 88. 89. 92-&, 98, 142, 148. 286. &7\ 
 
 J'.T. _'!. 
 
 of blood, 77, 78, 88, 89 
 
 of choleraic urine, 387, 388 
 
 ,,, ,.,.,, . MI.-*. H 
 
 of liver, 78, TO 
 
 of nic.it iii t\ pboid, 217 
 
 ofm,,s,-]e.7S I 7 ! ..88:W,a2.88,H2.143 
 
 of putrefactive product*, 88, 80, 91-9* 
 
 . ! 3 78, 125, 267, 268 
 
 the narcotic, of urine, 58, 125 
 
 the sialogenou* of urine. 56, 78, 125 
 
 watery, 64-57. 79, 91-08, 368 
 
 Fasces, acid, of dilated stomach, 169 
 alcoholic extract of, 04-08 
 alkaloids in the, 94, 97, 08, 189, 141, 150, 
 
 ammonia in. 98, 139 
 carbolic acid in, 141 
 charcoal acts on, 98, 100, 192
 
 294 
 
 INDEX. 
 
 Fasces, extractives in, 141 
 
 extracts of, 94-96, 98 
 
 fetid, 159 
 
 indol in, 141 
 
 intra-venous injections of extracts of, 
 94, 95, 98 
 
 minerals in, 139 
 
 naphthalin acts on, 99, 100 
 
 of cholera, 262 
 
 of dilated stomach, 159 
 
 of dyspepsia, 140 
 
 organic matter in, 139 
 
 poisons in. 139, 141 
 
 potass in, 96, 139 
 
 putrefactive products in, 94, 96 
 
 toxic power of, 94-96, 98, 139 
 
 watery extract of, 94-96 
 Fatigue, in dyspepsia, 140 
 Fats, excretory power of kidney for, 103 
 Five modes of action of microbes, 11, 12 
 
 (1) anatomical 
 
 (2) destructive 
 
 (3) ingestive 
 
 (4) obstructive 
 
 (5) productive 
 
 Five theories of uraemia, 107-128 
 
 (1) ammonaemia, 107, 115-117 
 
 (2) cerebral oedema, 107, 109-111 
 
 (3) extractives, 107, 117-119, 125 
 oxalic acid, 107 
 urochromes, 107, 119, 125 
 
 (4) minerals, 107, 120-126 
 
 (5) urea, 107, 112, 113 
 Flatulence, in dilated stomach, 159 
 Food, intestinal poisons due to, 96, 97, 138 
 
 uraemia due to, 126, 136 
 Formula for use of charcoal, 100, 218, 219 
 
 of iodoform, 100, 218, 219 
 
 of naphthalin, 100, 218, 219 
 Four pathogenic processes, 2-13 
 
 (1) disturbed nutrition 
 
 (2) elementary dystrophies 
 
 (3) infection 
 
 (4) nerve-reactions 
 
 Four sources of intestinal poisons, 138-15? 
 
 (1) bile 
 
 (2) faeces 
 
 (3) food 
 
 (4) putrefactive products 
 Four sources of toxic materials, 96 
 
 (1) food 
 
 (2) glands 
 
 (3) putrefactive products 
 
 (4) tissues 
 
 Four sources of uraemia, 126, 134-138 
 
 (1 ) disassimilation 
 
 (2) food 
 
 (3) putrefactive products 
 
 (4) secretions 
 
 Gangrene, in typhoid, 190 
 
 Gases, in intestine, 19, 140, 148. 149, 155 
 
 Gastric carcinoma, coma in, 167 
 
 dilated stomach due to, 175 
 toxaemia due to, 155 
 urine of, 142 
 
 catarrh, dilated stomach due to, 175 
 juice neutralizes poisons, 88, 93 
 ulcer, dilated stomach due to, 175 
 coma in, 167 
 milk in, 181. 182 
 Gastritis, coma in, 167 
 
 dilated stomach due to, 175 
 in dilated stomach, 159 
 
 astro-enteritis of children, symptoms of, 
 
 168 
 
 lands, a toxic source, 96 
 in jaundice, 230 
 in typhoid, 188 
 micro-organisms in, 188 
 Grlycaemia, 10, 245 
 GHycerin, in typhoid, 218, 219 
 intra-venous injection of, 28 
 toxic power of, 28 
 Glycocholates, vide Bile-salts 
 Glycocholic acid, in intestine, 18, 223 
 Glycosuria, 245 
 
 Goitre, exophthalmic, dilated stomach in. 
 175 
 
 Hsematemesis, in Bright's disease, 105 
 Haematuria, in intra-venous injections, 33, 
 
 51 
 
 laemoglobin, toxic power of, 78 
 Haemoglobinaemia, in jaundice, 230 
 Haemorrhages, in acute yellow atrophy of 
 liver, 232 
 
 in Bright's disease, 105, 106 
 
 in dilated stomach, 165 
 
 in intra-venous iniections, 33, 51, 73-75 
 
 in jaundice, 230, 232. 235 
 
 in nerve-reactions, 6 
 
 in typhoid, 200 
 Headache, and constipation, 145 
 
 in dilated stomach, 161 
 
 in uraemia, 108 
 Hepatic type of dilated stomach, 170 
 Hernia, toxaemia in, 145 
 Hippuric acid, toxic power of, 118 
 
 uraemia due to, 118 
 Hydatids, urticaria a complication of, 162, 
 
 163 
 Hydraemia. causes of, 104 
 
 in Bright's disease, 104, 105 
 
 in jaundice, 234 
 
 in lavdaceous disease, 104 
 
 uraemia due to, 107, 109-111 
 Hydrochloric acid, vide Acid, hydro- 
 chloric 
 Hydrogen sulphide, in blood, 15, 149 
 
 in excretions. 149. 155 
 
 in intestine, 140, 148, 149, 155 
 
 in urine, 149 
 
 toxaemia due to, 148, 149 
 Hydropathic treatment, ride Baths 
 Hyperpyrexia, vide Fyrexia 
 Hypochondriasis, constipation in, 14o 
 
 in dilated stomach, 171 
 
 Indican, and indol, 141 
 
 in urine, 141, 142 
 
 of intestinal disease, 141 
 Indigo, in portal blood, 15 
 Indol, and indican, 141 
 
 in faeces, 141 
 
 in intestine, 141 
 
 in putrefactive products, 93 
 
 micro-organisms produce, 12 
 Infection, abnormal metabolism precedes, 
 
 and intoxication, 89-91, 145, 160-153, 186, 
 
 190 
 
 in typhoid, 189 
 
 nervous influences precede, 6, 7 
 Infective disease, death in, 236, 237 
 dilated stomach a cause of, 176 
 due to, 175, 176
 
 INDEX. 
 
 295 
 
 Inhalations, in dilated stomach. 177 
 
 in uraemia, 128, 135 
 Injections, in uraemia, 130 
 
 intra-venous, albuiuinuria in, vide Al 
 buminuria 
 
 alimentary system in, vide Ali- 
 mentary system 
 
 circulatory system in, vide Circu- 
 latory system 
 
 coma in, vide Coma 
 
 convulsions in, vide Convulsions 
 
 cramps in, 264, 265 
 
 exophthalmos in, 33, 37, 38, 74 
 
 haematuria in, 33, 51 
 
 haemorrhages in, 33, 51, 73-75 
 
 morbid anatomy in, 88, 89, 143 
 
 myosis in, vide Myosis 
 
 nervous system in, vide Nervous 
 system 
 
 ocular symptoms in, vide Myosis 
 and Nervous system 
 
 of alcohol, 27, 28 
 
 of alcoholic extracts, 55-57, 77-79, 91, 
 95, 142. 143, 267, 268 
 
 of bile, 80, 81, 225, 226 
 
 of blood, 73, 143 
 
 of blood-extracts. 77, 78 
 
 cf blue pus, 243, 244 
 
 of choleraic urine, 263-267 
 
 of diabetic urine, 24, 25 
 
 of evening urine, 36-39 
 
 of extracts, vide Extracts 
 
 of faecal extracts, 94, 95, 98 
 
 of glycerin, 28 
 
 of jaundiced urine, 86, 87, 238 
 
 of liver-extract, 78, 79 
 
 of micro-organisms, 26, 188, 189, 243, 
 244 
 
 of morning urine, 36-39 
 
 of muscle-extracts, 78, 79, 88, 89, 92, 
 93, 142, 143 
 
 of pathological urines, 24-26, 34. 86, 
 
 of pus, 243, 244 
 
 of putrefactive products, 88, 89, 
 91-93, 142, 143 
 
 of pyrexial urine, 238, 239 
 
 of septic urine, 26 
 
 of serum, 74-76 
 
 of sleep, urine of, 36-18 
 
 of soda-lye, 52 
 
 of tetanic urine, 237, 238 
 
 of typhoid bacillus, IKS, 189 
 
 of urea, 49,50,61, 112, 113 
 
 of uric acid, 51, 52 
 
 of urine, 25^59. 86, 87, 237-240, 267, 
 268 
 
 of urochromes, 53 
 
 of water, 27, 75, 76, 111 
 
 of watery extracts, 54-56. 94-96, 268 
 
 reflexes in, vide Reflexes 
 
 renal system in, vide Kenal system 
 
 respiratory system in, vide Respi- 
 ratory system 
 
 salivation in, vide Salivation 
 
 temperature in, vide Temperature 
 
 the strength of, 28 
 
 urine in, 264-267 
 subcutaneous, albuminuria in, 24 
 
 of urine, 24 
 
 Insanity and constipation, 145 
 Intestinal antiseptics, 98-100, 186, 137, 191- 
 193, 199. 219 
 
 in dilated stomach, 174, 183, 184 
 
 Intestinal antiseptics, in dyspepsia, 141 
 
 in typhoid, l!)l-li)3, '10&-200, 218, 219 
 
 in uraemia, 136, 137 
 disease, indican and indol of, 141 
 
 urine of, 141, 142 
 fermentation, symptoms of, 139 
 gases of dyspepsia. 140, 148, 149 
 obstruction, circulatory system in, 144. 
 155 
 
 collapse in, 144 
 
 cramps in, 144 
 
 cutaneous system in, 144, 146 
 
 earthy pallor of, 144 
 
 erythema in, 155 
 
 lavage in, 147. 148 
 
 mydriasis in, 155 
 
 nervous system in, 144 
 
 reflex symptoms in, 144. 145 
 
 symptoms of. 144, 145, 155 
 
 sweating in, 1-14 
 
 toxaemia due to, 145, 155 
 
 treatment of, 147 
 
 tympanites in, 144 
 
 urine of, 142 
 
 vomiting in, 114 
 poisons, origin of, 138, 138 
 toxaemia, 138-192 
 
 acute, 138-153 
 
 anhidrosis in, 151 
 
 treatment of, 147, 148 
 Intestine, acetic acid in, 16 
 acids in, 16, 18. 141, 142,223 
 alkaloids in, 97, 98, 155 
 ammonia in, 140 
 bile-acids in, 18, 223 
 
 -pigment in, 223 
 
 -salts in, 223 
 butyric acid in, 16 
 carbolic acid in, lit, 141, 142 
 Cholalir acid in. IS. 223 
 cholic acid in, 18. 223 
 dyslysin in, 18, 223 
 gases in, 19, 140, 148, 149, 155 
 glycocholic acid in, 18, 223 
 hydrogen sulphide in, 140, 148, 148, 155 
 indol in, 141 
 lactic acid in, 16 
 minerals in, 138, 139 
 origin of poisons in, 188, 188 
 oxalic acid in, 16 
 taurocholic acid in. 1 
 Intoxication, and infection, 89-91, 145. 1 .10- 
 
 153, 187, 190 
 
 of blood, the three sources of the. K7, K8 
 lodoform, an antiseptic, im.im. !:;;. i:;7. 111. 
 
 171. 183, 1*1. 1'.'",. I!-!.. . 
 formulae for use of. 100. 218. 219 
 in cholera, 260, 261 
 in dilated stomach. 174. 183, 184 
 in typhoid, 193, 218, 219 
 in uramla, 186 
 
 Jaundice, aeholia in, 2'J8, 233, 284 
 Ibonlnnrta in, 231 
 
 bio..d of. at". 2:11 
 
 cerebral 0'<lein:i ill, i'il 
 
 cholaemia in, 283 
 
 circulatory system in, 230, 232, 234, 285 
 
 convulsions in, 233 
 
 convulsive urine of, 82, 8fi. 87, 238, 288 
 
 cutaneous system in, 230, 285 
 
 emaciation in, 82, 230 
 
 eptotaxta m. ..:;<> 
 
 erythema in, 235
 
 296 
 
 INDEX. 
 
 Jaundice, fatty degenerations in, 227, 230 
 glands in, 230 
 haemoglobinaemia in, 230 
 haemorrhages in, 230, 232, 235 
 hydraemia in, 234 
 
 in acute yellow atrophy of liver, 235 
 in dilated stomach, 159, 160, 170 
 intra-venous injection of urine of, 86, 
 
 87,238 
 
 kidneys in, 227, 228, 230-235 
 leucin in, 231 
 liver in, 228, 230-235 
 metabolism in, 227, 228, 230, 231, 233 
 prognosis of, 233 
 pruritus in, 230 
 pulse in, 230 
 purpura in, 235 
 pyrexia in, 235 
 
 renal system in, 227, 228, 230-235 
 spleen 'in, 230 
 symptoms in, 225, 230 
 temperature in, 235 
 theories of, 234 
 tissues in, 224-227, 229, 230 
 toxaemia in, 222-235 
 toxic power of urine of, vide Toxic 
 
 power 
 
 tyrosinin,231 
 uraemia in, 233-235 
 urea of, 228, 231 
 urine of, 82, 86, 87, 225-227, 229, 231, 233, 
 
 xanthin in, 231 
 
 Kidneys, excretion by the, 19, 21. 70, 71, 73, 
 
 86, 103, 116, 229, 230, 241, 242 
 floating, 160, 164, 170 
 in atrophy of liver, 232 
 in dilated stomach, 160, 164. 172 
 in jaundice, 227, 228, 230, 232, 235 
 in typhoid, 188 
 in uraemia, 106, 108, 131 
 micro-organisms in the, 188 
 vide Renal system 
 
 Lactic acid, vide Acid, lactic 
 Lardaceous disease, albuminuria in, 104 
 
 exhaustion diie to, 104 
 
 hydraemia in, 104 
 
 metabolism in, 104 
 
 peptones of, 104 
 
 Latent type in dilated stomach, 170 
 Lavage, in dilated stomach, 147, 178, 183, 184 
 
 in dyspepsia, 147, 148 
 
 in intestinal obstruction, 147, 148 
 
 in toxaemia, 147, 148 
 Leeches, use of, in uraemia, 129 
 Leucin, disease due to, 11 
 
 in blood, 231 
 
 in dough, 179 
 
 in muscle-extract, 79 
 
 in putrefactive products, 93 
 
 in tissues, 231 
 
 in urine, 231 
 
 toxic power of, 11, 78, 93, 119 
 
 uraemia due to, 119 
 Leucocythsemia, the breath in, 167, 247 
 
 urine of, 142, 238, 247 
 
 urochromes of, 142, 247 
 Leucorrhcea, exhaustion due to, 104 
 Liver, acute yellow atrophy of, 231, 232, 235, 
 
 atrophy of, 227, 228, 230-234 
 
 bile arrested, by, 80, 84, 222-224, 227 
 
 Liver, enlarged, ectopia due to, 160 
 
 -extract, intra-venous injection of, 78, 
 
 fatty degeneration of, 227 
 
 functions of the, 230, 231 
 
 in dilated stomach, 159, 160, 170 
 
 of jaundice, 228, 230-235 
 
 poisons arrested by, 17, 18, 22, 80, 84, 
 
 142-144, 222-224, 227 
 
 putrefactive products arrested by, 143 
 Lungs, excretion by the, 18, 20, 21, 23, 131 
 
 Measles, baths in, 216 
 Meat, tainted, toxaemia due to, 151-153 
 Meat-extract, in typhoid, 217 
 Mercury, advantages of, 200, 201 
 
 an antiseptic, 98, 99, 196, 199, 200, 218 
 
 and carbolic acid, 196 
 
 disadvantages of, 200 
 
 in typhoid, 199-201, 218 
 
 method of use of, 201 
 
 salivation by, 200 
 
 sequelae after use of, 200 
 
 toxic power of, 196 
 
 Metabolism, abnormal, acholia due to, 11 
 coma due to, 11 
 eclampsia due to, 11 
 uraemia due to, 126, 134, 135 
 
 and infection, 5 
 
 diminished, in uraemia, 135 
 
 in acute yellow atrophy of the liver, 
 
 in diabetes, 246 
 
 in iaundice, 227. 228, 230, 231, 233 
 
 in lardaceous disease, 104 
 
 in pyrexia, 204 
 
 in typhoid, 204 
 Micro-organisms, acid products of, 12 
 
 action of, on the tissues, 11, 12 
 
 alkaloids a product of, 12 
 
 ammonia a product of, 12 
 
 and peptones, 87 
 
 bacilli, vide Bacillus 
 
 carbolic acid a product of, 12 
 
 extractives a product of, 12 
 
 fatty acids a product of, 12 
 
 gaseous products of, 12 
 
 fn blood, 188 
 
 in dough, 179 
 
 in pus, vide Bacillus 
 
 in the glands, 188 
 
 in the kidneys, 188 
 
 in the spleen, 188 
 
 in the tissues, 11, 12 
 
 in the urine, 188, 243 
 
 indol a product of, 12 
 
 intra-venous injection of, 26, 188, 189, 
 243, 244 ' 
 
 modes of action of, 11. 12 
 
 of cholera, vide Bacillus 
 
 of typhoid, vide Bacillus 
 
 products of, 12 
 
 tests for, 243 
 
 the five modes of action of, 11, 12 
 
 the search alter, 9 
 
 toxic products of, 12 
 
 skatof a product of, 12 
 
 sulphuric acid a product of, 12 
 Migraine, in constipation, 145 
 
 in dilated stomach, 170 
 Milk, in dilated stomach, 180-182 
 
 in gastric ulcer, 181, 182 
 
 in typhoid, 217 
 
 in uraemia, 130, 135-137
 
 INDEX. 
 
 297 
 
 Minerals, as intestinal poisons, 138, 139 
 
 disease due to excess of, 10 
 
 in bile, 82. 83, 86 
 
 in blood, 87 
 
 in faeces, 139 
 
 in typhoid, 217 
 
 in urine, 57-59, 64, 65, 82, 83, 116, 117, 120, 
 122, 124-126 
 
 table of the toxic power of, 124 
 
 total toxic power of, 125, 126 
 
 toxic power of, vide Toxic power 
 
 uraemia due to, 107, 120-126. 233 
 Mixed urine, toxic power of, 42, 43 
 Morbid anatomy, in intra-venous injec- 
 tions, 88, 89, 143 
 
 of uraemia, 110 
 Morning, the urine of, 36-43 
 
 urine, intra-venous injection of, 36-39 
 Mortality of typhoid, 192, 193, 200, 220, 221 
 Muscle, alcoholic extracts of, 79, 142, 143 
 
 and urine, the toxic powers of, 93 
 
 -extract, composition of, 79 
 
 intra-venous injection of, 78, 79, 88, 
 89, 92, 93, 142, 143 
 
 putrefactive products of, 93 
 
 watery extract of, 79, 92, 93 
 Mydriasis, in intestinal obstruction, 155 
 
 in toxaemia, 151 
 Mydriatic alkaloids, 92 
 Myosis, and convulsions, 57, 63 
 
 in an u ri:i. 67 272 
 
 in cholera, 67, 124, 271, 272 
 
 in intra-venous injections, 26, 32, 33, 
 36-38, 46, 53, 55^57, 74, 79. 86, 87, 93, 
 237, 238, 240, 263 
 
 in uraemia, 67, 124 
 Myotic, the, of urine, 63, 125 
 
 Naphthalin, action of, on faeces, 99, 100 
 
 on urine, 99, 100 
 formula? for use of, 100, 218 219 
 in acute yellow atrophy of the liver, 
 
 231,232,263 
 
 in cholera, 232, 260. 261, 263 
 in dilated stoniarh. 171. Ki 
 in typhoid, litt, 218, 219, 232, 263 
 in uraemia. 136, 137 
 in urine, 99. 100, 232 
 Narcotic, the, of urine, 62, 125 
 
 urine, 41, 239 
 
 Nerve-reactions, a pathogenic process, 2-8 
 diarrhoea due to, 6 
 disease due to, 2-8, 66, 163 
 epistaxis due to, 6 
 haemorrhages in, 6 
 polyuria due to, 6 
 syncope due to, 6 
 -stimulation in uraemia, 129 
 Nervous debility, dilated stomach due to, 
 
 175 
 influences induce disease, 2-8, 66 
 
 precede infection, 6, 7 
 system, in ammonaeraia. 116 
 in anuria, 67,272 
 in Bright's disease, 106 
 in cholera, 67, 124, 271, 272 
 in constipation, 145 
 in diabetes, 167. 246, 247 
 in dilated stomach. 161, 167, 170, 171 
 in dyspepsia, 1 10, 1 17 
 in intra-venous injections, 26, 32-34, 
 36-38, 46, 47. 51, 5~3. S5-57. 74, 77, 79, 
 86, 87, 92-95. 233, 237-240, 263 
 in toxaemia, 140, 144, 145, 150, 151, 155 
 
 Nervous system, In uraemia, 66, 67, 106, 108- 
 
 type of dilated stomach, 170, in 
 Neuralgia, in dilated stomach, 161 
 Neurasthenia, dilated stomach due to, 175 
 Nodes, bony, in dilated stomach, 165, 166, 
 172,176 
 
 Obstructive anuria, 105, 110, 111, 113 
 Ocular symptoms, in anuria, 67, 272 
 
 in Bright's disease, 106 
 
 in cholera, 67, 124, 271, 272 
 
 in diabetes, 246 
 
 iu dilated stomach, 161 
 
 in dyspepsia, 140 
 
 in intra-venous injections, vide Myosis 
 
 in toxaemia, 151, 155 
 
 in typhoid, 92 
 
 in uraemia, 67, 106, 124 
 Odor, of breath, vide Breath 
 
 of sweat, in dilated stomach, 162 
 
 indicates disease, 20 
 CEdema, in Bright's disease, 105, 106 
 Organic, the, convulsive of urine, 62,63, 65 
 Osseous system, in dilated stomach, 165- 
 
 168, 172, 176, 185 
 Osteomalacia, in dilated stomach, 166, 167, 
 
 172 
 
 Oxalic acid, vide Acid, oxalic 
 Oxygen inhalations, in dilated stomach, 
 
 in uraemia, 135 
 
 Paralyses, in dilated stomach, 161 
 
 in toxaemia, 151 
 Peptones, and albumen, 10. 17, 104, 164, 165 
 
 and micro-organisms, 87 
 
 blood-cells transform, 17, 165 
 
 disease due to, 10 
 
 excretion of, 103 
 
 in dilated stomach. 182 
 
 in the urine. 164, 165 
 
 in typhoid, 217-219 
 
 of lardaceous disease, 104 
 
 toxic power of. 10 
 
 Percussion sign, in dilated stomach, 156 
 Pericarditis, in Bright's disease, 106 
 Phalungeal nodes, in dilated stomach, 165, 
 
 166, 172, 178 
 
 P ..ebitis, in dilated stomach, 165, 171 
 Phthisis, in dilated stomach. 1 
 Physical signs of dilated stomach. 1.56-158 
 Pityriasis versicolor, in dilated stomach, 
 
 162 
 Pneumonia, baths in, 216 
 
 quinine in, 198 
 Poison, uraemia is a complex, 109, 127, 128, 
 
 Poisons, amount of, necessary to produce 
 
 death, 78 
 blood a source of, 77, 78 
 
 arrests. 17 224 225 
 excretion of, 15, 18, 20-23, 66, 70-78, 102, 
 
 103 
 food a source of, 98, 97, 138 
 
 gastric juice neutralizes, 88, W 
 hi blood, is. 17. 70-73, bsTw 
 in faeces. 139, 141 
 in the alimentary system, 
 in tissues. 16. 22, 83, 98, 97, 
 in urine. 16. 141, 142 
 liver arrests, vide Liver 
 modes of arrest of, 144 
 origin of, 98, 87 
 
 87. 101
 
 298 
 
 INi)EX. 
 
 Poisons, purgatives remove, 132 
 
 putrefactive products a source of, 88- 
 
 90, 138, 139 
 
 Portal blood, 15, 17, 72, 143 
 indigo in, 15 
 
 sulphuretted hydrogen in, 15 
 toxic power of, 72, 143 
 
 vein, coma after ligature of, 143 
 Potassium, action of, as a toxic power, 
 122,123 
 
 an antiseptic, 196 
 
 as a convulsive, vide Convulsive 
 
 bromide, dangers of, 134 
 
 chloride, toxic power of, 122, 124 
 
 death by, 123 
 
 in bile, 82, 83, 86 
 
 in blood, 124 
 
 symptoms due to, 123 
 
 total toxic power of, 125, 126 
 
 toxic power of, vide Toxic power 
 
 uraemia due to, 107, 120-126, 233 
 Prognosis, of dilated stomach, 185 
 
 of jaundice, 233 
 Pruritus, in jaundice, 230 
 Ptisan, in typhoid, 217 
 Puerperal fever, quinine in, 198, 210 
 Pupil, vide Mydriasis and Myosis 
 Purgatives, in surgical operations, 148 
 
 in typhoid, 193, 218 
 
 in uraemia, 131, 132. 135 
 
 remove poisons, 132 
 Purpura, in Bright's disease, 105 
 
 in dilated stomach, 165 
 
 in jaundice, 235 
 Putrefactive products, alkaloids in, 91-93 
 
 ammonia in, 93, 96, 140 
 
 and urine, 93 
 
 a source of poisons, 88-90. 138. 139 
 
 charcoal acts on, 92, 136, 141 
 
 composition of, 93 
 
 extracts of, 88, 89, 91-93, 96, 142, 143 
 
 in blood, 88, 89 
 
 in faeces, 94, 96 
 
 intra-venous injection of, 88, 89, 91-93, 
 142, 143 
 
 liver arrests, 143 
 
 toxaemia due to, 139-141, 145, 149-153 
 
 toxic power of, vide Toxic power 
 principles in. 93 
 
 trypsin develops. 94 
 
 uraemia due to, 126, 134-136, 233 
 Pylorus, obstructed, dilated stomach due 
 
 to, 175 
 Pyrexia, artificial, 203 
 
 baths in, 206, 207, 212-217, 220 
 
 blood of, 205, 206 
 
 circulatory system in, 203, 204 
 
 convulsive urine of, vide Convulsive 
 
 diet in, 217-219 
 
 discussed, 202-209 
 
 effects of. 202, 203 
 
 heart in, 204 
 
 in jaundice, 235 
 
 in typhoid, 191 
 
 metabolism in, 204 
 
 multiple causes of. 205, 207-209 
 
 pathology of. 205. 200, 208, 209 
 
 quinine in, 198, 199, 206. 209-211, 219 
 
 salutary, 202 
 
 treatment of, 205-207. 209-217 
 
 urine of, vide Convulsive 
 
 urochromes of, 240 
 
 venesection in, 205 
 
 veratrin in, 205 
 
 an intermittent remedy, 210 
 death due to, 211 
 in ague, 198, 209 
 in pneumonia, 198 
 in puerperal fever, 198, 210 
 in pyrexia, vide Pyrexia 
 in typhoid, 198, 199, 206, 207, 210, 211, 219 
 limits of, 198, 206. 209 
 method of use of, 210 
 
 Recapitulation, general, 280-288 
 Reflex symptoms, in toxaemia, 144, 145 
 Reflexes, in intra-venous injections, 26, 33, 
 
 36-38, 47, 74 
 
 Renal system, in acute yellow atrophy, 232 
 in cholera, 271 
 in diabetes, 245, 247 
 in dilated stomach, 160, 164, 165, 171, 
 
 185 
 
 in dyspepsia, 140 
 
 in intra-venous injections, 25, 26, 
 32, 33, 36, 47, 55, 56, 87, 243. 264, 
 266,267 
 
 in jaundice, 227, 228, 230-235 
 vide Albuminuria and Kidneys 
 type of dilated stomach, 171 
 Respiratory system, in cholera, 271 
 in coma, 67, 167 
 in diabetes, 167, 247 
 
 in dilated stomach, 158, 163, 164, 167, 172 
 in intra-venous injections, 26, 36, 37, 46, 
 
 50, 74, 86, 89, 93 
 in typhoid, 190, 200 
 in uraemia, 66, 106, 108. 131 
 Revulsives, in uraemia, 129 
 Rheumatic type of dilated stomach, 171 
 Rheumatism, baths in, 216 
 Rickets, in dilated stomach, 166, 168, 172 
 
 Salivation, in intra-venous injections, 47, 
 55-57, 77, 79, 125 
 
 in uraemia, 67 
 
 mercurial, 200 
 Sausages, toxaemia due to, 151-153 
 Scarlatina, baths in, 216 
 Secretions, uraemia due to, 126, 134-136 
 Sepsine, an alkaloid, 91 
 Septic urine, intra-venous injection of, 26 
 Serum, intra-venous injection of, 74-76 
 Seven, the. toxic principles of urine, 60-65 
 
 (1) antipyretic 
 
 (2) convulsive, inorganic 
 
 (3) convulsive, organic 
 
 (4) diuretic 
 
 (5) myotic 
 
 (6) narcotic 
 
 ogueth of blood. 57, 77, 78 
 the, of urine, 56, 57, 62, 125 
 
 Sinapisms, in uraemia, 129 
 
 Skatol, in putrefactive products, 93 
 in urine, 12 
 micro-organisms produce, 12 
 
 Skin, vide Cutaneous system 
 
 Sleep, the urine of, 36-43 
 
 Soda, an antiseptic, 196 
 in the urine, 67 
 
 -lye, intra-venous injection of, 52 
 toxic power of, vide Toxic power 
 
 Spleen, the, vide Glands 
 
 Stercorsemia, 101 
 
 Stomach, dilated, acid faeces of, 159 
 acne in, 163, 171 
 albuminuria in, 164, 171, 185
 
 INDEX. 
 
 Stomach, dilated, alcoholism a cause of, 
 
 175 
 
 alimentary system in, 159 
 and typhoid, 176, 186 
 angina, false, in, 161, 171 
 antiseptics in, 174, 183, 184 
 aphasia in, 161 
 arthritis in, 165. 166 
 asthma in, 164, 171 
 asthmatic, type of, 167 
 baths in, 176, 177 
 bread in, 178, 179 
 bronchitis in, 164, 171 
 bulimia in, 159 
 carcinoma a cause of, 175 
 cardiac type of, 171 
 cardialgiain,159, 171 
 chlorosis in, 158, 172 
 circulatory system in, 158, 161, 165, 
 
 167, 171, 172 
 
 clinical types of, 170-172 
 coma in, 167 
 
 consumptive type of. 171, 172 
 contractions in, 161, 171 
 coryza in, 164, 171 
 cutaneous system in. 161-163, 171 
 cutaneous type of, 171 
 debility a cause of, 175 
 diathesis in, 165, 166, 169 
 diet in, 177-182 
 
 dyspepsia a cause of, 161, 174, 175 
 dyspeptic type of, 170 
 dyspnoea in. 164, 167 
 eczema in, 162, 163, 171 
 emaciation in, 165 
 enemata in, 182 
 enteritis in, 159 
 erythema in, 163 
 etiology of. 169, 174-176 
 faeces of, 159 
 fluids in, 178, 180, 181 
 gastric causes of, 175 
 
 Gastritis in. 159 
 aemorrhages in, 165 
 headache in, 161 
 hemiopia in, 161 
 hepatic type of, 170 
 heredity in. 169, 175 
 hydrochloric acid in 183, 184 
 hypochondriasis in, 171 
 improper diet a cause of, 174 
 in ataxia, 175 
 in goitre, 175 
 infectious disease a cause of, 175, 
 
 I7i; 
 
 infectious disease due to, 176 
 inhalations in, 177 
 jaundice in, ir.il. HiO, 170 
 kidneys in, 160. \M, 170 
 latent type of. 170 
 lavage in, 147, 178, 183, 184 
 litniasis in, 170 
 liver in, 159, 160, 170 
 mental causes of, 175 
 migraine in, 170 
 milk in, 180-182 
 nervous causes of, 175 
 nervous system in, 161. 107, 170, 
 
 171 
 
 nervous type of. 170, 171 
 neuralgia in, 161 
 night-sweats in. Hit 
 nodes, bony, in. UB, 166. 172, 176 
 ocular affections in, 161 
 
 Stomach, dilated, osseous system in, 165- 
 
 168, 172, 176, 185 
 osteomalacia in. 166, 167, 172 
 paralyses in, 161 
 peptones in, 182 
 percussion sign in, 156 
 phlebitis in, 165, 171 
 phthisis in, 158, 172 
 physical signs of, 156-158 
 pityriasis versicolor in, 162 
 prognosis of, 185 
 purpura in, 165 
 
 renal system in, l(K), 164, 165, 171, 185 
 respiratory system in, 158, 163, 164, 
 
 167, 172 
 
 rheumatic type of, 171 
 rickets in, 166, 168, 172 
 splashing sign in, 157, 158 
 stimulants in, 178, 181 
 succussion sign in, 156 
 symptoms of, 158-172 
 the breath in, 159, 163, 167, 247 
 the sweat of, 162 
 the ten clinical tvpes of, 170-172 
 toxaemia in, 155-m 
 treatment of, 174-186 
 urine of, 142, 164, 165, 171, 247 
 urochrouies of. 142. 165. 247 
 urticaria in, 162, 163, 171 
 vertigo in, 161 
 
 Succussion sign, in dilated stomach, 156 
 Sulphuretted hydrogen, vide Hydrogen 
 
 sulphide 
 
 Sulphuric acid, vide Acid, sulphuric 
 Summary of the treatment of typhoid, 
 
 218-220 
 
 of uraemia, 137 
 Sweat, vide Odor of 
 Symptoms, in anuria, 67, 272 
 in Bright's disease, 103-108 
 in jaundice, 225, 230 
 in potass poisoning, 123 
 in toxaemia, 150, 151 
 in typhoid, 1!M), 191, 200 
 in uraemia, 66, 67, 106. 108, 109 
 of aimnoiwmia, llli. 117 
 of dilated stomach. 158-172 
 of dyspepsia, 139-147 
 of gastro-enteritis, 168 
 of intestinal obstruction, 144, 145, 155 
 
 Table of the toxic power of minerals, 124 
 Taurocholic acid, in intestine, 18, 223 
 Teeth, changes in the, in dyspepsia, 139 
 Temperature, in ammonaMnia, 117 
 in cholera. 'J71 
 in coma, 108, 167 
 
 in intra venous injections, 25, 26, 38, 
 86-38. 47, 49, 58, 55-57, 238, 240, 243, 
 264. 265 
 
 in uraemia, 67, 108, 135 
 vide Pyrexia 
 Ten, the, clinical types of dilated stomach, 
 
 170-172 
 
 (1) asthmatic 
 ('_') cardiac 
 (3) consumptive 
 
 I 1 I cutaneous 
 
 (5) dyspeptic 
 
 (6) hepatic 
 
 (7) latent 
 
 (8) nervous 
 
 (9) renal 
 
 (10) rheumatismal
 
 300 
 
 Tests, for acetone, 142, 247 
 for alkaloids, 15, 16, 94, 262 
 
 INDEX. 
 
 , , , , 
 
 for bacillus pyocyaneus, 243 
 225 
 
 toxication of 
 
 for bile, 223, 
 
 Tetanus, the urine of, 237, 2:38 
 Therapeutics, general, 273-279 
 Three, the, sources of 
 blood, 87, 88 
 
 (1) bile 
 
 (2) minerals 
 
 (3) putrefactive products 
 Tissues, a toxic source, 96 
 
 acids in, 16, 79 
 alkaloids in, 15, 237 
 bile arrested by the, 224-227, 229, 230 
 in jaundice, 224-227, 229, 230 
 in uraemia, 112 
 leucin in, 231 
 
 micro-organisms in the, 11, 12 
 poisons in, vide Poisons 
 urea in the, 112 
 
 Toxaemia, acute intestinal, 138-153 
 auhidrosis in, 151 
 bile, 138, 139, 222-235 
 chronic intestinal, 155-186 
 constipation a cause of, 145 
 cutaneous system in, 140, 144, 151, 155 
 diarrhoea a cause of, 155 
 etiology of, 145, 155 
 food a source of, 96, 97, 138 
 four sources of, 96, 138-153 
 hydrogen sulphide a cause of, 148, 149 
 in dilated stomach, 155-172 
 in dyspepsia, vide Dyspepsia 
 in hernia, 145 
 in jaundice, 222-235 
 in typhoid, 190 
 
 methods of producing artificial, 23, 24 
 nervous system in, vide Nervous sys- 
 
 tem 
 
 ocular symptoms in, 151, 155 
 paralyses in, 151 
 putrefactive products a source of, vide 
 
 Putrefactive products 
 symptoms in, 148-151 
 tainted food a cause of, 149-153 
 treatment of, 147, 148 
 urine of, 140-142 
 urochromes of, 142 
 vertigo in ? 150 
 vomiting in, 150 
 
 Toxic accidents, why infrequent, 17 
 coefficient, 35, 47 
 materials, 96, 138-153 
 origin of cutaneous disease, 162, 163 
 Toxic power, of acid urine, 31, 32 
 of alcohol, 28 
 of alkaloids, 10, 14, 15, 18, 30. 54, 56, 58. 
 
 62, 67, 68, 77, 91-94, 125, 139, 151. 
 
 237, 239 
 
 of ammonia, 58, 96. 97, llfi, 117, 120 
 of anilin, 1% 
 of antiseptics, 99, 196, 197 
 of aromatics of urine, 53 
 of bile, 15, 18, 80-82, 84-S6, 96, 97, 119, 135, 
 
 139,2241235 
 
 and urine, 80 84, 85, 224 
 of bilirubin, 81, 119, 135, 139, 224, 229 
 of blood 69-78, 143 
 of carbolic acid, 196 
 of cholesterin, 81, 222 
 of creatin, 79, 118 
 of extractives. 117-119, 125 
 of faeces, 94-96, " 
 
 ["oxic power, of glycerin, 28 
 of haemoglobin, 78 
 of hippuric acid, 118 
 of jaundiced urine, 82, 86, 87, 229, 233, 
 
 of leucin, 11, 78, 93, 119 
 of leukaemic urine, 238 
 of mercury, 196 
 
 of minerals, 10, 15, 18, 43, 48, 53, 54, 57, 
 58, 61, 64, 65. 77-79, 82, 83, 86, 95-97, 
 120-126, 134, 138, 139. 196. 233, 240 
 of pathological urines, 34, 237-241 
 of peptones, 10 
 of pigments, vide Toxic power of bili- 
 
 rubin and urochromes 
 of potassium, vide Toxic power of min- 
 erals 
 
 of pus, 243 
 of putrefactive products, 87-93, 97, 139- 
 
 141, 150-153 
 
 of pyrexial urine, 123, 238-240 
 of secretions, 10, 15 
 of serum, 74-76 
 of soda, 57, 58, 61, 67, 121, 134 
 of sugar, 245 
 of tainted meats, 149-153 
 of typhoid urine, 92, 192, 238 
 of tyrosin, 119 
 of urea. 48-50, 57, 60, 61, 67, 107, 112-114, 
 
 126 
 
 of uric acid, 51, 52, 118 
 of urine, and bile, 80, 84, 85, 224 
 
 concentrated, 34, 48 
 
 decolorized, 86, 87 
 
 mixed, 42, 43 
 
 of evening. 36-40 
 
 of exercise, 43-45 
 
 of diarrhoea, 132 
 
 of jaundice, 82, 86, 87, 229, 233, 238 
 
 of leukaemia, 238 
 
 of morning, 36-43 
 
 of pvrexia, 123, 238-240 
 
 of sleep, 36-43 
 
 of typhoid, 92, 192, 238 
 
 of uraemia, 111, 112. 114, 238 
 
 pathological, 34, 237-241 
 
 the total, 125, 126 
 
 variations in the, 34-46, 48 
 of urochromes, 10, 11, 53, 119, 120, 125, 
 
 240 
 
 of water, 10. 48, 75 
 of xanthin, 119 
 the total, of alkaloids, 125 
 
 of bile, 224 
 
 of extractives, 125 
 
 of minerals, 121, 125,126 
 
 of pigments, 119, 120, 125 
 
 of urea, 120 
 
 of urine. 125, 126 
 Toxic powers, table of the, 124 
 
 of urine, antagonism of the, 62, 63, 122, 
 123 
 
 origin of the. 69 
 ratio o 
 
 of the. 120 
 
 the seven, 60-65 
 
 Treatment, antipyretic, vide Antipyretic 
 antiseptic, vide Antiseptic 
 hydropathic, vide Baths 
 of amiria, 130, 277 
 of cholera, 260, 261 
 of dilated stomach, 174-186 
 of dyspepsia, 147, 148 
 of measles, 216 
 of pneumonia, 207, 216
 
 301 
 
 Treatment, of puerperal fever, 198, 210 
 
 of rheumatism, 216 
 
 of scarlatina, 216 
 
 of typhoid, 191-220 
 
 of uraemia, 128-137 
 Trypsin develops alkaloids, 94 
 Typhoid, anaemia in, 200 
 
 and dilated stomach, 176, 186 
 
 baths in, vide Baths 
 
 blood of, 188 
 
 calomel in, 200, 201, 218 
 
 carbolic acid in, 193, 219 
 
 charcoal in, 191, 192. 218, 219 
 
 circulatory system in. 200 
 
 complications of, 190, 200 
 
 convulsions in, 240 
 
 cutaneous system in, 192, 215 
 
 diarrhoea in, 189 
 
 diet in, 217-219 
 
 emaciation in, 191, 204, 218, 240 
 
 endocarditis in, 200 
 
 enemata in, 193, 219 
 
 erysipelas in. 190 
 
 etiology of, 176, 189 
 
 glycerin in, 218, 219 
 
 haemorrhages in, 200 
 
 inoculation of, 188. 189 
 
 iodoform in, vide lodoform 
 
 metabolism in, 204 
 
 micro-organisms of, 188, 189 
 
 milk in. 217 
 
 minerals in, 217 
 
 mortality of, 192, 193, 200, 220, 221 
 
 naphthalin in, vide Naphthalin 
 
 ocular symptoms in, 92 
 
 peptones in, 217-219 
 
 ptfean in, 217 
 
 purgatives in, 193, 218 
 
 pyrexia in, 191 
 
 quinine in, vide Quinine 
 
 respiratory system in, 190,200 
 
 sequelae of, 200 
 
 summary of treatment of, 218-220 
 
 symptoms in, ](*>. 191, 200 
 
 the bacillus of. 188, 189 
 
 the breath in, 247 
 
 the glands in, 188 
 
 toxaemia in. I:MI 
 
 treatment of, 191-220 
 
 urea of. 204 
 
 urine of, 92, 141, 142, 188, 192, 238, 247 
 
 urochromes of, 142, 247 
 
 vegetable acids in, 217 
 Tvrosin. in blood, 2:11 
 
 in dough. 17!i 
 
 in muscle-extract, 79 
 
 in putrefactive products, 93 
 
 in uraemia. 119 
 
 in urine, 231 
 
 toxic power of, 119 
 
 Uraemia, a complex poison, 109, 127, 128, 
 
 . 
 abnormal metabolism :\ cause of, 126, 
 
 i :i. l.r, 
 alimentary system in, 108, 109, 126, 134, 
 
 ammonia a cause of, 107, 115-117 
 
 antidotes in. 131. 13."i 
 
 antiseptics in. i::i, 1 :' 
 
 baths m, 128 
 
 1.1 ..... 1 of. 78. 112, 116 
 
 bromides in ; their dangers, 134 
 
 caffeine in, 129 
 
 Uraemia, cerebral oedema a cause of, 107, 
 
 charcoal in, 136, 137 
 
 chloral in, 134 
 
 chloroform in, 134 
 
 coma in, 66, 106, 108 
 
 convulsions in, 66. 106, 108 
 
 creatin a cause of, 118, 119 
 
 cutaneous system in, 131 
 
 definition of, 96 
 
 diarrhoea in, 108, 132, 133 
 
 diet in, 136, 137 
 
 digitalis in, 129, 130 
 
 diminished metabolism in, 135 
 
 diuretics in, 129-131 
 
 dyspnoea in, 67, 108 
 
 emetics in, 131 
 
 enemata in, 130 
 
 etiology of, 109 
 
 extractives a cause of, 107, 117-119, 
 
 food a source of, 126, 136 
 
 four sources of. 126, 134-138 
 
 headache in, 108 
 
 hippuric acid a cause of. 1J8 
 
 hyursemia a cause of, 107, 109-111 
 
 in jaundice, 233-235 
 
 inhalations in, 128, 135 
 
 injections in. 130 
 
 iodoform in, 136 
 
 kidneys in. 106, 108. 131 
 
 leucin a cause of, 119 
 
 milk in, 130, 135-137 
 
 minerals a cause of, vide Minerals 
 
 morbid anatomy of, 110 
 
 myosis in, 67, 123 
 
 naphthalin in, 136, 137 
 
 nerve-stimulation in, 129 
 
 nervous system in, 66, 67, 106, 108-110 
 
 obstructive, 110, 111, 113 
 
 ocular symptoms in, 67, 106, 124 
 
 of cholera. 271 
 
 oxalic acid a cause of, 107 
 
 pathology of. 107-128 
 
 potass a eau-e ui. !/(/< Minerals 
 
 purgatives in, 131. 1 
 
 putrefactive, products a cause of, 126, 
 
 184-188,$ 
 
 respiratory system in, 66, 106, 108, 131 
 revulsives in, 129 
 salivation in, 67 
 
 secretions a source of, 12t>, 134-136 
 summary of the treatment of. 137 
 symptoms m , (Hi. 1-7. KKi. 10K, 100 
 the five theories of, 107-128 
 treatment of. 12S-137 
 tvroMii a cau-c of. lift 
 urea a cau-e ..f, lnT, 112. 113 
 urea in, 130, 131 
 
 uric acid a cail-e of. MX 
 
 urine of. M. ii7. Ins, nut, ni, 112, 114, 
 
 uroehromes a cause of, 107, 119, 125 
 
 \cne-i-ction in. 133 
 
 vicarious fum-iion- in, I'M 
 
 vomiting in. li-s. |::i 
 
 when does it occur ? 108 
 Uraemic symptoms, in dyspepsia, 140 
 
 in eXOMUTfl vomiting. 111) 
 l"iea. a diuretic, rir/r iMurctic 
 iction of, vide Excretion 
 
 in blood. 112. 116 
 
 in the tame*. ii-J 
 
 in uremia, 130, 131
 
 302 
 
 Urea, intra-venous injection of, vide In- 
 jection 
 
 of anuria, 112 
 
 of diabetes, 246 
 
 of jaundice, 228, 231 
 
 of typhoid, 204 
 
 toxic power of, vide Toxic power 
 
 urzemia due to, 107, 112, 113 
 Uric acid, excretion of, 103 
 
 intra- venous injection of, 51, 52 
 
 toxic power of, 51, 52, 118 
 
 uraemia due to, 118 
 Uricaemia, 10 
 Urine, acetic acid in, 16 
 
 acetone in, 142, 247 
 
 acids in, 16, 141, 142 
 
 albumen in, vide Albuminuria 
 
 alcoholic extract of, 55-57, 125, 267, 268 
 
 alkaloids in, vide Alkaloids 
 
 ammonia in, 115 
 
 and bile, toxic power of, 80, 84, 85, 224 
 
 and putrefactive products, 93 
 
 antagonism of the toxic powers of, 
 41-43, 62, 63, 122, 123, 239 
 
 aromatics of, 53 
 
 butyric acid in, 16 
 
 carbolic acid in, 16, 141, 142 
 
 charcoal acts on the, 54, 57, 98, 100, 125, 
 
 concentrated, toxic power of, 34, 48 
 
 convulsive, vide Convulsive 
 
 cresol in, 16, 142 
 
 decolorized, toxic power of, 86, 87 
 
 diabetic, 142, 245-248 
 
 excretion of, 103, 125 
 
 extractives of, uraemia due to, 107, 117- 
 
 119, 125 
 
 extracts of, 54-57, 78, 125, 267, 268 
 hydrogen sulphide in, 149 
 in diarrhoea, 132, 141, 142 
 indican in, 141, 142 
 intra-venous injections of, vide Injec- 
 
 tions 
 
 lactic acid in, 16 
 leucin in, 231 
 
 micro-organisms in the, 188, 243 
 minerals, their toxic power, vide Min- 
 
 erals and Toxic power 
 mixed, toxic power of, 42. 43 
 naphthalin acts on the, 99, 10 
 normal, toxic power of, 30 
 of acute yellow atrophy of liver, 232 
 of anaemia, 142. 247 
 of cholera, 112, 141,263 
 of constipation, 142 
 of day, and sleep, 41 
 
 is narcotic, 41 
 
 of dilated stomach. 142, 164, 165, 171, 247 
 of dyspepsia. 140-142, 246, 247 
 of evening, 36-40 
 of exercise, 43-45 
 of intestinal disease, 141, 142 
 
 obstruction, 142 
 
 ndice 
 e, 104 
 
 of leukaemia. 142, 238, 247 
 of morning. 36-43 
 of nerve-reactions, 6 
 of pyrexia, vide Convulsive 
 of sleep and day, 36-43 
 
 toxic power of, 36-43 
 of tetanus, 237, 238 
 of toxaemia, 140-142 
 Of typhoid, 92, 141, 142, 188, 192, 238, 247 
 
 ostructon, 142 
 of jaundice, vide Jaun 
 of lardaceous disease, 
 
 Urine, of uraemia, 66, 67, 108, 109, 111, 112, 
 114, 115, 238 
 
 origin of the toxic powers of, 69 
 
 oxalic acid in the, 16 
 
 pathological, 34, 237-241 
 
 peptones in, 164. 165 
 
 poisons in, 16, 141, 142 
 
 purgatives diminish toxic power, 132 
 
 septic, injections of, 26 
 
 skatol in, 12. 16 
 
 soda in, toxic power of, vide Toxic 
 power of soda 
 
 subcutaneous injection of, 25 
 
 sugar in the, 245 
 
 the antipyretic of, 63, 64, 117, 125 
 
 the diuretic of, 60, 61 
 
 the narcotic of, 62, 125 
 
 the seven toxic principles of, 60-65 
 
 the sialagogue of, 56, 57, 62, 125 
 
 total toxic power of, 125, 126 
 
 toxic power of, vide Toxic power 
 principles in, the seven, 60-65 
 
 ty rosin in, 231 
 
 urea the diuretic of, vide Diuretic 
 
 urochromes of, 10. 11, 119, 120, 125. 141, 
 142,232 
 
 watery extracts of, 54-56, 268 
 
 xanthm in, 231 
 Urochromes, intra-venous injection of, 53 
 
 of diabetes, 142, 247, 248 
 
 of dilated stomach, 142, 165, 247 
 
 of dyspepsia, 141, 142, 247 
 
 of leucocytbaemia, 142, 247 
 
 of pyrexia, 240 
 
 of toxaemia, 142 
 
 toxic power of, vide Toxic power 
 
 uraemia due to, 107, 119, 125 
 Urotoxic coefficient, the, 35, 47 
 Urticaria, a complication of hydatids, 162, 
 
 in dilated stomach, 162, 163, 171 
 toxic origin of, 162, 163 
 
 Valeric acid, in putrefactive products, 93 
 Variations in the toxicity of urine, 34-46, 48 
 Venesection, in anuria, 277 
 
 in uraemia, 133 
 Vertigo, in constipation, 145 
 
 in dilated stomach, 161 
 
 in dyspepsia, 140, 147 
 
 in toxaemia, 150 
 Vicarious functions, 19, 131 
 Vomiting, acid, 139 
 
 exhaustion due to, 103 
 
 in intestinal obstruction, 144 
 
 in toxaemia, 150 
 
 in uraemia, 108, 131 
 
 uraemic symptoms due to, 140 
 
 Water, disease due to, 10 
 
 intra-venous injections of, 27, 75, 76, 111 
 
 toxic power of, 10, 48, 75 
 Watery extracts, intra-venous injection 
 of, vide Injections 
 
 of choleraic urine, 268 
 
 of faeces. 94-96 
 
 of muscle, 79, 92, 93 
 
 of putrefactive products, 91-93, 96 
 
 of urine, 54-56, 58 
 
 Xanthin, in blood, 231 
 in urine, 231 
 of jaundice, 2S1 
 toxic power of, 119
 
 I 
 
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 (14)
 
 Date Due
 
 I! 
 
 A 000 498 886 
 
 QZUO 
 
 B752L 
 
 189U 
 
 Bouchard, Charles. 
 
 Lectures on auto-intoxication in 
 disease. 
 
 QZl*0 
 
 uchard, Charles. 
 
 Lectures on auto-intoxication in 
 Dsease. 
 
 MEDICAL SCIENCES LIBRARY 
 
 UNIVERSITY OF CALIFORNIA, IRVINE 
 
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