Lectures on auto-intoxication in disease, or, Self-poisoning of the individual

Lectures on auto-intoxication in disease, or, Self-poisoning of the individual

Digitized by the Internet Archive in 2011 with funding from Open Knowledge Commons and Harvard Medical School http://www.archive.org/details/lecturesonautoinOObouc


Professor or Pathology and Therapeutics; Member or the Academy of Medicine, and Physician to the Hospitals, Paris

Translated, with a Preface and New Chapters added


Professor of Physiology, Uniyersity of Durham; Physician to the Royal Infirmary, New castle-hpon-Tyne ; Formerly Examiner in Medicine, Royal College or Physicians, London


Philadelphia – F. A. DAVIS COMPANY, PUBLISHERS 1906


BY F. A. DAVIS COMPANY [Registered at Stationers’ Hall, London, Eng.]

Philadelphia, Pa., U. S. A.

The Medical Bulletin Printing House 1914-16 Cherry Street


In placing this revised translation of Professor Bouchard’s
“Lectures on Auto-intoxication in Disease” before my medical
brethren, I feel that I am performing a service useful to the
profession. No apology is required from me, unless it be for
the failures on my part to render fluently into English the mean-
ing of the French text.

For many months now I have been hoping that Professor
Bouchard would publish a new edition of this book. The de-
mands upon the time of this distinguished French savant, how-
ever, have been such that he does not feel equal to rewriting or
revising his original lectures at present. This is a loss to medical
science we all regret, for auto-intoxication is a subject particu-
larly his own. In giving to the profession a new edition of this
work I have tried, fully aware of my many inequalities as a sub-
stitute for Professor Bouchard to bring the subject of auto-toxis
up to date while yet retaining the rendering of the original

Bouchard deals, in his “Auto-Intoxication,” with subjects
of everyday interest to the medical practitioner. Many of the
facts therein alluded to can no longer be ignored. Putrefactive
processes in the intestinal canal and the development of physi-
logical and pathological alkaloids play an important part in
many disease processes until lately unknown or misunderstood.
These lectures may, therefore, be regarded as an inquiry into
the operation of poisons introduced from without or generated
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 indi-
viduals who are in the prime of life and in apparent good health,
and at the autopsy 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-
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 in consequence of these basic properties
and from their resemblance to vegetable alkaloids that ptomaines
are sometimes spoken of as putrefactive or vegetable alkaloids, —
the term leucomaines, or animal alkaloids, being reserved for
those basic substances resulting from tissue metabolism in the

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
detailed designation of them, — it is sufficient to state that not
all ptomaines are poisonous. Some are quite inert. Brieger
restricts the term ptomaine to the non-poisonous basic products,
while those that are poisonous he calls “toxins.” Ptomaines
contain nitrogen, and in this respect they resemble vegetable
alkaloids. Many of them contain oxygen, while in others this
is wanting.

The one invariable circumstance surrounding the develop-
ment 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
bacterium 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 characters of the micro-organisms
that have flourished upon it. Temperature exercises its own
peculiar influence. Some bacteria, too, require oxygen, while
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 differ from those produced under con-
ditions from which air is largely excluded. At all times they
are extremely subtle. Occurring as transition products in the
processes of putrefaction, ptomaines are to be regarded as “tem-
porary forms through which matter passes while it is being
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 played by 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
functional activity and multiplication of micro-organisms. Pas-
teur has isolated as many as seventeen microbes from the mouth.
Some of these dissolve albumin, gluten, and casein, while 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 fermenting
nature, — there must be produced substances of a highly complex
nature — alkaloids or ptomaines — which, when absorbed into the
system, 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 certain products formed within
the body as the result of microbial activity react upon the micro-
organisms themselves, thus limiting their longevity and dimin-
ishing their power for harm.

By this means man is rendered immune, and a defense is
raised in the human organism against disease. How far, speaking
generally, immunity is brought about by chemical or biological
methods it is difficult to say. Herter (“Lectures on Chemical
Pathology”) deals at considerable length with this important
subject. He considers that the chemical defenses of the body
are directed mainly against bacteria, bacterial toxins, and poi-
sons other than those toxins formed during digestion, during
metabolism, or introduced from without. The acidity of the
gastric juice, for example, is a means of defense against certain
micro-organisms; so, too, is the acidity of the urine. A much
more important defense against microbes is the bactericidal ac-
tion of the blood and lymph. This, according to Hankin, may
depend upon the alkalinity of these fluids, or it may be due to
the presence of proteids resembling enzymes derived from the
leucocytes. It is common experience that during acute infectious
fevers there is developed in the human body substances that
destroy bacteria or their toxins. During the early stages of pneu-
monia, for example, while the specific microbes or pneumococci
are multiplying the patient is often extremely ill and yet hardly
has the crisis been reached than, notwithstanding the continued
presence of these micro-organisms in the body as revealed in the
expectoration, or if the case has gone wrong in the discharge
from an empyema which has unfortunately formed, the patient
feels well and is little disturbed, although pneumococci are still
plentiful. This feeling of well-being must depend upon either the
pathogenic micro-organisms becoming destroyed by the bacterio-
lytic action of the blood or upon a neutralization of the products
formed by the pneumococci. It would appear that both bacterio-
lytic and antitoxic effects are capable of being produced. The
circulation of toxins in the blood is sooner or later followed by
the development of antitoxins. Ehrlich is of the opinion that
“toxins unite with the protoplasm of living cells much in the same
way as nutritive proteids become united to cells in the course of


normal assimilation, the term ‘haptophore group’ being applied
to the group of atoms by which either the toxin molecule or the
nutritive protrid molecule becomes attached to the receiving
group or ‘receptors’ of the cells. The resemblance between the
physiological assimilation of proteid and the union of cell re-
ceptors with toxins is illustrated by the fact that both nutritive
proteids and toxins are capable of inducing the formation of
‘anti-bodies’ which stand in a specific relation to the stimulating
agent. . . . The introduction of a toxin is followed by an
excessive production of receptors which are finally thrown off
into the circulation as unused ballast. The free circulating re-
ceptors are the antitoxin” (Herter, “Lectures on Chemical
Pathology,” page 11). The “side chain” theory of immunity
enunciated by Ehrlich seeks to explain the formation of anti-
toxin by a chemical affinity established between poisons and cer-
tain constituents of cells. Chemical compounds possess not only
a central group of atoms, but lateral groups as well, and it is
these that are more liable to be attacked by the toxin, the central
group perhaps not suffering at all. A close union is established
between the toxins and side chains of protoplasmic molecules
which may or may not interfere with the vitality of the cells.
On the other hand, the cells are stimulated to produce fresh “side
chains” which, becoming detached, circulate in the blood as anti-

As might be expected, there have been many objections raised
to this interesting “side chain” theory of Ehrlich. Metchnikoff
fails to see in the chemical theory any satisfactory explanation of
immunity. In the leucocytes and their phagocytic action is to
be found, according to him, those biological processes that create
immunity. There is much to support the contention, that it is
from healthy living cells and not from those that are diseased
or injured that antitoxins are formed, since there are normally
present in the blood of certain animals specific antitoxic bodies.

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 in the economy.
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. “Prom the normal intestinal mucus Babes has isolated
five species of bacteria, while an enormous number of micro-
organisms exist in the large intestine and faeces. All these or-
ganisms 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 certain
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 foetal 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
albuminous 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).

Metchnikoff has demonstrated that man is born free from
microbes. Their first implantation occurs in the act of parturi-
tion, for soon after birth the skin and mucous membrane become
infected with them either from the air or from the water with
which the infant is washed. As early as four hours after birth
bacteria have been found during warm weather in the intestinal
contents. Usually this is delayed until ten to seventeen hours
afterward. It is in the intestinal tract that microbic flora grow
most abundantly and it is observed that these vary with changes
of diet whether purely vegetable or animal. Their presence is
independent of food, for micrococci and bacilli have been found
in the meconium of infants before- any nourishment has been
taken. No sooner almost is a baby given his mother’s milk than
variations occur in the microbes of his intestine: the bacillus
bifidus appears. Cows’ milk also favors the development of this
micro-organism along with the colon bacillis, streptococci, staphy-


lococci, lactic acid bacilli, etc. According to Vignaland Suck-
dorf, an adult man passes daily in his faeces from 30,000,000,000
to 50,000,000,000 of bacteria. The harm these micro-organisms
do is through the products which they form and which, when
absorbed are toxic — e.g., indol and skatol. Although many of
the bowel micro-organisms in health are apparently harmless,
they can yet become extremely virulent when their surroundings
are altered, as is seen in accidental kinking of the intestine, in-
ternal strangulated hernia, or in a limited muco-enteritis.

Bouchard, in “Auto-intoxication,” clearly indicates that
man is constantly standing, as it were, on the brink of a prec-
ipice; 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 such excretory organs as the kid-
neys, 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.

Sir 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 microbes upon the
tissues. It is this fact which renders knowledge of the life-
history of bacteria so valuable to us, for, long after 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.

Scarcely a month passes without a death being reported and
traceable to a meal of tainted meat. Sir Thomas Stevenson, of
Guy’s Hospital, has recently demonstrated the far-reaching and
fatal consequences of such a diet. I myself have reported in the
Lancet a case of acute peripheral neuritis, ending in rapid death,
and due, in all probability, to certain viands consumed at a par-
ticular banquet. The cooking of meat tainted by microbes, while
it is destructive to the organisms, may yet allow the ferments


they have formed to carry on their work of decomposition. It
is thus that the cold meat or beef-steak pie which forms the prin-
cipal part of a Monday dinner, though eaten with impunity when
hot on the previous day, becomes a source of danger. Of this I
had a striking illustration a few years ago, in the Industrial
Schools of this city, to which I happen to be honorary physician.
A certain Sunday 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 dinner — although placed under the same
dietetic conditions, except as regards that one particular meal —
alone escaped. It is to subjects such as these that Bouchard
draws special attention, and of which I might still further write.

An almost similar event happened in a Northumberland
village just before going to press. I was summoned to see a
family, four of whom were extremely ill through having eaten
fish recooked in the form of pie. Fresh cod, apparently healthy,
had formed part of the menu for the early dinner. The re-
mainder was served up as pie the same evening. The husband
and wife and two grown-up daughters who had eaten the pie at
supper were seized during the night with vomiting and purging,
followed by extreme collapse, cold perspiration, irregularity of
the heart’s action, and feeble pulse. Only in the case of the
husband did the temperature rise slightly above the normal. He
also had severe headache. The symptoms of collapse were pro-
nounced in all the patients. As only those inmates of the house
suffered who had eaten the fish pie, clearly some chemical change
had occurred in the cod between midday and evening. These
cases resemble those described by Professor Bouchard on page

Setting aside the chapters on the “Toxicity of Urines,”
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 sur-
mounted, there are risks yet to be overcome — 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 success which has followed the administration of intes-
tinal antiseptics in enteric fever. In my own practice I have
used betanaphthol 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 ; he
had an almost imperceptible pulse, a temperature of 105° to
106° F., was almost in extremis, and whose life I consider was
saved by betanaphthol and other intestinal antiseptics. We know
that naphthalin is sparingly soluble, and that it passes to a
large extent unchanged through the alimentary canal. No one
denies to it the power of destroying the disagreeable odor of
the motions. Salol, or the salicylate of phenol, has also given
excellent results. Having passed through the stomach undecom-
posed, it comes into contact with the pancreatic juice in the duo-
denum, 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 sali-
cylate of betanaphthol is to be recommended instead. All the
substances belonging to the phenol class may be regarded as anti-
septics 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 compounds,
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 certain diseases
in which the blood is poisoned — e.g., ulcerative endocarditis, etc.
— has led me to place considerable reliance upon phenols. When
absorbed they no longer exercise a direct action upon the germs,
but they exert another influence, viz. : a depoisoning one. Seifert


and Hoelscher maintain that when the phenols are absorbed they
induce a depoisoning of the body by combining with and elimi-
nating the toxic albumins produced by the action of morbific
germs. Phenols are not found free in the blood. They are elimi-
nated in the urine as ethereal sulphates, in the form of salts that
have resulted from the oxidation of some compound of the phe-
nols with albumin, and, to a large extent, with toxic albumins,
the result of the vital activity of germs. It is believed that the
compounds of toxic albumins and phenols are non-toxic. They
quickly undergo oxidation; hence the appearance of phenols in
the urine as ethereal sulphates. Chemical disintegrations and
recombinations undoubtedly occur, and to these must be at-
tributed, by the process of depoisoning just described, the good
results that follow the administration of antiseptics in certain
forms of blood-poisoning. Under circumstances similar to the
above rigid intestinal antisepsis cannot but be of the greatest

Salols pass through the stomach without undergoing de-
composition. In the small intestine salols and phenols are split
up into their antiseptic constituents: salol into salicylic and
carbolic acids, betol into salicylic acid and betanaphthol, while
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 MedHcal Week, August 11, 1893,
there is a lengthy report upon the subject as discussed, at the
French Congress of Psychological Medicine, by Drs. Eegis,
Chevalier-Lavaure, and others. It has long been known that the
various fluids of the body undergo modifications in the insane.
Eecent investigation has shown that the urine is much less toxic
than normal urine in cases of mania, while the lethal action of
this fluid is increased in melancholia. The urine of maniacal
patients gives rise to excitement and convulsions when injected
into an animal, while the injection of urine from a case of mel-
ancholia 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 many of these disturbances are due to the
action of pathogenic organisms directly, or indirectly through
the influence of their toxins; according to the stage of the
illness, so is the character of the mental symptoms. By no
physicians more than those resident in lunatic asylums has the
subject of autotoxis been so carefully studied. The adminis-
tration of a large dose of calomel, followed hours afterward
by a saline purge will often clear a patient’s mind as well
as relieve his body during the delirium of acute mania. Toward
the terminal stages of chronic interstitial nephritis and dia-
betes, etc., psychoses of an hallucinatory nature are not un-
known. They are due to impaired cerebral nutrition or to the
circulation of some form of nerve poison in the blood consequent
upon defective elimination. To imperfect emunction is attrib-
uted the disagreeable odor so frequently observed in the insane.
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 theemunctories.

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. 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 trans-
lating and publishing this work.

In this (second) edition the new matter interposed in the
text by the editor, and for which he alone is responsible, is in-
closed in brackets [].

Thomas Oliver.
7 Ellison Place, Newcastle-upon-Tyne.



Lecture I. Pathogenic Processes in the Main 1

Lecture II. Production and Elimination of Poisons by the

Organism 15

Lecture III. Preliminaries to the Experimental Study of the

Toxicity of the Products of Emunction 24

Lecture IV. On the Toxicity of Urines 31

Lecture V. Causes of the Toxicity of Urine 47

Lecture VI. Toxic Principles in Urine — The Part They Play in

Producing Uraemia 60

Lecture VII. Origin of the Toxic Substances of Urine — Toxicity

of the Blood and Tissues 70

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 ) 84

Lecture IX. Origin of the Toxic Substances of Urine — Toxicity of

the Products of Putrefaction and of the Fasces 91

Lecture X. Intestinal Antisepsis 102

Lecture XL Pathogenesis of Uraemia — Distinction Between the
Symptoms of the Pre-Uraemic Period of Nephritis and the
Symptoms of Intoxication 107

Lecture XII. Pathogenesis of Uraemia — Discussion of the Ex-
clusive Theories 113

Lecture XIII. Pathogenesis of Uraemia — Discussion of the Ex-
clusive Theories 119

Lecture XIV. Pathogenesis of Uraemia — The Part Played by
Organic Substances and Mineral Matters in Uraemic Intoxica-
tion 125

Lecture XV. The Therapeutic Pathogenesis of Uraemia 132




Lecture XVI. Transitory or Acute Auto-Intoxication of Intes-
tinal Origin — Internal Strangulation and Constipation 143

Lecture XVII. Acute or Transitory Intestinal Auto-Intoxication

— Gastric Disorders — Indigestion — Poisoning by Tainted Meats. 153

Lecture XVIII. Chronic Gastrointestinal Auto-Intoxications —

Dilatation of the Stomach 162

Lecture XIX. Dilatation of the Stomach — Etiology, Pathogenesis,

and Therapeusis 184

Lecture XX. Auto-Intoxication of Intestinal Origin — Typhoid

Fever. 198

Lecture XXI. Pathogenic Therapeusis of Typhoid Fever — Anti-
sepsis of the Internal Medium 205

Lecture XXII. On the Pathogenic Therapeutics of Typhoid Fever

— The Treatment of High Temperature 212

Lecture XXIII. Pathogenic Therapeutics of Typhoid Fever — New

Mode of Bathing in Fevers; Dieting of Fever Patients 219

Lecture XXIV. Auto-Intoxication by Bile. Pathogenesis of

Jaundice 233

Lecture XXV. Malignant Jaundice : Aggravated Jaundice 240 ‘

Lecture XXVI. The Toxic Nature of Pathological Urines 247

Lecture XXVII. Pyocyanic Disease. Poisoning Accidents in

Diabetes 253

Lecture XXVIII. Poisoning by Pathological Poisons. Cholera…. 260

Lecture XXIX. Cholera (Continued) 268

Lecture XXX. Cholera (Conclusion) 276

Lecture XXXI. The General Therapeutics of Self-Poisoning 286

Lecture XXXII. General Recapitulation 293

Chapter I. Natural Defenses of the Organism Against Disease. . . . 305
Chapter II. Auto-Intoxication of Intestinal Origin 315

Index 329

Lectures on Auto-Intoxication.


Pathogenic Peocesses in the Main.

Preponderance of pathogenesis in 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 num-
ber 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 in the processes of infection.

Five hypotheses relative to the mode of action of pathogenic microbes.
Toxaemia of pregnancy. The r61e of microbes in the formation of certain
poisons normal to the organism.


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 any sense of the word, revived, but that she has simply
changed her attitude of observation.

After having devoted herself during many long years to the
verification of s} r mptoms, 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.

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,
and is directly brought under our notice by some cause, physical,
mechanical, or chemical; from the lightning-stroke to the in-
toxications, or by traumatism. If one neglects more than is
necessary the study of that simple process, it is because very
often it is complicated with effects of a local character, vascular
or otherwise, which are the reflex result of nervous 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 oppor-

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 centers 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
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 proc-
esses by which we can undertake the cure of diathetic diseases.
-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 [now
passed] century. It is what we call, or it is what, now particu-
larly, deserves to be called, conlagium 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
systems relative to contagion.


Demonstration has not been made for all contagious dis-
eases; 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 posi-
tive manner the solution has been universally agreed upon.
Contagion has always been recognized as the function of a vege-
table 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

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 con-
tagious 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 aston-
ishment the announcement of its discovery, and without un-
easiness the delays which might be caused by that demonstra-
tion. Let men trained to the difficulties and to the refinements
of microbiological research give us this fulfillment of demon-
stration, and it will be with thanks that we will praise every
one of their discoveries. The role of the physician is not exclu-
sively 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 eminently practical question : What are the conditions
which render possible the development of the microbe? What
are the conditions which may 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 developing
matter, and yet infection is uncommon. Infectious disease, too,
is only an accident, because the morbid agent finds only excep-
tional circumstances favorable, — I do not say to its penetration,
but to its development and its multiplication.

The healthy man is not attractive to the microbe. While
almost constantly invaded by infectious agents, he reacts against
them, and in this contest he keeps generally uppermost so that
often the disease does not even become apparent.

It is not thus with the man whose vitality is weakened;
then his means of defense diminish. Just as we see rushes be-
come covered with soil where certain unusual circumstances are
opposed to the natural flow of water, so certain microbes may
invade the human organism, whose health breaks down, when-
ever, by the fact of disordered nutrition, the chemical constitu-
tion is modified.

It is, therefore, a modification antecedent to nutrition which
renders infection possible. Disease is thus the result of two
different processes, one of which can only act by means of the
other. In short, pathogenic processes are rarely 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 traumatism will deter-
mine the putting into operation of new pathogenic processes,


infection, and nerve reactions. Disorganization of cells allows
the entrance of infections agents, and prepares in them the
matter 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 irritation 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

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 everyone, will you say ? Perhaps ; but especially
in those whose health is habitually or actually altered. Among
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
nondiathetic 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
transitory, — “it is the morbid opportunity,” 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.

Very often disease induced by nerve reflex — even disease
from cold — is an infectious illness, and we have not only 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 only by rendering this infection possible ;
by weakening the defense 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 fulfill in nature another part, but
which, destined to destroy dead matter, are also capable of de-
stroying 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 opportunity, it may also modify nutri-
tion 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 had 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 hy-
gienic errors, by the abuse of the table, by protracted studies
at night, by venereal excesses, by 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 type. And among these cells the
generative elements — ovule or spermatozoon — in their turn will
give birth to the cells of a new being, whose nutritive activity
will be similar to the individual that has begotten them. The
acquired diathesis has become hereditary; it does not recognize
for its cause in the descendants the vice of their own nerve re-
actions. In these, nevertheless, the diathetic state really arises
from nerve perturbations experienced by their ancestors. There
are certain historical families whose pathological genealogy we
ever 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 exam-
ple 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
injury. Disease thus called forth in the course of a diathesis is
an episode, a paroxysmal accident; but this accident, this epi-
sode, may appear spontaneously, as the consequence of the excess
of the nutritive disorder which oftenest recognizes as its deter-
mining 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 accident in the course
of a diathesis, is characterized by an acceleration 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 among arthritics that you see


developed by preference pityriasis versicolor? Is it not among
the scrofulous that you see erysipelas repeated with a truly dis-
heartening frequency? I have multiplied examples sufficiently
to be able to say that, without any preliminary change in nutri-
tion, 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, they 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 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 many 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 defense, inspiring himself constantly
with this truth : before every illness there is a disturbance in
life, — for nutrition is life. What can bring about this disturb-
ance, — the first step to be overcome before becoming ill ? It may
bring about a change in the production or distribution of the
forces which liberate certain substances elaborated by the living
organism. It may modify the matter itself, — augment or di-
minish it, — while preserving the normal proportion, or it may
bring about disproportion of the constituent elements; it may,
in short, cause the appearance of abnormal substances through
perversion of the changes associated with nutrition. From abso-


lute increase of normal matter, or the production of abnormal,
intoxication may be developed.

Substances the most essential to the constitution of the
body may become hurtful when they accumulate. If the sub-
traction 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 dialyzable material; it thus dis-
turbs their chemical constitution, and weakens or perverts their
functional activity. Mineral substances can, by their excess,
equally determine accidents that are truly toxic, — the salts of
potassium particularly. The most important excrementitious
material — carbonic acid — could not be retained in excess 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 exercise a poisonous influence, either local or
general. We find even in certain secretions — in saliva, for ex-
ample — products extremely 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 multiplying examples, you see that the augmentation of
normal substances, 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, uricasmia, cho-
lsernia, glycgemia.

Perverted nutrition leads up to the development of new sub-
stances which may become toxic. There are often formed in the
organism peptones, which are injurious in this sense, that, being
dialyzable, they escape by the urine, and thus bring about an
abnormal spoliation of the organism. There are thus produced
abnormal albumins, which escape by the kidneys, and seem
capable of destroying the nutrition of the renal epithelium and
of inducing certain forms of nephritis. Disease also causes the


appearance of abnormal coloring matter or of substances trans-
formable into coloring matter, among which are found those
that, in urines, take on a red coloration under the influence of
perchloride of iron — e.g., acetone. I also mention leucin, tyrosin,
and the imperfect excrementitious products which arise from
insufficient elaboration on the part of the liver ; many other toxic
substances, too, of which I know neither the names nor the
constitution, but whose presence in morbid urines I shall dem-
onstrate to you physiologically. All these substances are capable
of producing forms of intoxication, among which I will mention
eclampsia, acholia, diabetic coma, and many other grave con-
ditions, as also numerous indispositions.

[During pregnancy poisons are formed in the mother and
foetus which circulate in the maternal and foetal blood. Upon
the mother is thrown the burden of eliminating by the kidneys,
liver, intestine, skin, and lungs the bulk of the poison formed
within the two organisms. When these poisons are retained auto-
intoxication is produced which varies in degree from heighten-
ing of the arterial tension, headache, gastric disturbance, and
lassitude to convulsive seizures as in puerperal eclampsia. The
urine under these circumstances usually contains albumin. That
errors of diet often induce puerperal eclampsia there is no doubt.
I have seen pregnancy advance normally until some such im-
proper food as lobster, pork pie, etc., was eaten ravenously, when
as the result of the entrance into the blood of imperfectly di-
gested products or intestinal poisons eclampsia followed. The
presence of these toxins in the blood induces structural alterations
in the renal epithelia and as a consequence renal debris, tube
casts, are present in the urine along with albumin. If the
patient lives, the morbid changes are, for the most part, tem-
porary, for they disappear on cessation of the pregnancy. We
are familiar with the dropsical legs of women seen near the end
of pregnancy, but it occasionally happens that there is in addi-
tion to the auto-intoxication from intestines and kidneys, an
hepatic toxaemia as well. The liver becomes enlarged and tender,
the patient slightly icteric, the stools pale, fluid appears in the
abdominal cavity, and there are albumin and bile in the urine.
It is not until the pregnancy has been brought to a natural or an


artificial termination that the symptoms and physical signs dis-
appear. In such a case the liver has failed to arrest and destroy
the intestinal poisons as they pass through it and the result is
that owing to their excess in the blood and inability on the part
of the kidneys to eliminate them the patient is poisoned by
products formed within her own body.]

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 physiology 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 particularly those of
the lung and the kidney. The fact is perfectly demonstrated for
charbon and for the septicemia of Charrin; but the microbes
which live in the blood are rare — almost the exception. It is
also admitted that they may induce traumatic changes, — erode
and perforate cells. This is an hypothesis whose aid I called in
when I established the group of infectious nephritides. We
find microbes in the organism, — in urine, — and there is perhaps
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 microbes attack muscular fiber; in certain
catarrhs of the bladder and vagina they penetrate in large num-
bers the epithelial cells. I have demonstrated in blennorrhagia
that the micrococcus of ISTeisser inhabits essentially the proto-
plasm 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 among them
some which produce oedema, haemorrhage, suppuration, emphy-
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.

A fourth hypothesis has been enunciated, viz. : that the mi-
crobe, in order to nourish itself, consumes what is useful, and
it is the subtraction of this which is prejudicial to the organism.
The example of charbon has been quoted in support of this con-
tention; 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.

Last, 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 dem-
onstrated, indol, phenol, skatol, etc.; all can poison, for these
bodies are toxic. They form besides, 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 harmful 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
microscopical vegetable organisms. I have formerly shown you
the toxicity of intestinal matter ; it is in part due to the poison-
ous 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 in-
creasing abnormally, the accumulation of toxic matter may be-
come such that absorption produces intoxication in spite of the
integrity of the renal emunctory; it is to this cause that many
dyspeptic accidents should be referred. Thus, in the normal as
well as in the pathological 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.

Production and Elimination of Poisons by the Organism.

The healthy organism receives and forms poisons. Constant danger ol 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 putre-
factions; 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 demonstra-
tion: we find in the urine, naturally or modified, the same poisons as in
the digestive canal and in the tissues; they must, therefore, have traversed

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 capil-
laries (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 Schiff.

Role of the emunctory organs in the expulsion of poisons. Intestinal
emunction: the putrid diarrhoea of anatomists; salutary diarrhoeas. Illusions
relative to diarrhoea spoken of as supplementary to the renal emunction.
Cutaneous emunction: elimination of water; perspiration favorable to elim-
ination 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 kid-
ney can eliminate all toxic products except gas. Toxicity of urine: danger of
oliguria: critical polyuria at the decline of fevers. Toxicity of sweat.

I have said that the organism, in its normal, as in its
pathological state, is a receptacle and a laboratory of poisons.
Among these some are formed by the organism itself, others by
microbes, — minute 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 always 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 re-
sources which enable him to escape the intoxication which is
always threatening. He throws off these toxic substances into a
special reservoir, from which they afterward pass outward ; and,



besides, the blood contantly subtracts from the organs the poisons
as soon as they 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, while it transforms
albuminoid substances into peptones, also give birth to alka-
loidal poisons; and, last, 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. They pass out into
the extracellular 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 G-autier,
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 chloro-
form, alkaloids from 50 cubic centimeters of muscle of beef. These
alkaloids, soluble in chloroform, give precise reactions with the fol-
lowing reagents: Tanret’s solution, iodized iodine, phosphomolybdate
of soda and tannin. September 3, 1884, a healthy rabbit is killed, then
cut up into pieces; it weighs thus minced, without the abdominal vis-
cera, 1012 grams. It is digested in 2 liters of absolute alcohol, to which
has been added water acidulated with H 2 S0 4 , and this mascerates 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 centimeters. We evap-
orate 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 precipitates obtained are
abundant with the following reagents: Tanret, iodized iodine, phospho-
molybdate of soda, ferric cyanide, double iodide of potassium and
cadium. This residue, made alkaline by soda, is mixed well with ether.
We decant the ether, which, shaken up well with a little HO that has
been added to it, is distilled. The residue is an ethereal extract. It
is precipitated fairly well by means of the iodized iodine and molybdo-
phospate 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 neces-
sary 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 sulphophenic acid, or
phenyl-sulphurous ; bodies of the aromatic series, — indol, skatol,
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. Among 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
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 which carries them
there. One of the first authors occupied in the experimental
investigation of these intoxications (Stich) 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 dialyzer,
through the epithelial cells and through the walls of the capil-
laries. 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, while 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 destroying of itself the poisonous sub-
stances which it forms. This is a view of the matter of which we
have no demonstration.

According to Hoffmeister, the leucocytes play a part in the
transformation of peptones into albumin, since we no longer find
in the emunctories the peptones which we have injected into the
blood. We could, perhaps, apply this hypothesis of Hoffmeister
to the destruction of poisons, and say that the toxic substances
coming from the intestinal canal are neutralized in the blood by
the leucocytes. 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, cer-
tain portions of our food ; it impedes the passage of grape-sugar
and stores up glucose under the form of glycogen. It pla} r s also
a protective part in arresting alkaloidal substances. Heeger has
injected into the portal vein blood containing alkaloids (nicotine,
strychnine, morphine, 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.

Schiff has revived the question. He operates with nicotine.
The same dose of this substance which, introduced into a periph-
eral 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 intoxicated by
it. The same dose poisons the animal if we have ligatured its
portal vein, for then the toxic substance reaches the general cir-


culation 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 arrest-
ing these poisons; it destroys them. These facts have been
experimentally verified in my laboratory by C. H. Eoger, 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 alkaloids are not the
most poisonous substances of the organism. This explanation is
right as regards them, but is not applicable to all; it is neces-
sary to add to it this other piece of information, — that man
escapes intoxication by the activity of the intestinal, cutaneous,
pulmonary, and renal emunctories.

The part played by the intestinal emunctory in the elimina-
tion of certain poisonous substances is attested by the commonly
fetid stools of persons who frequent the postmortem theater.
Their fetid character recalls the putrid odor of the emanations
from the cadavera. 1 Sometimes this emunction is defective, for,
if the largest part of the toxic material is thus expelled, yet
some is absorbed ; there is a defective circle for certain molecules
of poisons. We find in the intestine toxic substances arising from
the disassimilation of such organic matter as taurocholic and
glycocholic acids, or their derivatives, cholic and cholalic acids,
and dyslysin, a body formed by the liver, afterward transformed
in the intestine. We find mineral salts formed out of bile or
secreted by the intestinal glands themselves. The intestine also
contains gases which are not all formed there; there are indi-
viduals 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 fermenta-
tion. We find hydrocarbons, sure enough; nitrogen probably;

1 1 have known medical men and students who could not attend
an autopsy in the postmortem theater of an infirmary without suf-
fering from diarrhoea. — T. 0.


perhaps carbonic acid, and even oxygen, 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 retaining the
appearance of perfect health, have seen their diarrhoea and their
health disappear at one and the same time. We may derive from
these facts some encouragement in inducing diarrhoea in certain
cases, without, however, raising exaggerated hopes in anyone, the
subject of a supplementary diarrhoea, of his being able to com-
pensate the insufficiency 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 secretions we remove a con-
siderable 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 gram of urea
for 1000 grams of water, the urine carries away 15 grams of
urea for every 1000. The sweat will only carry away 0.15 gram
for every 1000, exactly the proportion which is found, not in the
blood, but in the liquor sanguinis. Then 1 kilogram 1 of water,
which by the renal channel would have carried away 15 grams
of urea, only carries away 30 centigrams by the skin and the
intestine. One emunctory can scarcely vicariate for another.

By the skin are eliminated water, salts in small quantity,
carbonic acid, and some volatile fatty acids. Copious perspira-

1 1 Kilogram = 1000 grams = 15432.4 grains = about 2 lbs. 3 1 / i oz.

500 grams = 7716.2 grains = about 1 lb. 1 B /s oz.

100 grams = 1543.2 grains = about 3 1 / 2 oz.

25 grams = 385.8 grains = about Vs oz.

5 grams = 77.2 grains — about Ve oz.
1 gram or ~|
1000 milligrams / = 15 ” 4 S rama


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 in 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 perspiration in the cure of these morbid
states is the odor which the skin assumes under the influence
of certain disorders of nutrition. Among hypochondriacs — the
alienated, living in absolute inactivity, and with defective ali-
mentation — 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. [So
marked is the odor that, since it clings to newly washed clothes,
laundresses can name the patients to whom the clothes belong by
their peculiar smell.] 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 varnish 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
hematuria, 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 grams in
twenty-four hours), water, ammonia sometimes, and often vola-
tile 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 incom-
plete destruction of matter. By the lungs, too, are eliminated


poisonous substances scarcely known, to which du Bois-Eeymond
has drawn attention, especially the volatile poisons accidentally
introduced into the digestive canal (alcohols, ethers, chloroform,
asafcetida) .

But of all the organs of elimination the most important is
the kidney. One cannot, as in the case of the intestine, reproach
it with being a defective emunctory, capable of reabsorbing 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, in-
toxication, it is true, shows itself; it is then a complex thing,
resulting not only from the reabsorption 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 alto-
gether, is toxic. We have always regarded oliguria as a serious
thing, whereas, on the contrary, at the declination of fevers a
critical polyuria is nearly always useful, because it expels poison-
ous substances formed by the economy during the illness. There
may arise unpleasant symptoms, according to the relative im-
permeability of the kidney for certain substances.

[Beyond regulating the temperature of the body, and there-
fore acting in a purely physical manner, we know little of the
chemical composition of perspiration. The question has sometimes
been asked to what extent is sweat toxic ? Bohrig and Aquierolo
believes that it has very few toxic properties, while Arloing is of
opinion that the injection of 15 to 30 cubic centimeters of sweat
will kill an ordinary sized rabbit. Mavrojanis, who carried out
a series of experiments, found that the toxicity of sweat varied
according to muscular exertion and the amount and character
of the liquids taken, but that under all circumstances it had a


feeble toxicity. It required, on an average, 110 to 140 cubic
centimeters for every 55 to 75 kilograms of living tissue. Death
was never immediate; it never occurred until from twelve to
thirty hours after the injection. The principal effects observed
were a fall of temperature and hemoglobinuria. Cabitto in-
jected the perspiration of epileptics after convulsive attacks and
found that it killed animals in doses of from 15 to 20 cubic
centimeters. During the course of certain infectious diseases,
notably small-pox, Quierolo noticed that the toxicity of sweat
increased. This, too, occurred in malaria. As regards perspira-
tion, there is always the probability that the discharge contains
numerous microbes the influence of which must not be under-
rated when this liquid is injected into animals. Perspiration
contains from 990 to 995 parts of water per 1000 and urine
from 956 to 9G0. Charrin (“Les Defenses Naturelles de l’Or-
ganisms”) remarks that, while fatal accidents are induced after
injecting from 40 to 50 cubic centimeters of urine per kilogram
of animal, it requires 70 of sweat, and even with this quantity
death does not occur until several hours afterward. A liter of
liquid leaving the human body by the kidneys carries an amount
of poison capable of killing 20,000 grams of living matter, while
the same quantity of liquid escaping by the skin only destroys,
and that slowly, 14,000 grams.]


Preliminaries to the Experimental Study of the Toxicity
op 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 in-
troducing into the organism substances the toxicity of which he wishes to
study. Introduction by the digestive canal and subcutaneous injection
inconvenient. Advantages of intravenous injection. Its harmlessness; its
facility. Uniformity of the results obtained. Study of the action conse-
quent upon the liquids employed to serve as excipients 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
escapes by various means, thanks to the part played by the liver,
which forms an active barrier to poisons absorbed from the di-
gestive canal, but is insufficient for those formed in the tissues, — ■
thanks especially to the safeguard which is established through
the emunctory apparatus. In order that intoxication may be
avoided, it is necessary 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 intoxication, —
I seem to be formulating a syllogism which is indisputable. Yet
it is only a sophism, however, for asphyxia is a complicated thing,
and if intoxication from excess of carbonic acid is one of its
factors want of oxygen is another. There is, then, no fact so
reasonable as that which requires demonstration. Consequently,
we ought to prove that the retention of substances destined to be


eliminated by the errmnctories is capable of producing intoxica-
tion 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 elimi-
nated in twenty-four hours by all the emunctories combined,—
and what enables us to determine 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, among emunctories whose failure to functionate can
contribute to intoxication of the organism the lung is beyond
all dispute : without counting the other toxic substances it elimi-
nates, 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 embarrassing, on account of the small quantity of products
secreted and of the difficulty which we have of collecting them.
It is, therefore, from the urinary tract that we will seek for the
demonstration 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
materials 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 quantity of that which
we have introduced has been absorbed ? Besides, absorption from
the intestinal canal is very slow, and the organism has time to
protect itself by eliminating the poison. M. Morel-Lavallee has
communicated to the Clinical Society the following fact: In a
patient who had ingested 60 grams of laudanum from 2 o’clock
in the morning to 8 o’clock in the morning, washing out of the
stomach removed 45 grams 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 sub-
stances inoffensive which 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, while emunc-
tion is rapid. It is, therefore, difficult to form an exact apprecia-
tion 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 albuminuria; the injection of 4 cubic centi-
meters of water by the subcutaneous method in the case of a
rabbit induced this phenomenon.

There remains the intravenous 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
complete 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 intravenous channels and subcutaneously. When
this is introduced directly into the blood glycosuria shows itself
three minutes after the beginning of the injection.


On the 11th of December, 1S84, into a rabbit weighing 1G45 grams
we injected into the veins 133 cubic centimeters of urine containing
traces of albumin and 60 grams of sugar to the liter. The urine is
filtered and neutralized. The quantity of urine injected represents 4.85
grams of sugar for each kilogram of the animal and 63.05 grams for
each kilogram of blood. At the 33d cubic centimeter, emission of urine
already rich in sugar. Toward the 71st cubic centimeter, fresh emis-


sion 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 albumin.

December 23d. The animal is quite well.

The same quantity introduced by the cellular tissue does not
produ&e glycosuria, because absorption is so slow that the blood
destroys the sugar as it is absorbed, without giving it time to
reach the kidney.


Sixty-five cubic centimeters of the same urine are injected into
the cellular tissue of a rabbit weighing 1750 grams, — about, there-
fore, 2.2 grams of sugar for each kilogram of the animal. After the in-
jection 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 suppuration nor gan-
grene, but a reddish liquid, full of mobile organisms, round, very small,
which one also finds in the liver, and which appear also to exist in the

The intravenous method is the less harmful, much as this
may appear paradoxical. One hundred grams of fluid injected
into the blood are not followed by any accident. The same quan-
tity of this fluid, purified, or even previously raised to a tem-
perature 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 infective 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
opalescent by the presence of bacteria, there may result from this
no accident, or albuminuria at the most.



November 8, 1884. Urine of a patient the subject of arterio-
sclerosis. Quantity passed in twenty-four hours, 850 grams. This urine
is albuminous; it contains moving microbes, in the form of rods, short
and numerous enough. Neutralized, and slightly alkalinized and fil-
tered, it is injected into the veins of a rabbit weighing 15S0 grams.
The quantity injected is 135 cubic centimeters in eleven minutes, —
about 86 for each kilogram of the animal. The temperature of the rab-
bit before the injection was 40° C. (104° F.). It falls to 37.2° C.
(99° F.) immediately after. Myosia shows itself slowly: it only ap-
pears toward the 80th cubic centimeter. 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 perceptible. 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 calories = 3539 calories.

The urine has absorbed 12.2 X 0.135 calories = 1647 calories.

The rabbit, therefore, has made less by 1892 calories.

November 10th. The animal has traces of albumin.
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
millions of certain bacteria without the organism being the least
disturbed by it. 1

1 Watson Cheyne, in his “Lectures on Suppuration,” delivered at
the Royal College of Surgeons, London, February, 1888, has shown how
the disease which is experimentally produced stands related to the
number of micro-organisms injected. Taking cultivations of proteus
vulgaris, for example, he found that V 10 cubic centimeter of an undi-
luted 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 extensive 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


The process of intravenous injection is applicable to every-
thing that is soluble except oxygen. Nevertheless, it has been
proposed at the Academy of Sciences to make intravenous 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. Intravenous 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 centimeters of it for each kilogram of the
animal, — say, for 100 grams of blood 117 of water. Death en-
sues with 122 cubic centimeters for each kilogram of the animal;
that is, 157 grams of water to 100 of blood. Absolute alcohol is
toxic beyond 0.6 cubic centimeter for each kilogram of the
animal. The clot which it produces immediately redissolves in
the blood coming from other veins, and there arises no embolus
from it. The more alcohol is diluted, the more we can inject
of it. The degree of dilution the most favorable is 20 grams
for each 100 by volume, — 20 cubic centimeters of absolute alco-
hol for 80 cubic centimeters of water; 1.45 cubic centimeters
of absolute alcohol carried to this degree of dilution produce

septicaemia; the injection of a single bacillus has induced death, while
4 cubic centimeters 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 staphylococcus
pyogenes aureus, Cheyne showed (Brit. Med. Journal, March 10, 188S)
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 circumscribed abscess. — T. O.


narcosis and coma; 3 cubic centimeters kill. For each 100
grams of blood it is, then, necessary to take 2 cubic centimeters
of alcohol to produce narcosis and 3.9 cubic centimeters to bring
about death.

Glycerin is less toxic than alcohol. We cannot employ pure
glycerin; it produces viscid emboli. We must prefer dilution
of it to 50 for each 100. We establish that 5 cubic centimeters
of anhydrous glycerin for each kilogram of the animal produce
muscular tremors, and that 14 cubic centimeters induce death,
with immediate cadaveric rigidity. We know, then, for the
future, that the substance whose toxic power we wish to test by
intravenous injection ought not to be dissolved in more than 90
cubic centimeters of water, — in more than 1.45 cubic centime-
ters of alcohol, diluted in the proportion of 20 to each 100, or
5 cubic centimeters of glycerin, diluted in the proportion of 50
to 100 for each kilogram of the animal.

On the Toxicity of Urines.

Admitted from all time by physician!?, the toxicity of urine has only recently

been demonstrated. CI. 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: Muron. Positive conclusion: Feltz and Ritter, Bocchi and Schiffer.

Study of certain pathological urines: Lepine, Dupard, and Gue>in. My

own experiments upon the toxicity of normal urine injected en masse by
intravenous channel. Reply to certain objections raised against this method.

Choice of the rabbit as the animal to exhibit reactions. Physiological

phenomena consequent upon the intravenous injection of normal urine, —
myosis, accelerated respiration, torpor, polyuria, fall of temperature due to
diminished heat production; survival or death, according to the dose in-
jected. Discussion upon the possible causes of death. Determination of
the unity of toxicity. Urotoxy. Urotoxic coefficient. Toxicity of urines dif-
ferent 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 recognized the
necessity of verifying experimentally this view of the matter,
reasonable as it appears to us. From among possible demonstra-
tions we have chosen that which consists in proving that the
emunctories really cast out externally toxic substances and that
the excrementitous 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 intravenous in-
jection as the experimental method.

Are urines toxic? To this question we have at all times
replied in the affirmative, — so much so that there is no necessity
to raise the question again. Upon this undebated point has been
built the theory of urasmia. Urine is toxic : thus, when it ceases
to be secreted the organism is poisoned. We may say that this
is a true medical opinion of the matter; but, true as it appears



to be, it claims demonstration. CI. Bernard raised the question ;
Frerichs has followed it up. Physicians and physiologists 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 ques-
tion, but certain substances which we find in it or which are
developed in it in consequence of catalytic changes, — carbonate
of ammonia, for example. It is the study of certain toxic sub-
stances of the urine which we have at length broached, and not
that of the toxicity of urine in kind. We have blamed the color-
ing matter, odorous and volatile, also mineral matters, — potass.
in particular. These are, without doubt, toxic; but they con-
stitute 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 atro-
pine. 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 ap-
proach the solution of the problem.

The question, taken in its entirety, dates from 1868. 1
Muron, having made subcutaneous injections of urine, affirms
the nontoxicity of it; but the method which he adopted ought
to put us into a state of mistrust; we have seen why. MM.
Peltz and Eitter (in 1881) made intravenous injections of urine
just as it is, and have concluded for the toxicity of urine. Bocchi

‘■Experiments dealing with the injection of urine into the blood-
vessels of animals began as far back as the early part of the nine-
teenth century. Vauquelin and Segalas (Journal de Physiol. Exper.,
Paris, 1822, tome ii, p. 354) in 1822 caused the death of animals by in-
jecting urine into their veins. As their experiments were not conducted
under proper precautions it is more than probable that the fatal re-
sult was due to septicsemia and not to the toxicity of the urine.
Bichat and Courten are believed to have carried out a similar series of
experiments before 1812. — T. O.


(at the end of 1882) repeated the experiments, and also concluded
that urine is toxic, considered as a whole. He has subcutane-
ously injected normal urine into frogs, and has killed them;
but in mammals — 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 grams of urine, and
rabbits with a quantity of extract which represents 1 1 / 2 liters
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 experi-
ments, 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 an 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. Lepine, and afterward by MM. Lepine and Guerin; but
as these experimenters only made use of pathological urines, the
results obtained do not demonstrate the toxicity of normal urines.
It is necessary to return to the method suggested by Feltz and
Eitter, — 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 everything 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 centimeters of water for each kilogram 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 introduc-
tion of a normally acid body into an alkaline medium? Theo=»


retically we cannot afford to overlook this possible cause of error,
although there may be reason for 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 legitimate to compare the effects
of the retention of neutral urine 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 neu-
tralized 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 plrysiological 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 preliminary 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
laboratory, for there are economical necessities before which it
is necessary to bow.

The first phenomenon which follows the intravenous injec-
tion of normal urine is contraction of the pupil. After the
injection of 10, 12, or 15 cubic centimeters of urine there ap-


pears 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-
resis induced by the injection of distilled water is not to be
compared with that produced by the injection of normal urine.
At the same time the temperature falls. This fall is constant,
it is true, after every intravenous 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
explain the death.

We also notice a diminution of the palpebral and corneal
reflexes; often, too, exophthalmos. Death comes at last, with-
out convulsion or with moderate muscular tremors, with per-
sistence of the cardiac beats, and of contractility of the striated
and unstriated muscular fiber. 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 tem-
perature 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
observation for weeks or months, without our being able to ob-
serve in it any pathological accident. One fact to note is, that


we rarely set up albuminuria unless, for the most part, an albu-
minuria which is very slight and very fleeting in the animals
which survive. On the contrary, after the injection of patholog-
ical urines — certain kinds, at least — albuminuria is constant and
notable; one may observe, too, hematuria.

What quantity of normal urine is necessary to produce in-
toxication by intravenous injection? This is a difficult ques-
tion to decide. The oscillation habitually takes place between
30 and 60 cubic centimeters for each kilogram of the animal,
— 45 cubic centimeters, on an average. Pupillary contraction
often begins to show itself after the employment of 10 cubic
centimeters. The urine of a subject in whom abundant drinks
had produced a normal polyuria has been injected with im-
punity up to 97 cubic centimeters for each kilogram 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
centimeters for each kilogram 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 urines are 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 centimeters, 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. In 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 incon-
venience. Nor is death more to be attributed to the general


hydration of the body. If we reduce by evaporation the quantity
of urine by 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 in
the water. Whatever those substances may be, it is interesting
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

It has appeared to me necessary, for the clearness of later
explanations, to create a new name, and I excuse myself foi
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 toxicity “urotoxy”; that is to say, the toxic
amount necessary to kill a kilogram of living matter. This
unit we shall determine by experiment. I shall study thus the
urotoxic coefficients; that is to say, the quantity of urotoxies
which 1 kilogram of man can form in twent} r -four hours.

A healthy man, weighing 60 kilograms, passes in twenty-
four hours 1200 cubic centimeters of urine. If 50 cubic centi-
meters of this urine kill 1 kilogram of animal, 1200 cubic centi-
meters ought to kill 24 kilograms of the animal; 60 kilograms
of man make and eliminate therefore by the kidneys in twenty-
four hours what would kill 21 kilograms of animal. Thus, 1
kilogram of man forms in twenty-four hours what would kill
400 grams of an animal. In order to kill 1 kilogram it is
necessary to have 1 urotoxy. The urotoxic coefficient of this
man of 60 kilograms is thus 0.4. This is almost the normal
coefficient, which I have found to be, on an average, 0.464.

If 1 kilogram of man forms in twenty-four hours what
is sufficient to kill 464 grams 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 coefficient;, but they are
limited. In the pathological state the urotoxic coefficient rarely
exceeds 2 and rarely descends below 0.10.

The toxicity of normal urines varies according to numerous
circumstances, — cerebral activity, muscular activity, sleep, diet,
etc. The variations bear upon the intensity and upon the 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
toxic 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.


September 15, 1SS5. We gather the urine of twenty-four hours
of a healthy adult man weighing 81 kilograms and 700 grams. These
urines are collected in three portions coresponding 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 morn-
ing — to quarter past 3 after midday (morning period) ; the second por-
tion 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, 3G5 cubic
centimeters; 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 grams. The rectal temperature of the rabbit be-
fore 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 re-
ceived 25 cubic centimeters; at 33 cubic centimeters, emission of urine;
at 35 cubic centimeters, restlessness, respiratory arrest, loss of palpe-
bral 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 175Q = 20 cubic centi-

meters of urine for each kilogram of the animal.

Urine of the Eight Hours Belonging to the Evening Period. — Quan-
tity, 320 cubic centimeters; density, 1028; reaction, acid; neutralized


and filtered; this urine is injected into the vein of a rabbit weighing
1560 grams. At the beginning of the injection the rectal temperature
of this rabbit was 40° C. (104° F.). At 3 cubic centimeters, quickened
respiration; at 28 cubic centimeters myosis commences, and is com-
plete at 36 cubic centimeters; at 35 cubic centimeters, excessive move-
ment; at 39 cubic centimeters, convulsions, opisthotonos, death. The
heart continues to beat. The rectal temperture 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

— * = 25 cubic centimeters of urine for each kilogram of animal.

Urine of the Eight Hours of Sleep. — Quantity, 220 cubic centi-
meters; density, 1031; reaction, acid. This urine, neutralized and fil-
tered, was injected into a vein in the ear of a rabbit weighing 1600
grams. At the beginning of the injection the rectal temperature was
40.2° C. (104.5° F.). After 6 cubic centimeters had been injected there
was quickened respiration. At 21 cubic centimeters myosis had begun;
at 33 cubic centimeters, clonic convulsions; at 34 cubic centimeters, loss
of palpebral reflexes, exophthalmos, and momentary suspension of respi-
ration; at 46 cubic centimeters, very severe clonic convulsions; then
opisthotonos and death. The heart continued to beat. The rectal tem-
perature at the moment of death was 39.9° C. (103.8° F.). The tem-
perature of the urine injected was 23° C. (73.4° F.). The animal wan

therefore killed by the injection of — 1G00 — = 28.75 cubic centimeters of

urine for each kilogram 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 – 8 2 % 5 –
— 18.25 urotoxies. The totality of the urines of the evening period
represents – 3 2 2 5 °- = 12.8 urotoxies. The urines of the sixteen hours of
day represent, therefore, 31.05 urotoxies; or, by the hour, 1.9406; or,
by the hour and per kilogram of man who has furnished the urines.
0.02375. During one hour of wakefulness this man has therefore elim-
inated on an average per kilogram of his weight a quantity of urinary
poison capable of destroying 23.75 grams of living tissue. In equal vol-
umes, 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 kilogram of the man who has furnished the urines,
0.0117 urotoxies. One kilogram of man, during one hour of sleep,
eliminates, therefore, a quantity of urinary poison capable of destroy-
ing 11.7 grams of living tissue. In sixteen hours of wakefulness this
person has eliminated per kilogram what would kill 380 grams of
animal, and in eight hours of sleep he has eliminated what would kill
93.6 grams of animal. In the twenty-four hours (waking and sleeping)


he has thus eliminated a quantity of urinary poison capable of de-
stroying 437.6 grams of animal. The urotoxic coefficient of this man
was therefore 0.4736. From this we conclude that, to kill 1 kilogram
of living matter, it would have required for each kilogram of this
man two days, two hours, and forty-three minutes.

On September 19, 1S85, we gathered the urine of twenty-four hours
of a healthy adult man weighing 81 kilograms, 700 grams. 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 cubic cen-
timeters; density, 1028; urea, 24.4 grams for every 1000, or 17.08 grams
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 grams. The rectal temperature at the beginning of the
injection was 40.3° C. (104.6° F.). At the time that 23 cubic centi-
meters of urine have been injected myosis commences; the pupil is pin-
pointed at 33 cubic centimeters; at 36 cubic centimeters, exorbitism,
agitation; at 43 cubic centimeters, respiratory pause; at 46 cubic cen-
timeters, loss of eyelid 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

\Z = 26.74 cubic centimeters of urine for each kilogram.

Urine of the Eight Hours of Sleep. — Quantity, 225 cubic centi-
meters density, 1034; reaction, acid; urea, 27.2 grams for 1000, or,
for the whole of the eight hours of sleep, 6.12 grams. This urine, neu-
tralized and filtered, is injected into a vein in the ear of a rabbit
weighing 1610 grains. The rectal temperature at the commencement
of the injection was 40.2° C. (104.4° F.). Myosis commenced after 21
cubic centimeters had been injected; it was complete after 33 cubic cen-
timeters ; after 26 cubic centimeters, agitation ; at 46, clonic convulsions ;
at 48, strong convulsions while in opisthotonos; death. The heart con-
tinued to beat but feebly, except the auricles, which contracted with
force. The pupils remained contracted after death. The rectal tem-
perature at the time of death was 39.7° C. (103.4° F). The tempera-
ture of the urine injected was 22° C. (71.6° F.). This animal was,

therefore, destroyed by the injection of ^y^io – = 29.81 cubic centimeters
of urine for each kilogram. The urines of the sixteen hours of the
wakeful period represent r— – = 26.178 urotoxies, or, by the hour, 1.6361;


or, by the hour and per kilogram of man who has furnished this urine,
0.2002. A kilogram of man in one hour of the wakeful state eliminates,
therefore, what would kill 20.02 grams of living material.

2 9 5

The urines of the eight hours of sleep represent ^- = 7.88336
urotoxies, or, by the hour, 0.98542, and, by the hour and for each
kilogram of body-weight of the man who has furnished the urine,
0.01206. A kilogram of this man in one hour of sleep eliminates, there-
fore, what would kill 12.06 grams of living tissue. There results from
this that he eliminates what would kill, in sixteen hours of the wake-
ful period, 320.32 grams, and in eight hours of sleep, 96.48 grams of
animal. Therefore, in twenty-four hours he eliminates what would
kill 416.80 grams of living matter. The urotoxic coefficient of this
man is beyond 0.4168. It would require for each kilogram of this man,
in order to kill 1 kilogram 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 healthy adult I have gath-
ered 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 kilogram and for every hour, in the first period
(morning), what would kill 27.92 grams of living tissue; in
the second period (evening) what would kill 19.58 grams; and
in the third’ period (sleep) what would kill 11.70 grams. 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.

We observe that the minimum of this elimination of poison
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 wakefulness, and five times less than eight hours
later on, at the end of the period of sleep. We see that from the
minimum to the maximum, during the sixteen hours which rep-
resent sleep and the morning period of wakefulness, the intensity
of the 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 convulsive ; 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 theory of sleep, — that, according to
which, the activity of nerve-tissue is accompanied by the pro-
duction of a substance from disassimilation, whose action upon
nerve cells would be soporific. If this theory could be revived
it would be necessary, I believe, to expand it, and to attribute to
the whole of the economy the production of narcotic material.
What is certain is, that during the day the body forms a sub-
stance which, when accumulated, induces sleep, and that during
sleep it elaborates, instead of this narcotic substance, a convulsive
substance which, when accumulated, produces muscular twitch-
ings and induces waking.

The poisons of the day period and the poisons of sleep are
not only different as regards intensity and quality, 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
coefficient, — 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 necessary to determine respec-
tively 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 toxicity of the mixture of the two urines
we would get too small an index.


We gathered the urine of twenty-four hours passed by a young,
healthy man, aged 28, weighing 69 kilograms. 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 centimeters; density, 1024.
This urine, neutralized and filtered, was injected into a vein in the
ear of a rabbit weighing 1775 grams. Death supervened, after very
slight convulsions, when 91 cubic centimeters had been injected. The
animal had thus received for each kilogram 51.26 cubic centimeters of

Urine of the Day Period. — Quantity, 720 cubic centimeters; den-
sity, 1014. This urine, neutralized and filtered, was injected into a
vein in the ear of a rabbit weighing 1725 grams. Death supervened,
without convulsions, after 45 cubic centimeters. The animal had thus
received 26.08 cubic centimeters of urine for each kilogram.

Urine of Twenty-four Hours — We mixed one-third of the urine
of sleep (150 cubic centimeters) and one-third of the urine of the day
period (240 cubic centimeters). This mixture represented pretty ac-
curately the mixture of the urine of twenty-four hours. This urine,
neutralized and filtered, was injected into a vein in the ear of a rab-
bit weighing 1555 grams. Death supervened, without convulsions, after
73 cubic centimeters. The animal had thus received for each kilogram


46.94 cubic centimeters. The urine of sleep represented =– = 8.776 uro-

toxies. The urine passed during the day represented ^ = 27.607
urotoxies. The urine of the twenty-four hours represented, there-
fore, 8.778 + 27.607 = 36.385 urotoxies; but if we wished to estimate
this toxicity of the urine of the twenty-four hours by the experiment
which shows the toxicity of the mixture, we find that this toxicity

450 7”0
would only be ” =24.925 urotoxies. Thus, from the fact of then-

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 partly 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 kilogram of his own weight, every hour during sleep, suf-
ficient to kill 14.135 grams of living matter, and during the day 26.673
grams; that during the period of twenty-four hours (day and night)
he was eliminating sufficient urinary poison to kill 527 grams of living
matter. His urotoxic coefficient was therefore 0.527. To intoxicate 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.


We gathered the urine of the day and of sleep of a man of 81.7
kilograms, after a day of great bodily exercise, spent in the open air.
We have for the day urine 1070 cubic centimeters (density, 1020) and
for the urine of sleep 243 cubic centimeters (density, 1027). These
urines are acid. The urines of the day period were gathered on the
11th 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 re-
ceived from 10.30 p.m. to 7 a.m., i.e., during eight and a half hours.

Into a rabbit weighing 1360 grams we made an intravenous in-
jection of the urine of the day period. Death supervened after 72
cubic centimeters, preceded by some slight convulsive movements. It
had received, for each kilogram of its own weight, 52.94 cubic centi-
meters. The pupils were pin-pointed at the moment of death.

Into a rabbit weighing 13G0 grams we injected the urine of sleep.
Death occurred after 66 cubic centimeters, after severe convulsions and
retroflexion of the body in the form of opisthotonos. It had received,
for each kilogram of its weight, 49.26 grams. The pupils were pin-

Thus, during the fifteen hours and a half of the day period 1070
cubic centimeters of urine had been secreted. This urine killed a kilo-


gram of rabbit with a dose of 52.94 cubic centimeters. Man during the

day has therefore secreted what would kill — _ kilograms, and for

J 52.94 to ‘

each kilogram of man and for every hour = 0.01596 kilo-

grams. Therefore, during the day period 1 kilogram of man secreted
in one hour what would kill 15.96 grams of rabbit. During the fifteen
and one-half hours of the day 1 kilogram of man secretes what would
kill 247.38 grams of rabbit.

During eight and one-half hours of sleep 243 cubic centimeters of
urine had been secreted. This urine killed 1 kilogram of rabbit with a
dose of 49.26 cubic centimeters. Man, during eight and one-half hours

of sleep, killed kilograms, and in one hour — — — ; and 1 kilo-

r 49.26 6 49.26X85

gram of man secreted during one hour of sleep what would kill


” _ =7.103 gi~ams of rabbit. In eight hours and thirty min-

utes of sleep 1 kilogram of man secreted what would kill 60.38 grams
of rabbit. In twenty-four hours (night and clay) 1 kilogram of man
secreted sufficient to kill 247.38 + 60.38 = 307.76 grams of rabbit.

The urotoxic coefficient of this man is, in round figures, 0.308; 1
kilogram of man, in order to secrete what would kill 1 kilogram, re-
quires 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 relationship for the
toxicity of sleep compared with the toxicity of the wakeful period is
7.103 : 15.96 = 0.45.

On the whole, therefore, the urotoxic coefficient 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 Sep-
tember, — 0.474 and 0.417, or a mean of 0.445. The 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 effort in
the open air has therefore suppressed 3 /io of the toxicity. In this
man twice, on the occasion of sedentary work in town, the toxicity for
each kilogram and for every hour had been, during the day, 23.75
grams and 20.62 grams, — a mean of 21.88 grams, — and during sleep
11.70 grams and 12.06 grams, — a mean of 11.88 grams. By the fact
of severe bodily exercise in the open air it became, during the day, 15.96
grams and during sleep 7.10 grains. The amount ^gg = 0.729. The

amount 1™. = 0.597.

Muscular effort in the open air diminished thus from 27 for every

100 the toxicity of the day, and its influence extended also to the period

of sleep which followed work, causing a loss of 40 per cent, in 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

It is not sufficient to know that the urines have been ren-
dered toxic by the solid substances which they contain. What
are these substances? Amid 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.


Causes of the Toxicity of Urine.

R6sum6 of the physiological phenomena produced by the intravenous injection

of normal urine. Definition of urotoxy and the urotoxic coefficient.

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: Intravenous injection of urea. Experiments of MM. Grfihant and
Quinquaud by subcutaneous injection. Insignificant toxicity of urea. Uric
acid: Intravenous injection of uric acid. Feeble toxicity of uric acid.
Creatinin: Its toxicity nil (Ranke and Schiffer). Odorous substances.
Coloring matters. Intravenous injection of colored urine and of urine
decolored by means of carbon. Very important diminution of toxicity and
loss of the myotic power of 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 s} r stem, 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 respiratory muscles are quick-
ened, those of the locomotor muscles weakened. The loss of
the reflexes in the advanced phases of intoxication, somnolence,
and coma still show that the brunt is borne by the nervous sys-



tern. It is in the same sense that the disturbances of the secre-
tary apparatus are to be considered, — the frequent emission of
urine, the salivary hypersecretion, of which we shall speak soon,
and, last, the fall of the temperature by diminution of heat
production. That is the first fact, and it is the fundamental
one in the phenomena of intoxication.

Before going further, it is necessary to establish a standard
to estimate whether one individual forms in a given time more
toxic matter than another. 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 kilogram of living animal.
In order to study afterward the reports of the various toxicities,
I have established what the urotoxic coefficient is, of which a
brief argument will explain the necessity.

If to kill a kilogram of rabbit 30 cubic centimeters of the
urine of Peter and 60 cubic centimeters 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
conclusion thus : for if, in twenty-four hours, Paul has secreted
twice as much urine as Peter, the toxicity is equal in the two.
I go further: Two individuals eliminate in twenty-four hours
the same quantity of urine; they kill with the same dose a kilo-
gram of rabbit ; it does not necessarily follow from this that they
have the same toxic power, for another cause of variation may
intervene, — the weight of the individuals; if one, weighing less
by a half than the other, makes the same quantity of toxic mate-
rial, he has evidently a toxic power double that of the other.

We are thus led to define the coefficient 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
coefficient of an individual is the number of urotoxies formed
in twenty-four hours by a kilogram of that individual.

These premises granted, we come now to seek among the
constituent elements of urine for those to which the toxicity of
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
kilogram of rabbit with a dose of 60 cubic centimeters, we see
that this urine thus concentrated kills with a dose of 30 cubic
centimeters. 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 under-
gone 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 fermenta-
tion. Eise 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 anmionasniia.

The increase of toxicity on keeping the urine already allows
us to assume that it is not tbe 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 hypothe-
ses which have been enunciated on this subject, viz. : the causes
of the toxicity of urine. Formerly, for example, urea was con-
sidered the chief poisonous agent, after the teaching of Wilson.
The intravenous 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 condi-
tions of osmosis: by increasing in such proportions the density
of the blood and the liquids of the organism we physically 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 centimeters for
each kilogram, — a dose in which pure water kills.


October 16, 1884. Into a rabbit weighing 1690 grams we inject, in
ten minutes, into a vein in its ear, 100 cubic centimeters of an aqueous
solution, which contains exactly 4 grams of urea. The animal has thus
received per kilogram 2.366 grams of urea, and, as this urea has been
introduced into its blood, that makes 30.758 grams per kilogram of
blood, — about two hundred times the normal quantity (2.366X13 =
30.758). The temperature at the commencement was 39.7° C. (103.4°
F.) ; at the end of the experiment it was 3S.8° C. (101.8° F.). No mor-
bid phenomenon.

October 25th. The animal is well. t

October 28th. It renmins q ujt_e w ell.

The temperature of^m^T^in]/^ IhalNfallen in ten minutes nine-
tenths of a degree. TmeOJieat capacity -«fAl|he tissues being 0.8, the
animal has, therefore/uQT l69TrX B *1?ft~X – 0.9 =^r\l6.8 calories. On the
other hand, water iiwe«edjuwhroh-ftvfl«,Tai-jthe e^niVnencement, of a tem-
perature of 16 degrees, is heated to 22!S aegrees, and consequently has
absorbed 100 X 22.8 =^2280 cahiide^oJffiaJter has Vtheref ore, taken from
the body of the aniiimsj a/ quantity ot <heat^more considerable than
that which it lost in fallm§^r^tf^3A7^ue > g*^es to 38.8 degrees. Conse-
quently, the injection has not produced refrigeration by impeding heat
production; 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 grams of urea per each kilogram of the animal, or 82
grams per each kilogram of blood; a supposition that there is
ten times more urea than we have found in the blood of 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.


October 25, 1884. We injected, in thirty-five minutes, into a vein
in the ear of a rabbit weighing 1790 grains, 113 cubic centimeters of an


aqueous solution of urea at a / 10 — let us say 11.3 grams of urea; or,
for each kilogram, 6.31 grams; or, for the total mass of the blood (137
grams), 11.3 grams; or, for a kilogram of blood, 82.03 grams. After
injecting 35 cubic centimeters, respiratory disturbances were the first
to be noticed; respiration became slower. After 58 cubic centimeters,
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 au-
topsy we found the blood of a blackish-brown color; nothing in the
lungs; almost no urine in the bladder. 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 concentration, which might have modified the physi-
cal 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 Grehant and Quinquaud. Death
supervened, in their experiments, after injection of 6 grams of
urea for each kilogram 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 subcutaneous method. These experiments, inter-
esting from an experimental point of view, are without clinical

Six and thirty-one one-hundredths grams of urea are neces-
sary to kill 1 kilogram of animal ; to hill a man of 60 kilograms
it would require, therefore, that his blood should retain more
than 380 grams of it at one time. But 1 kilogram of man form-
ing, in twenty-four hours, only 0.33 grams of urea, or 20 grams
for each 60 kilograms, it would require, in order that his death
should be due to retention of urea, that he should make nineteen
times more of it ( ^ 80 = 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 toxicity
of urine. But it is made in our body in far too minute a quan-
tity (50 to 60 centigrams in twenty-four hours), and the gouty
man can have hundreds of grams of urate in his deposits without


being intoxicated by it. Besides, I have been able to inject
experimentally into the blood 30 centigrams of uric acid for
each kilogram of animal without apparent accident ; I have even
been able to inject as much as 64 centigrams of uric acid in
solution in 160 cubic centimeters of water, to which the neces-
sary additional quantity of soda had been added to produce its


March 8, 1886. We took 1 gram of uric acid, which we dissolved
in 1 cubic centimeter of soda-lye and distilled water. We obtained 250
cubic centimeters 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 grams. Injection into the auricular veins
of 250 cubic centimeters. The animal received 1 gram of uric acid, or,
per kilogram, 0.641; it received of the liquid 160.35 cubic centimeters.
It did not die. Removed, it was only sick. Urine alkaline, muddy,
containing blood. Heated, this urine became slightly clear. Albumin
was precipitated. We filtered it hot. On cooling, it again became
muddy, in a very notable manner, and gave an abundant precipitate
of basic urates. We filtered. Into the limpid liquid we poured a little
acetic acid. We had again an abundant precipitate of acid urates.
The murexide reaction was very distinct. One hour and three quarters
afterward very strong convulsions, which were repeated, until death,
— two hours and twenty minutes after the commencement of the experi-
ment. Autopsy: numerous foci of pulmonary apoplexy. Nothing in
the other viscera.

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 kilogram
of man forms, in twenty-four hours, 8 milligrams of uric acid.
We are far from accounting for, by means of this agent, the
intoxication which 10 to 20 cubic centimeters of urine produce.


March 10th. We made a solution of 1 cubic centimeter of the
same soda-lye which had served for the previous experiment in a quan-
tity of distilled water sufficient to make 250 cubic centimeters. We
passed through it a current of C0 2 until it was neutralized, and we in-


jected some of this into the veins of a rabbit weighing 1460 grams. It
received 236 cubic centimeters of this solution, or 160 cubic centimeters
of liquid per kilogram. The injection was made at 4 o’clock; it lasted
fifteen minutes. At 7.30 the urine was bloody, limpid, acid. After co-
agulation of the albumin by heat, filtration, and cooling, no precipi-
tate 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, while 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 centimeters — injected per kilogram of the ani-
mal, and we know that distilled water produces death after 122 cubic
centimeters. Therefore, with 64 centigrams per kilogram, uric acid is
not toxic. I add that we can never introduce into the veins of an ani-
mal 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 might also continue the demonstration for creatinin, but
the experiments, already old, of Eanke and Schiffer having estab-
lished that it is not toxic, enable us not to insist further upon
it. Besides, we shall return, on another occasion, to this experi-
mental investigation.

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 decolor it by charcoal. I inject this
decolored urine, and I ascertain that it has lost nearly one-third
of its toxicity. A quantity equal to that which killed only pro-
duces accidents that are scarcely perceptible. It produces par-
ticularly nothing more than pupillary contraction.


December 4, 1884. 1. We injected 65 cubic centimeters of a mix-
ture of urine, taken from two healthy men, filtered and neutralized,
into the auricular veins of a rabbit which weighed 1650 grams, or 39
grams for each kilogram.


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 to 38.4° C. (101.2°
F.), and then to 37.8° C. (100° F.).

2. We injected 102 cubic centimeters of the same urine, after hav-
ing decolored it, into a rabbit weighing 1670 grams, or 64 grams for
each kilogram. The pupil was not contracted. The animal appeared,
after the injection, much less indisposed than that in the previous ex-
periment. 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 removed by charcoal, 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 charcoal, and
nearly the whole of the alkaloids. If decolored 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 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 alcoholic extract, which
really contains the greater part of the alkaloids, is sensibly less
toxic than the residue insoluble in alcohol, which ought to con-
tain only a few of the alkaloids. Charcoal, therefore, removes
from urine the substance which causes contraction 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 of a rabbit of the aqueous

extract of normal urine insoluble in

alcohol; death.

November 11, 1884. We take 200 cubic centimeters out of the
whole quantity of 1300 centimeters 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 re-
tort to dryness; the residue is the extract soluble in alcohol. The resi-
due 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 centi-
meters. It is introduced by intravenous injection into a rabbit weigh-
ing 1610 grams.

After the entrance of 12 cubic centimeters the animal is seized
with tonic convulsions accompanied by straightening of the head. These
convulsions rapidly disappear after we discontinue the injections.

At the end of 42 cubic centimeters 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 im-
mediately after death. Temperature before injection, 39.2° C. (102.6°
F.) ; at the moment of death, 38.6° C. (101.5° F.). Symptoms com-
menced on the entrance of 31 grams of urine for each kilogram, and
death supervened when we had injected the insoluble extract from
108 grams of urine.


November 11, 1884. Of 200 grams 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 grams of
urea, is diluted with distilled water in such a manner as to have a vol-
ume of 39 cubic centimeters. Urea is found there to be one-tenth. We
inject 33 cubic centimeters of this solution into the veins of a rabbit
which weighs 1870 grams. We see the pupil contract rapidly; after
the tenth centimeter it is markedly contracted. Starting from this mo-
ment its diameter oscillates, but up to the end of the injection it re-


mains 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 veiy large. Dur-
ing this comatose period the rabbit salivates and urinates abundantly.
The initial temperature, which was 39.4° C. (102.9° F.), falls in a few
minutes (ten or more) to 38.8° C. (101.8° F.).

In this experiment, the contraction of the pupil was manifested,
under the influence of the soluble extract, from 27 grams of urine for
each kilogram. The last symptoms corresponded to the injection of the
soluble extract, from 90 cubic centimeters of urine for each kilogram.

November 12th. The animal died during the night. Nothing spe-
cial at the autopsy.

The toxicity varies according to the individuals who have
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 calorie 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 myosis, but a new s} r mptom is
caused, viz., salivation, — a salivation lasting three-quarters of
an hour, and 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 yet 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, diu-
resis, 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 which a very small quantity
(some salts of potass) pass into the alcoholic washing; that
the convulsions, myosis, and fall of temperature are not attrib-
utable to the mass of organic substances which have been caught
in the washing with alcohol. Coma, which the soluble substances
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
in a purely isolated form, is certainly diuretic. I therefore think
that it is 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-
ored 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 effects of these

Soda is convulsion-producing. Neutralized by carbonic acid,
■ — 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 experiment-
ally in 1869, severe convulsions appear with a dose of 1.20 grams
for each kilogram of animal, and death at 2.50 grams. But
urine contains at the most 8 grams of salts of soda per liter, —
that is to say, 48 centigrams for 60 cubic centimeters of urine.
Urine contains, therefore, scarcely half of the soda capable of
producing convulsions, and one-fourth of that capable of in-
ducing death.

Potass is infinitely more toxic. Bicarbonate of potass causes
death, with violent convulsions, in small doses of 5 centigrams
for each kilogram of animal, and convulsions come on after a
dose of 3 centigrams. Potass is forty-four times more toxic than
soda ; but if we find 2 grams of salts of potass per liter of urine,
— that is, 12 centigrams for 60 cubic centimeters, — 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 is
an excess of it in the blood, however 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 centigrams per kilogram, ammonia, regarded as an anhy-
drous substance, and neutralized in water by means of carbonic
acid, produces convulsions and then death. But normal urine
only contains doubtful quantities of ammonia.

In short, of the mineral matters, potass is the one substance
alone which, makes itself felt in the toxic totality.

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. Analysis and the isolation of various toxic principles
from the urine ought certainly in the future to be carried further.


Toxic Principles in Urine — the Part they Plat
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 injec-
tion of normal urine, because it is found to be masked by more toxic sub-
stances. 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. Comparison of the clinical symptoms of uraemia and of the

physiological properties of the toxic substances of urine. Coma or convul-
sions: 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. Reinstatement of the
urea. Additional toxic substances of urine, salts of soda, alkaloids. Hen-
ingham’s criticism of urinary toxicity.

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 thern. There
is, first, a diuretic substance, — fixed, of organic nature, since it
is destroyed by heat. It is not fixed by charcoal ; 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, while
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


every other substance, — like water itself, which, when 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 grams to 6.3 grams of urea per kilogram of
the weight of the animal. In the experiments in which we have
killed rabbits by the injection of urea we required from 71.5 to
82 grams for 1000 grams of blood. There are, therefore, few
bodies in the organism so feebly toxic as urea, if we except albu-
min and the water which naturally exists in the blood. Sugar is
more toxic; we can, experimentally, scarcely introduce more
than 5 grams per kilogram, or 65 grams per liter of blood. Yet,
in order to kill immediately by intravenous injection of a sucrose
liquid, we must introduce almost 10 grams per kilogram of the
rabbit, or 130 grams per kilogram of blood. In pathological
blood there may be 8 grams of sugar per kilogram of blood ; but
in pathological blood urea has been found in quantity at least
equal. Among the mineral substances the most inoffensive, even
bicarbonate of soda, which we so readily prescribe therapeutic-
ally, cannot be injected in a larger dose than 2.50 grams per
kilogram of animal, 32 grams per kilogram of blood. In order
to kill 1 kilogram of a rabbit 5 grams of chloride of sodium are
sufficient; 6 grams of phosphate of soda; 9 grams 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 nephrectomy followed by injection of urea: an experiment
already performed by Bernard. In one of my experiments of
the intravenous injection of urea in the rabbit, the animal was
dead after the introduction of 6.31 grams of urea per kilogram.
It had not urinated during the experiment, and at the autopsy
the bladder was empty. Besides, however active the renal cir-
culation may be, the rapidity with which the quantity of urea
that we inject is found, as having entered into the circulation
by our method of intravenous injection, is such that the elimi-
nation 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 charcoal; 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; that is, 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 charcoal, soluble in alcohol like the preceding, but it is dis-
tinct from urea as well as from the narcotic substance. It cer-
tainly 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
destroyed by carbonization, but retained by charcoal ; it is, there-
fore, 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 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 probably because the nar-
cotic substance kills the animal before the convulsive substance
has had time to exhibit its properties. In order to produce con-
vulsions it is necessary to remove first from the urine the poison
which kills rapidly. Of this convulsive substance we also do
not know the name. Then there is a substance which causes
contraction of the pupil; fixed, organic, attaching itself to char-
coal; nonmineral; consequently it is comparable in certain
respects with 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 color-
ing substance? It is possible. Alkaloid? Probably not, foi
the same reason that we have given when speaking of the con-
vulsive 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 neces-
sary to admit that the substance which convulses the sphincter
iridis is more energetic than that which brings on general con-

Urine produces pupillary contraction in small doses, from
10 cubic centimeters, and in general it causes death without con-
vulsion in doses of from 30 to 50 cubic centimeters. We ought,
with convulsive urines, at 60 cubic centimeters to see imme-
diately happen contraction of the iris, while 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 calories in
order to put it into equilibrium with its own temperature, for
when we inject a cold liquid into the circulation, we only pro-
duce a very slight fall of the temperature of the body ; in reality,


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 calories 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 or-
ganism 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 calories 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 charcoal and is not, therefore.
a mineral. It is insoluble in alcohol, like the preceding. It may
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 hypothermic 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 charcoal,
a convulsive substance which kills too rapidly, we might see
convulsions come on and due to potass. If, in dealing with the
extract which at one and the same time contains both the con-
vulsive 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. Alco-
hol, it is true, has removed a part of the potass; sometimes
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 con-
vulsions. This paradoxical result, which I have already men-
tioned 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 pro-
duced; the other, potass, a salt of which, viz., chloride of potas-
sium, is convulsive and toxic at 18 centigrams for every kilo-
gram of the animal. This neutralization of one toxic substance
through admixture with another is seen under many circum-
stances. Atropine can neutralize the physiological action of
pilocarpine. In the injections of normal urine the convulsive
properties of the salts of potass are neutralized by their mixture
with a substance which produces narcosis and coma. Thus, urines
contain the antidotes to certain of their own poisons.

When we destroy the extract of urine by heat, the con-
vulsive action of the residue is, perhaps, weakened by the vola-
tilization of a part of the potass. In every case there is good
cause for taking into account potass in the toxic phenomena
consequent 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 continues
to be introduced into the organism by 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,
— everything 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. This
analysis, long as it may seem, of the toxicity of urines, is only
an outline, which chemistry, without doubt, will complete, by
the aid of improved methods.

It is sufficient for us, for the moment, to have demonstrated
experimentally that urine removes poisons from the body; that
the kidney plays a useful role; that it is a good emunctory;


that its suppression would be fatally hurtful to the economy, —
an old opinion, which is sanctioned by the name of emunctory.
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 nephrectomy. 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 sup-
pressed, in certain experiments, the track along which they have
passed. Whatever the worth of this argument may be, in order
to clear away the last point which separates us from certainty, it
is necessary that we should find again in the symptoms of uraemia
the physiological 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 materials, — salts, extractives,
etc. ; from these differences in its permeability for such and such
a toxic substance might well result the predominance of coma-
tose or of convulsive uraemia, or one of a mixed nature.

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 choleraic
phenomena we see in succession the intoxication proper to cholera
and urasmic intoxication. When this latter arises myosis ap-


pears. All those suffering from the anuria of cholera have the
pupil contracted. Myosis has already been pointed out by Eob-
erts as one of the signs of anuria.

Salivation has been observed by A. Bobin in uraemia. A
subnormal temperature has been regarded as one of the com-
monest manifestations. What is wanting in the picture of
urasmia so that it may be identical with that which poisoning
by means of the toxic principles of urine produces? There is
only wanting 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 influ-
ence. Besides, when urea is no longer formed in the body, the
kidney — even when normal — ceases to show its functional activ-
ity. In hepatic uraemia, when the liver no longer forms urea,
although the kidney 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 scarecrow 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 scarcely toxic, like the salts of soda, or
because they are only found in the urine in very small quantity.
Such are the urinary alkaloids by which we have only recently
tried to explain the toxic accidents 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 indeterminate 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

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 what 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.

[In the Journal of Pathology and Bacteriology, August,
1899, Dr. W. P. Herringham, of St. Bartholomew’s Hospital,
discusses at considerable length the methods employed by Bou-
chard and the deductions he has drawn from his experiments.
Herringham does not consider that the injection of the con-
stituents of urine separately into the blood-vessels of animals
is a proper method, since this alters the relationship of the
various substances of the urine that contribute to its toxicity.
Feltz and Eitter in 1881 (“De Furemie experimentale,” Paris,
1881) showed that the urine of man and dogs was toxic, but
that when the urinary constituents were individually, injected
they produced no serious symptom. After destroying by burning
the organic constituents of urine they found that the injection of
inorganic salts was much more toxic than the original fluid and
they arrived at the same conclusion as Bouchard, viz. : that the
principal toxic substances in urine are the salts of potassium.

Herringham has repeated many of Bouchard’s experiments
and after giving in detail the symptoms he observed he, too, is of
opinion that potassium is the main poison. Bouchard’s methods
of experimentation are subjected to a lengthened criticism at the
hands of Herringham, especially the manner in which this
French physician reckons up the proportional toxicities of the
inorganic substances in the urine. The absence of chemical
analysis, too, it is maintained, weakens the value of his data,
while no physiological support can be given to the opinion that
the effect of small closes of any substance is similar to, but only
weaker than that obtained when the same substance is admin-
istered in larger quantity. In confirmation of Herringham’s
contention allusion is made to the fact that atropine in small


doses renders the pulse somewhat slow ; larger quantities exceed-
ingly rapid, while very large quantities again cause it to show
similar conditions being observed in the administration of dig-
italis. Herringham, like previous experimenters, also found that
potassium, reckoned as K0 2 , was the main toxic body in urine,
and that although the fatal dose of this substance lay between
0.1400 and 0.2100 gram per kilogram there were yet very wide
variations; also that death came about not by cessation of res-
piration, but by heart failure. Of the salts of potassium it is
the chloride that is the most toxic. Herringham states that the
value of Bouchard’s data is lessened by the fact that after in-
cinerating the urine the residue was not analyzed, for the injec-
tion of the ash solution is found to be sometimes less, sometimes
more, toxic than the original urine. Herringham observed, too,
a new set of symptoms, a series of slow, irregular spasms like
the athetoid spasms of hemiplegia, but upon what toxic agent
these depend he cannot say. A number of experiments carried
out by him went to prove that excess of pigment in the urine
such as that caused by the addition of urochrome to it did not
increase the urinary toxicity; also that there was nothing to
show that the urine secreted during the day contained narcotizing
material or that formed during the night contained convulsive
substances, but that both properties were alike present in equal
proportions in each urine. Herringham is distrustful of what he
calls the mathematical accuracy of Bouchard’s estimates of a
“urotoxy” or the dose that is fatal to a kilogram; also of the
“urotoxic coefficient,” the amount of poison excreted by each kilo-
gram per diem, urinary toxicity according to Herringham being
nothing else than “an inexact expression of the excretion of
potash.” This is found to vary even with ordinary diet from 27.8
to 15. 2 urotoxies per diem, while in disease it may fall as low as
8 urotoxies, probably owing to loss of appetite being followed
by diminished excretion of potash.]


Origin of the Toxic Substances of Urine — Toxicity
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. In-
crease of the toxicity of blood by the destruction of globules, which disen-
gage 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 creatinin. Intravenous injections of extracts
of muscle. Aqueous extracts of muscle produce convulsions, with the ex-
ception 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; they probably act only indirectly in
destroying anatomical elements and in setting at liberty mineral or or-
ganic products derived from cellular disintegration. Cholesterin possesses
only an insignificant toxicity. The coloring matters ought to play a very
important role in the toxicity of bile, since it, when once decolored, 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 toxicity? We have established the fact that the organism
forms toxic products, and that the kidney eliminates them. It
is now for us to show whether, on the side of the kidney, 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 reser-
voir from which it cannot be reabsorbed 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 is incessantly removing
toxicity from it. The blood is continually being traversed by
a current of toxic material. It is true that the poison is never
found in it but in harmless quantities. 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 quantity 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 quantity 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

The estimation of those fractions may 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
revolutions which take place in certain departments of the vas-
cular system. A man of 65 kilograms expels in twenty-four
hours 1350 cubic centimeters of urine, which kill 1 kilogram of
rabbit with a dosage of 45 cubic centimeters. This man elimi-
nates, therefore, in twenty-four hours, by his urine, sufficient to
kill L3 so. _ 30 kilograms of living matter. The whole quantity
of blood of this man is f § =5 kilograms. The 5 kilograms of
blood of this man are thus traversed in twenty-four hours by
a quantity of poison capable of killing 30 kilograms.

The number of complete circulatory revolutions is 1850 in
twenty-four hours. In each complete revolution the kidneys
remove from 5 kilograms of blood a quantity of poison capable
of killing j^ , and from 1 kilogram of blood 1850×5 =
0.003243 kilogram, or 3.243 grams. If, during a complete revo-
lution, each kilogram of blood discharges a quantity of poison
capable of destroying 3.243 grams of animal substance, in the
same time this mass of poison will be furnished to each kilo-
gram of blood by the organism, the ingoing being equal to the
outgoing. It follows from this that the blood ought to contain
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
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 kilograms eliminates in twenty-four hours,
by 1350 cubic centimeters of urine, 1300 grams of water and
24 grams of urea. In a complete circulatory revolution he
eliminates 1850 times less of each substance, — that is, 0.7 grams
of water and 0.01297 grams of urea. These quantities of water
and of urea are given up by 5 kilograms of blood. One kilogram
of blood gives, therefore, during one total revolution, five times
less, or 0.14 gram of water and 0.002592 gram of urea. But this
kilogram of blood only gives up these quantities of material from
its liquid part, — from its plasma, — which constitutes one-half of
the mass of blood; and the 500 grams of plasma in 1 kilogram
of blood contain only 450 grams of water and 0.16 gram of
urea. The calculation made, the blood loses, during a com-
plete revolution, ^ox? P ai ‘t of 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 fifty-two times
quicker than the water (–f^ 1 = 52).

If the rapidity of the elimination of the blood-poison was
equal to that of urea, 1 kilogram of blood would contain sixty-
two times the quantity of poison which this kilogram of blood
eliminates in a complete revolution; and as this quantity elimi-
nated is capable of killing 3.243 grams of living matter, 1 kilo-
gram of blood ought to contain sufficient poison to kill 3.243 X
62 = 201 grams of living matter, which represents 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 kilogram of blood ought to be 3214 times
the quantity eliminated by this kilogram of blood during a
complete revolution. One kilogram of blood would, therefore,
be capable of killing 3.243X3214=10,423 grams of living
tissue. This result is not preposterous; this maximum of tox-
icity would not be incompatible with life. With such a toxicity
of its blood the animal would poison itself, if 1 kilogram of


blood was distributed to 10 kilograms of its body ; but, in reality,
1 kilogram of blood is distributed to 13 kilograms of the organ-
ism. It is, moreover, extremely probable that the real toxicity
of the blood is less, and that it is comprised between these two

These hypothetical calculations only show us the extreme
limits of the possible toxicity of the blood. We can, fortunately,
approach the question from the experimental side. The injec-
tion of the blood of an animal into the veins of another animal
can produce death without the death being attributable to em-
bolism and without the augmentation of the mass of blood being
incriminated. The injection of 25 cubic centimeters of blood
per kilogram of animal is invariably fatal. 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 withdrawn. If, instead of drawing it
from the general venous system, we remove it from the portal
vein, 14 cubic centimeters 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 kilogram of animal contains 1 ^~ =
77 grams of blood. After the injection of 25 grams of blood, this
kilogram would contain 102 grams, and then the animal dies.
We may therefore say that 102 grams of blood are sufficient to
kill 1 kilogram of animal. In other words, 1 kilogram of venous
blood retains, in the normal state, sufficient poison to kill 9801
grams of living matter.

These conclusions would be strictly exact if the blood in-
jected came from an animal of the same species as that into
which we make the injection. But, in nry 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.
In experimental studies bearing upon transfusion, we have prop-
erly 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. While the blood of the dog kills a rabbit at the
dose of 25 cubic centimeters per kilogram, I have known the
blood of the dog injected into another dog to the extent of 30
cubic centimeters only produces a fleeting indisposition, while
in the rabbit, in order to cause death, it is necessary to inject 126
cubic centimeters of blood of rabbit. This amount is consid-
erable. It is true that it was a question of the injection of arte-
rial blood. Death supervened by convulsions, with moderate
pupillary contraction. The urine contained only traces of albu-
min, — none of blood, none of haemoglobin. There were no haem-
orrhages 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 kilogram of its body
was irrigated by 77 -f- 126 = 203 grams of blood. From this
we infer by calculation that 1 kilogram of rabbits’ blood is
capable of killing 4926 grams of rabbit, — in round numbers, 5
kilograms. And we still further draw the inference, if you wish
to refer to calculations just recently made, that by 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
withdrawal 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 pro-
duced 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
this study of the toxicity of blood, — the hypothesis, 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, — nonliving, — 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 grams of blood. The clot, after having been in
an icebox for twenty-four hours, has furnished to me 260 grams
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 centimeters of serum per kilo-
gram. 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, by convulsions, and by a frothy, sanguineous discharge
from the nostrils. The lungs, voluminous but pale, were dotted
with patches of pulmonary apoplexy. There were no haemor-
rhages at any other point in the body. The urine contained
neither blood nor albumin. 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 grams of blood. The animal had already in its vessels,
before the injection, 77 grams of blood. When it died, its tissues
had at their disposal, per kilogram of its weight, the poison of
327 grams of blood; from this I am obliged to conclude that 1
kilogram of blood is capable of killing about 3 kilograms of

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-
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. Eemember, however, that the animal died,
after having received into its veins 125 cubic centimeters of
serum, like the animal in the preceding experiment, after hav-


ing received 126 cubic centimeters of defibrinated blood. Ee-
member, too, that distilled water causes death when we intro-
duce into the vessels more than 122 cubic centimeters of it.
From this comparison you will be able to conclude that blood is
less toxic than pure water. It is only 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 any more by its mechanical action,
— by plethora; it kills by its physical action, by swelling out
the globules and dissolving out the hgemoglobin. 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 necessary, as I have done, to
inject into the veins water, to which a salt very slightly toxic
has been added, 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
kilogram 396 cubic centimeters 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 ex-
tremely distended, injection becomes difficult and laborious, and
the piston of the syringe is constantly driven back by the excess
of the intravenous tension. All the liquid injected remains in
the circulatory apparatus, for the urinary secretion is not in-
creased ; 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
decolored ; there has not been any chemical or toxic action, for
we have only injected 2.772 grams of sodium chloride, and to
kill a kilogram of rabbit we require 5.31 grams 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 a 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 ; some-
thing 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 animal into another of the same species.
That is what I have done; I have coagulated the albumin 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 grams of serum representing
800 grams 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 kilogram of blood would be capable
of killing at least 201 grams, and at the maximum 10,423
grams of living matter — experimentation has narrowed these
extreme limits. It shows us that a kilogram of blood could
destroy at the least 1250 grams, and at the greatest 3000 grams
of living matter. The true index, as yet undetermined, is be-
tween these two extremes. Besides the plasma, blood contains
globules. Do these globules increase the toxicity of the blood?
Experimentally, 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 have, like every cell, a frame-
work. What enters into the composition of this framework is
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 cells, 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 sub-
stance in urine. It is from the blood that the kidney gets this
substance which causes salivation. With the alcoholic extract of
blood narcosis is observed only under abnormal circumstances.
I have seen it produced in one case with the blood of a ursemic
patient who was not eliminating toxic substances, but with nor-
mal 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 consider 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 elimi-
nated by the kidneys ; it receives from the tissues an equal meas-
ure of it; it contains, therefore, in the normal state, always a
certain quantity. If elimination is prevented and the supply
of it continues, accumulation of toxic material produces intoxi-
cation. 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, fix the time necessary for 1 kilogram of blood to kill 1
kilogram of animal. This period is two days and four hours;
that is a theoretical average. In reality, the time necessary is
longer, because in ursemia 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 cells are
not toxic while 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
substances 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
produced 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. If it does not poison, that is
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 safeguard 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 stimu-
lating 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
salivation. An alcoholic extract of liver causes an excessive
salivation; the extract from 117 grams 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 sufficient to
precipitate it in the state of tartrate of potass. After this opera-
tion the extract of 216 grams 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 phenom-
ena of intoxication, during life, comparable 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 com-
bination 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 suffi-
cient; the respired oxygen does not explain the surplus of water
and carbonic acid; the oxidations, therefore, have been made
with the oxygen of the combinations; one-third of life is sup-
ported by oxidation without free oxygen.” Nutrition is thus,
on one side at least, comparable to fermentation when air is

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 tbat 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 intravenous 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. Yulpian has injected up
to 250 grams of it into a dog during several days, — 96 grams
in one day alone. He has omitted to mention the weight of
the dog. Supposing it to weigh 10 kilograms, the toxicity of the
bile would be 9 cubic centimeters per kilogram 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 centi-
meters of pure bile for each kilogram of animal. I have recog-
nized, besides, that bile decolored 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 kilogram of rabbit; the cholate
of soda, in the dose of 54 centigrams; and choleate of soda, in
the dose of 46 centigrams.

We might incriminate cholesterin, but we have only been
able to induce cholestersemia 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,
among old people, the atheromatous abscesses which we find
widely open in the aorta contain sometimes several grams of
cholesterin without there being any poisoning from them. The
coloring substances ought to be suspected by us as toxic agents,
since bile, once decolored, is much less toxic. Equally with M.
Tapret, I have shown that bilirubin kills in the dose of 5 centi-
grams per kilogram.

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 fibers 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 de-
velops but slowly.

People intoxicated by bile are, therefore, in the condition
of animals into whom we have injected aqueous or alcoholic
extracts of the tissues. Among 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.


Among 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 decolored, it
remains toxic; but it does not owe this property to the con-
vulsive material of normal urine, since this remains fixed in the
charcoal. 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


Origin of the Toxic Substances of Ueine — Toxicity of

the Fluids and of the Contents of the Intestine

(Bile 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 decoloring. 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, Panum,
Bergmann, Billroth. Koch’s argument.

If animal juices are scarcely toxic, although they contain
more poison than the quantity given up to the emunctories, the
cells inclose 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 substances are organized and mineral. Potass
occupies the first rank among them; in the normal state it is
a constituent of the anatomical elements, but not of the fluids.
In the economy of the living animal a measured quantity 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 fluids. 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 into par-
ticular canals, which conduct it to the exterior; e.g., the glands
of the skin, the liver.



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 Yulpian we see that 10 grams of bile
per kilogram of animal constitute a poisonous dose. We even
see it kill with 4, 5, or 6 grams one kilogram 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 postmortem 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 twenty-four hours. According to Beaunis, we may value at
about 1 kilogram the quantity of bile produced in twenty-four
hours in man. From observation in cases of biliary fistulas,
Banke found a mean of 14 grams of bile per kilogram of living
weight for twenty-four hours. Von Wittich has obtained from
such in a woman, in twenty-four hours, 528 cubic centimeters;
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 grams. 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.


A man of from G5 to 70 kilograms eliminates in twenty-four hours
1350 cubic centimeters of urine on an average, or about 20 grains of
urine per kilogram. This urine can kill an animal of 1 kilogram after
a dose of 45 cubic centimeters. Man, for each kilogram of his body-
weight, eliminates, therefore, in twenty-four hours, by his urine, suf-
ficient to kill — — — = 444 grams of living matter. A man of 37

kilograms eliminates in twenty-four hours 652 cubic centimeters of
bile; that is, 13.45 cubic centimeters per kilogram. This bile can kill
an animal of 1 kilogram at the dose of 5 cubic centimeters. Man, for


each kilogram of his hody-weight, eliminates, therefore, in twenty-four

hours, by bile, sufficient to kill * = 2690 grams of living matter.

From what precedes we may conclude (1) that 1 kilogram of living
matter being killed by 5 cubic centimeters of bile and by 45 cubic
centimeters of urine, bile is nine times more toxic than urine; (2) that,
the quantity of bile secreted in twenty-four hours by 1 kilogram of
man being capable of killing 2690 grams of living matter, while the
quantity of urine secreted by 1 kilogram of man in twenty-four hours
is capable of killing only 444 grams 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 and fifty-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 impedi-
ment placed in the way of the elimination of bile or from its
absorption. Fortunately, more than one-half is eliminated in
twenty-four hours by the digestive canal ; the water of the f asces
represents the water of 400 grams 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 destroy it?
Do the tissues change it? These two hypotheses 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 salts 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
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-
meters per kilogram; these urines owe, without doubt, a great
part of their toxicity to the presence of coloring matters, since,
once decolored, 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 among jaundiced people bears witness to,
and especially the potass, contribute to rendering jaundiced
urines very toxic.


March 11, 1885. Into a rabbit weighing 1650 grams we injected
22 cubic centimeters of a very pronounced jaundiced urine, coming
from a patient in the Saint Landry Ward (Hopital Lariboisiere), who
was passing 900 grams of it in twenty-four hours. After the sixth
cubic centimeter, agitation. At the ninth cubic centimeter, pupil in
great part contracted. At the fifteenth cubic centimeter, pupil pin-point;
spasms; hurried respiration. At the twentieth cubic centimeter,
screams; spasms. At the twenty-second cubic centimeter, death, — the
heart still beating. The animal received 13 cubic centimeters per kilo-


We completely decolored, 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 16S0 grams 50 cubic
centimeters of this urine. The injection was driven in pretty rapidly.
At the twenty-seventh cubic centimeter, slight tonic shaking, — stronger
at the forty-first cubic centimeter. At the forty-eighth cubic centi-
meter, spasms, — not ceasing even at the fiftieth cubic centimeter. At
this moment tonic convulsions, with opisthotonos. Respiration, which
had become rapid after the twenty-fifth cubic centimeter, stopped; but
the animal returned to life. At no moment had the pupil been con-
tracted. The rabbit had received 30 cubic centimeters per kilogram.
On the 12th of March the rabbit had diarrhoea and much albumin in ite
urine. On the 14th of March it was quite well.



March 14, 1885. Forty-five cubic centimeters of urine from the
same patient whose urine had served for the preceding experiments were
injected into a rabbit weighing 1450 grams. Spasms commenced after
12 cubic centimeters. At 20 cubic centimeters the pupil began to con-
tract. At 42 cubic centimeters it was punctiform. Spasms began and
death came after 45 cubic centimeters, or 31 cubic centimeters per kilo-


Into a rabbit weighing 1300 grams we injected 70 cubic centi-
meters of the preceding urine, decolored by means of charcoal. Spasm
came on after 68 cubic centimeters. The pupil was not contracted.
Death came after the seventieth cubic centimeter. That was 54 cubic
centimeters per kilogram.

If bile is toxic directly and indirectly, the intestine is
already, so far as bile is concerned, a source of intoxication,
feeble it may be, but still really so. From it there pass onward
into the blood, in addition, other materials which are eliminated
by the urine, — mineral salts {e.g., potass) introduced by the
food, and other toxic substances of alimentary origin. Never-
theless 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
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 deglutition, is
caught by the saliva, along with the micro-organisms which it


conceals. The conditions favorable for the maintenance of putre-
faction 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 fermentation. Experimentally, we know that 1.10 grams of
anhydrous hydrochloric acid per liter prevents all fermentation ;
but the gastric juice contains more. We find therein, per liter,
up to 3.30 grams, and even 5 grams, of hydrochloric acid, esti-
mated 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 recommences 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 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, capable 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
f aintness, diarrhoea, and vomitings ; hyperemia of mucous mem-
branes; then death; and at the autopsy ecchymoses of the
digestive canal were seen; also of the cellular tissues, — those
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


Magendie has studied intoxication by gases from the basins
of water-closets, — he had previous knowledge of the morbid in-
fluence 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 products
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 destroyed 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 necessary,
and the quantity 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.


Origin of the Toxic Substance 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. Attempt to isolate the

various products of putrefaction. Panum, Hemmer. The sepsine of Berg-

mann’and Schmiedeberg. Multiplicity of the alkaloids of putrefaction.

Zulzer and Sonnensteln, 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 nitration 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 fasces toxic. Demonstration of the toxicity of

fasces. Stich. My researches upon the alkaloids of fasces; their multi-
plicity and their chemical characters. Intravenous injections of the extracts
of faeces. Aqueous and alcoholic extract. Extract of fasces deprived of their
mineral substances. R6sum€ of the sources of toxicity. Kukula’s experi-
ments on intestinal obstruction. Hoppe-Seyler and Herter.

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 introduced
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-organisms
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
longer containing any formed corpuscle visible under the micro-
scope; he observed the same phenomena. Besides, I have re-
called 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 is sufficient to produce the most
severe accidents. We know that the physiological effects are, in
these cases, proportional to the mass of toxic matter introduced
into the organism.

The toxicity of the products of putrefaction, taken gener-
ally, 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. Bedissolving 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 years later Hemmer 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 body, com-
parable chemically to vegetable alkaloids, combining with acids
to form crystallizable salts, and producing the same physiolog-
ical 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
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 pres-
ence 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, which 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 toxicity ; 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.


April 30, 1885. We macerated, in the cold, 500 grains of muscle in
500 grams of water for twenty-four hours. We pressed it; we obtained
502 cubic centimeters of a distinctly colored liquid, and filtered it.
We injected into a rabbit weighing 1850 grams 50 cubic centimeters of
this liquid, or 27 cubic centimeters per kilogram. We observed a medium
myosis and great depression. The liquid was not sufficient to allow
of a larger injection.



May 5, 1885. 1. We macerated 1200 grams of muscle in 1200
grams of water, in a stove, for two days. The liquid, strongly colored
red, was filtered. Into a rabbit weighing 1720 grams we injected 40
cubic centimeters of this liquid. Death supervened, with dyspnoea and
convulsions, but with little myosis, after a dose of 23.25 cubic centi-
meters per kilogram.

2. We decolored, by means of charcoal, a certain quantity of this
same liquid. Into a rabbit of 1480 grams we injected 100 cubic centi-
meters. Death supervened, with slight convulsions and myosis. The
animal received 67.56 cubic centimeters per kilogram.

The pupillary contraction which the injection of normal
urine causes is also produced by the injection of putrid mate-
rial, even though it has been filtered through charcoal. The
toxicity of these substances is, therefore, due to another sub-
stance than that which exists in normal urine, since this, filtered
through charcoal, loses its power of causing contraction of the

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 alka-
loids have been studied with some care; but the toxicity of
putrefactive products is due to other causes than alkaloids.
There is yet another series of toxic substances which putrefac-
tion 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 tract, for the digestive canal
is a veritable putrefactive apparatus. Moisture, heat, and the
germs coming from the atmosphere concur in producing putre-
faction as soon as the hydrochloric acid or the bile has disap-
peared 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.
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, — trypsin. Since 1881 Tanret has seen that
ether and soda carry into the peptones some substances having
the characters of alkaloids, and which, in spite of certain anal-
ogies in chemical reaction, differ already from peptones by their
solubility in ether. In 1883 Brieger demonstrated that alkaloids
are developed during the act of peptonization. Faecal matter
contains also excretine, whose presence and toxicity Marcet has
drawn attention to. Strong as was the presumption in favor of
the toxicity of faecal substances, it was yet necessary to demon-
strate it briefly.

In 1853 Stitch 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 insol-
uble in chloroform, 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, phosphomolybdate of soda, tungstate of soda, and
tannin. I have isolated them in notable quantities, but insuf-
ficient to produce intoxication. I believe, therefore, that putre-
faction plays a part in the toxicity of faecal substances, but less
than is supposed. I have practiced intravenous 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.
I have seen the alcoholic extract from 17 grams of faecal matter
kill, having induced severe convulsions. Now, man forms, in
twenty-four hours, 400 grams 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, neu-
tralized 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 grams of
faecal matter that we must inject to induce toxic and fatal acci-
dents, but the extract of 298 grams.


April 28th. We collected on April 23d 600 cubic centimeters of
fsecal matter, which we exhausted with 1 liter of absolute alcohol. The
alcohol was filtered and distilled. The residue was taken up by 225
cubic centimeters of absolute alcohol. We afterward divided the liquid
into two parts, — one of 150 cubic centimeters, representing 400 grams
of fsecal matter; the other, 75 cubic centimeters, representing 200
grams of fsecal matter, (a) The second part (200 grams) was distilled
and taken up by water. After filtration we obtained 90 cubic centi-
meters of liquid, of which 1 cubic centimeter represented 2.22 grains of
fsecal matter. Into a rabbit of 1850 grams we injected 33 cubic centi-
meters of this liquid. At this moment convulsions, death. That is, 17.8
cubic centimeters per kilogram, or the extract of 39.5 grains of f&cal
matter. (b)The first part (400 grams) 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, fil-
tered, evaporated, and took up by absolute alcohol. Again we filtered,
evaporated, and took up by distilled water, and then filtered. We ob-
tained 35 cubic centimeters of liquid, of which 1 cubic centimeter repre-
sented 13.4 grams of fsecal matter. Into a rabbit of 1340 grams we in-
jected, by an intravenous channel, 35 cubic centimeters. No phenomena
were observable. The rabbit received 400 grams of fsecal matter, or the
extract of 298 grams of fwcal matter per kilogram.


We may, therefore, consider the following as contributing
to the toxicity of the faeces : on the one hand, potass and am-
monia chiefly ; on the other, something which is soluble in alco-
hol, and which is neither potass nor ammonia; then bile; and,
last, 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.

[In the preceding paragraphs Bouchard shows that it is
particularly the alcoholic extract of faeces that is energetically
toxic. Physicians are familiar with the fact that in patients
who are the subjects of intestinal obstruction there are shock
and a series of symptoms over and above those which neither
the vascular condition of the wall of the bowel nor the blocking
of the alimentary canal adequately explains. The prostration
and collapse, which are usually very great, are much more prob-
ably the result of absorption and therefore signs of auto-intoxi-
cation. With the view of determining, if possible, what the
substances are that produce the symptoms in intestinal obstruc-
tion Kukula (Archiv fur klin. Chirurgie, vol. lxiii, p. 773)
undertook a series of experiments. Two classes of poisons are
known to exist in the alimentary canal : 1. Those arising in
6mall quantities during normal digestion: e.g., (a) such prod-
ucts of carbonic acid fermentation as acetic, lactic, and butyric
acids; (b) those from the putrefaction of albumins as NH 3 ,
C0 2 , H 2 S, leucin, phenol, etc. 2. Chemical substances formed
in stagnant or fermenting faecal matter, e.g., pyridin, toxalbu-
mins, or ptomaines. Of these latter, Kukula attaches most im-
portance to such of the diamins as tetramethylene and penta-
methylene diamins, ethylene diamins, cholin and neurin. By
the term diamins we mean bodies “in which two amin (jSTH 2 )
groups are united to a diatomic alcohol radical of the olefine
series of hydrocarbons.” In health the peristaltic movements
of the bowel are promoted by the products of the first group
when they are present in small amount. Should these be in
excess they cause gastro-enteritis, whereas sulphuretted hydrogen,
ammonia, and phenol are really toxic. It is the products of the



second group, however, that principally cause auto-intoxication.
Kukula injected subcutaneously toxins obtained from filtrates
of intestinal contents into 39 animals, in most of whom no re-
action occurred. Of 9 of the animals in whom he produced arti-
ficial intestinal obstruction, only 1 died, and of 5 animals in
whom he produced strangulated hernia, 1 only died. The in-
testinal contents of the animals operated upon were not specially
toxic. In 12 dogs he attended to produce artificially intestinal
obstruction, and succeeded in 7. Of these, 4 died in a few days
with well-marked symptoms of intestinal obstruction, the lesion
being confirmed by postmortem examination. The other ani-
mals were killed before presenting any characteristic symptoms.
In the urine of all the animals Kukula found phenol and in-
dican; he noticed that these substances increased progressively
in the urine until the day of death or in the dogs that recovered
until the function of the intestine was restored. Taking the
intestinal contents of the obstruction cases he found that these,
whether they were injected pure or as filtrate, caused poisoning.
Like Bouchard, Kukula observed that the substances abstracted
from fasces by alcohol were powerfully toxic and were especially
so when administered by intraperitoneal injection than sub-
cutaneously. To pentamethylene diamin, sulphuretted hydrogen
and methylmercaptan is attributed the principal role in causing
symptoms : symptoms which in a general way recalled those that
are observed in man in intestinal obstruction and which are
probably due to absorption of septic matter through the intestinal
wall whose epithelial lining must become altered in this grave
affection. In intestinal auto-intoxication there is absorption
probably of more than one substance, gaseous or solid in solu-

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
products of intestinal putrefaction, among 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 reabsorbed by the intestinal mucous mem-


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 kidneys; if the kidneys are diseased the individual dies.
To all cases of death arising from suppression of the renal func-
tion we apply the term ursemia. But what we already know
enables us to foresee that a complexity of phenomena is hidden
under this name.

[Bouchard’s main contention in this chapter, while indi-
cating the sources of certain intestinal toxins, is that it is through
the eliminating powers of the emunctories that auto-intoxication
is prevented. To this safeguard we might add the influence of
chemical changes determined by processes of oxidation and de-
oxidation, hydration and dehydration, that are normally occur-
ring within the organism. The oxidative processes that are
constantly taking place at the normal temperature of the human
body are not known much beyond the fact that the red blood-
corpuscles are continually parting with oxygen to the various
tissues. While oxidation is therefore a vital act depending upon
a splitting in the oxygen molecules leading to a separation of
two atoms of active oxygen, which possesses the characters of
the nascent gas. Combustion processes occur, on the other
hand, in the liver whereby the complex molecules derived from
food products absorbed from the intestine are converted into
substances of a simpler chemical composition and less harmful
character. It was Hoppe-Seyler’s opinion that the oxygen is in
these processes set free by nascent hydrogen formed in the course


of certain decompositions, while Herter suggests that the iron
in nucleo-proteids may play a part in oxidation through ferric
salts being reduced to ferrous, these again becoming ferric by
the renewed absorption of oxygen; also that the presence of
hydroxyl (OH) ions in the blood and lymph may contribute
“either by taking the place of hydrogen atoms or by liberating
nascent oxgen simultaneous with the formation of water” (Her-
ter, “Lectures on Chemical Pathology,” p. 22), or it may be
that these hydroxyl ions act through the hydroxides dissolving
the carbonic dioxide that is constantly being formed by cells.
Were it not for the constancy of these oxidation processes the
human body would be much more frequently menaced by auto-
intoxication and the eliminating organs more surely taxed.
Taking indol as an example of a putrefactive alkaloid formed
in the intestine during digestion, this is known to possess poison-
ous properties. After absorption indol in its passage through
the liver is primarily oxidized by the hepatic cells into indoxyl,
which, subsequently combining with sulphuric acid, is converted
into indoxyl sulphate of potassium : a body not only less toxic
than indol, but one more easily thrown out by the kidneys. By
means of the oxidative and deoxidative processes that are taking
place in the organism not only is considerable help given to the
eliminating organs, but poisonous substances are deprived to a
large extent of their toxicity.

The word “ion” recently introduced into physical chemistry
calls for some explanation. An “ion” may be either an atom
or a group of atoms as seen in the following: Water is com-
posed of H 2 and its molecules are in constant movement; these
molecular movements become more energetic as the temperature
is raised. Because the molecules of which it is composed un-
dergo, practically speaking, no dissociation into their constituent
atoms pure water is not a conductor of electricity. When a sub-
stance like sugar is dissolved in water, the solution still remains
incapable of conducting an electrical current; the sugar mole-
cules do not undergo dissociation. “But if a substance like salt
is dissolved in the water, the solution is then capable of con-
ducting electrical currents, and the same is true for most acids,
bases, and salts. These substances do undergo dissociation, and


the simpler materials into which they are broken up in the water
are called ions. Thus, if sodium chloride is dissolved in water
a certain number of its molecules become dissociated into sodium
ions, which are charged positively with electricity, and chlorine
ions, which are charged negatively with electricity. Similarly a
solution of hydrochloric acid in water contains free hydrogen
ions and free chlorine ions. Sulphuric acid is decomposed into
hydrogen ions and ions of S0 4 .” . . . “Ions liberated by
the act of dissociation are charged with electricity, and when an
electrical current is led into such a solution, it is conducted
through the solution by the movement of the ions. Substances
which exhibit the property of dissociation are known as electro-
lytes. The liquids of the body contain electrolytes in solution,
and it is owed to this fact that they are able to conduct electrical
currents.” (Halliburton, “Essentials of Chemical Physiology,”
p. 200, 1901.)]


Intestinal Antisepsis.

R6sum6 of the causes of the toxicity of the contents of the digestive canal.
Potass and ammonia, bile, putrid substances. Poisons absorbed in the in-
testine must traverse the blood, since they are found in the urine. Parallel-
ism between the toxicity of urine and that of material contained in the in-
testine. 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 bring 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, disassimilation, 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 potass and ammonia,
from 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 dem-
onstrate 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

In 1882, while demonstrating the alkaloids found in normal
fsecal 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 milligrams per kilogram of fsecal
matter. I noticed that each time these alkaloidal substances
increase in the faeces they increase in the urine, although always
smaller in quantity. I noticed, too, that the parallelism is pre-


served not only from a quantitative point of view, but also 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 feecal matter.

The extract of 200 grams of fa?cal 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, while we killed with the extract of 17 grams,
of fascal matter not disinfected, per kilogram. 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 in-
testinal canal.

It is a long time since we have produced antisepsis without
knowing it, just in the same way as M. Jourdain 1 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, —
excellent antiseptic, — the sulphites, hyposulphites, phenic acid,
creosote (Pecholier), and boric acid. We have obtained nothing
by these means save, perhaps, with the sulphites (Semmola,
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

“■This refers to “Le Bourgeois Gentilhomme” of Molidre.


long journey from the mouth to the intestine the antiseptic
agent loses some of its power. One other inconvenience which
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 in-
fluence upon the organism. We must, therefore, use insoluble

Salicylate of bismuth and iodoform, extolled by A^ulpian;
naphthalin (Rossbach) ; calomel, which is changed into bichlo-
ride in the stomach and black sulphide in the intestine; black
sulphide 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 fecal 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

When we administer naphthalin the stools contain it. This
body, hitherto considered insoluble in water, is absorbed to the
extent of some centigrams for every 5 grams we have given. The
urine rapidly takes on a brownish-black coloration, different from
that of carbolic acid, which is tinted black, and from creosote,
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 naphthosulphurous acid, which may
be arranged as naphthosulphite of soda. This union can only
have occurred by sulphur having been borrowed from the organ-
ism ; that is to say, by destroying albumin or nitrogenous matter.


But this quantity of sulphur is insignificant, as I have been able
to ascertain by the aid of M. Eosenstichl. Prom the whole of
the urine passed by a woman who had taken for ten days 5
grams of naphthalin we were only able to remove 0.03 centi-
gram of naphthosulphite of soda per liter.

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 faecal matter without preventing fermentation.
Since then I have added iodoform to charcoal, which neutral-
izes putrid ferments, according to the formula: charcoal, 100
grams; iodoform, 1 gram.

Following Eossbach, 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 : 5 grams of naphthalin, mixed with an
equal quantity of sugar, made aromatic with 1 or 2 drops of
bergamot, divided into 20 powders, 1 of which is to be taken
every hour.

Faecal matter at length loses its odor, unless it is simply
masked by that of naphthalin. But a second and greater ad-
vantage is that faecal matter loses, to a great extent, its toxicity,
the putrefactions within the intestinal tube being completely

In the case of a man the subject of gastric trouble, 35 to
40 cubic centimeters of urine induced death for every kilogram
of animal. After disinfection of the faeces by naphthalin from
90 to 100 cubic centimeters of urine were harmless. This harm-
lessness of the urine lasted as long as the antisepsis of the
digestive canal. When antisepsis was suppressed the urine be-
came toxic again.

With charcoal I was less enlightened upon the cause of the
inoffensiveness 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 or-
ganism would be attributable to the poisons of disassimilation.
Here is research for the future.

To sum up : I have succeeded in demonstrating that not
only are there poisons in the intestine, but that they are a
constant 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 laden 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 stercorasmia
or coprasmia.

If I have written at such length upon physiological data,
it is because these were indispensable before undertaking the
analysis of pathological facts.


Pathogenesis of Uremia — 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 uremic period, — albuminuria, cachexia from hypo-albu-
minosis. Dropsy. Vascular and cardiac troubles; their effect upon the di-
gestive 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, vari-
ously associated. There would, therefore, be not one, but several uraemias.
Clinical investigation has, for some time past, established various sympto-
matic 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 physiological knowledge which
we have acquired only throws light upon some of the accidents
which complicate diseases of the kidney.

Among 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 accu-
mulation of toxic substances in the economy, and for symptoms
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
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 grams of urine which it secretes ordinarily in twenty-
four hours, a normal kidney can secrete as much as 25 liters of
urine, and more. Instead of 20 to 30 grams, it can eliminate
120 grams of urea, and more, as in a large number of cases
of diabetes insipidus. Instead of 55 centigrams of uric acid,
which the kidney eliminates in the normal state, it can, in
cirrhosis and in leukaemia, eliminate 8 grams of it, and more,
in twenty-four hours. It can, in addition, eliminate other ab-
normal substances, up to 140 grams of sugar per liter. 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 albumin.

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 there 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 oedema 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 centigrams — at the
most, a few grams — of albumin which the patient eliminates
each day. Such a slight spoliation is not capable of causing
deterioration of the system. A woman who is nursing loses,
without any injury, 40 to 50 grams of albumin or other proteid
matter by the lacteal secretion, and yet her 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
albuminuria becomes a cause of exhaustion, like abundant leu-


corrhcea, dysentery, suppurations, and frequently tapped ascites.
An elimination of albumin in considerable quantity may cause
impoverishment of the blood. There are large albuminurias, —
from 8 to 12 grams in twenty-four hours. This last limit is
seldom exceeded; we mention as very rare that of 16 grams.
I have seen a patient lose 19 grams daily of albumin, reckoned
as dry albumin ; it was in a case of amyloid degeneration of the
kidneys, liver, spleen, and stomach. In these cases we under-
stand 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 hydraemia.
There is produced a correlative increase of water, a relative
hydraemia, and, besides, often enough, an absolute hydraemia,
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-albumin 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 impermeability. We
cannot say that there is uraemia, nor even kidney disease; there
is a general disease of the organs concerned in assimilation.

Hydraemia 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, hydraemia 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 collec-
tion of conditions extremely complex, and all foreign to intoxi-
cation; therefore we do not pretend to explain by intoxication
most of the accidents of nephritis.

As a consequence of hypo-albumosis there appear oedema,
anasarca, and serous accumulations in the large cavities. Ac-
cording to Bartels, the hypothesis of Bright, which regards


hydrgemia as favorable to the diffusion of serum, is not sufficient.
Bartels believes that there is an hydraemic 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 albuminuria, but the
hypothesis of Bartels seems to me to be inadmissible.

In a goodly number of cases we must take into considera-
tion both vascular and cardiac disturbance, but in interstitial
nephritis, 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 hyper-

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 ex-
tremities; 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 how modi-
fications of the cardio-vascular system bring about secretory
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 haemorrhages, epistaxis,
haematemesis, 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.

Throwing out of consideration all the foregoing accidents,
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 it can no longer eliminate the toxic substances pro-
duced 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 passed 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
functionate normally. If both are diminished, there is danger
of intoxication.

We must not, in this estimation, take for our type the
quantity of urine secreted by a healthy man ; a sick man ingests
and destroys little. The numbers — e.g., of 1350 cubic centi-
meters 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. Last, 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. Eetinitis,
amaurosis, 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, bordering
upon inflammation which has not resolved. But these incom-
plete phlegmasias, cedenia of the glottis, hgemorrhagic and puru-
lent pericarditis, are, at any rate, only accidents farther re-
moved 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 removed 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 that has become excessive. Beyond this we
enter the domain of intoxication.

We find ourselves in the presence of an intoxication which
may be due to one of seven poisons, which analysis of the prod-


ucts of toxicity has revealed to us, or to several among them,
associated two by two, three by three, or to all the seven together ;
finally, water (the elimination of which may be prevented) 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 pathogenesis for the five
following theories, which include (1) cerebral oedema (Traube) ;
(2) urea (Wilson) ; (3) ammonia (Frerichs) ; (4) extractive
matters (Schottin), and, notably, oxalic acid (Bence- Jones),
urochrome (Thudicvim), and (5) potass (Feltz and Bitter).


Pathogenesis of Uremia — Discussion of the Exclusive


The ursemic period of nephritis is characterized by the appearance of chronia
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-ursemic period; for

example, cedemas. Clinical observation has established several modes of

grouping of symptoms of the uragmic phase while seeking to relate them to

certain anatomo-pathological forms. Every inventor of a pathogenic

theory has appealed to bedside observations for a justification of his opin-
ion. Traube incriminated, as the cause of ursemic accidents, the cerebral

oedema which might result from hydrasmic plethora. His opinion is want-
ing in anatomo-pathological proofs, and rests rather upon lnadmissable
physiological arguments. Chambrelent and Bois: diminished urinary tox-
icity in pregnancy. Wilson invoked excess of urea in the blood. Urea

cannot explain accidents in the quantity in which it exists in the blood of
urasmics. Injection of urea into the stomach, into the cellular tissue, Into
the veins after nephrectomy.

I have shown that many of the accidents called urasmic
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 twenty-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 pre-
paratory period persist. We still find cedemas, which increase
or diminish; alterations of temperature; sometimes hypother-
mia, 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 coexistence
of unusual symptoms and the presence or absence of low tem-
perature, cases of uraemia when observed clinically, seem so



different 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 form of 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 explana-
tion alone of all the nervous accidents which may appear in the
course of disease of the kidney. Besides, clinical observation
has endeavored to group a certain number of particular cases,
according to their symptomatic 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 diarrhoea, vomit-
ing, nor any other flux capable of carrying away water, and there
is oliguria; there is, therefore, retention of water in the or-
ganism. The other normal secretions continue; the tongue is
moist. We in vain seek for the presence of ammonia in the
expired air. In these cases are found reunited all the conditions
of hydremia or of hydramiic 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 explain, by the
theory of intoxication, the accidents which arise. There is, on
the contrary, an undoubted accumulation of water in the organ-
ism. Thus, the idea has arisen that the accidents called ursemic
are due to an accumulation of water.

Traube has actually thought that the consequence of hydre-
mia was a tendency to the production of oedema, and, notably,
to cerebral oedema. Coindet and Odier have seen in this suf-
ficient to explain the development of a ventricular dropsy. Ac-
cording to their manner of viewing the subject, interstitial oedema
or ventricular dropsy, by compressing the encephalon within and
without, diminishes the space left free for the blood; hence


cerebral anaemia involving the production of comatose conditions
when the anasmia is especially marked at the level of the con-
volutions, or convulsions if it predominate in the mesencephalon.

If we wished to furnish, like Traube, a general explanation
of the facts reputed to be uraemic, 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 drops, 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, be-
sides, 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 uraemic accidents pro-
duced in patients who are eliminating water in excess; their
urine is more than normal in quantity, and they discharge it from
the stomach and intestines.

Hydraemia should have, as an effect, oedema; but it would
be necessary to demonstrate experimentally this relationship,
for neither experimental pathology nor clinical observation con-
firms it.

Double calculous obstruction, suddenly developed, produces
uraemic accidents, at the end of a recognized time, without in-
ducing oedema. Thus is found broken one of the links in the
chain of reasoning of Traube.

Eichardson 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 everything 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.


But, in what form of disease of the kidneys do we find 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, Ave 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 quan-
tity. Death results from this injection when we have introduced
into the blood 122 grams of water per kilogram 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 Eichardson 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 there-
fore inactive. How can we compare this excessive hydraemia
with the moderate retention of water in the blood which may
exist in pathological cases ? In absolute anuria uraemic accidents
burst forth sometimes before the fifty-sixth hour, when a man
has not as yet accumulated more than 35 grams of water per
kilogram of his weight. But we know that injections of water
only begin to be injurious after 90 grams per kilogram.

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, hoAvever, if you please, cerebral oedema. I
am ready for all concessions. But then it Avill 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 among chemical accidents. But,
are there any chemical and toxic accidents in Bright’s disease?

We can furnish proof — yes, 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
urine fall, and Ave have been forced to believe that owing to the


whole of the solid substances being no longer eliminated, the
individual was about to become intoxicated. But on the day
in which nervous accidents called urasmic appear the urine ceases
to be toxic. The whole of the urine of twenty-four hours from
a urasmic patient cannot kill a rabbit, nor does it exceed the
toxicity of distilled water. And yet, while with 120 cubic centi-
meters of distilled water per kilogram of animal, used as an
intravenous injection, you are in danger of inducing death, with
this same dose of certain urines taken from uraemia subjects
you will determine no phenomenon, not even the pupillary con-
traction caused by normal urine.

[Numerous experiments made by later writers have confirmed
the statement just made that the urine of eclamptic women loses
its toxicity owing to the retention of poisons in the blood and
failure of the kidneys to eliminate these by the urine. In a
series of researches on the toxicity of urine in pregnant women
Chambrelent and Bois found a marked decrease in the toxicity
of the urine beginning with the second month of pregnancy, a
decrease which they believed to be due to functional hyperactiv-
ity on the part of the liver, for should hepatic inadequacy by any
means arise the toxicity of the urine invariably increases. So
long as the toxicity of the urine is at its maximum the individual
is free from the risk of auto-intoxication. In the permeability
of the kidney to poisons there is safety.]

There yet remains to be known what is or what are the
poisons which determine the toxic and chemical accidents of
uraemia. 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 uramiic
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 uraemia contains less urea. It has been shown that there
is in the blood as much as thirty-two times more urea than in
the normal state; that in the muscles there is as much as 1.20
grams instead of simply traces of it. I have met with it, among
those suffering from choleraic anuria, in the tissues where it is
not formed normally. The theory, therefore, would be legitimate
Bave for its demonstration.


Gallois has injected into the stomach, Treitz into the veins,
and Eichardson 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 any-
thing. 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 Ritter have repeated the experiment.
They have at length induced death as speedily in healthy animals
as in those upon whom they had performed nephrectomy. They
employed urea which they obtained from Germany, so as to have
it purer. On analysis this, however, was found to contain sul-
phate and chloride of ammonia. Ritter began to prepare pure
urea himself, and, setting out from the day in which he made
injections with this urea, he no longer determined 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 accidents
called uraemic.

In order to kill a man it would require the total quantity
of urea which he makes in sixteen days. But, in double calculous
obstruction, suddenly developed, uramiic accidents appear — some-
times at the end of the second day or at the commencement 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. During that time, as we know, he has been able to
accumulate a sufficiency of other toxic substances capable of
bringing about intoxication. Clinical observation is here, there-
fore, completely in accordance with experimentation in denying
to urea the power of producing the intoxication called urasmic.


Pathogenesis of Uraemia — Discussion of the Exclusive

Theory of ammonccmia (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? (Brenard and Grandeau,
Treitz, Jaksch.) Objection to the theory of ammonsemia as the absolute

explanation of uremic accidents. Theory which incriminates extractive

substances; that of Schottin, Scherer, Oppler, Chalvet. Creatinwmia 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
urasmic, with a diminution of the solid matter contained in the
urine of twenty-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 density.

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 ursemic

After this, while reviewing the various hypotheses which
have been built upon the nature of the poison or poisons, the
retention of which produces urasmic 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 uraemic 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 disin-
tegration of urea is the pathogenic poison of uraemia ; such is the
theory of ammoncemia. As was said when discussing oedema,
Borne have twisted the clinical aspect, in order to give a symp-



tomatic 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 albuminuria 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 theory. 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 density 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 dryness 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 normally we find trace’s 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 authorizes the admission of this transforma-
tion as the cause of uraemia, 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 Bitter). The amount of urea found
in the urine exceeds but slightly that of the injected urea;
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

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 elimi-
nated fifty times more quickly by the kidney than by any other
emunctory. If 1 kilogram of blood contains 16 centigrams of
urea, 1 kilogram of urine contains 16 grams. But it is the
plasma of the blood which delivers the urea, and 1 kilogram of
plasma contains 32 centigrams 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 ex-
plain the presence of ammonia in the digestive canal, it is quite
useless. There is enough of it normally, without the interven-
tion of urea. Can we say that ammonia may not play some
other part in uraemic 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 in-

Nevertheless, ammonaemia may be produced in cases of
absolute retention by the kidney. Ammonia is toxic, in mod-
erate doses, like potass; it produces convulsions and a great
fall of temperature. This symptom, which ammoniacal intoxi-
cation produces in the highest degree, is only an accident con-


tingent 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
ammonia in the blood. We reject ammonaemia as the absolute
explanation, while 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 once it is filtered through charcoal it loses this property.
Urinary ammonia passes through the filter, while the substance
which determines hypothermia is retained in 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, Schot-
tin, Oppler, Perls, and Chalvet. In this way has the theory of
poisoning by extractive substances originated which Jaccoud has
formulated, under the name of creatinwmia, without 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 regarding which Chalvet and those who share his
opinion have spoken, we see the amount of the extractives, of
urea, and coloring matter diminish in the urine; in the blood


extractives increase while 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 acci-
dents, 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 gram per kilo-
gram of the animal. Hippuric acid, according to Challon,
Feltz, and Eitter, can only become toxic in the quantities formed
by the animal in from 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 grams per kilogram 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
Eitter 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. Creatinin, 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 Eitter 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, there-
fore, 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, in the form of creatinin chloride, by an in-


travenous channel, does not hasten death by one minute, in the
ease of a dog, after nephrectomy. Death has been induced on
the third day, as ordinarily (Feltz and Bitter).

Leucin: All that water can dissolve of it produces no acci-
dent (Feltz and Eitter). 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 gram per kilogram of animal, is with-
out effect. Xantliin, hypoxanthin, and guanin do not produce
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 urtemia. We have seen already that normal
urine loses the one-half of its toxicity by decoloration ; decolored
bile is also less toxic. The coloring matters are, therefore, sus-
pected 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.,
urobilin. 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 material. I can only
say that, if bilirubin kills, after a dose of 5 centigrams per kilo-
gram, urobilin, in a dose of 15 centigrams, does not kill at all.


Pathogenesis of Uremia — The Part Played by

Organic Substances and Mineral Matters

in Uremic 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 fixed 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.

Earthly 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 by 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 they have
not been able to produce death, they deny to the organic sub-
stances every toxic action, without wishing to admit that their
partial toxicity could be regarded as an explanation of the com-
plete toxicity.

Let us see, however, with MM. Feltz and Eitter, what the
mineral substances can do? These are very numerous, but a
large number of them can be left out of consideration, on account
of their insignificant weight. A man of 75 kilograms eliminates
in twenty-four hours 1350 grams of urine, the density of which
is 1019. This urine contains 59 grams of solid matter, which
is decomposed into 43 grams of organic matter and 16 grams of
mineral. These last are composed of 2 grams of earthy salts
(salts of lime and magnesia), 4 grams of salts of potass, and 10
grams 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 liter of urine, we have : —

{Earthy salts, 1.50 grams.
Salts of soda, 7.50 grams.

The whole of the earthy salts do not come out well in ex-
periment, on account of the difficulty which there is in main-
taining them dissolved in the blood-plasma by intravenous in-
jection. I cannot, therefore, say anything about them. Besides,
they are in small quantity in the mineral mass. The alkaline
salts on the contrary, are very soluble. They are of large quan-
tity, and deserve our attention.

The salts of soda seem the more important on account of
their weight. In reality they have only a feeble toxicity. Chlo-
ride of sodium kills 1 kilogram of animals in the dose of 5.17
grams; but chloride of sodium is the most toxic of the salts
of soda of the urine. The soda of the urine of twenty-four hours

_ … f Organic, 32 grams. ,

Solid matter, 44 grams. ■! _ _, 1(1 <( Salts of potass, 3.00 grams.


would kill; at the outside, 2 kilograms, while this quantity of
urine kills 30.

It is otherwise with the salts of potass. They are occasion-
ally present in large quantity, — 3 milligrams per cubic centi-
meter of urine. Forty to sixty cubic centimeters of urine being
toxic (the mean 45), the quantity of urine which kills one kilo-
gram of animal would contain nearly 13 or 14 centigrams of
salts of potass. This would be nearly a sufficient quantity if all
the salts of potass were represented by chloride of potassium;
but there are the phosphate, sulphate, and phenysulphate of
potass, which do not have the same toxicity. The chloride of
potassium is the most toxic; it kills in the proportion of 18
centigrams per kilogram of animal. But the phosphate of
potass only determines toxic accidents after a dose of 26 centi-
grams. 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 Bitter, 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 centimeters 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 quantity of potass double that which the
usual quantity of urine causing death contains. Besides, this
quantity of potass kills in quite another way, viz. : with con-
vulsions; whereas normal urine, taken during the height of the
day, does not induce convulsions. In death by potass the heart
is arrested; this organ continues to beat, however, when it is
urine which has caused the poisoning. A normal, decolored
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
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 decolored, 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 framework 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 the urine becomes scanty, if, instead of 1000 grams,
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
liter, but not for the twenty-four hours; the emunction falls to
one-half or two-thirds of that which it ought to be and there
occurs 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, in ureemic phenomena, there may be, in certain
conditions, a predominance of the action of potass, which may
represent two-thirds of the toxicity, 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.

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 corpuscles, which
are so richly provided with and are so strong in their affinity
for it. Suppose even that there is an accumulation of potass in
the blood-plasma ; this would not explain uraemia, in which there
are only convulsions ; it would not explain the subjective symp-
toms which precede those or accompany them, — narcosis ; uraemic
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 toxicity 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. For Table of Substance, see next page.

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 kilogram of man eliminating in twenty-four hours a
quantity of urine capable of killing 461 grams of animal, the
proportional part of the mineral matter in this toxicity may be
indicated as follows: potass kills 217 grams; soda, 30 grams;
calcium, 10 grams ; magnesia, 7 grams. The whole of the miu-




eral matter kills 264 grams. On the other side, urea kills 63
grams. There remains to be destroyed 134 grams. We know
from other experiments that normal urine leaves behind in char-
coal one-third of its toxicity ; that charcoal, consequently, retains
matter which must be capable of killing 154 grams. Among
these substances fixed in charcoal there is one-sixteenth of the
total potass; this fraction of potass would kill 14 grams. The
organic substances capable of being fixed by charcoal would
therefore be capable of killing 140 grams. This figure passes by
6 beyond the 134 grams which remain to produce intoxication.
That is due to errors inherent in all these estimates; the cause
of it may be 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 coutaining poisons which are antagonistic,
— a fact which we have placed beyond doubt.

We may say that 1 kilogram of man eliminates in twenty-
four hours organic matter, capable of being fixed by charcoal,
which is able to destroy at least 134 grams 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, — one contracts the pupil, another is convulsive, and the
third lowers the temperature. Chemistry will also have to isolate,
in the alcoholic extract, the narcotic substance and the salivating,
which is perhaps toxic. I have thought that the alkaloids will

Name of Substance.

Index of

Quantity of Substancs
Necessary to Kill One
Kilogram of Animal.











0.180 gram.

0.181 gram.

0.263 gram.

5.17 grams.

9.00 grams.

6.00 grams.

0.463 gram.

0.542 gram.

1.011 grams.



only explain a very small portion of the 30 per cent, of the tox-
icity attributable to undetermined bodies.

In any case, we have come to this conclusion : It is that the
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
various 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 reabsorption of urine. The
sources of uraemia are : disassimilation, a certain number of
secretions, alimentation, — especially the alimentary mineral sub-
stances, — and, last, intestinal putrefactions. The knowledge of
these origins of uraemia furnishes, as we shall see, valuable indi-
cations from the point of view of treatment.


The Therapeutic Pathogenesis of Uraemia.

Resume 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 medica-
ments 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 grams removes as much poison as
280 grams of diarrhceic liquid, and as 100 liters 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 urasmic poisons. Inhalations of chloroform. Action of chloral. Bromide
of sodium. Traditional and pathogenic therapeutics. Milk regimen to di-
minish biliary secretion and to prevent putrescible intestinal residues.
Charcoal as the means of 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 uraemia, 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
demonstrated to you, differs, to a certainty, from the old doc-
trines and 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 uremic. 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 creatingemia —
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-
tion ; but to me this is only one of the sources of the production
of the toxic bodies, and it is necessary to add to them the poisons
furnished by the biliary secretion, alimentation, and intestinal

The pathogenic 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 by the impermea-
bility 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 the kidney to
be supplanted 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 deprivation
of water from the economy by increasing the perspiration, 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, unfortunately, that
which is toxic. We, perhaps, remove from the economy certain
toxic substances which ought normally to leave by the skin, but
not those which the kidney is charged with the duty of eliminat-
ing. 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 logically 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,
by means of revulsive (wet or dry cupping, leeches, sinapisms).
Sometimes we are obliged to stimulate the nervous system 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 many 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 you that
this medicine ought not to be indifferently employed at all peri-
ods in diseases of the kidney. When the function of the kidney
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 sub-
stances formed by the organism, there is then retained the
medicinal substances; the kidney is as impermeable for thera-
peutic poisons as for natural poisons, and the employment of
toxic medicines, in similar cases, has no other effect than to bring
about an association of medicinal intoxication with a urasmic.

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
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
that 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 immediately to 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 general 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 sys-
tem, in order to augment the general arterial tension and, in
consequence, stimulate the renal function to activity. This
result may be obtained 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 administer cool drinks, which, besides the stimulation which
they impress upon the contractility of the abdominal vessels, will
induce absorption of a certain quantity of water, in order still
to increase diuresis. Among the liquids which it is usual to
prescribe, milk is one of the most powerful medicaments which
we can oppose to ursemic 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 urasmia, and which, on its own side, even com-
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 quantity 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
liters in twenty-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

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 stomach,
and intestine ?

For a long time we have combated uraemia by inducing vom-
iting. 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 in-
creases the gastric secretion. It has, 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 they
have provoked hypersecretion by drastic purgatives. Purgatives
have been employed for a very long time, in accordance with
theoretical views. It is upon the theory of Wilson that physi-
cians 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
blood in the proportion in which it is found in the blood-plasma.
If the serum of blood contains, per liter, 32 centigrams of urea,
the liquid which exudes into the intestine under the influence
of purgatives contains exactly 32 centigrams of urea per liter.


On the other hand, if we remove one liter of water from the
blood by the intestinal tract, it is simply a liter of water less
that will pass away by the renal path; but this liter 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 ursemic 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, consequently, 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 and 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 wanting in the urine had been carried
away by the intestinal fluid.

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 grams
of blood you remove from it 50 centigrams of extractive sub-
stances; the daily elimination by urine is 8 grams; 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 centigrams 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 devel-
opment of fatal accidents.

In any case, it is certain that we remove from the economy
more extractives by bleeding than by any other channel, the
renal tract excepted, for a bleeding of 32 grams removes from
it as much as 280 grams of a liquid diarrhoea does, or as 100 liters
of perspiration. Besides, it is not only 32 grams of blood— the
quantity drawn by two leeches — which we have removed in
similar cases. Abercrombie, Marshall Hall, Eayer, and many
others in addition have employed copious bleedings for uraemic
accidents, and they have seen patients cured who were assuredly
threatened by death. It is chiefly in acute curable nephritis,
such as scarlatinal nephritis, that bleeding finds its formal
indication when ursemic accidents arise, for in these cases the
renal malady only demands cure when the patient does not suc-
cumb to the fleeting attack of uraemia. In these cases, therefore,
it is obligatory to practice bleeding, not only because it is theo-
retically 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 impoverishing his
blood. There is scarcely, therefore, cause for practicing bleeding
in the terminal uraemia of chronic nephritis, except once, viz. :
at that moment when accidents threaten immediate 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 anti-
dotes 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 of 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 bro-
mide of potassium than the nitrate. Under other conditions 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 program for uraemia, such
as our predecessors have bequeathed to us. Among all these
means, what of worth remains? Certain diuretic agents, — first,
such things as milk, and bleeding for certain cases. Yet per-
haps 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 derived from the
knowledge we possess of the sources of the accumulation of toxic
substances in the economy, — disassimilation, the secretion of
the liver, alimentation, and intestinal putrefactions. Let us see
if we cannot act upon one or other of these sources of intoxica-
tion, so as to exhaust or diminish them.

Can we delay disassimilation? Is there any indication for
administering those substances which have the reputation of
diminishing the exchanges of nutrition, and which have been
called the medicines that save 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,— intracellular
and extracellular; the circulation of matter through the cell no
longer goes on, except imperfectly; combustible substances and
the heat-producing agent, oxygen, no longer enter, but with diffi-
culty, 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 beyond the point wished for in our calculations. It is
useless, then, to think of further impeding oxidation, whose in-
sufficiency may, by itself alone, cause death. 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 the urinary toxicity. It is, there-
fore, rational to adopt the practice of Jaccoud, who speaks highly
of the inhalations 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 decolored bile
is much less toxic. We have the means of decoloring bile in the
digestive canal by administering charcoal 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 putres-
cible 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 satisfactory, 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 intoxica-
tion 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 pasty residues incessantly mashed by
the intestines, on the contrary, successively allow of the absorp-
tion 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 iodo-
form in charcoal, and in naphthalin, means which theoretically
permit us to practice this thoroughly. Salicylate of bismuth
may be employed for the same end, and, if ‘we were afraid of
the passage and accumulation in the blood of the small quantity
of salicylic acid absorbed, we might substitute for it the sub-
nitrate. In fact, my colleague, Dr. Tapret, has applied this
theoretical 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 uraemic
dyspnoea 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 im-
mediately 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.


Transitory or Acute Auto-intoxication of 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 in-
creased 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. Toxicity of indol.
Experiments of Schliff and of G. H. Roger. Utility of hardening the in-
testinal contents. Role of auto-intoxication of faecal origin, in internal
strangulation and the morbid states called intestinal septicaemia (Humbert).
The two periods of constipation: constipation with retention of liquid matter
causes symptoms of intoxication, and hardening of the substances renders
the second period of constipation less harmful.

We know that the poisons contained in the intestines, also
those which come from food, bile, or putrefaction, enter, on
the one hand, into the complex intoxication called urasmia.
We can, therefore, understand how, if the quantity of poison
increases in the intestines, an intoxication becomes possible;
also that disassimilation does not hand over to the blood a larger
amount of toxic material when the kidney remains permeable.

To-day we are going to study intoxication by reabsorption
of substances contained in the digestive canal, without the pres-
ence 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. Let us recall these sources : —

1. Foods — even the most inoffensive in appearance — and
the flesh of muscles 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.

2. Bile contains poison. The eight hundred or one thou-
sand grams of bile which are poured 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 sub-



stances: some known, — such as the biliary salts, — others un-

3. Putrefaction which occurs in the alimentary residues
develops poison. The extract of 2.5 grams of putrefied meat
is sufficient to kill.

4. Finally, we have learned that faacal 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
toxicity, — to the union of organic principles, in which are in-
cluded 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, also of ascertaining what
proportion each of the poisons inclosed in the intestines bears
to the toxicity of the whole.

We shall now see how, under normal conditions, the con-
tents of the intestines may become more toxic, and how, even
with a kidney functionally free, if the production of toxic mate-
rial is accidentally more abundant, it may yet accumulate in the
blood in a proportion capable of causing symptoms of intoxica-
tion 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
pharynx. It may induce acid vomiting, the acidity of which is
most frequently due to acetic acid, — rarely hydrochloric. 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 buttocks in the acid dyspepsias of infants. An
acid reaction is substituted for the normal of the intestinal con-
tents. 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 sulphur-
etted hydrogen, ammonia, and sulphate of ammonia, which re-
veal themselves to our senses by the odor of the gas expelled.

Parallel to these objective phenomena there exist those of a
subjective character, among which the most ordinary are fatigue,
depression, headache, buzzing in the ear and deafness, disturb-
ances of sight, and vertigo. With a kidney acting well things
may not go further; but, if the renal emunction is insufficient,
we may see developed a fraction of ursemic intoxication through
simple exaggeration of intestinal fermentation. If, for example,
abundant vomiting has caused oliguria, we may have coldness
established, paralysis of the vessels of the skin, cramps, convul-
sions, coma, paralyses, death even, while the kidney 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 conclude
that the quantity of urine passed is very important in the intoxi-
cation of intestinal origin; that variations of urinary toxicity
may be, in similar cases, the measure of the degree of intoxica-
tion; 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 sup-
press 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
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 kidney 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. Stacleler, in 1848, had found phenol 1
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, — cyanurin, — which is indican de-
rived from indol. In 1872 Jaffe made a subcutaneous injection
of indol, and he saw that indican appeared or increased in the
urine. The indol, therefore, which is formed in the fasces 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 Sena-
tor. 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 betwen the increase of indican in the urine and
indol in the fasces. That is to say, variations of urinary indican
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 Gubler’s pupils —
A. Bobin — studied its variations in typhoid fever. Carter and

1 Phenol, according to Brieger, is excreted to the extent of 15 milli-
grams daily. This is a much smaller amount than is given by most
authorities. — T. O.


Jaffe have shown that urinary indican increases in consequence
of the retention of fsecal matter in intestinal obstruction and in
internal strangulation. Senator showed the same fact in certain
kinds of constipation; in these the alvine secretions are main-
tained in a liquid or semisolid state.

[There is considerable discrepancy of opinion as to the
toxicity of indol, which, as already mentioned, is eliminated in
the urine in the form of indican or indoxyl-potassium-sulphate
to the extent of 12 milligrams in twenty-four hours. Jaffe
(Centralbl. f. d. Med. Wins., 1872, No. 1), Nencki (“Ber. d.
deutsch Chem. Gesellsch.,” ix, 299), and Baumann (P ‘ finger’s
Archiv, xiii, 825, and “Ber. d. deutsch Chem. Gesellsch./’ ix,
54) administered indol to dogs in their food, also by subcutaneous
injection. Jaffe did not find that any poisonous symptoms fol-
lowed the subcutaneous injection of indol, and it was not until
Nencki had administered to a dog 2 grams by the mouth in
twenty-four hours that there appeared diarrhoea. Frogs are sus-
ceptible to the influence of indol : 12 milligrams of a 1 per cent,
solution when administered subcutaneously caused death. Kov-
ighi (Maly’s “Jahresb. ii. Thier-Chem.,” xxvi, 456) found that
from 1.5 to 2 grams of indol when administered subcutaneously
to rabbits in twenty-four hours proved fatal, the symptoms being
torpor, somnolence, general muscular weakness, feebleness of
heart action, and a fall of temperature. Three healthy medical
students agreed to take under Herter’s observation (New York
Med. Jour., 1898, July 16 and 23) for a period of from six to
thirteen days indol in varying quantities from 0.025 to 2 grams.
In twenty-four hours on one occasion one of the students con-
sumed 2 grams. He had taken on the first day of the experiment
1 gram without any ill effects. On gradually increasing the dose
sleep became disturbed and headache was induced. Herter there-
fore does not attribute very highly toxic properties to indol.
Beattie Nesbitt (Journal of Experim. Med., vol. iv, No. 1, 1899)
did not find that the injection of indol, 0.1 gram, into the jugular
vein of a dog was followed by any marked change in the arterial
pressure and therefore is of the opinion that to account for the
symptoms in acute intestinal intoxication it is to the absorption
of other substances we must look than to to indol.]


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
denned 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, Eiess, and Litten, not only in aceton-
aemia 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 fermen-
tation 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 Cf. H. Roger.

The alcoholic extract of rotten meat is twice less toxic when
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
centimeters per kilogram, whereas it is necessary to use 23
cubic centimeters of blood removed from the liver.

These recent experiments seem to lend support to a hy-
pothesis put forward by Schiff 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 forty 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 destroying. 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.
Boger; 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 centimeters per kilo-
gram. 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 com-
parative toxicity of the portal and hepatic blood demonstrates
it. Only, in the experiment of Schiff, poisoning has no time
to be produced; the animal appears to succumb, as Claude
Bernard has said, to an intestinal hyperemia and consequent
cerebral anaemia. In order to study auto-intoxication, after
suppressing the function of the liver, it will be necessary to
join together the portal vein and the renal. The experiment


made by Holnikew, 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. [Medical men are familiar with the readi-
ness with which convulsions are induced in infants as the result
of imperfectly digested food passing down the intestine. Hepatic
insufficiency, either by not arresting or not transforming toxins
elaborated within the alimentary canal is also a cause of con-
vulsions in young children and in adults.]

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 dem-
onstrated 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 mat-
ter; 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


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 reconsider the question. It is not uncommon to observe cases
of strangulated hernia in which accidents continue when the
intestinal strangulation has been relieved, because putrid mate-
rial 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 sufferings
are chiefly subjective, are constipated. They experience a num-
ber of nervous disorders of sensibility, — buzzing in the ears and
psychical troubles. All the insane are constipated, and alienists
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 trouble when we cause to dis-
appear, at the same time as constipation, the unhealthy dispo-
sition of the nervous system.

Thus we see, in the two examples of septicaemia of Humbert,
and of constipation, the maximum and the minimum of accidents
attributable to the intoxication of intestinal origin.

[Bouchard himself partly answers the question raised higher
up : “Are constipated people healthy ?” A short while ago I
published notes of a case where the bowels had not been opened



for nearly forty days. In this woman, very shortly, almost im-
mediately, after the constipation was relieved her mental symp-
toms disappeared and her temper and disposition improved.
Constipation favors auto-intoxication by allowing absorption to
take place, and while it is true that, owing to the hardness of
the stools the poisons included therein do not readily escape,
still not only are there experienced by the patient headache,
migraine, and vertigo, but, as shown by Vanni (“SulF origine
intestinale della Chlorosi,” II Morgagni, p. 533, 1893), the red
blood-corpuscles become diminished in number and less resistant
to the action of destructive agents. Persons engaged in the
ordinary duties of life and who are daily taking exercise may
not for a time complain of symptoms due to constipation, but
some illness arrives, an accident occurs requiring surgical opera-
tion, or a woman is confined, then constipation, until then ap-
parently harmless, becomes a cause of feverishness and restless-
ness. It is good practice on the part of surgeons to prepare their
patients beforehand for abdominal and other operations by in-
ducing intestinal antisepsis by means of aperients.]


Acute or Transitory Intestinal Auto-intoxication —
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 in
constipation, the two extremes, — the maximum and the mini-
mum 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 peptogenic power is weakened; 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 para-
sitic ferments more putrescible material. In these conditions
of imperfect digestive secretions I see the possibility of a devel-
opment of anomalous fermentations. It is certain that the sub-
jective troubles felt by patients cannot be explained by an in-
sufficient alimentation of so short a duration. On the contrary,
the production of putrid fermentations explains the bitterness
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

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. In general, they experience bitterness in the
mouth; their breath and their skin have a disagreeable odor.
But all these inconveniences may disappear for a time by evacu-
ating the contents of the large intestine. The individual who
awakens with a sensation of lassitude may be deprived of it by
a simple injection. What I say to you in regard to this does
not constitute a demonstration, but it is more a reason for add-
ing to the probabilities in favor of the part played by intoxica-
tion 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 a 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. Chantemesse was able to verify the reality of this
in a patient, in my service, attacked with an intestinal obstruc-
tion from an unknown cause. Faecal vomiting bore witness to
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 liters of a horribly fetid liquid
were evacuated by means of the oesophageal tube, and we saw
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 reflex 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 lapa-
rotomy the fever cannot be explained, in many of the cases, by
a septic condition of the peritoneum, and we see it disappear
after getting rid of constipation (Kiistner). Accoucheurs know
quite well how certain febrile incidents which supervene in the
course of parturition disappear after alvine evacuation, either
spontaneously or induced by light purgatives. This hurtful
influence of the stagnation of matter in the intestines after op-
erations explains old traditions forgotten in surgical practice.
It was the rule in olden 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 con-
cluded, unless it be one upon the abdomen, we can, with advan-
tage, it would appear, and upon the evidence of M. Verneuil,
induce intestinal evacuation. These, then, are clinical facts
which agree with theory.

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 hydro-
gen produced 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-
ened paper impregnated with acetate of lead ; the stools and the
urine contained sulphuretted hydrogen. We could therefore
notice in these cases certain symptoms which contribute in part
to the classical picture of poisoning by H 2 S, as in certain dys-
pepsias. 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.

[Sulphuretted hydrogen gas is normally produced in small
amounts in the intestine. When thrown off in the urine it con-
stitutes the condition known as hydrothionuria. By some physi-
cians and physiologists the nervous phenomena observed in Sen-
ator’s case of hydrothionuria are not attributed to the circulation
of sulphuretted hydrogen in the blood. Herter, for example,
considers the question as unsettled. As to the toxicity of the gas
there is little doubt, for experiments and experience alike con-
firm the fact. It is largely a question of the amount. To the
production of this gas in the intestine putrefaction or fermenta-
tion contributes in no small degree. Many aerobic and most of
the anaerobic bacteria can, when the hydrochloric acid of the
gastric juice is deficient and oxygen is absent, bring about a
disintegration of proteid during which sulphuretted hydrogen is
given off.]

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 nondigestion ; 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 hydrating 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 or-

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 ordi-
nary symptoms of an indigestion, at first stomachal and then
intestinal. Diarrhoea lasted 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
microbes, in these cases, as one-third of the faecal mass. There
was an increase of the intestinal alkaloids, since from 12 grams
of faecal matter I was able to remove sufficient alkaloids to esti-
mate the proportion of it as 15 milligrams per kilogram 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 oue, 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, vomit-
ing, 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 daily. 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 alka-
loid, but without demonstrating its toxicity. Brouardel and
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 eat-
ing of tainted meats. Gaspard and Panum have shown that the
putrefaction of meat develops a poison capable of inducing acci-
dents both serious and fatal. But in these cases the symptoms
are quickly developed; they commence half an hour after the
ingestion of tainted meat. Besides, in a general way, we do not
eat meat actually putrefied and already capable of intoxicating
by itself. We ingest meat which is only beginning to putrefy,
in the depths of which microbes are at work determining a
fermentative process, which goes on, under conditions particu-
larly 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 from eight to eighteen
hours after the ingestion of suspected foods. In this period of
incubation no symptom reveals the explosion which is preparing;
but, once the poison is formed, toxic accidents are quickly


Krautzer has related a case of intoxication by sausages.
Four people had treated themselves to Wurtemberg 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 re-
mained 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 per-
spiration. 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 without analogy to atropine. And
yet, among the putrid alkaloids, there is one, endowed with
analogous properties, which I had formerly extracted from the
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 among the first consumers, the tainted meat
continues to be distributed among 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 wholesome — after ingestion putrefied in their

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 afterward, 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 infec-
tion. 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
tainted meat that were the best cooked, — the external parts, —
where the action of heat had in part neutralized the poison.

Thus, in the family 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 without any relation to intoxication, for there is no
question of a general infection, but of a surface infection. With-
out 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, secondarily to infection, there is,
in all probability, produced an intoxication. There are infec-
tious maladies in which microbes inhabit the blood; they can
subtract oxygen 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 deaths 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 by 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 nutritive 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.


Chronic Gastrointestinal Auto-intoxications —
Dilatation of 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. In-
credulity of a part of the medical public as regards the subject of dilatation
of the stomach. Its frequency demonstrated by clinical statistics. Why it
has been until now unknown. It can only be revealed by physical signs.
Insufficiency of percussion as the means of diagnosis of dilatation. Value of
the splashing sound as a means of delimitation of the stomach. Conse-
quences of gastric dilatation. Direct symptoms on the side of the gastric

tube and its annexes. Gastritis. Gastro-intestinal dyspepsia. Hepatic con-
gestion. 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 con-
striction. Accidents remote and at a distance. Disorders of innervation:

sensibility to cold. Disorders of the senses and intelligence. Disorders of
general nutrition and of the emunctories. Skin affections. Catarrh of mu-
cous membranes. Albuminuria and peptonuria. Inflammation of certain tis-
sues and of phlebitis. Alterations of the osseous tissues: deformity of the

phalango-phalangeal articulations of the fingers. Its semeiological value;
possible relation between dilation 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. Dila-
tation of the stomach is the result of an acquired diathesis. Gastrictetany:

Bouveret-Devic, Halleburton-McKendrick.

The facts enumerated in the preceding lecture do not all
constitute a strict demonstration of intoxication, — they only
cause it to be presumed. Nevertheless, there are some of them
which carry conviction, — that of Senator, for example, in which
one poison only — sulphuretted hydrogen — was found in the in-
testine and in all excreted products: that which is personal

.( 163 )


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 form a 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
Boutmy 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 by accidents simulating intoxication
by atropine, with scarlatinal redness, mydriasis, and acceleration
of the pulse.

We are now going to approach chronic intoxications having
as their point of origin the intestinal canal. They may be ob-
served in chronic diarrhoea, 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 Avhich I had personally ob-
served. I could bring forward to-day nearry 400 cases, of which
274 have been seen by me outside of the hospital, and the others
in my service. When I announced to you, last year, my views
upon the consequences of dilatation of the stomach, I had not
met opponents by word alone. But at the Medical Society 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 beyond the question; that they cannot judge
otherwise, because they were in want of facts to control my
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 say, 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 of
the 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, while very frequent in
the sick, it is relatively uncommon in the healthy; and I have
myself 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 a long 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 gastralgic 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.

I have 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 you do not hear it at
the first stroke, you 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 hori-
zontal, 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 (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 he 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 stom-
ach; afterward, we sew up the wall, and anew we observe chop-
ping 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 centimeters
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 stomachs
are 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 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 offering oppo-
sition 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 (both of which accompany gastric dilatation, — the
first in two-thirds of the cases, the second in four-fifths). 3.
Nervous or hypochondriac symptoms. We see men without


energy, who present themselves at the hospital because they can
no longer work, on account of physical and mental debility; we
regard them often as idlers, if not as hypochondriacs; we make
an error in diagnosis. 4. Last, other symptoms, so varied and
so numerous that their mention at first provokes general in-

I shall not return to the details which I gave last year upon
this subject. I ought, nevertheless, to make again a brief men-
tion of them. We meet, among patients whose stomach is dilated,
symptoms directly connected with the digestive tube. The ap-
petite is in general preserved ; it may be augmented. The most
of those who are the subjects of dilatation eat largely. Ingestion
is not at all painful. But, at the end of two, three, or four
hours, the stomach is blown out, eructations are produced, in-
odorous 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
fasces 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 twenty-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 fsecal matter are seen glairy secretions and sometimes blood
(membranous enteritis).

Besides the phenomena of gastro-intestinal dyspepsia, there
exists hepatic congestion. We find in people with dilated stom-
ach, a swollen liver, often indolent; sometimes there exists an
aching in the right hypochondrium ; sometimes jaundice with-
out colorless stools. This congestion of the liver is of short dura-
tion, and is modified very rapidly ; it may appear and disappear
in two or three days; it sometimes, too, passes unnoticed. Of
the 274 cases which I have observed outside the hospital, I have


found it 13 times in 100; that is to say, in one-eighth of the

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 mechan-
ically 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 kidney in all people whose stomach is dilated,
but only in those whose thorax is the seat of an habitual con-
striction at its base, in women and military men. Bartels has
recognized this fact. The corset and the abdominal band pre-
vent 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 vas-
cular attachments. We observe, in all the cases of dilatation of
the stomach, luxation of the kidney 14 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, dila-
tation 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-
mentations which are the consequence of it, is accompanied,
besides, by distant disturbance, many of which form part of the
classical series of dyspepsias and are considered to be reflex.


These are first the nervous symptoms of dyspeptics (dyspepsia is
accompanied by dilatation of the stomach in seven-eighths of the

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 round their head,
of headache, of feeling very depressed, an uneasy feeling gen-
erally; 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 Ktissmaul, Dujardin-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 contracture of the hands reappeared. It has entirely
disappeared since, thanks to the continued observance of a better

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 Chantemesse 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 are they to
be explained if not by 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 moldy bread, according to
the statement of some of the patients.

We notice among them eczema thirteen times out of one
hundred, pityriasis in front of the sternum or of the head,
pityriasis versicolor.

Urticaria is not uncommon among 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 shellfish. Are not all of these toxic causes?
Urticaria 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. While chef de clinique, I have seen a young
girl, the subject of an 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 Eecamier; 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
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
hooklets were detected by the microscope. He pushes the treat-
ment further, and there is seen to escape a jet of red blood from
a branch of the portal vein. And yet the only accident after this
was a general eruption of urticaria. It is evident that penetra-


tion 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 peritoneum.

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.

In 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, when.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 there-
fore, a series of links, and not an accidental association. For a
pathogenic explanation I propose to you, for the time being,

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 elimi-
nation by the respiratory mucous membrane. Besides, people
who are the subjects of dilatation of the stomach catch cold
easily, cough habitually; their bronchi secrete mucous sputa
which are with difficulty detached, and lead up to dyspnoea and
rhonchi. I have found 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 substances than a reflex act.

[Discussing the various causes of asthma Dr. James Adam
(“Glasgow Hospital Eeports,” p. 171, 1900) draws attention to
the possibility of some forms of asthma that exhibit periodicity
being toxasmic. Some patients who are afflicted with asthma
suffer from catarrh of the respiratory mucous membrane or
something akin to an internal urticaria. Whether uric acid alone
is the toxin in operation, Adam is of the opinion that between
asthma and excess of uric acid there exists a very close connec-
tion. Previously suspecting that indicanuria and asthma might
be concurrent, he made numerous observations, but these failed
to substantiate the existence of any constant relationship between
these two conditions. Adam concludes, therefore, that in certain
forms of asthma there is a convulsive or spasm-producing toxin
in operation upon the blood-vessels whereby are explained the
paroxysmal attacks of difficulty of breathing, the diarrhoea and
bilious vomiting that occasionally occur, and the peculiar noc-
turnal or rather early morning periodicity of the asthmatic

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, albuminuria is
extremely frequent, not only as a trace, but in measurably large
quantities, in the form of a retractile coagulum 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
with 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 irritation, 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. While in the normal state, peptone
cannot be discovered in the blood, either because it has been
transformed into albumin 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 nu-
trition in people whose stomachs are dilated. As a goodly num-
ber 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 urates 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 spon-
taneous phlebitis, and I have insisted upon the importance of
this point, which no longer permits us to accord to spontaneous
phlebitis coming on in the course of a chronic dyspepsia the
signification which Trousseau assigned to it. Purpura, which
indicates fragility 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 phalango-
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, simultaneously, these
deformities. Nearly always the patients are astonished when
we call their attention to these nodules ; they 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

Sometimes other joints may be deformed. I have noticed,
at the metacarpo-phalangeal 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 parallel
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 dyspepsia is. But, really, there is
no choice in this of rheumatic deformation. Chronic partial
rheumatism 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 secondarily the second articulations. Why do we not see,
in dilatation of the stomach, other joints seized, — the knees and
metacarpo-phalangeal ? Otherwise the subarticular signs of rheu-


matism are wanting in those who, having dilatation of the stom-
ach, 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 dila-
tation of the stomach.

We may see nodosities situated also at the second joint of
the 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
consequences 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
many 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 gastrointes-
tinal trouble. Whatever the disease of the stomach may be, cer-


tain functional disturbances are sufficient to cause the develop-
ment 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. Jaksch
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 minute, but
constituted by a deep and laborious inspiration, with great move-
ment of the larynx and a moaning, panting expiration. The
temperature is normal; the pulse small, frequent, and compres-
sible. The odor of the breath recalls that of chloroform ; prob-
ably it is due to the same substance as that which is exhaled in
the breath of diabetics, since we find it in urine with the same
chemical reaction. It has, besides, been also noticed in leuco-
cythamiia and pernicious angemia.

Is it astonishing, therefore, that severe nervous symptoms
should be caused by a simple dilatation of the stomach?

What occurs in the chronic gastro-enteritis 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, last, 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, deafness,
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 yet, what disturbances its diseases cause in the

organism !

What can it be, therefore, which is absorbed when the stom-
ach 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 impor-
tance 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-
tomatic 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 reunited several symptoms which recall arthritism, nodosi-
ties of joints, migraine, neuralgias, sibilant bronchitis, eczema,
and 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 symp-
toms of which I have just spoken.

But this assemblage of symptoms of an arthritic nature is
only the small coin, as it were, of arthritism ! 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 in diabetics and the gouty. They may, never-
theless, arise in such by way of dyspepsia, should they be dys-
peptic, and yet great eaters ; for they accumulate one meal upon
the preceding one not digested ; they thus take meals irregularly,


and in too great quantity. I do not say that arthritism is not
concerned as a predisponent in the pathogenesis of certain dila-
tations of the stomach. But there is another influence, the
direct heredity of this organic disposition. We very often see
a mother and her four children the subjects of dilatation. Is
it because they live in common and in the same manner, and
undergo the same hygienic trials? ISTo; it is that there are
families in whom the stomach has 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 that
would see in dilatation of the stomach an affection of an arthritic
nature. It is true that, in our time, men of the working class
have borrowed from the governing classes a certain number
of their faults and vices of hygiene. 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 discussion that one can
settle such questions, but only by facts. And yet, among 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 in all their patients? Among those who may wish to
do so, how many of them know how to do it ? And, among those
who can seek for the existence of a dilatation, how few are
preoccupied with the greatness of the question? If we now
examine under what appearances dilatation 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 con-
stipation. The hepatic form is constituted by congestion of the
liver, which shows itself by increased size in the volume of this
organ and by a 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-
tion, cerebro-cardiac neurosis, hypochondriasis, and 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
that disappear when the patient has succeeded in expelling the

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 stomachal origin, since seventeen times in
every one hundred albuminuria co-exists with dilated stomach.
Simultaneous^, 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 de-
fective, is characterized by the predominance of joint manifesta-
tions, 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 it in medical men
who had dilatation of the stomach and who considered them-
selves the subjects of rheumatismal phlebitis.

Last, 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

We could multiply these types, but around these ten may be
grouped all the other symptoms. 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
in young girls and pulmonary phthisis are often induced by
dilatation of the stomach. This latter exists in two-thirds of
the tuberculous, 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.

[Since Bouchard wrote the foregoing the subject of gastric
tetany following dilated stomach has received considerable atten-
tion. Although comparatively speaking a rare affection, it is
extremely fatal, and yet if diagnosed and treated early a fatal
termination may be warded off. The name tetanie was given
to the particular group of nervous phenomena by Corvisart in
1852, but it is to Newman (Deuts ch Kliniclc, 1861) and to
Kussmaul (Deutscli Archiv f. Jclin. Med., bd. vi, 1869) that we
are principally indebted for what we know of the association of
tetany and dilatation of the stomach. Of more recent writers I
would mention the exhaustive paper by Professor Halliburton
and Dr. John S. McKendrick in the British Medical Journal,
June 29, 1901, — a paper not only interesting from the phy-
sician’s point of view, but in which, on account of the complete-
ness of its references and the results obtained by experiments
upon animals, may be said to be focalized nearly all that is known
of this very important subject. The symptoms observed in their
patient, a man who had reached the middle term of life and who
had suffered off and on for fifteen years from “his stomach,”‘
were pain after food, relieved by vomiting large quantities of
sour-smelling material ; occasionally hydrochloric acid was pres-
ent in excess and sarcinae were frequently found in microscopical
examination of the vomit. For three years previously he had
used the stomach pump two or three times a day. The symptoms
of tetany had developed rather suddenly and without any ap-
parent cause so far as change of diet was concerned ; they were
preceded by severe frontal headache, a sense of tingling and
numbness of the fingers followed by spasmodic contraction of
the fingers as in the “accoucheur’s hand.” Patient passed rap-
idly into a state of coma which soon cleared up after large in-
testinal injections and drastic medicines.

During the tetanoid seizures the urine contained a trace of
albumin and acetone, and when the spasms subsided these gave
place to sugar. The urine had a specific gravity of 1028. The
vomit contained acetone ; hydrochloric, acetic, and butyric acids ;
but no sarcinae.


Albuminuria is not unknown in gastric dilatation and
tetany. The symptoms, however, can scarcely be attributed to
uraemia. After death the kidneys have been found to be healthy,
but in a few instances these organs have been the seat of patho-
logical changes. As the albuminuria is usually transitory, this
circumstance suggests that it is due to the action of some poison
in the blood upon the renal parenchyma. Nature, too, as we
have stated, may be a temporary constituent of the urine. Other
substances have also been found therein: e.g., sugar (Fenwick),
a picrin salt (Albu), and indican (Oddo and Sarles). In gas-
tric tetany Gumbrecht found the uro-toxic coefficient of the urine

With the object of ascertaining upon what particular sub-
stance absorbed from the stomach the nervous symptoms of tetany
depended Halliburton and McKendrick injected preparations of
the contents of their patients’ dilated stomach into animals.
This was followed by a marked fall in arterial pressure. On the
supposition that this might be caused by the acidity of the gastric
contents the fluid was gently neutralized by means of potash and
when this was injected the fall of pressure was extremely slight.
The presence of some acid substance therefore seemed to be
responsible for the fall of blood-pressure, which occurred whether
the vagi were intact or not, and was dependent upon some action
either direct or reflex, upon the cardio-inhibitory center. Bou-
veret and Devic (quoted in Lancet, November 26, 1898) injected
into the blood-vessels of animals varying percentages of hydro-
chloric acid. The normal amount of HC1 in gastric juice is 0.2
per cent. Beginning with 0.1 per cent, solution, they proceeded
to 0.9 per cent, solution; but it was not until 0.6 per cent, was
reached that there was observed a fall of temperature in the
animals. The injection of 0.9 per cent, solution of hydrochloric
acid was followed by general convulsions and death, and at the
autopsy a sero-sanguineous fluid was found in the peritoneal
cavity. The dose of hydrochloric acid that is fatal is 0.4 per
kilogram of animal. Weak solutions — e.g., 0.2 and 0.3 per cent.
— cause no inconvenience when injected into animals.

Halliburton and McKendrick’s experiments show that the
contents of a dilated stomach contain some material that is


more poisonous than hydrochloric acid. Beyond saying that
this substance has an acid reaction they do not attempt to define
it further or to give it a name. It does not necessarily follow-
that the acid substance that is circulating in the blood and which
is presumably the cause of the nervous symptoms of tetany
should have been absorbed from the stomach. More than likely
this acid may be the result of some faulty metabolism of the body
caused by the circulation of toxic material absorbed from the
gastro-intestinal tract.

It is still taught by many that the symptoms of tetany are
due to dehydration of the tissues consequent upon the exhalation
of large quantities of liquid through the gastric mucous mem-
brane and the vomiting of large amounts of this watery material.
It is to these circumstances that we must attribute the deficient
amount of urine passed by the patients. The protoplasm of ani-
mal cells can only bear the abstraction of a limited amount of
water, and therefore dehydration of the tissues may play a part
in the development of the symptoms, but it is more probable
that auto-intoxication plays the major part, since on almost
similar series of symptoms is observed in diabetic coma when
patients are not always emaciated.

What the poison is that causes gastric tetany it is impos-
sible to say — Brieger is of the opinion that it is a peptotoxin.
Bouveret and Devic injected into animals the toxin produced
during the peptonization of proteids in the presence of alcohol
and they found that it caused tetanic convulsions in large doses
and in smaller quantities the ordinary contractures of tetany.
It is believed that this peptotoxin is produced in a dilated stom-
ach when there is an excess of acid, but it is not yet known
whether it is an ethylamin hydrochlorate or an ethylene dianin.
Gumbrecht speaks of the poisonous substance as an albumose.
Without giving it a name, Halliburton and McKendrick de-
scribe the toxin obtained from the contents of a dilated stomach
as having an acid reaction, soluble in alcohol and normal saline
solution, and when injected into animals as causing, directly or
indirectly, reflex excitation of the cardio-inhibitory center and
probably of other centers in the brain and spinal cord.]


Dilatation of the Stomach — Etiology, Pathogenesis,
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 innervation; congenital or acquired debility of
the muscular tunic; reciprocal relations between typhoid fever and dilata-
tion 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. Substantial alimentation in small volume. Choice of foods. The
unsuitableness of alcoholic drinks and of everything which keeps up ex-
cessive fermentation in the stomach. Why insufficiently baked bread is not
easily digested. Recent researches upon the fermentation of bread. Neces-
sity 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 dyspepsia due to the use of liquids. Milk food as the pre-
paratory regimen in the cure of dilatation. Mixed regimen of eggs and milk.
Regimen of infrequent and complete meals. Nutritive enemata. Anti-
septic medication as an auxiliary to the dietetic regimen: chloroform-water,
hydrochloric lemonade. Indications for washing out the stomach. Treat-
ment of pyrosis and of ulcerative pastritis. 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 you 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
considering the therapeutics of this intoxication. I ought al-
ready to have dealt with, in a summary manner, intestinal anti-
sepsis, having been almost of necessity led to it, in order to
interpret uraemia and to study its therapeutics. I am now led



to undertake this question, while studying the treatment of in-
toxication from chronic dyspepsia; that is to say, chiefly from
dilatation of the stomach. But all the treatment of chronic in-
toxication of digestive origin does not lie in intestinal antisepsis.
It is not sufficient to neutralize or to delay fermentations. With-
out neglecting the employment of charcoal, which fixes the
products of putrefaction, of iodoform, 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, dilata-
tion 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 prolonged,
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 h) r gienic errors lead to the same result. To
eat too quickly, when we come to table with an excessive appe-
tite, 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 consequence 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 me-
chanically engender dilatation of the stomach. Other causes
may also be in operation, such as bad teeth, which prevent good

We can remedy all these causes in the premonitory period,
but when the stomach is thus dilated, 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
those which therapeutics could attack with the greatest chances
of success.


Mechanical distension sometimes follows from pathological
causes, — from an antecedent dyspepsia having determined habit-
ually too long retention of food in the stomach; from a chronic
catarrh of the mucous membrane, preventing physiological se-
cretion; cancerous or cicatricial constriction of the pylorus.
The puckered cicatrix of a cured ulcer of the pylorus may
progressively lead up, in quite a mechanical manner, to dis-
tension 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 exist in hys-
terical people and in ataxics — causes variations in the energy of
the central nervous system, whence there results distension ; but
this is rarely permanent. We notice, too, an intermittent dis-
tension in exophthalmic goiter, in convalescence from serious
affections, after grief, prolonged indisposition, sad mental pre-
occupation. All these distensions have not yet 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 heredity.
It is certain that in the same family dilatation of the stomach
exists in several individuals, without our being able to call to
our aid, in ojder to explain it, a group of hygienic defects. It
may be said of the stomach, as of the scrotum, which is habit-
ually retracted in certain people, that there is a weak condition
in some, owing to a natural muscular debility.

Last, debility of the muscular wall of the stomach may be
the result of a morbid degeneration. The study of degenerations
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 intoxication, to lesions
of the intestinal and central nervous system, and, finally, to
infectious diseases.

These causes are probably attributable to debility of the
gastric muscular wall. It is developed after typhoid fever;


oftener it arises at the beginning and even before the commence-
ment of the disease. It is not rare for typhoid fever to be devel-
oped in persons whose stomachs have already been dilated. I
have seen, in the course of the last two 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 dila-
tation of the stomach. We might ask the question, had dilata-
tion prepared the way for the introduction of the infectious
agent ? I content myself, for the moment, by an empirical state-
ment 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 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
fibers, general stimulants can indirectly give advantageous re-
sults; these 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 by astringent bitters. We may give atten-
tion to the general nervous system in its cutaneous and peripheral
expansions; we may prescribe dry or aromatic friction, change
or 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 necessary
during meals, which it is well to take in pleasant company.
These are small measures, but their utility is be} r ond 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
revives the stomach; it is simply a question of improving func-
tion. With a bad tool a workman may do pretty good work.
Sulphurous and saline baths, sea-baths, cold baths, and baths of


Plombieres may be useful. I can scarcely believe in the favorable
influence of electricity, despite 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

Last and chiefly, we must pay attention to alimentary hy-
giene. This includes the whole of the means which cause diges-
tion 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 men-
tal worry. It is necessary to abstain altogether from work imme-
diately 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 its being indulged in to the extent of

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 by 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
be necessary to proceed with the artificial evacuation of the


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 by 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 depuration might be
prevented. We would not allow liquids at other than meal-
times; 375 grams of drink at each meal, or three-fourths of a
liter in twenty-four hours, ought, in a general way, to be suffi-

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
necessary to avoid, as much as possible, even’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 water one-fourth
of white wine, one-third of beer, or a teaspoonful of brandy.

Bread is generally badly borne by dyspeptics, but rice, bar-
ley, oatmeal, and unfermented pastes are allowed. As regards
bread, we may allow only the crust or grated crumb. The reason
for this restriction is this : Baking, having interrupted the fer-
mentation of the dough, has not stopped it altogether; conse-
quently, this fermentation reappears when moisture and tempera-
ture are again favorable to it. In thoroughly baked bread fer-


mentation 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 cerealin (diastase) starch is broken up into maltose
and dextrin. Maltose, under the influence of saccharomyces
minor, forms two sugars, — dextrose and lsevulose. The two
sugars, under the influence of the saccharomyces, ferment, pro-
ducing 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 fermenta-
tion, 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 acids,
supposing we only employ gluten without starch, and lactic
acid with pure gluten. We also find leucin, tyrosin, phenol;
that is to say, the products of the fermentation of a nitrogenous

What undergoes fermentation in dough is, therefore, the glu-
ten, which gives girth to the products of acetic fermentation in
the presence of a bacterium, — the bacillus glutinis. But this
resists the temperature to which the center 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 unfermented 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 amel-
ioration, 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 taken at regular hours ;
that, if it is possible to obtain consent from patients for only
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 strongly 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, compotes of
fruit. Of fresh fruits these only will be allowed: strawberries,
peaches, and grapes. I do not know why they 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

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 grams { 1 / i liter). In the
summertime, for patients who perspire profusely, we should mod-
erate, somewhat, the rule, in order to make some compensation
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 con-
tains 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 suffi-
cient 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

The third is fulfilled by the employment 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 number
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 frequeut doses and in small quantities, in order that
its digestion may be rapid and complete. Milk diet is a prepar-
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 liter daily
in ten equal doses; that is to say, 100 grams every two hours, — i


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 liters in the twenty-four
hours, which are sufficient for the sustenance of any man. Last,
2 1 / 2 liters, in ten doses of 250 grams, should not be exceeded.
And then we should proceed, by insensible transition, to mixed
diet. We add, first, a yelk 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 substi-
tution 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 com-
plete 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 be-
guile 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
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. Creosote


( which has been employed for more than thirty years, 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 derangements ;
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 fermenta-
tions and aids physiological digestion. No fermentation is pos-
sible in a liquid which contains for every 1000 parts 1.10 grams
of anhydrous hydrochloric acid, equivalent to 3.30 grams of the
fuming hydrochloric acid of commerce. The liquor which I
employ is a solution with this formula: —

Fuming hydrochloric acid, pure 4 grams.

Water 1000 grams.

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 grains 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 re-
moved. 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.g., the dim-
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 hemorrhages and ulceration of the mucous
membrane. But there is no inconvenience whatever in intro-
ducing iodoform (in pill), creosote, 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
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 reappear 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 symp-
toms which may yield at the end of a few hours, even certain
sibilant rales of bronchitis, which arise from intoxication, and
are due to gastric fermentation; certain anginal cardiac symp-
toms (dyspnceal), and the cutaneous, and especially renal, mani-
festations. Albuminuria rapidly improves and totally disappears,
at the same time that it is accompanied by cardiac reduplication.
The alterations in the joints, caused and maintained by the
excess of acetic fermentations, may even retrocede.

1 The possibility of obtaining similar results is a reason, in
my opinion, for insisting upon the indications to be fulfilled and

1 Since these lectures were delivered, M. P. le Gendre has studied
more particularly certain points in the history of dilatation of the
stomach, and he has published the result of his researches in an inau-
gural thesis, “Dilatation of the Stomach and Typhoid Fever. Semei-
ological 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 centimeters of water, basing
his remarks upon an examination of 60 stomachs of cadavera taken
haphazard; he believed that he might conclude that this average was
less than 1300 cubic centimeters. But in 12 cases, in 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 centimeters.

M. le Gendre has described very minutely, from a morphological
and anatomical point of view, the knotty condition of the phalange-


the rules to be followed in the treatment of chronic intoxication
of a digestive origin, the type of which is dilatation of the

phalangeal joints of the fingers, the semeiological value of which I have
made known. In what refers to those who are the subjects of dilata-
tion, and are predisposed to contract typhoid fever, I am reminded that,
in 19 cases of this disease which have come under my care within the
last two and a half years, the contagion had exerted itself nearly al-
ways upon patients attacked with dilatation of the stomach; it had
even attacked 4 authentic cases of relapse of typhoid fever, — facts cer-
tainly very rare concerning the subjects of dilatation. He draws at-
tention to the relative frequency with which we meet with taenia and
the lumbrici in individuals whose stomachs are imperfectly fulfilling
their functions; which shows that the digestive canal of the subjects
of dilatation is particularly favorable for the lodgment of disease-pro-
ducing 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 obstruc-
tion, continued febricula, synocha; choleriform, gastro-intestinal ca-
tarrh, — many of which are, perhaps, attenuated forms of typhoid fever.

Auto-Intoxication 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 ulcerations are a cause of intoxication, either by in-
creasing 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 infec-
tions, 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 fascal 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 study of intoxication of intestinal origin does not ap-
pear to lead naturally to a digression upon typhoid fever. This
is an infectious disease, and not a toxic one, and yet, when we
come to study its therapeutics, it is necessary to deal with intoxi-
cation. In typhoid 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 transitionally 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.


The organism which may be the infective agent of enteric
fever has been known for a long time, — since 1871, by Beckling-
hausen; then by Klein, Sokolof, Browitz, and Fischl, in 1878.
I 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 nephritides. 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, Friedliinder, and Gaffky. But does this fact,
although agreed upon, prove that the microbe is the pathogenic
agent of typhoid fever? Certainly not; it is necessary 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 by 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 or-
ganism, 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 always
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 meth-
ods, and intravenous injection. I have inoculated quantities 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
an evening rise of temperature, in which the thermometric curve
is broken up into a series of ascending oscillations — a stadium
or plateau — and a line of descending oscillations. Eecovery took
place in the two pigs operated upon. Had they had a bastard
typhoid fever? In these cases I ought to have communicated
to them immunity for the future. Yet fresh intravenous injec-
tions 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 characteristic 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 center
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 microscopical, 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 gan-
grene of certain parts of the intestine, then in excessive putre-
factions, which are in this way developed, showing themselves
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.

If the faecal 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;
also 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 counterbalanced by the activity
of the circulation and nervous system.

We sometimes see, in the course of typhoid fever, certain
infective processes superadded, such as parotitis. Inflammation
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.g., by the kidney when it is no
longer in function, and when the bladder is the seat of inflam-
mation (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 super-
added 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 only. 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.


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° P.), which brings about
unusual metamorphoses in living matter, depriving it of oxygen ;
induces modifications which are subversive of nutrition and per-
versive of disassimilation. This excessive temperature produces
effects which are harmful to muscular fiber and the nervous sys-
tem. Sometimes the patients die simply from the persistent
hyperthermia. 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 clown general indications; there are still special indi-
cations for such and such a disease, such and such a particular

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 re-
cently, 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 toxicity, 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-


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 grams of charcoal in medicated
cachets. As for myself, who gave 100 grams daily, spoonfuls
by the mouth every two hours, I have obtained liquid stools, —
black, odorless, and not resembling feecal matter. Such matter
has not only optical and olfactory properties which are less dis-
agreeable, but intravenous 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 easy 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 con-
vulsive. We must employ from 90 to 120 cubic centimeters of
urine in order to kill 1 kilogram of animal.

Owing to the disinfection of the stools, we also obtain other
beneficial results. The patients have no longer the earthy com-
plexion, but a clear skin, white and red ; the intestinal distension
diminishes; the tongue remains moist; eschars are extremely

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,
without exception, which have come under my hospital care : the
patients who have not been submitted to this treatment are 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 com-
parison 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, intes-
tinal antisepsis. After numerous attempts, after having em-
ployed creosote like Pecholier, salicylic acid, and mercurial prepa-
rations, I have returned to the true principles of intestinal
antisepsis by applying substances capable of acting throughout


the whole length of the digestive canal; that is, insoluble sub-
stances, — the salicylate of bismuth, iodoform, naphthalin. I
have only employed phenic 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 gram of
iodoform, finely powdered and representing a surface of 60
square meters. I obtain, by this method, as the faecal matters
are deodorized and discolored, a diminution of the alkaloids
which the filtered liquid contains, a diminution of the toxicity
of the faecal 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 dry.

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,
while 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.


Pathogenic Therapeusis of Typhoid Fever — Antisepsis
of 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 medica-
ments is not paralleled by their toxic power. Therapeutic and antiseptic

equivalents. Antisepsis is proposed not so much in order to destroy

microbes as to prevent their reproduction. A simple change of the medium

is sufficient to cause large vegetables to become sterile. Experience 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 antisepsis 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 infec-
tious 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



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

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, <r 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


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 Eaulin, 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 vege-
table cells in a dose not at all hurtful to animal cells. On the
contrary, certain inferior vegetables live preferably in media
poisonous to the animal (solutions of quinine, arsenic, and anti-
mony in doses fatal to man). We must, therefore, differentiate
antiseptic substances so as to state precisely those which are very
hurtful to vegetable cells, and yet innocent so far as the ele-
mentary 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
fortiori, 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 any 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.

Not all mercurial salts have an antiseptic action propor-
tionate to their toxicity. The biniodide, eminently antiseptic,
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 liter of soup, we must
add to it 48 grams of iodide of potassium or 50 grams 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 but one-fortieth as hurtful to the animal as iodide of potas-


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 in 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 mercury than is that of the bacterium of fermenting soup, — a
long bacterium whose sensibility is as 2, while that of the typho-
genetic agent is 3. Finally, as a last argument, it is said in
objection that we cannot kill pathogenic bacteria without de-
stroying 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 convincing 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 modifica-
tion of the medium, while leaving to vegetable organisms their
vital integrity and all their energy, can render them incapable of
multiplication. The liquid of a malignant-pustule culture in-
oculated 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 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 applica-
tion of this idea of reproduction, 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 multiplica-
tion. Let us propose to ourselves only to oppose the latter, and
let us merely try to impede the activity of this multiplication.

En resume, 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 by some tenths of a degree; it
does not reduce it in other febrile diseases. In fibrinous lobar
pneumonia 3 to 4 grams 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 erysipelas
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 cessa-
tion of the fever which is the consequence of it.

It is not so with phenic acid. Phenic 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 grams of crystallized phenic acid
was administered to two of my patients, at intervals of two


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
liters of water. The patients were already in a state of coma,
in which they remained for several hours, their temperature being
35° C. (95° P.). 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° P.) was apyretic the next
day with a temperature of 37° C. (98.6° P.), and remained con-
valescent ; the disease was destroyed, but the patient was nearly
killed. This is also true of alcohol; I observed it in the case
of a young woman who had caught typhoid fever in Borne.
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° P.). 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 returned to 37° C. (98.6°
P.), it remained at this point for four days. The malady re-
sumed its course; the microbes had merely been dormant; they
required a certain time to reproduce the pyretic symptoms.

Almost all the drugs that reduce temperature in typhoid
fever are antiseptic. All those that are reputed specifics or are
generally considered useful are antiseptic : chlorine, iodine, sul-
phurous acid, the sulphites and hyposulphites, the mercurials,
essence of terebinthine, creosote, thymic acid, benzoic acid, sali-
cylic acid, boric acid, iodoform, quinine, resorcin, kairin, anti-
pyrin, thallin. I think, therefore, that experience confirms the
general opinion as to their usefulness, and that, practically as
well as theoretically, a favorable effect may be obtained in the
course of infectious diseases by the employment of the above-
named substances. Of these, one especially has been considered a
specific, viz. : mercury. It is long since calomel has been ad-
ministered in large doses, or the black sulphide. Mercurial fric-


tion was used by Serres, and by Becquerel, until salivation and
ulceration of the mouth were produced. Since that time calomel
has been recognized as a valuable agent in Germany and Eng-
land, and in France by M. Salet, of Saint-Germain. He recom-
mends a method which consists in administering 1 centigram
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
centigrams of calomel a day, in doses of 2 centigrams every
hour, until mercurial salivation was produced. 1 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 con-
clusions. I may merely 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

But I did not continue this treatment, although the patients
recovered more quickly, and seemed to recover more completely,
as it has the disadvantages of causing a long period of conva-
lescence, great debility^ and anaemia. Certain accidents, too,
seemed to me more frequent : epistaxis ; intestinal hasmorrhage ;
dysenteric, sanguinolent, and mucous stools. Other patients suf-
fered 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 hereafter.

1 Forty centigrams equal 6.2 grains; 2 centigrams equal 0.31 grain.


On the Pathogenic Therapeutics of Typhoid Fever —
The Treatment of 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 cot 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 antithermic

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
centigrams of calomel, divided into 20 doses, which are taken
every hour, without either trying to produce or obtaining saliva-
tion. 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, varying, at the end of four days, between 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


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

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 physical medium that is unfavorable to the infectious

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 lecithin which enters into the composition of the nervous
elements 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 experi-


merited upon. We note muscular agitation and acceleration in
the beating of the heart and of the respiratory movements. The
phenomena of osmosis are modified by elevation of the tempera-
ture. Water is retained in the cells. The tissues of those suf-
fering 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, more-
over, the elevation of temperature in illness does not reach 44°
C. (111.2° F.), or even 43° C. (109.4° P.), unless it is, ex-
ceptionally, at the moment of death or a little while after it.

Naunyn and Eosenthal 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 suppressed ;
the animal, continuing to produce heat, accumulated it. The
effects thus obtained by the gradual elevation of temperature 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 haemorrhages under the
pleura and the pericardium, we observed, four hours after the
commencement of the elevation of temperature, fatty degenera-
tion 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 Eosenthal found that
no similar effect was produced in animals at the excessive tem-
peratures observed in man when suffering from disease.

On the other hand, elevation of temperature does not seem
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 sup-
posed to be necessary for the production of excessive elevation
of temperature are compensated for, the diminution in weight
being quite insignificant, whereas, when they enter upon conva-
lescence, the diminution in weight is rapid, and attains its maxi-
mum 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, therefore, that it
indicates the gravity of the disease, but does not cause it. Eleva-
tion of temperature announces, but does not constitute, the
danger. It is even an established fact that the accelerated action
of the heart which accompanies elevation of temperature cannot
produce exhaustion of the heart; the functional incapability
through excess of work is a myth, for the mechanical work
effected by the heart is less when the contractions are so rapid
(200 to 300 pulsations). The relaxation 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
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 eleva-
tion of temperature, nevertheless drugs or modes of treatment
that lower this excessive temperature cause some of these com-
plications 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 pro-
ducing 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
according to different diseases. Are they normal processes car-
ried to excess, or are they abnormal processes that raise the tem-
perature to fever height? It has been suggested that there are
microbes 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 Traube, that in a fever patient the heat radiation
is less than in a healthy person. A square decimeter of his skin
loses a smaller number of calories than a square decimeter of
the skin of a person in normal health. It is possible that a
diminution in the abstraction of calorie results from this.

The rapid diminution of the corpuscles of blood in febrile
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 re-
appear. They remain suspended in some part of the body during
the fever. Bockmann and Naunyn admit that they are tern-


porarily withdrawn from the general circulation. This would
account for the great increase in volume of the spleen. Hiiter
has observed, in septic and pysemic disorders, stagnation of cor-
puscles in certain parts of the capillary blood-vessels; this fact
may be mentioned as corroborating the theory of a temporary
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 calorie. If, therefore, certain
fevers may be caused by the retention of heat, it may be sug-
gested that the radiation of the latter should be increased. Eiess,
experimenting upon animals suffering from infectious diseases,
lowers their temperatures artificially until they become normal;
but the diseases continue and death ensues. The danger, there-
fore, does not lie wholly in the excessive elevation of temperature.

Nevertheless, I repeat that clinical experience shows that
the antipyretic 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, hydrotherapeutic 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 salicylic 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 cuta-
neous 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.

Theoretically, the cold-bath 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 treatment
retards calorification. In typhoid fever, according to Sassetzky,
the patient does not give off more carbonic acid and does not
excrete more urea when he is subjected to refrigeration. Taking
into account the uncertainties of theory, we are justified in con-
cluding that the causes of fever are various; that it depends
sometimes on an increase of the normal calorification, some-
times on the life of 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 antipyretic treatment does not offer the same


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. An-
tithermic 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

Galen was not troubled with these uncertainties. To him
fehris was color prceter 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.



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
unstable 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 dimin-
ished, 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 hypotheses on
this subject. Remember what I said about uraemia. We have
found poisons, but not the poison of uraemia. 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

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 pyrexia, intermittent


fever, and in one form of infection of women in childbed its
action is undoubtedly favorable, although only temporarily.

Phenic acid has a certain antipyretic action, but perhaps
not a favorable one; antipyrin has also this action, but its in-
fluence is unfavorable. When the temperature is at 40 0l or 41°
C, a sufficient 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 evidently 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 Joffroy 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 grams 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 following day the fever has reached its original height.
Should quinine, therefore, be administered in the evening as a
preventive? The second dose, moreover, 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 sufficient? As for myself, I never give a second dose
of quinine until after an interval of seventy-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 grams during the
first and second periods of seven days ; 1 1 / 2 grams in the third
period; 1 gram in the fourth and after. I never give less than
this ; V 2 gram 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

1 Forty degrees C. equal 104° F. To convert Centigrade degrees
into Fahrenheit multiply by 9, divide by 5, and add 32 to the result.


by quinine; it aims only at an accident, viz.: the excessive
elevation 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 pro-
duces 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 hap-
pened 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 predominated. 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 postmortem examination showed that in
the patients that had died suddenly the heart was contracted and
absolutely empty of blood. Now, the toxicology 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 pyrexia
this treatment has failed. In pneumonia, pleurisy, and ery-
sipelas, we obtain, as a rule, neither a fall of temperature nor
an improved general condition.

Abstraction of heat is the only nonmedicinal means of low-
ering 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.


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 meth-
ods is very slight. Wrapping in a wet sheet is painful for some

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
contrivances of Dumontpallier and Clement produce a real
refrigeration, but these processes are little used as yet, and I
am not, therefore, in a position to express an opinion as to their

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 tem-
perature 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 com-
plete, and he is often taken out in an alarming state. Our feel-
ings 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 temperature, viz.: 28° C, which might as well be called a
cold bath; for to a man whose temperature is 40° C. the sensa-
tion 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
falls 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 Kiess’s continuous bath, which lasts
twenty-four hours a day at a temperature of 34° C. The tem-
perature is moderated by this method, which may be useful.
The mortality would be 6 per cent., according to Eiess, but his
statistics are only derived from forty-eight cases. This contin-
uous tepid bath becomes rapidly unbearable, and the patients
prefer the cdld 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 any 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 center 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
experiences 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 minutes if it is 38° C.

No feeling of nervous shock and no peripheral vascular
spasm occur during this long period. The pulse is not con-
stricted. At about 33° C. the patient finds his bath cool; at


32° C. he finds it cold, but even at 30° C. he continues to speak
and talk, showing a wonderful mental condition. He has noth-
ing 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
patients can thus pass half the day in the water. The lowering
of the temperature is more lasting than with the cold bath, and
sudden rise of temperature is 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
according 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 exceptions
should be mentioned. For instance, in certain patients the tem-
perature is not reduced; we even observe a rise of temperature
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 devel-
oping in them an insurmountable repugnance and keen irritation.

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 hath.

The differences in the lowering of the temperature in the
baths 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
average 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 morn-
ing 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
besides 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 antipyrin 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 that earthy
pallor that denotes the thorough poisoning of the system. It is
white and often even pink in those patients that have a fine skin.

Last, the need of sleep manifests itself after each bath, and
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
twenty-four hours, the intervals between them should be a little
shorter from 3 o’clock to midnight. Speaking of the advantages
of 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, very 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 pus
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
haemorrhage or pulmonary hepatization. When, in a female
patient, the menstrual period occurs during the course of typhoid
fever, I do not generally find it necessary 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 to make up for the waste caused by com-
bustion, 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 urinary 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 rigorously 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 barley ; 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 plays the
part of middle-man in organic changes. Chloride of sodium is
indispensable for the phenomena of osmosis ; phosphates are the
media 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.

Last, I administer substances that are both plastic and
combustible, — peptones. I give 50 grams 1 per day, reckoning
the dry peptone. These peptones, which are chemically pure,
and prepared properly, and which are very different from certain

1 I.e., a little more than 1 V» ounces of dry peptone.


products 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
grams of glycerin, and yet 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 grams 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 kilogram per day for from 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 pyrexia 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 grams of sulphate of magnesia).

(I) Forty centigrams 1 of calomel per day, in 20 doses of
2 centigrams (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 grams of powdered vegetable charcoal with 1 gram of iodo-
form and 5 grams of naphthalin. The whole is mixed with 200

1 Forty centigrams equal 6.2 grains.


grams of glycerin and with the 50 grams of peptone 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
tablespoonful every two hours in a third of a glass of water.

1 wash out the bowels regularly every morning and evening by
means of an injection containing 1 part in 1000 of phenic acid,
each injection consisting of 50 centigrams of phenic acid to 500
grams of water.

(d) From 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 grams during the first two periods of seven days, 1 1 / 2 grams
during the third period, and 1 gram during the fourth and fifth.
These quantities are administered in large doses — 50 centigrams
— 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 morning
or 41° C. in the evening. Often the baths dispense with the
use of quinine and constitute in themselves a sufficient system
of antithermic treatment.

(e) The diet comprises : broth cooked with barley and ad-
ministered freely (1 1 / 2 liters to 2 liters a day) ; glycerin (asso-
ciated, as I have said, with charcoal, iodoform, and naphthalin,
and also with peptones) ; lemonade made from lemons, with the
addition of a little wine.

This is certainly a complicated system of therapeutics; it
cannot be otherwise, as the indications to be fulfilled are complex.

This systematic treatment, be it understood, does not exclude
the treatment of certain accidents; for instance, excessive or
prolonged delirium by opium, peritonitic complications by means
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 illness general features
without which they would not have the disease at all. Why
should I be reproached for employing a systematic mode of


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 twenty-nine, 1 out of
which there have been nine deaths, showing a mortality of 7
per cent. The mean duration of the illness has been nineteen
days. The frequent relapses which attack 20 per cent, of the

*At the date of this publication (November, 18S6) the number of
cases of typhoid fever treated by M. Bouchard’s staff at the Lariboisiere
Hospital since April 1, 1884, is 226, out of which there have been 31
deaths, or a mortality of 11.7 per cent. Is this increased rate of mor-
tality to be attributed to a chance accumulation of critical cases, or
to a modification introduced into the treatment, salicylate of bis-


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.

muth having been substituted for the charcoal, and the peptones hav-
ing 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.

Auto-intoxication by Bile. Pathogenesis of Jaundice.

The elements constituting bile. Experimental studies of the toxic nature of
bilirubin 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 reabsorbed.
When bile passes into the blood, the white connective tissues, by fixing
the bilirubin, 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 reabsorption of bile takes place, no doubt, with some in-
tensity in the duodenum, but it is principally inoffensive matter
that is reabsorbed, and, moreover, if the noxious portion of the
bile is reabsorbed 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 centimeters in twenty-four
hours; and it may even amount to 1200 and 1300 cubic centi-
meters. It is a diffusible liquid, passing by 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 albumin;
but mucin is found in it, and this gives to it its viscosity; it
also contains cholesterin, which is erroneously considered poi-
sonous, as we find considerable quantities in atheromatous ab-
scesses of the aorta; olein, margarin; coloring matter, — impor-



tant from a toxic point of view; the biliary salts and the alkaline
soaps, by means of which ingredients the cholesterin is held in

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 chyme, which renders it
insoluble and prevents it from being reabsorbed. We must take
into account the biliary salts whose base is sodium, which is a
nonpoisonous base. The glycocholic and taurocholic acids of
Lehmann, still known as cholic and choleic acids, are very un-
stable. 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. : dyslysin, 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 intensity of its reabsorption, no poi-
soning takes place, even when the kidney is only slightly per-
meable. But these transformations are neither immediate nor
constant. In certain persons we find, even near the anus, bili-
rubin still intact, and biliary acids that have not undergone trans-
formation, owing to the rapidity and intensity of the contrac-
tions of the intestines.

Even in a normal state of health a certain quantity of the
toxic matter may be reabsorbed in the duodenum. But the liver,
as Schiff has shown, arrests these poisonous substances and re-
stores them to the intestines or transforms them into harmless


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 experiments,
from 4 to 6 cubic centimeters of bile are required to kill in con-
vulsions a living animal weighing 1 kilogram, and, since the
daily secretion of bile is about 1000 cubic centimeters, 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 kilogram producing enough to kill more than 2800 grams 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 decolored
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. Tapret and myself — have demonstrated it by an intravenous
injection of this substance dissolved in water by means of a
little soda. Bilirubin kills rabbits in a dose of 5 centigrams
per kilogram. 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
takes 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


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 role :
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

Is it the same when the bile is reabsorbed 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 reabsorbed in the intes-

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 fibers, the vitreous
body, all the epithelial cells, the synovial 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 twenty-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 intravenous injection of bile and kill the animal
in a few minutes, without the skin having taken the jaundiced


tinge or the urine having been colored. This is an experimental
fact that contradicts clinical experience. It has even been
asserted that the intravenous injection of bile cannot produce
jaundice. 1 Feltz and Eitter never succeeded in obtaining it.

Vulpian injected 250 cubic centimeters 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 Vulpian’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 centigrams of
bilirubin that are sufficient to kill one kilogram of living animal
matter are also sufficient to cause intense jaundice during the
few minutes that elapse between the commencement of the in-
jection 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 fibers, 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

x 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 cir-
culation 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. 0.


sufficiently slow, the white fibers, 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
thus, both experimentally and clinically, obtain icteric colora-
tion without poisoning, providing the injection or reabsorption
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 fibers
of the connective tissue are being incessantly colored, while the
blood reabsorbs only gradually, nervous accidents are thus
averted. The tissues serve to protect the organism against cer-
tain poisons. Experience shows us that the most intense form
of jaundice, viz. : black jaundice, does not kill, precisely 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. Last, the kidneys also take part
in the elimination of the biliary acids; we find, in the urine
of those suffering from jaundice, sulphur incompletely 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 fiber, the epithelial
elements, and according as the kidney 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 dis-
integration 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
atrophy of the liver, viz.: suppression of the final processes of

The substances disassimilated no longer undergo all the
metamorphoses to which they are normally subjected in the liver.
The matter that is decomposed no longer takes the form of
excrement; the albuminoid substances remain colloid, instead of
being crystalloid and therefore dialyzable. 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 matter.

The greatest danger in jaundice is renal impermeability.
On the other hand, severe cases of jaundice may be cured if the
kidneys remain permeable.


Malignant Jaundice: Aggbavated 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 poi-
sons. The relation of the various accidents attendant upon aggravated

jaundice: cholasmia, acholia, urasmia. 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 jaun-

Ekom 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 biliary salts, which have always 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, a new 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 carry off part of the pigment
and the biliary acids and their derivatives, therefore the urine
becomes poisonous; I have found that jaundiced urine kills in
the proportion of ten and even as low as seven cubic centimeters
per kilogram of the animal. On the other hand, the fibers of the
connective tissue retain the most important of the poisons of
bile, viz. : the coloring matter. The tissues, by becoming colored,
withdraw from the circulation, in increasing proportion, this


poison, and exercise gradually a sort of condensing power.
Nevertheless, 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 condi-
tions of piosoning increase. Now, the kidneys often act insuf-
ficiently in jaundice, frequently through a cause that is inde-
pendent 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
kidne} r s, owing to infectious agencies having reached it. Last,
the impermeability of the kidneys may be the consequence of the
jaundice itself altering the epithelial cells. The consequence of
the impermeability of the kidney is the retention of the coloring
matter and of the biliary salts. The biliary impregnation of the
red corpuscles, also of the hepatic cells, muscular fiber, epithelial
cells, and the vascular membranes causes destructive modifica-
tions 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 ; these, too, 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.

Subsequently 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; 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
concerned 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 intestines — 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-


plete the development of the materials produced by disassimila-
tion ; before they pass into the excretory channels, 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 condition for being excreted. Proteid sub-
stances no longer reach the state of urea; therefore the urea
diminishes. Now, this is the most important physiological diu-
retic, forcing the water to pass away through the kidneys and
to carry off at the same time other solid excrementitious sub-

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 albumins,
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 at-
rophy of the liver a substance which, under 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, naphthalin — is not accom-
plished according to the normal processes. Instead of being


eliminated 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. Eosenstiehl’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 al-
ready 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
fabricated 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 re-
tention of poisons in the system. Last, the vessels also become
affected; extravasations are produced, and in some cases, which
cannot be called exceptional, renal haemorrhage still further in-
creases the impermeability of the kidneys. Thus, while the
chances of biliary poisoning diminish, causes of secondary poi-
soning appear, which continually increase in consequence of the
renal impermeability, 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.


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; last,
self-poisoning, of a mixed nature, through acholia, — i.e., through
the retention of anomalous toxic products ; and through uraemia,
— i.e., through the nonelimination of the normal toxic products,
which should be carried off by the urine.

This uraemic element cannot always 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 poi-
soning from reabsorption of bile, since the latter ceases to be
secreted; the putrefactions of intestinal origin certainly con-
tribute to it as one cause, but it is principally a poisoning by
the normal or abnormal refuse thrown 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 kidneys.
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 decolored 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 convulsions.

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
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 liters of urine were
secreted daily. Is all that I have said applicable to the partic-
ular malady which Eokitansky has called acute yellow atrophy
of the liver? to the form of severe jaundice described by Ozanam?
to the typhoid jaundice of Lebert? to the essential haemorrhagic
jaundice of Monneret? or to the essentially grave jaundice of
Genouville? 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 hypothe-
ses have been proposed. We need not discuss jaundice proceed-
ing 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 ursemia.

Buhl’s theory is that severe jaundice is the result of cere-
bral oedema; that, elimination of water by the bile being sup-
pressed, hydremia ensues, and then cerebral oedema. Can we
admit that the 800 or 1200 grams of water in the quantity of
bile formed daily can produce such effects when we know that,
normally, the intestines reabsorb 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 only, 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
the fluids and the tissues, but because at the same time we find
fever ; purpura ; a polymorphous erythema ; scarlatinif orm ; cir-


cinate, and globular eruptions on the skin, the pharynx, and the
palate; and because an acute nephritis exists, with parallel de-
terminations 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.

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-adynamic
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 albumins. We find drugs undergo unusual transforma-
tions, naphthalan, 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 con-
jecture, 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 in 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

Extracts were taken from all the organs of five animals that
had died of septicemia. These extracts were injected into
healthy animals and produced poisoning, but with extracts from



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. Of the substances that may be sus-
pected we have particularly studied the alkaloids. We have
extracted alkaloids from the bodies of animals that have died
of infectious diseases; we also find alkaloids in the tissues of
healthy animals, although, perhaps, in smaller quantities. How-
ever, the quantity of alkaloids extracted from the bodies of five
animals that had died of septicasmia was not sufficient to pro-
duce 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 reappeared. On
being injected into the veins of an animal, it produced mild
tremors after the sixth cubic centimeter ; myosis appeared ; the
pupils were punctiform at ten cubic centimeters. After twelve
cubic centimeters there were violent tonic spasms and convul-
sions up to the thirty-fourth cubic centimeter; death then en-
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


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 centimeters per kilogram of
the animal, as a minimum, the average proportion being thirty-
eight cubic centimeters. We observe in the animal the ordinary
signs of poisoning by normal urine, — myosis and lowering of
temperature; but, besides these symptoms, we get tonic convul-
sions absolutely similar to those produced by the urine of a pa-
tient suffering from tetanus, spasms with lasting muscular rigid-
ity, and, finally, death from opisthotonos. The urine of patients
suffering from pulmonary splenization killed animals, when in-
jected in quantities of twenty-two cubic centimeters, with the
same convulsions. In typhoid fever, at its commencement, be-
fore intestinal antiseptic action has yet been effected, I have
seen the urine produce only those toxic phenomena that belong
to normal urine, — no convulsions, very little pupillary contrac-
tion, narcosis; death ensues at fifty, sixty, and seventy cubic

In lead poisoning sixty-six cubic centimeters of urine per
kilogram have produced death without convulsions. In leu-
cocythasmia the urine has caused death in convulsions at fifteen
cubic centimeters. 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 centi-
meters 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


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 the 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. We reproduce, by the injection
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 dis-
ease, but the reproduction of some predominating symptom. I
did obtain an anomalous symptom, but this was produced indis-
criminately 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


increased. The weight of the body sometimes diminishes several
kilograms 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 pa-
tients ; 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 decolored 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 con-
vulsive organic matter. Is it not a striking fact that febrile
urine, in which the coloring matter is from ten to twenty times
as abundant 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
associated 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 poi-
sonous, do not poison the patient? Precisely because the urine
i6 poisoning, — i.e., because it carries off the poison. But if the


kidneys begin to work defectively, complications appear — con-
vulsions, the final ataxo-adynamic phenomena of every disease
— 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.

Pyocyantc 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? Dehy-
dration is the cause of nearly all the accidents of diabetes. Acetonaemia.
Diabetic coma.

Having been led by theory to seek for one poisonous sub-
stance in disease, I have found, in the bodies of patients, sub-
stances which may be poisonous ; but they occur in such propor-
tions 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 consuming nature,
I have found that the coloring matter produced in excess, also
potass liberated by the too rapid destruction of cells, both of
which have convulsive properties, may cause poisoning if the
kidney becomes impermeable, whether it is attacked with nephri-
tis or whether its action is suspended as in febrile or agonic
oliguria. During the last phases of disease we may observe the
appearance 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 these distinctions:
the poisoning is produced by exaggerated disassimilation, and
is retained in the blood through the inadequate action of the

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.



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 cult-
ures. 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 pyocyanine. The sub-
cutaneous injection seems harmless, but an animal that is sub-
jected to an intravenous injection of 1 or 2 cubic centimeters
of liquid, prepared in this way, becomes feverish and ceases 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 eliminated by
the urine and f secal 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 heat and
filtration or filtration by means of tested Chamberland cylin-


ders 1 ; we find in the filtered liquids all the reactions of pyocya-
nine, and we can, moreover, make sure by cultivation that these
liquids no longer contain any microbes. If, under these condi-
tions, 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 centimeters
of the liquid. The animals, upon receiving these injections,
which are made antiseptically, show only transitory effects, and
in some cases can be cured ; whereas, when the same liquids, con-
taining 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 pyocyanine, or a liquid containing pyocyanine de-
prived of microbes; whereas, when we inject a liquid culture
containing microbes, if the animal survive a certain number of
days, nephritis is established permanently, 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 chem-
ical 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 dis-
ease. 2

1 See Wilson’s “Hygiene,” page 232.

2 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 r6le of
the chemical substance. Recent experiments have shown him that the


We must now endeavor to find out whether the poisons are
produced in consequence of a disordered state of the general

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 1 in 1000
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
hyperglycemia deranges the quantity of the urine. In fact,
when sugar is eliminated, it carries away 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 secre-
tion, it must be incessantly receiving water, which is either con-
veyed 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 hyperglycemia the renal
secretion could be diminished or suppressed. But as long as
there is in the blood water and sugar in excess, there is produced

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 pyocyanine, but possesses a
different degree of toxicity and acts differently.


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 the plasmas and the tissues. One of
the primary effects of poisoning by sugar is, therefore, the ex-
traction of water from the system. Then a modification is pro-
duced 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 sensation of thirst appear.
A diminution ensues in the aptitude of the water to leave the
blood ; the pulmonary exhalation diminishes as well as the cuta-
neous exhalation.

Under normal conditions one-third of the total quantity 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 dehydrat-
ing the body by means of sugar or salt is not cataract; it dis-
appears when the tissues have regained their normal percentage
of water. Diabetic cataract, on the contrary, is permanent, and
we not infrequently see it developed in patients that are suffering
from oedema, in which case there is no question of dehydration.

As results of the derangement of nutritive processes, we
note the appearance of anomalous products of disassimilation,
anomalous albumins, so frequent in diabetic subjects, and an
increase of the extractives or urea; these features are not the
unfailing rule, but they are accidents that might be explained by

The dehydration of the tissues, when it exists only in a
moderate degree, provokes certain functional disturbances, which,
in the nerve elements, take the form of an exaggerated excitabil-
ity and rapid fatigue, and which in the muscular elements are
manifested by cramp, as in cholera. A higher degree of dehydra-



tion is attended by nervous accidents of great gravity, in which
category we may perhaps include diabetic coma.

When we were discussing typhoid fever and dyspepsias, we
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 reac-
tion is met with in certain forms of dyspepsia, in typhoid fever,
scarlatina, leucoeythsemia, and in pernicious ansemia; it is very
frequent in diabetes. Nevertheless, in many diabetic subjects,
we may observe for years the chloroformic 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 coloration
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 probable that
in these cases poisoning exists similar to that of severe dyspepsia.
I know nothing of the pathogenic conditions of those forms of
poisoning termed acetonemic. The clinical fact having been
observed by Brieger, at the clinic of Prerichs, under various
pathological conditions; by Senator, by Jaksch in carcinoma of
the stomach and in severe forms of dyspepsia, and by myself in
typhoid fever and in a very great number of cases of dilatation
of the stomach, it seems to me probable that the cause of it is
some morbid substance elaborated in the intestines. These acci-
dents can be reproduced in every feature experimentally, as has
been shown by the experiments of M. de Gennes.


However this may be, we note in certain diseases, not neces-
sarily infections, a body, or a series of bodies, which, on being
eliminated by the urine, give a red coloration upon the addition
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. Among
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 prognostic indi-

Two years ago the odor of the breath enabled me to form
the diagnosis in a case in which a child had been suddenly at-
tacked 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.

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 treat-
ment. Mode of propagation of cholera. Importance of the transmission by
water. Other possible modes of contagion. Attempts to discover the agent
of infection. The French Commission in Egypt. The researches and opin-
ions of Koch. The value of the comma bacillus. Studies of the trans-
missibility 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. Travelers
generally were also suspected, — not only those who were in-
fected, 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 harmony with these etiolog-
ical chimeras. It was necessary to avert the divine wrath by
L (260)


expiatory deeds, by penances and fastings imposed on evildoers.
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, I 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 among 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
Eussia to Western Europe. Its progress has also been traced
from Hedjaz into Egypt, to Alexandria, where it forms a fresh
center, 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


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 have begun to
ask themselves whether the latter had ever deserved this confi-

Often still, when we follow the dissemination of cholera
through France, we can trace it to linen that has not been dis-
infected. On studying the history of a great number of local
epidemics, we find that laundresses have been attacked first. The
dissemination of cholera has also been attributed to water. It
is probable that several centers 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 any rate, in the last epidemic ; and the districts
first attacked were a part of the Faubourg Saint-Antoine and the
Eue Sainte-Marguerite, — those to which the water of the Ourcq
was brought by direct canalization.

In hospitals where water is economized, where infected and
unfiltered water might be used for culinary and pharmaceutical
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 may be
attributed the disastrous infection of the Asylum for Old People,
in the Eue de Breteuil. As regards the other centers of infection.


it is impossible to explain their origin categorically , on account
of the mixing of the water of the Dhuys and the Vanne with
that of the Ourcq, in consequence of the ansastomoses 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 can-
not believe that there is any truth in the assertion that the in-
fection may be conveyed up the river, along the Ehone 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 contamina-
tion by drinking. We have naturally been led to consider cholera
as a disease that is indirectly 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 in liquids where microbes constantly exist. Regu-
lar, systematic investigations did not commence until the Eu-
ropean commissions were sent to Alexandria in 1883 ; these
researches were instituted by the French Commission, which in-
cluded in its members Messrs. Straus, Eoux, Nocard, and Thuil-
lier, and by the German Commission of E. Koch. The great
secrecy observed by the French Commission was fully justified.
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.

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 while desquamation is going on, or be-
tween them and penetrating into the interior of the intestinal
glands and into the superficial parts of the mucous membrane;
but he has never found them anywhere else, having searched for
them vainly in the ganglia, the kidneys, 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 follows:
length, from 1 1 / 2 to 2 1 / 2 microns; breadth, from 0.6 to 0.7
microns. These comma microbes may be found linked together
by twos or threes, so as to form a little chain; they may be
curved in opposite directions 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 empirical 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 explained how this organism causes the dis-
ease. Koch says that, after it has left the intestine, he can con-
tinue 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 con-
tained any of these organisms 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 ad-
mitted. If it were true, how is it that in Paris and in Germany,
where the cultivation of cholera germs has been studied un-
ceasingly, the various laboratories have not been infected ? How
is it that the disease has not broken out among the experimen-
talists ?

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 system.

Other investigators — M. Emmerich at Vienna and M. Doyen
here — think, moreover, that they have found pathogenic microbes
in some of the viscera. M. Emmerich, who states that he has
seen them, did not recognize among 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
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 the infection of cholera,
cultivated 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 succeeded
in killing animals, probably by communicating to them certain
forms of septicaemia, but not by reproducing cholera; and yet
they 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 mo-
ment of death. This fact contradicts the theory of the supposed
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 disease 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

When we introduce the agents, that are supposed to gen-
erate cholera, directly into the duodenum, the action of the bile
being suppressed by means of a ligature around the bile-duct
(Nicati and Eietsch), accidents are produced which resemble
those of cholera; and as it is found at the postmortem 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. But it is because the patient has cholera that we
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;
these have been caused to die sometimes from peritonitis, from
septicaemia, or from poisoning, but not from cholera.


Cholera (Continued).

Objections to the pathogenic value of the comma bacillus. Introduction of the
microbe by the hypodermic method; M. Ferran’s inoculations. Experimental
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 secretions. The
intravenous injection of the urine of cholera patients into animals repro-
duces most of the symptoms of cholera.

In the critical examination which I have made of the
pathogeny of cholera I have examined the claims of Koch’s ba-
cillus, 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 at-
tacked with cholera, of special organisms not found in the intes-
tines of healthy people, nor in those of patients suffering from
other diseases ; it is, in fact, the presence of these organisms from
the very commencement of the choleraic attacks, often in con-
siderable 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.

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 grams of tincture
of opium per kilogram 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 septicEemia. No results calculated to convince us of the truth
of the theory were obtained ; only Messrs. Nicati, Eietsch, 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 sys-
tem, 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.
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. 1 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

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 intravenous injections. On the other hand, I knew
the uselessness of all empirical modes of treatment. Opium,

1 At the time this lecture was delivered we had no definite in-
formation to enable us to form an opinion on the experiments of Fer-
ran. 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 con-
cerned. 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 experi-
ments on symptomatic charbon. But what is true of one pathogenic
agent of disease may be false as regards another, and we should there-
fore, 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, com-
posed 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 preparation of his lymph, or, if he gives
an explanation, he abandons it a few days after for another. Last,
the statistics that he publishes, although numerous, are far from 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 this verdict has been in no way
weakened by the later reports of the other Commissions (Belgian,
American, Italian, and Spanish) that were sent to Valencia for the
same purpose.


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.

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, au-
thoritatively, 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 ali-
mentary canal. Therefore, if Koch was right, it was necessary
to introduce into the alimentary canal a substance capable of
destroying life in all the microbes, — a nonabsorbable and, con-
sequently, an insoluble substance. I Avas 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 meters ; I gave 1 gram a day in conjunction with 5 grams
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 follow-
ing 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 influ-
enced by iodoform or by naphthalin. This resistance would be
surprising on the part of an organism that is more vulnerable
than most of the known microbes, since it is killed by heat and
desiccation. 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

It may also be said that the treatment was instituted too
late, the morbid poison being already formed and absorbed. I
answer by 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

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 cholera in the course of
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 alimentary 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

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,
at any rate, must exist; and we should not be justified in deny-
ing 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 dis-
ease. But, granting that there must be a certain pathogenic
agent in cholera, let us ask ourselves if this agent does not pro-
duce 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
reproducing in other living beings symptoms similar to those of

M. Gabriel Pouchet has discovered the existence of an alka-
loid in the discharge 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 fascal matter of both the
sick and the healthy.

Even before these discoveries, on September 20, 1884, in the
case of a ragpicker 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 centimeters of intestinal matter, a con-
siderable quantity of an alkaloiclal substance, — a quantity which
certainly 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 charac-
teristics, not having been able to obtain a sufficient quantity 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 organism? I know that in cholera patients matter is
formed 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 atrophy 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, as-
sumed 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 naph-
thalin. 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 dis-
solve in ether. This anomalous fact is probably owed 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 symp-
toms of poisoning by normal urine.

Myosis is generally defective. Instead of appearing at the
tenth cubic centimeter, 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 stretch-
ing of the hind limbs, followed by four or five spasms at the end
of a minute and a half, another rigid extension of the limbs, and
fresh spasms; eight, ten, or fifteen similar contractions 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 injec-
tion of choleraic urine the animal is seized with pea-soupy diar-
rhoea, 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 be-
comes more marked, and the animals die, with a rectal tempera-
ture of 33° or 34° C. On the bodies being examined, the intes-
tine is found to be congested and filled with pea-soupy, diarrhceic
matter, constituted mainly by the intestinal desquamation, re-
sembling 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 toxic material.


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. Ef-
fects produced on animals by the substances soluble and insoluble in alcohol
and contained in choleraic urine. The poison which causes the choleraic
symptoms in animals in soluble in alcohol and 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 ursemia.
Myosis in cholera patients that are anuric. This terminal uraemia in cholera
differs from ordinary uraemia, as several of the sources of the urasmic
poisons are suppressed. The toxins of cholera. Brunton, Roger, Besson.
Treatment of cholera.

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, among 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 contrac-
tion, 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 intravenous 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; diarrhceic evacuations, which may occur with certain nor-
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 epithelial
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 in-
terval 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 in-
stance), 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
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
intravenous 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 al-
ways 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 centimeters. All of those that died received
more than 17 cubic centimeters, and some as much as 90 cubic
centimeters. From the two reasons given above, I conclude that
the experimentally 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 alco-
hol, 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 diarrhcea, and die
within two days. These last accidents — albuminuria, colorless
diarrhcea, 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.


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. Last, 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. In
regard to 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 centimeters per kilogram of the animal. I evaporated
400 cubic centimeters of choleraic urine ; the extract was reduced
to ashes and the residuum washed in distilled water, which car-
ries 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 of a


toxic substance? 2. Does the comma bacillus really possess a
special pathogenic property, — i.e., does inoculation with it pro-
duce 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 grams, with from 3.8 to 35
cubic centimeters 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 grams, 20 cubic centimeters
of the liquid heated to 63° C. Neither at the time of the inocu-
lation 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 intravenous
method, I experimented on a rabbit. I injected into the veins
of the ear of a rabbit, weighing 1800 grams, 79 cubic centime-
ters of the culture fluid, which had neither been heated nor
filtered from the bacilli, — that is, 43 cubic centimeters per kilo-
gram. 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
postmortem 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. Last, another rabbit,
weighing 1990 grams, received into the veins of its ear in five
minutes 92 cubic centimeters of the liquid, which had been heated
and filtered from the bacilli, or 46 cubic centimeters per kilo-
gram. The temperature fell 8 / 10 degree 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 argu-
ments. They fully justify me in giving a negative answer to the
first question: the liquids in which the comma bacilli are culti-
vated contain no substance of a toxic nature.


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. As Koch did, I intro-
duced into the stomach of my guinea-pigs 11 cubic centimeters
of the liquid, after having first, according to the German scien-
tist’s method, alkalized the stomach by means of 5 cubic centi-
meters of a 5 per cent, solution of carbonate of soda, and arrested
all motion in the intestine by the intraperitoneal injection of 3
cubic centimeters of tincture of opium. I must own that the
results I obtained were the same as those secured 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, diarrhceic 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-
meters of an old charbon culture-fluid and into others 11 cubic
centimeters 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 common 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 centers,
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
exists 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


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 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 an-
other 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 reabsorption, since there is no
jaundice at the time, and the absorption cannot be effected by
the intestine. The poison in this case comes from disassimila-
tion. This uraemic period has long been designated the period of
reaction, the external temperature being higher, — i.e., equilib-
rium being established between the rectal and peripheral tem-
peratures, — a singular reaction, in which torpor appears instead
of spasms, and in which we can only see inertia of the whole
nervous system ! 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 reac-
tion, — a designation that is certainly less open to criticism, for


in the condition of the patients there is certainly something that
reminds us of typhoid fever. But the pathogenic conditions are
not absolutely the same. In cholera patients whose intestines are
subjected to antiseptic treatment there is no intestinal putrefac-
tion; 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 (1.20 grams and
1.30 grams of urea per kilogram of muscular tissue). This
period can be foreseen when anuria sets in ; after pupillary con-
traction 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 dehydration has
drawn off with the water all the potass of the fluids and a por-
tion 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 grams of the
patient’s urine did not cause convulsions in an animal. We see
that cholera furnishes us with an example of double self-poisori-
ing: 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.

[Bouchard in discussing the subject of cholera in the three
preceding chapters shows by the questions he has raised and


answered that the pathology of the malady is far from regarded
as settled. Although Asiatic cholera is usually attributed to the
spirillum discovered by Koch in 1883 there is a growing opinion
that it is due not so much to the bacillus itself as to the absorp-
tion of a toxin formed in the intestine by the micro-organism.
In his book “On Disorders of Assimilation and Digestion,” page
267, Sir Lauder Brunton states that the symptoms of cholera
are identical with those caused by muscarine, an alkaloid ob-
tained from poisonous mushrooms; hence his suggestion of the
employment of atropine as an antidote. Albuminous matter, in
decomposing, gives birth to such poisons as cholin, neurin, and
muscarine. Eoger, in “Les Maladies Infectieuses,” page 175,
speaks of the cholera poison as a toxopeptone, while Gamaleia
regards it as a very unstable form of nucleo-albumin contained in
the body of the cholera bacillus. From cultures of this organism
there is recovered a protein or nuclein which resists heat and
which kills animals with all the symptoms of cholera. In “Tech-
nique Microbiologique et Serotherapique,” by Besson, on page
511 it is stated that Petri found those cultures the most toxic
that were grown in a 5 to 10 per cent, solution of peptone and
that the toxin thus prepared was extremely fatal to guinea-pigs
and was not destroyed by boiling : a point of difference between
it and the diphtheria toxin, which he also named toxopeptone.
Brieger and Frankel regard the poison as an albuminoid of an
indeterminate nature resembling diastase and which is called
by them toxalbumin.

The symptoms of cholera can be caused by the comma ba-
cillus of Koch, but Bouchard, Brunton, and others are of the
opinion that this bacillus has not the monopoly of producing the
malady. Gautier, “Les Toxines Microbiennes,” page 581, holds
the opinion that there are various kinds of cholera microbes, —
e.g., the bacillus of Asiatic cholera (Koch, Haffkine), the ba-
cillus of Hamburg cholera (Pfeiffer), that of Massowah and
Cassino. From a specially prepared culture of Koch’s bacillus
there is obtained a product composed of proto- and deutero- albu-
mose. This is toxic and is capable of producing immunity
against fatal doses of the cholera microbe. D. D. Cunningham
failed to determine the presence of Koch’s bacillus in the dejecta


of cholera patients, but he found 11 other kinds of micro-organ-
isms therein. Several other physicians, therefore, as well as
Bouchard, maintain that, although the comma bacillus is the
micro-organism that is most frequently present in cholera, other
micro-organisms can replace it, and since the injection of poison-
ous substances obtained from the stools of cholera patients is
followed by symptoms of the disease it would appear as if the
malady was due rather to the absorption of a toxin formed by
bacilli present in the intestine than caused by the circulation of
bacilli in the blood or their presence in the tissues of the body.
Whatever may be the nature of the poison, and we have seen
that opinions differ very much in regard to it, there is in all
probability required a preparedness of the soil or a receptivity
of the individual upon which the poison can act.

The treatment of cholera should be twofold : (a) antiseptic,
to destroy the bacillus in the intestine and (b) the use of reme-
dies to neutralize the poison formed by the micro-organism. As
antiseptics, Brunton recommends the internal administration of
liquor hydrargyri perchloridi, mxv to 5j, with or without small
doses of calomel and as an antidote the internal administration
of atropine. Since the toxalbumins of cholera, when injected
subcutaneously, are excreted by the mucous membrane of the
stomach, from which cavity they may be reabsorbed into the
system, lavage is well worthy of a trial.]

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 de-
stroyer of poisons; last, to encourage the elimination of poisons by the skin,
the lungs, the intestines, and the kidneys. Sudorifics, purgatives, diuret-
ics, bleeding, inhalations of compressed air and oxygen; intravenous injec-
tions 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 system by preventing its ab-
sorption. 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. Last, if the poison has escaped the action of
the liver it should be eliminated by the skin, the lungs, the intes-
tines, 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 strik-
ing 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 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, disassimila-
tion 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 poisoning; 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 precipitated.
Of the poisons which it contains one, which is eminently poison-
ous, — the coloring matter, — is precipitated when brought into
contact with acid chyme; the other — the biliary salts — is trans-
formed 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
putrefaction, 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 intravenous or subcutaneous processes.
I know a patient who takes daily 20 grams 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 centimeters per kilogram. I
might conclude that the poisons of the opium have been de-
stroyed, but in stating this conclusion I must make 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 Eoger have recently verified in my laboratory. 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 complete
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 poisonous
matter by instituting intestinal antiseptic treatment.

I have mentioned bleeding, which can carry off in one opera-
tion, by the abstraction of 32 grams of blood, more poisonous
matter, it is said, than 100 liters of perspiration. I have sketched
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

In most diseases the morbid poison is a natural one, and
the ataxic or adynamic accidents of pyretic diseases are the
consequence of febrile oliguria; these are auto-intoxications re-
sulting from more intense disassimilation, or from more rapid
cell destruction, which sets at liberty imperfectly oxidized nitrog-
enous 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 have penetrated
further into the secrets of the pathogenic processes, in cases
where a morbid poison is really formed by perversion of the
nutritive 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 caDnot act upon
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, fistula?, 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 diminu-
tion in the dryness of the mouth, and alterations of the cardiac
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 establishment of meta-
static centers, 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 circulation, 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 mechan-

What can we do against poisons in the circulation? En-
deavor 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
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 centers ; 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 grams to several liters and the result is an improvement,
it is very probable that this is owed to the expulsion of toxic
matter through the urinary passages. Last, 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 proportion
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-
aclynamic fevers, opium, musk, and sometimes chloral, which can
neutralize certain poisonous effects; diffusible stimulants, alco-
hol, coffee, injections of ether. Even if the morbid poison is
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 intravenous 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 treat-
ment by the intravenous method, it was necessary to attack first
those diseases 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
malignant 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 biniodide
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 milligrams. If we exceed this quantity we provoke
protracted albuminuria. This quantity is dissolved by means
of an equal quantity of iodide of sodium in from 5 to 12 cubic
centimeters 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 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
experimental 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 reinoculated 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.

General Eecapitulation.

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-

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 in-
direct 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. Last, 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 intoxi-
cation. When nutrition is lessened, — as in obesity and gout, for
instance, — we frequently observe certain nerve troubles, — apathy,
dejection, inaptitude for work, and headache, — and we generally
note in the renal, cutaneous, or pulmonary excretions some in-



complete oxidized products of disassimilation, — oxalic acid and
the volatile fatty acids. It is admitted, not without an appear-
ance 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 simi-
lar nervous disorders, may, in people who are in good general
health, be produced superabundantly or destroyed insufficiently,
owing to excesses, late hours, mental anxiety, 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 sj^stem.
This is another example of the first signs of poisoning due to a
pathogenic nerve reaction. Of 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 centers, the lungs, the liver, the
kidneys, or the heart; if they only exist — suppose it is a case
of septicaemia — in the cellular tissue of the region contaminated,
it is quite natural to attribute the general symptoms to the ab-
sorption 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, cer-
tain 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 a mephitic gas, but
also when he is attacked by certain diseases. When 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 secre-
tion of a microbe, it must be considered as anomalous substance,
either as regards its nature or its quantity. But normal poisons

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
creates them by disassimilation, and he forms them in his secre-


tions. The human body is the theater of the toxic elaborations
carried on by the normal microbes which constantly inhabit the
alimentary canal. And yet man is not poisoned. He is de-
fended 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 intes-
tine by the portal vein, in order to neutralize them or throw
them back into the intestine. Then the excretory system expels
the poisons which are in circulation. This is not a purely theo-
retical 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 Muron; its truth was only established in 1880, by
Feltz and Eitter. 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 uri-
nary toxicity.

I found first what mass of living matter can be killed by the
poisons which each kilogram of the body of a healthy man sup-
plies in twenty-four hours to the renal secretion. I thus pos-
sessed 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 help 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 show-
ing that it contains at least seven toxic substances: a diuretic
substance (urea) ; a narcotic substance ; a substance that pro-
duces 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 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 the poisons
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 kilogram to be able to kill or even seriously injure 13 kilo-
grams 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 confined.
I have been led to the conclusion that a kilogram of living blood
contains in its plasma, and only in its plasma, enough poison
to kill more than 1250 grams of living matter, and that a man
would die toxsemic if his blood came to contain ten times as
much poison as it does in its normal condition. But if the
plasma of the blood is only slightly 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 disassimilation or by the de-
struction of the cell itself. Among 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 disassimilation and secre-
tion, and mineral substances, at the head of which we must place

Among 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
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, Selmi, Gautier, Brouardel and Boutmy. Then
I studied intestinal putrefaction; I showed that alkaloids exist
in faecal matter, that these alkaloidals are of several kinds, 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 toxicity of faecal matter. I analyzed tbe ele-
ments of this toxicity, and showed that it is due mainly to potass
and ammonia, but that, when freed from these two elements,
faecal matter still retains a certain degree of toxicity which must
not be overlooked. I have shown that intestinal antiseptic treat-
ment, 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 nonpoisonous symptoms that arise in diseases of the
kidneys, — albuminuria, haemorrhage, cardiac and arterial in-
juries, and oedema, including cerebral oedema. Thus, as you
know, I only admit as uraemic 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 uraemic
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.
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 ursemic 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 quan-
tity 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 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 mi-
crobes, continuing to multiply with greater rapidity in the ali-
mentary 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 infectious
agents form a poison, and the infection ends in poisoning. But


the most common condition in which we find intoxication occur-
ring 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 recog-
nized as being attendant upon the various forms of dyspepsia,
seem to me to cause many other disorders. It engenders, espe-
cially, a habitually chronic albuminuria, which may become per-
manent, 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 gastric fermentation,
by rendering excessive intestinal fermentation, by preparing poi-
sons, 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, rachitis. 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 pathogenic influence is most mani-
festly shown : chlorosis and pulmonary 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 fibers of
which retain within themselves the excess of coloring matter
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 intestinal 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 cholasmia, acholia, and uraemia. In fact, in jaundice,
the true safeguard against poisoning is the kidney. 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 exaggerated
disassimilation. If the kidneys perform their work of depura-
tion 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 albumins, 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. Among these anomalous substances 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 perchloride
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 anaemia, leucocytheemia, and I have
observed it in dilatation of the stomach and in typhoid fever.
It has been experimentally established, as you know, that this
substance is toxic. Unlike the greater number of auto-intoxica-
tions that we have met with up to the present, what we call


acetonemia 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 ex-
istence 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
disease, a secondary intoxication through the retention of the
normal poisons, and I indicated myosis as the clinical criterion
of the appearance of this uragmic 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 cer-
tain 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



By Thomas Oliver.




Natural Defenses of the Organism against Disease.

New school of pathology: Charrin, Herter, Miiller, and Brieger. Chemical de-
fenses of the body. Bacteria and their products. Hasmolysines and bac-
teriolysines. Alkalinity of the blood an important defense. Metchnikoff
and the Doctrine of Phagocytosis. Disease and individual idiosyncrasy.
Internal secretions and Brown-Sequard. Thyroid gland. Reverdin, Kocher,
and Horsley. Effects of thyroidectomy. Functions of thyroid gland. Bau-
mann, Notkin, and Blum. Opotherapy and its limits. Enlargement of the
spleen in fever and in blood conditions. Jawein’s experiments: blood dis-
integration and splenic enlargement.

In the preceding lectures on auto-intoxication Bouchard’s
main contention is that the human body forms poisons which
but for the watchful activity of the eliminating organs, especially
the kidneys, would injuriously react upon the body and endanger
life. Although he discusses the subject of the entrance of poisons
rib extra, he does not deal at any length with the question of how
the body protects itself against the invasion of microbes. Since
Bouchard’s book was published a new school of pathologists has
arisen. These men, working on different lines, have not only
indicated how auto-intoxication may be prevented by the activity
of the healthy emunctories, but have also shown how the body
itself may be protected against disease by the operation of certain
chemical and bio-chemical processes. Of recent writers who have
given considerable attention to this question mention here need
only be made of the work done by Charrin 1 and Herter, 2 also by
Miiller and Brieger. The subject, however, although still in its
infancy, has not been ignored by Bouchard as his scattered writ-
ings show.

In an earlier section of this revised edition I have inter-
posed fresh material in the text and have thus to some extent

“Les Defenses Naturelles de 1’Organisme,” Paris, 1898.
: Hertei – , “Lectures on Chemical Pathology.”

20 (305)


anticipated much that in the following pages may be said of
those chemical defenses of the organism which are associated
with the structure and activities of the cells that compose the
tissues. Disease is a complex matter; sometimes due to the
entrance of bacteria into the body or caused by the absorption
of their toxins; it is against these that the human body pro-
jects such natural defenses as an alkalinity of the blood, acid-
ity of the gastric juice and urine, acidity of the perspiration
and of the vaginal secretion. When micro-organisms have en-
tered the body the question naturally suggests itself: are the
symptoms due to a mechanical disturbance caused by the pres-
ence of these microbes or do they depend upon the circulation
of poisonous products formed by the minute organisms? Med-
ical opinion rather leans toward the latter view. In some dis-
eases — e.g., diphtheria — the microbes are at first only upon the
surface of a mucous membrane, and yet there are very marked
constitutional symptoms. The injection of fluid cultures of
bacteria from which the bacilli have been removed by filtration
* is also capable of causing disease. Without knowing exactly
how, the serum of blood can destroy pathogenic bacteria. This
power may depend upon the presence of proteids like enzymes
since serum loses this property if it is exposed for more than
an hour to a temperature of 56° C, while no loss of its anti-
bacterial virtues is induced by simply drying the fluid. To
the bactericidal substance present in serum Hankin has given
the name of alexin. The substance itself is probably derived from
leucocytes. It is no uncommon thing for the blood of one animal
when injected into the veins of another of a different species to
cause the colored blood-corpuscles of the receiving animal to un-
dergo disintegration, and, should this occur to any considerable
extent, there is usually hajmoglobinuria. The chemical substances
that confer upon blood this globulicidal property are called Jicemo-
lysins. By some writers the term b act erioly sins is applied to
those chemical compounds in blood-serum that destroy bacteria.
While both of these protective substances are spoken of as alexins,
it would be better to discard the term alexin altogether, since
hemolysins and bacteriolysins are of a more complex chemical
nature than are alexins generally.


One other natural defense of the body claims attention, and
that is what is known as phagocytosis or the destruction of bac-
teria by leucocytes, a doctrine first enunciated by Prof. Elie
Metchnikoff, of the Pasteur Institute, Paris. Metchnikoff has
shown that when the human body is refractory and is invaded at
a particular locality by disease-bearing microbes, the bacterial
toxins exert a chemical influence or chemiotaxis, whereby leu-
cocytes are drawn to the part affected. There occur (1) a dia-
pedesis of white corpuscles from the blood, and (2) phagocytosis
in which warfare is waged between the microbes on the one hand,
and the living cells on the other. In a refractory organism the
polynuclear, nuclear corpuscles, or microphages, a type of leuco-
cyte, kill the microbes and retire, leaving them to be taken up
and digested by mononuclear corpuscles or macrophages, which
are larger cells than those just mentioned. By this destruction
of the microbes health is retained and disease averted. It is
otherwise with the human body when it is run down or is in a
receptive condition, for then the toxins exert a negative chemio-
taxis; and as there is neither diapedesis nor phagocytosis, the
microbes multiply, disease develops, and the infectious malady
runs its course.

To the alkalinity of the blood must be ascribed some of the
antibactericidal power which this fluid possesses since it has
been found that this property varies with and is proportional
to its alkalinity. The alkalinity of the blood is therefore a
great defense. Increased acidity of the plasma weakens vital re-
sistance and predisposes to disease. Certain morbid processes of
themselves tend to increase this acidity. It is known, for exam-
ple, that fever causes a diminished alkalinity of the plasma. Of
the several sources from which the blood receives its acid con-
stituents, we might mention food, gastro-intestinal fermentation,
deranged metabolism giving rise to oxaluria and rheumatism;
also disintegration of the nervous system followed by the pres-
ence of excess of phosphoric acid. The coma and stupor observed
in the terminal stages of diabetes are generally admitted to be
due to the presence of acid in the blood. The sodium carbonate,
which is normally present in blood and which confers upon it
a degree of alkalinity, is in diabetes neutralized by organic acids,


particularly beta-oxybutyric acid. The sodium, thus freed from
the carbonate, combines with the acid and is eliminated by the
kidney, thereby removing, as Herter maintains, some of the
harmful material. Similar combinations are probably formed
with the ammonia of the blood, and, as a consequence, while
there is a diminished excretion of urea, there is a rise in the total
nitrogen of the ammonia elements from 2 to 5 per cent, in health
to 25 per cent, in this malady. In dilated stomach, too, the
absorption of organic acids from this viscus is followed by acid-

Into the subject of the agglutinating action of blood, or the
power conferred in certain infectious diseases upon blood by
toxins that have found their way thereto, whereby are brought
about cessation of movement and a clumping together of the
specific micro-organisms, as seen in Widal’s reaction in typhoid
fever, we cannot enter, nor can we deal with antitoxins, since
these are beyond the scope of this book, and, besides the subject
is still obscure. So far as antitoxins, however, concern us here,
it is an interesting fact that where an animal has once been
poisoned, either with pathogenic bacteria or with their products,
there is conferred upon that animal an immunity to subsequent
invasions _of the micro-organisms which is due to the presence
of specific products arising either out of the reaction of its leu-
cocytes to the microbes, or they come from the bacteria alone and
act by diminishing the receptivity of the organism and stimu-
lating its natural powers of defense.

Some persons are known to be more susceptible to poisons
than others. There is such a thing as individual idiosyncrasy.
One person may suffer very readily and severely from the effects
of a poison, while another scarcely suffers at all. This is seen
in the action of morphine and alcohol ; also in lead poisoning. 1
I am unable to offer any explanation of this individual pecul-
iarity, but if the inquiry were pushed to its ultimatum the cause
would be found to reside in the cells of the body.

It is only within recent years that the formation of an
“internal secretion” by various glands of the body has come to

1 “Lead Poisoning.” Gulstonian Lectures delivered at Royal Col-
lege of Physicians, London. Thomas Oliver, M.D.


be recognized, particularly of such glands as the pancreas, thy-
roid, and suprarenal. There may be several purposes served by
such a secretion. Probably some of these secretions are pro-
tective. It would appear as if the thyroid gland destroyed
substances that induce oedema, low temperature, and debility,
etc. In order to bring about these accidents it is only necessary
to extirpate the thyroid gland. After removal of the pancreas,
for example, diabetes occur. It was Brown-Sequard who drew
attention to the rejuvenating effects of testicular juice. The
beneficial influences of internal secretions and of the interaction
of glands are seen in the retardation of cancer of the breast by
removal of the ovaries and by castration in the treatment of
osteomalacia in the female. To Beatson, of Glasgow, we are
indebted for much that we know of this subject.-

For centuries the function of the thyroid gland was unknown.
It was not until Beverdin and Kocher, of Switzerland, and Hors-
ley, of London, extirpated the gland that we got to know some-
thing of its function, while as regards the therapeutic value of
thyroid juice in the treatment of myxcedema my colleague, Dr.
George Murray, of this city, can lay claim to having been one of the
earliest pioneers. It was the two Swiss surgeons who showed not
only that removal of the thyroid was followed by myxcedema, but
that a peculiar condition was observed in children when the gland
was congenitally defective. They also drew attention to the fact
that when the gland is enlarged and too much thyroid juice enters
the economy the processes of metabolism are hastened, palpita-
tion is experienced, and there occur exophthalmos, muscular
tremors, and slight rise of temperature. It is only recently,
however, that some of these symptoms have come to be attributed
to auto-intoxication. From the gland ISTotkin has removed two
substances: tliyroproieid, a genuine toxin; and thyro-iodine,
from which two albuminous bodies can be obtained, — one a
globulin and the other an enzyme. It is to the operation of
thyro-iodine, or iodothyrin as it is sometimes called that Bau-
mann attributes the special action of the thyroid gland, the
gland itself forming this substance from iodine elements in the
food. Notkin’s thyro-proteid is toxic. When injected into
animals it causes symptoms analogous to those observed in


cachexia strumipriva. This substance represents the colloid
material of the gland, and is considered to be, not a product
of secretion, but an effete substance which the gland eliminates.
After thyroidectomy it is this substance which, accumulating
in the body, is believed to be the cause of the particular symp-
toms that follow ablation of the gland. In the normal state
this material is destroyed or neutralized by the other element
just spoken of as an enzyme and which is really secreted by the
gland. Other bodies have been isolated, e.g., a phospho-albu-
minated substance resembling the thyro-nucleo-albumin of Ham-
marsten. Morktonne holds the view that it is the function of
the thyroid to collect the mucin contained in the blood and to
transform it synthetically into nucleo-albumin in the gray cor-
tical substance of the viscus. When the gland is extirpated this
transformation ceases, mucin accumulates in different parts of
the body and gives rise to myxcedema. Opinions are still divided
as to the function of the thyroid gland, but, according to Charrin,
it would appear as if it removed from the blood a phosphorated
nucleo-albumin which has a slightly acid reaction ; also that the
gland secretes an alkaloidal leucomaine or thyro-antitoxin which
neutralizes the nucleo-albumin just mentioned and forms with it
a new substance necessary for the nutrition and development of
the body. The thyroid gland would thus have a double function
to perform : antitoxic and nutritive. The theories just enun-
ciated all include removal of poisons from the blood. Bunge 1
is opposed to this teaching and he bases his opposition upon
what he observed after incomplete removal of the gland. It is
a well-known fact that if a small portion of the thyroid is left
the usual symptoms that follow thyrotomy do not develop.
Bunge’s contention is that it is extremely unlikely the small
portion left could remove from the blood what had hitherto been
removed by the whole gland. His opinion, therefore, is that
the thyroid gives off to the blood small quantities of a ferment
that influences the metabolism of the body.

An account of the supposed functions of the thyroid gland
would scarcely be complete in a book on auto-intoxication which
failed to take notice of the ingenious theory enunciated by Dr. I\

“Physiological and Pathological Chemistry,” Bunge.


Blum in Vir chow’s Archiv, 1901. To him the function of the
thyroid gland is not so much to form an internal secretion which
passes into the blood as to seize upon and render harmless certain
toxic substances that are formed in the intestine and find their
way into the circulation. Taking a certain number of dogs
upon whom he had performed thyroidectomj^ he fed some of
them upon milk and others upon meat. Among tbe animals fed
upon meat the mortality was as high as 96 per cent.; whereas,
of the dogs fed upon milk or milk and bread, 40 per cent, sur-
vived the twentieth day after the operation. Eighty per cent,
remained well as long as the milk diet was continued, but many
of them died very quickly when meat was substituted for milk.
It is not for a moment maintained that meat is in itself toxic
and that it is rendered innocuous by the secretion of the thyroid
gland. What is admitted is that certain toxins are formed in
the intestinal canal by the operation of bacteria upon food and
that meat favors their production, while the micro-organisms in
milk rather suspend the development of the ordinary microbes
usually met with in the alimentary canal. According to Blum,
it is these bacterial toxins of intestinal origin, enterotoxins,
that the thyroid gland seizes and destroys. When the thyroid
gland is absent or diseased the absorbed toxins from the intes-
tine produce changes in the body resembling myxcedema, viz. :
tetany, cretinism, and other neuroses. On microscopical exam-
ination the kidneys of the dogs operated upon often exhibited the
changes observed in interstitial nephritis. Blum, still further
theorizing, states that the circulating enterotoxins are seized by
the thyroid gland and converted by it into a fresh toxic sub-
stance containing iodine and named by him thyreotoxalbumin,
a substance which is said to correspond more or less closely with
the artificially isolated iodothyrin. To these experiments con-
siderable clinical importance must be attached. They show, at
any rate, that the production of toxins in the intestinal canal
can be limited by a milk diet.

Several of the glands of the body are functionally inter-
related, e.g., the thyroid and pituitary, thyroid and ovary or
testis. In cretins the testes are usually atrophied. Most physi-
cians are familiar with the enlargement of the thyroid that occurs


during pregnancy and often too at menstruation. In one of my
own patients removal of the uterus and ovaries was followed
within a few weeks by acute enlargement of the thyroid and
marked exophthalmos, with tremor and palpitation of the heart.

It was Brown- Sequard 1 who first directed attention, to the
internal secretion of the testes. For much that we know of
the function of the suprarenal bodies we are indebted to Schafer
and George Oliver. These glands according to Zucco, Supino,
and Albanese, protect the economy against muscular poisons.
They are supposed to remove worn-out pigments from the blood
and either to store them up as chromogens or transform them so
that they can be eliminated by the urine. When the adrenals
are destroyed there is loss of muscular power and a sense of very
great feebleness, as in Addison’s disease. It is worth remem-
bering from a therapeutic point of view that, while the injection
of thyroid juice effects great improvement in myxedematous
patients, in those who are suffering from Addison’s disease supra-
renal extract is practically without influence. Opotherapy is
therefore not without its limits, and experience has shown that
it is not without its dangers, as witness the emaciation that fol-
lows the administration of thyroid juice. The removal of the
suprarenal bodies even under careful antiseptic precautions is
always a severe operation. Animals, as a rule, do not survive
the operation well, although a dog experimented upon by Pol
lived four and one-half months. Eats probably bear the opera-
tion best of all animals. The rich supply of nerve-fibers to the
glands and the close connection of the latter with the sympathetic
nervous system explain why it is that extirpation of the adrenals
is borne so badly.

The pituitary body is often found to be enlarged after
extirpation of the thyroid ; also in sporadic cretinism and goiter.
Iodine, too, is found in the pituitary. These facts suggest that
the thyroid gland and pituitary body are somewhat interrelated
in function. Disease of the pituitary body leads to malnutrition
and to what is known as acromegaly.

The liver is one of the most important glands of the body,
and has a distinct sentinel duty to perforin. Healthy meat

iComptes Rendus, vol. xliii, p. 422, 1856; vol. xlv, p. 1036, 1857.


foods can become toxic when badly digested or imperfectly
transformed. Grave uraernic symptoms develop in dogs in
whom an Eck fistula has been made whereby the vena porta is
made to pour its contents into the vena cava so that the blood
coming from the intestine does not pass through the liver at all.
So long as animals that have undergone this operation are nour-
ished upon milk and bread they do well, but they become sleepy,
convulsed, and comatose when fed upon meat. Nencki has shown
that these symptoms are mostly due to the presence in the blood
of carbamate of ammonia, the precursor of urea. This harm-
ful carbamate can be got from the products of digestion of
meat in vitro as well as from the stomach.

It is unnecessary to deal with the functions of the other
glands of the body. When the spleen, for example, is removed
Laudenbach found that animals thus experimented upon became
the subjects of a form of cachexia that in time proved fatal. For
the blood to remain normal the spleen must be intact. Febrile
processes are largely due to operations taking place in the paren-
chyma of this organ through the intensity of phagocytic action.

In acute infectious fevers and in certain forms of poisoning
there is often found enlargement of the spleen. G. Dawein, 1 in
trying to solve experimentally the problem as to why the spleen is
enlarged in some fevers and not in others found, that if large
doses of sodium and potassium chlorate were given to dogs the
resulting splenic enlargement was directly proportional to the
number of red corpuscles destroyed by the drugs. He found that
a decrease of 1,000,000 erythrocytes in 1 cubic millimeter of
blood corresponded to a spleen twice, and a decrease of 3,000,000
to a spleen five times, its normal size. In rabbits potassium chlo-
rate does not cause disintegration of blood-cells, and therefore the
spleen rather shrinks than enlarges. Splenic enlargement is
therefore not due to any specific action of the drug upon the spleen
or upon the splenic nerves. Toluylendiamin produces the same
results by breaking up the red blood-cells. The splenic enlarge-
ment is due to the spleen harboring the broken-down blood-cor-
puscles. This functional activity is followed by hypersemia and
by hyperplasia. In order that the spleen shall enlarge the poison

1 Virchow’s Archiv, Bd. 161, ht. 3, p. 461.


must cause disintegration of the blood-corpuscles. There must,
in fact, be a rapidly progressing anaemia. The products of
broken-down blood-corpuscles when seized upon by the cells of
the splenic pulp probably have a stimulating influence upon the
latter, and as a consequence hypersemia and overgrowth occur.
In chlorosis there is no enlargement of the spleen, because there
is rather a deficiency in the formation of blood than destruction
of it. When we remember that the splenic arteries communicate
directly with the splenic pulp it is easy to understand how the
cells have every opportunity of retaining and destroying abnor-
mal or dead blood-corpuscles. If another example were required
of the spleen being the grave of blood-corpuscles mention need
only be made of the condition of this organ in leukaemia. This
disease is no longer regarded as a primary affection’ of the spleen.
The enlargement of the spleen in this malady is partly due to the
fact that its pulp is often packed with dead leucocytes. Some
cases of leukaemia are the result of an auto-intoxication that prob-
ably had an intestinal origin. In a few instances I have seen it
follow typhoid fever, while in others there has been a history of
some obscure form of intestinal illness.


Auto-intoxication of Intestinal Origin.

Bouchard and auto-intoxication. Mtiller, of Marburg, and his limitations of the
term auto-intoxication. Too exclusive a limitation. Hemmeter: auto-intoxl-
cation. Indicanuria. Estimation of indican in the urine. Albu and his
classification of auto-intoxications. Micro-organisms in the alimentary
canal: virulence of. Infection versus auto-intoxication. Stercorasmia: symp-
toms of. Stercorsemia in pregnancy, intestinal obstruction, and uraemia. The
uncontrollable vomiting of pregnancy and auto-intoxication. Pinard, Bouffe
de Saint Blaise, Dirmoser and Marcel Huge. Overfatigue and auto-intoxica-
tion. Views of A. v. Poehl and Verworn. Acid products in excess in the
tissues. The “dyspeptic liver” and cirrhosis. Opinions of Boix and Rivoghi.
Intestinal antisepsis. Views of authors pro and con.

Bacteriology as an explanation of the cause of disease
is in these days supplemented by the doctrine of poisons.
Nearly all writers on this subject admit that it was Bouchard
who gave the theory of auto-intoxication its proper position in
medical literature. Prior to him, as Albu has pointed out,
observations had been made in Germany, but it was the French
physician who gathered together the data from which he wove
his theory of auto-intoxication whereby he seeks to explain self-
poisoning of man by metabolic products formed by the organism
itself or by toxins produced within the gastro-intestinal canal.
Deranged metabolism must alter the character of terminal or-
ganic products just as imperfect elimination leads to their accu-
mulation within the body. Symptoms of poisoning, therefore,
may be due either to overproduction or to retention of physio-
logical or pathological products. Dr. F. Miiller, of Marburg,
prefers rigidly to limit the term auto-intoxication. He would
not include the effect produced by poisons that have been intro-
duced from the outside, nor the influence of toxins formed in
the interior of the body by microbes, as in infectious fevers,
but would restrict it to such conditions as carbonic acid poisoning
and its slowly asphyxiating consequences; also ursemia, diabetic
coma, and such pathological conditions as are due to imperfect
thyroid and suprarenal gland activity. It is to be remembered
that many of the poisons formed within the alimentary canal are



products not of the organism itself, but of the microbes that
inhabit the intestinal tract. Into the intestine there pass
from many sources both harmless and harmful substances. The
pancreas and liver, as well as the tubular glands of the mu-
cous membrane, are constantly diverting into the alimentary
canal numerous bodies, including ferments of all kinds, of
which the economy tries to rid itself. The lining mucous mem-
brane of the intestine is excretory as well as secretory, for if
corrosive sublimate be injected into the vein of the ear of a rabbit
the animal dies and at the autopsy there is found ulceration of
the large intestine. Arsenic injected into the blood is in a
similar, but in a less severe manner eliminated by the mucous
membrane of the stomach. In the contents of the gastrointes-
tinal canal two disintegrating processes are at work: fermenta-
tion of the carbohydrates from decomposition and putrefaction
consequent upon the breaking down of proteids, a process which
is attended by the formation of substances that give off an
extremely unpleasant odor.

We feel disposed to embrace within the term auto-intoxica-
tion more than Muller allows. In one form of auto-intoxication
poisons are formed in the interior of the cells of the body
as a result of metabolism: in another they are formed within
the intestinal canal from decomposition or putrefaction of the
food as a consequence of the operation of formed and unformed
ferments, or they originate in a deranged chemistry of diges-
tion which allows of the production of toxic bodies from in-
gested food. Hemmeter 1 doubts the reality of some of the
hitherto accepted forms of auto-intoxication on the ground
that the presence of chemical toxins has not been demonstrated
in the blood of patients; also that if auto-intoxication is
such a common thing people ought to become accustomed
to the presence in the blood of these toxins just as they do to
morphine and alcohol. He is of the opinion that the attacks
come and go too abruptly to be due to poisoning; but it is
this very fact that suggests the probability of their being tox-
emic, since there must be in the intestine at times sudden
evolutions of poison and almost just as quickly a rapid elimina-

1 “Diseases of the Intestines,” vol. i, p. 335.


tion of them. No one can watch a case of septicemia without
being struck by these facts, and, although septicaemia and auto-
intoxication from an intestinal source are not exactly parallel
conditions, and therefore comparable, yet there is in many re-
spects a considerable similarity between these two forms of tox-
aemia. Hemmeter considers that many of the symptoms usually
attributed to intestinal autotoxis are reflex in their nature. Miiller
is of the opinion, on the other hand, that one important cause
in operation is hereditary predisposition. While not altogether
discarding the theory, Hemmeter pleads for caution in accepting
all that is attempted to be explained on the terms of auto-intoxi-
cation. One of the best criteria of the putrefaction of proteid food
in the intestine is the presence of an increased amount of ethereal
sulphates in the urine. The putrefactive products in the intes-
tine vary with the microbes present. Sometimes the products
formed are harmless amido-acids and phenols, at other times
they are toxalbumins. In the human intestine under normal
circumstances there are formed as a consequence of the putre-
faction of proteid food such aromatic bodies as indol, skatol,
and phenol. One portion of each of these bodies is eliminated
in the fasces, while the other is reabsorbed and oxidized. Finally,
in the liver the absorbed portion enters into sulphur combi-
nations and is excreted by the kidneys combined with potas-
sium salts, principally in the form of indoxyl-sulphate of po-
tassium. While indican and the sulphur conjugated acids are
present in small quantity in normal urine, they are sometimes
found there in large quantities under pathological conditions.
They are increased, for example, in intestinal obstruction, diar-
rhoea, typhoid fever, peritonitis, in internal abdominal suppura-
tion, and in cancer of the stomach. Indicanuria has been
found in lead and arsenical poisoning and in severe types of
anaemia and chronic phthisis. A comparatively easy method of
detecting indican in the urine is that recommended by Iafle,
viz. : fill one-half of a test tube with urine and add nearly the
same quantity of hydrochloric acid, 2 to 3 cubic centimeters of
chloroform, and a drop or two of liquor ferri perchloridi. Ee-
verse the tube a few times. The chloroform separates out and
is colored blue. On gently heating the tube a red reaction is


obtained. The quantitative test for indican is a color one, but
it is tedious to apply. The average quantity of indican in the
urine of 24 hours is, according to Hoppe-Seyler, 0.17 gram to
0.27 gram. Since, however, it is in the liver that the putre-
factive bodies already mentioned are converted into conjugated
sulphur compounds we would naturally expect that in hepatic
inadequacy these would be diminished in the urine. As a matter
of fact, that occurs. The complex sulphur bodies have been
found to be diminished in cirrhosis and in cancer of the liver.

Albu 1 classifies auto-intoxications under four groups: (1)
auto-intoxication caused by loss of function of an organ, — e.g.,
myxoedema, pancreatic diabetes, Addison’s disease, etc.; (2)
auto-intoxication due to general abnormalities of metabolism, —
e.g., gout and oxaluria; (3) auto-intoxication from retention
of physiological products of metabolism in the various organs,
as witness the toxic phenomena observed after extensive burns
of the skin; (4) auto-intoxication caused by overproduction of
physiological and pathological products of the organisms, — e.g.,
acetonuria and the coma of diabetes and cancer. Attention is
drawn to Albu’s classification only as a convenient mode of
grouping together the phenomena of auto-intoxication, and not
with any intention of adhering to it in these pages.

Of the diseased conditions that are generally attributed to
abnormal decompositions occurring in the intestine mention need
only be made of a few, — e.g., gastro-intestinal catarrh, epilepsy,
leuksemia, rickets, certain skin affections, chlorosis, etc. Taking
any one of these maladies, what proof have we that such and such
a disease is the result of intestinal decomposition or putrefaction ?
The ingestion of decomposing animal food, for example, may be
followed by symptoms not unlike those observed in typhoid
fever, ptomatropin poisoning, and gastro-enteritis. Quite apart
from the character of the food taken, it is known that stagnation
in the intestinal tract is followed by decomposition and putre-
faction of the contents in a particular part of the alimentary
canal. Wherever such a delay occurs micro-organisms flourish.
Decomposition takes place in the stomach when this organ has

1 “Autointoxicationen des Intestinal Tractus,” Berlin, 1895, S. 7.


become incapable of propelling its contents. Ileus and strangu-
lation of the intestine produce similar results. The normal
habitat of micro-organisms has only to be disturbed for serious
consequences to follow. There are myriads of microbes normally
in the mouth and gastro-intestinal tract of adult man. When
these have their surroundings altered or when they pass into
other places or organs it is then that they cause disease. Proof
of this is seen in the operations of pneumococci. The bacterium
coli, too, which is harmless when in the intestine, causes fatal
peritonitis when it finds its way into the abdominal cavity, and
pyelonephritis when in the urinary tract. It is not always easy
to demonstrate the path by which microbes pass into the system
from the intestinal canal. Nocard, Desonby, and Porcher 1 are
of opinion that “during the absorption of food whole battalions
of microbes pass from the intestine into the chyle and blood-
vessels ; that these are rendered harmless in the lungs and other
organs and are, for the most part, eliminated by the urine.” It
is when the vitality of the tissues is reduced that microbes find
conditions most favorable for their development. A healthy man
can resist the action of microbes. It is when he gets run down
in health that he becomes a prey to them. Neisser has shown
that the chyle, blood, and internal organs of healthy animals
can remain free from germs after the administration of food
rich in microbes. The intestinal mucous membrane is not always
a protective barrier. Virulent bacteria, for example, when intro-
duced by the mouth can penetrate the intestinal wall, as is shown
in meat poisoning and tuberculosis caused by contaminated milk.
An unhealthy condition of the intestinal wall facilitates the
passage of such microbes through it as the colon bacillus. In
children who have died from acute gastro-enteritis the blood
and internal organs have been found by Czerny and Heubner
to contain bacteria that had evidently escaped from the intestinal
canal. In strangulated hernia, too, bacteria have been found in
the sac. Miiller, while not accepting in toto the theory of auto-
intoxication, considers such cases as those just mentioned to be
rather of a contagious character and due to the entrance into

1 Congress fur Int. Medic, Wiesbaden, 1898, quoted from Miiller.


the system of microbes from without; also that, even when the
bacillus coli is found away from the intestinal tract, this microbe
was probably introduced from without by means of food. He is
of the opinion, too, that microbes when introduced from without
are always more dangerous than those that have been for a period
inhabiting the intestinal canal, since the individual under these
circumstances ought to have developed an immunity to their
products. It is sometimes extremely difficult to differentiate
between infection and auto-intoxication. The greater the length
of the period of incubation after exposure, the presence of en-
largement of the spleen and f everishness, suggest infection ; but
it is well to remember that with certain classes of poisons there
may be a period of incubation of one or two days before symp-
toms develop.

Stercorgemia is a complex condition. The symptoms ob-
served are vomiting, collapse ; cold, clammy perspiration ; small,
rapid pulse; retention of the intelligence, and death from
asthenia. It is not necessary that there should be intestinal
obstruction to cause stercorgemia. While chronic constipation
causing obstruction may induce it, stercorgemia may yet occur
without this. It occasionally develops in persons whose kid-
neys are diseased, and may therefore be urgemic. I have also
seen it occur and prove fatal in a case where after abdominal
section the surgeon in closing the wound had inadvertently
stitched a piece of intestine to the abdominal wall and where
a fistulous opening subsequently formed. Here, although there
was free escape for the intestinal contents, fatal poisoning still
occurred either from absorption of toxins or from the pas-
sage of microbes through the injured wall of the intestine.
Maci 1 brought before the Obstetrical Society of France (April,
1901) three cases of stercorgemia occurring during pregnancy.
In one of the cases abortion in the second month of pregnancy
seemed imminent: there were albuminuria and a rise of tem-
perature, but the use of enemata, coupled with the administra-
tion of saline aperients was followed by the escape of hardened
fgeces, and thereafter the uterine hgemorrhage ceased, the tem-

1 L’Obstr6trique, May 15, 1901, quoted in Supplem. to Brit. Med.
Journal, Aug. 24, 1901.


perature fell, and the pregnancy proceeded. In another of
Maci’s cases hyperemesis was very pronounced. By means of
enemata and purgatives large faecal masses were passed and
pregnancy advanced. In a third case there were albuminuria
and vomiting, with constipation of several days’ duration. All
of these symptoms ceased after the administration of rhubarb
and benzo-naphthol. One feature present in Maci’s patients was
obstinate constipation. Budin, the French obstetrician, taught
that constipation in pregnant women who are the subjects of
albuminuria was often due to milk diet. Stercoraemia itself
may be a cause of albuminuria, rise of temperature, and vom-

Suppression of urine in uraemia is indirectly a cause of
vomiting. It is difficult to say, when vomiting has continued
for a length of time, whether the emesis of itself may not be the
cause of the oliguria. The relation of cause and effect is not
always quite clear. A short while ago I had under my care in
the Newcastle-upon-Tyne Infirmary a man, aged 60, who for
twenty-eight years had worked in a lead factory. His case was
supposed to be one of lead colic at first, and subsequently of
intestinal obstruction. He was extremely ill on admission, and
during the few days he was in the surgical ward there was fre-
quent vomiting, the material brought up being a thin, greenish-
yellow liquid, strongly faecal in odor. It was stated that the
bowels had not been opened for eight days. The faecal vomiting
and history of constipation suggested intestinal obstruction, but
there was no distension of the abdomen, and although patient
was extremely thin no mass could be felt. The man, when first
I saw him, looked very ill: his eyes were prominent and fixed;
his heart’s sounds were feeble, the pulse was small and there was
a sense of air-hunger which, with no physical signs of disease
in the chest, the deepest respirations did not seem to appease.
The case presented all the characters of an auto-intoxication.
Although enemata and salines brought away large quantities of
faecal matter patient was not relieved, for the stercoraemia con-
tinued. There was very marked oliguria from the first, followed
by suppression. A catheter passed into the bladder drew off three
or four teaspoonfuls of urine which on examination was found


to be highly albuminous. On the third and fourth day after he
entered the infirmary the man died, his symptoms of faecal vom-
iting, etc., never having abated. At the autopsy the gastro-
intestinal tract was found throughout to be quite healthy, but
the kidneys were cystic and contracted and belonged to the type
known as the small, granular kidney. How to explain the ster-
coraemia in this patient is rather difficult on any other lines than
that in the early stages of the illness the vomiting was ursemic.
Since in previous pages I have more than once alluded to
autotoxis in pregnancy, this is perhaps the proper place to draw
attention, at greater length, to the mixed form of auto-intoxica-
tion that occurs during pregnancy and which is believed to be
partly renal, hepatic, intestinal, and the consequence of altered
metabolism. Women who are with child are often the subjects
of digestive derangements of which uncontrollable vomiting is
a most distressing and exhausting accompaniment. Morning
sickness as a sign of pregnancy may occur at any stage, but the
vomiting to which I wish particularly to refer is that severe
form met with usually in the latter months of utero-gestation,
not necessarily in the morning, but at any hour of the day, and
which if not checked may lead to death. Numerous theories have
been brought forward to explain it. Many physicians regard it
as hysterical and therefore speak of it as a neurosis; others
maintain that it is reflex in its causation and due to some ab-
normal development of the gravid uterus or to organic disease
of the adnexa, while by an increasing number of observers it is
believed to be a symptom of auto-intoxication. Since in some
instances the vomiting of pregnancy is controlled by bromides,
this circumstance suggests that it can be of purely nervous
origin. How far it is due to heightened tension of the cervix
(Copeman), retroversion or anteversion of the womb (Caseaux
and Grailly Hewitt), ulceration of the “os” (Bennett), hyper-
esthesia or rigidity of the internal “os,” alternate rhythmic dis-
tension and contraction of the uterus, it is unnecessary to dis-
cuss. Here we are rather concerned with the possibility that in
many pregnant women the vomiting is the expression of a tox-
aemia due to the absorption of poisons subsequently to be men-


During pregnancy it is generally admitted that the blood
becomes altered in composition, and that as effete matter is
present in excess a burden is imposed upon the eliminating organs
for its removal. The developing foetus contributes its quota of
waste material to the maternal blood, but that it is not the source
of poisoning is shown by the occurrence of eclampsia in women
who are the subjects of hydatidiform mole. Should, through
any cause, an important emunctory fail to accomplish its proper
amount of work, such nervous derangements as vomiting and
convulsions are liable to arise. It is impossible, when these
symptoms appear, always to name the particular eliminating
organ that is at fault. Probably there is more than one. Albu-
minuria in a pregnant woman is regarded as a menace to health
and as an indication of toxaemia. Pinard and Bouffe de Saint
Blaise have drawn attention to the important part played by
the liver and kidneys in auto-intoxication. They regard the
vomiting of pregnancy as a sign of hepatic toxaemia and of
similar significance to eclampsia, ptyalism, and other disorders.
Dirmoser in 1897 expressed the opinion that the intractable
vomiting of pregnancy is due to the absorption of such putre-
factive products as indol and skatol. In analyzing the urine in
6 grave cases he found (1) urobilin, (2) the coloring matter of
blood in 4 cases, (3) trace of albumin, (4) peptone in 4 cases,
(5) acetone in 4 cases, (6) excess of oxalic acid, (7) excess of
indol and skatol, and (8) hyaline and granular tube casts in 3
cases. Dirmoser therefore maintains that (a) metabolism is
increased in all the patients; (b) that such abnormal bodies as
albumin, urobilin, acetone, and peptone are found; (c) occa-
sionally that acute nephritis is present. Just as it is not a single
poison that is present so probably there is at fault more than
one defective organ. Since the causes of the vomiting of preg-
nancy are therefore many, auto-intoxication probably plays a
part, and that not the least important. The patient vomits be-
cause she is poisoned. Marcel Huge {Gazette Hebdomadaire de
Medecine, etc., September, 1901) considers auto-intoxication to
be the commonest cause of the vomiting of pregnancy. He holds
that pregnancy, by overloading the blood, imposes burdens upon
the emunctories ; also that it impedes the functions of previously


healthy organs by the pressure exercised by the gravid uterus or
it may be that there is the development of some unusual form
of toxins.

One other cause of auto-intoxication must be alluded to,
and that is the overexcitement inseparable from the undue haste
and the abnormal conditions of modern life. Alex. v. d. Poehl, of
St. Petersburg, 1 has recently contributed a paper to the elucida-
tion of this question which formed the subject of discussion by
Professor Verworn at a meeting of German naturalists and
medical men in 1901. Verworn draws a distinction between
overexcitement of the nerves and their exhaustion. Indepen-
dently of each other, these two physicians carried out a series of
researches bearing upon the subject of overexcitement, mentally,
bodily, and sexually. Verworn arrived at the conclusion that
in consequence of overexertion there is induced a toxgemia to
which excess of carbon dioxide in the tissues largely contributes.
He explains the sense of exhaustion after laborious work on the
theory of the available oxygen that is normally stored up in the
nerve centers having been largely consumed. Poehl holds a
similar opinion : he considers that there is diminished tissue or
internal respiration due to altered nerve metabolism resulting
from overexcitement. Urinary analysis strengthens this sup-
position. Overexertion reduces the alkalinity of the tissues.
Not only does the urine become more acid, but the tissues them-
selves exhibit a similar chemical reaction owing to the accumu-
lation therein of such products as lactic acid. Fatigue lowers
the energy of the normal oxidation processes of the tissues.
Whenever internal respiration is diminished lactic and other
acids are not sufficiently oxidized ; they accumulate and act both
as local and general poisons. A sense of undue fatigue is re-
moved by breathing fresh air and by draughts of alkaline mineral
waters. To the causation of toxaemia consequent upon over-
excitement such intermediary assimilation products as xanthin,
hypoxanthin, and neurin, as well as lactic acid, in all probability
contribute especially by the influence they exert upon the renal
cells while being eliminated by the kidneys. So far as the ques-

• Therapist, March, April, May, 1902.


tion of overfatigue is concerned, nerve centers are more sus-
ceptible than are nerve trunks or nerve endings in muscle, for
nerve centers have the more intense metabolism. Their freer
vascular supply, while indicating that these centers are the seat
of greater activity, is, on the other hand, a means whereby they
are more exposed to the injurious influences of effete material
that may be circulating in the blood.

However numerous may be the causes of auto-intoxication,
there is not the least doubt that it is from the gastro-intestinal
tract that the poisons are principally absorbed. The term auto-
intoxication might be more appropriately applied to the produc-
tion of poisons formed within the tissues and due to such a cause,
for example, as that mentioned in the last paragraph, viz.’:
overfatigue, but for some reason or other, probably through
Bouchard having mainly insisted upon the association, it has
come to be more generally applied to constitutional states that
are the outcome of a toxaemia caused by the absorption of gastro-
intestinal products. The lassitude after a heavy meal, for exam-
ple, is due, among other things, to the resorption of toxic pep-
tones. Miiller is opposed to this teaching, for he holds that the
lassitude appears too early after the meal has been taken. Since
it does not occur therefore when absorption is at its height he
thinks it must be the result of mechanical overdistension of the
stomach or the outcome of certain vasomotor influences. The
symptoms, be it remembered, are less proportional to the amount
of food taken than to its nature and composition. The liver is
the organ through which most of the absorbed digested products
pass. Sentinel-like, this organ refuses passage to some of these
substances. If off its guard, some of them slip through that
ought not. As a consequence of the prolonged action of abnor-
mally prepared digested products upon the liver Bouchard and
Hornot maintain that cirrhosis of this organ may develop. This
so-called “dyspeptic liver” commences as a simple enlargement of
the viscus. In patients from whom alcohol and syphilis can be
excluded this dyspeptic liver may possibly be the origin of some
of the hitherto unexplained forms of cirrhosis of that organ.
Boix has witnessed in animals a simple enlargement of the liver
become transformed into a veritable cirrhosis by the administra-


tion of butyric and acetic acid in the food. Eivoghi from his
experiments concluded that indol, skatol, and phenol might pos-
sibly also induce cirrhosis. Out of 64 cases of cirrhosis of the
liver he believed 4 to be due to dyspepsia. That the liver can
become affected in acute intestinal disease and in intoxication
is proved by phosphorus and sausage poisoning. The patho-
logical changes in the liver are frequently the result of the action
of toxins, for bacteria have been found in the organ. Deranged
functional activity of the liver is sufficient to cause symptoms
of toxaemia, especially if nitrogenous food is administered. In-
creased urinary toxicity almost invariably follows diminished
antitoxic function of the liver. Bouchard names the quantity of
urotoxies which an individual makes per kilo. This in health
equals 0.464, the urotoxic coefficient, and he finds when the liver
cells have become altered in structure that the urotoxic coefficient
is higher than in the normal state. It may be doubled or tripled.
Ammonia, potass, and extractive matters contribute to this
hypertoxicity : ammonia itself is 40 times more toxic than urea.
In the earlier part of this book Bouchard deals with the subject
of the day and night variations of urinary toxicity : the toxicity
of the day urine equals 31 urotoxies and that of the night 8.
There is no need to reproduce here his arguments except to re-
peat that a day of muscular activity spent in the country in the
fresh air diminishes by one-third the urinary toxicity — a diminu-
tion that is continued into the period of repose; also that after
laborious exercise the urine often contains, if not immediately,
then later on, more urea, more uric acid and other acid products
as well as excess of chloride of sodium, whereas after brain work
the urine is richer in sulphates and phosphates. Overfatigue, as
already mentioned, adds acid substances to the blood and reduces
the resistance of the human body to disease.

If, as Bouchard has demonstrated, the gastro-intestinal tract
is the source of the largest number of poisons that cause auto-
intoxication, then clearly this is the part of the body that calls
for special attention and treatment. Prevention takes precedence
of cure. Nitrogenous food is much more likely to induce auto-
intoxication than will carbohydrates. The freer use of milk and
the return to a simpler diet are called for since their use is fol-


lowed by a reduction of ethereal sulphates in the urine. Con-
stipation must be overcome by diet and by aperients. When these
fail the administration of intestinal antiseptics becomes a neces-
sity and medicines of this class, if they are to do any good, must
possess little solubility and be therefore slowly absorbed so that
they can traverse the length of the intestines. Muller is not a
believer in intestinal antiseptics; he doubts their efficacy; he
maintains that there is no proof that iodoform, naphthol, men-
thol, and the salicylic preparations diminish the quantity of
ethereal sulphates in the urine or that these drugs influence in-
testinal putrefaction. My own experience is quite contrary to
that of Muller. Again and again I have seen the most marked
benefit follow the administration of intestinal antiseptics. In
dilated stomach, where decomposition is often very great, anti-
septics may do little good, but after all this is only a limited
portion of the alimentary tract. The excessive acidity of the
contents of the stomach has first to be neutralized. As the
quantity of formed and unformed ferments in this viscus is too
great to be readily influenced by antiseptics it becomes necessary
to wash out the stomach perhaps on more than one occasion. I
have never seen intestinal antiseptics do harm, but it is with
these drugs, as with all synthetic preparations, there is a limit
to their safety, as witness the effects of taking internally carbolic
and salicylic acids in doses larger than medicinal.

Hemmeter, 1 although not a staunch supporter of the theory
of gastro-intestinal intoxication, still considers that it is not
without reasonable foundation : he has therefore in his book laid
down four lines of treatment for intestinal auto-intoxication,
viz. : prophylactic, dietetic, hydriatic, — i.e., lavage, — and medic-
inal. In prophylaxis is included the avoidance of all food that is
capable of undergoing fermentation and putrefaction. As there
is an idiosyncrasy in some people to certain kinds of food experi-
ence must be the guide as to what is to be included in the dietary.
Since albuminuria of a transitory character can be induced by
the action of abnormally prepared digested products upon the
kidney, a chemical examination of the urine should from time to

‘Diseases of Intestine,” vol. i, p. 337, 190L


time be made, for under treatment and simpler diet the albu-
minuria may quickly disappear and with it the severe headache
and the accompanying sense of malaise. Lavage of the colon
and anything that will promote the normal peristalsis of the
intestine are of service. Hemmeter holds the view that in our
efforts to combat intestinal auto-intoxication we may weaken
by the administration of antiseptics the bactericidal powers
which the normal intestine possesses. E. Vidal (Revue de Chi-
rurgie, October 10, 1900) maintains that the secretion which is
poured out from healthy intestinal mucous membrane possesses
antitoxic properties, and that “in intestinal occlusion the fatal
results are not exclusively due to the mechanical obstruction, but
to a stercorEemic infection consequent upon loss of power of the
intestinal wall to exert its antitoxic effect.” E. Schiitz (Berliner
Tclinische Wochenschrift, 1900, No. 25) found that both castor-
oil and calomel, under certain conditions, injured “the normal
provisions for disinfection of the intestine.” Experience, after
all, must be our teacher. It is very improbable that the belief
in the efficacy of calomel when carefully administered and in
proper cases is likely to be shaken by the statements of opponents
of intestinal disinfection, for improved peristalsis is one of the
best means of ridding the system of toxic products. Calomel is
too soluble a substance and it stays too short a period in the
digestive canal to be an intestinal antiseptic in the ordinary sense
of the word. Charrin found after administering 4 grams of
naphthol-beta in twenty-four hours to three patients who were
suffering from chronic enteritis that he had succeeded in sup-
pressing one-third of their urinary toxicity. In hepatic disease
Surmount similarly diminished urinary toxicity by one-half. It
is the sparingly soluble intestinal antiseptics such as salol, thy-
mol, and naphthalin that do good. The treatment of auto-
intoxication by means of intestinal antiseptics is of little use
without due attention being also paid to such prophylactic
measures as careful dieting and the administration of suitable


Acetonemia, 258, 259
Acetone, in urine, 11, 148, 258

tests for, 148, 258
Acholia, abnormal metabolism a cause
of, 11
in jaundice, 239, 244, 245
Acid, acetic, in dough, 190

in. intestine, 17

in muscle-extract, 80

in putrefactive products, 17, 94

in tissues, 17, 80

in urine, 17

phalangeal nodes due to, 180
Acid bile, 144

Acid, boracic, an antiseptic, 103
butyric, in dough, 190

in intestine, 17

in muscle-extract, 80

in putrefactive products, 17, 94

in tissues, 17, 94

in urine, 17
carbolic, an antipyretic, 209, 221, 222

an antiseptic, 103, 207

and mercury, 207

in dough, 190

in faeces, 148

in intestine, 17, 146, 148

in putrefactive products, 17, 93, 94

in tissues, 17

in typhoid, 204, 219, 230

in urine, 17, 146, 148

micro-organisms produce, 13

toxic power of, 207
cholic, in intestine, 19, 234
cholalic, in intestine, 19, 234
diarrhoea, 144, 145, 176
dyspepsia, 144, 145
fasces of dilated stomach, 167
glycocholic, in intestine, 19, 234
hippuric, toxic power of, 123
hydrochloric, an antiseptic, 89, 156,
166, 194, 195

functions of, 156

in dilated stomach, 194, 195
lactic, in intestine, 17

in tissues, 17

in urine, 17
odor of breath, 167
oxalic, in intestine, 17

in tissue, 17

in urine, 17

uraemia due to, 112
stools, 144, 145, 167

sulphuric, micro-organisms produce,

a putrefactive product, 94
taurocholic, in intestine, 19, 234
uric, vide Uric acid
valeric, in putrefactive products, 94
vomiting, 144
Ac.ds, bile excretion of, 238
fatty, micro-organisms produce, 13
in dough, 190
in intestine, 17, 19
Acids, in muscle-extract, 80
in putrefactive products, 17, 94
in tissues, 17
in urine, 17, 146, 148
toxic power of, 33, 34

Acids, vegetable, in typhoid, 228
Acne, in dilated stomach, 171

rosacea, in dilated stomach, 171, 179
Acquired diathesis, 7, 8
Acute atrophy of liver circulatory sys-
tem in, 243
haemorrhages in, 243
jaundice in, 246
kidneys in, 243
metabolism in, 243
naphthalin in, 242, 243, 274
renal system in, 243
urine of, 243
Adam: toxaemia in asthma, 164
Advantages of the intra-venous method

of study, 26
Ague, quinine in, 209, 220
Albu, auto-intoxicationen, 318
Albumin, and peptones, 10, 18, 109, 173
nephritis due to, 10
white blood-cells from, 18
Albuminuria, exhaustion due to, 109
hydraemia due to, 109
in Bright’s disease, 108
in diabetes, 257

in dilated stomach, 173, 179, 182, 196
in intra-venous injections, 27, 2S, 36,

52, 74, 87, 234, 277, 278
in jaundice, 242
in lardaceous disease, 109
in subcutaneous injections, 26
oedema in, 109
Albumose, poison, 183
Alcohol, intra-venous injections of, 29

toxic power of, 29
Alcoholic extract, intra-venous injec-
tions of, 55, 78, 92, 96, 148, 149, 278,
of blood, 78

of choleraic urine, 278, 279
of faeces, 94
of liver, 79
of muscle, 79, 148

of putrefactive products, 92, 97, 148
of urine, 55, 129, 268, 278, 279
the narcotic of, 57, 129
the sialagogue of, 57, 79, 129
Alcoholism, dilated stomach due to, 186
Alexin, 306

Alimentary method of producing artifi-
cial toxasmia, 25
system, in dilated stomach, 169
in dyspepsia, 144, 153
in gastric fullness, 153
in intestinal obstruction, 150
in intra-venous injections, 79, 87, 88,

95, 256, 278
in uraemia, 113
poisons in the, 89, 94, 102, 106
uraemia, 131, 135, 139, 140
Alkaloid, sepsine an, 92
Alkaloids, in blood, 16, 18, 78
in faeces, 95, 102, 144, 146, 157, 262, 273
in intestine, 102, 163
in putrefactive products, 92
in tissues, 16, 237, 248
in urine, 10, 17, 32, 55, 67, 68, 78, 93,
102, 103. 130, 146, 158, 163




Alkaloids, intestinal poisons due to, 144

micro-organisms produce, 15

mydriatic, 92

of cholera, 273

tests for, 16, 95, 278

the total toxic power of, 130

toxic power of, vide Toxic power

trypsin develops, 95
Amaurosis, in Brights’ disease, 111
Ammonaemia, 49, 112, 119, 122

convulsions in, 121

temperature in, 122
Ammonia, an antipyretic, 64, 121, 122

in blood, 120

in faeces, 97, 144

in intestine, 145

in putrefactive products, 93, 94, 97, 145

in urine, 120

micro-organisms produce, 13

toxic power of, 99, 125

uraemia due to, 112, 120, 122
Anaemia, pernicious, odor of breath in,
176, 258

urine of, 148, 258

urochromes of, 148
Angina, false, in dilated stomach, 169,

171, 179
Anhidrosis, in toxaemia, 159
Anilin, antiseptic power of, 207

toxic power of, 207
Antagonism of the toxic powers of

urine, 42, 44, 62, 63, 127, 12S, 250
Antidotes, in uraemia, 135, 139, 140
Antipyretic, ammonia as an, 64, 121, 122

antipyrin as an, 210, 217, 221, 222, 226

carbolic as an, 209, 211, 22

quinine as an, 209, 210, 217, 220, 222, 230

the. of urine, 63, 64, 122, 130

treatment, 216-227
baths in, 217, 223-227
limits of, 216, 227
Antiseptics, anilin, 207

bile, 89, 94

boracic acid, 103

calomel, 103, 104, 210, 211, 229

carbolic acid, 103, 207

charcoal, 103, 105, 141, 185, 195, 202, 229

combined, the more effective, 208

creosote, 103

formulae for use of, 105, 229

general, discussed, 205, 211

hydrochloric acid, 89, 156, 166, 194

in dilated stomach, 174, 185, 194

in typhoid, 202, 204, 209, 211, 229, 230

intestinal, 103, 106, 141, 142, 202, 204,
210 229

iodoform, 104, 105, 141, 145, 185

naphthalin, 194, 204, 229, 230

potassium iodide, 207

sodium iodide, 207

toxic power of, 104, 207, 208

uraemia, 141
Anuria, choleraic, 79, 117, 282

enemata in, 135

myosis in, 67, 283

obstructive, 110, 116, 118

ocular symptoms in, 67, 283

treatment of, 135, 290

urea of, 112, 117

venesection in, 277, 290
Aphasia, in dilated stomach, 169
Arsenic, eliminated in stomach, in-
jected in blood, 316
Arthritic diathesis, 6-8
Arthritis in dilated stomach, 174, 175
Artificial toxaemia, methods of produc-
ing, 25, 26
Ascites, exhaustion due to, 109

Asphyxia, death by, 24

normal substances a cause of, 10

toxic origin of, 24, 25
Asthma, in dilated stomach, 172, 179

periodicity, 172
Asthmatic type in dilated stomach, 179
Ataxia, dilated stomach in, 186
Auto-intoxication, term limit, 315

Bacillus glutinis, 190
of cholera, 263-266, 268 et seq
of typhoid, 199, 200

injections of, 199, 200
pyocyaneus, 254, 255

injections of, 254

tests for, 243, 254
Bacteriolysin, 306
Baths, in dilated stomach, 187, 1S8
in measles, 227
in pneumonia, 227
in rheumatism, 227
in scarlatina, 227

in typhoid, 218, 219, 223-228, 230, 231
in uraemia, 133
inflammations due to, 227
limits of, 227, 228
methods of use of, 223-225
the results of, 214-216, 227-229
Bile, acid, 145
acids, disease due to, 10

excretion of, 238

in intestine, 19, 234
amount secreted per diem, 85, 144, 233
an antiseptic, 89, 94
and urine, toxic power of, 81, 85, 86,

blood arrests, 235, 236
charcoal acts on, 82, 140, 141, 235
composition of, 233, 234
excretion of, 86, 238, 240
in urine, 240

intestinal toxaemia due to, 143, 144
intra-venous injections of, 81, 82, 237
liver arrests, 81, 85, 233-235, 238
minerals, toxic power of, 83, 84, 87
of dyspepsia, 145
pigment, vide Bilirubin
poisons in, 144
potass in, 83, 84, 87
salts, tests for, 236

toxic power of, 82, 235, 238, 240
suppression of, 242
tests for, 234, 236
tissues arrest, 235-238, 240, 241
total toxic power of, 235
toxaemia, 233-246
toxic power of, vide Toxic power
Bilirubin and bile-salts, toxic power of,
235, 238
in intestine, 234

intra-venous injections of, 235, 237
properties of, 234
tests for, 234, 236
tissues arrest, 236, 238
toxic power of, vide Toxic power
Blood, agglutination, 3^8
alcoholic extract of, 78, 79
alkalinity, 307
alkaloids in the, 16, 18, 78
ammonia in, 120
amount of poisons in, necessary to

produce death, 74
cells, from albumen, 18, 173

destroy poisons, 18

liberate poisons, 77-79
extract, intra-venous injections of,
77, 79

toxic power of, 77, 79



Blood in diarrhcea, 109

indigo in, 16

intoxication of the, 88

intra-venous injections of, 74, 149

leucin in, 242

micro-organisms in, 199

minerals in, 88

of Bright’s disease, 109, 110

of cholera, 79

of diabetes, 256, 257

of jaundice, 241, 242

of lardaceous disease, 109

of pyrexia, 216, 217

of typhoid, 199

of uraemia, 79, 117, 121

peptones in, 18, 173

poisons in the, vide Poisons

portal, 16, 18, 73, 149

potassium in, 130

putrefactive products in, 89, 90

sugar in, 256

sulphuretted hydrogen in, 16, 156

the sialagogue of, 57, 78, 79

the three sources of intoxication of,
88, 89

toxic power of, 70-79, 149

tyrosin in, 242

urea in, 117, 121

xanthin in, 242
Blum, F. D., 145, 310, 311
Bread, the fermentation of, 190
Breath, odor of, in coma, 176, 258

in diabetes, 176, 258, 259

in dilated stomach, 167, 171, 176, 258

in dyspepsia, 154, 258

in leukaemia, 175, 258

in pernicious anaemia, 175, 258

in typhoid, 258
Bright’s disease, albuminuria in, 108,

amaurosis in, 111

blood of, 109, 110

cerebral haemorrhage in, 110

circulatory system in, 110, 111

coma in, 111

convulsions in, 111

cutaneous system in, 110

entorrhagia in, 110

epistaxis in, 110

haematemesis in, 110

haemorrhages in, 110, 111

hydraemia in, 109, 111

inflammations in. 111

nervous system in, 111

ocular symptoms in, 111

oedema in, 110, 111

pericarditis in. 111

prurigo in, 110

purpura in, 110

retinitis in, 111

symptoms in, 108-111
Bronchitis, in dilated stomach, 172, 179
Brunton Lauder: Cholera, 283
Bulimia, in dilated stomach, 166
Butyric acid, vide Acid, butyric

Cachexia strumipriva, 310
Caffeine, in uraemia, 134
Calomel, an antiseptic, 103, 104, 210, 211,
in typhoid, 211, 212, 229
disadvantages of, 211
Canquoin paste, a caustic, 170
Carbolic acid, vide Acid, carbolic

enemata in typhoid, 204, 230
Carcinoma, gastric, coma in, 175
dilated stomach due to, 186
toxaemia due to, 163

Cardiac type of dilated stomach, 179
Cardialgia, in dilated stomach, 167

in dyspepsia, 144
Cerebral haemorrhage, in Bright’s dis-
ease, 110

oedema, in jaundice, 245
in uraemia, 112, 114-116
Charcoal acts on bile, 82, 140, 141, 235

on faeces, 103, 105, 203

on putrefactive products, 93, 141, 146

on urine, 55, 58, 103, 105, 130, 203
Charcoal, an antiseptic, 103, 105, 141,
185, 194, 202, 203, 229, 23U

formulae for use of, 105, 229, 230

in typhoid, 202, 2U3, 229, 230

in uraemia, 141, 142
Charrin, 22
Chemistry of putrefactive products, 92,

Cheyne-Stokes respirations, in cholera,

in uraemia, 113
Chloral, in uraemia, 139
Chloroform, in dilated stomach, 194, 195

in uraemia, 139
Chlorosis, in dilated stomach, 166, 180
Cholaemia, in jaundice, 244

normal substances a cause of, 10
Cholalic acid, in intestine, 19, 234
Cholera, alkaloids of, 273

anuria of, 79, 116, 282

bacillus of, 263-266, 26S et seq.

blood of, 79

Cheyne-Stokes, respirations in, 282

etiology of, 260-263

experimental, 263-271

faeces of, 273

iodoform in, 271, 272

muscarin poison, 284

myosis in, 6S, 130, 2S2, 283

naphthalin in, 243, 271, 272, 273

nervous system in, 68, 130, 282, 283

pathology of, 268-280

renal system in, 282

respiratory system in, 282

symptoms in, 68, 130, 2S2, 283

temperature in, 2S2

toxines, 283

treatment of, 271, 272, 285

uraemia in, 282

urine of, 117, 145, 274
Choleraic urine, extracts of, 279, 2S0

intra-venous injection of, 274-278
Cholesteraemia, 82
Cholesterin, toxic power of, 82, 233
Cholic acid, in intestine, 19, 234
Cholin, 284

Circulatory system, in acute yellow
atrophy of liver, 243

in Bright’s disease, 110, 111

in coma, 176

in diabetes, 176, 256, 257

in dilated stomach, 166, 169, 173, 175,
179, 180

in dyspepsia, 145

in intestinal obstruction, 150, 163

in intestinal toxaemia, 145, 150, 163

in intra-venous injections, 35, 38-40,
47, 75, 87, 89

in jaundice, 241, 243, 245, 246

in pyrexia, 214, 215

in typhoid, 211
Cirrhosis of the liver, 325
Clinical types, the ten, of dilated stom-
ach, 178-180
Coefficient, urotoxic, 326
Coma, abnormal metabolism a cause of,



Coma, diabetic, 175, 256-258
dyspnoea in, 175
in Bright’s disease, 111
in dilated stomach, 175
in dyspepsia, 145, 175
in gastric carcinoma, 175
in gastric ulcer, 175
in intra-venous injections, 34, 48, 55-

57, 78
in toxaemia, 145
in uraemia, 67, 111, 113
ligature of portal vein a cause of, 149
odor of breath in, 175, 257
pulse in, 175
respirations in, 67, 175
temperature in, 113, 175
the breath in, 175
urine of, 257
Constipation, headache in, 151
in dyspepsia, 152
in hypochondriasis, 151
in insanity, 151
migraine in, 151
nervous system in, 151
toxaemia in, 151
urine of, 147
vertigo -in, 151
Consumptive type of dilated stomach,

179, 180
Convulsions, and myosis, 57, 63
in ammonaemia, 121
in Bright’s disease, 111
in dyspepsia, 145
in emaciation, 251
in infants, 150

in intra-venous injections, 36, 39, 40,
52, 55-57, 78, 80, 87, 88, 94, 95, 244,
in jaundice, 244
in typhoid, 251
in uraemia, 67, 111, 113
Convulsive, of urine, the inorganic, 65,
66, 130, 250
the organic, 62, 63, 65, 130, 250
potassa, 58, 64, 65, 79, 80, 83, 96, 127,

128, 244, 251
urine of jaundice, 83, 87, 88, 244, 249
of pyrexia, 128, 244-249
of sleep, 39, 42
Copraemia, 105

Coryza, in dilated stomach, 172, 180
Cramps, in dyspepsia, 145
in intestinal obstruction, 150
in intra-venous injections, 275, 276
Creatin, toxic power of, 80, 123

uraemia due to, 123, 124
Creatineemia, 122, 133
Cresol, in putrefactive products, 94

in urine, 17, 147
Cupping, in uraemia, 134
Cutaneous eruptions, toxic origin of,
170, 171
system, excretion by, 18-21, 25, 136
in Bright’s disease, 110
in diabetes, 257
in diarrhoea, 144, 176
in dilated stomach, 171-173, ISO
in dyspepsia, 144, 145, 153
in gastric fullness, 153
in gastro-enteritis, 176
in intestinal obstruction, 150, 163
in intestinal toxasmia, 145, 146, 158
in intra-venous injections, 274
in jaundice, 241, 246
in typhoid, 203, 226
in uraemia, 136
type of dilated stomach, 179

Cyanosis, in intra-venous Injections,


Deafness, in dyspepsia, 145
Death, amount of poison necessary to
produce, 74

by potassium, 128

by quinine, 222

in infectious diseases, 247, 248
Debility, dilated stomach due to, 186
Definition, of diathesis, 3

of uraemia, 97

of urotoxic cofficient, 37, 39
Deoxidation processes, a defense to or-
ganism, 96, 97
Diabetes, acetonaemia in, 258, 259

albuminuria in, 257

blood of, 256, 257

breath in, 175, 257, 258

cataract in, 256

circulatory system in, 175, 255, 256

coma of, 175, 256-258

cutaneous system in, 256

metabolism in, 256

nervous system in, 175, 256, 257

ocular changes in, 256

odor of breath in, 175, 257, 258

renal system in, 255, 257

respiratory system in, 175, 256

symptoms in, 175, 256-258

urea of, 256

urine of, 147, 255-258

urochromes of, 147, 257, 258
Diaphoretics, in urasmia, 133
Diarrhoea, acid, 144, 145, 176

erythema in, 144, 176

in dyspepsia, 144, 145

in intra-venous injections, 88, 89, 95,
254, 275, 277, 278

in typhoid, 200

in uraemia, 113, 137, 138

nerve-reactions a cause of, 6

salutary, 20

toxaemia due to, 163

toxic power of urine diminished by,

urine of, 137, 147
Diathesis, acquired, 7, 8

arthritic, 6-8

definition of, 3

in dilated stomach, 174, 175, 178
Diet, improper, dilated stomach due to,

in dilated stomach, 188-193

in typhoid, 227-229

in urasmia, 141, 142

toxic power of the urine varies with,
Digitalis, in uraemia, its dangers and

uses, 134, 135
Disease, abnormal metabolism a cause
of, 9-12

albumins a cause of, 10

Bright’s, vide Bright’s disease

excess of minerals a cause of, 10
of water a cause of, 10

four pathogenic processes in, 2-13

infectious, dilated stomach a cause
of, 187
dilated stomach due to, 186, 187

lardaceous, 109

micro-organisms, a cause of, 4, 5, 9
in urine of, 199

nerve-reactions, a cause of, 2-8, 66,

normal substances, a cause of, 10, 12

odor of sweat indicates, 21

pathogenic processes in, 2-14



Disease, peptones, a cause of, 10

secretions, a cause of, 10

sweat indicates, 21

the causes of, must be combined, 9

urochromes of, 146, 147, 243, 257, 258
Diseases, causing exhaustion, 109

due to abnormal me’tabolism, 10, 12

skin, in dilated stomach, 170, 171
Diuretic, the, of urine, 60, 61

urea as a, 57, 60, 61, 68, 121, 135, 136,
239, 242
Diuretics, in uraemia, 134-136
Dysentery, a cause of exhaustion, 109
Dyslysin, in intestine, 19, 234
Dyspepsia, acid, 144, 145

acid diarrhoea in, 143, 145
vomiting in, 144

alimentary system in, 144, 145, 152, 153

breath in, 153, 257

cardialgia in, 144

circulatory system in, 145

coma in, 145, 175

constipation in, 152

convulsions in, 145

cramps in, 145

cutaneous system in, 143, 145, 153

deafness in, 145

diarrhoea in, 144, 145

dilated stomach due to, 169, 185, 186

erythema in, 144

faeces in, 144, 145

fatigue in, 145

headache in, 145, 153

intestinal antiseptics in, 145

intestinal gases of, 145, 154, 155

lavage in, 153, 154

nervous system in, 145, 157

ocular symptoms in, 145

paralyses in, 145

pyrosis in, 144

renal system in, 145

secretions of, 144, 152, 153

sulphuretted hydrogen in, the intes-
tines of, 145, 155, 15G, 163

symptoms of, 144, 145, 153, 154

taste in, 141

teeth in, 144

toxaemia in, 145, 155, 156, 163

treatment of, 153, 154

uraemic symptoms in, 144

urine of, 145-147, 256, 257

urochromes of, 145, 146, 257

vertigo in, 145, 153

vision disturbed in, 145

vomiting of, 143
Dyspeptic liver, 325
‘ type of dilated stomach, 178
Dyspnoea, in coma, 175

in dilated stomach, 172

in uraemia, 67, 113

Eclampsia, abnormal metabolism a
cause of, 12

errors in diet, causing, 11
Eczema, in dilated stomach, 170, 171, 179

in gastro-enteritis, 176
Emaciation, convulsions in, 251

in dilated stomach, 173

in jaundice, 83, 241

in typhoid, 202, 215, 228, 251
Emetics, in uraemia, 136
Enemata, in anuria, 135

in dilated stomach, 193

in typhoid, 204, 230

in uraemia, 135
Enteritis, in dilated stomach, 167

gastro-, of children, 177
Enterotoxins, 311

Entorrhagia, in Bright’s disease, 109
Epistaxis, in Bright’s disease, 109

in jaundice, 241

in nerve-reactions, 6

in typhoid, 201
Erysipelas, in typhoid, 201
Erythema, in diarrhcea, 144, 176

in dilated stomach, 171

in dyspepsia, 144

in gastro-enteritis, 177

in intestinal toxaemia, 163

in jaundice, 246
Etiology, of cholera, 260-263

of dilated stomach, 17S, 185-187

of typhoid, 187, 200

of uraemia, 114
Evening, the urine of, 36-41
Excretion, of albumin, 108

of bile, 88, 238, 240

of bile-acids, 238

of fats, 108
by the kidneys, vide Kidneys

of peptones, 108

of poisons, vide Poisons

of sugar, 108

of urea, 72, 108, 121, 215, 218

of uric acid, 108

of urine, 108, 130
Excretory power of kidneys, 108
Exercise, urine of, 44, 46
Exhaustion, causes of, 10S, 109
Exophthalmic goiter, dilated stomach

in, 186
Exophthalmos, in intra-venous injec-
tions, 35, 39, 41, 75
Extractives, in faeces, 146

in putrefactive products, 94

micro-organisms produce. 13

toxic power of, 122-124, 130

uraemia due to, 112, 122-124, 130
Extracts, acids in, 80

alcoholic, 55, 57, 78-80, 92, 95-97, 130,
147, 149, 278, 279

in typhoid, 228

intra-venous injections of, 54, 55, 78-
80, 89, 90, 93-96, 103, 147, 148, 247,
248, 278, 279

of blood, 78, 79, 89, 90

of choleraic urine, 278, 279

of faeces, 95-97, 103

of liver, 79, 80

of meat in typhoid, 228

of muscle, 79, 80, 89, 90, 91, 92, 147, 149

of putrefactive products, 89, 90, 92-94,
97, 147, 148

of urine, 54, 55, 79, 130, 278, 279

the narcotic, of urine, 56, 130

the sialogenous, of urine, 56, 79, 130

watery, 54-57, 80, 92-97, 279

Faeces, acid, of dilated stomach, 167
alcoholic extract of, 95-97
alkaloids in the, 95, 102, 103, 144, 146,

157, 273
ammonia in, 144
carbolic acid in, 146
charcoal acts on, 103, 105, 203
extractives in, 146
alcoholic extracts, 97
fetid, 167
indol in, 146
intra-venous injections of extracts of,

95, 96, 103
minerals in, 144
naphthalin acts on, 104, 105
of cholera, 273
of dilated stomach, 167
of dyspepsia, 145



Faeces, organic matter in, 144

poisons in, 144, 146

potass in, 97, 144

putrefactive products in, 95, 97

toxic power of, 95-97, 103, 144

watery extract of, 95-97
Fatigue, in dyspepsia, 145
Fats, excretory power of kidney for, 108
Fermentation, 316
Five modes of action of microbes, 12, 13

(1) anatomical

(2) destructive

(3) ingestive

(4) obstructive

(5) productive

Five theories of uraemia, 117-133

(1) ammonaemia, 112, 120-122

(2) cerebral cedema, 112, 114-116

(3) extractives, 112, 122-124, 130
oxalic acid, 112
urochromes, 112, 124, 130

(4) minerals, 112, 125-131

(5) urea, 112, 117, 118
Flatulence, in dilated stomach, 167
Food, intestinal poisons due to, 97, 102,

uraemia due to, 131, 141
Formula for use of charcoal, 105, 229,
of iodoform, 105, 229, 230
of naphthalin, 105, 229, 230
Four pathogenic processes, 2, 14

(1) disturbed nutrition

(2) elementary dystrophies

(3) infection

(4) nerve-reactions

Four sources of intestinal poisons, 143-

(1) bile

(2) fasces

(3) food

(4) putrefactive products

Four sources of toxic materials, 97

(1) food

(2) glands

(3) putrefactive products

(4) tissues

Four sources of uraemia, 131, 139-143

(1) disassimilation

(2) food

(3) putrefactive products

(4) secretions

Gangrene, in typhoid, 201
Gases, in intestine, 20, 145, 155, 156, 163
Gastric carcinoma, coma in, 176
dilated stomach due to, 186
toxaemia due to, 163
urine of, 147
catarrh, dilated stomach due to, 186
juice neutralizes poisons, 89, 94
ulcer, dilated stomach due to, 186
coma in, 175
milk in, 192, 193
Gastric tetany, causes and pathology

of, 180
Gastritis, coma in, 175
dilated stomach due to, 186
in dilated stomach, 1G7
Gastro-enteritis of children, symptoms

of, 168, 176
Glands, a toxic source, 97
in jaundice, 241
in typhoid, 199
micro-organisms in, 199
Glycaemia, 10, 256
Glycerin, in typhoid, 229, 230
intra-venous injection of, 30

Glycerin, toxic power of, 30

Glycocholates, vide Bile-salts
Glycocholic acid, in intestine, 19, 234
Glycosuria, 256

Goiter, exophthalmic, dilated stomach
in, 186

Haematemesis, in Bright’s disease, 109
Hematuria, in intra-venous injections,

35, 52
Haemoglobin, toxic power of, 79
Haemoglobinaemia, in jaundice, 241
Haemolysin, 306

Haemorrhages, in acute yellow atrophy
of liver, 243

in Bright’s disease, 110, 111

in dilated stomach, 174

in intra-venous injections, 35, 52, 74-76

in jaundice, 241, 243, 246

in nerve-reactions, 6

in typhoid, 211
Headache, and constipation, 151

in dilated stomach, 169

in pregnancy, 11

in uraemia, 113
Hepatic type of dilated stomach, 178
Hernia, toxaemia in, 151, 319
Herringham on toxicity of urine, 67
Herter, 102, 147
Hippuric acid, toxic power of, 123

uraemia due to, 123
Hydatids, urticaria a complication of,

170, 171
Hydraemia, causes of, 109

in Bright’s disease, 109, 110

in jaundice, 245

in lardaceous disease, 109

uraemia due to, 112, 114-116
Hydrochloric acid, vide Acid, hydro-
Hydrogen sulphide, in blood, 16, 156

in excretions, 156, 163

in intestine, 145, 155, 156, 163

in urine, 156

toxaemia due to, 155, 156
Hydropathic treatment, vide Bath3
Hyperpyrexia, vide Pyrexia
Hypochondriasis, constipation in, 151

in dilated stomach, 179

Indican, and indol, 146

in urine, 146, 147, 317, 318

of intestinal disease, 146, 317, 318
Indigo, in portal blood, 16
Indol, and indican, 146

in faeces, 145

in intestine, 146

in putrefactive products, 94

micro-organisms produce, 13

toxicity of, 143, 147
Infection, abnormal metabolism pre-

and intoxication, 90-92, 151, 157-160,

197, 201
in typhoid, 200

nervous influences precede, 6, 7

Infective disease, death in, 247, 248

dilated stomach a cause of, 187

due to, 186, 187

Inhalations, in dilated stomach, 188

in uraemia, 133, 140
Injections, in uraemia, 135
intra-venous, albuminuria in, vide
alimentary system in, vide Ali-
mentary system
circulatory system in, vide Circu-
latory system



Injections, intra-venous, coma in, vide

convulsions in, vide Convulsions
cramps in, 275, 276
exophthalmos in, 35, 39, 41, 75
hsematuria in, 35, 51
hemorrhages in, 35, 52, 74-76
morbid anatomy in, 89, 90, 149
myosis in, vide Myosis
nervous system in, vide Nervous

ocular symptoms in, vide Myosis

and Nervous system
of alcohol, 29, 30
of alcoholic extracts, 55-57, 78-SO,

92, 96, 147, 149, 278, 279
of bile, 81, 82, 236, 237
of blood, 74, 149
of blood-extracts, 78, 79
of blue pus, 254, 255
of choleraic urine, 274-278
of diabetic urine, 26, 27
of evening urine, 38-41
of extracts, vide Extracts
of fascal extracts, 95, 96, 103
of glycerin, 30

of jaundiced urine, 87, 88, 249
of liver-extract, 79, 80
of micro-organisms, 28, 199, 200, 254,

of morning urine, 38-41
of muscle-extracts, 79, 80, 89, 90, 93,

94, 147, 149
of pathological urines, 26-28, 36, 87.

88, 248, 251
of pus, 254, 255
of putrefactive products, 89, 90, 92-

94, 147, 149
of pyrexial urine, 249, 250
of septic urine, 28
of serum, 75-77
of sleep, urine of, 38-44
of soda-lye, 53
of tetanic urine, 248, 249
of typhoid bacillus, 190, 200
of urea, 49, 50, 51, 62, 117, 118
of uric acid, 52, 53
of urine, 27-59, 87. 88, 248-251, 278, 27-
of urochromes, 54
of water, 29, 76, 77, 116
of watery extracts, 54-56, 95-97, 279
reflexes in, vide Reflexes
renal system in, vide Renal system
respiratory system in, vide Respi-
ratory system
salivation in, vide Salivation
temperature in, vide Temperature
the strength of, 30
urine in, 275-278
subcutaneous, albuminuria in, 26
of urine, 26
Insanity and constipation, 151
Intestinal antiseptics, 103-105, 141, 142,

202-204, 210, 230
in dilated stomach, 185, 194, 195
in dyspepsia, 146

in typhoid, 202-204. 209, 210, 229, 230
in ursemia, 141, 142
disease, indican and indol of, 146

urine of, 146, 167
fermentation, symptoms of, 143
gases of dyspepsia, 145, 155, 156
obstruction, circulatory system in,

150, 163
collapse in, 150
cramps in, 150
cutaneous system in, 150, 151
earthy pallor of, 150

Intestinal obstruction, erythema in, 163

products found in experimental, 95

lavage in, 154, 155

mydriasis in, 163

nervous system in, 150

reflex symptoms in, 150, 151

symptoms of, 150, 151, 163

sweating in, 150

toxaemia due to, 151, 163

treatment of, 153

tympanites in, 150

urine of, 147

vomiting in, 119
poisons, origin of, 143, 144
toxaemia, 143-203

acute, 143-161

anhidrosis in, 158

treatment of, 153, 154
Intestine, acetic acid in, 17
acids in, 17, 19, 146, 147, 234
alkaloids in, 102, 103, 163
ammonia in, 145
bile-acids in, 19, 234

pigment in, 234

salts in, 234
butyric acid in, 17
carbolic acid in, 17, 146, 147
cholalic acid in, 19, 234
cholic acid in, 19, 234
dyslysin in, 19, 234
gases in, 20, 145, 154, 155, 163
glycocholic acid in, 19, 234
hydrogen sulphide in, 145, 154, 155, 163
indol in, 146
lactic acid in, 17
minerals in, 143, 144
origin of poisons in, 143, 144
oxalic acid in, 17
taurocholic acid in, 19, 234
Intoxication, and infection, 90-92, 151,
152, 161, 198, 201
of blood, the three sources of the, 88,
Iodoform, 104, 105, 141, 145, 185, 194, 204,
210, 229, 230
an antiseptic, 104, 105, 140, 141, 146,
in dilated stomach, 185, 194, 195
185, 194, 195, 204, 210, 229, 230
formulae for use of, 105, 229, 230
in cholera, 271, 272
in typhoid, 204, 229, 230
in uraemia, 141
lodothyrin, Baumann, 309
Ions, 101-103

Jaundice, alcoholia in, 229, 244, 245
albuminuria in, 242
blood of, 241, 242
cerebral oedema in, 245
cholaemia in, 244

circulatory system in, 241, 243, 245, 246
convulsions in, 244

convulsive urine of, 83, 87, 88, 244, 249
cutaneous system in, 241, 246
emaciation in, 83, 241
epistaxis in, 241
erythema in, 246
fatty degenerations in, 238, 241
glands in, 241
haemoglobinaemia in, 241
haemorrhages in. 241, 243, 246
hydraemia in, 245

in acute yellow atrophy of liver, 246
in dilated stomach, 167, 168, 178
intra-venous injections of urine of, 87,

88 249
kidneys in. 238, 239, 241-246
leucin in, 242



Jaundice, liver in, 239, 241-246
metabolism in, 238, 239, 241, 242, 243
prognosis of, 244
pruritis in, 241
pulse in, 241
purpura in, 246
pyrexia in, 246

renal system in, 238, 239, 241-246
spleen in, 241
symptoms in, 236, 241
temperature in, 246
theories of, 245
tissues in, 235-238, 240, 241
toxaemia in, 233-246
toxic power of urine of, vide Toxic

tyrosin in, 245
uraemia in, 244-246
urea of, 239, 245
urine of, 83, 87, 88, 236-238, 240, 242,

244, 249
xanthin in, 245

Kidneys, excretion by the, 20, 22, 71, 72,
74, 87, 108, 121, 240, 241, 252, 253
floating, 168, 172, 178
in atrophy of liver, 243
in dilated stomach, 16S, 172, 180
in jaundice, 238, 239, 241, 243, 246
in typhoid, 199
in uraemia, 111, 113, 136
micro-organisms in the, 199
vide Renal system

Kukula, 95

Kusmaul: Gastric tetany, 180

Lactic acid, vide Acid, lactic
Lardaceous disease, albuminuria in, 10J

exhaustion due to, 109

hydra?mia in, 109

metabolism in, 109

peptones of, 109
Latent type in dilated stomach, 178
Lavage, in dilated stomach, 154, 189,
194, 195

in dyspepsia, 154, 155

in intestinal obstruction, 154, 155

in toxaemia, 154, 155
Lead poisoning, 308
Leeches, use of, in uraemia, 134
Leucin, disease due to, 12

in blood, 242

in dough, 190

in intestines, 97

in muscle-extract, 80

in putrefactive products, 94

in tissues, 242

in urine, 242

toxic power of, 12, 79, 94, 124

uraemia due to, 124
Leucocytes and toxic substances, 18
Leucocythasmia, the breath in, 176, 258

urine of, 147, 249, 258

urochromes of, 147, 258
Leucorrhcea, exhaustion due to, 109
Liver, acute yellow atrophy of, 242, 243,
246, 274

atrophy of, 238, 239, 241-245

bile arrested by, 81, 85, 233-235, 238

defense, natural, 312

enlarged, ectopia due to, 168

-extract, intra-venous injection of,
79, 80

fatty degeneration of, 238

functions of the, 241, 242

in dilated stomach, 167. 168, 178

of jaundice, 239. 241-246

poisons arrested by. 18, 19, 23, 81, 85,
147-150, 233-235, 238

Liver, putrefactive products arrested

by, 149
Lungs, excretion by the, 19, 21, 22, 25,


Macrophages, 307

Measles, baths in, 227

Meat, tainted, toxaemia due to, 158-160

Meat-extract, in typhoid, 228

Mercury, advantages of, 211, 212

an antiseptic, 103, 104, 207, 210, 211, 229

and carbolic acid, 207

disadvantages of, 211

in typhoid, 200-212, 229

method of use of, 212

salivation by, 211

sequelae after use of, 211

toxic power of, 207
Metabolism, abnormal, alcholia due to,
coma due to, 12
eclampsia due to, 12
uraemia due to, 131, 139, 140

and infection, 5

diminished, in uraemia, 140

in acute yellow atrophy of the liver,

in diabetes, 257

in jaundice, 238, 239, 241, 242, 244

in lardaceous disease, 109

in pyrexia, 215

in typhoid, 215
Micro-organisms, acid products of, 13

action of, on the tissues, 12, 13

alkaloids a product of, 13

ammonia a product of, 13

and peptones, 88

bacilli, vide Bacillus

carbolic acid a product of, 13

extractives a product of, 13

fatty acids a product of, 13

gaseous products of, 13

in blood. 199

in dough, 190

in pus, vide Bacillus

in the glands, 199

in the kidneys, 199

in the spleen, 199

in the tissues, 12, 13

in the urine, 199, 254

indol a product of, 13

intra-venous injection of, 28, 199, 200,
254, 255

modes of action of, 12, 13

of cholera, vide Bacillus

of typhoid, vide Bacillus

products of, 13

tests for, 254

the five modes of action of, 12, 13

the search after, 9

toxic products of, 13

skatol a product of, 13

sulphuric acid a product of, 13
Microphages, 307
Migraine, in constipation, 151

in dilated stomach, 178

milk, in dilated stomach, 191-193

in gastric ulcer, 192, 193

in typhoid, 228

in uraemia, 135, 140-142
Minerals, as intestinal poisons, 143, 144

disease due to excess of, 10

in bile, 83, 84, 87

in blood, 88

in faeces, 144

in typhoid, 228

in urine, 57, 59, 64, 65, 83, 84, 121, 125,
127, 129-131

table of the toxic power of, 129



Minerals, total toxic power of, 130, 131
toxic power of, vide Toxic power
uraemia due to, 112,125-131, 244
Mixed urine, toxic power of, 43, 44
Morbid anatomy, in intra-venous injec-
tions, 89, 90, 149
of uraemia, 115
Morning, the urine of, 38-44

urine, intra-venous injection of, 38-41
Mortality of typhoid, 203, 204, 211, 231,

Muscle, alcoholic extracts of, 80, 147,
and urine, the toxic powers of, 97
-extract, composition of, 80
intra-venous injection of, 79, 80, 89,
90, 93, 94, 147, 149
putrefactive products of, 97
watery extract of, 80, 93, 94
Mydriasis, in intestinal obstruction, 163

in toxaemia, 158
Mydriatic alkaloids, 93
Myosis, and convulsions, 57, 63
in anuria, 67, 283
in cholera, 67, 129, 282, 283
in intra-venous injections, 28. 34, 35,
38-40, 47, 53, 55-57, 75, 80, 87, 88, 94,
248, 249, 251, 274
in uraemia, 67, 129
Myotic, the, of urine, 63, 130

Naphthalin, action of, on faeces, 104, 105
on urine, 104, 105
formulae for use of, 105, 229, 230
in acute yellow atrophy of the liver,

242, 243, 274
in cholera, 243, 271, 272, 274
in dilated stomach, 174, 183, 185, 194
in typhoid, 204, 229, 230, 243, 274
in uraemia, 141, 142
in urine, 104, 105, 243
Narcotic, the, of urine, 63, 130

urine, 42, 250
Nerve-reactions, a pathogenic process,
diarrhoea due to, 6
disease due to, 2-8, 67, 171
epistaxis due to, 6
haemorrhages in, 6
polyuria due to, 6
snycope due to, 6
-stimulation in uraemia, 134
Nervous debility, dilated stomach due
to, 186
influences induce disease, 2-8, 66

precede infection, 6, 7
system, in ammonaemia, 121
in anuria, 68, 283
in Bright’s disease, 111
in cholera, 68, 129, 282, 283
in constipation, 151
in diabetes, 75, 257, 258
in dilated stomach, 169, 175, 178, 179
in dyspepsia, 145, 154
in intra-venous injections, 28, 34-36,
38-40, 47, 48, 52, 54, 55-57, 75, 78, 80,
87, 88, 93-96, 244, 248-251, 274
in toxaemia, 145, 150, 151, 157, 158.

in uraemia, 67, 68, 111, 113-115
type of dilated stomach, 178, 179
Neuralgia, in dilated stomach, 169
Neurasthenia, dilated stomach due to,

Neurin, 284
Nodes, bony, in dilated stomach, 173,

174, 180, 187
Obstructive anuria, 111, 115, 116, 118

Ocular symptoms, in anuria, 67, 283
in Bright’s disease, 111
in cholera, 67, 129, 281, 283
in diabetes, 257
in dilated stomach, 169
in dyspepsia, 145

in intra-venous injections, vide Myo-
in toxaemia, 158, 163
in typhoid, 93
in uraemia, 67, 111, 129
Odor, of breath, vide Breath
of sweat, in dilated stomach, 170

indicates disease, 21
of washed cloth, 21
CEdema, in Bright’s disease, 110, 111
Organic, the, convulsive of urine, 62,

63, 65
Osseous system, in dilated stomach,

173-176, 180, 187, 196
Osteomalacia, in dilated stomach, 174,

175, 180
Overexcitement, 324, 325
Overexertion, 324, 325
Oxalic acid, vide Acid, oxalic
Oxidation processes, a defense to or-
ganism, 97, 99
Oxygen inhalations, in dilated stomach,
in uraemia, 140

Paralyses, in dilated stomach, 169

in toxaemia, 158
Peptones, and albumen, 10, 18, 109, 172,

and micro-organisms, 88

blood-cells transform, 17, 18, 173

disease due to, 10

excretion of, 103

in dilated stomach, 193

in the urine, 172, 173

in typhoid, 228-230

and leucocytes, 18

of lardaceous disease, 109

toxic power of, 10
Percussion sign, in dilated stomach, 164
Pericarditis, in Bright’s disease, 111
Perspiration, see Sweat
Phagocytosis, 307
Phalangeal nodes, in dilated stomach,

173, 174, 180, 187
Phosphoric acid, in excess, 307
Phlebitis, in dilated stomach, 173, 179
Phthisis, in dilated stomach, 156, 180
Physical signs of dilated stomach, 164-

Pituitary glands, 312
Pityriasis versicolor, in dilated stom-
ach, 170
Pneumonia, baths in, 227

quinine in, 209
Poison, uraemia is a complex, 114, 132,

133, 143, 244
Poisons, amount of, necessary to pro-
duce death, 74

blood a source of, 78, 79
arrests, 18, 235, 236

excretion of, 16, 19, 20-25, 67, 71-74,
107, 108

food a source of, 97, 102, 143

gastric juice neutralizes, 89, 94

in blood, 16, 18, 71-74, 89, 97

in faeces. 144, 146

in the alimentary system, 89, 94, 102,

in tissues, 17. 24, 84 ,97, 102, 235-238

in urine, 17, 146, 147

liver arrests, vide Liver



Poisons, modes of arrest of, 150

origin of, 97, 102

phosphorus, 326

purgatives remove, 137

putrefactive products a source of, 89-
91, 143, 144
Portal blood, 16, 18, 73, 149
indigo in, 16

sulphuretted hydrogen in, 16
toxic power of, 73, 149

vein, coma after ligature of, 149
Potassium, action of, as a toxic power,
69, 127, 128

an antiseptic, 207

as a convulsive, vide Convulsive

bromide, dangers of, 139

chloride, toxic power of, 127, 129

death by, 128

in bile, 83, 84, 87

in blood, 129

symptoms due to, 128

total toxic power of, 130, 131

toxic power of, vide Toxic power

uraemia due to, 112, 125-131, 244
Pregnancy, toxaemia of, 12

urine of, 117, 322
Prognosis, of dilated stomach, 196

of jaundice, 244
Pruritus, in jaundice, 241
Ptisan, in typhoid, 228
Puerperal fever, quinine in, 209, 221
Pupil, vide Mydriasis and Myosis
Purgatives, in surgical operations, 155

in typhoid, 204, 229

in uraemia, 136, 137, 140

remove poisons, 137
Purpura, in Bright’s disease, 112

in dilated stomach, 173

in jaundice, 246
Putrefactive products, alkaloids in, 92-

ammonia in, 94, 97, 145

and urine, 94

a source of poisons, 89, 90, 143, 144

charcoal acts on, 93, 141, 146

composition of, 94

extracts of, 89, 90, 92-94, 97, 147-149

in blood, 89, 90

in faeces, 95, 97

intra-venous injection of, 89, 90, 92-94,
147, 149

liver arrests, 149

toxaemia due to, 144-146, 151, 156-161

toxic power of, vide Toxic power
principles in, 94

trypsin develops, 95

uraemia due to, 131, 139-141, 244
Putrefaction, 316
Pylorus, obstructed, dilated stomach

due to, 186
Pyrexia, artificial. 214

baths in, 217, 218, 223-228, 231

blood of, 216, 217

circulatory system in, 214, 215

convulsive urine of, vide Convulsive

diet in, 228-230

discussed, 213-220

effects of, 213, 214

heart in, 215

in jaundice, 246

in typhoid, 202

metabolism in, 215

multiple causes of, 216, 218-220

pathology of, 216, 217, 219, 220

quinine in, 209, 210, 217, 220-222, 230

salutary, 213

treatment of, 216-218, 220-228

urine of, vide Convulsive

Pyrexia, urochromes of, 251
venesection in, 216
veratrin in, 216

Quinine, an intermittent remedy, 221
death due to, 222
in ague, 209, 210
in pneumonia, 209
in puerperal fever, 209, 211
in pyrexia, vide Pyrexia
in typhoid, 209, 210, 217, 218, 221, 222,

limits of, 209, 217, 220
methods of use of, 221

Recapitulation, general, 293-301
Reflex symptoms, in toxaemia, 150, 151
Reflexes, in intra-venous injections, 28,

35, 38-40, 48, 75
Renal system, in acute yellow atrophy.
in cholera, 282
in diabetes, 256, 258
in dilated stomach, 108, 172, 174, 179,

in dyspepsia, 145

in intra-venous injections, 27, 28, 34,
35, 38, 48, 55, 56, 88, 254, 275, 277, 278
in jaundice, 238, 239, 241-246
vide Albuminuria and Kidney
type of dilated stomach, 179
Respiratory system, in cholera, 282
in coma, 67, 175
in diabetes, 175, 258
in dilated stomach, 166, 171, 172, 175,

in intra-venous injections, 28, 38, 39,

47, 50, 75, 87, 90, 94
in typhoid, 201, 211

in uraemia, 66, 111, 113, 136
Revulsives, in uraemia, 130
Rheumatic type of dilated stomach, 179
Rheumatism, baths in, 227
Rickets, in dilated stomach, 174, 176,

Salivation, in intra-venous injections,

48, 55-57, 78, 80, 130
in uraemia, 67
mercurial, 211

Sausages, toxaemia due to, 159-161, 326

Scarlatina, baths in, 227

Secretions, uraemia due to, 131, 139-141

Sepsine, an alkaloid, 92

Septic urine, intra-venous injection of,

Serum, intra-venous injection of, 75-77
Seven, the, toxic principles of urine, 60-


(1) antipyretic

(2) convulsive, inorganic

(3) convulsive, organic

(4) diuretic

(5) myotic

(6) narcotic

(7) sialagogue

Sialagogue, the, of blood, 57, 78, 79

the, of urine, 56, 57, 62, 130
Sinapisms, in uraemia, 134
Skatol, in putrefactive products, 94

in urine, 13

micro-organisms produce, 13
Skin, vide Cutaneous system
Sleep, the urine of, 38-43
Soda, an antiseptic, 207

in the urine, 67

-lye, intra-venous injections of, 52

toxic power of, vide Toxic power



Spleen, the, 313

Stercoraemia, 106, 326

Stomach, dilated, acid faeces of, 167

acne in, 171, 179

albuminuria in, 172, 179, 196

alcoholism a cause of, 186

alimentary system in, 167

and typhoid, 187, 197

angina, false, in, 169, 179

antiseptics in, 185, 194, 195

aphasia in, 169

arthritis in, 173, 175

asthma in, 172, 179

asthmatic type of, 176

baths in, 187, 188

bread in, 189, 190

bronchitis in, 172, 179

bulimia in, 167

carcinoma a cause of, 186

cardiac type of, 179

cardialgia in, 167, 179

chlorosis in, 166, 180

circulatory system in, 166, 169, 173,
175, 179, 180

clinical types of, 178-180

coma in, 175

consumptive type of, 179, ISO

contractions in, 169, 179

coryza in, 172, 179

cutaneous system in, 169-171, 179

cutaneous type of, 179

debility a cause of, 1S6

diathesis in, 173, 174, 177

diet in, 188-193

dyspepsia a cause of, 169, 185, 186

dyspeptic type of, 178

dyspnoea in, 172, 175

eczema in, 170, 171, 179

emaciation in, 173

enemata in, 193

enteritis in, 167

erythema in, 171

etiology of, 177, 185-1S7

feces of, 167

fluids in, 189-191, 192

gastric causes of, 1S6

gastritis in, 167

haemorrhages in, 173

headache in, 169

hemiopia in, 169

hepatic type of, 178

heredity in, 177, 186

hydrochloric acid in, 194, 195

hypochondriasis in, 179

Improper diet a cause of, 186

in ataxia, 186

in goiter, 186

infectious disease a cause of, 186,

infectious disease due to, 187

inhalations in, 188

jaundice in, 167, 168, 178

kidneys in, 16S, 172, 178

latent type of, 178

lavage in, 154, 189, 194, 195

lithiasis in, 178

liver in, 167, 16S, 178

mental causes of, 186

migraine in, 178

milk in, 191-193

nervous causes of, 186

nervous system in, 169, 175, 178, 179

nervous type of, 178, 179

neuralgia in, 169

night-sweats in, 169

nodes, bony, in, 173, 174, 180, 187

ocular affections in, 169

Stomach, osseous system in, 173-176,
180, 1S7, 196
osteomalacia in, 174, 175, 180
paralyses in, 169
peptones in, 193
percussion sign in, 164
phlebitis in, 173, 179
phthisis in, 166, 180
physical signs of, 164-166
pityriasis versicolor in, 170
prognosis of, 196
purpura in, 173

renal system in, 168, 172, 173, 179, 196
respiratory system in, 166, 171, 172,

175, 180
rheumatic type of, 179
rickets in, 174, 176, 180
splashing sign in, 165, 166
stimulants in, 189, 192
succussion sign in, 164
symptoms of, 166-180
the breath in, 167, 171, 175, 258
the sweat of, 170
the ten clinical types of, 178-1S0
tetany in, 180
toxaemia in, 163-180
treatment of, 185-197
urine of, 147, 172, 173, 179. 258
urochromes of, 147, 173, 258
urticaria in, 170, 171, 179
vertigo in, 169
Succussion sign, in dilated stomach, 164
Sulphuretted hydrogen, vide Hydrogen

Sulphuric acid, vide Acid, sulphuric
Summary of the treatment of typhoid,
of uraemia, 142
Suprarenal bodies, 312
Sweat, odor of, 21

toxicity of, 22, 23
Symptoms, in anuria, 67, 2S3
in Bright’s disease, 108-111
in jaundice, 236, 241
in potass poisoning, 125
in toxaemia, 157, 158
in typhoid, 201, 202, 211
in uraemia, 66, 67, 101, 113, 114
of ammonaemia, 121, 122
of dilated stomach, 166-180
of dyspepsia, 144-154
of gastro-enteritis, 176
of intestinal obstruction, 150, 151, 163

Table of the toxic power of minerals,

Taurocholic acid, in intestine, 19, 234
Teeth, changes in the, in dyspepsia, 144
Temperature, in ammonaemia, 122
in cholera, 282
in coma, 113, 175

in intra-venous injections, 27, 28, 35,
38-40, 48, 50, 53, 55-57, 249, 251, 254,
275, 276
in uraemia, 67, 113, 140
vide Pyrexia
Ten, the, clinical types of dilated stom-
ach, 178-180

(1) asthmatic

(2) cardiac

(3) consumptive

(4) cutaneous

(5) dyspeptic

(6) hepatic

(7) latent

(8) nervous

(9) renal

(10) rheumatismal



Testicular juice, 309
Tests, for acetone, 147, 258
for alkaloids, 16, 17, 95, 273
for bacillus pyocyaneus, 254
for bile, 234, 236
Tetany, gastric, pathology of, 181, 182
Tetanus, the urine of, 248, 24a
Therapeutics, general, 286-292
Three, the, sources of intoxication of
blood, 88, 89

(1) bile

(2) minerals

(3) putrefactive products
Thyroid gland, 309

supposed function of, 145, 309
Tissues, a toxic source, 97

acids in, 17, 80

alkaloids in, 16, 248

bile arrested by the, 235-238, 240, 241

in jaundice, 235-238, 240, 241

in uraemia, 117

leucin in, 242

micro-organisms in the, 12, 13

poisons in, vide Poisons

urea in the, 117
Toluylendiamia, 313
Toxaemia, acute intestinal, 143-161

anhidrosis in, 159

bile, 143, 144, 233-246

chronic intestinal, 163-197

constipation a cause of, 151

cutaneous system in, 145, 150, 159, 163

diarrhoea a cause of, 163

etiology of, 151, 163

food a source of, 97, 102, 143

four sources of, 97, 143-161

hepatic, 11

hydrogen sulphide a cause of, 155, 156

in dilated stomach. 163-180

in dyspepsia, vide Dyspepsia

in hernia, 151

in jaundice, 233-246

in typhoid, 201

methods of producing artificial, 25, 26

nervous system in, vide Nervous sys-

ocular symptoms in, 159, 163

of pregnancy, 1, 11

paralyses in, 159

putrefactive products a source of, vide
Putrefactive products

symptoms in, 155-159

tainted food a cause of, 156-161

treatment of, 154, 155

urine of, 145-147

urochromes of, 147

vertigo in, 157

vomiting in, 157
Toxalbumin, 284
Toxic accidents, why infrequent. 18

coefficient, 37, 48

materials, 97, 143-161

origin of cutaneous disease, 170, 171
Toxic power, of acid urine, 33, 34

of alcohol, 30

of alkalies, 10, 15, 16, 19, 32, 54, 56, 57,
58, 59, 62, 67, 68, 78, 92-95, 130, 144,
159, 248, 250

of ammonia, 59, 97, 102, 121, 122, 125

of anilin, 207

of antiseptics, 104, 207, 208

of aromatics of urine, 54

of bile, 16, 19, 81-83, 85-87, 97, 102, 124,
140, 144, 235-246
and urine, 81, 85, 86, 235

of bilirubin. 82, 124, 140, 144, 235, 240

of blood, 70-79, 148

of carbolic acid, 207

Toxic power, of cholesterin, 82, 233
of creatin, 80, 123
of extractives, 122-124, 130
of faeces, 95, 96, 103, 144
of glycerin, 30
of haemoglobin, 79
of hippuric acid, 123
of jaundiced urine, 83, 87, 88, 230, 244,

of leucin, 12, 79, 94, 120
of leukaemic urine, 249
of mercury, 207

of minerals, 10, 16, 19, 44, 49, 54, 57, 58,
61, 64, 65, 78-80, 83, 84, 87, 96-102,
125-131, 139-143, 144, 207, 244, 251
of pathological urines, 36, 248, 252
of peptones, 10

of pigments, vide Toxic power of bili-
rubin and urochromes
of potassium, vide Toxic power of

of pus, 254
of putrefactive products, 88-94, 102,

144-146, 157-161
of pyrexial urine, 128, 248-251
of secretions, 10, 16
of serum, 75-77
of soda, 58, 61, 67, 126, 139
of sugar, 256
of tainted meats, 156-161
of typhoid urine, 93, 203, 249
of tyrosin, 124
of urea, 49-51, 57, 60, 61, 67, 112, 117-

119, 125
of uric acid, 51, 52, 123
of urine, and bile, 81, 85, 86, 235

concentrated, 36-49

decolorized, 87, 88

mixed, 43, 44

of evening, 38-41

of exercise, 44-46

of diarrhoea, 337

of jaundice, 83. 87, 88, 330, 244, 249

of leukaemia, 249

of morning, 38-44

of pyrexia, 128, 249-251

of sleep, 38-44

of typhoid, 93, 203, 249

of uraemia, 116, 117, 129, 249

pathological, 36, 248-252

the total, 130, 131

variations in the, 36-47, 49
of urochromes, 10, 12, 54, 124, 125, 130,

of water, 10, 49, 76
of xanthin, 124
the total, of alkaloids, 130

of bile, 235

of extractives, 130

of minerals, 126, 130, 131

of pigments, 124, 125, 130

of urea, 125

of urine, 130, 131
Toxic powers, table of the, 129
of urine, antagonism of the, 62, 63,
127, 128

origin of the, 70

ratio of the, 125

the seven, 60-65
Toxopeptone, 284

Treatment, antipyretic, vide Antipy-
antiseptic, vide Antiseptic
hydropathic, vide Baths
of anuria, 135, 290
of cholera, 271, 272
of dilated stomach, 185-187
of dyspepsia, 154, 155



Treatment of measles, 227

of pneumonia, 218, 227

of puerperal fever, 209, 221

of rheumatism, 227

of scarlatina, 227

of typhoid, 202-231

of uraemia, 128-137
Trypsin develops alkaloids, 95
Typhoid, anaemia in, 211

and dilated stomach, 176, 186

baths in, vide Baths

blood of, 199

calomel in, 211, 212, 229

carbolic acid in, 204, 230

charcoal in, 202, 203, 229, 230

circulatory system in, 211

complications of, 201, 211

convulsions in, 251

cutaneous system in, 203, 226

diarrhoea in, 200

diet in, 228-230

emaciation in, 202, 215, 229, 251

endocarditis in, 211

enemata in, 204, 230

erysipelas in, 201

etiology of, 187, 200

glycerin in, 229, 230

haemorrhages in, 211

inoculation of, 199, 200

iodoform in, vide Iodoform

metabolism in, 215

micro-organisms of, 199, 200

milk in, 228

minerals in, 228

mortality of, 203, 204, 211, 231, 232

naphthalin in, vide Naphthalin

ocular symptoms in, 93

peptones in, 228-230

ptisan in, 228

purgatives in, 204, 229

pyrexia in, 202

quinine in, vide Quinine

respiratory system in, 201, 211

sequelae of, 211

summary of treatment of, 229-231

symptoms in, 201, 202, 211

the bacillus of, 199, 200

the breath in, 258

the glands in, 199

toxaemia in, 201

treatment of, 202-231

urea of, 215

urine of, 93, 146, 147, 199, 203, 249. 258

urochromes of, 147, 258

vegetable acids in, 228
Tyrosin, in blood, 242

in dough, 190

in muscle-extract, 80

in putrefactive products, 94

in uraemia, 124

in urine, 242

toxic power of, 124

Uraemia, a oomplex poison, 114, 132, 133,

143, 244
abnormal metabolism a cause of, 131,

139, 140
alimentary system in, 113, 114, 131,

139, 140
ammonia a cause of, 112, 120, 122
antidotes in, 139, 140
antiseptics in, 141, 142
baths in, 133
blood of, 79, 117, 121
bromides in; their dangers, 139
caffeine in, 134
cerebral oedema a cause of, 112, 114-


Uraemia, charcoal in, 141, 142

chloral in, 139

chloroform in, 139

coma in, 66, 111, 113

convulsions in, 66, 111, 113

creatin a cause of, 118, 119, 123, 124

cutaneous system in, 136

definition of, 97

diarrhoea in, 113, 137, 138

diet in, 141, 142

digitalis in, 134, 135

diminished metabolism in, 140

diuretics in, 134-136

dyspnoea in, 67, 113

emetics in, 136

enemata in, 135

etiology of, 114

extractives a cause of, 112, 122-124,

food a source of, 131, 141

four sources of, 131, 139-143

headache in, 113

hippuric acid a cause of, 123

hydraemia a cause of, 112, 114-116

in jaundice, 244-246

inhalations in, 133, 140

injections in, 135

iodoform in, 141

kidneys in, 111, 113, 136

leucin a cause of, 124

milk in, 135, 140-142

minerals a cause of, vide Minerals

morbid anatomy of, 115

myosis in, 67, 129

naphthalin in, 141, 142

nerve-stimulation in, 134

nervous system in, 66, 67, 111, 113-115

obstructive, 115, 116, 118

ocular symptoms in, 67, 111, 129

of cholera, 282

oxalic acid a cause of, 112

pathology of, 112-133

potass a cause of, vide Minerals

purgatives in, 136, 137, 140

putrefactive products a cause of, 131,
139-141, 244

respiratory system in, 66, 111, 113, 136

revulsives in, 134

salivation in, 67

secretions a source of, 131, 139-141

summary of the treatment of, 142

symptoms in, 66, 67, 111, 113, 114

the five theories of, 112-133

treatment of, 133-142

tyrosin a cause of, 124

urea a cause of, 112, 117, 118

urea in, 135, 136

uric acid a cause of, 123

urine of. 66, 67, 113, 114, 116, 117, 119,
120, 249

urochromes a cause of, 112, 124, 130

venesection in, 138

vicarious functions in, 136

vomiting in, 113, 136

when does it occur? 113
Uraemic symptoms, in dyspepsia, 145

in excessive vomiting, 145
Urea, a diuretic, vide Diuretic

excretin of, vide Excretion

in blood, 117, 121

in the tissues, 117

in uraemia, 135, 136

intra-venous injection of, vide Injec-

of anuria. 117

of diabetes, 257

of jaundice, 239, 242

of typhoid, 215



Urea, toxic power of, vide Toxic power

uraemia due to, 112, 117, 118
Uric acid, excretion of, 108

intra-venous injection of, 51, 52

toxic power of, 51, 52, 123

uraemia due to, 123
Uricaemia, 10
Urine, acetic acid in, 17

acetone in, 147, 258

acids in, 17, 146, 147

albumen in, vide Albuminuria

alcoholic extract of, 55-57, 130, 278, 279

alkaloids in, vide Alkaloids

ammonia in, V

and bile, to- power of, 81, 85, 86, 235

and putrefy, .ve products, 94

antagonism of the toxic powers of, 42,
44, 62, 63, 127, 128, 250

aromatics of, 53

bile, 11

butyric acid in, 17

carbolic acid in, 17, 146, 147

charcoal acts on the, 54, 57, 103, 105,
130, 203

concentrated, toxic power of, 36, 49

convulsive, vide Convulsive

cresol in, 17, 147

decolorized, toxic power of, 87, 88

diabetic, 147, 256-259

excretion of, 108, 130

extractives of, uraemia due to, 112,
122-124, 130

extracts of, 54-57, 79, 130, 278, 279

hydrogen sulphide in, 156

in diarrhoea, 137, 146, 147

indican in, 146, 147

intra-venous injections of, vide Injec-

lactic acid in, 17

leucin in, 242

micro-organisms in the, 199, 254

minerals, their toxic power, vide
Minerals and Toxic power

mixed, toxic power of, 43, 44

naphthalin acts on the, 103, 105, 243

normal, toxic power of, 32

of acute yellow atrophy of liver, 243

of anaemia, 147, 258

of cholera, 117, 146, 274

of constipation, 147

of day, and sleep, 42

of dilated stomach, 147, 172, 174, 179,

of dyspepsia, 145-147, 257, 258
of eclampsia, 117
of evening, 38-41
of exercise, 44-46
of intestinal disease, 146, 147

obstruction, 167
of jaundice, vide Jaundice
of lardaceous disease, .109
of leukemia, 147, 249, 258
of man and dogs, 68
of morning, 38-44
of nerve-reactions, 6
of pyrexia, vide Convulsive
of sleep and day, 38-44

toxic power of, 38-44
of tetanus, 248, 249
of toxaemia, 145-147
of typhoid, 93, 146, 147, 199, 203, 249,

of uraemia, 66, 67, 113, 114, 116, 117,

119, 120, 249
origin of the toxic powers of, 70
oxalic acid in the, 17

Urine, pathological, 36, 248-252

peptones in, 172, 173

poisons in, 17, 146, 147

purgatives diminish toxic power, 137

septic, injections of, 28

skatol in, 13, 17

soda in, toxic power of, vide Toxic
power of soda

subcutaneous injection of, 27

sugar in the, 256

suppression of, 321

the antipyretic of, 63, 64, 122, 130

the diuretic of, 60, 61

the narcotic of, 62, 130

the seven toxic principles of, 60-65

the sialagogue of, 56, 58, 62, 130

total toxic power of, 130, 131

toxic power of, vide Toxic power
principles in, the seven, 60-65

tyrosin in, 242

urea the diuretic of, vide Diuretic

urochromes of, 10, 12, 124, 125, 130, 147,

watery extracts of, 55-57, 279

xanthin in, 242
Urochromes, intra-venous injection of,

of diabetes, 147, 258, 259

of dilated stomach, 147, 173, 258

of dyspepsia, 146, 147, 258

of leucocythasmia, 147, 258

of pyrexia, 251

of toxaemia, 147

toxic power of, vide Toxic power

uraemia due to, 112, 124, 130
Urotoxic coefficient, the, 37, 48
Urticaria, a complication of hydatids,
170, 171

in dilated stomach, 170, 171, 179

toxic origin of, 170, 171

Valeric acid, in putrefactive products,

Variations in the toxicity of urine, 36-

47, 49
Venesection, in anuria, 290

in uraemia, 138
Vertigo, in constipation, 151

in dilated stomach, 169

in dyspepsia, 145, 154

in toxaemia, 157
Vicarious functions, 20, 136
Vomiting, acid, 143

exhaustion due to, 108

in intestinal obstruction, 150

in pregnancy, 322, 323

in toxaemia, 157

in uraemia, 113, 136

uraemic symptoms due to, 145

Water, disease due to, 10

intra-venous injections of, 29, 76, 77,

toxic power of, 10, 49, 76
Watery extracts, intra-venous injection
of, vide Injections

of choleraic urine, 279

of faeces, 95-97

of muscle, 80, 93, 94

of putrefactive products, 92-95, 97

of urine, 54-56, 58

Xanthin, in blood, 242
in urine, 242
of jaundice, 242
toxic power of, 124