appreciable to the naked eye. These movements present a real alternation, comparable in a certain measure to what takes place in the auricles and ventricles of the heart, and thus you have a rhythm of the stomach as well as a rhythm of the heart.

Much more complex is the study of the gastric juice, and you will see that, notwithstanding the numerous works that have been written on this subject, there remain still many obscure points connected with this question.

I need not recall to your minds the structure of the gastric mucous membrane, or of the glands whose secretion constitutes its principal function. I must, however, tell you that the view of Kölliker, that there is an abrupt line of demarkation between the pepsin glands occupying the great cul-de-sac of the stomach and the mucous glands surrounding the pylorus, is no longer tenable; and since the labors of Haidenhain, Rollet, and Ebstein, it is now known that there is an intermediary zone, where there are both mucous glands and pepsin glands.

If there seems to be agreement respecting the mucous glands, which are characterized solely by superficial cells, there is not the same agreement respecting the pepsin glands, which contain at the same time voluminous cells with large nuclei, and certain cells surrounding the orifice of the glands, and which are called border cells. In fact, some have maintained that the principal cells (or the large cells) secrete exclusively the gastric juice; others affirm that this rôle belongs exclusively to the border cells. Lastly, there is a third doctrine, which affirms that the gastric juice is secreted both by the border cells and the large cells. I pass now to the study of the gastric juice.

That which characterizes essentially the gastric juice is its extreme acidity. This is one of the most striking facts connected with this secretion. There has been much discussion as to the nature of the acid, some maintaining that it is lactic, others hydrochloric acid. To-day there is general agreement as to the following facts: There exist in the normal state in the gastric juice lactic acid and hydrochloric acid; but the lactic acid is always the product of digestion, while the hydrochloric acid is the acid of the gastric juice, and appears in this secretion at the moment of the entrance of the food into the stomach. The researches of Ewald are in this respect absolutely demonstrative.

I do not speak of the opinion of Poulet, of

Plancher-les-Mines, who has insisted that this acid is hippuric; this view is not held by any physiologist. So, then, hydrochloric acid is the normal acid of the gastric juice. Is it free or is it combined with other products? Here widely-diverging views have been put forth.

Ewald, as well as Hayem, has maintained that the acid is not free, and that it is combined with the various albuminoid substances which are in contact with it. At the same time, Ewald rejects the hypothesis of Richet, -viz., that the hydrochloric acid is combined with leucin, this substance, like tyrosin, being always a product of the decomposition of the ingesta.

*

Hayem, in continuing his interesting researches with Winter on the stomachal chemism in the normal and pathological states, thinks that the hydrochloric acid is combined with albumen in the gastric juice in the state of hydrochlorate of the amide acids. These amide acids result from a breaking up of the primitive albuminoid molecule.

It has also been a matter of dispute whether the stomach when empty secretes gastric juice, and Peck affirms that this secretion ceases during fasting, or is so much diminished that it may be considered as nil.

Besides the hydrochloric acid, the gastric juice contains two ferments,-pepsin and the lab-ferment, or pexine. I shall say but little about pepsin. We know that it transforms albuminoids into peptones, but despite numerous researches made on this subject, we are ignorant of the true nature of these peptones. We know only that to each kind of albumen correspond special peptones, and, since the researches of Heninger, there is pretty general agreement in considering these peptones as hydrates of albuminoid matters.

The lab-ferment or pexine is a substance which causes the coagulation of milk, and those of you who would like to know more about this pexine would do well to consult the thesis of Dr. Pagès.t

The new microbial theories, for which we are so largely indebted to Pasteur, have but little modified our notions as to these two ferments, pepsin and pexine. If Duclaux and Vignal have shown that the buccal cavity contains a great number of microbes, whose effect is to peptonize albuminoids, Dastre, on the other hand, has demonstrated that by sterilizing gastric juice, we do not destroy,

* Hayem and Winter, "Researches on the Stomachal Chemism in the Normal and in the Pathological State" (Bull. Med., 1889).

"Researches on Pexine" (Thèse de Paris, 1888).

though we attenuate, its digestive power considerably, so that we are warranted in saying that certain microbes are favorable to peptonization.

As for the origin both of the acid and of the ferment of the gastric juice all is obscurity. The old theory of peptogenous substances, so much in vogue several years ago, seems to be abandoned, and there is a general admission that the stomach does not directly form pepsin, but a body called pepsinogen or propepsin, which then transforms itself into pepsin.

As for the hydrochloric acid, it is believed to come from the decomposition of the chlorides contained in the blood, and the recent researches of Professor Hayem tend to justify this view.

After these preliminary observations, I come to the study of the new processes which enable us to understand both the movements of the stomach and the chemism of this organ. Let us begin with the methods of investigating the movements of the stomach.

I have just told you that we may in certain cases observe de visu the movements of the stomach through the abdominal walls. But these are only exceptional cases, and to judge of the contractility of the stomach we must make use of processes more or less complex; the most simple and advantageous is most certainly that of Leube.

Basing himself on physiological data, Leube maintains that seven hours after a normal meal the stomach, in the healthy state, should be entirely empty. It is sufficient then to give to the patient a meal of meat, eggs, and bread, then to practice lavage of the stomach seven hours after this meal, and you will find the stomach devoid of food.

Klemperer has proposed a process derived from the same method, but much more complex. It is called the oil process. It is based on this fact, that, in the physiological state, seventy to eighty grammes of oil pass from the stomach into the intestine in two hours. The operator then introduces, by the aid of the œsophageal sound, one hundred grammes of oil; then, with the stomach-pump, he aspirates, at the end of two hours, the contents of the stomach. The stomach is next washed out with water, which is allowed to settle, the oil is dissolved out by ether, and a calculation is made of how much oil has passed into the intestine. This is a process which is much more complicated than that of Leube, and does not seem to present any advantage over the latter.

The third means is based on chemical reactions. There is a substance to-day very much used in surgery,-salol,-which results from the combination of salicylic acid with phenic acid. One of my pupils, Dr. Lombard, has shown all the therapeutic applications which may be made with salol.*

This body in the presence of alkalies is decomposed into phenic acid and salicylic acid. Ewald has utilized this property in order to determine the contractility of the stomach. He administers 1 gramme of salol to the patient, and examines the urine to find at what moment salicylic, or rather salicyluric, acid appears in that secretion. In the normal state this acid makes its appearance at the end of half or three-quarters of an hour. When there is a delay, Ewald affirms that this is due to the fact that the stomach, through sheer inactivity, has not let its contents pass into the intestine.

Certain objections may be made to this test. In a thesis which bore a prize from the faculty, and which was written by one of my best pupils, Mlle. Dr. Chopin,† it appears that the elimination of salicylic acid depends. in great part on the condition of the kidney, and it may be considerably retarded in old people. On the other hand, it depends on the nature of the meal, and especially on the nature of the liquid ingested. We may cause the appearance of the salicylic acid to vary considerably, as Bourget has shown.

The same objections may be made to the modifications of Ewald's method proposed by Hubert, who examines the urine not only to ascertain at what moment the salicylic acid appears there, but also to find out the time when the reaction disappears, a period quite remote from that of the ingestion of food in persons with inactive stomachs.

Hence I am disposed to make little account of these chemical processes, and adhere exclusively to the method of Leube. I come now to the clinical means put in use for the study of the gastric juice.

All these clinical means are exclusively based on the employ of the stomach siphon, furnished or not with a pump to aspirate the liquid from the stomach. I have already in my "Alimentary Hygiene" set forth the processes heretofore employed to obtain gastric juice.t All these processes are aban

*Lombard, Thèse de Paris, 1887.

+ G. Chopin, "On the Elimination of Salicylic Acid" (Thèse de Paris, 1889).

Dujardin-Beaumetz, "Hygiène Alimentaire," 1889,

p. 201.

juice, it is necessary to give the patient a repast, called the trial meal.

Many trial meals have been recommended. Thus Riegel, Gluzinski, Jaworski, Boas, Ewald, Ritter, Hirsch, and Professor Sée have each proposed a trial meal.

From a clinical point of view, two only need be retained, that of Ewald and G. Sée. That of Ewald is almost exclusively employed in Germany, where it bears the name of probefrühstück. It consists of a little white bread, weighing thirty-five grammes (about an ounce), of a tumbler and a half (three hundred grammes) of water, or of light tea, without milk or sugar. This meal is given in the morning, on an empty stomach, and the gastric juice is examined one hour after the ingestion of the food.

Sée gives a meal which is more complex, composed of meat (sixty to eighty grammes) hashed very fine, of white bread (one hundred to one hundred and fifty grammes), and of a glass of water. He recommends to the patient a prolonged mastication. The examination of the gastric juice is made two hours after the ingestion of this meal.

Georges maintains that this meal gives rise to the production of lactic acid. Hence he prefers Ewald's test meal, to which he adds two eggs in the shell. It is well understood that the aspiration made with the pump should not be too energetic, and it suffices to obtain from twenty to twenty-five cubic centimetres of gastric juice in order to practise the examination. The gastric juice is filtered, then is

tained from coal tar, and I will begin by the reagent which has been longest in use,methyl violet.

It was Laborde and Dusart,* who, in 1874, sixteen years ago, were the first to propose methyl violet for the study of the modifications of the gastric juice. It is true that they applied it rather to physiological than to clinical studies. Since then Maly has taken up again the method of Laborde, and in 1887 applied it to practical use.†

To apply this test you thus proceed :

Into fifty cubic centimetres of water let fall three or four drops of methyl violet, called Paris violet; then pour into the solution the gastric juice which you are to examine, and if hydrochloric acid be present, the violet will turn to deep blue. An amount of hydrochloric acid equal to .5 per thousand is needed to produce this reaction.

Lactic acid also gives the same coloration, but it must be very concentrated (at least ten per cent.). The presence of peptones, in the proportion of four per cent., prevents the reaction from taking place, even when hydrochloric acid exists to the extent of one per thousand in the solution.

* Laborde, "The Coloring Matters applied to the Research and Determination of the Free Acid of the Gastric Juice" (Bulletin Général de Thérapeutique, t. cxii. p. 86, 1889).

Richard Maly, "Untersuchungen über die Mittel zur Säure Bildung in Organismus und über einige Verhältnisse der Blutserum" (Zeitschrift für Physiologische Chemie, t. i. p. 174, 1887).

The second process is that of tropœoline, recommended by Leube, and in 1884 I published several articles, making known the advantages which may be obtained from this test.*

This is the way to test gastric juice by tropooline, or the Poirrier Orange, No. 4: Into a watch-glass, placed on a white piece of paper, or other white surface, you pour one of the following solutions, either a small quantity of an aqueous solution of tropœoline, one per cent., or of an alcoholic solution, containing 1 part of alcohol to 3 parts of distilled water, with enough tropooline to make a centesimal solution; then to the liquid in the watch-glass you add a part of the gastric juice to be examined, and if there be hydrochloric acid present, the liquid assumes a very characteristic carmine-red color, which is in striking contrast with the normal yellow color of the tropœoline solution.

Like the methyl violet, this reaction may also be obtained with lactic acid, but a large proportion is needed, as much as two per thousand; this test is very sensitive, and is but little influenced by peptones. Hence it is that Georges places it at the head of the tests to be employed.

It is also on a change of color that the tests with Congo red and "brilliant green" are based. In applying the first reagent, test-papers saturated with the pigment (or a solution of the pigment) may be used; these, under the influence of hydrochloric acid, pass from a clear red to a blue color. To obtain this reaction, one milligramme per thousand of hydrochloric acid is sufficient. There would be required as much as 1.20 grammes per thousand of lactic acid in order to give the same reaction. Georges regards this as an excellent test.

The "brilliant green" test was proposed by Professor Lépine. He makes use of a two per cent. solution, and the presence of the acid makes the mixture pass from a greenish blue to a deep green. The inconvenience lies in the difficulty of appreciating the passage from a greenish blue to green.

Lastly, Gunzburg's test, especially vaunted by Germain Sée and his pupils, is the most sensitive of all. It will reveal the presence of one-twentieth per thousand of hydrochloric

Dujardin-Beaumetz, "On the Diagnostic Value of the Processes for the Recognition of the Acidity of the Gastric Juice" (Société Médicale des Hôpitaux, December, 1884, and Gazette Hebdomadaire, December 4, 1884, p. 804).

acid, only the process is quite complex, and heat is needed in order to bring out the reaction; so that this test is not so well adapted for clinical test as some others. This is the composition of this reagent:

B Phloro-glucine, 2 grammes;
Vaniline, I gramme;

Alcohol at 80°, 100 grammes. M.

This solution is of a reddish-yellow color. Into a porcelain capsule you will put ten or twelve drops of the gastric juice to be examined, and add three or four drops of the reagent. Then you will heat the mixture slightly, taking care not to raise the temperature above 38° to 40° C.; there will then appear along the borders of the capsule a cinnabar-red coloration.

If this reagent is extremely sensitive, it presents the serious disadvantage that its reactions are masked by the peptones and albuminoid bodies, hence I think that we should trust chiefly to the tropooline and methyl violet tests, and only make use of the Gunzburg test in exceptional cases.

In certain circumstances it is desirable to test for lactic acid. For this there is but one reagent,-viz., that proposed by Uffelmann. The solution must be extemporized for the occasion, according to Lyon's recommendation. Drop into a mixture of twenty cubic centimetres of distilled water and ten cubic centimetres of phenic acid (four per cent.), two or three drops of the liquor ferri perchloridi. The mixture takes on an amethyst hue, which turns to bright yellow in presence of lactic acid.

There remains yet the process for testing the acidity of the gastric juice. I shall not speak of the methods of Leon and of Winter, which are laboratory methods, and shall only mention the clinical processes. The following is a convenient method: Take ten cubic centimetres of gastric juice, and add a few drops of a solution of phenol-phtaleine, which has the property of changing to a lively red in the presence of a free alkali. Then add, drop by drop, a standard solution of soda,one-tenth, and make your calculation on the basis that one cubic centimetre of the solution neutralizes .003646 of HCl. In the normal state it takes from four to six cubic centimetres of this decimal solution of soda to produce the reaction.

Lastly, it is well to test the digestive power of the gastric juice by practising with it artificial digestions. For this purpose, you will put into a test-tube five cubic centimetres of

gastric juice and a little block of albumen,from five to six millimetres square. Place the whole in a stove, and expose it to a temperature of 38° to 40° C. You may make at the same time, for purposes of comparison, artificial digestions by the aid of pepsin.

But, in order to give you an idea of the minutiæ of the processes employed in Germany to test the digestive power of the gastric juice, allow me to quote the method counselled by Gunzburg to ascertain the chemical power of the stomach. This method is based on the presence of iodide of potassium in the saliva, when this salt has been absorbed into the circulation.

Gunzburg takes a pastille of iodide of potassium, and. encloses it in an envelope of caoutchouc, which is closed by means of threads of fibrin that have been preserved in alcohol. These little pastilles are dipped into glycerin; then one of them is taken and placed in a gelatin capsule, and the patient is made to swallow it. Then the saliva of the patient is examined, and the moment noted when the presence of iodine is revealed by the starch test. By the time which has elapsed, one is able to decide as to the digestive value of the gastric juice, for this fluid must first destroy the threads of fibrin before the pastilles of iodide of potassium are set free.

I do not know whether the method of Gunzburg is much employed in Germany, but it must be admitted that in France it is really impracticable. It must be confessed, in fact, that the patient and the physician will need a great deal of patience in order to subject for several hours, and from moment to moment, the saliva of the patient to a chemical examination which shall reveal the presence of iodine, and when the iodine is detected, nothing is solved thereby, for the pastille may have passed into the intestine before its threads are dissolved. Therefore, I think that it is just as well to reject these too complicated methods, which belong rather to the laboratory than to the department of clinical medicine.

You are now in possession of three orders of means which will enable you to detect the presence of free hydrochloric acid, the presence of lactic acid, the acid value of the gastric juice, and, lastly, its digestive power. With all these methods, can you dispense with the clinical examination, and on these data alone establish your diagnosis and your therapeutics?

No, gentlemen; and when you come to realize all the time and pains and care

which these chemical researches necessitate, and the meagre results which they bring, you will be tempted to say that the mountain has labored and brought forth a mouse. In fact, as Georges has well said, the diseases of the stomach, from a.chemical point of view, group themselves into two classes,those where there is hypersecretion of hydrochloric acid, and those where there is hyposecretion.

In the first group there is but one disease, viz., simple ulceration of the stomach; in the second are grouped all the other affections, gastritis, dilatation of the stomach; in a word, affections the most widely different. Hence, Hayem, in his recent researches, has shown that the presence of free hydrochloric acid does not enable one to decide respecting the diagnosis of the affections of the stomach, since its presence is an exceptional fact.

Do I mean by this that we must abandon these researches? By no means. These researches furnish us a complement of information which enables us to confirm, in a certain measure, the diagnosis to which we may have arrived by the other and really chemical means. But it is always the latter which should have the first place, and the study of the treatment of the divers diseases into which I am about to enter will be an absolute proof of what I maintain, and this proof I shall endeavor to make as complete as possible when I take up, as I intend to do in the next lecture, with the help of all the new light of modern research, the consideration of cancer of the stomach and its treatment.

A RESEARCH TO DETERMINE THE ACTION OF NITROUS OXIDE, NITROGEN, OXYGEN, AND CARBONIC

ACID UPON THE CIRCULATION,

WITH ESPECIAL REFERENCE TO NITROUS OXIDE ANESTHESIA.

By H. C. WOOD, M.D., ASSISTED BY DAVID CERNA, M.D., PHILADELPHIA, PA.

(Continued from page 515.)

PART II.

The first series of experiments in the second part of this research was made to determine the effect in the inhalation of oxygen upon the pulse and arterial pressure.

In the first of these experiments (Experiment 12), after the inhalation of pure oxygen gas for two minutes, the pulse was four beats