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, 1910

} New Series, Vol. V., No. 10.

thus connected with the abdominal wall Their stomach, although out of use, has through a fistula. Returning to the upper continued to develop in the usual manner, end of the oesophagus, I bring the same showing very evidently the trophic inin contact with the duodenum, and as wide fluence of the pneumogastric nerves, dia termino-lateral anastomosis as possible vision of which leads to atrophy of the oris made between the oesophagus and the gan, even when it continues in its funcduodenum at a distance of 10, 12, or 15 tion. centimeters from the pylorus. Now there Certain interesting modifications take is nothing left to be done but to close the place at the level of the oesophago-duoabdomen by a suture in three layers. denal anastomosis, the duodenum dilating

Provided that strictest asepsis is ob- into a kind of new stomach. At the same served, the animal promptly recovers from time, the walls of the oesophagus and the this operation. At the end of eight days, intestine become hypertrophied, plainly ilthe stomach is washed through the fistula, lustrating their adaptation to a new funcand at the end of a fortnight, the collecting tion. It appears to me to be certain that of the gastric juice can begin. This col- part of the gastric juice flows into this lection is made twice daily, about forty- pouch, and that the digestion is therefore five minutes after the animal has been fed, continued in a perfectly normal manner. for at this time, the stomach is filled to the This is the reason why the general conmaximum degree. It is almost empty dition of the operated animals remains so when the animal is fasting. An hour af- favorable. ter eating it begins to empty itself towards Liquids swallowed by the animal do not the bowel.

flow back towards the stomach, as I conFor the collection of the gastric juice, vinced myself through the introduction of the animal is suspended by means of a colored Auids. A few solid particles do suitable harness, and a catheter is inserted penetrate into it, however, meaning that into the fistula. The flow is started by a mass of solid matter forms at the level aspiration; the gastric juice runs easily. It of the small duodenal stomach, identical is at once passed through a cloth then in every way with that of the normal filtered over cellulose, and collected in ster- stomach, and carrying a few pulverized ile flasks. It then remains under observation remnants of food towards the pylorus. and study during three days in a water- The gastric juice which I collected by bath, at 38° C. and all flasks which be- means of the above outlined procedure, is come turbid are removed; the clear flasks accordingly a physiological gastric juice. are bottled in sterile phials, according to It is identical in every way with the gastric the methods of the Pasteur Institute. After juice of pigs, obtained simply through a the phials have been corked and sealed, they fistula, the appearance, the color, and the are again placed in the hot water bath for chemical reaction are identical, but it neverthree days, and are ready then for use. theless differs considerably from the gas

I pointed out that my animals continued tric juice obtained after a total isolation to develop after the operation; some of of the stomach, with enclosure of the pythem were operated upon when about six lorus. Whereas the latter is colorless, months old, weighing 50 kilogrammes. slightly opalescent, of identical composition as that of man, of medium acidity, the Boas, Tchlenoff, Boldyreff, Volhard, juice from a stomach which has been Kaltzenstein, have established by trypsin simply excluded, is yellowish, more viscid, demonstrations the very frequent co-exvery weakly acid, almost neutral, poorer istence of pancreatic juice in the stomach; in organic salts, relatively richer in min- and Miga, in Pawlow's laboratory, showed eral salts, having a weak proteolytic ac- that when an acid solution is introduced tion on raw albumen, and none on boiled into the stomach, the acidity of this soalbumen.

lution rapidly diminishes on account of the These characteristics are attributable to compensating influx of the secretions of the a peculiar anatomical configuration of the intestine into the stomach, by way of the pig. The choledochus in this animal opens pylorus. He showed that this part neutralat the level of the pyloric region. If the ization is even necessary, in order to bring pylorus is divided, it is sure to be divided about the passage of the foods through also. It does not unite, as in man, with the pylorus towards the intestine. the Wirsangian canal, which on the con- In the beginning of my investigations, trary opens by itself into the duodenum, I noted that one to two dessertspoonsful of at a distance of 15-20 centimeters. This the juice, which the animal secretes in arrangement brings it about that in normal hundreds of grammes, sufficed to re-estabcondition, a part of the bile is poured into lish profoundly impaired digestive functhe stomach and neutralizes the acidity of tions in man and I decided that such a small the juice; it is even capable of neutral- quantity certainly does not act through izing a quantity of acid greater than the supplementing the digestive Auids. I normal quantity, for when hydrochloric thought that the gastric juice, especially acid is added to the juice, the acid is found the juice obtained by me contained a “quid in the analysis only in the form of chlorine. ignotum" which is the secret of its

The juice obtained by me, although in efficiency, and which is neither hydroevery way analogous with the physiologic chloric acid nor pepsine. This seemed so gastric juice, does not satisfy various au- much the more evident, as I had seen a thors (Loeb, Flexner, Mathieu), who claim number of patients react favorably to the that this gastric juice was either not nor- gastric juice, after they had taken for mal or that it could not have an efficient months without results hydrochloric acid therapeutic action. These objections were lemonade and pepsine. When Professor at first very distressing to me, as I could Von Noorden, in 1904, furnished me with only reply to them by my therapeutic re- the results of his analysis, which showed sults, and therapeutic result is always open that the dyspeptic patients treated by him to suspicion, or at least discussion. At the with my gastric juice had experienced a present day, however, these objections have return of their gastric juice secretion and ceased to trouble me, for I am no longer a return of the secretory processes towards alone in affirming that under normal normal, it afforded me the evidence that physiological conditions, the bile and the this almost neutral juice certainly conpancreatic juice flow back into the stomach tained an excito-secretory substance, which and thus neutralize in part the acidity of

was neither the hydrochloric acid nor the its secretion.

pepsine; and I did not hesitate, when reporting these results before the Societé de quantity six

quantity six times. This animal died Biologie, to assert the existence of this shortly afterwards as a result of pansubstance and to credit it with the thera- creatitis, which illustrated at the same time peutic efficiency which many others hal al- the very powerful excito-secretory action ready observed.

of my ordinary gastric juice, (the other In the year 1905, Frouin with whose animal succumbed at the end of three work I was entirely unacquainted, pub- weeks to a gastric hemorrhage, from a lished before the Societé de Biologie, the round ulcer at the cardiac end of the stominvestigations which he had carried out in ach). the Pasteur Institute with the neutralized Since that time the investigations of Edgastric juice of dogs. These ably con- kins (Journal of Physiology, 1906, Vol. ducted investigations showed that both XXXIV) have demonstrated the existence when ingested and when injected sub- of a gastric “Stimuline” which he obtained cutaneously, the strictly neutralized gastric like the intestinal “Stimuline” of Bayliss juice exerts upon the gastric mucosa a and Starling, by boiling pyloric mucosa powerful excito-secretory influence, which with acid, water or peptone. This "Stimuis not referable to the hydrochloric acid line” when injected into the jugular vein or to the pepsine, hence, there must have and carried to the stomach by the circulabeen in the gastric juice an excito-secre- tion, is alone capable of causing the retory substance, independent of the classical

appearance of the stomach secretion in an constituents.

animal, the psychic secretion of which has I immediately began experimenting in been stopped by division of the pneumoorder to ascertain the presence of this ex- gastric nerves. It is secreted only by the cito-secretory substance in the gastric juice pyloric glands, not by the glands of the of pigs, as obtained by my method.

stomach. For this purpose the stomachs of two Supported by this set of concurrent animals were entirely isolated by dividing proofs, I can assert to-day that the gasthem a little above the pylorus, so as not to tric juice, as obtained by me, owes its acinjure the choledochus, and by implanting tion to a specific excito-secretory subthe oesophagus into the duodenum, as was stance; and that this gastric juice serves my habit to do. During a fortnight, I to arouse the gastric secretion and to remeasured daily

daily the

the gastric secretion establish the normal function of the of each animal; this secretion amounted stomach. This accounts in a very simple on average to 450 cubic centi- way for the favorable action of weak doses, meters daily in one animal. I then studied drops for children, teaspoonfuls or dessertupon this animal the influence of an injec- spoonfuls for adults, which was altogether tion of artificial serum, upon the gastric incomprehensible by attributing to the secretion; it was found to be very weak. remedy a direct digestive function entirely I then injected under the skin 100 centi- out of proportion to its real action and meters of perfectly neutralized gastric dosage. juice, and succeeded by means of successive This leads me to consider briefly how injections, not only in doubling and tripling the gastric secretion must be interpreted, the normal secretion but increasing its from the higher physiological point of

an

view. It begins, as has been positively line" (the "hormone” of Edkins), into the shown by Pawlow, with the secretion of intestine. This chemical stimulus renders psychic or appetite juice. Pawlow's ex- all the digestive secretions interdependent periment consists in dividing the oesoph- and self-dependent, conjointly responsible, agus at the neck and attaching its two ends as it were. separately to the skin of the neck and then

In my personal opinion, this view beto create a gastric fistula. When the ani- sides justifying the old assumptions exmal eats, the food escapes through this pressed by me at the Madrid Congress of fistula, while its stomach secretes a juice, 1903, at the same time justified my prothe secretion stopping as soon as the ani- cedure for the obtaining of a natural gasmal stops eating. This experiment is al- tric juice, namely the unilateral gastric exways successful in dogs, animals having cision, with an open pylorus; this operaa lively imagination, whereas it regularly tion permits the animals to regularly mainfails in the pig, even when the animal tain their gastric secretion by pouring gaskeeps on eating for an hour and longer, tric "stimuline" into the intestine; it alone with indefatigable greed.

permits us to collect the total juice of the Hence, if the psychic secretion repre- pyloric and fundus glands, whereas the sents for man and for intelligent dogs the small stomach of Pawlow yields only the first secretion, this secretion being absent juice of the fundus glands, without the in all other species, as demonstrated by "stimuline," it alone permits, due to the me—it is not possible for it to be, by a slight alimentary reflux from the intesreflex process, the cause of the secondary tine towards the stomach through the open alimentary secretion, as held by Pawlow. pylorus, the collection of an active "stimuThere was

a reason to think that the line” by means of the necessary mixture of gastric secretion, as well as the intestinal dextrine and pyloric juice, according to secretion, has a chemical stimulus, and that Edkins; it alone permits the producing this chemical stimulus is contained in the animal to remain in good health, a necesgastric secretion itself, which is thus kept sary requirement in order to utilize its up constantly by means of this stimulus. natural secretion.

The gastric secretion is mainly a chem- Compared to these advantages, what ical secretion with its agent contained in matters the drawback of furnishing a weakthe gastric juice itself; in animals whose ly acid gastric juice, of low proteolytic stomach empties itself rapidly and com- power, the principal objection which has pletely, and which are also active and in- been raised by some against my gastric telligent animals, a new psychic secretion juice? I reply to them by saying, that I is necessary to arouse again the inter- prefer to introduce into the stomach an mittent, suspended secretion, by the ab- absolutely harmless neutral remedy as long sorption of a new quantity of stimuline. as it is known to me to possess a superior In indolent non-intelligent animals, such therapeutic efficiency, and that I care little as pachyderms, solipeds, the pig, whose for the very uncertain additional advantage stomach is never completely emptied, the of providing to a very slight degree, an gastric juice secretion is more or less con- artificial digestion which would be more tinuous, always pouring the gastric "stimu- satisfactorily accomplished by an artificial

, 1910.

New Series, Vol. V., No.

XVI. 527 juice composed of hydrochloric acid and of gastric juice daily. In all, the changed pepsine, if the gastric opotherapy, with a secretory relations show a tendency to benatural juice, had no other object but this come normal secretion in

some,

and acdigestion.

tually surpassing it in one patient, who Having shown how my gastric juice is developed hyperchlorhydria. obtained, how it is composed, and why it In a few very grave cases of total acts, I shall now discuss as concisely as anachlorhydria (achylia gastrica), the efpossible under what circumstances good fect is but slightly marked or absent; but and often excellent therapeutic results may these patients, like the former, are imbe obtained from its use.

proved from a functional point of view, Gastric Insufficiency:- Deduction from the pains frequently ceasing after the first above facts suggests at once that such a doses, and with returned appetite, cheermedicinal agent is indicated in all those fulness and strength are regained, and the cases in which there is failure of gastric body weight increased. secretion, either through an anatomical We are here confronted with a striking change of the stomach glands, or through phenomenon, which certainly indicates a a functional stoppage of their secretion and specific action, all the more remarkable also in the disturbances resulting from the with a liquid (which some refuse to enadulteration or absence of this secretion. dorse, because it contains no free hydro

This deduction is entirely confirmed by chloric acid) causing the total chlorhydria clinical observation. I am indebted to to return to normal. Professor Von Noorden, and to Professor I therefore feel obliged to insist on emSurmont of Lille, for the most complete phasizing certain points which I have studand extensive studies of the action of the ied particularly: namely the favorable acpig's gastric juice, in gastric insufficiency, tion of the pig's gastric juice on the anoillustrated by perfectly concurrent analyti- rexia and gastric disturbances of tubercal data.

culous patients, and its excellent effect upon The article of Professor Von Noorden diarrhoeas in general, but especially those appeared in the December number 1903, of of infantile gastroenteritis, for which ailTherapieder Gegenwart,Professor Sur- ment our stock of useful remedies is so mont's work formed the foundation of Dr. limited. Ericart's inaugural dissertation (These de Tuberculosis:-As tuberculosis patients, Lille, 1907). The patients subjected to with rare exceptions, are also sufferers from these investigations were all suffering from gastric insufficiency, I believed since my a gastric insufficiency, either primary, or first investigations that the stimulating gassecondary through chlorosis, incipent tu- tric juice must be the remedy of choice berculosis, or chronic dysentery. In all for their anorexia and digestive disthese cases, it was noted that the in- turbances. My expectations were readily sufficient gastric secretion, after resisting confirmed by practical experience, the gasvarious diets and treatments, was very tric juice proving serviceable in all the promptly and distinctly improved, per- stages of tuberculosis. In dealing with a manently so in a number of cases, by the case of incipient tuberculosis, afebrile, with employment of two to three tablespoonfuls anorexia and emaciation, it is exceptional

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