Page images
PDF
EPUB

, 1910

Series, Vol. V.

thus connected with the abdominal wall through a fistula. Returning to the upper end of the oesophagus, I bring the same in contact with the duodenum, and as wide a termino-lateral anastomosis as possible is made between the oesophagus and the duodenum at a distance of 10, 12, or 15 centimeters from the pylorus. Now there is nothing left to be done but to close the abdomen by a suture in three layers.

Provided that strictest asepsis is observed, the animal promptly recovers from this operation. At the end of eight days, the stomach is washed through the fistula, and at the end of a fortnight, the collecting of the gastric juice can begin. This collection is made twice daily, about fortyfive minutes after the animal has been fed, for at this time, the stomach is filled to the maximum degree. It is almost empty when the animal is fasting. An hour after eating it begins to empty itself towards the bowel.

For the collection of the gastric juice, the animal is suspended by means of a suitable harness, and a catheter is inserted into the fistula. The flow is started by aspiration; the gastric juice runs easily. It is at once passed through a cloth then filtered over cellulose, and collected in sterile flasks. It then remains under observation and study during three days in a waterbath, at 38° C. and all flasks which become turbid are removed; the clear flasks are bottled in sterile phials, according to the methods of the Pasteur Institute. After the phials have been corked and sealed, they are again placed in the hot water bath for three days, and are ready then for use.

I pointed out that my animals continued to develop after the operation; some of them were operated upon when about six months old, weighing 50 kilogrammes.

523 Their stomach, although out of use, has continued to develop in the usual manner, showing very evidently the trophic influence of the pneumogastric nerves, division of which leads to atrophy of the organ, even when it continues in its function.

Certain interesting modifications take place at the level of the oesophago-duodenal anastomosis, the duodenum dilating into a kind of new stomach. At the same time, the walls of the oesophagus and the intestine become hypertrophied, plainly illustrating their adaptation to a new function. It appears to me to be certain that part of the gastric juice flows into this pouch, and that the digestion is therefore continued in a perfectly normal manner. This is the reason why the general condition of the operated animals remains so favorable.

Liquids swallowed by the animal do not flow back towards the stomach, as I convinced myself through the introduction of colored fluids. A few solid particles do penetrate into it, however, meaning that a mass of solid matter forms at the level of the small duodenal stomach, identical in every way with that of the normal stomach, and carrying a few pulverized remnants of food towards the pylorus.

The gastric juice which I collected by means of the above outlined procedure, is accordingly a physiological gastric juice. It is identical in every way with the gastric juice of pigs, obtained simply through a fistula, the appearance, the color, and the chemical reaction are identical, but it nevertheless differs considerably from the gastric juice obtained after a total isolation of the stomach, with enclosure of the pylorus. Whereas the latter is colorless, slightly opalescent, of identical composition

as that of man, of medium acidity, the juice from a stomach which has been simply excluded, is yellowish, more viscid, very weakly acid, almost neutral, poorer in organic salts, relatively richer in mineral salts, having a weak proteolytic action on raw albumen, and none on boiled albumen.

These characteristics are attributable to a peculiar anatomical configuration of the pig. The choledochus in this animal opens at the level of the pyloric region. If the pylorus is divided, it is sure to be divided also. It does not unite, as in man, with the Wirsangian canal, which on the contrary opens by itself into the duodenum, at a distance of 15-20 centimeters. This arrangement brings it about that in normal condition, a part of the bile is poured into the stomach and neutralizes the acidity of the juice; it is even capable of neutralizing a quantity of acid greater than the normal quantity, for when hydrochloric acid is added to the juice, the acid is found in the analysis only in the form of chlorine.

The juice obtained by me, although in every way analogous with the physiologic gastric juice, does not satisfy various authors (Loeb, Flexner, Mathieu), who claim that this gastric juice was either not normal or that it could not have an efficient therapeutic action. These objections were at first very distressing to me, as I could only reply to them by my therapeutic results, and therapeutic result is always open to suspicion, or at least discussion. At the present day, however, these objections have ceased to trouble me, for I am no longer alone in affirming that under normal physiological conditions, the bile and the pancreatic juice flow back into the stomach and thus neutralize in part the acidity of its secretion.

Boas, Tchlenoff, Boldyreff, Volhard, Kaltzenstein, have established by trypsin demonstrations the very frequent co-existence of pancreatic juice in the stomach; and Miga, in Pawlow's laboratory, showed that when an acid solution is introduced into the stomach, the acidity of this solution rapidly diminishes on account of the compensating influx of the secretions of the intestine into the stomach, by way of the pylorus. He showed that this part neutralization is even necessary, in order to bring about the passage of the foods through the pylorus towards the intestine.

I

In the beginning of my investigations, I noted that one to two dessertspoonful of the juice, which the animal secretes in hundreds of grammes, sufficed to re-establish profoundly impaired digestive functions in man and I decided that such a small quantity certainly does not act through supplementing the digestive fluids. thought that the gastric juice, especially the juice obtained by me contained a “quid ignotum" which is the secret of its efficiency, and which is neither hydrochloric acid nor pepsine. This seemed so much the more evident, as I had seen a number of patients react favorably to the gastric juice, after they had taken for months without results hydrochloric acid lemonade and pepsine. When Professor Von Noorden, in 1904, furnished me with the results of his analysis, which showed that the dyspeptic patients treated by him with my gastric juice had experienced a return of their gastric juice secretion and a return of the secretory processes towards normal, it afforded me the evidence that this almost neutral juice certainly contained an excito-secretory substance, which was neither the hydrochloric acid nor the pepsine; and I did not hesitate, when re

, 1910

Series, Vol. V.

porting these results before the Societé de Biologie, to assert the existence of this substance and to credit it with the therapeutic efficiency which many others hal already observed.

In the year 1905, Frouin with whose work I was entirely unacquainted, published before the Societé de Biologie, the investigations which he had carried out in the Pasteur Institute with the neutralized gastric juice of dogs. These ably conducted investigations showed that both when ingested and when injected subcutaneously, the strictly neutralized gastric juice exerts upon the gastric mucosa a powerful excito-secretory influence, which is not referable to the hydrochloric acid or to the pepsine, hence, there must have been in the gastric juice an excito-secretory substance, independent of the classical constituents.

I immediately began experimenting in order to ascertain the presence of this excito-secretory substance in the gastric juice of pigs, as obtained by my method.

For this purpose the stomachs of two animals were entirely isolated by dividing them a little above the pylorus, so as not to injure the choledochus, and by implanting the oesophagus into the duodenum, as was my habit to do. During a fortnight, I measured daily the gastric secretion of each animal; this secretion amounted on an average to 450 cubic centimeters daily in one animal. I then studied upon this animal the influence of an injection of artificial serum, upon the gastric secretion; it was found to be very weak. I then injected under the skin 100 centimeters of perfectly neutralized gastric juice, and succeeded by means of successive injections, not only in doubling and tripling the normal secretion but increasing its

quantity six times. This animal died shortly afterwards as a result of pancreatitis, which illustrated at the same time the very powerful excito-secretory action of my ordinary gastric juice, (the other animal succumbed at the end of three weeks to a gastric hemorrhage, from a round ulcer at the cardiac end of the stomach).

Since that time the investigations of Edkins (Journal of Physiology, 1906, Vol. XXXIV) have demonstrated the existence of a gastric "Stimuline" which he obtained like the intestinal "Stimuline" of Bayliss and Starling, by boiling pyloric mucosa with acid, water or peptone. This "Stimuline" when injected into the jugular vein and carried to the stomach by the circulation, is alone capable of causing the reappearance of the stomach secretion in an animal, the psychic secretion of which has been stopped by division of the pneumogastric nerves. It is secreted only by the pyloric glands, not by the glands of the stomach.

Supported by this set of concurrent proofs, I can assert to-day that the gastric juice, as obtained by me, owes its action to a specific excito-secretory substance; and that this gastric juice serves to arouse the gastric secretion and to reestablish the normal function of the stomach. This accounts in a very simple. way for the favorable action of weak doses, drops for children, teaspoonfuls or dessertspoonfuls for adults, which was altogether incomprehensible by attributing to the remedy a direct digestive function entirely out of proportion to its real action and dosage.

This leads me to consider briefly how the gastric secretion must be interpreted, from the higher physiological point of

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 to create a gastric fistula. When the animal eats, the food escapes through this fistula, while its stomach secretes a juice, the secretion stopping as soon as the animal stops eating. This experiment is always successful in dogs, animals having a lively imagination, whereas it regularly fails in the pig, even when the animal keeps on eating for an hour and longer, with indefatigable greed.

Hence, if the psychic secretion represents for man and for intelligent dogs the first secretion, this secretion being absent in all other species, as demonstrated by me-it is not possible for it to be, by a reflex process, the cause of the secondary alimentary secretion, as held by Pawlow.

There was a reason to think that the gastric secretion, as well as the intestinal secretion, has a chemical stimulus, and that this chemical stimulus is contained in the gastric secretion itself, which is thus kept up constantly by means of this stimulus.

The gastric secretion is mainly a chemical secretion with its agent contained in the gastric juice itself; in animals whose stomach empties itself rapidly and completely, and which are also active and intelligent animals, a new psychic secretion is necessary to arouse again the intermittent, suspended secretion, by the absorption of a new quantity of stimuline. In indolent non-intelligent animals, such as pachyderms, solipeds, the pig, whose stomach is never completely emptied, the gastric juice secretion is more or less continuous, always pouring the gastric "stimu

In my personal opinion, this view besides justifying the old assumptions expressed by me at the Madrid Congress of 1903, at the same time justified my procedure for the obtaining of a natural gastric juice, namely the unilateral gastric excision, with an open pylorus; this operation permits the animals to regularly maintain their gastric secretion by pouring gastric "stimuline" into the intestine; it alone permits us to collect the total juice of the pyloric and fundus glands, whereas the small stomach of Pawlow yields only the juice of the fundus glands, without the "stimuline," it alone permits, due to the slight alimentary reflux from the intestine towards the stomach through the open pylorus, the collection of an active "stimuline" by means of the necessary mixture of dextrine and pyloric juice, according to Edkins; it alone permits the producing animal to remain in good health, a necessary requirement in order to utilize its natural secretion.

Compared to these advantages, what matters the drawback of furnishing a weakly acid gastric juice, of low proteolytic power, the principal objection which has been raised by some against my gastric juice? I reply to them by saying, that I prefer to introduce into the stomach an absolutely harmless neutral remedy as long as it is known to me to possess a superior therapeutic efficiency, and that I care little for the very uncertain additional advantage of providing to a very slight degree, an artificial digestion which would be more satisfactorily accomplished by an artificial

juice composed of hydrochloric acid and pepsine, if the gastric opotherapy, with a natural juice, had no other object but this digestion.

Having shown how my gastric juice is obtained, how it is composed, and why it acts, I shall now discuss as concisely as possible under what circumstances good and often excellent therapeutic results may be obtained from its use.

Gastric Insufficiency:-Deduction from above facts suggests at once that such a medicinal agent is indicated in all those cases in which there is failure of gastric secretion, either through an anatomical change of the stomach glands, or through a functional stoppage of their secretion and also in the disturbances resulting from the adulteration or absence of this secretion.

This deduction is entirely confirmed by clinical observation. I am indebted to Professor Von Noorden, and to Professor Surmont of Lille, for the most complete and extensive studies of the action of the pig's gastric juice, in gastric insufficiency, illustrated by perfectly concurrent analytical data.

The article of Professor Von Noorden appeared in the December number 1903, of "Therapieder Gegenwart," Professor Surmont's work formed the foundation of Dr. Ericart's inaugural dissertation (These de Lille, 1907). The patients subjected to these investigations were all suffering from a gastric insufficiency, either primary, or secondary through chlorosis, incipent tuberculosis, or chronic dysentery. In all these cases, it was noted that the insufficient gastric secretion, after resisting various diets and treatments, was very promptly and distinctly improved, permanently so in a number of cases, by the employment of two to three tablespoonfuls

of gastric juice daily. In all, the changed secretory relations show a tendency to become normal secretion in some, and actually surpassing it in one patient, who developed hyperchlorhydria.

In a few very grave cases of total anachlorhydria (achylia gastrica), the effect is but slightly marked or absent; but these patients, like the former, are improved from a functional point of view, the pains frequently ceasing after the first doses, and with returned appetite, cheerfulness and strength are regained, and the body weight increased.

We are here confronted with a striking phenomenon, which certainly indicates specific action, all the more remarkable with a liquid (which some refuse to endorse, because it contains no free hydrochloric acid) causing the total chlorhydria to return to normal.

I therefore feel obliged to insist on emphasizing certain points which I have studied particularly: namely the favorable action of the pig's gastric juice on the anorexia and gastric disturbances of tuberculous patients, and its excellent effect upon diarrhoeas in general, but especially those of infantile gastroenteritis, for which ailment our stock of useful remedies is so limited.

Tuberculosis:-As tuberculosis patients, with rare exceptions, are also sufferers from gastric insufficiency, I believed since my first investigations that the stimulating gastric juice must be the remedy of choice. for their anorexia and digestive disturbances. My expectations were readily confirmed by practical experience, the gastric juice proving serviceable in all the stages of tuberculosis. In dealing with a case of incipient tuberculosis, afebrile, with anorexia and emaciation, it is exceptional

« PreviousContinue »