Harry Shay

A Quantitative Method for Measuring Spontaneous Gastric Secretion in the Rat

In 1945 we described a simple method for uniformly producing ulceration in the rumens of properly fasted rats by allowing the spontaneously secreted gastric juice to accumulate in the empty stomach with its pylorus ligatedl . Since we were able to show that the ulceration of the rumen mucosa was due to acid-pepsin digestion, we also suggested in that report that the rat preparation might serve as a useful screening tool for antacid, antipeptic and other antiulcer agents. In the last category we had in mind agents that might be uncovered that would increase mucosal resistance to ulceration. We have already shown that a high protein diet probably acts in such a capacity2. In neither our first publicationl nor in any subsequent one2-11 have we stated or intimated that we thought the rat rumen ulcer produced by our technic in any manner resembled chronic peptic ulcer pathologically in man, but we do believe that it would be of interest to evaluate in man any agent shown capable of protecting the rats rumen mucosa against acid-pepsin erosion. In this sense we felt, our rat preparation could serve as a useful tool-as a test tube in vivo. With the introduction of Banthine and the active search for anticholinergic drugs, this rat preparation came to be used widely for the initial screening of these compounds. From a study of the reports of these and other investigations12 -2v we were impressed by the variations in technic which must necessarily lead to differences in observed results. We considered such factors to include: (1) weight of the animal, (2) state of hydration, (3) anesthetic agent used, (4) whether the animal was anesthetized only during operation or throughout the experimental period, (5) care of operative procedure, (6) collection of the gastric juice-whether allowed to accumulate in the stomach or removed continually through a gastric canula, and (7) duration of period in which gastric juice was collected. Because of these variables we were prompted to undertake the present investigation in the hope of offering a standard technic for the study of gastric secretion in the rat that might permit a comparison of results obtained with this preparation in different laboratories-a comparison not possible at the present time.

External Pancreatic Secretion in Diabetes Mellitus

Excerpt Whether changes in external pancreatic secretion can occur in diabetes mellitus has long been debated. Early investigators, using a single lumen (1) or a double lumen tube (2-4) for the col...

The Combined Study of Serum Enzymes and Duodenal Contents in the Diagnosis of Pancreatic Disease

Summary 1.A combined study of the serum amylase and lipase activities and of volume, bicarbonate, and amylase activity of the duodenal contents after pancreozyminsecretin stimulation is described. Pancreozymin was given first, followed in 10 minutes by secretin, intravenously. 2.Pancreozymin-secretin test gave positive serum enzyme responses in 9 of 18 patients with chronic pancreatitis, in all of 3 cases of carcinoma of the ampulla of Vater, and in only one of 5 cases of carcinoma of the pancreas. A comparative study of pancreozymin and secretin and of secretin alone as the stimulant in some of these patients showed that the addition of pancreozymin increased the yield of positive serum enzyme responses. 3.Five of the 9 cases of chronic pancreatic disease with positive serum enzyme responses showed normal findings of the duodenal contents. On the other hand, the other 9 cases with normal serum enzyme response showed low values of the duodenal contents. 4.We recommend that in cases of suspected pancreatic disease, the provocative serum enzyme test with pancreozymin and secretin be done first; if negative, to be followed by a duodenal intubation study. The provocative serum enzyme test could be included as one of the tests in the routine investigation of chronic pancreatic disease.

A self regulatory duodenal mechanism for gastric acid control and an explanation for the pathologic gastric physiology in uncomplicated duodenal ulcer.

By a direct approach in the human subject we have demonstrated the presence in the normal duodenum of a mechanism which is brought into play by a concentration of acid peculiar to the individual. This concentration for any meal, is represented by the peak of free acidity reached after the particular meal. When this concentration of acid reaches the duodenum a mechanism is activated that depresses gastric secretion and is responsible for the descending limb of the normal gastric curve. In the failure of the normal response of such a mechanism, obtunded by the ulceration and inflammation produced by duodenal ulcer, we believe lies the explanation for the high acid extra-gastric curve seen in this disease. That such a failure of response does occur, we have demonstrated in duodenal ulcer patients. If we combine our present findings regarding gastric secretion with the influence of the duodenum upon gastric motor function which we have previously described, we have for the first time, in the disturbance of one mechanism an explanation for the characteristic clinical gastric findings in uncomplicated duodenal ulcer—hyperperistalsis, hypertonicity, hypermotility and hypersecretion.

GASTRIC ACID SECRETION IN DIABETES MELLITUS

Excerpt Earlier investigators have noted a high incidence of achlorhydria among diabetic patients. Bowen and Aaron1found achlorhydria in 29% of 61 diabetic subjects, and Marble2reported an incidenc...

Concerning the influence of glucose on the response of the human stomach to test meals

With a two tube technique in man, the influence of glucose solutions instilled intraduodenally and intravenously upon the response of the stomach to test meals was investigated. An attempt was made to separate the duodenal effect upon gastric acidity resulting from the osmotic changes produced by hyper-tonic glucose and the possible effect of the resultant hyperglycemia. Our evidence at present indicates the most striking effect to be dependent upon the altered osmotic conditions in the duodenum, while the hyperglycemia plays only a secondary role. The latter, however, may be sufficient to explain the higher-than-average incidence of anacidity in diabetes.

Experimental studies in gastric physiology in man: the mechanism of gastric evacuation after partial gastrectomy as demonstrated roentgenologically.

Partial gastric resection apparently causes no basic changes in gastric evacuation. If the altered gastric chemistry which results from the resection is taken into consideration, then gastric evacuation is modified in the same way by the same agents that modify gastric-emptying of the intact stomach to a similar chemical response, except, of course, for quantitative differences. These differences appear to be due to the loss of the pyloric sphincter. The remaining gastric muscle-fibers appear to offer a substitution mechanism, but are not so efficient as was the pylorus. The response is similar to that of the intact stomach whether the test substances are ingested or are applied directly to the intestinal mucosa. The evidence also indicates that, even in a partially resected stomach, the mechanism of gastric evacuation is controlled from the intestinal side.

Roentgen Studies of Esophageal Transport in Patients with Dysphagia Due to Abnormal Motor Function

Summary Esophageal transport of a water-barium mixture was studied in 40 patients with dysphagia. From the changes produced in transport by parasympathetic stimulation or depression, we can divide these patients into two groups: one with cardiospasm and a second group which we propose to call dysrhythmia of the esophagus. Characteristic of cardiospasm was esophageal dilatation and retention of the water-barium mixture in the esophagus during the control period. Spasm of the lower esophagus, frequently associated with substernal pain and vomiting, occurred in this group after the administration of Urecholine. Dibuline relaxed the Urecholine-induced spasm and resulted in slightly better esophageal emptying. Xitroglycerin was the most effective drug in promoting esophageal evacuation in the cardiospasm group. The patients with dysrhythmia had greater intermittency of symptoms, and dilatation of esophagus was not found in this group. Hiatal hernia and/or constriction ring of the lower esophagus were found in 16 of 23 in this group, and esophagitis occurred in approximately 25 per cent. Characteristic of patients with dysrhythmia was the disorganization of esophageal motor waves. Urecholine administration resulted in improvement in esophageal emptying but Dibuline increased the esophageal retention. In conclusion, our results indicate that abnormal esophageal transport may result, aside from anatomical obstructive lesions, from one of two disturbances: one, cardiospasm, the result of damaged or absent parasympathetic plexuses of the lower esophagus including the sphincters and/or vestibule; the other due to disorganized motor function of the esophagus which we suggest be called dysrhythmia of the esophagus. These two varieties may be separated by their respective pharmacologic responses to parasympathomimetic and parasympatholytic drugs. The response to these drugs not only enables a differential diagnosis of the type of abnormal esophageal transport but also supplies a basis for therapy.

An Evaluation of the Starch Tolerance Test in Pancreatic Insufficiency

Summary The starch tolerance test was performed in 101 patients without pancreatic disease and in 43 patients with pancreatic disease. The possible pitfalls of the test are discussed. Positive results were observed in 15 of the 27 cases with chronic relapsing pancreatitis and in 8 of the 9 cases with carcinoma of the pancreas. The test gave a normal result in 100 patients and a false positive result in 1 patient without pancreatic disease. When the starch tolerance test was positive, it appeared to be a reliable indicator of pancreatic disease. A negative starch tolerance test did not rule out pancreatic disease.

THE EFFECT OF DUODENAL STIMULATION IN MAN UPON ALIMENTARY AND ADRENALIN HYPERGLYCEMIA

Excerpt As early as 1825, Leuret and Lassaigne33from studies on the horse and dog wrote that the causes which determined the secretion of pancreatic juice were analogous to those which influenced t...