David C. H. Sun

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.

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 Controlled Study on the Use of Propantheline and Amylopectin Sulfate (SN-263) for Recurrences in Duodenal Ulcer

The effect of long term administration of an antipeptic agent, SN-263, an anticholinergic drug, propantheline bromide, and their combination for prevention of recurrences was investigated in 75 patients with chronic duodenal ulcer, utilizing a double blind study. The results indicate a recurrence of 75% in the placebo group, 39% in the propantheline group, 16% in the SN-263 group, and 12% in the combined propantheline and SN-263 group. These data confirm the role of gastric proteolytic activity in chronic duodenal ulcer and demonstrate the efficacy of antipeptic agent in the prevention of recurrence.

Normal Values For Pancreozymin-Secretin Test

Summary A combined study of the serum amylase and lipase activities and of volume, bicarbonate, and amylase activity of the duodenal contents in 68 patients without pancreatic disease is described. Pancreozymin was given first, followed in 10 minutes by secretin, intravenously. A statistical analysis of the serum enzyme values and of the duodenal content data was accomplished. The least scatter of data in the duodenal contents was in the postsecretin 60-minute volume rate of secretion in milliliters per kilogram, the maximal bicarbonate concentration and the combined postpancreozymin-secretin amylase output, and they were used in the analysis for the norms. Norms have been established for the serum amylase and lipase response and for the volume, bicarbonate, and amylase response to the intravenous administration of pancreozymin and secretin.

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.

Synergistic action of chlorpromazine and tricyclamol on basal gastric secretion in duodenal ulcer patients.

Summary 1.The effect of chlorpromazine alone on basal gastric secretion was studied in 15 patients with duodenal ulcer; 7 received the drug intramuscularly in a dose of 12.5 mg., 8 in a dose of 25.0 mg. A significant decrease in volume, free acidity, total acid and pepsin output after the administration of chlorpromazine was observed. 2.Five additional patients with duodenal ulcer were each tested with chlorpromazine and tricyclamol alone and in combination at three different dose levels as well as in two control studies, making a total of 11 tests on each patient. Chlorpromazine or tricyclamol was found to inhibit the total acid output of the basal gastric secretion; the degree of inhibition increased with increasing dose of each drug alone. The average inhibition produced by chlorpromazine was found to be significantly less than with tricyclamol for the dose levels selected. 3.When chlorpromazine was used in combination with tricyclamol a synergistic inhibition on total acid output of basal gastric secretion was demonstrated.

Effect of tricyclamol on gastric emptying and intestinal transit; comparative studies with placebos, single dose, and optimal effective dose.

SummaryThe effects of a placebo, 50 mg. dose, and the “O.E.D.” of Tricyclamol on gastric emptying and intestinal transit of a standard barium mixture and Ewald meal were compared in nine patients with duodenal ulcer. Each patient served as his own control. The medicament was given half an hour prior to the ingestion of the barium mixture and Ewald meal. Serial x-rays of the abdomen were then taken.No significant differences were found in the rate of gastric emptying following the placebo or a 50 mg. dose of Tricyclamol. However, the “O.E.D.” of Tricyclamol produced a delay in gastric emptying of the barium and Ewald mixture at 1- and 2-hour intervals, but none at the 4-hour period. Thus, the “O.E.D.” of Tricyclamol, though a multiple of the 50 mg. dose, did not produce excessive delay in gastric emptying of the barium mixture and Ewald meal. However, some but no important delay in the progress of the barium along the intestine was noted after Tricyclamol as compared to that produced by the placebo.

MASSIVE NECROSIS OF THE LIVER FOLLOWING IPRONIAZID

Excerpt The hydrazine derivatives of isonicotinic acid (isoniazid and iproniazid) have been used effectively in the treatment of human tuberculosis. However, significant side-effects have occurred ...