Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer.

Nocturnal pain and gastric hypersecretion are common in duodenal ulcer. Therefore, we investigated the antisecretory effects of a new H2-receptor antagonist, cimetidine, in 200-, 300- or 400-mg doses, taken orally at bedtime. The 200-mg dose did not cause a statistically significant change in nocturnal (midnight to 7 a.m.) acid output and had only a borderline effect on pH. However, the 300-mg and 400-mg doses significantly (P less than 0.001) lowered acid output and increased (P less than 0.01) intragastric pH. All doses caused substantial decreases in secretory volume output. After a 400-mg dose, half the patients remained anacidic for eight hours. Dose-related increases of drug blood levels were observed and correlated with the degree and duration of inhibition of acid output. Serum gastrin levels were unaffected. Cimetidine appears to be a potent inhibitor of nocturnal gastric secretion.     

Impaired proximal duodenal mucosal bicarbonate secretion in patients with duodenal ulcer

The defensive factors that prevent the human duodenal mucosa from acidic and peptic damage have not been fully evaluated. To determine whether duodenal mucosal bicarbonate production was altered in patients with inactive duodenal ulcer, we measured basal and acid-stimulated bicarbonate output from the duodenal bulb and the distal duodenum in healthy subjects and patients with inactive duodenal ulcer. As compared with 16 normal subjects, the 12 patients had significantly less mean (+/- SE) basal proximal duodenal mucosal bicarbonate secretion (185 +/- 13 vs. 107 +/- 18 mumol per centimeter per hour; P less than 0.001). Moreover, in response to a physiologic amount of hydrochloric acid (2 mmol per five minutes) instilled directly into the duodenal bulb, peak proximal duodenal bicarbonate output in the patients was 41 percent of the normal response (263 +/- 65 vs. 642 +/- 77 mumol per centimeter per hour; P less than 0.01). There was little overlap between groups. In contrast, bicarbonate outputs in the distal duodenum were similar in the two groups. We conclude that most patients with duodenal ulcer disease have decreased proximal duodenal mucosal bicarbonate production at rest, in response to hydrochloric acid, and in relation to peak gastric acid secretion. Impaired proximal duodenal mucosal bicarbonate secretion may be an important factor in the development and natural history of duodenal ulcer.     

Effect of mifentidine on peptone meal-stimulated gastric acid secretion and plasma gastrin levels in duodenal ulcer patients

Mifentidine is a new H₂-receptor antagonist with distinct characteristics of potency and long plasma half-life. The aim of this study was to evaluate the effects of mifentidine on peptone meal-stimulated gastric acid secretion. Nine duodenal ulcer patients in remission were enrolled in the study and given in double-blind and at random, on two different occasions, a single tablet of 10 or 20 mg mifentidine or placebo according to an incomplete balanced block design. Ninety min after ingestion of the drug, basal gastric secretion was collected for 30 min and volume, pH and acid output determined. Thereafter, the acid output following peptone meal-stimulation was measured for 2 h by a modified version of the intragastric titration method of Thompson and Swierczek. Plasma samples were collected for gastrin and mifentidine determinations. Basal acid output was strongly inhibited by both the low dose (–78%) and the high dose (–98%) (p<0.01). The peptone meal-stimulated acid output was reduced in a dose-dependent manner (–45% by 10 mg and –90% by 20 mg). The drug did not affect the fasting serum gastrin levels but increased, although not significantly, the gastrin response to food. The log of the area under the mifentidine plasma levels correlated linearly with total acid output (p<0.01).The results of this study indicate that mifentidine dose-dependently suppresses basal acid secretion and reduces peptone-stimulated gastric acid secretion in duodenal ulcer patients.This study was supported by a grant from Boehringer Ingelheim, Italy.     

Gastroduodenal incretory cells in duodenal ulcer with different levels of gastric secretion

Immunomorphological PAP method was used in 20 patients with duodenum ulcer and in 10 control individuals to study gastrin (G)-, somatostatin (D)- and calcitonin-gene-related peptide (CGRP) cells in biopsies of the stomach and duodenum. The gastrin and pepsinogen level in the blood, basal and acid production stimulated by pentagastrin were also studied. All patients are subdivided into two groups by their acid production: those with hypersecretion and those with normal secretion. The group with hypersecretion was not homogeneous: some patients had deficiency of D-cells (sometimes in combination with G-cell hyperplasia) and others had a relative and absolute decrease of the number of CGRP cells in combination with foci of parietal cells in pylorus. These patients showed a tendency to the hypergastrinemia and significant hyperpepsinogenemia I in the blood. Stomach hyperplasia in the duodenum, multiple duodenal ulcers, erosive gastroduodenitis and ulcers in close relatives occurred more frequently in these patients. G- and CGRP cells are found to be similar in the form and localization. It is not excluded that G-cell contains, apart from gastrin 1-17, calcitonin-gene related peptide.     

Inhibition of gastric acid secretion in the dog by the histamine H2-receptor antagonists ranitidine and cimetidine

The H₂-receptor antagonists ranitidine and cimetidine inhibit gastric acid secretion elicited by a test meal in the dog. Ranitidine is approximately 10 times more potent than cimetidine in this respect.     

Impaired histamine binding by gastric juice of patients with duodenal ulcer

Histamine binding by gastric juice from 32 patients with duodenal ulcer and 22 control subjects was tested in vitro. The patients had substantially decreased histamine binding both in basal output as well as in pentagastrin stimulated output. The authors suggest that this phenomenon is involved in etiopathogenesis of chronic ulcer disease.     

Helicobacter-associated duodenitis and gastric metaplasia in duodenal ulcer patients.

Biopsy specimens were taken from the duodenal bulb and the distal duodenum in 45 duodenal ulcer patients before and after treatment with histamine-2 antagonists, prostaglandin analogues or antacids. After four weeks of treatment, the ulcer had healed in 31 patients. The treatment did not lead to a reduced frequency of helicobacter-associated duodenitis or gastric metaplasia of the duodenal epithelium. We found gastric metaplasia in 52.3% of all biopsy specimens from the duodenal bulb, chronic active duodenitis in 71.9% and helicobacter-like structures in 15.9%. The helicobacter organisms were found only in areas of gastric metaplasia, and an accompanying chronic active duodenitis was found in 94.1%. In the distal duodenum, we observed chronic active duodenitis in 15.0% of the specimens. Here the inflammation was not associated with gastric metaplasia or helicobacter-like structures. These observations support the hypothesis that Helicobacter pylori colonizes the duodenal mucosa only in areas of gastric metaplasia, and that such colonization may lead to an active duodenitis.     

The effect of cimetidine treatment on suppressor T cells in duodenal ulcer patients

Changes in the suppressor T-lymphocyte activity were studied in 11 patients with duodenal ulcer during treatment with cimetidine. The drug was administered intravenously in a dose of 200 mg four times a day for a fortnight. Suppressor T-cell activity was determined by the Shou et al. method using two-stage culture before treatment, after 4 days of the treatment, just before drug withdrawal, and 2 days and 2 wk after the treatment. Suppressor T-cell activity significantly decreased soon after starting the treatment, remained low throughout the treatment, and rapidly and significantly increased following drug withdrawal.     

Phagocytic and bactericidal activities of neutrophils in duodenal ulcer patients during cimetidine treatment

Phagocytic and bactericidal activities of neutrophils relative to Staphylococcus aureus 209 P strain were studied in 16 duodenal ulcer patients who were intravenously administered cimetidine in doses of 4 X 200 mg for 8 days and in a group of untreated healthy subjects. The investigations were made before the treatment on the last day of cimetidine administration, and one week after drug withdrawal. The bactericidal activity of neutrophils was found to be higher in duodenal ulcer patients than in the healthy controls. Cimetidine does not have a significant effect on the phagocytic activity of neutrophils and it has a moderately inhibitory effect (p less than 0.05) on the bactericidal activity relative to the ingested intracellular bacteria. This shows that cimetidine may modify some of the neutrophil functions in duodenal ulcer patients.