Basal Acid Hypersecretion Research Articles

Rebamipide Contributes to Reducing Adverse Effects of Long-Term Administration of Omeprazole in Rats

Proton pump inhibitors (PPIs) have become of great importance for the treatment of peptic ulcer disease and gastroesophageal reflux disease. However, these drugs have several adverse effects, including worsening of corpus atrophic gastritis in patients with H. pylori infection, various histological changes including fundic gland-type polyps, inhibition of glycoprotein production, and hypergastrinemia. On the other hand, it has been reported that rebamipide, a gastroprotective drug, has the potential to increase mucous secretion and basically regulate physiological defensive functions aimed to maintain tissue integrity. In this study, we attempted to clarify whether rebamipide improves morphological changes and hypergastrinemia after administration of omeprazole (OPZ) for 1 year in rats. Eight-week-old male Wistar rats were used. Rats were divided into four groups according to diet as follows: 100 mg/kg body weight OPZ group, 100 mg/kg body weight OPZ and 30 mg/kg body weight rebamipide (OPZ + trebanipide group), 30 mg/kg body weight rebamipide, and normal diet (CRF-1). Morphological changes in gastric mucosa in all groups were studied using hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemical staining for alpha-amylase. Serum gastrin level and basal acid secretion were also examined. In the OPZ group, cystic degenerations with amorphous eosinophilic contents, decreased mucous secretion, decreased chief cells, and development of pancreatic acinar cell metaplasia were detected. However, in the OPZ+rebamipide group, these morphological changes were significantly milder than in the OPZ group. Serum gastrin level and basal acid secretion in the OPZ group increased significantly compared to those in the control group. But these factors in the OPZ+rebamipide group were almost normalized (similar to those of control animals). In conclusion, long-term OPZ treatment causes various morphological changes, hypergastrinemia, and basal acid hypersecretion. The present results suggest that rebamipide contributes to reducing these adverse effects caused by long-term OPZ treatment in rats.

Helicobacter pylori in peptic ulcer: have Koch's postulates been fulfilled?

This brief review considers whether or not Koch's postulates have been fulfilled for Helicobacter pylori and peptic ulceration. The histological features of peptic ulcer disease in man are active chronic gastritis with antral predominance, duodenal gastric metaplasia and active duodenitis. Other features are hyperpepsinogenaemia, relative postprandial hypergastrinaemia and basal acid hypersecretion. The macroscopic features are duodenal bulb ulceration or lesser curve and antral gastric ulceration. At present, gastric colonization with H. pylori has been produced in small animal species (rats and mice), but the infection is difficult to establish in immunocompetent animals, and histological gastritis is unconvincing. In larger animals the germ-free pig has been the most reliable model but the gastritis tends to be chronic with little activity. The best examples of acute infection are in three 'self-administration' experiments in humans. In these cases acute gastritis with hypochlorhydria developed which, when it converted to active chronic gastritis, tended to be asymptomatic. Either the circumstances were incompatible with ulceration, or the experiments were not continued for the many years necessary to develop peptic ulceration. It is concluded that only one of the many steps required for the development of peptic ulceration has so far been fulfilled, i.e. the ability of H. pylori to produce histological gastritis in a susceptible host.

Zollinger-Ellison syndrome and antral G-cell hyperfunction in patients with resistant duodenal ulcer disease.

We measured basal and pentagastrin-stimulated acid secretion, as well as basal and meal-stimulated plasma gastrin concentration to determine, in 67 patients affected by resistant duodenal ulcer, whether their condition could be related to gastric acid secretion and/or gastrin-related syndromes. We then compared them to 46 duodenal ulcer control patients. The outpatients were investigated consecutively. The resistant duodenal ulcer patients differed from the controls only in their higher complication rates (bleeding or perforation, P < 0.05). We identified five patients in the resistant duodenal ulcer group with Zollinger-Ellison syndrome and 12 with antral G cell hyperfunction, whereas in the control group only one patient was affected by antral G cell hyperfunction. IgG anti-Helicobacter pylori antibodies were positive for the presence of infection in 7 of the hypergastrinaemic patients. When Zollinger-Ellison syndrome or antral G cell hyperfunction were excluded, no differences could be found in gastric acid secretion, or basal and meal-stimulated plasma gastrin levels, between the resistant and control duodenal ulcer patients, except for basal acid hypersecretion (resistant duodenal ulcer 16% vs duodenal ulcer 2% P = 0.0144). In the presence of duodenal ulcer disease resistant to H2-blockers, it is mandatory to measure basal plasma gastrin concentration since it was possible to diagnose the gastrin-related syndromes, Zollinger-Ellison syndrome and antral G cell hyperfunction, in 26% of this group of patients.

Gastric acid response to modified sham feeding in patients with duodenal ulcer: Is increased vagal tone the cause of basal acid hypersecretion?

In order to test the hypothesis that increased basal vagal tone causes basal acid hypersecretion in duodenal ulcer (DU), the effect of sham feeding on gastric acid secretion was studied in 26 patients with DU and 20 healthy controls. Basal acid output (BAO), sham feeding-stimulated acid output (SAO) and peak histamine-stimulated acid output (PAO) were significantly higher in DU patients compared with healthy controls (P less than 0.01). The BAO/PAO ratio in DU patients (0.28 +/- 0.03) was not significantly different from that of healthy subjects (0.19 +/- 0.03), indicating that the higher BAO in DU patients group, as a whole, was due to a higher parietal cell mass. The basal subtracted response to sham feeding expressed as a fraction of secretory capacity [(SAO-BAO)/PAO], which correlates inversely with the basal vagal tone, was not significantly different in the patients and control subjects (0.27 +/- 0.03 versus 0.3 +/- 0.03; P greater than 0.05). Based on the data from the healthy controls, a ratio of BAO/PAO greater than 0.44 was defined as abnormal (using 95% confidence limits) and it indicated marked basal acid hypersecretion. Four of 26 DU patients had basal acid hypersecretion (that is, BAO/PAO greater than 0.44), but only two of them did not show an increase over their basal rate of secretion in response to sham feeding. All other DU patients, including two with marked basal acid hypersecretion, and all healthy controls showed an appreciable increase in their acid secretion in response to sham feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Marked Basal Gastric Acid Hypersecretion and Peptic Ulcer Disease

SummaryThree children with peptic ulcer disease had recurrent symptoms unresponsive to cimetidine or ranitidine therapy alone. Acid secretory studies showed a marked basal acid hypersecretion, which was atropinesensitive in two of three patients and was best suppressed by ranitidine in combination with an anticholinergic drug. Marked reduction in acid output following intravenous atropine suggested that the hypersecretion was under vagal, muscarinic control. However, in one patient, large doses of the selective m1‐muscarinic antagonist pirenzepine were ineffective in suppressing basal acid hypersecretion. Given the efficacy and safety of drug therapy used in these children over a 3‐year period, we conclude that medical management is an effective alternative to surgery for pediatric patients with refractory or recurrent peptic ulcer disease.

Gastric Acid Hypersecretion in Short Bowel Syndrome in Infants

Summary:To determine the frequency of gastric acid hypersecretion in infants with chronic malabsorption due to short bowel syndrome, acid secretory function was determined in 23 infants with malabsorption 2‐22 months following small bowel resection and in a control group of 14 chronically ill, age‐ and weight‐matched infants who did not undergo bowel resection. The prevalence of basal acid hypersecretion (defined as acid output 2 SD above the mean for the control group) was 17% (4 of 23). Basal gastric acid hypersecretion was associated with two factors: massive small bowel resection and initiation of enteral feeding. Basal acid hypersecretion was present on the initial study in 3 of 7 infants with less than one‐third of the small bowel remaining, but in only 1 of 16 with more than one‐third intact (p &lt; 0.05). Hypergastrinemia was present in 3 of 6 infants following massive bowel resection, but in only 1 of 15 with more than one‐third intact (p &lt; 0.05), but hypergastrinemia was not consistently associated with hypersecretion. In each of six previously unfed infants, a trial of enteral feeding resulted in increased basal and maximal acid output. Three infants developed basal acid hypersecretion during initiation of enteral feeding. There was no evidence of pentagastrin‐stimulated maximal acid hypersecretion in any of the infants.

Gastric Acid Hypersecretion in Short Bowel Syndrome in Infants

Summary: To determine the frequency of gastric acid hypersecretion in infants with chronic malabsorption due to short bowel syndrome, acid secretory function was determined in 23 infants with malabsorption 2-22 months following small bowel resection and in a control group of 14 chronically ill, age- and weight-matched infants who did not undergo bowel resection. The prevalence of basal acid hypersecretion (defined as acid output 2 SD above the mean for the control group) was 17% (4 of 23). Basal gastric acid hypersecretion was associated with two factors: massive small bowel resection and initiation of enteral feeding. Basal acid hypersecretion was present on the initial study in 3 of 7 infants with less than one-third of the small bowel remaining, but in only 1 of 16 with more than one-third intact (p < 0.05). Hypergastrinemia was present in 3 of 6 infants following massive bowel resection, but in only 1 of 15 with more than one-third intact (p < 0.05), but hypergastrinemia was not consistently associated with hypersecretion. In each of six previously unfed infants, a trial of enteral feeding resulted in increased basal and maximal acid output. Three infants developed basal acid hypersecretion during initiation of enteral feeding. There was no evidence of pentagastrin-stimulated maximal acid hypersecretion in any of the infants.

Gastric Acid Hypersecretion in Short Bowel Syndrome in Infants

To determine the frequency of gastric acid hypersecretion in infants with chronic malabsorption due to short bowel syndrome, acid secretory function was determined in 23 infants with malabsorption 2-22 months following small bowel resection and in a control group of 14 chronically ill, age- and weight-matched infants who did not undergo bowel resection. The prevalence of basal acid hypersecretion (defined as acid output 2 SD above the mean for the control group) was 17% (4 of 23). Basal gastric acid hypersecretion was associated with two factors: massive small bowel resection and initiation of enteral feeding. Basal acid hypersecretion was present on the initial study in 3 of 7 infants with less than one-third of the small bowel remaining, but in only 1 of 16 with more than one-third intact (p less than 0.05). Hypergastrinemia was present in 3 of 6 infants following massive bowel resection, but in only 1 of 15 with more than one-third intact (p less than 0.05), but hypergastrinemia was not consistently associated with hypersecretion. In each of six previously unfed infants, a trial of enteral feeding resulted in increased basal and maximal acid output. Three infants developed basal acid hypersecretion during initiation of enteral feeding. There was no evidence of pentagastrin-stimulated maximal acid hypersecretion in any of the infants.

Duodenal ulcer with unexplained marked basal gastric acid hypersecretion

Out of 1012 gastric analyses performed in 6 yr, 40 persons had basal acid output ≥ 15 mmol/hr. Of these, 8 had known causes for hypersecretion (6 had Zollinger-Ellison syndrome and 2 systemic mastocytosis); 1 died before further study, leaving 31 with unexplained basal acid hypersecretion (19.5 ± 0.60 mmol/hr) and peptic ulcer (30 duodenal ulcer and 1 gastric ulcer). All were male compared with the 72:28 M : F ratio in the duodenal ulcer population from which these were drawn. From among the same 1012 patients 29 male controls with duodenal ulcer and basal acid output < 6 mmol/hr (2.7 ± 0.31 mmol/hr) were matched for age, sex, and length of follow-up (3–81 mo). The hypersecretion group had higher fasting residual volume (154 ± 14 vs. 76 ± 8 ml, P < 0.01) and peak acid output (53 ± 3 vs. 33 ± 3 mmol/hr, P < 0.01). In 17 of the 31 subjects repeat testing of basal secretion (r = 0.64) was not significantly different (P > 0.1). In controls basal acid output was related to body weight (r = 0.65) but in the hypersecretors it was not (r = 0.11). In the hypersecretors, however, basal acid output was related to length of ulcer history (r = 0.71), but in the controls it was not (r = 0.06). A significant cholinergic contribution to the hypersecretion was inferred from >90% reduction by either atropine (15 μg/kg) or vagotomy in all 12 of the 31 hypersecretion subjects who were so studied. The clinical course of the two groups was not different as regards number of hospitalizations, episodes of bleeding, number of operations, number of perforations or obstruction, and the same proportion (9/31 vs. 8/29) remained free of complications during the average 12.5-yr period of total ulcer history. The finding of massive basal acid hypersecretion does not necessarily imply a Zollinger-Ellison syndrome nor call for unusually extensive surgery for peptic ulcer, vagotomy being sufficient to correct the hypersecretion.

Effect of vagotomy in Zollinger-Ellison syndrome

We evaluated the effect of vagotomy on gastric acid secretion and the clinical course in 3 patients with Zollinger-Ellison syndrome. Basal acid hypersecretion was reduced by 49, 86, and 96%, and peak acid output in response to pentagastrin was reduced by 36, 39, and 71% in the 3 patients. In one patient, 300 mg cimetidine reduced basal acid secretion from 65 to 20 meq/hr before vagotomy; whereas after vagotomy basal acid secretion was reduced from 36 to 0.6 meq/hr by the same dose of cimetidine. One patient has required no antisecretory therapy for 14 yr, whereas 2 patients have also been treated with cimetidine with excellent results. We conclude that vagotomy facilitates control of acid secretion in Zollinger-Ellison syndrome, and we recommend vagotomy and cimetidine rather than total gastrectomy or cimetidine alone for the management of these patients. This combined surgical and medical approach should also allow discovery and removal of isolated tumors in about 10% of patients.

Zollinger-Ellison Syndrome: Provocative Diagnostic Tests

Excerpt Features of the Zollinger-Ellison syndrome (gastrinoma) include peptic ulcer disease, basal acid hypersecretion, and fasting hypergastrinemia. Its diagnosis is strongly supported by a serum...

Reversible basal gastric hypersecretion with parathyroid adenomas and duodenal ulcer.

Summary: Profound hypersecretion of gastric acid, basally, was detected in a duodenal ulcer patient with familial primary hyperparathyroidism. Repeated fasting serum gastrin estimations were normal. Following surgical treatment of the hyperparathyroidism, there was a sustained fall in basal acid output from 34 to 4.5 mEq per hour. Two years later, an infusion of calcium intravenously re-produced dramatic gastric acid hyper-secretion, up to 64 mEq per hour, confirming the extreme hypersensitivity to mild hypercalcaemia. The infusion also provoked a rise in serum gastrin levels. This study has demonstrated that pronounced basal acid hypersecretion with ulcer may occur in hyperparathyroidism in the absence of the Zollinger-Ellison syndrome. Thus, parathyroid adenomas do sometimes influence gastric secretion like a gastrin-producing tumour, or a retained excluded gastric antrum. This exaggerated response may be mediated by rises in serum gastrin, stimulated by calcium.