Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial

BACKGROUND: Helicobacter pylori gastritis may progress to glandular atrophy and intestinal metaplasia, conditions that predispose to gastric cancer. Profound suppression of gastric acid is associated with increased severity of H pylori gastritis. This prospective randomised study aimed to investigate whether H pylori eradication can influence gastritis and its sequelae during long term omeprazole therapy for gastro-oesophageal reflux disease (GORD). METHODS: A total of 231 H pylori positive GORD patients who had been treated for > or =12 months with omeprazole maintenance therapy (OM) were randomised to either continuation of OM (OM only; n = 120) or OM plus a one week course of omeprazole, amoxycillin, and clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy sampling as well as symptom evaluation were performed at baseline and after one and two years. Gastritis was assessed according to the Sydney classification system for activity, inflammation, atrophy, intestinal metaplasia, and H pylori density. RESULTS: Corpus gastritis activity at entry was moderate or severe in 50% and 55% of the OM only and OM triple groups, respectively. In the OM triple group, H pylori was eradicated in 90 (88%) patients, and activity and inflammation decreased substantially in both the antrum and corpus (p<0.001, baseline v two years). Atrophic gastritis also improved in the corpus (p<0.001) but not in the antrum. In the 83 OM only patients with continuing infection, there was no change in antral and corpus gastritis activity or atrophy, but inflammation increased (p<0.01). H pylori eradication did not alter the dose of omeprazole required, or reflux symptoms. CONCLUSIONS: Most H pylori positive GORD patients have a corpus predominant pangastritis during omeprazole maintenance therapy. Eradication of H pylori eliminates gastric mucosal inflammation and induces regression of corpus glandular atrophy. H pylori eradication did not worsen reflux disease or lead to a need for increased omeprazole maintenance dose. We therefore recommend eradication of H pylori in GORD patients receiving long term acid suppression

Effect of cimetidine, ranitidine, famotidine and omeprazole on hepatocyte proliferation in vitro

Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 70% partial hepatectomy and result in an increased mortality following this procedure. The present study was designed to determine whether three H2 blocking agents (cimetidine, ranitidine, famotidine) and a new, powerful antisecretory drug (omeprazole) specifically influence hepatocyte proliferation in primary culture. Hepatocytes were isolated from livers of normal male rats by the standard collagenase perfusion technique. Hepatic DNA synthesis and percent of labelled nuclei were determined after 48 h incubation. Hepatocytes in culture were incubated with the H2 blocking agents and omeprazole or with different concentrations of serum obtained from shamoperated or 70% hepatectomized rats treated or not with the same agents. Rats were injected intraperitoneally at 8:00 a.m. on two consecutive days. In hepatectomized rats, the first dose was injected at 8:00 a.m. immediately after surgery, the second, 24 h later. The serum of sham-operated or 70% hepatectomized rats that did not receive drugs served as control. No changes in DNA synthesis, percentage of labelled nuclei and transaminase were detected when the agents were added to the hepatocytes in culture at concentrations within the effective pharmacological dosage and 30 times higher. Similarly, no changes in these parameters were obtained when different concentrations of serum obtained from sham-operated rats treated with H2 blocking agents or omeprazole were added to the basal culture medium. However, a significant inhibition of DNA synthesis and of percentage of labelled nuclei was observed when hepatocytes were incubated in the presence of serum from 70% hepatectomized rats that had been treated with cimetidine or with ranitidine. The serum of 70% hepatectomized rats treated with famotidine and omeprazole had no effect on hepatocyte proliferation in vitro. No effect on transaminase was found in these conditions. © 1989

Omeprazole and Ranitidine in the Prevention of Relapse in Patients with Duodenal Ulcer Disease

BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse

Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials

BACKGROUND: Gastric ulcers are a frequent problem in the United States. Proton pump inhibitors have been shown to increase healing rates and improve clinical symptoms. The objective of this study is to compare gastric ulcer healing rates for patients treated with a proton pump inhibitor (PPI) (omeprazole, rabeprazole, pantoprazole, or lansoprazole), an histamine 2- receptor antagonist (ranitidine) or placebo. METHODS: A literature search was conducted to identify randomized, controlled clinical trials that included a PPI in at least one treatment arm and assessed the gastric ulcer healing rates endoscopically. The healing rates were estimated for each treatment at specific time points, and Rate Ratios (RR) and 95% confidence intervals (CI) were estimated for each trial. RESULTS: Sixteen trials met the inclusion criteria: four compared a PPI versus placebo, nine compared a PPI versus ranitidine (no trials of rabeprazole versus ranitidine met the inclusion criteria), and three compared a newer PPI (lansoprazole, pantoprazole or rabeprazole) versus omeprazole. In relation to ranitidine, the pooled RR of PPIs (lansoprazole, omeprazole and pantoprazole) was 1.33 (95% CI 1.24 to 1.42) at four weeks. In each trial, greater improvement in the studied clinical symptoms was found with the newer PPIs (rabeprazole, pantoprazole and lansoprazole) when compared to omeprazole. CONCLUSION: In this study treatment with PPIs resulted in higher healing rates than ranitidine or placebo. This evidence suggests that the first choice for gastric ulcer treatment for the greater relief of symptoms is one of the newer PPIs

Omeprazole ameliorates aspirin-induced gastroduodenal injury

Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) damage the gastroduodenal epithelium by two mechanisms: direct toxic effects and effects related to the depletion of endogenous prostaglandins. The prostaglandin-depleted mucosa has increased suceptibility to luminal aggressive factors, yet the role of acid in the pathogenesis of the NSAID ulcer is controversial. In humans, standard doses of H 2 -receptor antagonists prevent only duodenal injury and provide no protection for the gastric mucosa. It is not known whether more potent suppression of acid can prevent NSAID damage. Twenty healthy volunteers were randomized to a double-blind, placebo-controlled, crossover study to determine if omeprazole, 40 mg/day prevents gastroduodenal injury due to two weeks of aspirin administration (650 mg four times a day). The severity of mucosal injury was quantitated by endoscopy and stratified by a scale from 0 (normal) to 4 (ulcer). Fourteen of the 20 subjects had less gastric injury during cotherapy with omeprazole. All six with no difference received aspirin plus omeprazole in the first treatment period. Omeprazole significantly decreased aspirin-induced gastric mucosal injury ( P <0.001, Wilcoxon signed-rank test). Omeprazole protected 85% of subjects from extensive gastric erosions (often associated with evidence of intraluminal bleeding) or ulceration, whereas 70% of the subjects developed aspirin-induced grades 3 and 4 gastric injury on placebo ( P <0.01 by X 2 ). No subject taking omeprazole developed duodenal injury of any grade, while 50% taking placebo developed erosions and 15% had ulcer ( P <0.001). Medication side effects were mild in the majority of subjects. Heartburn occurred in seven subjects on aspirin and placebo vs one on aspirin and omeprazole ( P <0.01). Salicylate levels were 7.39±4.72 mg/dl (535±340 µmol/liter) in the placebo group and 6.95±4.3 mg/dl (503±311 µmol/liter) in the omeprazole group. We conclude that omeprazole, 40 mg/day eliminates duodenal injury and markedly ameliorates gastric injury due to administration of aspirin 2600 mg/day. Omeprazole prophylaxis of NSAID injury deserves further study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44420/1/10620_2005_Article_BF02090067.pd