Treatment of refractory peptic ulcer with omeprazole or continued H2 receptor antagonists: a controlled clinical trial.

We tested the hypothesis that the gastric H+/K+ adenosine triphosphatase inhibitor, omeprazole, because of its different mode of action and pronounced inhibitory effect on gastric acid secretion, may be more effective in peptic ulcer that is refractory to histamine H2 receptor antagonist treatment than continuing the same therapy. Altogether 107 patients (duodenal ulcer, n = 88; prepyloric ulcer, n = 14; gastric ulcer, n = 3; mixed sites, n = 2) with refractory peptic ulcer - that is ulcer unhealed after at least two months' treatment with cimetidine 0.8 g or 1 g daily or with ranitidine 0.3 g daily - were randomly allocated to receive either omeprazole 40 mg daily (n = 54) or to continue treatment with the same H2 receptor antagonist and at the same dose (n = 53) for up to eight weeks. The patients in the two treatment groups were well matched demographically. Healing by 'intent to treat' analysis was as follows: at four weeks, omeprazole 46 of 54 (85%), H2 receptor antagonist 18 of 53 (34%) (p less than 0.0001); and at eight weeks, 52 of 54 (96%) and 30 of 53 (57%) respectively (p less than 0.0001). One patient was lost to follow up but of the 22 patients whose ulcers were shown to be unhealed at endoscopy after receiving continued H2 receptor antagonist treatment, 21 healed in four to eight weeks when changed to omeprazole. Daytime epigastric pain cleared at four weeks in 43 of 47 (91%) patients on omeprazole and in 32 of 46 (70%) on H2 receptor antagonists (p=0.01) and relief of all dyspeptic symptoms occurred in 39 of 47 (83%) and 23 of 45 (51%) (p=0.0009) patients respectively. Adverse events occurred in 11 of 54 (20%) patients on omeprazole and in 12 of 35 (34%) on cimetidine but in none on ranitidine. The events were mild and none required treatment withdrawal. The commonest event in patients on omeprazole was loose stools or diarrhoea (n=5). Omeprazole was significantly better than continued H2 receptor antagonist treatment for the short term management of refractory peptic ulcer as judged by healing rate and pain relief, and it was safe.

Omeprazole in the treatment of erosive oesophagitis refractory to high dose cimetidine and ranitidine.

Forty five patients with refractory oesophagitis, defined as persisting erosive changes or ulceration despite a minimum of three months' treatment with cimetidine 3.2 g daily or ranitidine 0.9 g daily, were treated in an open trial with omeprazole 40 mg daily for up to eight weeks. Endoscopically defined healing was observed in 73% of patients after four weeks' treatment and in 91% after eight weeks' treatment. Symptoms were completely relieved in 60% of patients, improved in 34%, unchanged in 4%, and worsened in 2%. After healing patients returned to maintenance treatment with cimetidine 1.6-3.2 g daily, depending on the severity of their illness before treatment with omeprazole. By six months and 12 months only 55% and 33% of patients respectively were still in remission. This study suggests that when erosive oesophagitis is refractory to treatment with high dose cimetidine or ranitidine, treatment with omeprazole 40 mg daily for up to eight weeks is effective in inducing healing and relieving symptoms.

Double blind comparison of omeprazole (40 mg od) versus cimetidine (400 mg qd) in the treatment of symptomatic erosive reflux oesophagitis, assessed endoscopically, histologically and by 24 h pH monitoring.

This double blind, double dummy study compares the rate of healing of erosive reflux oesophagitis, assessed endoscopically, with four and eight weeks treatment using omeprazole or cimetidine, and the effect of four and eight weeks treatment of reflux oesophagitis with omeprazole or cimetidine on reflux symptoms, microscopic healing, and in a subgroup of patients, oesophageal pH measurements. Omeprazole 40 mg once daily achieves (i) greater and more rapid symptom relief, (ii) more rapid and sustained endoscopic and histological healing, and (iii) greater reduction of oesophageal acid exposure than cimetidine 400 mg four times daily.

Thin-film antimony-antimony-oxide enzyme electrode for penicillin determination.

A potentiometric penicillinase electrode is reported in which the base pH transducer is a thin-film antimony-antimony-oxide electrode deposited by vacuum evaporation. Several enzyme immobilization procedures have been examined and a crosslinked protein film found to be the most appropriate to this type of sensor. The use of an adjacent antimony-antimony-oxide track as a pseudoreference electrode was successfully demonstrated. The overall response was shown to be independent of the stirring rate above 100 rpm, but the kinetics of the response were found to depend markedly on the stirring rate. The intrinsic linear response range was 3 x 10(-4)M to 7 x 10(-3)M penicillin G. Linearizing transforms that extend the useful range were examined.

Misoprostol-induced increases in adherent gastric mucus thickness and luminal mucus output.

Gastroduodenal mucus can be separated into two phases: insoluble mucus gel adherent to the mucosal surface, and luminal mucus, which is removed by washing out the lumen. The adherent mucus gel is part of the mucosal protective barrier to acid and pepsin in the gastric juice. Luminal mucus, which is mobile, probably does not significantly protect against gastric juice, but functions as a lubricant, protecting the adherent mucus layer and underlying mucosa from mechanical damage. Adherent mucus is observed on the mucosal surface as a thin, continuous, gelatinous layer of variable thickness, about 50-450 microns (median, 180 microns) in man and 10-230 microns (median 80 microns) in the rat. Thickness of this adherent mucus layer in the rat stomach is increased significantly (up to threefold) following topical administration of misoprostol in vivo 1 hr before measurement. Simultaneous increases are observed in the content of luminal mucus following misoprostol administration. Seventy percent of maximum response is observed within 5 min of topical prostaglandin administration, compatible with the release of preformed mucus. Such prostaglandin-stimulated increases in mucus thickness will improve the protective capacity of the adherent mucus gel. The thickness of the adherent mucus layer is not changed following topical exposure, in vivo 1 hr before measurement, to exogenous mucosal-damaging agents (eg, ethanol, indomethacin and taurocholate. However, since such damaging agents permeate the mucus gel, it appears to offer little initial protection to the underlying epithelium. The mucus barrier primarily guards against the natural aggressors acid and pepsin, protecting the epithelium and its repair following acute mucosal damage.

Adherent and soluble mucus in the stomach and duodenum.

Gastroduodenal mucus is present as a water insoluble gel adherent to the mucosal surface and as a viscous mobile solution in the lumen. The protective properties of the mucus against acid (with bicarbonate), pepsin (diffusion barrier) and mechanical damage depend on the quality (structure) and quantity (thickness) of the adherent mucus gel layer. Adherent mucus is a viscoelastic gel which is 95% (v/v) water. It is permeable to ions and smaller molecules (Mr c. 1000), but is impermeable to large proteins (Mr c. 17,000) including pepsins. However, mucus is solubilized rapidly by pepsin, more slowly (greater than or equal to 1 h) by thiol agents, and is unchanged following exposure to bile, acid and ethanol (less than 40%). Glycoprotein macromolecules (Mr greater than or equal to 2 X 10(6] are the structural components of the mucus gel and have a polymeric structure of glycoprotein subunits (Mr c. 5 X 10(5), for gastric mucus) joined by disulphide bridges between their protein cores. This glycoprotein polymerization, which is essential for gel formation and hence function, is the site of action of proteolytic enzymes and thiol agents. The glycoprotein polymeric structure is deficient in antral mucus from patients with peptic ulcer disease. In vivo, adherent mucus forms a thin but continuous cover of variable thickness (50-450 micron in man, about two-fold less in rat) over the gastroduodenal mucosa. Pepsin in gastric juice will rapidly dissolve this mucus cover and can be active up to luminal pH values of 5.(ABSTRACT TRUNCATED AT 250 WORDS)