Gastro-oesophageal reflux disease (GORD) results from an abnormally prolonged dwell time of acidic gastric contents in the oesophagus. Although GORD is primarily a motor disorder, the injurious effects of gastric acid are central to the pathogenic process of oesophagitis, and the severity of disease correlates with the degree and duration of oesophageal acid exposure. In the majority of patients with mild disease, oesophageal acid exposure occurs predominantly during post-prandial periods. Conventional doses of H²-receptor antagonists cannot overcome the integrated stimulus to acid secretion resulting from a meal, and are thus relatively ineffective in preventing daytime, post-prandial oesophageal acid exposure. In patients with more severe grades of oesophagitis, there are abnormally high levels of nocturnal acid exposure, with the intra-oesophageal pH being less than 4.0 for 36% of the time, compared with 5% of the time in patients with mild GORD. Control of nocturnal acid secretion thus becomes increasingly important. This may be made worse by relative gastric acid hypersecretion in some patients with severe GORD. The long duration of action and effective inhibition of meal-stimulated acid secretion probably explains the superiority of omeprazole in treating GORD. Preliminary meta-analysis shows that the healing rate of erosive oesophagitis at 8 weeks by antisecretory agents is directly related to the duration of suppression of gastric acid secretion achieved over a 24-hour period (r = 0.87; p < 0.05).

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We examined mucosal injury in the jejunum of the rat during infection with the nematode parasite, Nippostrongylus brasiliensis (Nb). Injury was documented morphologically (increase in crypt length with or without villus atrophy) and biochemically (activities of digestive or proliferative enzymes) and related to mast cell activation and leukotriene generation. At day 4 crypt length and thymidine kinase activity were increased; no changes in villus parameters were recorded. No evidence of mast cell activation was found and leukotriene levels in the mucosa were normal. At day 7, the gut was acutely inflamed and edema was present at the tips of the villi. This progressed to enterocyte detachment, resulting in villus atrophy with decreased activities of brush border enzymes. At this stage mucosal histamine was decreased and rat mast cell protease II (RMCP II) was increased in serum, indicating mast cell activation. In addition, mucosal leukotrienes (LTB4, LTC4, LTE4) were present in significant quantities. Following worm expulsion, the villus abnormalities resolved and serum RMCP II returned to normal. However, the crypt hyperplasia persisted. Our results suggest that during Nb infection at least two components of injury can be identified. One component, epithelial injury at the villus tips, may be related to activation of mucosal mast cells.

Howden CW, Burget DW, Hunt RH. Appropriate acid suppression for optimal healing of duodenal ulcer and gastro-oesophageal reflux disease. Scand J Gastroenterol 1994;29 Suppl 201:79-82. Comparisons of the effectiveness of treatments for healing duodenal ulcer are essential to determine optimal management strategies for both economic analysis and quality-of-life evaluation. Differences are usually made on the basis of the proportion of ulcers healed at varying time intervals. It has been shown by meta-analysis that healing of duodenal ulcers with antisecretory drugs is directly correlated to the degree of acid suppression. More recently, sophisticated meta-analysis of 24-hour intragastric acidity data and clinical trials of antisecretory drugs has demonstrated that the optimal degree and duration of gastric acid suppression for healing duodenal ulcer can be achieved by an aggregate time above pH 3 of 18-20 hourdday. These conditions predict 100% ulcer healing at 4 weeks. Antisecretory drug regimens that approach these criteria should achieve faster healing than other agents, with a concomitant acceleration of symptom resolution. Regression analysis was performed on the healing-time curves for each drug class to determine the rate of ulcer healing per week. The mean proportion of ulcers healed, irrespective of treatment duration, was highest for omeprazole, which also provided a significantly faster rate of duodenal ulcer healing than all other drug classes (p < 0.001). It has recently been shown that healing of erosive oesophagitis with antisecretory drugs is directly correlated with both the duration of acid suppression over the 24-hour period (p < 0.05) and the elevation of intra-oesophageal pH above 4. Furthermore, oesophageal acid exposure time can be normalized by maintaining the intra-oesophageal pH above 4 for at least 96% of the 24-hour period. Such conditions might be expected to accelerate the healing of oesophagitis. Omeprazole showed significantly faster healing, as a proportion of patients healed per week, than placebo and all other drugs classes (p < 0.005). Alleviation of heartburn was also shown to be more rapid than with other treatments. There are, therefore, potential economic advantages to the use of omeprazole. Scand J Gastroenterol Downloaded from informahealthcare.com by McMaster University on 11/26/14 For personal use only.