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).

No abstract

No abstract

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.

SUMMARY Although omeprazole has a long duration of action and has usually been given in the morning, there are theoretical advantages in administering antisecretory drugs in the evening as has been shown for the H2‐receptor antagonists. The aim of this study was to compare the effects of placebo and 20 mg omeprazole given either in the morning or evening, on gastric acidity, plasma gastrin levels and plasma omeprazole in 6 duodenal ulcer patients. The 24‐hour mean pH (± S.E.M.) was: placebo 1.7 ± 0.1; morning doing, 3.9 ± 1.8 (P < 0.01); evening dosing, 2.9 ± 1.1 (N.S.). There was a large inter‐individual variability of intragastric acidity in response to omeprazole, which was reflected both in the plasma gastrin and in the area under the plasma omeprazole concentration–time curve. Morning administration of omeprazole is optimal, but variability in the patient response to 20 mg omeprazole is still seen.

SUMMARY The effects of a specific H2 receptor agonist impromidine, on gastric acid secretion were measured in six patients with duodenal ulcer in clinical remission before and after three months treatment with ranitidine 150 mg nocte. After treatment basal acid output increased from 1 2 to 2-8 mmol/h and after maximal impromidine stimulation from 36-9 (4 7) to 44-2 (6 2) mmol/h (p<002). Intravenous ranitidine 50 mg was given at the end of the impromidine infusion on each study day; the antisecretory effect of intravenous ranitidine was accentuated after the treatment with ranitidine from a trough acid output of 8 5 (1-2) mmol/h before, to 3-8 (1-5) mmol/h (p<0 05) after, treatment. The increased response to the H2 agonist impromidine and the H2 antagonist ranitidine after treatment with ranitidine suggests an enhanced sensitivity of the H2 receptor. This might be explained on the basis of an increase in the number of H2 receptors ('up-regulation'). a highly potent, and specific agonist for the H2 receptor' exhibiting up to 27 times the affinity of histamine.9 In this study we have examined the effect of three months of treatment with ranitidine 150 mg nocte on impromidine stimulated gastric acid secretion in six patients with duodenal ulcer in remission.

de Gara CJ, Burget DW, Sivakumaran T, Hunt RH. The effect of temperature and pH on the stability of human pepsin in stored gastric juice. A method to prevent activity loss. Scand J Gastroenterol 1986, 21, 650-654The mechanisms controlling pepsin secretion are controversial. A contributory factor may be storage-dependent effects. We have studied the effects of temperature, pH, and storage time on human gastric pepsin. Gastric juice samples taken from three healthy volunteers under both basal and post-pentagastrin-stimulated (6 pg/kg subcutaneously) conditions were separated into four aliquots. Each aliquot was titrated to pH 1,4, or 6 or left at ambient pH. Aliquots were then stored at 4°C or frozen at -70°C and stored. On days 1, 3, 7, and 28 aliquots were removed and assayed by the kinetic albumin-bromphenol blue method. In a second experiment we determined the effects of different concentrations of glycerol on the preservation of peptic activity. From these experiments we conclude that pepsin is unstable when stored frozen at low pH but not when stored above pH 2. This pH-dependent stability may explain the variable conclusions other workers report on optimal methods of storing gastric juice. In addition, we have confirmed the suitability of glycerol as a preservative of peptic activity and recommend that gastric juice be stored frozen with 11.5% glycerol.