Background-Omeprazole has a greater intragastric pH elevating eVect in Helicobacter pylori positive than negative subjects. Ammonia production by H pylori has been suggested as a probable mechanism. Aims-To assess the eVect of H pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole eYcacy in infected subjects. Methods-Twenty H pylori positive and 12 H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured. Results-Prior to omeprazole, measurements were similar in the H pylori positive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pylori positive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for each). This eVect was not explained by neutralisation by ammonia. Conclusion-The presence of H pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The eVect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained. (Gut 1999;44:468-475)

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylon infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/ minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmoVI (range 0.3-1.6) to and this resulted in an increase in the ammonium concentration from 2-3 mmol/l (range 1.3-5.9) to 6*1 mmoil/ (range 4.2-11.9) (p<001). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p<005). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0 4 mmolIl (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.

The mechanism of the hypergastrinaemia associated with Helicobacterpylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We In an attempt to elucidate the mechanism of the hypergastrinaemia associated with H pylori infection, we have examined the effect of inhibiting the bacterium's urease activity and ammonia production on serum gastrin in duodenal ulcer patients. Patients and methods STUDIES IN PATIENTS WITH H PYLORI INFECTIONSix patients confirmed endoscopically to have duodenal ulceration within the previous year but currently in clinical remission were studied. Their median age was 39 years (range 26-52) and three were women. In each patient, an antral biopsy specimen obtained endoscopically within the preceding three months had shown gastritis associated with H pylori like organisms.The patients reported fasted and a venous blood sample was removed at 8 am for gastrin determination. Immediately after this they drank 50 ml water and further blood samples were taken at 30 minute intervals for two hours. At 10 am they took a standard meal consisting of two beef cubes (OXO Ltd, Croydon, England) dissolved in 200 ml water at 50°C. Further blood samples were taken at 10 minute intervals for 70 minutes and a final one at 90 minutes after the OXO drink. Immediately after this sample a "C urea breath test was performed to measure H pyloni urease activity. For this they drank 250 ml Ensure Plus (Abbott Laboratories, England) to delay gastric emptying, followed by 0 4 MBq 14C urea (Amersham International) in 25 ml water. Breath samples for 14C-Co2 analysis were obtained at 10 minute irtervals for 90 minutes.