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In the past five years 12 patients have been identified presenting with chronic duodenal ulcer (DU) disease and with no evidence of current or recent Helicobacter pylori (H pylori) infection. Four of them were taking regular non-steroidal anti inflammatory agents, one was subsequently found to have Crohn's disease of the duodenum, and one to have the Zollinger-Ellison syndrome. The remaining six patients with idiopathic DU disease were remarkable for their absence of the A1 blood antigen gene. Detailed studies of gastric function were performed in these six patients and compared with H pylon positive patients with DU and with healthy volunteers. The median integrated gastrin response in the patients with idiopathic DU (2810 (range 750-8750) ng/l min) was similar to that of the H pylori positive patients with DU (3355 (550-8725)) and higher than that of the H pylon negative healthy volunteers (560 (225-1125)). The median peak acid output in the patients with idiopathic DU (37 mmol/h, range 17-52) was similar to that of the H pylon positive patients with DU (40 (15-57)) and higher than that ofthe non-ulcer controls (22 (16-29)). The median percentage of a liquid meal retained in the stomach at 60 minutes was less in the patients with idiopathic DU (23 (15-33)) than in Hpyloni negative healthy volunteers (34 (30-53) p<0-01). The median percentage of a solid meal retained at 60 minutes was less in the patients with idiopathic DU (54 (9-83)) than in either H pylon negative healthy volunteers (87 (49-95) p<001) or H pylon positive patients with DU (79 (51-100) p<0-01). In conclusion, three abnormalities of gastric function are prevalent in patients with H pylon negative idiopathic DU disease -hypergastrinaemia, increased acid secretion, and the one feature distinguishing them from H pylon positive patients with DU -rapid gastric emptying of both liquids and solids. Each of these abnormalities will increase the exposure of the duodenal mucosa to acid and thus explain its ulceration. The absence of the blood group A1 antigen gene is consistent with a genetic basis for the disturbed gastric function linked to the ABO blood group antigen genes. (Gut 1993; 34: 762-768) More than 95% of patients with chronic duo-

No abstract

Helicobacter pylon infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylon. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that >90% of the circulating gastrin consisted ofgastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmolIl (8-39) (p<0-05), entirely because of a fail in G17 from 6 pmol/l (<2.4-25) to <2-4 pmoil/ (<2.4-23) (p<0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmolll (38-114) to 33 pmol/ (19-88) (p<0 005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmolfl (<2-4-52) (p<0-001).The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmolll, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylon infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylon predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration ofgastrin in Hpylon infection is the result of an increase in one of the main biologically active forms of the hormone. (Gut 1993; 34: 757-761)

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.

Duodenal ulcer patients have increased serum pepsinogen I (PGI) concentrations and an increased prevalence of Helicobacter pylori infection. We have examined the effect of eradicating the infection on PGI. In 12 duodenal ulcer patients in whom H. pylori was successfully eradicated, the median basal PGI was 90 ng/ml (range, 37-252) before treatment and fell to 74 ng/ml (28-197) 1 month after treatment (p less than 0.01). In 12 patients in whom therapy failed to eradicate the infection, the PGI was 87 ng/ml (35-128) before treatment and remained unchanged at 83 ng/ml (36-119) 1 month after treatment. In the group with successful eradication the median basal plasma gastrin was 43 ng/l (15-95) before treatment and fell to 30 ng/l (17-75) 1 month after treatment (p less than 0.003), but there was no change in the corresponding values in the group without eradication (55 ng/l; range, 25-120, and 45 ng/l; range, 5-175; p = 0.9). In conclusion, eradication of H. pylori results in a fall in PGI and plasma gastrin, and these changes are not due merely to the anti-H. pylori drugs themselves or to discontinuation of previous ulcer therapy.

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their Hpylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0-8 mmol/I (0.5-2.9 mmol/l), which was lower than th9t in the uninfected subjects (2.1 mmolIl ,(1I0-3-7 mmol/l)) (p<0001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (10-13-0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p<0001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated -the ratios ranged from 0 04-0*7 (median 0.26) and from 1-1-113 (median 3.4) in infected and uninfected subjects respectively (p<0001