Symptomatic benefit 1-3 years after H. pylori eradication in ulcer patients: impact of gastroesophageal reflux disease.

OBJECTIVES: Eradication of Helicobacter pylori (H. pylori) infection markedly reduces the recurrence of duodenal and gastric ulcers. However, there is little information regarding its efficacy in resolving dyspeptic symptoms in ulcer patients. The primary aim of this study was to assess the effect of eradicating H. pylori infection on dyspeptic symptoms in ulcer patients. The secondary aim was to identify predictors of symptomatic response to H. pylori eradication. METHODS: A total of 97 dyspeptic patients with active duodenal and/or gastric ulceration associated with H. pylori infection and unrelated to NSAID use had the severity and character of their dyspeptic symptoms measured before and again 1-3 yr after H. pylori eradication therapy. RESULTS: Pretreatment, the median dyspepsia score was 12 (4-16). Posttreatment, 55% of those eradicated of H. pylori had resolution of dyspepsia (score <2) compared with 18% of those not eradicated of the infection (95% CI for difference, 11-62%). Of the ulcer patients 31% had symptoms and/or endoscopic evidence of coexisting gastroesophageal reflux disease (GERD) at initial presentation and this influenced the symptomatic response to eradication of H. pylori. Of the 22 patients with heartburn or acid reflux as the predominant presenting symptom, but no endoscopic esophagitis, only 27% experienced resolution of dyspepsia after H. pylori eradication, compared with 68% of the 59 without those as predominant symptoms (95% CI for difference, 18-63%). Only one of the five patients with coexisting endoscopic esophagitis at initial presentation experienced resolution of dyspepsia after H. pylori eradication. Symptomatic benefit was unrelated to time lapsed since the infection was eradicated. Only three of 50 subjects developed de novo GERD symptoms after eradication of H. pylori, whereas 21 of 36 subjects experienced resolution of GERD symptoms after eradication of the infection. CONCLUSIONS: A substantial proportion of ulcer patients have symptoms and/or signs of coexisting GERD at initial presentation and this reduces the symptomatic benefit from H. pylori eradication. However, we have found no evidence that eradicating H. pylori induces de novo GERD symptoms in ulcer patients.

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori.

BACKGROUND & AIMS: Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. METHODS: H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. RESULTS: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. CONCLUSIONS: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects.

Molecular forms of gastrin in the circulation of patients with achlorhydria.

BACKGROUND/AIM: To study circulating gastrin profile, both fasting and postprandially, in patients with achlorhydria due to auto-immune atrophic gastritis, comparing these with normal healthy controls. METHODS: Circulating gastrins were measured using three region-specific radio-immunoassays: amidated gastrins (R98), N-terminal G34 (R526) and N-terminal G17 (GP168). Samples were analysed further using gel chromatography. RESULTS: Fasting gastrin concentrations were elevated in achlorhydria as measured using all three antisera: median 714 pmol/l (range 107-5176) in achlorhydria versus 12 pmol/l (2-33) in controls (R98), 343 pmol/l (45-4316) versus 10 pmol/l (5-41) (R526), and 720 pmol/l (14-6000) versus 2 pmol/l (1-10) (GP168). In patients, 47% of gastrin was amidated (95% in controls) and 30% was processed N-terminally only to G71 (4% in controls). Gastrin rose significantly postprandially: 1643 pmol/l (269-7142) in patients versus 24 pmol/l (5-142) in controls (R98), 432 pmol/l (113-4756) versus 15 pmol/l (7-45) (R526) and 2189 pmol/l (304-7150) versus 15 pmol/l (7-45) (GP168). Only 25% was amidated in the patient group (93.5% in controls) and 21% remained as component I (4% in controls). CONCLUSIONS: This abnormal gastrin profile associated with hypergastrinaemia secondary to achlorhydria is consistent with saturation of the enzymes involved in the processing of the pro-hormone, in particular amidation of the C-terminus.

Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia.

BACKGROUND: The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers. The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known. METHODS: We performed a randomized, placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily, 500 mg of amoxicillin three times daily (with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin), and 400 mg of metronidazole three times daily (160 patients) with that of omeprazole alone (158 patients) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy. Symptoms were assessed with the Glasgow Dyspepsia Severity Score, with resolution of symptoms defined as a score of 0 or 1 in the preceding six months (maximal score, 20). One year later the patients were assessed to determine the frequency of the resolution of symptoms. RESULTS: One month after the completion of treatment, 132 of 150 patients (88 percent) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori, as compared with 7 of 152 (5 percent) in the group assigned to receive omeprazole alone. One year later, dyspepsia had resolved in 33 of 154 patients (21 percent) in the group given omeprazole and antibiotics, as compared with 11 of 154 (7 percent) in the group given omeprazole alone (95 percent confidence interval for the difference, 7 to 22 percent; P<0.001). Among the patients in the group given omeprazole and antibiotics, the symptoms resolved in 26 of the 98 patients (27 percent) who had had symptoms for five years or less, as compared with 7 of the 56 patients (12 percent) who had had symptoms for more than five years (P=0.03). CONCLUSIONS: In patients with H. pylori infection and nonulcer, or functional, dyspepsia, treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone.

Current or recent proton pump inhibitor therapy markedly impairs the accuracy of the [14C]urea breath test.

BACKGROUND: There are increasing indications for assessing Helicobacter pylori status by non-invasive means in dyspeptic patients. There is also increasing use of proton pump inhibitor therapy for dyspeptic disease. AIMS: To determine the effect of proton pump inhibitor therapy on the accuracy of the [14C]urea breath test. PATIENTS: [14C]Urea breath tests were performed in 20 H. pylori-positive and 13 H. pylori-negative dyspeptic patients before commencing omeprazole and after 4 weeks of treatment with 40 mg/day and then 6 months of treatment with 20 mg/day. Further studies were done in H. pylori-positive patients to examine the time course of the onset and resolution of the effect observed. RESULTS: False negative results occurred in 45% of the H. pylori-positive subjects after 4 weeks of omeprazole 40 mg/day and in 28% after 6 months of 20 mg/day. False positive results occurred in 15% of the H. pylori-negative subjects after 4 weeks of omeprazole 40 mg/day. In the H. pylori-positive subjects time course studies showed increasing suppression of the breath test result over the first 2-4 weeks of treatment. It took a similar time for the breath test result to recover after stopping treatment. There was no significant change in H. pylori IgG serology in the H. pylori-positive patients after 7 months of omeprazole treatment. CONCLUSIONS: Proton pump inhibitor therapy markedly impairs the accuracy of the [14C]urea breath test and, in particular, produces a high proportion of false negative results. The effect is dose related and may persist for 2-4 weeks after stopping therapy. Patients should be carefully questioned about recent proton pump inhibitor therapy before accepting a negative breath test result as reliable.

Assessment of symptomatic response as predictor of Helicobacter pylori status following eradication therapy in patients with ulcer.

BACKGROUND: Helicobacter pylori eradication therapy is routinely used for treating patients with peptic ulcer disease. AIMS: To assess the value of symptomatic response to H pylori eradication therapy as a marker of post-treatment H pylori status. PATIENTS AND METHODS: One hundred and nine dyspeptic patients with active duodenal or gastric ulceration association with H pylori infection had their symptoms measured by a validated questionnaire before and three months following H pylori eradication therapy. The symptomatic response was compared with post-treatment H pylori status as determined by the 14C urea breath test. RESULTS: An eradication rate of 84% was achieved. Of the 92 patients eradicated of H pylori, 47% experienced complete or near complete resolution of dyspepsia. Of the 17 patients in whom the infection was not eradicated, only one (6%) experienced resolution of dyspepsia. Resolution of dyspepsia was therefore a powerful predictor of eradication of H pylori with a predictive value of 98%. In contrast, persistence of dyspepsia was a weak predictor of persisting infection with a predictive value of only 25%. Excluding patients with endoscopic evidence of coexisting oesophagitis and/or retrosternal discomfort or reflux at initial presentation did not increase the predictive value of persisting dyspepsia for persisting infection. CONCLUSIONS: Complete resolution of dyspeptic symptoms is a powerful predictor of eradication of H pylori infection in ulcer patients. Persistence of symptoms is a weak predictor of persisting infection and patients with persisting dyspepsia must have their H pylori status rechecked to guide future management.

Eradicating Helicobacter pylori reduces hypergastrinaemia during long-term omeprazole treatment.

BACKGROUND: Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. AIMS: To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. METHODS: Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment. RESULTS: In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p < 0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95). CONCLUSION: Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long-term proton pump inhibitor treatment.

Helicobacter pylori infection and chronic gastric acid hyposecretion.

BACKGROUND & AIMS: We have identified a subgroup of Helicobacter pylori-infected subjects with low or absent gastric acid output. The aim of this study was to document the morphological and functional abnormalities in these subjects and to assess the effect of eradicating the infection. METHODS: The 16 hypochlorhydric subjects (6 men) had a mean age of 55 years (range, 36-79 years). They underwent a 14C-urea breath test, H. pylori serology, fasting gastrin, gastric autoantibodies, gastroscopy with antral and body biopsies, and measurement of peak acid output to pentagastrin (PAO(PG)). Their histology was compared with that of age- and sex-matched duodenal ulcer and nonulcer dyspepsia patients (16 each). H. pylori infection was eradicated in the hypochlorhydric subjects, and the investigations were repeated 6 months later. RESULTS: Compared with controls, the hypochlorhydric subjects had less dense H. pylori colonization, body-predominant colonization and gastritis, and increased prevalence of body atrophy and intestinal metaplasia. Median PAO(PG) before eradication in the hypochlorhydric subjects was 1.1 mmol/h and increased to 12.6 mmol/h after eradication (P < 0.001), with no significant change in body atrophy or intestinal metaplasia. CONCLUSIONS: In some subjects, chronic H. pylori infection produces a body-predominant gastritis and profound suppression of gastric acid secretion that is partially reversible with eradication therapy.

The Helicobacter pylori breath test: a surrogate marker for peptic ulcer disease in dyspeptic patients.

BACKGROUND: There is interest in noninvasive H pylori testing as a means of predicting diagnosis and determining management in dyspeptic patients. AIMS: To assess the value of the 14C urea breath test as a predictor of peptic ulcer disease in patients presenting with dyspepsia. PATIENTS AND METHODS: 327 consecutive patients referred for investigation of dyspepsia had a 14C urea breath test performed before endoscopy. Patients were not included if they had previously confirmed ulcer disease, previous gastric surgery, or were taking non-steroidal anti-inflammatory drugs. RESULTS: Of the 182 patients with a positive 14C urea breath test, duodenal and/or gastric ulcers were present in 45% and erosive duodenitis in a further 2%. Oesophagitis was present in 12% of the breath test positive patients with two thirds of the oesophagitis patients having co-existent ulcer disease. The prevalence of ulcer disease in the H pylori positive dyspeptic patients was independently related to smoking and previous investigation status. If previously uninvestigated, the prevalence of ulcers was 67% in smokers and 46% in non-smokers. If previous upper gastrointestinal investigations were negative, the prevalence of ulcers was 53% in smokers and 28% in non-smokers. Of the 136 patients with a negative breath test, only 5% had peptic ulcers. The most frequent endoscopic finding in these H pylori negative subjects was oesophagitis, being present in 17%. CONCLUSIONS: This study demonstrates that a positive H pylori test is a powerful predictor of the presence of underlying ulcer disease in dyspeptic patients, especially if smokers, and that a negative H pylori test is a powerful predictor of the absence of ulcer disease. It also indicates that a negative upper gastrointestinal investigation does not preclude subsequent presentation with ulcer disease.

Effect of Helicobacter pylori infection on intragastric urea and ammonium concentrations in patients with chronic renal failure.

AIM: To assess the value of measuring the gastric juice urea:ammonium ratio in detecting Helicobacter pylori infection in patients with chronic renal failure. METHODS: Twenty three (12 men) patients with established chronic renal failure and dyspepsia were studied. Gastric juice (2 ml) was aspirated during endoscopy to measure urea and ammonium. The upper gastrointestinal tract was routinely inspected and two antral biopsy specimens obtained. The 14C-urea breath test was conducted within 14 days of endoscopic examination to determine H pylori antibody response. RESULTS: The median (range) serum urea concentration in 11 patients with renal failure and H pylori infection was similar to that in 12 without H pylori infection. The median gastric juice urea concentration in subjects with infection was lower than that in the subjects without infection (p < 0.01). The median gastric juice ammonium concentration in subjects with the infection was higher compared with subjects without infection (p < 0.01). There was an overlap of the urea and ammonium concentrations in gastric juice from both H pylori positive and negative subjects. The urea:ammonium ratio was 0.16 (0.01-1.11) for subjects with H pylori compared with 1.63 (1.0-18.9) in subjects without infection (p < 0.001). CONCLUSION: The urea:ammonium ratio differentiated both groups, with the exception of one false negative result. The urea:ammonium ratio proved almost as effective in identifying the presence of H pylori infection in subjects with chronic renal failure as it had in subjects with normal renal function.

A study of the pathogenesis of Helicobacter pylori negative chronic duodenal ulceration.

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 pylori 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 pylori 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 pylori positive patients with DU (40 (15-57)) and higher than that of the 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 H pylori 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 pylori negative healthy volunteers (87 (49-95) p<0.01) or H pylori positive patients with DU (79 (51-100) p<0.01). In conclusion, three abnormalities of gastric function are prevalent in patients with H pylori negative idiopathic DU disease - hypergastrinaemia, increased acid secretion, and the one feature distinguishing them from H pylori 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.

Measurement of urea and ammonium concentrations in gastric juice.

AIM: To study the effect of known interference in the measurement of urea and ammonium concentrations in samples of gastric juice. METHODS: The effect of pH and ammonium concentration on the o-pthalaldehyde method, the diacetylmonoxime method, a Berthelot linked method and an enzymatic urease method for the measurement of urea in gastric juice was therefore conducted. An enzymatic method of the measurement of ammonium in gastric juice was also assessed. RESULTS: The o-pthalaldehyde and the enzymatic urease methods were unaffected by a low gastric juice pH, ammonium concentrations of 10 mmol/l, and had interassay coefficients of variation of 3.9-5.6% and 2.8-10.6%, respectively, over a urea concentration of 2.5 mmol/l-20 mmol/l. The Berthelot linked method resulted in low gastric juice urea concentrations. The enzymatic method of ammonium measurement also proved suitable when the effect of low gastric juice pH was controlled. CONCLUSION: Interference by low pH did not explain the differences in reports of gastric juice urea or ammonium concentrations.

Role of ammonia in the pathogenesis of the gastritis, hypergastrinaemia, and hyperpepsinogenaemia I caused by Helicobacter pylori infection.

Studies were performed in patients with and without renal failure to investigate the role of bacterial ammonia production in the pathogenesis of the mucosal abnormalities caused by Helicobacter pylori. The high rate of H pylori ammonia production in uraemic patients should accentuate any ammonia induced effects. The median (range) gastric juice ammonium concentration in the H pylori positive patients with renal failure was 19 mmol/l (II-43) compared with 5 mmol/l (1-11) in the H pylori positive patients without renal failure (p < 0.005). In the H pylori negative patients the values were 3 mmol/l (0.5-11) and 0.7 mmol/l (0.1-1.4) respectively in the patients with and without renal failure (p < 0.01). Despite the much higher ammonia production in the H pylori positive uraemic patients, the nature and severity of their gastritis was the same as that in the H pylori positive non-uraemic patients. The median (range) fasting serum gastrin concentration was raised in the uraemic patients compared with the non-uraemic patients but was similar in the uraemic patients with (95 pmol/l (52-333)) or without (114 pmol/l (47-533)) H pylori infection. The median (range) serum pepsinogen I concentration was also high in the uraemic compared with the non-uraemic patients and was significantly higher in uraemic patients with H pylori (352 ng/ml, range 280-653) than in those without H pylori infection (165 ng/ml, range 86-337) (p < 0.01). These findings indicate that the gastritis and hypergastrinaemia associated with H pylori infection are not the result of mucosal damage induced by the organism's ammonia production.

The diagnosis of Helicobacter pylori infection in uremic patients.

Two urease-based tests--the urease slide test and the radiolabeled urea breath test, are commonly used for the diagnosis of Helicobacter pylori infection of the stomach. The reliability of these tests in chronic uremia was compared with serological tests for H pylori antibodies, and with direct detection of the organism by microscopy or culture of gastric antral biopsies. Twenty-seven patients with chronic renal failure and dyspepsia underwent upper gastrointestinal endoscopy. Twelve of these patients (46%) were judged to be infected with H pylori on the basis of identification of the organism on microscopy or culture of antral biopsy. Both urease-based tests were able to determine H pylori status, despite the markedly increased concentrations of urea in the gastric juice found in chronic renal failure. The urease slide test performed on antral biopsies obtained at endoscopy proved reliable in determining H pylori status with no false-positive nor false-negative results after 20 minutes and 24 hours of incubation. The 14C-urea breath test also differentiated the infected from the uninfected patients. The 20-minute 14CO2 excretion (kg %dose/mmol CO2 x 100) ranged from 50 to 834 in the H pylori-infected patients, compared with 0.3 to 27 in the H pylori-noninfected patients (P < 0.0001); the 90-minute values ranged from 88 to 398 in the former, compared with 1 to 79 in the latter (P < 0.0001). The excretion of 14CO2 (derived from bacterial hydrolysis of ingested 14C-urea) was higher in all the uremic patients compared with nonuremic controls, and in half of the H pylori-noninfected uremic patients there was a late increase in 14CO2 excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.

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 H pylori 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/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). 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 less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.

Effect of inhibition of Helicobacter pylori urease activity by acetohydroxamic acid on serum gastrin in duodenal ulcer subjects.

The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection.

Plasma gastrin, daytime intragastric pH, and nocturnal acid output before and at 1 and 7 months after eradication of Helicobacter pylori in duodenal ulcer subjects.

Nine patients with Helicobacter pylori-related antral gastritis and history of duodenal ulceration were studied before and at 1 and 7 months after eradication of the infection by a 4-week course of tripotassium dicitrato bismuthate, metronidazole, and amoxycillin. The median basal gastrin concentration before eradication was 30 ng/l (range, 20-60) and fell to 20 ng/l (5-20) at 1 month (p less than 0.02) and 15 ng/l (5-20) at 7 months (p less than 0.01) after eradication. The integrated gastrin response to a peptide meal was 3650 ng/l.min (range, 1875-6025) before treatment compared with 1800 ng/l.min (range, 1200-3075) at 1 month (p less than 0.01) and 1312 ng/l.min (875-2625) at 7 months (p less than 0.03). Daytime intragastric pH (0900-2100 h) was similar before treatment (median, 1.4; range, 1.1-2.1) and at 1 month (1.4; 1.1-2.3) and 7 months (1.4; 1-2.2) after eradication. In five of the patients nighttime acid output (2300-0900 h) was also studied and was similar before (median, 86 mmol/10 h; range, 52-114) and at 1 month (76 mmol/10 h; 50-143) and 7 months (94 mmol/10 h; 63-106) after eradication. In conclusion, eradication of H. pylori is accompanied by a sustained fall in serum gastrin concentrations but is not accompanied by an early or late reduction of daytime intragastric acidity or nighttime acid output.