The acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori–infected healthy subjects

doi:10.1016/S0016-5085(98)70632-8

Gastroenterology

Volume 114, Issue 1, January 1998, Pages 50-57

https://doi.org/10.1016/S0016-5085(98)70632-8 Get rights and content

Abstract

Background & Aims: Helicobacter pylori–induced hypergastrinemia is accompanied by increased acid secretion in patients with duodenal ulcer (DU) but not in infected healthy volunteers. The aim of this study was to investigate the mechanism underlying this difference. Methods: Thirty-four H. pylori–negative and 20 H. pylori–positive healthy volunteers and 15 H. pylori–positive patients with DU were studied. Maximal acid output and sensitivity to gastrin (gastrin concentration required to achieve 50% maximal acid output) were assessed by examining the dose response to gastrin 17. Inhibitory control was tested by comparing the maximal acid response to cholecystokinin octapeptide with that for gastrin 17. Results: Sensitivity to gastrin was similar in patients with DU (median, 69.5 ng · L⁻¹; range, 26.2-142) and H. pylori– negative healthy volunteers (median, 82.2 ng · L^minus;1; range, 17.7-410); H. pylori–positive healthy volunteers were less sensitive than either (164.5 ng · L^minus;1; range, 44.8 to >3360 ng · L⁻¹). Patients with DU had higher maximal acid output (51.2 mmol · h^minus;1; range, 30.8-73.7 mmol · h⁻¹) than either infected healthy volunteers (37.8 mmol · h⁻¹; range, 0.0-65.0 mmol · h⁻¹; P< 0.04) or uninfected healthy volunteers (35.3 mmol · h⁻¹; range, 21.3-67.3 mmol · h⁻¹; P < 0.002). The maximal acid output in both groups of healthy subjects was similar. The proportion of maximal acid output to gastrin 17 achieved by cholecystokinin was similar in patients with DU (36.6%; range, 21.5%-58.2%) and H. pylori–negative healthy volunteers (28.7%; range, 5.9%-85.8%). Conclusions: A combination of decreased sensitivity to gastrin in infected healthy volunteers and increased maximal acid secretory capacity in patients with DU underlies their different acid response to H. pylori–induced hypergastrinemia.

GASTROENTEROLOGY 1998;114:50-57

Section snippets

Subjects studied

Fifteen H. pylori–positive patients (12 men) with chronic DU disease were included in the gastrin 17 (G-17) study. Nine of them were smokers. Each had been confirmed to have DU disease by endoscopic examination within the past 2 years, and current H. pylori infection was confirmed by the [¹⁴C]urea breath test. All patients were symptomatically healed using a 6-week course of ranitidine, 150 mg twice per day (12 patients), or omeprazole, 20 mg twice per day (3 patients). In addition, before the

Basal plasma gastrin and basal acid output

Median basal gastrin concentration increased to a similar extent in the H. pylori–positive HVs (25 ng · L^minus;1; range, 5-1360 ng · L⁻¹) and H. pylori–positive DUs (30 ng · L^minus;1; range, 10-70 ng · L⁻¹) compared with the H. pylori–negative HVs (20 ng · L^minus;1; range, 5-42 ng · L^minus;1; P < 0.04 and 0.01, respectively; Figure 1).

. Basal plasma gastrin concentration and basal acid output in H. pylori–negative HVs, H. pylori–positive HVs, and patients with DU. Median of values indicated by

Discussion

Numerous studies have shown that H. pylori infection reversibly increases basal and stimulated serum gastrin concentrations and that the degree of increase is similar in patients with DU and HVs.14, 15, 30, 31, 32, 33 However, it has been shown previously that both basal and GRP-stimulated acid secretion is considerably greater in H. pylori–positive patients with DU than in infected HVs.12, 13 The patients with DU, therefore, have a greater acid response to gastrin stimulation than H. pylori

Acknowledgements

The authors thank Drs. R. Mitchell and R. J. Perry of the Scottish National Blood Transfusion Service for their very generous provision of albumin. They also thank Dr. Andrew Kelman for his advice on the appropriate pharmacokinetic analysis of the gastrin/acid secretion data.

References (71)

BJ Marshall et al.
Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration
Lancet
(1984)
DY Graham
Campylobacter pylori and peptic ulcer
Gastroenterology
(1989)
EM El-Omar et al.
Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease
Gastroenterology
(1995)
S Levi et al.
Campylobacter pylori and duodenal ulcers: the gastrin link
Lancet
(1989)
KEL McColl et al.
Lowered gastrin and gastric acidity after eradication of Campylobacter pylori in duodenal ulcer
Lancet
(1989)
IM Modlin et al.
The gastric enterochromaffin-like cell: an enigmatic cellular link
Gastroenterology
(1996)
C Prinz et al.
Histamine secretion from rat enterochromaffin-like cells
Gastroenterology
(1993)
ML Schubert et al.
Neural and paracrine regulation of gastrin and gastric acid secretion
Gastroenterology
(1996)
R Eissele et al.
Role of cholecystokinin in the control of gastric somatostatin in the rat: in vivo and in vitro studies
Regul Pept
(1991)
C Beglinger et al.
A physiological role for cholecystokinin as a regulator of gastrin secretion
Gastroenterology
(1992)

G Oderda et al.

Amoxycillin plus tinidazole for Campylobacter pylori gastritis in children: assessment by serum IgG antibody, pepsinogen I and gastrin levels

Lancet

(1989)

D Johnston et al.

The use of pentagastrin in a test of gastric acid secretion

Lancet

(1967)

MI Grossman

What do you do with basal in dose-response studies? A suggested answer

Gastroenterology

(1973)

G Varga et al.

Role of gastrin and cholecystokinin in regulation of peptone-stimulated gastric acid secretion in conscious rats

Eur J Pharmacol

(1993)

N Langhans et al.

Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor–deficient mice

Gastroenterology

(1997)

EM El-Omar et al.

Helicobacter pylori infection and chronic gastric acid hyposecretion

Gastroenterology

(1997)

DR Cave et al.

Effect of a Campylobacter pylori protein on acid secretion by parietal cells

Lancet

(1989)

LL Huang et al.

Purification and characterisation of an acid-inhibitory protein from Helicobacter pylori (abstr)

Gastroenterology

(1995)

A Robert et al.

Interleukin-1 is cytoprotective, antisecretory, stimulates PGE₂ synthesis by the stomach and retards gastric emptying

Life Sci

(1991)

M Feldman et al.

Effect of aging and gastritis on gastric acid and pepsin secretion in humans: a prospective study

Gastroenterology

(1996)

B Ryberg et al.

Trophic effects of continuous infusion of [Leu¹⁵]-gastrin 17 in the rat

Gastroenterology

(1990)

B Ryberg et al.

Gastrin stimulates the self-replication rate of enterochromaffin-like cells in the rat stomach

Gastroenterology

(1990)

EA Mayer et al.

Reassessment of gastric acid inhibition by cholecystokinin and gastric inhibitory peptide in dogs

Gastroenterology

(1982)

GM Short et al.

Effect of antibodies to somatostatin on acid secretion and gastrin release by the isolated perfused rat stomach

Gastroenterology

(1985)

D Graham et al.

Effect of age on frequency of active Campylobacter pylori infection diagnosed by the ¹³C-urea breath test in normal subjects and patients with peptic ulcer

J Infect Dis

(1988)

TA McDonagh et al.

Lack of independent association of H. pylori and coronary heart disease

Gut

(1996)

G Watkinson

The incidence of chronic peptic ulcer found at necropsy

Gut

(1960)

IS Levi et al.

A post mortem study of gastric and duodenal peptic lesions

Gut

(1963)

N Figura et al.

Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only

J Clin Microbiol

(1989)

JE Crabtree et al.

Mucosal IgA recognition of Helicobacter pylori 120kDa protein, peptic ulceration and gastric pathology

Lancet

(1991)

AH James et al.

The role of gastric acidity in the pathogenesis of peptic ulcer

Clin Sci

(1949)

KEL McColl et al.

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

Scand J Gastroenterol

(1991)

SF Moss et al.

Acid secretion and sensitivity to gastrin in patients with duodenal ulcer: effect of eradication of H. pylori

Gut

(1993)

E El-Omar et al.

Eradicating Helicobacter pylori infection lowers gastrin-mediated acid secretion by two-thirds in patients with duodenal ulcer

Gut

(1993)

HL Waldum et al.

Gastrin-histamine sequence in the regulation of gastric acid secretion

Gut

(1991)

Cited by (92)

Helicobacter pylori in Childhood
2020, Pediatric Gastrointestinal and Liver Disease, Sixth Edition
Helicobacter pylori is a slow-growing, gram-negative organism that colonizes the gastric mucosa and can lead to antral gastritis and peptic ulcer disease. Infection is acquired during the first decade of life and unless eradicated causes lifelong infection. Although H. pylori infects children worldwide, approach to diagnosis, interventions, and treatment differ widely. The majority of children who are infected with H. pylori are asymptomatic, and investigation is only indicated if the intention is to treat a positive result. An updated guideline was published by the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) in 2017 to address the recommendations in the diagnosis and management of children with H. pylori infection. Pediatricians and pediatric gastroenterologists must consider carefully appropriate methods of investigation and therapeutic intervention, while ensuring appropriate utilization of preventive medicine in minimizing future ill health.
Regulation of Gastric Acid Secretion
2012, Physiology of the Gastrointestinal Tract, Two Volume Set
A population-based study on the association between gastric ulcers and erectile dysfunction in Taiwan
2012, Journal of Sexual Medicine
Citation Excerpt :
The gastric fluids of the stomach are composed of numerous chemicals, including hydrocholoric acid, which is titrated to a gastric pH of around 2–3, which is necessary for proper digestion and protection [18]. In cases where the gastric fluids become hyperacidic on account of increased acid secretion, there is an increased risk of duodenal ulcers [19]. Yet, this is not the case with GU, which has been found to be characterized by hypoacidity, being even less acidic than healthy controls [18].
While erectile dysfunction (ED) and cardiovascular disease have long been known to share endothelial dysfunction as a common contributory underlying mechanism, little research has been conducted taking endothelial dysfunction as common ground to investigate the potential association between ED and gastric ulcers (GUs).
This population‐based case‐control study aimed to investigate the association of ED with GU.
This study used data from the Longitudinal Health Insurance Database 2000 in Taiwan. The study group comprised 6,906 patients who visited ambulatory care centers or were hospitalized with a diagnosis of ED. The comparison group was 20,718 randomly selected enrollees. Conditional logistic regression was used to examine associations between ED and prior GU.
The prevalence and risk between cases and controls were calculated of having been previously diagnosed with GU.
Of the sampled subjects, 3,861 (14%) were diagnosed before the index date, 1,358 (19.7%) were cases, and 2,503 (12.1%) were controls (P < 0.001). After adjusting for hypertension, diabetes, hyperlipidemia, renal disease, coronary heart disease, obesity, alcohol abuse/alcohol dependence syndrome, and socioeconomic status (SES), conditional logistic regression analysis revealed that cases were more likely to have been diagnosed with GU than controls (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.53–1.77). Stratification by age revealed that the youngest group (18–29) of ED patients had the most increased likelihood of having been previously diagnosed with GU when compared with matched controls (OR = 4.12, 95% CI = 2.41–7.03). The likelihood decreased with age, with the oldest group of ED patients having the least increased likelihood of prior GU when compared with matched controls (OR = 1.44, 95%CI = 1.23–1.68).
Our findings suggest a positive association between prior GU and a subsequent diagnosis with ED. Keller JJ, Lin H‐Yu, Chung S‐D, and Lin H‐C. A population‐based study on the association between gastric ulcers and erectile dysfunction in Taiwan. J Sex Med 2012;9:686–693.
Regulation of Gastric Acid Secretion
2012, Physiology of the Gastrointestinal Tract
The Prevalence and Incidence of Helicobacter pylori-Associated Peptic Ulcer Disease and Upper Gastrointestinal Bleeding Throughout the World
2011, Gastrointestinal Endoscopy Clinics of North America
Citation Excerpt :
However, some patients chronically infected with H pylori have antral-predominant inflammation.29 These patients produce increased amounts of acid as a result of reduced antral somatostatin, and elevated basal and stimulated gastrin secretion.44–46 The mechanism by which somatostatin secretion is decreased is not known.29
Helicobacter pylori infection and peptic ulcers
2011, Medicine
Nearly all peptic ulcers are caused by either Helicobacter pylori infection or non-steroidal inflammatory drug (NSAID) use, including aspirin. As H. pylori infection is becoming less prevalent in developed countries, NSAIDs are an increasingly important cause of ulceration, particularly ulcers complicated by bleeding. Only about 15% of H. pylori-infected people develop an ulcer in their lifetime; virulence of the H. pylori strain, host genetics and environment (particularly smoking) determine the risk. NSAID ulcers are largely the result of suppression of gastro-protective cyclo-oxygenase 1 (COX-1). The presence and type of ulcers cannot be predicted accurately from symptoms and the differential diagnosis is wide. Older dyspeptic patients and those with ‘alarm’ symptoms or signs require endoscopy to exclude upper GI cancer and make a diagnosis; younger patients with simple dyspepsia are treated empirically with a course of proton pump inhibitors (PPIs) or an H. pylori ‘test and treat’ strategy. For H. pylori-associated ulcers, H. pylori treatment induces healing and prevents relapse. NSAID ulcers are treated by NSAID withdrawal and a PPI course. Treatment of functional dyspepsia is difficult and requires a multi-factorial approach.

View all citing articles on Scopus

^☆: Address requests for reprints to: Kenneth E. L. McColl, M.D., F.R.C.P., University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, G11 6NT, Scotland. Fax: (44) 141-339-2800.

View full text

Alimentary TractThe acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori–infected healthy subjects☆

Abstract

Section snippets

Subjects studied

Basal plasma gastrin and basal acid output

Discussion

Acknowledgements

Lancet

Gastroenterology

Gastroenterology

Lancet

Lancet

Gastroenterology

Gastroenterology

Gastroenterology

Regul Pept

Gastroenterology

Lancet

Lancet

Gastroenterology

Eur J Pharmacol

Gastroenterology

Gastroenterology

Lancet

Gastroenterology

Life Sci

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Effect of age on frequency of active Campylobacter pylori infection diagnosed by the 13C-urea breath test in normal subjects and patients with peptic ulcer

J Infect Dis

Lack of independent association of H. pylori and coronary heart disease

Gut

The incidence of chronic peptic ulcer found at necropsy

Gut

A post mortem study of gastric and duodenal peptic lesions

Gut

Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only

J Clin Microbiol

Mucosal IgA recognition of Helicobacter pylori 120kDa protein, peptic ulceration and gastric pathology

Lancet

The role of gastric acidity in the pathogenesis of peptic ulcer

Clin Sci

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

Scand J Gastroenterol

Acid secretion and sensitivity to gastrin in patients with duodenal ulcer: effect of eradication of H. pylori

Gut

Eradicating Helicobacter pylori infection lowers gastrin-mediated acid secretion by two-thirds in patients with duodenal ulcer

Gut

Gastrin-histamine sequence in the regulation of gastric acid secretion

Gut

Alimentary Tract
The acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori–infected healthy subjects☆

Effect of age on frequency of active Campylobacter pylori infection diagnosed by the ¹³C-urea breath test in normal subjects and patients with peptic ulcer