Helicobacter pylori: clinical aspects.
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Drug Therapy, Combination↗
Biomedical subjects
K E McColl
Publications and source records attributed to K E McColl.
Eradication of Helicobacter pylori: an objective assessment of current therapies.
The purpose of the present review was to determine objectively the optimal treatment for the eradication of H. pylori amongst the currently used regimens. A comprehensive literature search provided a data-base relating to the following treatments: dual therapy with an anti-secretory drug plus either amoxycillin or clarithromycin; standard triple therapy, with or without additional anti-secretory drugs; proton pump inhibitor triple therapy; and H2-receptor antagonist triple therapy. Emphasis was placed on intention-to-treat analyses of eradication rates using all of the available evidence. The criteria used to select the optimal treatment were efficacy (eradication rates), frequency of side-effects, simplicity of the regimen (number of tablets per day and duration of treatment) and cost. The analysis showed that proton pump inhibitor triple therapy (that is, a proton pump inhibitor plus any two of amoxycillin, clarithromycin or a nitroimidazole) was the preferred treatment for the eradication of H. pylori. In particular, the 1-week, low-dose regimen with omeprazole plus clarithromycin plus tinidazole produced the highest eradication rates (> 90%) with the lowest frequency of side-effects and at only modest cost.
Anti-Bacterial Agents↗
Helicobacter pylori infection and coronary heart disease in the North Glasgow MONICA population.
AIM: Recent evidence suggests that Helicobacter pylori infection is associated with coronary heart disease. We investigated whether H. Pylori infection is related to prevalent coronary heart disease, in a random sample of 1428 men and women aged 25-74 years. METHODS AND RESULTS: Coronary heart disease was assessed by questionnaire and electrocardiography (ECG). Standard risk factors for coronary heart disease, fibrinogen concentration and serum concentrations of H. pylori-specific IgG antibody were measured. H. pylori seropositivity increased with age (P < or = 0.001) and was significantly more prevalent in men than women. H. pylori infection was associated with current smoking and a higher systolic blood pressure in men but not in women. There was no significant increase in the odds ratio in those seropositive for H. pylori with regard to any manifestation of coronary heart disease, after adjustment for age, standard cardiovascular risk factors and social class. Likewise, age-adjusted plasma fibrinogen was no higher in seropositives. CONCLUSION: Seropositivity to H. pylori is associated with a trend towards a greater prevalence of coronary heart disease. However, that association is likely to be spurious and can be adequately explained by the much stronger association of H. pylori infection with age and social class, both of which are linked with coronary heart disease.
Adult↗
Helicobacter pylori and acid secretion: where are we now?
It is now widely recognized that H. pylori gastritis can produce marked alterations in gastric acid secretion. In subjects with an antral predominant gastritis there is increased release of gastrin and consequently increased acid secretion. Such subjects are at risk of developing duodenal ulcers. In other subjects the infection produces a marked body gastritis and this is associated with marked hyposecretion of acid or complete achlorhydria. These subjects have an increased risk of developing gastric cancer. Between these two ends of the disease spectrum lie the majority of H. pylori-infected subjects who have gastritis of both the antrum and body and no overall change in acid secretion. The reason why the infection exerts these divergent effects on gastric morphology and function remains unclear and is a challenge for ongoing research.
Cell Count↗
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.
Adolescent↗
Helicobacter pylori does not release cysteamine into gastric juice.
AIM: To determine whether Helicobacter pylori releases cysteamine into gastric juice as cysteamine is known to be ulcerogenic. METHODS: Samples of fasting gastric juice were collected from 22 individuals (four women); 10 subjects were H pylori negative. The presence of infection was confirmed by examination and culture of gastric biopsies. Cysteamine in gastric juice was measured by reversed phase gradient high performance liquid chromatography with a detection limit of 10 mumol/l. RESULTS: Cysteamine was not detected in any of the gastric juice samples or in extracts of cultured H pylori. CONCLUSIONS: If H pylori produces cysteamine then the amounts produced are insignificant and are unlikely to explain the association between H pylori infection and the development of duodenal ulcer disease.
Chromatography, High Pressure Liquid↗
Pathophysiology of duodenal ulcer disease.
Before the discovery of Helicobacter pylori infection some 12 years ago, three major disturbances in gastric physiology had been identified in patients with duodenal ulcer disease. These abnormalities were: impaired acid inhibition of gastrin release from the antral mucosa, increased basal and stimulated acid secretion by the body of the stomach and increased acid load in the duodenum. Some of these abnormalities in gastric function can now be explained by the effects of H. pylori infection. The increased release of gastrin by the antral mucosa in duodenal ulcer patients, for example, can be entirely explained by the effects of this organism. Other abnormalities, however, appear to have a genetic basis or may be due to environmental factors. Much work has been conducted on the relationship between H. pylori and the development of duodenal ulcer disease and this paper aims to review recent studies in the field and to give an overview of the latest understanding of the pathophysiology of this disease.
Duodenal Ulcer↗
The role of Helicobacter pylori in the pathophysiology of duodenal ulcer disease and gastric cancer.
Helicobacter pylori infection is now recognized to be an important acquired factor in the pathogenesis of duodenal ulcer disease. There is also an association between H pylori and the subsequent development of gastric cancer. The mechanism of the association between the infection and those disorders is incompletely understood but there is increasing evidence that H pylori-induced disturbances of gastric function play a pivotal role. In this article we review the role of H pylori infection in the pathophysiology of these important upper gastrointestinal diseases.
Ascorbic Acid↗
The role of H. pylori infection in the pathophysiology of duodenal ulcer disease.
The discovery of H. pylori infection and the recognition of its effects on gastric physiology has significantly advanced our understanding of the pathophysiology of ulcer disease, In DU patients H. pylori gastritis is mainly confined to the antral mucosa. It stimulates increased release of gastrin by the antral mucosa and this is accompanied by high acid output by the oxyntic mucosa. This high acid response to gastrin stimulation by the oxyntic mucosa in DU patients is due to the combination of a high parietal cell mass and the fact that the function of these parietal cells is not impaired by any body gastritis. The increased acid secretion results in an increased duodenal acid load with the development of gastric metaplasia within the duodenal bulb and then actual ulceration. The reason why only some subjects develop this antral predominant pattern of H. pylori gastritis and associated acid hypersecretion is unclear but may be explained by a premorbid high acid output protecting the oxyntic mucosa form H. pylori gastritis.
Duodenal Ulcer↗
Alterations in gastric physiology in Helicobacter pylori infection: causes of different diseases or all epiphenomena?
Helicobacter pylori infection exerts variable effects on gastric acid secretion. It may increase acid secretion, decrease acid secretion or produce no overall change. The effect of the infection on acid secretion depends upon the relative extent to which the Helicobacter pylori gastritis affects the antral and body mucosa of the stomach. When there is antral predominant, body-sparing gastritis, there is increased gastrin release and this is accompanied by increased acid secretion. When there is a significant body gastritis, acid secretion is reduced and subjects may be completely achlorhydric. The majority of subjects have both antral gastritis and body gastritis and this results in no overall change in gastric acid secretion. There is now increasing evidence that the alteration which Helicobacter pylori infection exerts upon gastric acid secretion is a pivotal factor in determining the clinical outcome of the infection. Subjects in whom the infection produces acid hypersecretion develop duodenal ulcer disease due to the increased duodenal acid load. In subjects in whom the infection induces marked hypochlorhydria, there is an increased risk of gastric cancer. The hypochlorhydria probably plays an important role in the carcinogenic process as high intragastric pH markedly raises intragastric nitrite levels, profoundly lowers gastric juice ascorbic acid and allows colonization by nitrosating bacteria. The reason for the different functional responses to Helicobacter pylori infection is unclear but may be related to the host's pre-morbid acid secretory status.
Duodenal Ulcer↗
Helicobacter pylori infection and its role in human disease--an overview.
Helicobacter pylori (H. pylori) is probably the commonest chronic bacterial infection in humans. The bacterium colonizes the gastric epithelium and induces inflammation of the underlying mucosa. The recognition that this infection is the most important acquired factor in the pathogenesis of duodenal and gastric ulcers has transformed the management of these common disorders. Most patients with ulcers can be cured by a 1-week course of anti-H. pylori therapy, thereby removing the need for long-term acid inhibitory therapy. Eradication of the infection involves taking complex combinations of drugs and simpler eradication regimens are required. Recent epidemiological data indicate an association between H. pylori infection and the subsequent development of gastric carcinoma. If this association is established as causal, then widespread eradication of the infection may be indicated. Global eradication of H. pylori will probably rely on prophylactic or therapeutic vaccination and this approach is being actively investigated.
Clinical Enzyme Tests↗
Sucralfate suppresses Helicobacter pylori infection and reduces gastric acid secretion by 50% in patients with duodenal ulcer.
BACKGROUND & AIMS: The mechanism(s) by which sucralfate heals duodenal ulcers remains unclear. The aim of this study was to determine the effect of sucralfate on Helicobacter pylori infection and on the accompanying hypersecretion of gastric acid the infection induces in patients with duodenal ulcer. METHODS: Basal and gastrin-releasing peptide (GRP) stimulated gastrin release and acid secretion. H. pylori density, gastric urease activity, and severity of gastritis were studied in patients with duodenal ulcer who were positive for H. pylori before, during, and after 4 weeks' treatment with sucralfate (2 g twice daily). RESULTS: The density of H. pylori decreased by 70% during sucralfate treatment and returned to the pretreatment level after discontinuation of therapy. This suppression of H. pylori infection was accompanied by an 80% decrease in gastric urease activity. GRP-stimulated plasma gastrin concentrations, GRP-stimulated acid output, and basal acid output all decreased by approximately 50% during sucralfate therapy and returned to pretreatment levels after treatment was discontinued. CONCLUSIONS: These findings indicate that sucralfate markedly suppresses H. pylori infection and the accompanying hypersecretion of acid the infection induces in patients with duodenal ulcer. These effects are likely to be important mechanisms by which the drug promotes duodenal ulcer healing.
Adult↗
The Glasgow Dyspepsia Severity Score--a tool for the global measurement of dyspepsia.
OBJECTIVE: There is currently no reliable tool for providing a global measurement of the severity of dyspepsia in patients with a variety of upper gastrointestinal disorders. We have designed a questionnaire which records frequency of symptoms, effect on routine activities, time off work, frequency of medical consultations, clinical investigations and use of over-the-counter and prescribed medications. The objective of the paper was to assess this questionnaire with respect to reproducibility, validity, responsiveness and performance time. METHODS AND RESULTS: For intra-observer variation, one author interviewed 50 subjects (25 males) including 20 healthy volunteers and 30 with a variety of upper gastrointestinal pathologies. The interview was repeated one week later by the same author who was blinded to the dyspepsia score for the first interview. The second author, who was blinded to the diagnoses and subject identity, scored all the questionnaires. The mean dyspepsia score was 6.78 on Day 1 and was similar at 6.80 on Day 2. The coefficient of variation between Days 1 and 2 was 2%. For inter-observer variation, 30 patients with non-ulcer dyspepsia (NUD) were interviewed by one author and the interview was repeated on a separate occasion within 24 h by a second author who was blinded to the score from the first interview. The mean dyspepsia score for the first author was 10.7 and for the second author 10.9 with a coefficient of variation between the two authors of 8%. Validity was assessed by comparing the dyspepsia scores in healthy volunteers and patients with upper gastrointestinal diseases. The mean score in 80 healthy volunteers was 1.16 (range: 0-7) and was significantly higher in 70 duodenal ulcer (DU) patients (mean score 11.1, range: 6-16) and 80 NUD patients (mean score 10.5, range: 6-17) (P < 0.001 for both vs. healthy volunteers). Responsiveness was assessed by comparing dyspepsia scores before and one year after eradication of Helicobacter pylori infection in 42 DU patients. The mean dyspepsia score before eradication was 11.4 (range: 6-16) and fell to 1.33 (range: 0-11) one year after eradication (P < 0.001). The mean time taken to complete 150 questionnaires was 4 min (range: 3-5.5 min). CONCLUSION: This new questionnaire for assessing the severity of dyspepsia is highly reproducible and has high validity and responsiveness. In addition, it is simple and rapid to perform. It provides a valuable tool for assessing the response to treatment in patients with dyspepsia.
Adolescent↗
Helicobacter pylori utilises urea for amino acid synthesis.
Helicobacter pylori has one of the highest urease activities of all known bacteria. Its enzymatic production of ammonia protects the organism from acid damage by gastric juice. The possibility that the urease activity allows the bacterium to utilise urea as a nitrogen source for the synthesis of amino acids was investigated. H. pylori (NCTC 11638) was incubated with 50 mM urea, enriched to 5 atom% excess 15N, that is the excess enrichment of 15N above the normal background, in the presence of either NaCl pH 6.0, or 0.2M citrate pH 6.0. E. coli (NCTC 9001) was used as a urease-negative control. 15N enrichment was detected by isotope ratio mass spectrometry. H. pylori showed intracellular incorporation of 15N in the presence of citrate buffer pH 6.0 but there was no significant incorporation of 15N in unbuffered saline or by E. coli in either pH 6.0 citrate buffer or unbuffered saline. The intracellular fate of the urea-nitrogen was determined by means of gas chromatography/mass spectrometry following incubation with 15N enriched 5 mM urea in the presence of either 0.2 M citrate buffer pH 6.0 or 0.2 M acetate buffer pH 6.0. After 5 min incubation in either buffer the 15N label appeared in glutamate, glutamine, phenylalanine, aspartate and alanine. It appears, therefore, that at pH and urea concentrations typical of the gastric mucosal surface, H. pylori utilises exogenous urea as a nitrogen source for amino acid synthesis. The ammonia produced by H. pylori urease activity thus facilitates the organism's nitrogen metabolism at neutral pH as well as protecting it from acid damage at low pH.
Amino Acids↗
Helicobacter pylori, gastric acid, and duodenal gastric metaplasia.
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Duodenal Ulcer↗
Helicobacter pylori and disturbance of gastric function associated with duodenal ulcer disease and gastric cancer.
Helicobacter pylori is now recognized as the major acquired factor in the pathogenesis of duodenal ulcer disease (DU). There is also an association between H. pylori infection and the subsequent development of gastric cancer. The mechanisms by which such infection predisposes the host to these diseases are incompletely understood, but disorders induced by the bacterium in gastric function play a pivotal role. In most patients, H. pylori infection stimulates acid secretion, leading to a predisposition to DU development. However, in some patients, the infection is associated with a significant decrease in acid secretion, a predisposition to gastric cancer. These divergent effects of H. pylori on gastric acid secretion explain the early conflicting reports on changes in acid secretion associated with the infection. The reason why H. pylori infection produces divergent effects on gastric acid secretion is unclear, but may be related to differences in bacterial strains or genetic, dietary or other environmental factors.
Duodenal Ulcer↗
Marked rebound acid hypersecretion after treatment with ranitidine.
OBJECTIVES: Dyspeptic symptoms frequently recur rapidly after withdrawal of H2 antagonists, and this might be related to rebound acid hypersecretion. We have studied this phenomenon in healthy volunteers with and without Helicobacter pylori infection. METHODS: Basal and gastrin-releasing peptide (GRP) (40 pmol/kg/h) stimulated acid output, and gastrin concentration were measured in 18 healthy volunteers (nine were H. pylori positive). Studies were performed before and at 60 h and 10 days after completion of a 60-day course of ranitidine 300 mg nocte. RESULTS: In the H. pylori-negative healthy volunteers, basal acid output increased by a median of 137% 2 days after stopping ranitidine therapy compared with pretreatment values (p = 0.01) and returned to pretreatment values by day 10 posttreatment. Their GRP-stimulated acid output increased by a median of 108% 2 days post ranitidine (p < 0.01) and remained slightly increased at day 10. In H. pylori-positive healthy volunteers, basal acid output increased by a median of 96% 2 days after ranitidine therapy ceased (p < 0.01) and returned to pretreatment values by day 10 posttreatment. Their GRP-stimulated acid output also increased by a median of 56% 2 days posttreatment and returned to pretreatment values by day 10. The increase in acid output both basal and in response to GRP was not accompanied by any rise in gastrin concentration in either the H. pylori-positive or -negative subjects. CONCLUSIONS: Ranitidine therapy is associated with marked rebound hypersecretion of acid, and this may contribute to rapid resurgence of symptoms after therapy has been discontinued.
Anti-Ulcer Agents↗
Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease.
BACKGROUND & AIMS: The mechanism by which Helicobacter pylori predisposes to duodenal ulcers (DUs) remains unclear. The aim of this study was to investigate the effect of the infection on acid secretion. METHODS: Acid output was examined basally and in response to gastrin-releasing peptide (GRP) and gastrin in healthy volunteers with and without H. pylori infection and in patients with DUs before and after eradication of the infection. RESULTS: Compared with H. pylori-negative healthy volunteers, patients with DUs with H. pylori had the following abnormalities of acid secretion: (1) threefold increase in basal acid output, (2) sixfold increase in acid response to GRP, (3) increased maximal acid response to exogenous gastrin, (4) increased ratio of basal acid output to maximal gastrin-stimulated output, and (5) increased ratio of maximal GRP-stimulated acid output to maximal gastrin-stimulated output. All of these abnormalities resolved fully after H. pylori eradication except for increased maximal acid output to gastrin, which was unchanged. Infected healthy volunteers showed a threefold increase in acid response to GRP that resolved after eradication of H. pylori infection. CONCLUSIONS: These disturbances in acid secretion caused by H. pylori infection are consistent with impaired inhibitory control and are likely to be relevant to the mechanism by which the infection predisposes to DU.
Amoxicillin↗