Treating Helicobacter pylori.
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2-Pyridinylmethylsulfinylbenzimidazoles↗
Biomedical subjects
R H Hunt
Publications and source records attributed to R H Hunt.
Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer.
BACKGROUND & AIMS: Reports in the literature regarding the relationship of Helicobacter pylori infection to gastric cancer are conflicting. The aim of this study was to identify the source of heterogeneity between studies. METHODS: Meta-analysis of cohort or case-control studies with age- and/or sex-matched controls, providing raw data on H. pylori infection detected by serology, was used. RESULTS: A fully recursive literature search identified 19 qualified studies with 2491 patients and 3959 controls. Test for homogeneity found a significant difference in odds ratio between patients with early and advanced gastric cancer (6.35 vs. 2.13; P = 0.01), patients with cardiac and noncardiac gastric cancer (1.23 vs. 3.08; P = 0.003), and population- and hospital-based controls (2.11 vs. 1.49; P < 0.001). The summary odds ratio for gastric cancer in H. pylori-infected patients is 1.92 (95% confidence interval [CI], 1.32-2.78), 2.24 (95% CI, 1.15-4.4), and 1.81 (95% CI, 1.16-2.84) for all studies, cohort, and case-control studies, respectively. H. pylori-infected younger patients have a higher relative risk for gastric cancer than older patients with odds ratios decreasing from 9.29 at age < or = 29 years to 1.05 at age > or = 70 years. H. pylori infection is equally associated with the intestinal or diffuse type of gastric cancer. CONCLUSIONS: H. pylori infection is a risk factor for gastric cancer. The heterogeneity of reported results is caused by differences in the selection of controls, patient age, and the site and stage of gastric cancer.
Aging↗
Dose-response relationship of lansoprazole to gastric acid antisecretory effects.
BACKGROUND: Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and gastro-oesophogeal reflux disorders. Optimal healing rates of antisecretory therapy for peptic acid disease is dependent upon the degree and duration of acid suppression and the length of treatment. OBJECTIVE: To evaluate the extent and duration of gastric acid suppression of several lansoprazole regimens, administered for 5 consecutive days in 32 healthy adult male subjects. METHODS: Intragastric 24-h pH monitoring was performed in 32 healthy subjects in a randomized, double-blind, four-way crossover study. Sixteen subjects (Group 1) received lansoprazole 30 mg o.d. (once daily), 15 mg b.d. (twice daily), 30 mg b.d. and 30 mg t.d.s. (three times a day) for 5 days; and 16 subjects (Group 2) received lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. for 5 days. RESULTS: Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 15 mg b.d., 30 mg b.d. and 30 mg t.d.s. were 4.47, 4.57, 5.07 and 5.63, respectively. Multiple-dose regimens of lansoprazole 30 mg b.d. and t.d.s. produced greater acid suppression compared to lansoprazole 30 mg o.d. and 15 mg b.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 15 mg b.d. Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. were 4.13, 4.45, 5.19 and 5.13, respectively. Multiple-dose regimens of lansoprazole 60 mg b.d. and t.d.s. produced significantly greater acid suppression compared to lansoprazole 30 mg o.d. and 60 mg o.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 60 mg o.d. Lansoprazole 30 mg t.d.s., 60 mg b.d. and 60 mg t.d.s. produced significantly greater percentage time above pH 3, 4, 5 and 6 than did lansoprazole 30 mg o.d. Post-regimen serum gastrin values increased by 50-130% from pre-study mean values but remained within normal range and returned to pre-study values 7-14 days post-dosing. CONCLUSIONS: Multiple-dose regimens of lansoprazole (> or =30 mg b.d. for 5 days) produce significantly increased intragastric pH and significantly longer duration of increased intragastric pH than does lansoprazole 30 mg administered once daily.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Review article: olestra and its gastrointestinal safety.
Olestra is a fat substitute made from sucrose and vegetable oil. Olestra is neither digested nor absorbed, and therefore adds no calories or fat to the diet. Because the gut is the only organ that is exposed to olestra, the potential for olestra to affect gastrointestinal structure and function, and the absorption of nutrients from the gut, has been investigated. Histological evaluations performed after long-term feeding studies have shown no indications that olestra causes injury to the gastrointestinal mucosa. Olestra is not metabolized by the colonic microflora, and has no meaningful effects on the metabolic function of these organisms. Studies of gastrointestinal transit have shown that the consumption of olestra with food does not affect gastric emptying, or small or large bowel transit times. Olestra does not affect the absorption of macronutrients, water-soluble vitamins or minerals. It causes a dose-responsive decrease in the availability of the fat-soluble vitamins A, D, E and K; however, this potentially adverse effect is offset by the addition of vitamins to olestra-containing foods. Olestra has no consistent effect on the amount of total bile acids excreted in the faeces, and therefore probably has no significant effect on bile acid absorption. The occurrence of gastrointestinal symptoms, including diarrhoea, loose stools, gas and abdominal cramping, after consumption of olestra under ordinary snacking conditions is comparable to that following consumption of triglyceride-containing snacks.
Animals↗
Hpall endonuclease distinguishes between two species in the Anopheles funestus group.
The Anopheles funestus group consists of at least eight species that are currently identified mainly on morphological criteria. Until recently, only An. funestus s.s. was implicated in the transmission of malaria in Africa, but recent work in Tanzania has shown that An. rivulorum is also involved, albeit to a lesser degree than An. funestus. The constraints in the identification of the species and the need to clarify better their epidemiological role have led to the development of a PCR-RFLP method for the identification of two anthropophilic members of the group. Using PCR primers developed from the D3 region in the 28S ribosomal gene, amplified products were digested with the restriction endonuclease Hpall. This produced two distinct fragments on an agarose gel that could be used to separate An. funestus from An. vaneedeni. The technique needs to be tested on natural populations of these two species as well as on other members of the An. funestus group.
Animals↗
The case for treatment of dyspeptic patients infected with H. pylori.
H. pylori is probably the commonest bacterial infection worldwide and associated with a number of clinical outcomes including chronic active gastritis, peptic ulcer, gastric adenocarcinoma, gastric MALT lymphoma and possibly dyspepsia. Treatment to eradicate H. pylori infection has changed significantly the natural history of peptic ulcer disease and is now the recommended approach to patients with non-NSAID gastric and duodenal ulcers. Controversies remain as to whether H. pylori infection is a cause of dyspepsia and non-ulcer dyspepsia. However, results from several economic models evaluating a "test and treat" strategy have suggested that eradication of H. pylori infection as an initial choice is the most cost-effective approach and has a long-term benefit in a significant proportion of patients with dyspepsia. The conclusion of H. pylori as a group 1 human carcinogen by the IARC and the subsequent analyses have added further to the recommendation for eradication of the infection.
Dyspepsia↗
Acid-related disorders in the new millennium: European, Japanese and North American perspectives.
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Anti-Inflammatory Agents, Non-Steroidal↗
Helicobacter pylori: from art to a science.
Helicobacter pylori infection is widely prevalent especially in developing countries. Increasing knowledge of the pathophysiology associated with H. pylori is leading to an understanding of the mechanisms of mucosal inflammation and gastritis and how this leads to peptic ulcer disease, gastric mucosal associated lymphoid tissues (MALT), lymphoma and gastric cancer. More accurate diagnostic testing for the infection is now possible with both endoscopic and non-endoscopic tests to identify patients most appropriate for eradication therapy. Modern treatments tend to overcome the problems of metronidazole resistance and compliance seen with two week bismuth triple therapy and widely studied is a proton pump inhibitor given with clarithromycin and amoxicillin or metronidazole for one week. These achieve amongst the highest eradication rates and have also been shown to be cost effective. This paper reviews these recent advances and addresses areas of clinical interest and future directions.
Gastrointestinal Diseases↗
Adding once-daily omeprazole 20 mg to metronidazole/amoxicillin treatment for Helicobacter pylori gastritis: a randomized, double-blind trial showing the importance of metronidazole resistance.
OBJECTIVE: We compared the Helicobacter pylori eradication rate after a 14-day treatment with amoxicillin 500 mg t.i.d. and metronidazole 500 mg t.i.d. with or without omeprazole 20 mg once daily. METHODS: This was a randomized, controlled trial in which omeprazole was given in double-blind fashion. Patients with H. pylori-associated gastritis were enrolled in four centers in Canada from July 1991 to January 1994. Eradication of H. pylori was assessed by histological evaluation and culture of endoscopic biopsies obtained from the antrum and corpus of the stomach. RESULTS: The H. pylori eradication rate was 73% (33 of 45) in the omeprazole-amoxicillin-metronidazole group, compared with 66% (31 of 47) in the amoxicillin-metronidazole group. This 7% difference was not statistically significant (p = 0.43, 95% confidence interval for difference -11% to 26%). Metronidazole primary resistance in the prestudy cultures was found more frequently in the omeprazole-amoxicillin-metronidazole group than in the amoxicillin-metronidazole group. Resistance to metronidazole was an important predictor of treatment failure. The H. pylori eradication rate was 61% (19 of 31) for patients infected with metronidazole-resistant H. pylori strains, compared with 91% (30 of 33) eradication for those infected with metronidazole-sensitive strains (p < 0.01). Vaginal candidiasis was reported in four patients. CONCLUSIONS: The H. pylori eradication rate was higher (73%) for omeprazole-amoxicillin-metronidazole than for the dual antibiotic therapy given without omeprazole (66%); however, this difference was not statistically significant. Metronidazole resistance significantly reduces H. pylori eradication rates.
Adolescent↗
Guidelines for the management of Helicobacter pylori infection. Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology.
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Helicobacter Infections↗
Description of Anopheles (Cellia) seretsei sp. nov. from Kasane, Botswana.
Anopheles (Cellia) seretsei, a new mosquito species from Kasane, northern Botswana, is described on the basis of the examination of a type series of 37 females and 18 males. Diagnostic features of the egg, larva, and pupa are presented. Comparisons of the new species with close relatives (Anopheles listeri and Anopheles azevedoi) are made.
Animals↗
Bionomics and cytogenetics of Anopheles seretsei Abdulla-Khan, Coetzee, and Hunt, a new species from northern Botswana.
Morphological analysis of anopheline mosquitoes from Kasane, Botswana, revealed a new species, Anopheles seretsei, that is closely related to Anopheles azevedoi and Anopheles listeri. A description of the type locality and biological characteristics of An. seretsei is given. Comparisons are made with An. listeri and An. azevedoi. The banding patterns of the giant polytene chromosomes of An. seretsei were compared with those of An. listeri and found to be homosequential.
Animals↗
Helicobacter pylori: new developments and treatments.
The authors highlight new developments in research on Helicobacter pylori. There is now consensus that all patients with newly diagnosed or recurrent duodenal or gastric ulcers who have a positive test result for H. pylori should be treated for the infection. Patients presenting with complications of ulcers, such as bleeding, should also be treated. H. pylori has recently been classified as a definite human carcinogen by the International Agency for Research on Cancer. In treatment, new combination regimens, consisting of 3 or 4 different drugs, cure the infection in more than 80% of patients. Currently, the best combinations are: (1) omeprazole (or another proton-pump inhibitor), clarithromycin and metronidazole, (2) omeprazole (or another proton-pump inhibitor), clarithromycin and amoxicillin, (3) bismuth subsalicylate, tetracycline and metronidazole, and (4) omeprazole, bismuth subsalicylate, tetracycline and metronidazole.
Algorithms↗
Review and analysis of the effects of olestra, a dietary fat substitute, on gastrointestinal function and symptoms.
Olestra, a dietary fat substitute, was recently made available to consumers in savory snacks in three cities. Early reports of gastrointestinal complaints attributed to olestra attracted media coverage and fostered confusion among physicians and consumers about the nature of olestra and its effects on the digestive system. We reviewed all published studies of olestra's gastrointestinal effects and all relevant unpublished studies submitted to the Food and Drug Administration. Each study was analyzed by a group of expert gastroenterologists and epidemiologists. The symptoms reported with olestra ingestion are similar to those reported with ingestion of fiber and sorbitol, although the mechanisms involved in changing stool characteristics differ among these food additives. Olestra's effects on stool habit and characteristics are due to its presence in the stool. Large amounts are more likely to induce gastrointestinal symptoms than small amounts. There is no evidence that olestra induces pathological change in bowel function: there is no increased fluid or electrolyte nor is there altered gastrointestinal motility or microflora. Olestra and triglyceride ingestion resulted in a similar frequency of symptoms in normal adults and children and in people with chronic inflammatory bowel disease in remission. Olestra traverses the digestive tract intact to become a stool additive. Some subjects develop a change in bowel habit and stool characteristics due to the presence of more olestra in the stool. These changes resemble those associated with ingestion of sorbitol and fiber.
Controlled Clinical Trials as Topic↗
What role does Helicobacter pylori play in dyspepsia and nonulcer dyspepsia? Arguments for and against H. pylori being associated with dyspeptic symptoms.
A major role for Helicobacter pylori gastritis in nonulcer dyspepsia (NUD) is controversial. Gastroduodenal dysfunction may be associated with H. pylori infection, but there is little evidence for a causal link with dyspepsia. Population-based studies with appropriate methodology have generally failed to confirm an association between H. pylori and NUD. Furthermore, no definite association between subgroups of NUD (ulcer-like, dysmotility-like, reflux-like, and nonspecific) and H. pylori has been identified however the subgroups have been defined, and no specific symptom pattern characterizes patients with H. pylori infection. Whether H. pylori-induced alterations of gastric physiology can explain NUD remains open to debate while we await the results of more specific experiments. Although acid secretion in response to gastrin-releasing peptide may be increased in a subset of NUD patients who are infected with H. pylori, uninfected patients with NUD have not been assessed and the results require confirmation. Most studies suggest no association between H. pylori and gastroduodenal motor or sensory dysfunction in NUD. Treatment trials have been unconvincing. The trials with bismuth therapy have not been adequately blinded. Furthermore, some studies suggest that H. pylori-negative patients with NUD may respond to bismuth treatment, although the results have not been uniform. Therapies aimed at curing H. pylori infection have produced mixed results, with small positive and negative trials. The trials that have used adequate outcome measures have more often than not been negative. Based on current evidence, H. pylori is not established to be of causal importance in NUD.
Dyspepsia↗
Modulation of neurocardiac function by oesophageal stimulation in humans.
1. The heart and the oesophagus have similar sensory pathways, and sensations originating from the oesophagus are often difficult to differentiate from those of cardiac origin. We hypothesized that oesophageal sensory stimuli could alter neurocardiac function through autonomic reflexes elicited by these oesophageal stimuli. In the present study, we examined the neurocardiac response to oesophageal stimulation and the effects of electrical and mechanical oesophageal stimulation on the power spectrum of beat-to-beat heart rate variability in male volunteers. 2. In 14 healthy volunteers, beat-to-beat heart rate variability was compared at rest and during oesophageal stimulation, using either electrical (200 microns, 16 mA, 0.2 Hz) or mechanical (0.5 s, 14 ml, 0.2 Hz) stimuli. The power spectrum of beat-to-beat heart rate variability was obtained and its low- and high-frequency components were determined. 3. Distal oesophageal stimulation decreased heart rate slightly (both electrical and mechanical) (P < 0.005), and markedly altered heart rate variability (P < 0.001). Both electrical and mechanical oesophageal stimulation increased the absolute and normalized area of the high-frequency band within the power spectrum (P < 0.001), while simultaneously decreasing the low-frequency power (P < 0.005). 4. In humans, oesophageal stimulation, whether electrical or mechanical, appears to amplify respiratory-driven cardiac vagoafferent modulation while decreasing sympathetic modulation. The technique provides access to vagoafferent fibres and thus may yield useful information on the autonomic effects of visceral or oesophageal sensory stimulation.
Adolescent↗
Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis.
BACKGROUND & AIMS: Esophagitis healing proportions are often incorrectly called the healing rate. The aim of this study was to compare different drug classes by expressing the speed of healing and symptom relief through a new approach. METHODS: A fully recursive literature search to July 1996 identified 43 articles on gastroesophageal reflux disease (GERD) (7635 patients) meeting strict inclusion criteria: single- or double-blind randomized studies in adults with endoscopically proven erosive or ulcerative esophagitis. For each drug class, linear regression analysis estimated the average percentage of patients who were healed and heartburn free per week. RESULTS: Mean overall healing proportion irrespective of drug dose or treatment duration (< or =12 weeks) was highest with proton pump inhibitors (PPIs; 83.6% +/- 11.4%) vs. H2-receptor antagonists (H2RAs; 51.9% +/- 17.1%), sucralfate (39.2% +/- 22.4%), or placebo (28.2% +/- 15.6%). Correcting for patients without baseline heartburn, the mean heartburn-free proportion was highest with PPIs (77.4% +/- 10.4%) vs. H2RAs (47.6% +/- 15.5%). PPIs showed a significantly faster healing rate (11.7%/wk) vs. H2RAs (5.9%/wk) and placebo (2.9%/wk). PPIs provided faster, more complete heartburn relief (11.5%/wk) vs. H2RAs (6.4%/wk). CONCLUSIONS: More complete esophagitis healing and heartburn relief is observed with PPIs vs. H2RAs and occurs nearly twice as fast. This semiquantitative expression of speed of healing and symptom relief permits comparisons for future economic evaluation and quality-of-life assessments.
Adolescent↗
Detection of hybrids in natural populations of the Anopheles gambiae complex by the rDNA-based, PCR method.
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Animals↗