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Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 55 records · Page 3Linked to original sources
PubMed2000

Implications of antibiotic resistance in the management of Helicobacter pylori infection: Canadian Helicobacter Study Group.

Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori-associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori, formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

Anti-Bacterial Agents↗
PubMed2000

Obscure gastrointestinal bleeding: an approach to management.

Obscure gastrointestinal bleeding provides an uncommon but frustrating and resource-intensive challenge for clinicians. Such patients hemorrhage recurrently from sites within the gastrointestinal tract that are not detected by routine endoscopy or radiography, and require a special diagnostic approach to localize or exclude less common bleeding sources such as small bowel angioectasia or neoplasia. The differential diagnosis of obscure gastrointestinal hemorrhage is discussed, and the performance of available endoscopic, radiological and surgical diagnostic tools including enteroscopy are examined critically. A stepwise management algorithm that progresses from the history and physical examination to surgical exploration is offered to facilitate early and efficient diagnosis.

Angiography↗
PubMed2000

Local plants as repellents against Anopheles arabiensis, in Mpumalanga Province, South Africa.

OBJECTIVE: To assess the repellency effect of three local plants; fever tea (Lippia javanica), rose geranium (Pelargonium reniforme) and lemon grass (Cymbopogon excavatus) against laboratory reared Anopheles arabiensis mosquitoes. DESIGN: A laboratory experimental study. SETTING: Mpumalanga Province, South Africa. SUBJECTS: Three adult male volunteers. MAIN OUTCOME MEASURES: Affordable alternatives to synthetic repellents against biting of Anopheles arabiensis mosquitoes. RESULTS: All three alcohol plant extracts provided significantly more protection (p = 0.012) than alcohol control. The alcohol plant extract of L. javanica provided 76.7% protection against An. arabiensis after a four hour period, and C. excavatus and P. reniforme provided 66.7% and 63.3% protection for three hours, respectively. At five hours post application only L. javanica alcohol extract provided appreciable protection (59.3%) against An. arabiensis. CONCLUSION: The results of this study indicate that L. javanica, P. reniforme and C. excavatus protect against An. arabiensis mosquito bites with the repellent effect of L. javanica lasting significantly longer than that of the other two plants.

Animals↗
PubMed1999

Gastrointestinal safety profile of nabumetone: a meta-analysis.

Individual comparative studies suggest that nabumetone has a gastrointestinal (GI) safety profile superior to comparator NSAIDs but lack power to show a statistical difference. The aim of this study was to evaluate systematically the difference in GI adverse events--especially the rate of perforations, ulcers, and bleeds (PUBs)-- between studies, meta-analyses of comparative trials of nabumetone and conventional NSAIDs, and postmarketing, open-label studies of nabumetone meeting predefined inclusion and exclusion criteria. A fully recursive literature search identified 13 studies consisting of 29 treatment arms and 49,501 patients that met the predefined criteria. Tests for heterogeneity found no significant difference between studies of each subgroup. Overall, the dyspeptic symptoms flatulence, constipation, and diarrhea were the most commonly reported adverse events accounting for 98.6% of the total GI adverse events. Significantly more patients treated with a comparator NSAID experienced GI adverse events than did those taking nabumetone (P = 0.007). After adjustment for patient-exposure years, PUBs were 10 to 36 times more likely to develop in patients treated with a comparator NSAID than with nabumetone. This was consistently seen in patients in nonendoscopic (n = 7,468) and endoscopic studies (n = 244). In the analysis of postmarketing or open-label studies of nabumetone, only one PUB was reported per 500 patient-exposure years over 17,502 treatment years (n = 39,389). GI adverse event-related dropouts and hospitalizations were increased by 1.3- and 3.7-fold if patients were treated with a comparator NSAID than with nabumetone. Significantly fewer treatment-related GI adverse events, especially PUBs, are seen in patients treated with nabumetone than with a comparator NSAID. Nabumetone is very safe for the GI tract.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Importance of pH control in the management of GERD.

The degree of esophageal mucosal injury that occurs in patients with gastroesophageal reflux disease depends on duration of exposure and pH of the refluxate. Evidence suggests that an intraesophageal pH of less than 4.0 directly correlates with the degree of mucosal injury. The advent of acid secretory inhibitors such as the histamine2-receptor antagonists (H2RAs) and, more recently, the proton pump inhibitors (PPIs) has revolutionized the treatment of patients with reflux disease. However, the evidence linking the degree of mucosal damage to pH of the refluxate has prompted investigators to reevaluate the effectiveness of these agents. The PPIs are significantly more effective than the H2RAs in achieving and sustaining an intragastric pH above 4.0. The results of clinical trials performed with the PPIs indicate a faster rate of healing of erosive esophagitis and of symptom relief than treatment with H2RAs.

Drug Administration Schedule↗
PubMed1999

Accurate flow cytometric membrane potential measurement in bacteria using diethyloxacarbocyanine and a ratiometric technique.

BACKGROUND: Membrane potential (MP) plays a critical role in bacterial physiology. Existing methods for MP estimation by flow cytometry are neither accurate nor precise, due in part to the heterogeneity of size of the particles analyzed. The ratio of a size- and MP-sensitive measurement, and an MP-independent, size-sensitive measurement, should provide a better estimate of MP. METHODS: Flow cytometry and spectrofluorometry were used to detect red (488 --> 600 nm) fluorescence associated with aggregates of diethyloxacarbocyanine (DiOC2(3)), which, in the monomeric state, is normally green (488 --> 530 nm) fluorescent. RESULTS: In bacteria incubated with 30 microM dye, aggregate formation increases with the magnitude of the interior-negative membrane potential. Green fluorescence from stained bacteria predominantly reflects particle size, and is relatively independent of MP, whereas red fluorescence is highly dependent on both MP and size. The ratio of red to green fluorescence provides a measure of MP that is largely independent of cell size, with a low coefficient of variation (CV). Calibration with valinomycin and potassium demonstrates that the method is accurate over the range from -50 mV through -120 mV; it also accurately tracks reversible reductions in MP produced by incubation at 4 degrees C and washing in glucose-free medium. CONCLUSIONS: The ratiometric technique for MP estimation using DiOC2(3) is substantially more accurate and precise than those previously available, and may be useful in studies of bacterial physiology and in investigations of the effects of antibiotics and other agents on microorganisms.

Calibration↗
PubMed1999

Development of a health-related quality-of-life questionnaire for individuals with gastroesophageal reflux disease: a validation study.

This study was conducted to test the psychometric properties of a newly developed health-related quality-of-life (HRQoL) questionnaire. A total of 172 symptomatic GERD patients completed a 57-item questionnaire (containing the SF-12; symptom frequency/bothersomeness; problems related to activities, sleep, work disability; overall HRQoL; and treatment satisfaction) at baseline, week 1 [retest (N = 25)], and week 4 [follow-up (N = 100)]. Internal-consistency reliability was acceptable for most scales (range: 0.74-0.92). Test-retest reliability was acceptable for most scales (ICC: 0.74-0.85). Construct validity was demonstrated based on observed correlations. Known-groups validity was upheld, as patients who experienced more symptom days and patients who reported higher pain reported worse HRQoL than those with less symptoms or less severe pain. When categorized according to change in pain severity, Guyatt's statistic for the "improved" and "worse" groups demonstrated responsiveness, although many of the scales for the "stable" group were also responsive. In conclusion, the HRQoL questionnaire was found to be reliable, valid, and responsive.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Anti-ulcerogenic properties of endothelin receptor antagonists in the rat.

BACKGROUND: Endothelins have been implicated in gastric mucosal damage in a variety of animal models. Exogenous ET-1 and ET-3 are causally associated with experimental gastric ulcers. Furthermore, clinical reports also show elevated plasma and gastric mucosal endothelin-1 levels in patients suffering from peptic ulcers. AIM: To study the possibility that endothelin receptor antagonists may have beneficial effects and prevent the development of gastric ulcers. We have tested in rats the orally-active endothelin antagonist bosentan (Ro 47-0203) and Ro 48-5695, which is 10-30 times more potent than bosentan on endothelin receptors. METHODS: Water immersion restrained stress (WIRS) and indomethacin were used to provoke gastric mucosal damage. Endothelin receptor antagonists were administered orally prior to the induction of gastric damage. The gastric lesion index (mm), assessed macroscopically, and myeloperoxidase (MPO) activity were used as markers of the extent of mucosal injury. RESULTS: Bosentan at 100 and 30 mg/kg administered orally caused attenuation of gastric damage in the WIRS model by 58% and 42%, respectively. Bosentan also caused complete reduction of MPO activity. In indomethacin-induced gastric damage, 100 mg/kg bosentan attenuated gastric damage by 45% and 61% as measured by the gastric lesion index and MPO activity respectively. Ro 48-5695 was at least 30 times more potent than bosentan in reducing indomethacin-induced mucosal damage and at 3 mg/kg, caused a decrease of 49% in the gastric lesion index and a reduction in MPO activity of 41%. Bosentan and Ro 48-5695 possess weak antisecretory properties as tested in the mouse gastric gland assay, than cannot, alone, account for their anti-ulcer properties. CONCLUSIONS: Both endothelin receptor antagonists prevented the development of gastric mucosal injury in the rat. Disturbances in the gastric microcirculation are responsible for the development of experimental gastric ulcers. The anti-ulcer properties of these two endothelin antagonists suggest possible new therapeutic approaches to controlling gastric inflammation.

Animals↗
PubMed1999

The importance of clarithromycin dose in the management of Helicobacter pylori infection: a meta-analysis of triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole.

BACKGROUND: It is not clear which dose of clarithromycin (500 mg b.d. or 250 mg b.d.) is more effective for Helicobacter pylori eradication in proton pump inhibitor-based triple therapies. METHODS: We undertook a meta-analysis of the effect of 7-day triple therapies consisting of a proton pump inhibitor (P), and clarithromycin (C) and amoxycillin (A) or metronidazole (M). A meta-analysis of all clinical trials performed in an adult population and published in English up to March 1998 was undertaken. Studies with doses of clarithromycin 500 mg b.d. or 250 mg b.d. only were included. RESULTS: A total of 82 studies (31 papers and 51 abstracts) involving 110 treatment arms and 6123 patients were analysed that met the predetermined inclusion and exclusion criteria. In the PAC combination, the pooled eradication rate in patients treated with clarithromycin 500 mg b.d. was 89.5% (95% CI: 86.9-92. 0%) by per protocol analysis and 86.6% (95% CI: 81.0-89.3%) by intention-to-treat analysis. These rates are significantly higher than those achieved with clarithromycin 250 mg b.d. (83.3% by per protocol and 78.2% by intention-to-treat analysis, both P < 0.0001). This difference was confirmed in head-to-head comparative studies. In the PMC regimen, clarithromycin 500 mg b.d. eradicated 90.8% (95% CI: 87.0-94.5%) of the infections compared to 88.5% (95% CI: 85.5-91. 5%) in patients treated with clarithromycin 250 mg b.d. by per protocol analysis (P = 0.082). The corresponding rates by intention-to-treat analysis for clarithromycin 500 mg b.d. and 250 mg b.d. was 88.3% and 86.7%, respectively (P = 0.259). CONCLUSIONS: Seven-day triple therapies with a proton pump inhibitor, clarithromycin and amoxycillin or metronidazole are highly effective treatments for the eradication of H. pylori. Clarithromycin 500 mg b. d. should be used in these combinations to achieve the best first treatment results, which can minimize the subsequent development of bacterial resistance to clarithromycin and metronidazole.

Adult↗
PubMed1999

A systematic overview of the use of diary cards, quality-of-life questionnaires, and psychometric tests in treatment trials of Helicobacter pylori-positive and -negative non-ulcer dyspepsia.

BACKGROUND: Our aim was to evaluate the use of diary cards, quality-of-life questionnaires, and psychometric tests in treatment trials of non-ulcer dyspepsia. METHODS: Data sources were a Medline search (up to 1966) and a manual search of five gastrointestinal journals (up to 1980) for original, randomized, double-blind, placebo-controlled trials with at least 20 patients which evaluated treatment regimens for non-ulcer dyspepsia. RESULTS: Of the 67 eligible studies, 31 used diary cards. Diary cards were used alone in 15 of the 31 studies (48%), whereas the others (52%) also used a physician assessment. The symptoms assessed by diary cards were epigastric pain (100%), nausea/vomiting (65%), heartburn (52%), belching (39%), regurgitation (29%), fullness (29%), and bloating (23%). Forty-five per cent also recorded antacid use. Severity of outcome measures was assessed by a visual analogue scale in 5 of the 31 studies (16%), Likert scales in 17 studies (55%), and unclear methods in 3 studies (10%). For statistical analysis daily averages of symptoms were used in 5 of the 31 studies (16%), weekly averages in 11 studies (35%), and 2-week intervals during the treatment period in the rest, with some studies using a combination (such as daily and weekly averages). Only 3 of the 31 studies (8%) checked for compliance with diary card data. None of the studies mention anything about missing data and how this was handled. One study evaluated quality of life questionnaires and one evaluated a psychometric test. CONCLUSIONS: Non-ulcer dyspepsia treatment trials frequently use diary cards but need to be much clearer about how information was obtained and how it was used in the statistical analysis. Not much information is available to comment on the use of quality-of-life questionnaires or psychometric tests for evaluation of outcome measures.

Dyspepsia↗
PubMed1999

Single-strand conformation polymorphism analysis for identification of four members of the Anopheles funestus (Diptera: Culicidae) group.

Members of the Anopheles funestus Giles group are difficult to identify because of the morphological overlap that exists within the group. This inability to distinguish species, as well as the fact that the species vary in their behavior and biting preferences, complicate the successful planning and maintaining of malaria control programs. In this article we discuss the use of a single-strand conformation polymorphism (SSCP) assay to distinguish 4 members of the An. funestus group collected at 10 different localities in Africa. rDNA genes differ at numerous sites among closely related species. Using conserved primers, the D3 domain in the 28S gene was amplified, electrophoresed on SSCP gels, and species-specific patterns were observed. Intraspecific variation was detected in An. funestus specimens from East and West Africa. Analyzing 108 An. funestus, 78 An. vaneedeni Gillies & Coetzee, 21 An. rivulorum Leeson, and 2 An. lessoni Evans, we concluded that SSCPs can be used successfully as a molecular tool for the identification of these species.

Animals↗
PubMed1999

Replication-defective adenovirus infection reduces Helicobacter felis colonization in the mouse in a gamma interferon- and interleukin-12-dependent manner.

Helicobacter infection leads to chronic inflammation of the stomach. Although the infection persists in spite of an immune response, animal studies have shown that adjuvant-based oral vaccines can protect against infection and even eliminate established infection. These vaccines are thought to induce a Th2 immune response, counterbalancing the Th1 response seen with natural infections. As a prelude to using adenovirus vectors carrying cytokine genes to modulate the immune response to established Helicobacter felis infection, we first examined the effect of the replication-defective adenovirus (RDA) vector itself. C57BL/6 mice chronically infected with H. felis (8 to 10 weeks) received intramuscular injections of RDA. The effect of RDA on the severity of H. felis colonization and the degree of gastric inflammation was assessed 2 weeks later. RDA caused a significant decrease in H. felis colonization without significantly altering the associated inflammation. RDA did not alter the H. felis-specific immunoglobulin G1 (IgG1), IgG2a, and IgA responses in the serum but was associated with an increase in gamma interferon (IFN-gamma)-producing CD8(+) spleen cells. To determine if IFN-gamma or Th1 cytokines were involved in the response to RDA, we examined RDA treatment of H. felis infection in mice lacking either IFN-gamma or interleukin-12 (IL-12). RDA failed to alter H. felis colonization in either of these two mouse strains. Thus, viral infection of mice chronically infected with H. felis led to a significant decrease in H. felis colonization in an IFN-gamma- and IL-12-dependent manner. These results demonstrate that Th1 responses associated with systemic viral infection can influence an established H. felis infection.

Adenoviridae Infections↗
PubMed1999

Treatment after failure: the problem of "non-responders".

Although the currently most effective treatment regimens cure about 90% of infections, 10% of patients remain Helicobacter pylori positive. Several factors contribute to treatment failure. These include patient compliance, bacterial resistance to antibiotics, and treatment related issues. Treatment failure leads to the development of bacterial resistance to metronidazole and clarithromycin. Retreatment can be undertaken after considering several different strategies: to repeat the same regimen with full doses of medications and a longer treatment duration, or to choose different regimens to avoid the antibiotic previously used, or to switch to proton pump inhibitor (PPI) based quadruple therapy or ranitidine bismuth citrate (RBC) based triple therapy. In principle, full doses and longer treatment durations are advisable. As retreatment is always difficult, choosing the best available first line treatment regimen is still the best "rescue" treatment.

Drug Resistance, Microbial↗
PubMed1999

Canadian Helicobacter pylori Consensus Conference update: infections in adults. Canadian Helicobacter Study Group.

The first Canadian Helicobacter pylori Consensus Conference took place in April 1997. The initial recommendations of the conference were published in early 1998. An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations. Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it was decided that the urea breath test (not serology) should be used for routine diagnosis of H pylori infection unless endoscopy is indicated for another reason; and recommended therapies were a twice daily, seven-day regimen of a proton pump inhibitor (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) or ranitidine bismuth citrate 400 mg, plus clarithromycin 500 mg and amoxicillin 1000 mg, or plus clarithromycin 500 or 250 mg and metronidazole 500 mg. The need was reiterated to have funding for readily accessible, accurate testing for H pylori infection with the urea breath test. It was strongly recommended that regional centres be established to monitor the prevalence of antibiotic-resistant H pylori infections. The initial consensus document referred to pediatric issues that were not addressed in this update but were the subject of a subsequent Canadian Helicobacter Study Group meeting, and will be published later in 1999.

Adult↗
PubMed1999

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter pylori Infection in Children and Adolescents.

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

Adolescent↗
PubMed1999

Cytogenetic evidence for a species complex within Anopheles pseudopunctipennis theobald (Diptera: Culicidae).

Anopheles pseudopunctipennis was collected from Acapulco, Mexico and Sallee River, Grenada, West Indies and used in cross-mating experiments. Larvae from the cross, Mexico female X Grenada male, died in the third instar. However, adult progeny were obtained from the reciprocal cross Grenada female x Mexico male. These hybrid males had testes with apparently normal appearance but some without viable sperm. Polytene chromosomes obtained from hybrid females exhibited extensive asynapsis of the X chromosomes. Previously undescribed fixed inversion differences between the two populations were noted on the X chromosome. It is concluded that the two populations belong to different species. The Grenada population is designated An. pseudopunctipennis species C, since it is the third taxon recognized in this species complex.

Animals↗
PubMed1999

Evaluation of a polymerase chain reaction assay for detection of pyrethroid insecticide resistance in the malaria vector species of the Anopheles gambiae complex.

A published polymerase chain reaction assay proved reliable for detecting nerve-insensitivity (kdr-type) resistant and susceptible alleles to the pyrethroid insecticide permethrin in the malaria vectors Anopheles gambiae s.s. and An. arabiensis and the nonvector species An. quadriannulatus. The assay detects pyrethroid susceptible and resistance alleles mediated by a mutation in region II of the para-type sodium channel gene, showing that resistance is conferred by pyrethroid target site insensitivity. Analysis of results of the assay suggests that more than 1 mechanism conferring pyrethroid resistance is operating in an An. gambiae s.s. strain from Côte d'Ivoire. The value of the assay as a tool for monitoring this mode of insecticide resistance in wild populations is discussed.

Animals↗