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Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 91 records · Page 5Linked to original sources

Ribosomal DNA-polymerase chain reaction assay discriminates between Anopheles quadriannulatus and An. merus (Diptera: Culicidae).

A ribosomal DNA polymerase chain reaction technique (rDNA-PCR) that distinguishes the 5 more common and widespread members of the Anopheles gambiae complex failed to consistently identify specimens of Anopheles merus Dönitz collected in South Africa and Tanzania. When the original rDNA-PCR assay was applied to field-collected specimens or specimens from laboratory colonies established from these populations, bands diagnostic of both An. merus and An. quadriannulatus (Theobald) were amplified from all individual specimens. However, all the specimens tested had the polytene chromosome banding morphology or the superoxide dismutase isozyme that were diagnostic for An. merus. Replacement of the original An. quadriannulatus-specific primer with a new primer derived from another region of the rDNA intergenic spacer resulted in an alternative rDNA-PCR assay that accurately and consistently differentiated among specimens of An. merus, An. quadriannulatus, and An. arabiensis Patton. Anopheles gambiae Giles also may be distinguished by this assay if high percentage agarose gels or gels of other matrices with better resolving powers are used.

Animals↗

Hormonal therapy for bleeding gastrointestinal mucosal vascular abnormalities: a promising alternative.

Recurrent bleeding from an obscure gastrointestinal source is a common but often frustrating clinical challenge. Frequently these bleeds can be attributed to vascular anomalies in the upper or lower gastrointestinal tract. Traditional management has included surgical resection and endoscopic fulguration. However, these methods are often ineffective when vascular lesions are diffuse, difficult to identify, or endoscopically inaccessible. Hormone therapy with a combination of oestrogen and progesterone represents a promising alternative. Since initial reports of success in patients with epistaxis from hereditary haemorrhagic telangiectasia, growing evidence supports its role in reducing bleeding from gastrointestinal vascular anomalies. Existing literature is critically reviewed and management strategies incorporating hormone therapy are suggested.

Arteriovenous Malformations↗

Review: eradication of Helicobacter pylori. Problems and recommendations.

The successful isolation of Helicobacter pylori from stomachs of patients with gastritis and peptic ulcer has revolutionized our concepts of the pathogenesis of gastritis, peptic ulcer, gastric cancer and gastric B cell lymphoma. Eradication of H. pylori heals gastritis and H. pylori-related peptic ulcer. After a successful cure of H. pylori infection, virtually no recurrence of duodenal ulcer is seen. However, treatment to cure the infection has proved difficult. Numerous clinical trials have been attempted, but as yet no ideal regimen has been identified. Monotherapies have many drawbacks and should be avoided. Dual therapies combining a proton pump inhibitor (PPI) and an antimicrobial agent provide higher eradication rates than those involving two antimicrobial agents. Bismuth-based triple therapies are more effective than dual therapies in eradicating H. pylori infections. However, poor compliance and frequent adverse effects have made these combinations less favourable in clinical practice. Proton pump inhibitor-based triple therapies have shown more consistent and higher eradication rates with a short duration of treatment, good patient compliance, fewer side effects, prompt symptom relief and fast ulcer healing. Results from PPI-based quadruple therapies are promising; however, large multicentre clinical trials are needed to confirm the effect and the complex regimen again may compromise compliance outside of the clinical trial setting. Eradication of H. pylori infection is cost-effective in the long-term management of peptic ulcer disease compared with maintenance therapy with antisecretory drugs.

Drug Therapy, Combination↗

Effects of smoking on cure of Helicobacter pylori infection and duodenal ulcer recurrence in patients treated with clarithromycin and omeprazole.

BACKGROUND: Smoking may affect adversely the cure rate for Helicobacter pylori infection in patients treated with amoxicillin and omeprazole. Therapy with clarithromycin and omeprazole was tested for its effectiveness in the treatment of H. pylori infection in smokers and nonsmokers. MATERIALS AND METHODS: Patients with verified duodenal ulcer and H. pylori infection received clarithromycin 500 mg tid, in combination with omeprazole 40 mg/ day, for 2 weeks, followed by omeprazole (20 or 40 mg daily) for 2 additional weeks according to a randomized, double-blind, multicenter design. Patients were analyzed by their smoking status for the cure of H. pylori infection, ulcer healing, and prevention of duodenal ulcer recurrence. RESULTS: After treatment with clarithromycin and omeprazole, H. pylori infection was cured in 71% of the smokers and in 77% of the nonsmokers (evaluated 4-6 weeks after treatment). Overall ulcer healing was 95%, and overall ulcer recurrence was 19%. For H. pylori-negative patients, ulcer recurrence was 12% in both smokers and nonsmokers. None of these values was significantly different when smokers were compared to nonsmokers. CONCLUSIONS: Therapy with clarithromycin and omeprazole is effective for cure of H. pylori infection in smokers and nonsmokers. Smoking has no effect on duodenal ulcer healing or duodenal ulcer recurrence for patients treated with this regimen.

Adult↗

Peptic ulcer disease: defining the treatment strategies in the era of Helicobacter pylori.

Peptic ulcer disease continues to be a major health care problem costing the public billions of dollars each year. Recent evidence confirms a major role for Helicobacter pylori infection in the natural history of most cases of peptic ulcer disease. The most established and effective antibiotic treatment for the eradication of H. pylori has been the classic bismuth "triple therapy" regimen containing bismuth, metronidazole, and tetracycline. However, pretreatment resistance to metronidazole, poor compliance, and side effects have limited the widespread acceptance of bismuth triple therapy for routine use. Recent studies suggest that the combination of one or two antibiotic agents and a proton pump inhibitor offers a better tolerated regimen than bismuth triple therapy. Efficacy is similar with respect to eradication of H. pylori, and the combined use of a proton pump inhibitor assures rapid symptom relief and ulcer healing. Although the mechanisms by which H. pylori eradication is effected, the optimal dosing schedules, and the specific antimicrobial agents to be administered require further study, the combination of a proton pump inhibitor and one or two antibiotics promises to be an appropriate first-line treatment for peptic ulcer disease.

Anti-Bacterial Agents↗

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used. SURGERY: Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation. HEALTH ECONOMICS: There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.

Canada↗

Controversial issues in gastroesophageal reflux disease.

The management of gastroesophageal reflux disease (GERD) has advanced dramatically in the past 20 years because of increased understanding of its pathophysiology and improvements in available treatments. A number of important new ideas arousing controversy include the place of over-the-counter H2 receptor antagonists; the role of endoscopy in diagnosis of reflux symptoms; initial treatment options with regard to stepping up therapy to the most effective as needed or stepping down therapy from a proton pump inhibitor given initially because of its superior efficacy in all grades of reflux disease; the optimal choice of long term management of patients with GERD or GERD complicated by Barrett's metaplasia; the risk of Barrett's metaplasia; and the role of surveillance of this population. This paper reviews these topics and addresses the controversial issues.

Barrett Esophagus↗

An orally active non-selective endothelin receptor antagonist, bosentan, markedly reduces injury in a rat model of colitis.

Activation of endothelial cells by vasoactive mediators, such as endothelins, may be an early, strategically important step in the initiation of inflammation in the intestine. In view of recent evidence that inflammatory bowel disease is associated with elevated intestinal concentrations of endothelins and upregulated expression of endothelin receptors on vascular endothelium in intestine, endothelins may become therapeutic targets in inflammatory bowel disease. The recent availability of an orally active, mixed endothelin receptor antagonist, bosentan, allowed us to examine the role of endothelins in a rat model of colitis. Colitis was induced by intra-rectal administration of trinitrobenzene sulphonic acid. In each treatment group, rats were treated with bosentan (10-60 mg/kg p.o.) 24 and 2 h prior to (pre-dose) or 1 h after the induction (post-induction) of colitis and all animals were treated every 24 h thereafter for 5 days. On day 6, stool consistency and the presence of adhesions in the peritoneal cavity were accessed. Colonic tissue samples were removed for determination of macroscopic and microscopic tissue injury, and myeloperoxidase activity. Colitis was typified by tissue ulceration in the distal colon and a corresponding 35-fold increase in myeloperoxidase activity compared to non-inflamed controls. Daily treatment with bosentan dose-dependently reduced colonic damage and myeloperoxidase activity when bosentan was given prior to induction of colitis. In the pre-dose group, the greatest beneficial effect of bosentan was observed at 60 mg/kg; colonic damage and granulocyte infiltration were attenuated by > 80%. A partial therapeutic effect of bosentan was also observed at 60 mg/kg when the pre-treatment regimen was excluded. These findings demonstrate that an orally active, mixed endothelin receptor antagonist has marked protective and therapeutic effects in an animal model of colitis.

Administration, Oral↗

Eradication of Helicobacter pylori infection.

Helicobacter pylori is probably the most common bacterial infection worldwide and the accepted cause of chronic active gastritis. It has a critical role in duodenal ulcer, where the prevalence of infection is 90-95%. There is a dramatic reduction in the rate of ulcer recurrence after successful eradication of the organism to about 4% per annum compared with up to 80% when the infection persists. What is true for duodenal ulcers is also true for patients with gastric ulcer who are infected with H. pylori. The risk of recurrent ulcer complications with bleeding is virtually abolished following successful eradication of H. pylori; in contrast, the risk of rebleeding is about 33% in patients still harboring the organism. The treatment of H. pylori infection in patients with confirmed peptic ulcer on first presentation or recurrence has been advocated by a Consensus Conference of the National Institutes of Health. The most evaluated regimens include dual therapy with a proton pump inhibitor and either amoxicillin or clarithromycin, and bismuth-based triple therapy with metronidazole and tetracycline. The use of a proton pump inhibitor-containing regimen offers the advantage of rapid symptom relief and the highest rates of duodenal ulcer healing. Moreover, combinations of a proton pump inhibitor and clarithromycin show more predictable and higher eradication rates than amoxicillin combinations. Newer triple therapies with a proton pump inhibitor plus two antibacterial agents given for 7-1O days are being increasingly described and may become the treatment of choice if initial results are confirmed. However, the optimum dosage regimen needs to be established. A new combination of ranitidine bismuth citrate and clarithromycin has also recently been shown to be effective. At this time it is reasonable to consider all patients with confirmed duodenal or gastric ulcer for eradication of H. pylori, and no patient should be considered for elective surgery without first being offered eradication therapy.

Amoxicillin↗

Habit, prejudice, power and politics: issues in the conversion of H2-receptor antagonists to over-the-counter use.

H2-receptor antagonists have been widely prescribed in the last 20 years and are considered to rank among the safest drugs known. In several countries they have been switched to over-the-counter (OTC) status, and a similar move is under consideration in Canada. Some concerns have been raised as to the effectiveness of these drugs in the treatment of dyspepsia and heartburn, their safety when taken for self-diagnosed symptoms, and the potential for their use to delay diagnosis or mask serious disease. The author presents evidence to support the use of OTC H2-receptor antagonists in the treatment of dyspepsia. He argues that the safety record of these drugs is reassuring and that they are unlikely to mask gastric cancer. Finally, he describes the appropriate place of OTC H2-receptor antagonists in the overall management of acid-related disorders.

Attitude of Health Personnel↗

Time to maximum effect of lansoprazole on gastric pH in normal male volunteers.

BACKGROUND: The time to maximum inhibition of gastric acidity resulting from repeated oral dosing with lansoprazole 30 mg daily for 7 days was studied in nine healthy male volunteers. METHODS: Twenty-four hour intragastric pH monitoring was performed before treatment and on days 1, 3, 5 and 7 of dosing with lansoprazole. Blood samples were taken for the estimation of plasma lansoprazole concentrations. RESULTS: Lansoprazole 30 mg increased mean 24-h intragastric pH to 3.57 on day 1 compared with baseline mean pH of 2.11 (P < 0.05). The mean intragastric pH during the morning period (08.00-13.00 h) was significantly higher on days 3, 5 and 7 than on day 1, but no consistent differences between day 1, 3, 5 and 7 were noted for subsequent periods (13.00-18.00, 18.00-21.00 and 23.00-07.00 h). There were no differences in mean pH between days 3, 5 and 7. Intragastric pH was maintained above pH 3 for 54.7, 60.1, 61.9 and 67.4% of the time on days 1, 3, 5 and 7, respectively. Lansoprazole pharmacokinetic parameters did not change with daily dosing. The area under the lansoprazole plasma concentration-time curve correlated with the intragastric pH (P < 0.005). CONCLUSIONS: Lansoprazole 30 mg raised intragastric pH significantly from baseline on day 1 to a maximum effect as early as 6 h after the first dose. The degree and duration of acid suppression confirm the usefulness of lansoprazole for the treatment of acid-related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Clinical economics review: cost-effectiveness of treatment alternatives for gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is a chronic recurring disorder, which is widespread, especially in Western societies. Faced with increasing health costs and finite resources, an increasingly important part of evaluating new treatments is economic appraisal. In this paper, we review critically the published economic studies of the cost-effectiveness of treatments for gastro-oesophageal reflux disease. Proton pump inhibitors are considered the best choice for the management of grades II-IV oesophagitis and are more cost-effective than H2-receptor antagonists because of their fast healing of oesophagitis, early relief of symptoms, and prevention of recurrent oesophagitis and development of complications.

Cost-Benefit Analysis↗

The polymerase chain reaction method as a tool for identifying members of the Anopheles gambiae complex (Diptera:Culicidae) in northeastern Tanzania.

Polymerase chain reaction (PCR) primers developed at the Centers for Disease Control in Atlanta for the identification of members of the Anopheles (Cellia) gambiae Giles complex were tested on material collected in the Bagamoyo and Muheza districts of northeastern Tanzania. Part of the sample from Bagamoyo was chromosomally identified and correlated with the PCR identifications. This sample contained 170 Anopheles arabiensis, 328 An. gambiae, and 58 Anopheles merus, of which 121, 237, and 54 specimens, respectively, were identified with both PCR and chromosomes. Three specimens identified chromosomally as An. merus gave only the PCR fragment characteristic for Anopheles quadriannulatus, but on retesting gave the correct result. The Muheza sample consisted of 771 An. arabiensis, 852 An. gambiae, 43 An. merus, and 4 specimens producing the fragment characteristic for An. quadriannulatus. Because An. quadriannulatus has never been recorded from mainland Tanzania and due to the high number of specimens that produced no result (193), it is probable that DNA degradation led to misidentification of An. merus specimens as An. quadriannulatus. The overall probability of correct identification by PCR was 99.685% at first testing, which compares favorably with other genetic methods currently in use.

Animals↗

Why guidelines are required for the treatment of Helicobacter pylori infection in children.

Helicobacter pylori is firmly established as a human pathogen; it fulfils all of Koch's postulates as the infectious agent causing chronic, active (type B) gastritis. Infection is strongly associated with duodenal and gastric ulcer. Recently, gastric mucosal-associated lymphoid tissue lymphoma has been successfully treated by curing H. pylori infection. Because of the evidence that the organism causes chronic gastritis and an increased risk of gastric cancer, it has been classified as a category 1 carcinogen by the World Health Organization. However, the overwhelming majority of people infected have no symptoms. Current eradication therapy is not ideal; there are treatment failures and substantial side effects. As a result, therapy should be reserved for people with clinical symptoms and complications. The infection, if present, should be treated in patients who have endoscopic evidence of mucosal ulcers in the stomach or duodenum. Current evidence does not support treating the infection to prevent gastric carcinogenesis or to alleviate symptoms of abdominal discomfort in the absence of peptic ulcers.

Child↗

The role of Helicobacter pylori in pathogenesis: the spectrum of clinical outcomes.

Helicobacter pylori is probably the commonest bacterial infection worldwide and is now accepted as the cause of chronic active type B gastritis. Most patients continue through life with a chronic superficial gastritis while some develop either duodenal or gastric ulcer. In a very small proportion the lymphoid reaction to H. pylori infection appears to progress to become a mucosal associated lymphoid tissue (MALT) lymphoma, while in others the evidence suggests that chronic superficial gastritis progresses to atrophy, the loss of gastric acid secretory capacity and the development of gastric cancer. The mechanisms involving H. pylori infection in peptic ulceration are increasingly well understood and H. pylori is now accepted as having a critical role in duodenal ulcer, where the prevalence of infection is 90 to 95%. More important is the dramatic reduction in duodenal ulcer recurrence after successful eradication of the organism to about 4% in a year compared to recurrences of up to 80% in those who ulcers have been healed but in whom the infection persists. There is also increasing evidence for the involvement of H. pylori in gastric ulcer, where infection is seen in between 60 and 80%, and there is a similar dramatic reduction in recurrence following cure of H. pylori infection. The progression of H. pylori gastritis from the acute infection to chronic superficial gastritis, predominantly antral gastritis or a pangastritis with increasing atrophy appears to be associated with the differing outcomes seen in this disease. Moreover, there is increasing data on the roles played by bacterial heterogeneity and the virulence of the organism, host factors such as the HLA genotype and immune response, environmental factors and the age of acquisition of infection play in determining these clinical outcomes of the disease.

Gastric Acid↗