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Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 163 records · Page 9Linked to original sources
PubMed1990

Acid and barriers. Current research and future developments for peptic ulcer therapy.

Medical therapy for peptic ulcer disease has been targeted at inhibiting acid secretion based on the belief that ulcers occur due to an imbalance between aggressive and protective factors. New antisecretory agents are unlikely to show any dramatic improvement over the success and safety of histamine H2 receptor antagonists or the recently introduced H+K+ATPase proton pump antagonist omeprazole. The development of specific muscarinic M3 and gastrin receptor antagonists will provide useful agents to suppress acid and pepsinogen secretion by alternative means and may prevent the associated hypergastrinaemia seen with anti-secretory therapy. Enhancement of mucosal defence by site protective agents will be based on a better understanding of the vascular and immune factors involved in maintaining mucosal integrity and the growth factors that regulate wound healing. Molecular techniques are likely to produce the 'model anti-ulcer' agent which will effectively inhibit acid secretion and also enhance wound healing thus providing a cure for this chronic disease.

Antacids↗
PubMed1990

Control of pepsinogen synthesis and secretion.

The heterogeneous group of proteinases known as pepsinogens are synthesized, stored, and upon appropriate stimulation released from gastric mucosal chief cells. Under the acidic conditions of the lumen of the stomach, the proenzymes, pepsinogens, are converted to "pepsin", which plays an important physiologic role as a digestive enzyme. The potential roles for pepsin in upper gastrointestinal diseases such as gastric or duodenal ulcer and gastroesophageal reflux disease along with the recent development of in vitro gastric gland and isolated chief cell preparations have renewed interest in the study of the control of pepsinogen synthesis and secretion. In this article the authors briefly summarize current knowledge of the biology of pepsinogens and emphasize more recent findings concerning the control of the chief cell, which is related to the synthesis and secretion of pepsinogens in vitro.

Animals↗
PubMed1990

14C-urea breath test for the detection of Helicobacter pylori.

The high urease activity of Helicobacter pylori can be used to detect this bacterium by noninvasive breath tests. We have developed a 14C-urea breath test which uses 5 microCi 14C with 50 mg nonradioactive urea. Breath samples are collected at baseline and every 30 min for 2 h. Our study compared the outcome of the breath test to the results of histology and culture of endoscopically obtained gastric biopsies in 84 patients. The breath test discriminated well between the 50 positive patients and the 34 patients negative for Helicobacter pylori: the calculated sensitivity was 100%, specificity 88%, positive predictive value 93%, and negative predictive value 100%. Treatment with bismuth subsalicylate and/or ampicillin resulted in lower counts of exhaled 14CO2 which correlated with histological improvement in gastritis. The 14C-urea breath test is a better "gold standard" for the detection of Helicobacter pylori than histology and/or culture.

Biopsy↗
PubMed1989

A parasitological, cytogenetic and biochemical study of Anopheles gambiae (Diptera: Culicidae) from the People's Republic of Congo.

A sample of 41 live adult members of the Anopheles gambiae complex were obtained from Yaka Yaka, near Brazzaville, People's Republic of Congo. They were collected resting in human habitations. Thirty-seven specimens were identified as A. gambiae s.s. using cytogenetic and electrophoretic criteria. Of the identified sample, one specimen was heterozygous for a previously undescribed inversion on chromosome arm 3. One female and the progeny of a second were found to be polymorphic for a superoxide dismutase electromorph previously only found in A. bwambae and A. arabiensis. Thirty-four specimens were examined for plasmodia. Five had oocysts on their stomachs and 2 had sporozoites in the salivary glands.

Animals↗
PubMed1989

Initial therapy and relapse of duodenal ulcer: possible acid secretory mechanisms.

Review of the four studies investigating the effect of initial therapy on ulcer relapse indicates that there is an increased rate of relapse after treatment with H2-receptor antagonists compared with placebo or other classes of drugs when combined. When individual drugs are considered, this appears to hold true for colloidal bismuth alone. There are several possible reasons for these differences. The most likely candidate mechanism to account for these differences is an alteration in gastric secretion, which might arise from alterations in gastrin, altered receptor regulation, parietal cell sensitivity, or peptic activity. However, the evidence for such an alteration in secretion is far from conclusive. Other factors that may be important include mucosal defense factors, smoking, Campylobacter pylori, and the statistical methodology.

Duodenal Ulcer↗
PubMed1989

Can gastritis symptoms be evaluated in clinical trials? An overview of treatment of gastritis, nonulcer dyspepsia and Campylobacter-associated gastritis.

We carried out a review of the literature on Campylobacter pylori-associated gastritis and nonulcer dyspepsia (NUD) to determine whether or not symptoms related to these conditions can be measured reliably and whether or not any study to date has shown that treatment alters symptoms. Search strategies consisted of online Medline searching, a forward search of three articles using the Science Citation Index, a manual search of five gastroenterological journals, and a fully recursive search of cited references. Inclusion and quality criteria were applied to all retrieved studies. Nine of 23 studies did not fulfill the inclusion criteria. Of the 14 studies analyzed, two measured symptoms reliably. Neither showed a therapeutic benefit on symptoms. The difficulties encountered in conducting such studies and the methods of recording symptoms reliably are discussed. We conclude that to date, no treatment is of proven benefit in the relief of symptoms associated with C. pylori gastritis and NUD.

Campylobacter Infections↗
PubMed1989

The effect of tripotassium dicitrato bismuthate on pepsin activity.

We have studied the effect of tripotassium dicitrato bismuthate on the peptic activity of gastric juice, both basal and pentagastrin-stimulated, from five healthy volunteers using porcine pepsin solution as a control. Tripotassium dicitrato bismuthate showed no inhibition of the proteolytic activity of either the pure porcine or the human pepsin in the gastric juice. The ulcer healing efficacy of tripotassium dicitrato bismuthate is unlikely to be related to a gastric anti-protease effect.

Animals↗
PubMed1989

Does misoprostol given as a single large dose improve its antisecretory effect?

H2-receptor antagonists have been shown to be effective in the suppression of nocturnal acidity. This double-blind, randomized, crossover Latin-square study of 24-h intragastric pH in 12 normal volunteers investigated the effect of large single-dose administration of misoprostol on intragastric acidity. Efficacy of 800 micrograms misoprostol h.s., 600 micrograms h.s., 400 micrograms h.s. and 800 micrograms after supper was compared to placebo and 200 micrograms misoprostol q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. 2.2 +/- 0.3, 800 micrograms p.m. 2.6 +/- 1.1, 400 micrograms h.s. 2.6 +/- 0.7, 600 micrograms h.s. 2.6 +/- 0.4, 800 micrograms h.s. 2.6 +/- 0.5. The effect of misoprostol on gastric acidity was short and limited to the nocturnal period. Only misoprostol 800 micrograms and 600 micrograms reduced 24-h acidity compared to placebo (P less than 0.04).

Adult↗
PubMed1989

Optimization of a medium for the rapid urease test for detection of Campylobacter pylori in gastric antral biopsies.

We developed a buffered azide-free urea medium which is sensitive, specific, and nontoxic for rapid detection of Campylobacter pylori in gastric biopsies. Detection of urease produced by the organism provides the basis for the test. The substrate is urea in monobasic sodium phosphate buffer, and phenol red provides indication of the pH change that results from urease activity. A rapid change from yellow to red occurs in the presence of C. pylori, even at low concentrations of the organism. A slower color change occurs with higher concentrations of other urease producers, such as Yersinia enterocolitica and Proteus mirabilis. Experience with 51 patients with our medium showed excellent results in detection of C. pylori in gastric mucosal biopsies. In clinical research and practice, a rapid bedside test will be helpful for rapid diagnosis of C. pylori-positive patients.

Azides↗
PubMed1989

Do H2 receptor antagonists have to be given at night? A study of the antisecretory profile of SKF 94482, a new H2 receptor antagonist which has a profound effect on daytime acidity.

Evening dosing has become standard for H2 receptor antagonists, because available agents inhibit nocturnal basal acid secretion more effectively than daytime stimulated secretion. We studied the optimal time of administration of a new high affinity long acting H2 receptor antagonist, SKF 94482, for the suppression of intragastric acidity using intragastric telemetry. Sixteen healthy subjects received SKF 94482 200 mg or placebo at 07:30, 17:30, and 21:30 h during four separate studies. Time (h) above pH 4 was (mean (SD] 1.1 (1.2) on placebo, 7.8 (5.0) on SKF 94482 given at 07:30, 5.75 (3.6) on SKF 94482 given at 17:30, and 6.1 (2.9) when given at 21:30. All treatment regimens were effective in increasing time above pH 4 (p less than 0.01). The efficacy of the morning dose of SKF 94482 indicates that the best time to give H2 receptor antagonists depends on their pharmacological properties.

Adult↗
PubMed1989

Effect of hydrochloric acid and prostaglandins on pepsinogen synthesis and secretion in canine gastric chief cell monolayer cultures.

The actions of hydrochloric acid, natural PGE1, PGE2 and a synthetic commercial PGE1 preparation, Enisoprost (Searle) on pepsinogen synthesis and secretion were studied in canine chief cell monolayer cultures. Hydrochloric acid, applied directly to the apical surface of chief cells using culture plate inserts (Millipore) had no effect on secretion, nor did it affect the action of any secretagogue in the basolateral medium. All prostaglandins tested showed significant stimulation of pepsinogen secretion. Basal secretion of pepsinogen after 90 min was 9.4 (1.3)% to total initial monolayer content. At 10(-6) M, PGE1 stimulated secretion was 26.1 (3.8)%; PGE2 27.9 (4)% and Enisoprost 28.8 (4.2)% of initial pepsinogen content. Stimulations by all tested prostaglandins were additive with carbachol (10(-4) M) and CCK (10(-9) M), but not with VIP (10(-6) M), dbcAMP (10(-3) M) or forskolin (10(-6) M) responses. All three prostaglandins stimulated pepsinogen synthesis as measured by 14C labelled amino acid incorporation into pepsinogen. Time course experiments were similar to those for forskolin and showed shorter time delays between stimulus and increased synthesis rate than carbachol but longer than dbcAMP. Stimulated pepsinogen secretion was inhibited by high pepsin concentrations (greater than 800 micrograms/ml) in the medium. The inhibited abolished simultaneous carbachol induced stimulation of synthesis but prostaglandin or forskolin stimulation only after two hours. Combined with the shorter response time, as compared with carbachol, these data support our previous findings that potent stimulators of cAMP production can stimulate pepsinogen synthesis directly by stimulation of mRNA synthesis, independently from an increased secretion. The additivity of effects with carbachol or CCK and similarity with forskolin stimulated synthesis supports the suggestion that the actions of prostaglandins are mediated by cAMP.

Animals↗
PubMed1989

Validation of pH dataloggers for pharmacologic studies.

Twenty-four-hour gastric aspiration studies have been superseded by dataloggers that continuously record intragastric pH. We have studied both techniques in a practical pharmacologic study, comparing early evening versus nighttime dosing with ranitidine and nizatidine against placebo. Whereas there was a highly significant point correlation between aspiration and datalogger pH, the slope was significantly less than 1. The correlation was poorer during the day (r = 0.51) than at night (r = 0.83). Irrespective of the techniques used, however, conclusions reached on drug efficacy were similar, but direct comparison of data from the two techniques is not possible.

Circadian Rhythm↗
PubMed1989

Relationship between inhibition of acid secretion and healing of peptic ulcers.

Although current concepts of ulcer pathophysiology postulate an imbalance between the principal aggressive factors of acid and pepsin and an impairment of mucosal defence, effective acid reduction by a variety of antisecretory drugs is associated with a significant acceleration of duodenal and gastric ulcer healing in controlled clinical trials. The healing of duodenal ulcer is related to the degree and duration of acid reduction with currently available H2-receptor antagonists. The highly significant correlation between the reduction of nocturnal acidity and ulcer healing reflects the ability of these drugs to inhibit basal and nocturnal acid secretion to a greater extent than stimulated daytime secretion. The extent to which the addition of daytime acid inhibition to that of nocturnal acid inhibition is responsible for further accelerating ulcer healing has not yet been determined, although a model has been proposed recently to explore this effect. Omeprazole has a marked effect on the duration and the degree of inhibition of intragastric acidity which is dose-dependent. In clinical trials of duodenal ulcer treatment, this efficacy and duration of effect is associated with an increased rate of healing and a leftward shift of the healing time curve.

Dose-Response Relationship, Drug↗
PubMed1989

Exocrine pancreatic function tests.

Despite the development in the last two decades of new imaging techniques for the detection of pancreatic disease, discrepancies between functional and morphological findings can be remarkable. Pancreatic function tests may aid in the detection of disease at an earlier stage in some patients and can assess the degree of functional damage which is helpful in assessing patients for supplemental therapy. While direct intubation methods are invasive and time consuming, they remain the gold standard against which the other investigations have to be assessed. An indirect test, such as the pancreolaural test, has been shown to be a useful addition to ultrasound for the screening of pancreatic disease. Pancreatic markers and radioisotope methods have failed to live up to early promise, but fecal tests can be used effectively to monitor enzyme replacement. A judicious combination of pancreatic function tests and imaging techniques may be able to rationalize investigation and treatment of pancreatic disease.

Diagnostic Imaging↗
PubMed1989

Smoking and duodenal ulcer disease.

Cigarette smoking has long been thought to be associated with duodenal ulcer disease, there being an increased incidence and an adverse outcome in both healing and relapse. This review evaluates this evidence and the possible mechanisms that might account for a poor outcome in smokers.

Animals↗