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Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 199 records · Page 11Linked to original sources
PubMed1987

The effects of intravenous famotidine on pentagastrin-stimulated gastric secretion in man.

Eight healthy male volunteers were each studied on four occasions in a 7 hour double-blind, placebo-controlled experiment. Three continuous 6 hour intravenous (i.v.) infusion rates of famotidine, calculated to achieve steady-state plasma concentrations of 10, 30 and 90 ng ml-1, were compared to placebo. Commencing at the third study hour, hourly incremental step-up i.v. infusions of pentagastrin 0.1, 0.2, 0.5, 1.0 and 2.0 micrograms kg-1. hour were administered on each of the four study days. Hourly blood samples were taken for the subsequent determination of plasma famotidine concentration. The three famotidine infusion rates inhibited basal gastric secretion. Pentagastrin-stimulated secretion was inhibited in a dose-dependent manner. The highest dose of famotidine (38.7 micrograms kg-1.hour) inhibited each infusion rate of pentagastrin-stimulated gastric secretion between 92 and 96%. The lowest dose of famotidine (4.3 micrograms kg-1.hour) inhibited pentagastrin 0.1 micrograms kg-1.hour stimulated secretion by 50% but, when stimulated with pentagastrin 2.0 micrograms kg-1.hour, gastric secretion was inhibited by only 25%. This study indicates that the intravenous preparation of famotidine is a potent inhibitor of pentagastrin-stimulated gastric acid secretion.

Adult↗
PubMed1987

Marked suppression of stimulated gastric acid and pepsin secretion by enisoprost, a new PGE1 analogue.

The gastric antisecretory effects of three different doses of enisoprost, a new synthetic PGE1 analogue, were compared with placebo and misoprostol in 20 healthy male volunteers. Enisoprost 100, 200 and 400 micrograms all significantly (P less than 0.0001; ANOVA) suppressed histamine-stimulated acid and pepsin output when compared with placebo or misoprostol 200 micrograms. Misoprostol produced a significant decrease of stimulated acid output when compared with placebo (P = 0.0012). The concentration of pepsin in gastric juice was significantly (P less than 0.0001) decreased by enisoprost at the commencement of histamine stimulation. This effect was short-lived, and was maximal with enisoprost 400 micrograms. There was a significant dose-response relationship for enisoprost for inhibition of stimulated acid output (P = 0.0065). Enisoprost was well tolerated, and no consistent drug-related adverse effects were detected. The profile of antisecretory effect of enisoprost, producing marked suppression of both acid and pepsin secretion independently, is unusual. This combination of activity along with any mucosal protective properties might be particularly effective in the treatment of peptic ulcer disease.

Adult↗
PubMed1987

Location of genes on chromosome arms in the Anopheles gambiae group of species and their correlation to linkage data for other anopheline mosquitoes.

The use of paracentric inversions as genetic markers in the Anopheles gambiae group of mosquitoes is described. The gene for dieldrin resistance is assigned to chromosome 2 which in turn is correlated to the previous assignment of the gene to linkage group II. The locus of the enzyme phosphoglucomutase 2 (Pgm 2) is similarly assigned to chromosome 2 and evidence is presented for possible linkage between Pgm 2 and dieldrin resistance. There was no linkage or correlation of chromosome 2 and loci of the enzymes superoxide dismutase (Sod) and octanol dehydrogenase (Odh). These genes are therefore assumed to be on chromosome 3 (linkage group III). Evidence that such gene linkage group/chromosome correlations may extend to other species for which chromosome maps and homologies have been worked out is discussed.

Alcohol Oxidoreductases↗
PubMed1987

Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs.

FVMany different dosage schedules of antisecretory drugs for the treatment of duodenal ulcer are recommended. The relationship between degree of acid suppression and therapeutic efficacy has not been precisely defined for these drugs. We have examined the association between suppression of intragastric acidity and duodenal ulcer healing rates for a number of therapeutic regimens. For the H2 receptor antagonists alone, the most significant correlation with healing rates was with suppression of intragastric acidity at night (r = 0.926; p = 0.0001). When other classes of drug: high dose antacid, omeprazole and a synthetic prostaglandin (enprostil) were included in the analysis, the closest correlation was with suppression of total 24 hour intragastric acidity (r = 0.911; p less than F0.0001). Stepwise linear regression analysis was used to investigate the relative contributions to healing of suppression of acidity during the day and night. Suppression of nocturnal acidity was found to be the single most important factor in explaining healing rates. No further benefit was obtained with daytime suppression for H2 receptor antagonists; suppression of acidity at night accounted for 86.1% of the observed variation in healing rates among different regimens of H2 receptor antagonists. When all classes of drugs were analysed, inclusion of daytime suppression produced a significant improvement in correlation over nocturnal suppression alone. Drug regimens providing potent suppression of nocturnal acidity produce the highest healing rates in controlled clinical trials. The healing rate for any dose regimen of an antisecretory drug can be predicted from a knowledge of its effect on intragastric acidity. For the H2 receptor antagonists, suppression of nocturnal acidity is the most relevant in this context. Moderate suppression of acidity achieves ulcer healing rates at four to eight weeks which are comparable with those seen with potent suppression at two to four weeks. Increasing degrees of suppression merely accelerate healing.

Anti-Ulcer Agents↗
PubMed1987

A double-blind randomized study comparing different dose regimens of H2-receptor antagonists on 24-hour gastric secretion in normal subjects and duodenal ulcer patients.

Duodenal ulcer therapy with H2 antagonists initially aimed to control acid secretion throughout the 24-h period, but recently nighttime suppression has been advocated. The effect of single nighttime regimens of cimetidine 400 mg BID, cimetidine 800 mg HS, ranitidine 150 mg HS, and placebo on 24-h intragastric acidity, nocturnal acid output, and pepsin secretion were studied in four healthy volunteers and four patients with healed duodenal ulcer. A nonrandomized dose of cimetidine 1200 mg HS was also studied. For all four treatments, daytime (0730-2230 h) intragastric acidity was reduced by 4-30% in the normals and by 10-44% in the duodenal ulcer patients (NS), while 24-h intragastric acidity was reduced by 44-46% and 40-64%, respectively (p less than 0.05). Reduction in nocturnal acid output was 82-96% in normals and 91-99% in duodenal ulcer, respectively. Pepsin concentration was unaffected by treatment but pepsin concentration was significantly (p less than 0.05) lower in patients than in normals. Mean 24-h gastric acid secretion was reduced by a single nighttime treatment with an H2-receptor antagonist, while nocturnal acid secretion was virtually abolished. H2 antagonists given only at night deserve further clinical evaluation to determine the minimal effective dose and optimal duration of suppression to achieve ulcer healing.

Cimetidine↗
PubMed1987

Reversibility of increased intestinal permeability to 51Cr-EDTA in patients with gastrointestinal inflammatory diseases.

Intestinal permeability in adults with inflammatory gastrointestinal diseases was investigated by measuring the 24-h urinary excretion of orally administered 51Cr-EDTA. Eighty controls along with 100 patients with Crohn's disease, 46 patients with ulcerative colitis, 20 patients with gluten-sensitive enteropathy, and 18 patients with other diseases were studied. In controls, the median 24-h excretion was 1.34%/24 h of the oral dose. Patients with Crohn's disease (median 2.96%/24 h), ulcerative colitis (median 2.12%/24 h), and untreated gluten-sensitive enteropathy (median 3.56%/24 h) had significantly elevated urinary excretion of the probe compared to controls (p less than 0.0001). Increased 24-h urinary excretion of 51Cr-EDTA had a high association with intestinal inflammation (p less than 0.0001). Test specificity and sensitivity were 96% and 57%, respectively. A positive test has a 96% probability of correctly diagnosing the presence of intestinal inflammation, whereas a negative test has a 50% probability of predicting the absence of disease.

Adult↗
PubMed1987

The limitations of current therapy in peptic ulcer disease.

The current therapeutic approach to peptic ulcer disease includes agents that reduce gastric acidity and hence peptic activity, inactivate or adsorb pepsin, create a physical barrier against the effects of acid and pepsin, or enhance mucosal defence. Profound gastric acid reduction may predispose to infection, and it has been suggested that carcinogenesis is possible, although a cause-effect relationship has never been established. The side-effects of therapy are well-described, and may limit the therapeutic approach. Healing rates correlate closely with acid suppression in duodenal ulcer, but not entirely in gastric ulcer. Maintenance therapy lowers the relapse rate, but does not alter the ulcer diathesis. The optimal strategy for long-term management remains unclear, but in the future one should consider outcome measures which include a decrease in pain, improvement in the quality of life, reduction work loss, and a reduction of complications, in addition to ulcer healing. The ideal therapy should be efficacious, safe, and convenient--with no side-effects--and cost-effective. New agents should suppress acid and peptic activity, while enhancing the gastric mucosal defence mechanisms (such as mucosal blood flow, mucus, and bicarbonate secretion) and stimulating gastric cellular regeneration and restitution.

Antacids↗
PubMed1986

Scientific requirements for diagnostic tests in gastroenterology.

Diagnostic tests in gastroenterology ought to help clinicians provide effective patient care. However, this may not be achieved if a promising new test is widely advocated before it has undergone a thorough scientific evaluation. Adherence to a set of common sense scientific requirements, such as those presented here, both provides quality control for diagnostic test research and assists clinicians to appraise critically the results of this research and determine for themselves the accuracy and usefulness of a new diagnostic test.

Biliary Tract↗
PubMed1986

Comparison of the effects of gastric antisecretory agents in healthy volunteers and patients with duodenal ulcer.

Thirty published studies of the clinical pharmacology of gastric antisecretory agents in normal volunteers and duodenal ulcer patients were reviewed. The aim was to investigate the relationship between antisecretory effect in the two populations. There was a significant correlation between effect in patients and normal subjects for suppression of 24 hour intragastric acidity (r = 0.732; p = 0.0068), nocturnal intragastric acidity (r = 0.861; p = 0.0033) and nocturnal acid output (r = 0.964; p = 0.0069). The regression lines for 24 hour and nocturnal acidity were very similar. The expected antisecretory effect of a particular dosage regimen in patients with duodenal ulcer can be predicted mathematically from data derived from studies in normal volunteers.

Anti-Ulcer Agents↗
PubMed1986

Spontaneous hypochlorhydria in man: possible causes and consequences.

There have been many reports of the development of achlorhydria in individuals and in groups of subjects with previously normal levels of gastric acid secretion. The evidence that this phenomenon is due to an infective agent has been considered. Retrospective identification of CLO in gastric mucosal biopsies from some of these patients is an interesting observation, but does not conclusively prove a causal relationship. The exact significance of CLO remains speculative at present; there is more evidence to suggest that it plays a role in gastritis than in peptic ulceration. Ongoing research in this area may have major consequences for the medical treatment of gastritis, 'non-ulcer dyspepsia' and perhaps also for peptic ulcer disease.

Achlorhydria↗
PubMed1986

The effect of temperature and pH on the stability of human pepsin in stored gastric juice. A method to prevent activity loss.

The mechanisms controlling pepsin secretion are controversial. A contributory factor may be storage-dependent effects. We have studied the effects of temperature, pH, and storage time on human gastric pepsin. Gastric juice samples taken from three healthy volunteers under both basal and post-pentagastrin-stimulated (6 micrograms/kg subcutaneously) conditions were separated into four aliquots. Each aliquot was titrated to pH 1, 4, or 6 or left at ambient pH. Aliquots were then stored at 4 degrees C or frozen at -70 degrees C and stored. On days 1, 3, 7, and 28 aliquots were removed and assayed by the kinetic albumin-bromphenol blue method. In a second experiment we determined the effects of different concentrations of glycerol on the preservation of peptic activity. From these experiments we conclude that pepsin is unstable when stored frozen at low pH but not when stored above pH 2. This pH-dependent stability may explain the variable conclusions other workers report on optimal methods of storing gastric juice. In addition, we have confirmed the suitability of glycerol as a preservative of peptic activity and recommend that gastric juice be stored frozen with 11.5% glycerol.

Cold Temperature↗
PubMed1986

Nocturnal gastric acid secretion: its importance in the pathophysiology and rational therapy of duodenal ulcer.

The importance of nocturnal acid secretion has long been acknowledged. The aim of therapy at present is to control acid secretion throughout the entire 24-h period. However, the fact that in DU patients a 400-mg nighttime dose of cimetidine is more effective than a 200-mg one, along with the observation that poorly responsive patients also show little decrease in H+ activity, suggests that a larger single nocturnal dose is an effective primary treatment for DU patients. In studies investigating the effects of different regimens of H2 antagonists on 24-h H+ activity and nocturnal acid secretion in DU patients and healthy volunteers, 400 mg cimetidine twice daily was compared with 800 mg cimetidine at night, 150 mg ranitidine twice daily, 300 mg ranitidine at night, and placebo. In 12 DU patients no significant difference was observed between twice daily or nighttime cimetidine and twice daily or nighttime ranitidine in the reduction of 24-h H+ activity. Cimetidine at night was significantly more effective than the twice daily regimen in reducing nocturnal acid output. Ranitidine, 300 mg at night, decreased nighttime H+ activity more than 800 mg cimetidine at night, although no significant differences in overnight acid output were observed. In another study of four DU patients and four volunteers, 400 mg cimetidine twice daily was compared with 800 or 1200 mg cimetidine at night, 150 mg ranitidine at night, and placebo. All treatments were equally effective at night but had no effect during the day. Hence, early reports seem to confirm that daytime administration of H2 antagonists is unnecessary.

Administration, Oral↗