Search PubMed⌕ Search

Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 127 records · Page 7Linked to original sources
PubMed1993

H1 contractile and H2 relaxant receptors in canine gastric muscularis mucosae.

Histamine had two effects on the contractility of canine gastric muscularis mucosae in vitro: relaxation at or below 10 microM and contraction at higher concentrations. Selective agonists and antagonists were used to test the possibility that these effects were mediated by different receptor subtypes. The H1-selective agonist 2-pyridylethylamine (2-PEA) and the H2-selective agonist dimaprit contracted and relaxed this muscle, respectively, while the H3-selective agonist R-alpha-methylhistamine had no effect. The H1- and H2-selective antagonists mepyramine and ranitidine selectively blocked 2-PEA-mediated contractions and dimaprit-mediated relaxations, respectively. Agonist responses, were unaltered by tetrodotoxin, suggesting a site of action other than nerves. Our results indicate that canine gastric corpus muscularis mucosae possesses both contractile H1 and relaxant H2 receptors.

Animals↗
PubMed1993

Can severity of symptoms be used as an outcome measure in trials of non-ulcer dyspepsia and Helicobacter pylori associated gastritis?

Most trials of non-ulcer dyspepsia (NUD) and Helicobacter pylori associated gastritis (HPAG) have not used validated methods of measuring symptoms. Three attributes are necessary for use of symptom severity scoring systems as outcome measures in clinical trials: reproducibility, responsiveness to change and validity compared to corroborating measures. The objective of this study was to establish that selected gastrointestinal symptoms recorded as a series of 5-point Likert Scales meet the 3 criteria for use as outcome measures in clinical trials. Patients with NUD (Helicobacter pylori-negative) and HPAG were studied. A preliminary assessment of 24 patients was used to select the 8 most frequently occurring and most severe symptoms. These symptoms were then scored in a further 55 patients to assess their utility as outcome measures. Observations were made at 3 time points, enrollment (T1), after 1 week with no intervention (T2) and after 4 weeks of therapy for either disease (T3). The study took place in a university hospital outpatient gastroenterology service. Symptom scores were reproducible before treatment (symptom scores at T1 and T2 were correlated), responsive (symptom scores changed after treatment between T2 and T3) and valid (symptom score changes corresponded to changes in general health status). Scoring of gastrointestinal symptom severity using 5-point Likert Scales satisfies the 3 criteria for use as outcome measures in clinical trials of NUD and HPAG.

Clinical Trials as Topic↗
PubMed1993

Assessment of neurological injury due to circulatory arrest during profound hypothermia. An experimental study in vertebrates.

To investigate brain changes in induced deep core hypothermia (15 degrees C) with circulatory arrest, five groups of neonatal pigs were subjected to cardiopulmonary bypass (CPB), with circulatory arrest (CA) periods varying from 70-120 min. The parameters analysed were: 1. Histology and electron microscopy of the brain six hours post-CPB, 2. Creatinophosphokinase (CPK) from cerebrospinal fluid (CSF), 3. Vasointestinal neuropeptide (VIP) and 7B2 specific neuropeptide both in plasma and brain tissue. The earliest morphological changes were seen after 90 min CA and were highly significant after 120 min arrest. These changes involved mainly the Purkinje cells of the interior half of the cerebellum with vacuolation in their cytoplasm. A rise in CPK in CSF occurred in all piglet-groups. The differences among the various groups were highly significant at 2 and 5 h post-CPB. (P < 0.05). Statistically significant differences were not exhibited among the various groups both in serum and brain tissue total mean values of VIP and 7B2 neuropeptides. We suggest that 1. The cerebellar region is the most sensitive where ischemic lesions attain their maximal severity and extent; the frequency and pattern of selective vulnerability of the cerebellum may be related primarily to its pattern of blood supply 2. The maximum time of CA without histopathological sequelae should not exceed 70 min.

Anesthesia, General↗
PubMed1993

Enzyme variation at the aspartate aminotransferase locus in members of the Anopheles gambiae complex (Diptera: Culicidae).

The enzyme aspartate aminotransferase (AAT) currently is used to identify Anopheles quadriannulatus Theobald, the animal-biting, nonmalaria vector species of the Anopheles gambiae complex. Samples of An. quadriannulatus from South Africa and An. gambiae Giles s.str. from the island of Grand Comoros and the People's Republic of Congo have shown variation in electromorph frequencies that indicate that AAT has five alleles. The three slowest alleles are found in An. quadriannulatus and the three fastest in An. gambiae, An. arabiensis Patton and An. merus Dönitz. One of these is common to both An. quadriannulatus and An. gambiae. This overlap indicates a potential misidentification of 0.3% of unknown females with a further 2.1% being unidentifiable. However, all of the specimens in the overlap area were classified correctly using octanol dehydrogenase (ODH). Variation at the ODH locus in An. quadriannulatus is recorded for the first time, with four of 157 specimens being heterozygous for the fast allele. The probability of both AAT and ODH giving an incorrect or indecisive identification is 0.0005. The slowest AAT alleles were present in samples from a single locality, indicating the lack of gene flow between subpopulations of An. quadriannulatus in close geographic proximity in the Shingwedzi area, South Africa. A modified method for multiple gel casting is given.

Alleles↗
PubMed1993

Evaluation of the polymerase chain reaction method for identifying members of the Anopheles gambiae (Diptera: Culicidae) complex in southern Africa.

Chromosomally and electrophoretically identified field samples of members of the Anopheles gambiae Giles complex from southern Africa and colony material were used to test the polymerase chain reaction (PCR) method of identification. The samples included An. arabiensis Patton, An. quadriannulatus Theobald, and An. merus Donitz. Only one of the 217 specimens examined was disputed. Twenty specimens (9%) were reamplified because of the presence of multiple bands or lack of amplification after the first assay. Specimens of An. merus from this region displayed both the diagnostic An. merus PCR band as well as the An. quadriannulatus band, possibly because of interspecific hybridization or random variation within the population. This work extends the geographical range over which the PCR technique has been verified to southern Africa.

Africa, Southern↗
PubMed1993

Cerebral-evoked potential responses following direct vagal and esophageal electrical stimulation in humans.

Cerebral evoked responses following direct electrical stimulation of the vagus and esophagus were compared in 8 epileptic subjects and with those recorded after esophageal stimulation in 12 healthy nonepileptic controls. Direct vagal stimulation was performed using a left cervical vagal pacemaker, which is used in the treatment of epilepsy. Esophageal stimulation was obtained with the use of an esophageal assembly incorporating two electrodes positioned 5 and 20 cm orad to the lower esophageal sphincter. Evoked potential responses were recorded with the use of 20 scalp electrodes. The evoked potential responses consisted of three distinct negative peaks and were similar with the use of either vagal or esophageal stimulation. The measured conduction velocity of the afferent response was 7.5 m/s in epileptic subjects and 10 m/s in healthy controls, suggesting that afferent conduction is through A delta-fibers rather than slower C afferent fibers. We conclude that the cortical-evoked potential responses following esophageal electrical stimulation are comparable to direct electrical stimulation of the vagus nerve and involve mostly A delta-fibers. This approach provides a method for the assessment of vagal afferent gastrointestinal sensory pathways in health and disease.

Adult↗
PubMed1993

Hp and pH: implications for the eradication of Helicobacter pylori.

Helicobacter pylori infection causes inflammation of the gastric and duodenal mucosae, which results in a disturbance of the regulatory mechanisms for gastrin, gastric acid and pepsin secretion. Acid secretion may be decreased, normal or increased, depending on the stage of infection, although the meal-stimulated gastrin response is invariably elevated. The exact mechanisms involved are not known but may be due to the release of cytokines in response to bacterial toxins. H. pylori colonization is reduced by effective acid suppression with proton pump inhibitors, although it is not eradicated. In combination with amoxycillin, omeprazole, up to 40 mg twice daily, eradicated the organism in up to 82% of cases. This synergistic effect may be due to a direct effect of omeprazole on the organism, the protection of amoxycillin from acid degradation, or enhancement of host defence mechanisms accompanying acid suppression.

Amoxicillin↗
PubMed1993

Neuropathological features of profoundly hypothermic circulatory arrest: an experimental study in the pig.

Twenty-four neonatal pigs were exposed to periods of circulatory arrest of between 70 and 120 min under profound hypothermia at 15 degrees C. Brain tissue taken 6h after cardiopulmonary bypass was examined histologically and by electron microscopy for evidence of hypoxic damage. Specimens from control pigs and animals subjected to 70 min arrest showed no morphological changes in the cerebral or cerebellar neurones. The earliest changes were seen after 90-min arrest; these were highly significant after 120 min. The changes involved mainly the Purkinje cells of the cerebellum with vacuolation in the cytoplasm; the inferior half of the cerebellum was particularly affected. The frequency and pattern of selective vulnerability of the cerebellum may be related primarily to the nature of its blood supply.

Animals↗
PubMed1993

Quality of Life--the challenges ahead.

The economic and social impact of our investigational and therapeutic strategies is attracting increasing attention and, more importantly, is being subjected to formal evaluation. An evaluation of the economic benefits and an assessment of the improvement in the Quality of Life obtained by different strategies of therapeutic intervention are increasingly being included as an essential part of the clinical assessment and benefit both the patient and society. This paper summarizes the most important parameters to be considered in the evaluation of future treatment strategies.

Cost-Benefit Analysis↗
PubMed1993

Brain damage after profoundly hypothermic circulatory arrest: correlations between neurophysiologic and neuropathologic findings. An experimental study in vertebrates.

Five groups of neonatal pigs were subjected to cardiopulmonary bypass with circulatory arrest periods that varied from 70 to 120 minutes for the investigation of brain changes in induced deep-core hypothermia (15 degrees C) with circulatory arrest. The parameters that were analyzed were (1) microscopy of the brain in animals at 6 hours after bypass procedures and (2) intraoperative monitoring of somatosensory evoked potentials. Microscopic cellular damage appeared in all animals with a circulatory arrest period of more than 70 minutes. These changes involved mainly Purkinje's cells of the cerebellum, and they affected particularly the inferior half of the cerebellum. The prolongation of latency in the cortical responses, which reflects a slowing of the neural transmission with hypothermia, occurred in all animals. The late evoked potentials remained absent in all piglets with circulatory arrest periods of 90, 105, and 120 minutes, but they were fully recovered in all piglets of the control group and those with 70-minute arrest times. We concluded that the cerebellar region is the most sensitive site in which ischemic lesions attain their maximal severity and extent, and the maximum time of circulatory arrest without histopathologic and neurophysiologic sequelae should not exceed 70 minutes.

Animals↗
PubMed1992

Effect of acupuncture on gastric acid secretion in healthy male volunteers.

Six randomized, placebo controlled studies were performed to investigate the effect of electroacupuncture on gastric acid output in 38 healthy males. Electroacupuncture decreased basal acid output when compared to placebo acupuncture [from 3.50 +/- 0.59 mmol/hr to 2.54 +/- 0.56 mmol/hr (P < 0.05)] as well as sham feeding-stimulated acid output [from 18.52 +/- 2.25 mmol/hr to 5.38 +/- 2.11 mmol/hr (P < 0.005)], but had no effect on the pentagastrin stimulated acid output. The inhibitory effect of acupuncture on sham feeding-stimulated acid output was not affected by local anesthesia of the acupoint, but was prevented by a prior intravenous naloxone injection. Acupuncture did not alter plasma gastrin levels (20.7 +/- 7.6 micrograms/liter, vs control 21.2 +/- 7.2 micrograms/liter) but naloxone increased it (26.1 +/- 14.5 micrograms/liter) (P < 0.05). We conclude that the antisecretory effects of electroacupuncture do not result from decreased gastrin release or decreased parietal cell sensitivity to gastrin, but are mediated through naloxone-sensitive opioid neural pathways and vagal efferent pathways.

Acupuncture Points↗
PubMed1992

Mucosal damage during intestinal anaphylaxis in the rat. Effect of betamethasone and disodium cromoglycate.

In this study, two antiallergic compounds, betamethasone and disodium cromoglycate were tested in an animal model of intestinal anaphylaxis. Rats, immunized with Nippostrongylus brasiliensis, were challenged intravenously with whole worm antigen or saline. Antigen challenge resulted in significant abnormalities: epithelial damage with shorter villi, decreased activity of digestive enzymes, decreased levels of mucosal histamine, a mast cell mediator, and increased blood uptake of [51Cr]EDTA from the lumen. Low-dose betamethasone, 24 and 48 hr before antigen, was not effective in preventing the effects: villus damage and increased [51Cr]EDTA uptake were seen, although mucosal mast cell numbers were significantly reduced by the drug. High-dose betamethasone completely prevented intestinal anaphylaxis: villus height, digestive function, and [51Cr]EDTA recovery in antigen-challenged animals were not significantly different from controls. Mucosal histamine levels and mast cells were significantly reduced in the high dose betamethasone group. Oral disodium cromoglycate did not prevent the abnormalities but provided a slight beneficial effect.

Analysis of Variance↗
PubMed1992

Role of T lymphocytes in intestinal mucosal injury. Inflammatory changes in athymic nude rats.

To determine the role of T cells versus mast cells in mucosal injury, we documented structural and functional changes in the intestine of congenitally athymic nude rats during infection with the enteric parasite, Nippostrongylus brasiliensis. Studies were conducted at days 4, 7, 10, and 21 postinfection; controls were uninfected. Villus damage was indicated by morphological abnormalities at days 7, 10, and 21 and reduced activities of disaccharidase enzymes at days 10 and 21. The activity of the proliferative enzyme, thymidine kinase, was increased only at day 21, at which time the crypts were elongated. Epithelial permeability increased significantly: 5-hr recovery (in urine and blood) of the probe molecule, [51Cr]EDTA, following injection into ligated jejunal segments, was elevated at days 7 and 10. Uptake of a protein antigen, ovalbumin, from lumen to blood followed a similar pattern. No evidence of functional T cells was demonstrated. However, mucosal mast-cell activation was indicated by elevated serum levels of rat mast-cell protease II at days 7 and 10. We conclude that the absence of thymus-derived T cells does not preclude mucosal damage involving impaired barrier and digestive function. Mucosal mast cells may be involved in causing the injury in this model.

Animals↗
PubMed1992

Effects of misoprostol on the pharmacokinetics of indomethacin in human volunteers.

The effects of misoprostol (200 micrograms as a single dose or q.i.d. as a multiple dose) on the pharmacokinetics of indomethacin (100 mg single-dose administration or 50 mg t.i.d. multiple-dose administration) were studied in 16 healthy human volunteers under single-dose and steady-state conditions in a randomized, double-blind, placebo-controlled, balanced three-period study design. The overall absorption as shown by the values for area under the concentration curve of indomethacin was unaffected by concurrent administration of misoprostol. However, misoprostol did significantly enhance the steady-state maximum concentration of indomethacin by 32%. Thus misoprostol does not interfere with the absorption of indomethacin despite the known inhibitory effects of this protaglandin analog on acid secretion.

Administration, Oral↗
PubMed1992

Omeprazole (20 mg) daily given in the morning or evening: a comparison of effects on gastric acidity, and plasma gastrin and omeprazole concentration.

Although omeprazole has a long duration of action and has usually been given in the morning, there are theoretical advantages in administering antisecretory drugs in the evening as has been shown for the H2-receptor antagonists. The aim of this study was to compare the effects of placebo and 20 mg omeprazole given either in the morning or evening, on gastric acidity, plasma gastrin levels and plasma omeprazole in 6 duodenal ulcer patients. The 24-hour mean pH (+/- S.E.M.) was: placebo 1.7 +/- 0.1; morning doing, 3.9 +/- 1.8 (P less than 0.01); evening dosing, 2.9 +/- 1.1 (N.S.). There was a large inter-individual variability of intragastric acidity in response to omeprazole, which was reflected both in the plasma gastrin and in the area under the plasma omeprazole concentration-time curve. Morning administration of omeprazole is optimal, but variability in the patient response to 20 mg omeprazole is still seen.

Double-Blind Method↗
PubMed1992

Effects of chronic left vagal stimulation on visceral vagal function in man.

We examined the effects of chronic left vagal electrostimulation on afferent and efferent gastrointestinal vagal function in eight patients. Afferent function was assessed using cortical evoked responses to electrical stimulation of the esophagus and to direct vagal stimulation using the implanted left vagal electrode. Efferent gastrointestinal vagal function was measured by examining the basal, maximal, and sham fed stimulated gastric acid output prior to and with chronic left vagal electrostimulation. Esophageal electrostimulation produced a cortical evoked response consisting of three negative and three positive peaks within 400 msec after stimulation. Prior to vagal electrostimulation the mean conduction velocity of the afferent signal was measured at 8.72 +/- 3.39 m/sec, compatible with A-delta fibers involvement. Basal, maximal, and sham fed acid output were 1.11, 21.87, and 9.37 mmol/hour, respectively. The evoked response to esophageal electrical stimulation was not changed with chronic left vagal electrostimulation. Direct vagal stimulation also produced evoked potentials that were comparable to those obtained with esophageal stimulation. The mean conduction velocity was 6.26 +/- 2.72 m/sec (NS) so that there was no evidence of loss of myelinated fibers with chronic stimulation. No differences were detected in basal (1.29 mmol/h), maximal (21.64 mmol/h), or sham fed stimulated (8.03 mmol/h) acid output, showing that vagal electrostimulation has no effect on either total or vagally mediated acid output, an efferent vagal function. In conclusion, chronic left vagal electrostimulation has no significant adverse effect on gastrointestinal vagal function.

Adult↗
PubMed1992

Evidence of impaired afferent vagal function in patients with diabetes gastroparesis.

Two patients, a 28-year-old male and a 70-year-old female, with chronic insulin dependent diabetes mellitus and evidence of autonomic neuropathy were studied using cortical evoked responses following esophageal balloon and electrical stimulation. Both patients had symptomatic gastroparesis, poor gastric emptying, and reduced gastroduodenal motility including abnormal results of scintigraphy and manometry. There was slowing of afferent vagal conduction but good evoked potential responses were recorded even though one patient could not feel electrical stimulation of either the proximal or distal esophagus. It is improbable that the gastric symptoms are due to an afferent autonomic neuropathy, but symptoms may well be related to impairment of motor vagal pathways. Nevertheless, afferent vagal pathways are involved in severe diabetes mellitus. The clinical significance of this delay in conduction velocity of afferent pathways remains to be established.

Adult↗