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Biomedical subjects

R Fraser

Publications and source records attributed to R Fraser.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of fractionated abdominal irradiation on small intestinal motility--studies in a novel in vitro animal model.

Disordered small intestinal motility occurs frequently during acute radiation enteritis. However, the characteristics and time course of the motor dysfunction are poorly defined. These parameters were assessed in a novel animal model of radiation enteritis. Ileal pressures were recorded in vitro with perfused micromanometric catheter using an arterially perfused ileal loop in 22 ferrets following fractionated abdominal irradiation (9 doses 2.50 Gy thrice weekly for 3 weeks). Tissue damage was graded histologically. Studies were performed 3 to 29 days after irradiation. Tissue from 7 control animals was also studied. All treated animals developed diarrhoea. Histology showed changes consistent with mild to moderate radiation enteritis. Following irradiation, there was an initial increase in frequency followed by a non-significant reduction in the frequency, but not the amplitude of ileal pressure waves. The frequency of pressure waves showed an inverse relationship with time after radiation (r = -0.634, p < 0.002). There was no relationship between motility and histology. We conclude that abdominal irradiation is associated with a time-dependent reduction in ileal motility which does not correlate with light microscopic changes.

Animals↗
PubMed1996

Plasma angiotensin II, predisposition to hypertension, and left ventricular size in healthy young adults.

BACKGROUND: We studied the correlates of left ventricular mass (LVM) in 84 healthy young adults aged 16 to 24 years from the general population. Subjects were selected according to predisposition to hypertension into four groups with either high or low personal blood pressures and either high or low parental blood pressures. METHODS AND RESULTS: LVM was measured by echocardiography, and measurements of blood pressure, heart rate, body dimensions, and plasma concentrations of components of the renin-angiotensin system were made under resting conditions. LVM was similar in individuals predisposed to hypertension (high personal and parental blood pressures) and those with contrasting predisposition (low personal and parental pressures). Regression analysis of the combined groups showed that LVM correlated closely with body size, particularly lean body mass (r=.69, P<.0001) and systolic (r=.35, P<.0001) but not diastolic blood pressure. Plasma angiotensin II (r=.39, P<.0001), renin (r=.302, P<.01), and angiotensin-converting enzyme (r=.22, P<.05) showed significant correlation with LVM. Multiple regression analysis revealed that plasma angiotensin II was the most important component of the renin-angiotensin system and that its effect was independent of systolic blood pressure and body size. CONCLUSIONS: These findings provide evidence in humans that angiotensin II exerts a direct on myocardial size. This association may have important implications for the complications and treatment of left ventricular hypertrophy.

Adolescent↗
PubMed1996

The effect of acute hyperglycaemia on small intestinal motility in normal subjects.

The effects of hyperglycaemia on postprandial small intestinal motor activity are unclear. Duodenal and jejunal pressures and duodeno-caecal transit were measured in eight healthy male volunteers during euglycaemia (blood glucose 4-6 mmol/l) and hyperglycaemia (blood glucose 12-15 mmol/l). Duodenal and jejunal pressures were recorded with a manometric assembly during intraduodenal infusion of 100 ml nutrient liquid comprising 14% protein, 31.5% fat and 54.5% carbohydrate together with 15 glactulose. Duodeno-caecal transit was determined by a breath hydrogen technique. The number of duodenal (p < 0.05) and jejunal (p < 0.01) pressure waves, excluding phase III episodes was reduced during hyperglycaemia compared to euglycaemia Hyperglycaemia was associated with earlier onset of phase III activity (30 +/- 12 vs 132 +/- 20 min; p < 0.05) Duodeno-caecal transit was slower during hyperglycaemia when compared to euglycaemia (114 +/- 17 vs 49 +/- 6 min, p < 0.01). We conclude that induced hyperglycaemia has major effects on postprandial small intestinal motility. The reduction in duodenal and jejunal motor activity is likely to explain the retardation of small intestinal transit during hyperglycaemia.

Acute Disease↗
PubMed1996

Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomach in vitro.

Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO2 and bicarbonate whereas, during normal acid, secretion cytoprotective CO2/HCO3- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in an in vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO2 supply. Without acid inhibition there was no mucosal damage at any level of serosal CO2/HCO3- supply. Acid inhibition reduced metabolic CO2 production by 29% (P < 0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P < 0.05). Although, 1% CO2 supply completely replaced the reduction in metabolic CO2, it did not protect against mucosal damage. Overreplacement by 5% serosal CO2/HCO3- was required to prevent damage. There was no correlation between luminal CO2/HCO3- output and mucosal damage. The protection by endogenous or exogenous CO2/HCO3- appears to act intracellularly rather than by intragastric or intercellular neutralization.

Acid-Base Equilibrium↗
PubMed1996

11 beta-Hydroxylase activity in glucocorticoid suppressible hyperaldosteronism: lessons for essential hypertension?

Corticosteroid 11 beta-hydroxylation is catalysed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and in patients with Conn's syndrome. Based on both 11-deoxycortisol:cortisol (S:F) and 11-deoxycorticosterone:corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate-limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimaeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone and DOC concentrations, appeared to be more sensitive to ACTH in GSH than the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in the condition, and may contribute to the phenotypic variability.

Adrenocorticotropic Hormone↗
PubMed1996

Intraluminal micromanometry: an evaluation of the dynamic performance of micro-extrusions and sleeve sensors.

Conventional manometric techniques are unsuitable for studies in premature infants and small laboratory animals. We have therefore developed silicone rubber 5-lumen and 10-lumen micromanometric extrusions with an o.d. 2.0 mm and lumina of 0.35 mm i.d. This study evaluates the suitability of microextrusions for intraluminal perfusion manometry. Pressure offset, post-occlusion pressure rise rate and sphincter model studies were used to assess the manometric performance of the extrusions and a miniature sleeve sensor (25 mm long) at infusion rates of 0.01-0.1 mL min-1. Micro-extrusions (5-lumen/10-lumen, respectively) had offsets (per 100 cm of length) of 3.8/5.0 mmHg at 0.01 mL min-1 and 25.6/26.2 mmHg at 0.1 mL min-1 and rise rates (in 160 cm lengths) of 64/43 mmHg sec-1 at 0.01 mL min-1 and 330/224 mmHg sec-1 at 0.1 mL min-1. Infusion rates 0.025 mL min-1 produced rise rates 100 mmHg sec-1. The miniature sleeve sensor had minimal resistance to perfusion, rise rates of 3 mmHg sec-1 at 0.01 mL min-1 and 23 mmHg sec-1 at 0.1 mL min-1 and recorded pressure as accurately as a side hole. We conclude that the performance of micromanometric extrusions and sleeves is sufficient for intraluminal perfusion manometry.

Animals↗
PubMed1996

Corticosteroids in essential hypertension: multiple candidate loci and phenotypic variation.

1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function. 2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics. 3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11 beta-hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine. 4. The genes encoding 11 beta-hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5' regulatory regions from 11 beta-hydroxylase and 3' coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition. 5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11-deoxycortisol/cortisol, consistent with reduced activity of 11 beta-hydroxylase in the zona fasciculata. 6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.

Adrenal Cortex Hormones↗
PubMed1996

Sodium status, corticosteroid metabolism and blood pressure in normal human subjects and in a patient with abnormal salt appetite.

1. A patient with severe hypertension was found to have mildly impaired 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity on the basis of urinary steroid metabolite ratios, low plasma aldosterone, angiotensin II and renin levels and marginally low levels of plasma potassium. 2. The patient also had a compulsively high salt intake. 3. We tested the hypothesis that high salt intake may affect 11 beta-HSD activity. 4. High salt intake in normal subjects did not significantly alter either blood pressure or 11 beta-HSD activity. 5. We suggest that the potentially small hypertensive effect of the partial enzyme deficiency in our patient, also reported in patients with essential hypertension, has been markedly amplified by the very high salt intake.

Adrenal Cortex Hormones↗
PubMed1996

The Cathlocator: a novel non-radiological method for the localization of enteral tubes.

Safe placement of nasogastric tubes requires reliable positioning of the tip of the tube within the stomach. Radiology and aspiration are currently used to confirm tube position, but suffer from significant problems of cost and efficacy, respectively. We have developed a novel method to locate the position of a catheter tip within the body, using the detection of low energy electromagnetic field generated in a coil located in the catheter with an external hand-held unit (Cathlocator). In vitro, the unit detected the distance of the coil from the detector with an accuracy of 0.1 cm over a range of 4-12 cm. In vivo studies were performed in 11 healthy volunteers using a purpose-built manometric assembly that incorporated the signal generating coil in its tip. In all subjects the Cathlocator showed the position of the signal generating coil to be cranial to the xiphisternum when manometric and transmucosal potential difference criteria showed it to be located above the lower oesophageal sphincter. When the coil was within the stomach, the Cathlocator identified its position within the epigastric, umbilical and left hypochondrial regions of the abdomen. The distance of the coil from the surface was significantly greater when in the duodenum mean (+/- s.e.m. 7.6 +/- 0.3 cm; P < 0.001) and oesophagus (8.6 +/- 0.2 cm; P < 0.002) than the stomach (5.0 +/- 0.4 cm). In one subject studied twice there was a close correlation between the location and depth measured by the device on each occasion. The Cathlocator is a novel non-radiological device that has the potential to be useful in the placement of gastrointestinal catheters.

Adult↗
PubMed1996

Measurement of proximal and distal gastric motility with magnetic resonance imaging.

The precise motor mechanisms associated with gastric emptying of nutrient liquids are unclear, in part because of difficulties in measuring the motility from the proximal and distal stomach simultaneously. We have now examined proximal and distal gastric motility, using a novel magnetic resonance imaging (MRI) technique. In seven healthy volunteers (4 males, 3 females; 27-37 yr), gastric emptying and motility were determined on two occasions after ingestion of 500 ml 10% and 25% dextrose labeled with 1 mM gadolinium tetraazacyclododecane tetraacetic acid, using a 1.5-tesla Philips Gyroscan ACS II scanner. Gastric emptying was determined every 15 min with a series of transaxial scans. After each series of transaxial scans, 120 coronal scans, 1.2 s apart, were performed through the antrum and proximal stomach. For each coronal slice the diameters of the proximal stomach and the antrum were measured to determine the number of contractions per minute and depth (%basal diameter). Gastric emptying (half-emptying time) was faster after ingestion of 10% compared with 25% dextrose (49 +/- 15 vs. 118 +/- 37 min; P < 0.01). After both meals, the diameter of the proximal stomach remained relatively constant, whereas there were marked fluctuations in the diameter of the antrum. Mean (+/- SD) frequency (2.8 +/- 0.6 vs. 2.0 +/- 0.8/min; P < 0.001) and depth (40 +/- 17% vs. 34 +/- 16%; P < 0.04) of antral contractions were higher after 10% dextrose compared with 25% dextrose. Rapid MRI techniques allow simultaneous measurement of both gastric emptying and motor function of different gastric regions. The increase in the frequency and depth of distal gastric contractions during ingestion of 10% compared with 25% dextrose supports the concept that the antrum contributes to the regulation of gastric emptying of nutrient liquids.

Adult↗
PubMed1996

Prevalence of Helicobacter pylori infection and chronic dyspeptic symptoms among immigrants from developing countries and people born in industrialized countries.

The relationship between Helicobacter pylori infection and chronic dyspepsia is controversial. To determine the effect of H. pylori infection on dyspeptic symptoms, we compared the prevalence of H. pylori infection in immigrants from developing countries and people born in industrialized countries. Upper abdominal symptoms were assessed by a questionnaire and H. pylori infection was determined with a 13C-urea breath test and serology. H. pylori infection was found in 63% of subjects from developing countries and 11% of subjects from industrialized countries. There was no difference in the prevalence of dyspeptic symptoms between the 2 groups. The lack of difference in chronic dyspeptic symptoms between the groups, despite a major difference in the H. pylori prevalence, suggests that H. pylori infection is not a major contributor to chronic dyspepsia.

Adolescent↗
PubMed1996

Altered 11 beta-hydroxylase activity in glucocorticoid-suppressible hyperaldosteronism.

Corticosteroid 11 beta-hydroxylation is catalyzed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and patients with Conn's syndrome. Based on both 11-deoxycortisol/cortisol (S:F) and 11-deoxycorticosterone/corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with the basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all of these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone, and DOC concentrations appeared to be more sensitive to ACTH in GSH than in the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in this condition and may contribute to the phenotype variability.

Adrenal Cortex Neoplasms↗
PubMed1996

Undergraduate teaching in the community: can general practice deliver?

BACKGROUND: All UK medical schools are revising their curricula following the General Medical Council recommendations to increase general practice involvement in undergraduate education. However, workload in general practice has increased in recent years, raising questions about its ability to maintain, let alone extend, its educational activities. AIM: The aim of this study was examine whether recent changes in general practice have affected delivery of practice-based undergraduate education and to assess the extent to which practices will be able to increase their involvement in teaching. METHOD: A postal questionnaire survey was conducted of the lead clinical teachers and their partners in the practices to which students from Leicester Medical School had been attached in the last 2 years. RESULTS: The questionnaire was completed by 32 out of the 39 lead teachers and 134 of the 150 partners, an overall response rate of 88%. There was widespread support for departmental teaching requirements, but only 17 lead teachers (44%) felt that the suggested reduction by 25% of patients seen per session while teaching was feasible. A total of 14 lead teachers (47%) felt that the ability of their practice to deliver high-quality teaching had declined since 1990. Altogether, 113 (87%) of all doctors in teaching practices felt that time pressures had increased during this period, and 139 (88%) felt that present levels of remuneration were inadequate. The majority of these doctors felt that general practice was the preferred location for learning generic clinical skills and were interested in participating. Nevertheless, most were not prepared to increase their involvement in teaching under present arrangements. CONCLUSION: Practice-based teachers appreciate the need for quality teaching, remain enthusiastic about teaching and are, in principle, willing to take an increased teaching load. However, recent changes have made delivery of teaching more difficult, and if an expansion in practice-based teaching is to occur, more realistic levels of funding and support are a prerequisite.

Attitude of Health Personnel↗
PubMed1995

Regulation of murine acid secretion by CO2.

To determine whether endogenous metabolic sources alone provide sufficient CO2 for acid secretion in mammals, basal and stimulated acid secretion and metabolic CO2 production were measured concurrently in mouse stomachs, in vitro, without exogenous CO2, and after addition of 5% CO2 serosally. Basal acid secretion was varied by changing luminal pH from 3.2 to 4.0. In the absence of an exogenous supply of CO2 acid secretion was stable under basal conditions and increased during cholinergic stimulation with carbachol. Serosal CO2 supply increased basal and stimulated acid secretion. The increase in basal acid secretion depended on the initial level of acid secretion. At pH 4.0, exogenous CO2 increased acid output (mean +/- SD) by 13% from 112 +/- 11 nmol/min to 126 +/- 8 nmol/min (P < 0.03), whereas at pH 3.6 the increase was 40% (63 +/- 14 to 88 +/- 20 nmol/min, P < 0.04) and 157% at pH 3.2 (21 +/- 13 to 54 +/- 14 nmol/min, P < 0.002). Following cholinergic stimulation a maximal acid output of 321 +/- 38 nmol/min was attained without serosal CO2, whilst addition of 5% CO2 to the serosal solution increased maximal acid secretion by 49% to 479 +/- 96 nmol/min (P < 0.005). Metabolic activity, measured as total gastric CO2 production, was greater as acid secretion rates increased [239 +/- 20 nmol/min at 21 +/- 13 nmol/min (luminal pH 3.2) versus 406 +/- 28 nmol/min at 321 +/- 17 nmol/min (after cholinergic stimulation)]. The data support the concept that basal and sub-maximal acid secretion can be maintained by CO2 available from metabolic sources, but full expression of the acid secretory apparatus requires exogenous CO2.

Animals↗
PubMed1995

Effects of the glucocorticoid antagonist RU486 in spontaneously hypertensive and Sprague Dawley rats.

The effect of a low dose of the gluco-corticoid receptor antagonist, RU486, was tested in spontaneously hypertensive (SHR) and in Sprague Dawley (SD) rats. In SD rats, RU486 (50 micrograms/day, 18 days) significantly increased growth rate and thymus weight, probably by antagonising the actions of endogenous glucocorticoid hormones. Blood pressure and plasma corticosterone levels were not affected by RU486 at this dose. In leucocytes, RU486 treatment in vivo reduced the number of glucocorticoid binding sites but did not affect binding affinity. In contrast, growth rate and thymus weight were not altered in SHR when treated with the same dose of RU486 for a longer period (60 days). Blood pressure was unaffected as were leucocyte glucocorticoid receptor characteristic. Glucocorticoid receptor binding characteristics for RU486 were similar for liver cytosol of SD and SHR. We conclude that the apparent difference in sensitivity to RU486 between strains is probably not due to differences in interaction of the antagonist with the glucocorticoid receptor but may be caused by differences in pharmacokinetics of RU486 between strains.

Adrenal Glands↗