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Biomedical subjects

R Fraser

Publications and source records attributed to R Fraser.

At least 127 records · Page 7Linked to original sources
PubMed1995

Delayed gastric emptying as a factor in delayed postprandial glycaemic response in pregnancy.

OBJECTIVE: To determine whether an alteration in gastric emptying contributes to an altered postprandial glycaemic response in normal pregnancy. DESIGN: A longitudinal study in normal pregnancy and postpartum. SETTING: Teaching hospital in Sheffield. SUBJECTS: Primigravid women with uncomplicated pregnancies. INTERVENTIONS: Simultaneous meal tolerance and paracetamol absorption tests. MAIN OUTCOME MEASURES: 1. Gastric emptying: maximum concentration (Cmax) and time to maximum concentration (Tmax) of paracetamol; 2. glycaemic response: Cmax, Tmax, and area under the curve of plasma glucose; 3. insulinaemic response: Cmax, Tmax, area under the curve of plasma insulin. RESULTS: An increased, but not delayed, insulin response, and an increased initial glucose response to a test meal in the third trimester were not accompanied by any simultaneous delay in gastric emptying. CONCLUSION: Gastric emptying does not seem to be a factor in the glycaemic response of pregnancy.

Acetaminophen↗
PubMed1995

Effect of Helicobacter pylori status on intragastric pH during treatment with omeprazole.

To test the hypothesis that Helicobacter pylori infection is associated with a decreased intragastric acidity during omeprazole therapy, ambulatory 24 hour dual point gastric pH recordings were performed in 18 H pylori positive and 14 H pylori negative subjects. There was a four to six week washout period between the two pH recordings made in each subject after one week courses of placebo or omeprazole, 20 mg daily. During placebo, median 24 hour pH values were not different in the corpus (H pylori positive = 1.5, negative = 1.4; p = 0.9) or antrum (H pylori positive = 1.3, negative = 1.2; p = 0.1). However, during omeprazole treatment, median 24 hour pH values were higher in H pylori positive subjects, both in the corpus (H pylori positive = 5.5, negative = 4.0; p = 0.001) and antrum (H pylori positive = 5.5, negative = 3.5; p = 0.0004). During placebo treatment, the only difference between the two groups was a higher later nocturnal pH in the antrum in the H pylori positive group. During omeprazole treatment, gastric pH was higher both in the corpus and in the antrum in the H pylori positive group for all periods, except for mealtime in the corpus. These data indicate that omeprazole produces a greater decrease in gastric acidity in subjects with H pylori infection than in those who are H pylori negative. It is not, however, known whether there is a causal relationship between H pylori infection and increased omeprazole efficacy.

Adult↗
PubMed1995

Effects of posture on gastric emptying of nonnutrient liquids and antropyloroduodenal motility.

The effects of posture on gastric emptying, intragastric distribution, and antropyloroduodenal motility after ingestion of a nonnutrient liquid have been evaluated. In seven healthy volunteers antropyloroduodenal pressures were measured for 30 min after ingestion of 150 ml of normal saline in two different positions: sitting and left lateral. Saline drinks were radiolabeled and ingested both before and after intravenous atropine (4 micrograms/kg). Rates of emptying from both the total (P < 0.05) and the proximal (P < 0.05) stomach were faster in the sitting position than in the left lateral position. There were more long (> 6 cm) antropyloric pressure waves (P < 0.05) and isolated pyloric pressure waves (P < 0.05) in the sitting position. Intravenous atropine slowed emptying in both positions (P < 0.05) and in the sitting position decreased (P < 0.05) the number of antropyloric pressure waves. After atropine, gastric emptying was also faster in the sitting compared with the decubitus position (P < 0.05), although there was no difference in antropyloric or isolated pyloric pressure waves between the two postures. We conclude that the effects of gravity on gastric emptying of nonnutrient liquids are likely to reflect changes in both antropyloric motility and intragastric distribution.

Adolescent↗
PubMed1995

Evidence of coexisting changes in 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activity in subjects with untreated essential hypertension.

We compared corticosteroid metabolite excretion rates and patterns in a group of 68 subjects with untreated essential hypertension and a matched group of 48 normotensive control subjects. The ratio of tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone and the ratio of allotetrahydrocortisol to tetrahydrocortisol were significantly higher in the hypertensive group. This is qualitatively similar to the situation found in patients with the syndrome of apparent mineralocorticoid excess or subjects treated with licorice or carbenoxolone where hypertension is known to arise from deficiencies of 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activities. The equivalent ratios for corticosterone metabolites were not different between groups, but total corticosterone metabolite excretion was higher in the hypertensive group. Plasma cortisol levels were lower in hypertensive than in control subjects, but corticosterone levels were higher. This evidence supports a previous suggestion that the activities of these two enzymes may be reduced in essential hypertension, but the contribution of these changes to hypertension is not known.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Constrictive bronchiolitis obliterans following gold therapy for psoriatic arthritis.

A 41 year old male with psoriatic arthritis developed progressive dyspnoea and airflow obstruction following 4 months of intramuscular gold therapy. Open lung biopsy revealed bronchiolitis obliterans of the constrictive type. This case suggests a possible aetiological role for gold in the pathogenesis of constrictive bronchiolitis obliterans, or alternatively an association between psoriatic arthritis and this inflammatory airway condition.

Adult↗
PubMed1995

Focal suppression-burst on electrocorticography after temporal lobectomy.

Of 40 patients with cortical resections for epilepsy, three had focal suppression-burst (S-B) on postresection intraoperative electrocorticography (ECoG). Eighteen to 24 months later, two patients were seizure-free and one had rare seizures. Follow-up neuropsychological testing and MRI did not reveal unexpected postoperative abnormalities. Follow-up scalp surface EEGs did not show S-B. Although S-B on postresection ECoG suggests severe localized cortical damage, this pattern near anterior temporal lobectomy resection margins was not associated with postoperative deficits.

Cerebral Cortex↗
PubMed1995

Postaxial polydactyly in forelimbs of CRABP-II mutant mice.

The cytoplasmic retinoic acid (RA)-binding protein CRABP-II is expressed widely throughout early morphogenesis in mouse embryo, but its expression becomes more restricted as organogenesis progresses. CRABP-II expression remains strong in the developing limb bud suggesting a role for this protein in limb patterning. Here, we show that the CRABP-II promoter can direct expression of a lacZ transgene in a specific posterior domain during limb bud development. In order to investigate in more detail the role played by CRABP-II in RA signal transduction, we have also generated mice homozygous for a null mutation of this gene. CRABPII-/- mice are viable and fertile but show a developmental defect of the forelimb, specifically an additional, postaxial digit. This digit is generally, but not exclusively, limited to a single forepaw of an individual animal. The penetrance of the phenotype varies according to the genetic background, occurring most frequently on the inbred 129Sv background (50%), less frequently on the C57Bl/6 background (30%) and rarely on the outbred CD1 background (10%). This developmental abnormality implies a role for CRABP-II in normal patterning of the limb.

Animals↗
PubMed1995

The origin of nocturnal intragastric pH rises in healthy subjects.

BACKGROUND: Duodenogastric reflux (DGR) can produce transient increases in gastric luminal pH. It has been proposed that intragastric pH-metry is a reliable method for the detection of DGR. Our aim was to test the hypothesis that nocturnal increases in antral pH are due solely to DGR. METHODS: Gastric pH was monitored overnight using two glass pH electrodes, one in the antrum adjacent to the tip of a nasogastric tube and one in the corpus. Scheduled antral aspirations were performed hourly to determine base-line concentrations of total bile acids (TBA; a marker of DGR) and thiocyanate (SCN; a marker of swallowed saliva). Additional, triggered aspirations were performed if antral pH exceeded 3.0 for 1 min or more (PHAP; period of high antral pH). TBA and SCN were considered to be increased if they exceeded the 90th percentile of values determined in scheduled aspirates (TBA, 0.88 mM; SCN, 0.67 mM). RESULTS: In 28 of the 62 samples whose aspiration was triggered by a PHAP the pH was less than 3.0, and the sample was not considered to be representative. In the remaining 34 samples the antral luminal pH and the sample pH were concordant; TBA alone was increased in 6 samples, SCN alone was increased in 6 samples, and TBA and SCN were both increased in another 3 samples. Thus, DGR and swallowed saliva alone or in combination accounted for only 15 (45%) of the PHAP in which adequate gastric samples were obtained. CONCLUSION: Samples of gastric antral contents often do not reflect accurately the acidity of gastric fluid in contact with a luminal antral pH electrode. Nocturnal increases in antral pH, detected by a luminal electrode, are frequently due to mechanisms other than duodenogastric reflux or swallowed saliva. Thus, antral pH-metry is not suitable for monitoring the occurrence of duodenogastric reflux.

Adult↗
PubMed1995

Histopathological effects of acute exposure to chlorine gas on Sprague-Dawley rat lungs.

It is now recognized that acute inhalational exposure to irritant gases such as chlorine can cause an asthma-like abnormality known as reactive airways dysfunction syndrome (RADS). The aim of this study was to evaluate the effects of exposure to various levels of chlorine on airway mucosa and lung parenchyma in an attempt to develop an animal model of this syndrome. Seventy-four Sprague-Dawley rats were exposed to air (controls) or to 50, 100, 200, 500, and 1500 ppm of chlorine for 2 to 10 min. Histological assessment was performed at 1, 3, 6, 12, 24, and 72 h after exposure. The results show that exposure to low concentrations (500 ppm) did not induce significant histological changes. Exposure to 1500 ppm for 2 min induced perivascular edema and the appearance of focal mild inflammation, whereas exposure to the same concentration for 10 min caused profound histological changes, including (1) 1 h: airspace and interstitial edema associated with bronchial epithelial sloughing; (2) 6 to 24 h: decreased edema and the appearance of mucosal polymorphonuclear leukocytes, maximal at 12 h; (3) 72 h: epithelial regeneration, manifested by hyperplasia and goblet cell metaplasia. We conclude that acute exposure to chlorine at a concentration of 1500 ppm for 10 min induces significant airway mucosal abnormalities that vary over a short period of time. Whether these abnormalities are related to the subsequent development of RADS awaits further experiments.

Animals↗
PubMed1995

Mildly raised corticosterone excretion rates in patients with essential hypertension.

In a large group of patients with untreated hypertension, excretion rates of tetrahydrocorticosterone (THB), allotetrahydrocorticosterone (alloTHB) and tetrahydro-11-dehydrocorticosterone (THA) were all significantly higher than in a group of matched normotensive controls. Using the sum of these metabolites as an index of corticosterone secretion rate suggests that this variable is also higher. The increase was small (all excretion rates remained within the normal range) and corticosterone has low glucocorticoid and mineralocorticoid potency calling the clinical significance of this finding into question. However, it is possible that in combination with mildly deficient 11 beta-hydroxysteroid dehydrogenase activity such increases in corticosterone levels might affect blood pressure.

Corticosterone↗
PubMed1995

Dexamethasone-suppressible hyperaldosteronism: clinical, biochemical and genetic relations.

Clinical, biochemical and molecular data on five kindreds with dexamethasone-suppressible hyperaldosteronism are reviewed. The clinical phenotype varies from severe, early onset hypertension to much milder blood pressure elevation; hypokalaemia is usually mild. The genetic basis of the syndrome reflects the presence of a chimaeric gene derived from an unequal crossover between CYP11B1 and CYP11B2, resulting in ACTH-sensitive aldosterone synthase activity. In five kindreds, at least three different mutations have been identified, suggesting that allelic predisposition might lead to increased geographical prevalence of the condition in Celtic populations.

Adrenal Cortex Hormones↗
PubMed1995

Lipoproteins and the liver sieve: the role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis.

The liver sieve, formed by the fenestrated hepatic sinusoidal endothelium, is a dynamic biofilter separating the hepatic blood from the plasma within the space of Disse. It filters macromolecules of differing sizes, especially lipoproteins. More specifically, it acts as a barrier to the large triglyceride-rich parent chylomicrons, while permitting the smaller triglyceride-depleted but cholesterol- and retinol-rich remnants to enter the space of Disse. There the remnants contact specific receptor sites on the hepatocyte microvilli. Thus, the liver sieve is the first site of hepatic selection and consequent metabolism of dietary cholesterol and fat-soluble vitamins, as well as rejection of dietary triglycerides. Therefore, perturbations of the porosity of the sieve, whether from changes in size, number of fenestrae, or composition of the underlying extracellular matrix within the space of Disse, will have a profound influence on the metabolism of lipoproteins. This disturbance of the homeostasis of lipids, including fat-soluble vitamins and cholesterol, as well as other macromolecules, may tilt the balance between health and disease in a variety of organs and tissues, such as the liver, kidney and arteries.

Animals↗
PubMed1994

Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI.

Current MR meal markers may interfere with gastric motility and secretion restricting the use of MRI in the measurement of gastric physiology. We therefore evaluated Gd-DOTA as a liquid phase marker, in vitro by determining dissociation, and adherence to the solids, and in vivo by simultaneous MRI (0.35 T scanner, multiple T1-weighted sections of the upper abdomen) and double indicator (perfusion marker PEG 4000, meal marker 99mTc-DTPA) measurements of emptying and secretion, following ingestion of 500 ml 10% glucose. In vitro Gd-DOTA was stable at a pH > 2 with < 2% dissociation at 24 h during incubation with HCl. Dissociation during incubation with HCl was linearly dependent on H+ concentration (0.77 < pH < 2.02). Less Gd-DOTA was absorbed onto the solid phase than 99mTc-DTPA (25% cf 36%). In vivo Gd-DOTA marked gastric contents provided strong positive contrast. Similar emptying curves were observed with both MRI and double-indicator techniques (r = 0.987, P < 0.001). Gd-DOTA has the potential to be a useful liquid phase contrast agent in MR studies on gastric function.

Adult↗
PubMed1994

Disordered gastric motor function in diabetes mellitus.

The application of novel investigative techniques has demonstrated that disordered gastric motility occurs frequently in diabetes mellitus. Gastric emptying is abnormal in about 50% of diabetic patients and delay in gastric emptying of nutrient-containing meals is more common than rapid emptying. The blood glucose concentration influences gastric motility in diabetes. In IDDM patients, gastric emptying is retarded during hyperglycaemia and may be accelerated by hypoglycaemia. Gastroparesis therefore does not necessarily reflect irreversible autonomic neuropathy and blood glucose concentrations must be monitored when gastric motility is evaluated in diabetic patients. There is a poor relationship between gastric emptying and gastrointestinal symptoms and the mechanisms by which abnormal motility causes symptoms are unclear. The introduction of new gastrokinetic drugs has improved therapeutic options for the management of symptomatic patients with gastroparesis considerably. The contribution of disordered gastric emptying to poor glycaemic control is unclear, but the demonstration that the rate of gastric emptying is a major factor in normal blood glucose homeostasis suggests that this is likely to be significant.

Diabetes Complications↗
PubMed1994

Gastric motility measurement by MRI.

The motor mechanisms associated with gastric emptying of nutrient liquids are unclear. Gastric emptying and motility were determined in seven healthy volunteers using an MRI technique following ingestion of 500 ml of (1) 10% and (2) 25% dextrose labeled with 1 mM Gd-DOTA. Emptying was determined with transaxial scans and motility during fast coronal scans 1.2 sec apart. Emptying was slower after ingestion of 25% dextrose. Following both meals, proximal gastric diameter remained relatively constant, while antral contractile frequency and depth varied markedly. These variations were greater after 10% dextrose. These studies suggest that antral motility changes contribute to slowing of gastric emptying by nutrient meals.

Animals↗
PubMed1994

Measurement of gastric emptying and gastric motility by magnetic resonance imaging (MRI).

Hitherto it has been impossible to measure noninvasively gastric emptying and motility from multiple regions of the stomach in humans. We describe the development of a novel methodology to achieve this using magnetic resonance imaging (MRI). Initial validation studies performed in five healthy volunteers demonstrated similar gastric emptying curves and secretion rates after ingestion of 10% dextrose labeled with [Gd]DOTA, assessed by MRI ([Gd]DOTA as meal marker) and a simultaneous double-indicator technique. Comparison between MRI and scintigraphy in five patients also gave similar results. Application of newer MRI technology allowing a series of coronal scans 1.2 sec apart permitted quantification of wall motion in the proximal and distal stomach in seven healthy volunteers. These results indicate that MRI provides new insights into the mechanisms responsible for both normal and disordered emptying.

Contrast Media↗