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Biomedical subjects

G Neale

Publications and source records attributed to G Neale.

At least 55 records · Page 3Linked to original sources
PubMed1986

Investigation of auranofin-induced diarrhoea.

Gastrointestinal function was assessed in six patients with rheumatoid arthritis who had developed diarrhoea on treatment with Auranofin. With the administration of Auranofin whole gut transit time decreased markedly (to 50% or less of control values) in five of six patients. The speed of passage of intestinal contents through the colon was certainly increased but attempts to assess transit through the upper gastrointestinal tract failed because the breath hydrogen method gave inconclusive results. There was no evidence of colitis and in all cases biopsy of the rectal mucosa appeared normal by light microscopy. In the five patients with rapid intestinal transit faecal weight increased more than two-fold (range +44 to +335%) although in only three cases were the changes sufficient to cause an increased frequency of bowel action. Overall the concentration of sodium in faecal water increased three-fold (mean values rose from 10.6 to 38.3 mmol/l). There were no significant changes in the concentrations of either potassium or chloride but bicarbonate was reduced. Faecal pH fell from a mean value of 7.5 (range 6.8-7.9) to a mean value of 6.4 (range 6.0-7.4). In the three patients who developed overt diarrhoea and in two others taking Auranofin the intestinal uptake of 51Cr-EDTA was increased on average three-fold and there was a similar change in the ratio of the absorption of lactulose/mannitol. The mean clearance of alpha-1-antitrypsin from the circulation into the gastrointestinal tract was doubled. These data indicate an increase in intestinal permeability. In contrast the absorption of vitamin B12 was unaffected and there was no significant change in the excretion of faecal fat although one patient developed mild steatorrhoea. Thus in a selected group of subjects with rheumatoid arthritis the administration of Auranofin caused diarrhoea in association with a reversible defect in intestinal permeability but without significant change in the absorption of nutrients.

Adult↗
PubMed1985

Is continuous sulfasalazine necessary in the management of patients with ulcerative colitis? Results of a preliminary study.

The efficacy of continuous and "on-demand" sulfasalazine in the maintenance of remission of ulcerative colitis was tested in a randomized trial. Patients were reviewed at four monthly intervals for one year. Twenty-eight patients completed the trial. Ten took continuous sulfasalazine and three relapsed, while 18 took "on-demand" sulfasalazine and seven relapsed (N.S.). Rectal biopsies from each patient group were compared at each attendance, and no significant difference in histologic score was found. It is concluded that "on-demand" sulfasalazine may be as effective as continuous sulfasalazine in the maintenance of remission of ulcerative colitis.

Adult↗
PubMed1985

Alanine and glutamine release from the human forearm: effects of glucose administration.

The effect of glucose infusion alone (175 mg/kg bolus dose followed by 4 mg min-1 kg-1 for 70 min) and in combination with forearm exercise on the exchange of glucose, alanine, glutamine and other metabolites and amino acids across forearm muscle was studied in six healthy individuals after an overnight fast. Arterial and deep venous blood was sampled and a mercury strain gauge plethysmograph was used to measure forearm blood flow. Total body energy expenditure and net glucose and fat oxidation were assessed by indirect calorimetry. The infusion of glucose increased the mean arterial blood glucose concentration from 4.95 +/- 0.19 (SEM) to a plateau of 9.6-9.9 mmol/l (P less than 0.01). The arterial blood concentrations of alanine and glutamine were not significantly altered but that of lactate increased from 0.50 +/- 0.02 to 0.65 +/- 0.05 mmol/l (P less than 0.02) and that of pyruvate increased from 46 +/- 5 to 72 +/- 6 mumol/l (P less than 0.01). In the resting state glucose administration did not significantly affect the lactate/pyruvate ratio in arterial or venous blood. Arterial plasma insulin concentration increased four-fold and total ketone body concentration decreased two- to three-fold. After glucose administration, alanine release was suppressed (in all subjects) from a mean value of 153 +/- 22 to 57 +/- 16 nmol min-1 100 ml-1 of forearm (P less than 0.02) whereas that of glutamine was not significantly affected (160 +/- 30 to 143 +/- 29 nmol min-1 100 ml-1 of forearm). Lactate release, like that of alanine, decreased, whereas pyruvate was slowly released in the basal state and was taken up during glucose administration (P less than 0.01). These changes were associated with a decrease in the uptake of total ketone bodies to one-fifth to one-tenth of that in the basal state. The net amino acid balance across the forearm muscle bed was negative throughout the study but decreased from a mean value of -567 in the basal state to -300 nmol min-1 100 ml-1 of forearm after glucose administration for 60 min. This was predominantly due to decreased release of effluxing amino acids, particularly alanine.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Factors affecting maximal momentary grip strength.

Maximal voluntary grip strength has been measured in normal adults aged 18-70 years (17 f, 18 m) and compared with other indices of body muscle mass. Grip strength (dominant side) was directly proportional to creatinine excretion (r = 0.81); to forearm muscle area (r = 0.73); to upper arm muscle area (r = 0.71) and to lean body mass (r = 0.65). Grip strength relative to forearm muscle area decreased with age. The study of a subgroup of normal subjects revealed a small but significant postural and circadian effect on grip strength. The effect on maximal voluntary grip strength of sedatives in elderly subjects undergoing routine endoscopy (n = 6), and of acute infections in otherwise healthy individuals (n = 6), severe illness in patients requiring intensive care (n = 6), chronic renal failure (n = 7) and anorexia nervosa (n = 6) has been assessed. Intravenous diazepam and buscopan produced a 50 per cent reduction in grip strength which returned to normal within the next 2-3 h. Acute infections reduced grip strength by a mean of 35 per cent and severe illness in patients in intensive care by 60 per cent. In patients with chronic renal failure grip strength was 80-85 per cent of that predicted from forearm 'muscle area' (P less than 0.05). In anorectic patients the values were appropriate for their forearm muscle area. Nevertheless nutritional rehabilitation of one anorectic patient did not lead to a consistent improvement in grip strength.

Adolescent↗
PubMed1984

Mineral metabolism during short-term starvation in man.

Plasma and urine electrolytes were measured in five healthy non-obese young adults before, during and after a four-day period of total starvation (distilled water only). Plasma sodium, chloride and bicarbonate concentrations decreased in all subjects by a mean value of 4 mmol/l, whereas the sum of acetoacetate and hydroxybutyrate concentrations increased by 4-6 mmol/l. These changes occurred without alterations in the state of hydration or vascular volume. Hydroxybutyrate and ammonium ions became the main urinary ions during starvation, whereas sodium and chloride, which were quantitatively the most important urinary electrolytes before starvation, decreased four-fold, and potassium two-fold. Plasma zinc concentrations rapidly increased in all subjects by a mean of 4 mumol/1 (25%) and returned to normal on refeeding. The excretion of zinc in urine trebled and continued to rise on refeeding. There were no major changes in the excretion of calcium, magnesium, phosphate or sulphate during the starvation period. From knowledge of the intracellular concentrations of various minerals and extent of breakdown of lean tissues (N excretion), it is suggested that most of the urinary calcium, magnesium and phosphate probably originates from bone, and that the amount of zinc in urine is only a small fraction of that which is likely to be released from the breakdown of lean tissues. It is also suggested that the continued excretion of zinc on refeeding is due to release of zinc from tissues which 'buffered' it during the starvation period. This study provides useful data in non-obese individuals with which to compare changes which occur in post-traumatic and post-infective starvation.

Adolescent↗
PubMed1984

Synthesis of prostaglandin F by cultured human endometrial cells.

Human endometrial cells were dispersed with collagenase and maintained in culture overnight. The synthesis of PGF by the dispersed cells incubated at 37 degrees C in serum-free medium was stimulated by estradiol (10(-7)M - 10(-5)M), histamine (5X10(-7)M - 5X10(-5)M), bradykinin (10(-6)M), phorbol myristate (PMA, 3X10(-8)M) and arachidonate (5X10(-6)M). Preincubation of the cells for 3 h with cortisol (5X10(-7)M - 5X10(-5)M), progesterone (10(-6)M) or mepacrine (10(-6)M - 2X10(-4)M) inhibited the response to histamine, bradykinin and PMA but not to arachidonate. Perfusion of the cultured cells in filtration chambers yielded similar results to those obtained in the incubation system but differences in the onset and duration of the responses to stimuli were found. In the perifusion system the responses to histamine and bradykinin were rapid and of short duration (peak response in less than 60 min) while the responses to PMA and arachidonate were of longer duration with a slower onset. We conclude that these observations using dispersed endometrial cells are consistent with previous work showing that histamine, bradykinin and PMA act by stimulating acylhydrolase activity, thereby liberating precursors such as arachidonic acid which are converted to prostaglandins by the cyclo-oxygenase complex.

Arachidonic Acid↗
PubMed1984

Rectal organ culture as a model for the investigation of bacterial adhesion and invasion.

A system was developed for the in vitro culture of human rectal mucosa. Its viability was proved by histological appearances and by metabolic studies. Biopsy samples were cultured in the presence of appropriate bacteria isolated from the faeces of patients with ulcerative colitis or with dysenteric illnesses. Attempts to show adhesion of bacteria to the mucosa or invasion of the cultured tissue failed. Problems with the use of this model are discussed.

Adhesiveness↗
PubMed1984

Energy metabolism during exercise in normal subjects undergoing total starvation.

Energy expenditure and the circulating concentration of various intermediary metabolites, insulin and glucagon, were measured in five lean subjects at rest and during a 20-min period of a standardized exercise (50-75 watts). Measurements were made before starvation, at the end of a 4-d period of total starvation and 24-32 h after refeeding. The respiratory quotient decreased in all subjects during starvation from 0.85 +/- 0.03 (s.e.m.) to 0.70 +/- 0.01 (P less than 0.01), and rose again on refeeding to 0.85 +/- 0.04. Resting metabolic rate (RMR) was not significantly affected by starvation. 'Work efficiency' (mechanical work done X 100 divided by metabolic rate during work - RMR) decreased in all subjects from a mean value of 23.9 per cent before starvation to 22.2 per cent during starvation and rose again on refeeding to 23.9 per cent, but with small numbers these differences did not reach statistical significance. All subjects felt that the work load (assessed on the Borg scale for perceived exertion) was greater during starvation than either before or after starvation (P less than 0.01). During exercise the circulating concentrations of glucose and glucagon remained virtually unchanged whereas insulin tended to decrease. In contrast, concentrations of lactate, pyruvate and alanine increased. The changes in the concentration of lactate, pyruvate and alanine were greater during starvation than before starvation, and are consistent with inhibition of the pyruvate dehydrogenase complex by ketone bodies, the circulating concentrations of which were elevated 20-fold during starvation. It is suggested that this inhibition may increase glucose recycling between muscle and liver and cause a small increase in energy expenditure.

Adult↗
PubMed1981

Bile acid inhibition of vitamin B12 binding by intrinsic factor in vitro.

The effect of conjugated and unconjugated bile acids on the binding of vitamin B12 to intrinsic factor was investigated. The dihydroxy bile acids (deoxycholic, glycodeoxycholic, taurodeoxycholic, glycochenodeoxycholic, and taurochenodeoxycholic) inhibit the binding of intrinsic factor to vitamin B12 at physiological concentrations. On the other hand, the trihydroxy bile acids (cholic, glycocholic, and taurocholic) are not effective in this respect. The inhibition is dependent both on concentration and time, and its pattern is similar to that previously reported for duodenal juice. On column chromatography, there is a close correlation between the degree in intrinsic factor inhibition and the total acid concentration in the duodenal juice. The binding of vitamin B12 by R protein in saliva is not affected by bile acids. The results show that bile acids at concentrations found in duodenal juice inhibit intrinsic factor vitamin B12 binding. It is suggested that this observation may have physiological significance for vitamin B12 absorption.

Bile Acids and Salts↗
PubMed1980

Effect of bile on vitamin B12 absorption.

The standard double-isotope Schilling test was used to study vitamin B12 absorption in seven patients with obstructive jaundice and 10 with T-tube bile duct drainage after cholecystectomy and bile duct exploration. In three and five of these patients respectively absorption was impaired. In the second group six patients were restudied after removal of the T tube, and in each case absorption was improved. Similar results were obtained after bile duct ligation in rats. Bile exclusion produced a 50-60% reduction in renal and hepatic uptake of vitamin B12 from the intestinal lumen. The malabsorption was corrected by replacing bile. These studies suggest that bile plays a part in the normal absorption of vitamin B12.

Adult↗