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Biomedical subjects

G Neale

Publications and source records attributed to G Neale.

At least 37 records · Page 2Linked to original sources

Effect of total starvation and very low calorie diets on intestinal permeability in man.

1. The effect of total starvation for 4-5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5g), [14C]mannitol (0.5 microCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 microCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g). [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P less than 0.025), 33% in group 2 obese subjects (P less than 0.05) and 41% in group 3 obese subjects P greater than 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine

Factors affecting the integrity of the intestinal mucosa of Gambian children.

The interrelationship between diarrhea, malnutrition, and small bowel integrity was investigated prospectively in 68 Gambian infants aged 0-18 mo. Profiles of growth and morbidity were recorded for 8 mo. Each month intestinal permeability was measured by the differential uptake of orally administered lactulose (L) and mannitol (M). In well infants the mean L:M ratio was 0.42 (range 0.11-1.42). This ratio was increased slightly for underweight (60-80% wt for age) infants (mean 0.52) but considerably for those with marasmus (less than 60% wt for age) (mean 1.3, p less than 0.001), for those with acute or chronic diarrhea (mean 1.0 and 2.85, respectively; p less than 0.001), or with measles (mean 1.4, p less than 0.001). Sequential studies of ward patients with malnutrition and diarrhea showed a rapid fall in L:M ratios with resolution of diarrhea. These studies suggest that damage to the small intestine may play an important part in the development of infant malnutrition in The Gambia.

Carbohydrate Metabolism

Radionuclide tests for the assessment of intestinal permeability.

14C labelled-D-mannitol and aquo (ethylene-diaminetriacetoacetic acid) 51chromium (III) (51Cr EDTA) have been evaluated as markers of intestinal permeability in twenty-four healthy control subjects, sixteen patients with recently diagnosed coeliac disease and twenty subjects with coeliac disease in remission on a gluten-free diet. The percentage excretion of 14C mannitol in urine collected for 6 h was significantly less in patients with coeliac disease (mean 6.7%) than controls (mean 13.5%). Conversely the excretion of 51Cr EDTA was significantly greater in patients with coeliac disease (mean 1.23%) compared with controls (mean 0.28%). The mean ratio of the percentage excretion of 51Cr to the percentage excretion of 14C was 0.29 in patients with untreated coeliac disease compared with 0.023 for healthy control subjects (P less than 0.001). Patients with untreated coeliac disease were clearly separated from control subjects by use of the 51Cr EDTA: 14C mannitol ratio but not by the excretion of independent markers.

Adult

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

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

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

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

Diagnosis and management of obscure gastrointestinal bleeding.

Twelve consecutive patients presenting with unexplained recurrent gastrointestinal bleeding were investigated by selective visceral angiography. A cause for the bleeding was shown in all 12 cases, and in eight the lesion responsible was diagnosed radiologically as an area of angiodysplasia. Abnormal areas were pinpointed by fluoroscopy and examination of the resected bowel with a dissecting microscope after injecting the vessels with barium. Histologically these areas had various microvascular abnormalities. Angiodysplasia is a useful descriptive radiological term, but does not seem to represent a single pathological entity.

Adult

Serum and faecal lysozyme in inflammatory bowel disease.

Lysozyme (EC 3.2.1.17) concentrations were measured in the serum and stools of patients with inflammatory bowel disease and compared with the concentrations in similar material from normal controls, patints with non-inflammatory gastrointestinal disease, and patients without gastrointestinal disease. By the turbidometric method, values of lysozyme (microgram/ml +/- SD) are considerably greater in the serum of patients with active Crohn's disease (9.2 +/- 2.7) than in the serum of healthy controls (4.4 +/- 2.0). They do not, however, distinguish individual patients with Crohn's disease from those with ulcerative colitis nor from those with a variety of other gastrointestinal conditions. The lysoplate method gives much higher values for serum lysozyme than the turbidometric method but there is a considerable overlap between the results for patients with Crohn's disease (60.1 +/- 30.7) and normal controls (27.4 +/- 17.5). There is only a moderate correlation between the results given by the two methods (r = 0.56) and it is suggested that factors other than enzyme activity and methodological variation are responsible for the observed differences. This is supported by the finding that, with Crohn's disease in remission, serum lysozyme values (lysoplate) return to normal values but with the turbidometric method remain raised. Mean faecal lysozyme levels, expressed either as a concentration or as total daily excretion, in patients with inflammatory bowel disease are very significantly greater than values in healthy controls and in diseased subjects without diarrhoea but are not significantly different from those subjects with other causes of diarrhoea.

Colitis, Ulcerative

Lysosomal changes in liver tissue from patients with the Dubin-Johnson-Sprinz syndrome.

1. Clinical, morphological and biochemical data, including data obtained from the application of subcellular fractionation techniques to liver biopsy specimens, are presented for two patients with the Dubin-Johnson-Sprinz (DJS) syndrome. 2. Subcellular fractionation experiments demonstrate that the lysosomes, which have strikingly reduced equilibrium densities, accumulate melanin. Morphological studies confirm the presence of pigments within lysosomes. 3. Although there are increased activities of lysosomal acid hydrolases in the liver tissue from patients with the DJS syndrome, the integrity of these organelles is essentially normal and therefore the accumulation of pigment would not be expected to initiate liver damage. The DJS syndrome is thus a benign type of secondary lysosomal storage disease.

Adult

Functional and biochemical evidence of damage to enterocytes induced by triparanol: role of lysosomes and the effect of gluten-free diet.

1. Functional and biochemical studies were performed on the small intestine of control rats, and the results were compared with similar studies on animals given triparanol at a dosage of 0.114 mmol/kg daily for 10 days. The animals given triparanol were fed with either standard rat food or a gluten-free diet. 2. By using a recirculating-perfusion technique in vivo, it was shown that absorption of galactose from an 8 mmol/l solution was impaired in the ileum but not in the jejunum of the triparanol-treated rats. 3. Assays of marker enzymes for the principal subcellular organelles were performed on isolated jejunal and ileal enterocytes. In the ileum there was a striking decrease in lysosomal enzyme activities and a smaller but significant decrease of lactate dehydrogenase, catalase and malate dehydrogenase activities. In the jejunum there was no significant change in the activities of these enzymes. 4. Measurements of lysosomal integrity indicated that ileal lysosomal fragility was markedly increased and that jejunal lysosomes were affected to a much smaller extent. 5. These effects of triparanol could not be ameliorated by feeding with a gluten-free diet.

Acetylglucosaminidase

A familial abnormality of circulating vitamin B12 binding proteins: occurrence in a family of high serum concentrations of transcobalamin II.

A family is described in which two members (a father and a daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE-23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti-TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the beta, gamma region. This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed.

Blood Proteins