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Biomedical subjects

G N Thompson

Publications and source records attributed to G N Thompson.

At least 55 records · Page 3Linked to original sources

Rapid measurement of whole body and forearm protein turnover using a [2H5]phenylalanine model.

Whole body protein turnover was measured in six normal adults using a model based on a primed constant infusion of [2H5]phenylalanine and, independently, by an established method of a primed constant infusion of [1-13C]leucine. Isotopic plateau in plasma was achieved within 2 h for [2H5]phenylalanine and, in four of the subjects who received a priming dose of [2H4]tyrosine, for [2H4]tyrosine. In all subjects whole body protein turnover measured with the phenylalanine model (mean protein synthesis, 2.65 +/- (SD) 0.16 g.kg-1.24 h-1; catabolism, 3.58 +/- 0.26 g.kg-1.24 h-1) was similar to that measured using the leucine model (synthesis, 3.09 +/- 0.27 g.kg-1.24 h-1; catabolism, 3.70 +/- 0.35 g.kg-1.24 h-1). Mean forearm fractional muscle protein synthesis calculated by the phenylalanine model was 0.06 +/- 0.03%/h, which compares closely with literature values derived by other methods. The phenylalanine model allows the rapid assessment of whole body and muscle protein turnover from plasma samples alone, obviating the need for measurement of expired air CO2 production or enrichment.

Adult↗

Stable isotopes as tracers in clinical research.

The increased availability of an extensive range of stable isotope-labelled substrates and their ever decreasing cost, as well as the availability of sensitive analytical instruments, suggests that stable isotopes will increasingly be employed in all branches of medical research. It seems likely that within the near future they will totally replace radioactive isotopes in quantitative metabolic studies involving human subjects.

Clinical Trials as Topic↗

Assessment of taurine deficiency in cystic fibrosis.

Bile acid taurine deficiency is common in cystic fibrosis (CF) and is thought to be associated with impaired fat absorption. The relationship between the glycine: taurine bile acid conjugation ratio (bile acid G/T ratio) and taurine concentrations in plasma, urine and leucocytes was examined in 27 CF children aged 4-15 yr. The bile acid G/T ratio was elevated in serum in 14 of the 27 and in duodenal juice in 5 of 6 children. Subgroups of CF children with elevated and normal bile acid G/T ratio and controls (n = 8) all had similar plasma, urine and leucocyte taurine concentrations. The results suggest that either taurine measurement in plasma, urine and leucocytes does not accurately reflect stores elsewhere in CF, or that taurine deficiency is confined to bile acids.

Adolescent↗

Relationships between plasma isotope enrichments of leucine and alpha-ketoisocaproic acid during continuous infusion of labelled leucine.

The ratio at steady-state of alpha-ketoisocaproic acid (KIC) to leucine 13C enrichments in plasma during continuous infusion of [13C]leucine was examined in 58 studies under a variety of conditions. The ratio was lower (P less than 0.001) in 'arterialized' venous plasma (mean +/- SD 0.85 +/- 0.09) than in deep venous plasma (0.95 +/- 0.08), the sampling site enrichment differences being greater for leucine than for KIC. Variation in the ratio between the various conditions studied was largely explained by analytical variation. Three normal subjects were given an intravenous bolus dose of L-[1-13C, 15N]leucine. Both [13C]KIC and [13C]leucine appeared quantitatively in plasma within 10 min, indicating that both transamination of leucine and KIC, and their equilibration between intracellular fluid and plasma, is rapid. This study suggests that changes in sampling site, rather than in study conditions, are more likely to lead to variation in the KIC:leucine enrichment ratio. The lesser variation for KIC, and the rapid equilibration of the [13C]leucine bolus, favour KIC as tracee for [13C]leucine protein turnover studies.

Adult↗

Taurine uptake by normal and cystic fibrosis fibroblasts.

Taurine deficiency recently has been proposed to be clinically significant in cystic fibrosis (CF). Uptake of [14C]taurine by four cystic fibrosis (CF) and three control fibroblast lines was examined to determine whether a generalized defect in taurine transport could contribute to the deficiency. The time course of uptake was linear up to 20 h and was similar in both CF and control fibroblasts. Taurine was avidly retained after uptake, and the effect of metabolic (chlorpromazine) and competitive (hypotaurine, L-leucine) inhibitors was similar in both CF and control cells. In contrast, while taurine uptake in a calcium-free medium was impaired in both CF and control fibroblasts, the impairment was significantly less in CF cells. The findings suggest that a generalized abnormality in taurine transport is unlikely to be responsible for the taurine deficiency in CF.

Calcium↗

In vivo bile acid uptake from terminal ileum in cystic fibrosis.

The cause(s) of excessive fecal bile acid loss in cystic fibrosis (CF) has not yet been fully determined, but in vitro studies have suggested that a primary mucosal defect in ileal bile acid uptake may be of importance. To examine this mechanism in vivo, the terminal ileal uptakes of taurocholate and glycocholate were determined using a marker-perfusion technique in three CF infants and four controls. Normal and CF ileal conditions were stimulated by varying the taurocholate:glycocholate concentration ratio (normal 1:1, CF 1:4) and pH (normal 7.8, CF 6.0) of the perfusate. The mean bile acid uptake under normal perfusate conditions was not significantly different in CF subjects (taurocholate 0.124 mumol/min/cm ileum +/- SD 0.127, glycocholate 0.117 mumol/min/cm ileum +/- 0.114), and controls (0.142 +/- 0.164 and 0.115 +/- 0.120 respectively). Similarly, under CF conditions, bile acid uptake values in CF subjects and controls were similar. The results are not consistent with deranged ileal bile acid reabsorption being a major cause of fecal bile acid loss in CF.

Bile Acids and Salts↗

Taurine supplementation, fat absorption, and growth in cystic fibrosis.

The effect of taurine supplementation (30 to 40 mg/kg/24 hr) on fat absorption and related measurements was examined in 21 preadolescent children with cystic fibrosis (CF) using a 12-month double-blind crossover technique. The mean coefficient of fat absorption was unchanged by taurine both in the unselected study group (without taurine, mean +/- SD 84.0% +/- 11.9%; with taurine, 84.4% +/- 11.8%, n = 20) and in a subgroup of seven children with moderately severe fat malabsorption (without taurine, 75.6% +/- 15.6%; with taurine, 74.8% +/- 14.6%). The mean fecal split fat/total fat ratio, which generally reflects bile acid-related fat malabsorption, was also unchanged. Linoleic and arachidonic acid deficiencies noted in plasma before supplementation showed no significant improvement with taurine supplementation. Likewise, plasma/serum vitamin A, E, and D levels were unchanged. Standard scores for height and weight were not affected significantly. This study does not support the use of taurine supplementation in the nutritional management of CF.

Body Height↗

Protein metabolism in cystic fibrosis: responses to malnutrition and taurine supplementation.

Increased protein breakdown has been cited as an important cause of nutrient loss in cystic fibrosis (CF). Taurine deficiency, which is common in CF, may contribute to the increased breakdown. The occurrence of and the benefit of taurine supplementation to abnormal protein metabolism in apparently optimally treated CF were assessed using a 12-mo double-blind crossover technique in 14 well-nourished and seven mildly-moderately malnourished infection-free preadolescent CF children. Muscle protein breakdown (urinary 3-methylhistidine technique) was significantly decreased in well-nourished (1.35% degraded/24 h +/- 0.15, p less than 0.05) and malnourished (1.24 +/- 0.11, p less than 0.001) CF children compared with controls (1.50 +/- 0.17, n = 13). Whole-body protein flux, synthesis, and catabolism ([15N]-glycine technique) were similar in all groups. Net protein gain was greater in CF children, particularly those who were well-nourished (0.55 g/(kg X 10 h) +/- 0.35, p less than 0.01) compared with controls (0.16 +/- 0.26). Taurine supplementation did not significantly affect any of the indices. In the absence of infection, protein metabolism in CF children responds appropriately to malnutrition.

Child↗

Determinants of serum vitamin D levels in preadolescent cystic fibrosis children.

The effects of liver disease, fat malabsorption and sunlight exposure on serum vitamin D levels were determined in 21 optimally treated preadolescent cystic fibrosis (CF) children over a 12-month period. Manifest liver disease and fat malabsorption appeared not to affect the vitamin D level. However, the level fell significantly in winter, although not below the normal range, suggesting that sunlight exposure is a more important determinant of vitamin D levels in preadolescent CF children than liver disease and fat malabsorption.

Child↗

Type V hyperlipoproteinaemia in neonates.

A boy investigated for neonatal jaundice was noted to have lipaemic serum and was subsequently shown to have type V hyperlipoproteinaemia. Dietary treatment was maintained for five years and he followed a typical clinical course. Circumstantial evidence suggested an autosomal recessive inheritance pattern.

Humans↗

Management and outcome of children with congenital hypothyroidism detected on neonatal screening in South Australia.

Thirty-eight congenitally hypothyroid children who were detected in a neonatal screening programme have been treated for a mean period of 3.8 years (range, 0.5-8.5 years) by the maintenance of the free thyroxine index in the upper normal range as the main determinant of the dose of thyroxine. Only excessive elevation of, or serial rises in, thyroid stimulating hormone (TSH) level influenced the dose of thyroxine. This treatment strategy, which aims to avoid the potentially adverse effects of thyroxine overdosage, has often resulted in delayed return of TSH levels to normal, especially in athyrotic children (mean TSH +/- SD at one year of age in athyrotic children, 72 +/- 90 mU/L; in children with ectopic thyroid glands, 24 +/- 16 mU/L; normal range, 0-7 mU/L). The mean thyroxine dose of about 100 micrograms/m2 did not change significantly with age, and is lower than the doses that are sometimes quoted in the literature; athyrotic children require significantly more thyroxine (P less than 0.05) than those with ectopic thyroid glands. Symptoms and signs of congenital hypothyroidism, although subtle, were significantly more common (P less than 0.05 for symptoms and P less than 0.001 for signs) in athyrotic children compared with those with ectopic glands. No physical or developmental abnormality related to congenital hypothyroidism has been demonstrated on follow-up; mean height and weight percentiles approximate the 50th percentile at ages one to six years and mean developmental scores +/- SD at about two years of age by the Griffiths Mental Development Scale and at 4.5-6.5 years by the Wechsler Preschool and Primary Scale are 102.4 +/- 10.4 and 111.2 +/- 12.2, respectively. Long-term follow-up studies are necessary to exclude more subtle developmental and neurological abnormalities.

Age Determination by Skeleton↗

Post-traumatic psychoneurosis: evaluation of drug therapy.

This study evaluates the results of drug therapy and psychotherapy in post-traumatic psychoneurosis. The study was undertaken because of the frequent need to estimate the costs of treatment since the illness may at times be the result of a compensable injury. Patients with this illness are frequently parties in litigation. Over the past twelve years, fifty patients that had been diagnosed as having Post-Traumatic Psychoneurosis were treated. In order to attempt to evaluate the effects of treatment the patients were selected alternately for therapy with psychotherapy or with drug therapy. The results of therapies are compared and evaluated.

Amitriptyline↗