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Biomedical subjects

R Wootton

Publications and source records attributed to R Wootton.

At least 163 records · Page 9Linked to original sources
PubMed1982

Long-term treatment of osteoporosis with 24,25 dihydroxycholecalciferol.

Five patients with involutional osteoporosis were treated with 24,25 dihydroxycholecalciferol (24,25-(OH)2D3) for 6 months, in doses sufficient to double plasma levels at that time. Dietary calcium absorption transiently improved by nearly 2 mmol Ca per day at 2 weeks, but this effect was lost by 6 months. The calcium and phosphate balances followed the trends in calcium absorption. Only twenty-five dihydroxyvitamin D levels changed little. Histomorphometric and kinetic indices of new bone formation and bone blood flow remained stable but there was an increase in urine hydroxyproline at 6 months, which was of borderline statistical significance. Treatment at this dosage of 24,25(OH)2D3, which increased plasma levels within the physiological range, conferred no measurable long-term benefit on our patients. Larger doses, or combination therapy, may warrant further clinical evaluation in osteoporosis.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Skeletal blood flow in Paget's disease of bone.

Using a modified plasma clearance technique, with 18F as a tracer, it is possible to measure blood flow to bone in man. In the normal adult skeleton, blood flow amounts to about 300 ml/min. In untreated Paget's disease of bone there is a striking increase, which is proportional to the biochemical severity of the disease : total blood flow to the skeleton is approximately doubled at an alkaline phosphatase of 50 KAu/dl (i.e. about four times the normal upper limit). Treatment with calcitonin brings a rapid return to normal, possibly before there is a detectable biochemical response. This may explain the rapid pain relief often reported on starting treatment with calcitonin.

Adult↗
PubMed1981

Total body-glucose turnover in normal and intra-uterine growth-retarded neonatal piglets.

1. Because studies of the metabolic problems of the human intra-uterine growth-retarded neonate are limited by ethical considerations we have used the intra-uterine growth-retarded piglet as an animal model. Total body-glucose kinetics were measured in 16 intra-uterine growth-retarded and 11 normal piglets from the same litters with [3H]glucose as a tracer. 2. The intra-uterine growth-retarded animals had marginally smaller brains than their normal littermates, but substantially smaller livers. Liver weight was reduced in proportion to body weight. 3. Total body-glucose turnover rate was significantly lower (P less than 0.001) in the intra-uterine growth-retarded animals in comparison with their normal littermates, but was appropriate for their smaller body and liver weights. Brain weight was only slightly reduced in the intra-uterine growth-retarded group so that glucose turnover adjusted to a common brain weight was significantly lower (P less than 0.001) in these animals. 4. Total body-glucose pool size was lower in the intra-uterine growth-retarded animals (P less than 0.01), but was appropriate for their body and liver weights. It was significantly reduced in relation to brain weight (P less than 0.001). 5. Resting plasma glucose concentration was lower in the intra-uterine growth-retarded animals (P less than 0.001). There was no relationship between concentration and turnover in either group. 6. It is suggested that the observed differences in total body-glucose turnover may be associated with profound differences in cerebral metabolism in the intra-uterine growth-retarded animals.

Animals↗
PubMed1981

Steady state glucose kinetics and their relation to plasma glucose concentration in the premature and full term neonatal piglet.

Steady state glucose kinetics were measured in 19 premature and 16 full-term piglets. Bodyweight, plasma glucose concentration, total body glucose turnover rate, and glucose pool size were not significantly different between the two groups. This suggests that the premature piglet is capable of maintaining glucose homeostasis during the first 24 h of life. Although there appeared to be a correlation between glucose turnover and plasma glucose concentration, analysis of covariance showed that it was spurious, suggesting that glucose utilization proceeds independently of the glucose concentration in plasma. Glucose turnover rate in the premature piglet is closely comparable with that reported in the premature human infant. These findings encourage the use of the neonatal piglet as an animal model for the study of the problems of the neonatal human.

Analysis of Variance↗
PubMed1980

Biological variation in free serum hydroxyproline concentration.

Improvements in the accuracy of single estimations of biochemical constituents such as the serum free hydroxyproline (FSHP) concentration can only result from control of biological variation as well as analytical variation. In this context two experiments were carried out to determine whether a significant diurnal rhythm in FSHP concentration exists in man, and whether a worthwhile reduction in intra-individual variance can be achieved by eliminating dietary sources of hydroxyproline. A significant (p < 0.001) diurnal variation in FSHP concentration was detected in a group of normal subjects, with a range of about 20% of the mean. In a second group of eight normal subjects, there was a substantial reduction in the within-subject variation after the start of dietary control. For the most precise determination of FSHP concentration therefore, dietary hydroxyproline sources must be controlled, preferably eliminated, and blood should be sampled at a standardised time of day.

Adult↗
PubMed1980

The reproducibility of double-isotope deconvolution measurements of intestinal calcium absorption.

1. Radiocalcium absorption was measured in duplicate in 10 subjects by the double-isotope method, with calcium as the oral carrier (2.5 mmol). Analysis of variance gave 95% confidence limits for a single measurement of fractional absorption and maximum absorption rate in a given individual of +/- 16.5% of administered dose and +/- 18.2% of dose/h respectively. 2. The size of these within individual variations suggests that alterations in the rate of calcium absorption may contribute to the week-to-week stabilization of some other controlled variable, such as plasma concentration of calcium. 3. In six of the subjects, calcium absorption was also measured with calcium loads at concentrations of 0.5, 5.0 and 20 mmol. Significant falls in fractional absorption, maximum absorption rate and mean transfer rate occurred as the load increased, together with a rise in mean transit time. Although between-individual differences at a given load were considerable, given a single-test result with a known carrier load, it is possible to predict quite accurately the results which would be obtained if a different carrier load were to be given.

Analysis of Variance↗
PubMed1980

Deficit of trabecular and cortical bone in elderly women with fracture of the femoral neck.

1. The mean attenuation coefficients of trabecular and cortical bone in the radius were measured in 32 female patients with fractured proximal femur, and in 28 age-matched female controls, with a special-purpose computed tomography-scanner. 2. The largest difference between the two groups was in the mean attenuation coefficients for trabecular bone in the distal radius. The mean value for fracture patients (0.53 cm-1) was significantly lower (P < 0.02) than the mean value for the controls (0.62 cm-1). These results are consistent with the view that a loss of trabecular bone predisposes to fractures of the proximal femur.

Aged↗
PubMed1980

Total body glucose metabolism in the conscious, unrestrained piglet and its relation to body- and organ weight.

1. Neonatal hypoglycaemia is a relatively common clinical problem in children but ethical constraints limit the investigations that may be made in the newborn. 2. As a preliminary step to assess the suitability of the piglet as a model for glucose metabolism in man, whole-body glucose turnover and glucose pool size were measured using [2-3H]glucose in forty piglets from ten litters. 3. Glucose pool size was linearly related to brain weight. However, multiple regression showed that the most useful predictors of pool size were body-weight and resting plasma glucose concentaration. 4. Glucose turnover was related to both brain weight and body-weight alone, but multiple regression showed that better predictors of turnover were liver weight, spleen weight and pancreas weight. 5. Similarities between our own results in piglets and those obtained in human neonates by Bier et al. (1977) extend not only to glucose turnover, but also to its relationship with body- and brain weight. These findings suggest that the piglet may be a useful model for the study of glucose metabolism in babies.

Animals↗
PubMed1980

Quantitative studies of very low density lipoprotein: conversion to low density lipoprotein in normal controls and primary hyperlipidaemic states and the role of direct secretion of low density lipoprotein in heterozygous familial hypercholesterolaemia.

Autologous 131I-labelled very low density lipoprotein (VLDL) and 125I-labelled low density lipoprotein (LDL) were injected into seven normal subjects and twenty-eight genetically classified hyperlipidaemic patients to quantitate lipoprotein interconversion. The apoprotein B specific activity--time curves for VLDl and intermediate density lipoprotein (IDL, density = 1 . 006--1 . 019 g/ml) intersected at or before the IDL-B maximum in thirty-one studies (five normal controls and twenty-six hyperlipidaemic subjects) implying that all IDL-B may be derived from VLDL-B. The fractional conversion of VLDL-B to LDL-B (density 1 . 019--1 . 063 g/ml) following a simultaneous spike injection of 131I-VLDL and 125-LDL was obtained by deconvolution of the 125I and 131I-LDL-B activity curves. 21--65% (mean = 44%) of VLDL-B was converted to LDL-B in twenty-three subjects studied. The mean conversion time ranged from 10 to 24 h in ten normotriglyceridaemic subjects and from 19 to 42 h (mean = 33 h) in twelve hypertriglyceridaemic subjects. In one patient with broad-beta disease the mean conversion time was 55 h. LDL-B production from VLDL-B and total LDL-B synthetic rate were essentially equal in normal controls and normocholesterolaemic subjects and in the patient with broad-beta disease. But in all six patients with familial hypercholesterolaemia LDL-B synthetic rate significantly exceeded LDL-B production from VLDL-B, indicating direct secretion of 20--72% of LDL-B at a rate which correlates positively with plasma LDL concentration. Three of five patients with familial combined hyperlipidaemia showed a lesser but nevertheless significant direct secretion of LDL-B.

Humans↗
PubMed1980

The interaction of human haemoglobin with allosteric effectors as a model for drug-receptor interactions.

1 The release of bound oxygen from oxyhaemoglobin by allosteric effectors is considered as a model for those drug-receptor interactions where the primary response to agonist binding is the release of a second messenger species. 2 A theory of haemoglobin oxygenation, based on the two-state model of Monod, Wyman & Changeux (1965) is used to predict the relationship between 'pharmacological' response and dose of agonist. This relationship is the same as that derived from classical pharmacological occupancy theory. 3 The potency of an agonist is a weighted average of its affinities for the two conformational states of the receptor. 4 The efficacy of an agonist depends not only upon its binding to one of the two conformational states, but also on its ability to alter the functional properties of that state by lowering the affinity of the state for the second messenger. 5 2,3-Diphosphoglycerate and adenosine triphosphate are approximately equipotent and of similar efficacy, but inositol hexaphosphate is about 500 times more potent and has a higher efficacy.

Adenosine Triphosphate↗
PubMed1980

Fetal development in relation to gestational age in the piglet.

Body and organ weights were measured in piglets from 44 litters which had been delivered by caesarean section at various times during the last 20 days of gestation. An attempt has been made to assess the usefulness of these measurements as predictors of gestational age. In this series of animals there was a highly significant correlation between mean litter weight and age. However, a considerable degree of uncertainty about the true gestational age must be accepted if mean litter weight is to be used as the sole predictor: at a mean litter weight of 1 kg, the 95% confidence limits were found to be +/- 10.2 days. No extra information was afforded by the inclusion of the organ weight data one the mean litter weight was known.

Animals↗
PubMed1979

The clinical measurement of urinary total hydroxyproline excretion.

The effect of dietary control on the day-to-day variation in total hydroxyproline excretion has been examined in two studies. In the first, a normal volunteer ate a controlled diet containing varying gelatin supplements for several weeks. In the second, the effect of removing hydroxyproline-containing foods from the diets of 8 volunteers was examined. Both studies confirm that the day-to-day variation in total hydroxyproline excretion falls when the gelatin content of the diet is decreased, whether the results are expressed as total hydroxyproline excretion rate or as the total hydroxyproline: creatinine ratio. This fall in variation takes place within 24 h of dietary control beginning and therefore longer periods of dietary restrictions to achieve optimum precision in the measurement of total hydroxyproline are unnecessary. For some analytical methods, results are better expressed as the ratio total hydroxyproline:creatinine than as the total hydroxyproline excretion rate.

Adult↗