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Biomedical subjects

V Wynn

Publications and source records attributed to V Wynn.

At least 73 records · Page 4Linked to original sources

Autonomic and electrophysiological studies in patients with signs or symptoms of diabetic neuropathy.

Thirty-five patients with symptoms or signs of diabetic neuropathy were tested for autonomic neuropathy by measuring heart rate and blood pressure changes during an orthostatic tilt test, a single deep breath and the Valsalva manoeuvre and these results were related to electrophysiological measurements made on the common peroneal and sural nerves. The sural sensory action potential (SAP) was more strongly correlated with these tests of autonomic function (particularly with the brake index of the orthostatic tilt test (P less than 0.001) and the fall in systolic blood pressure 1 min after tilt (P less than 0.001], than the common peroneal nerve compound motor action potential, its minimum F wave latency or nerve conduction velocities. Patients with a detectable sural SAP had significantly higher brake indices than those with absent sural SAPs. Significant correlations were also obtained with the common peroneal motor nerve conduction velocity (MNCV) and autonomic tests and patients with MNCV less than and greater than 38 m/sec showed significant differences in many autonomic tests. The sural SAP amplitude, being less susceptible to factors that influence nerve conduction velocity, may be useful in identifying patients with an autonomic neuropathy.

Action Potentials↗

Changes in bone and muscle constituents during dieting for obesity.

The effects of dietary carbohydrate (CHO) content and of tri-iodothyronine (T3) administration on calcium, zinc and phosphate balances and on urinary hydroxyproline output were examined in eight obese subjects undergoing therapy with low energy (2741-3301 kJ/day), high calcium (28.9-35.1 mmol/day) diets. Calcium balances were generally positive at the high levels of intake used, but significantly more calcium was retained when dietary CHO intake (as proportion of total energy intake) was increased. Zinc balances were more positive when the proportion of dietary CHO was high and correlated both with nitrogen balance and with daytime insulin concentration. Urinary hydroxyproline output generally increased with dieting irrespective of dietary CHO content. Administration of T3 (30-80 micrograms/day) markedly increased zinc loss without affecting calcium balance.

Adolescent↗

Insulin action and dynamics modelled in patients taking the anabolic steroid methandienone (Dianabol).

Plasma glucose and insulin concentrations were measured during oral (OGTT) and intravenous (IVGTT) glucose tolerance tests in nine patients off- and on-treatment with the anabolic steroid, methandienone (Dianabol). On-treatment, the tolerance tests showed a markedly increased insulin response accompanied by impairment of glucose tolerance, characteristics normally attributed to insulin resistance. However, fasting plasma glucose (FPG) and insulin (FPI) concentrations were significantly reduced, whereas the pattern normally associated with insulin resistance is for both to be raised. IVGTT glucose and insulin profiles were analysed using an algorithm derived from the minimal models of glucose and insulin dynamics originally proposed by R. Bergman and co-workers. Measures for the following parameters were thus obtained: Si, the sensitivity of glucose disposal to insulin; Sg, net insulin independent glucose disposal; phi 1, the integral concentration of insulin delivered during the first phase of insulin secretion relative to the initial increase in glucose concentration above a model-derived threshold; phi 2, the sensitivity of the rate of rise of insulin concentration in the second phase of insulin secretion to the concentration of glucose above a model-derived threshold; kappa, the fractional clearance rate of insulin; and tau 1/2, the insulin half-life. S1 was significantly reduced on treatment by a factor of 4. Sg, phi 1, phi 2 and tau 1/2 were all significantly increased, and kappa was significantly reduced. The increases in Sg and phi 1 both showed significant correlations with the increase in weight on-treatment. The reduction in FPG and FPI can be explained by the combined effects of the increase in Sg and Dianabol-induced resistance to glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Paradoxical effects of the anti-androgen cyproterone acetate on lipid and lipoprotein metabolism.

The effects on fasting serum lipids of the potent anti-androgen, cyproterone acetate (CA) and the oestrogen, ethinyl oestradiol (EO) given both alone and in combination were examined in women acting as their own controls. Cyproterone acetate alone caused significant reductions in total cholesterol, high density lipoprotein subfraction 2 cholesterol (HDL2) and low density lipoprotein cholesterol (LDL). Ethinyl oestradiol alone significantly increased triglycerides, HDL and HDL2 and reduced LDL, and there was also a significant increase in the HDL/LDL and HDL2/LDL ratios. The two steroids were administered in combination according to a reverse sequential regime. The 28-day treatment cycle thus included Phase A during which both drugs were given followed by Phase B when EO alone was given. Triglycerides rose significantly in Phases A and B to the same extent as for the group taking EO alone. High density lipoprotein cholesterol was unchanged but HDL2 was reduced in both phases and this effect could not be overcome by increasing the dose of oestrogen. Low density lipoprotein cholesterol fell and the HDL/LDL ratio rose during the two Phases and these changes were significant during Phase A. The effects of EO demonstrated in this study are consistent with previous reports. Cyproterone acetate, however, has properties conventionally ascribed to both synthetic androgens (e.g. lowering of HDL2) and oestrogens (e.g. lowering of LDL). The limitations of the terms androgenic and oestrogenic activity in relation to their conventional associations with changes in lipid and lipoprotein levels are discussed.

Acne Vulgaris↗

The effect of ovine corticotrophin releasing factor (oCRF), bromocriptine and TRH on the secretion of ACTH and alpha-MSH in Nelson's syndrome and Cushing's disease.

The circulating levels of ACTH and alpha-melanocyte stimulating hormone (alpha-MSH) were measured in 9 patients with Nelson's syndrome after the administration of saline, ovine corticotrophin releasing factor (oCRF), bromocriptine or TRH. The concentrations of ACTH were grossly elevated and alpha-MSH levels ranged from undetectable to higher than the normal range. In seven of eight subjects there was a rapid corticotrophic response, but no change in the alpha-MSH level, following oCRF. This response was delayed in one subject. Following oCRF injection, the plasma oCRF profile was variable but circulating oCRF was detectable even at the end of the experiment in all cases. There was no significant change in circulating ACTH or alpha-MSH following either bromocriptine or TRH. Cultured tumour cells from one case of Cushing's disease showed a corticotrophic response but no change in alpha-MSH to oCRF and the response was enhanced by vasopressin. Bromocriptine added to the same tumour depressed ACTH secretion without affecting the output of alpha-MSH. The present data suggest that the tumours in these subjects are responsive to oCRF and arise from corticotrophs rather than melanotrophs.

Adrenocorticotropic Hormone↗

Effects of oral contraceptives on carbohydrate metabolism.

Both estrogens and progestogens modify carbohydrate metabolism, and their ultimate effect depends upon the ratio of one to the other. The effect of progestogens themselves, which are responsible for increased insulin secretion and for insulin resistance, varies according to their androgenicity but increases according to the series pregnane, estrane and gonane. In contrast, estrogens impair the initial secretion of insulin by the pancreas. The prolonged use of combined oral contraceptives containing the powerful progestogen levonorgestrel is associated with mild but continuing glucose intolerance and with marked insulin resistance.

Blood Glucose↗

A common DNA polymorphism of the low-density lipoprotein (LDL) receptor gene and its use in diagnosis.

A cloned gene probe coding for the low-density lipoprotein (LDL) receptor was used to detect a restriction fragment length polymorphism with the enzyme Pvu II. The frequency of the rare allele is approximately 0.2 both in normal controls and individuals with familial hypercholesterolaemia (FH). About 30% of individuals are heterozygous for the polymorphism, and are potentially informative for family studies and for early diagnosis of FH. This polymorphism was used to follow the inheritance of the LDL receptor gene in two families with FH. In these families, the polymorphism co-segregates with the disease unambiguously, and therefore can be used for early diagnosis.

Alleles↗

Method for estimating rate of fat loss during treatment of obesity by calorie restriction.

Rates of weight and fat loss in sixteen female and nine male obese patients during calorie restriction (655-789 kcal/day) for up to 120 days were studied by a method for estimating daily changes in body composition. Fat mass is calculated by subtracting daily fluid (calculated from sodium and potassium balances) and protein mass changes from daily weight changes. After the natriuresis of the first 4 days, there was a slower rate of weight loss between days 5 and 28 due largely to a decreasing contribution from fluid and protein losses. No significant change in the rate of weight loss could be shown after the first 28 days. The rate of fat loss did not change significantly from day 5 onwards suggesting no significant change in total energy expenditure during the study period. After 68 days, 93.4% of the weight loss was fat.

Adipose Tissue↗

Identification of a deletion in the low density lipoprotein (LDL) receptor gene in a patient with familial hypercholesterolaemia.

DNA samples from 60 unrelated UK patients with familial hypercholesterolaemia (FH) were screened by Southern blot hybridisation to detect gross alterations in the low density lipoprotein (LDL) receptor gene. One patient was found to have a 2kb deletion in the 3' part of the gene. The deletion cosegregates with the FH phenotype in his family. This finding is compatible with the deletion being the cause of FH in this case and makes a presymptomatic test based on DNA analysis available for this family. The defects in most of the other patients are likely to be due to point mutations.

Chromosome Deletion↗

Variation in serum lipid and lipoprotein levels associated with changes in smoking behaviour in non-obese Caucasian males.

A population of healthy male caucasians was analysed with respect to lipid and lipoprotein parameters, according to differences in current and previous smoking patterns. High density lipoprotein (HDL) cholesterol, and the HDL2 subfraction were significantly higher in non-smokers compared to current smokers. In ex-smokers, the levels of these 2 parameters increased with the length of time since giving up the habit, until levels were no longer distinguishable from non-smokers. A similar increase was observed for weight, although both triglyceride and very low density lipoprotein (VLDL) levels decreased. Low density lipoprotein (LDL) levels showed no significant variation in any of the comparisons. Lower alcohol consumption in both the ex-smokers, and in the non-smokers may account partially for the changes in triglyceride and VLDL, although the same observation is contrary to the effects observed in both HDL and HDL2.

Alcohol Drinking↗

Corticotrophin, cortisol, prolactin and growth hormone responses to insulin-induced hypoglycaemia in normal subjects given sodium valproate.

Plasma corticotrophin (ACTH), cortisol, prolactin and growth hormone (GH) responses to insulin-induced hypoglycaemia were measured in normal healthy subjects of both sexes before and after three weeks' treatment with sodium valproate (Epilim, 200 mg three times a day). The drug had no effect on fasting plasma glucose levels, or the extent of hypoglycaemia induced by insulin (0.15 U/kg). There was no significant difference between pre- and post-treatment values for basal or stress-induced concentrations of ACTH and cortisol (n = 12), prolactin (n = 7) or GH (n = 9). The results suggest that treatment of normal subjects with sodium valproate has no effect on the response of the hypothalamo-pituitary-adrenocortical axis to hypoglycaemia, which is in contrast to its inhibitory effects on ACTH secretion in patients suffering from Nelson's syndrome. This implies that in the disease state, there may be a unique sensitivity to GABA-ergic manipulation.

Adrenocorticotropic Hormone↗

The effects of triiodothyronine on energy expenditure, nitrogen balance and rates of weight and fat loss in obese patients during prolonged caloric restriction.

We studied ten obese patients on prolonged caloric restriction by metabolic balance techniques two weeks before and two weeks after the start of treatment with triiodothyronine (T3) (0.36-1.01 micrograms/kg/d). The rate of weight, nitrogen and fat loss calculated from metabolic balance increased during T3 therapy and these effects were maximal in the second week of treatment. In seven patients studied continuously for four weeks on T3 therapy, the rates of weight and fat loss during the fourth week of treatment were not significantly different from pretreatment values while nitrogen loss was still significantly greater. The increase in nitrogen loss, studied after the period of adaptation to caloric restriction, implies that prolonged treatment with T3 can result in significant losses of lean tissue in addition to that resulting from caloric restriction alone. Mean weight loss increased by 92 g/d during T3 therapy. T3 significantly increased the metabolic rate as measured by two other independent measures: the resting energy expenditure (REE), measured by indirect calorimetry (fourteen patients), and the sleeping heart rate (six patients).

Adolescent↗