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Biomedical subjects

V Wynn

Publications and source records attributed to V Wynn.

At least 91 records · Page 5Linked to original sources

A double blind placebo controlled trial of mixed gangliosides in diabetic peripheral and autonomic neuropathy.

Twenty-six patients with signs or symptoms of diabetic neuropathy who also had motor or sensory neurophysiological abnormalities, were intensively studied in the first double-blind, placebo controlled trial of a ganglioside mixture in the U.K. (Cronassial, Fidia Farmaceutici, Abano Terme, Italy; 6 weeks of 20 mg daily intramuscularly). Diabetes control was good in both groups and there was no deterioration in either group during the course of the trial. Of the five neurophysiological parameters measured - the motor nerve compound action potential, motor nerve conduction velocity and minimum f wave latency of the common peroneal nerve and the sensory action potential and conduction velocity of the sural nerve - only the mean motor nerve action potential and conduction velocity increased though the changes were not significant. Four patients showed improvements of greater than 1.0 mV after treatment with Cronassial while none of the placebo group did so (p less than 0.05). Of the four patients who showed dramatic improvements in motor nerve action potentials, three also showed improvements in motor nerve conduction velocity. There were no significant changes in three tests of autonomic function after Cronassial therapy (orthostatic tilt reactions, single deep breath and Valsalva maneuver). Four patients in the Cronassial group (not those showing neurophysiological improvement) but only one in the placebo group reported marked improvements in their symptomatic complaints after treatment. We conclude that Cronassial is a promising new drug for the treatment of diabetic peripheral neuropathy with clear benefits for some patients.

Action Potentials↗

The effects of cyproterone acetate and ethinyl oestradiol on carbohydrate metabolism.

Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as anti-androgen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and women were studied in two groups: the first when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13 to 22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to intravenous tolbutamide was increased by 50% but there was no accompanying change in the glucose nadir as compared with controls. These results show that the combination of CA and EO causes insulin resistance. Plasma C-peptide concentrations following oral glucose were unchanged compared with controls. This shows that the observed hyperinsulinaemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. We propose that these effects are due to a CA-induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C-peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide but this was not significant. We conclude that these results are explained by a reduced but persisting effect of CA.

Acne Vulgaris↗

Low-density lipoprotein metabolism by cultured human fibroblasts: relationship with aging and atherosclerosis.

22 male subjects aged 21-55 years with normal plasma lipid concentrations were divided into two groups on the basis of the presence or absence of proven coronary artery disease and/or peripheral vascular disease. The rates of uptake and degradation of low-density lipoprotein (LDL) by fibroblast cultures obtained from each subject were assessed using 125I-labelled LDL, and an attempt was made to relate them to the presence or absence of atherosclerosis and to the age of the subject. Atherosclerosis was found to be significantly correlated with elevated rates of LDL uptake and degradation. On the other hand, aging was shown to be associated with a significant reduction in cellular LDL metabolism.

Adult↗

Comparison of haematological indices between women of four ethnic groups and the effect of oral contraceptives.

Six-hundred-and-eighty-two women volunteers from four ethnic groups--Black, Indian, Oriental and White took part in a study to assess differences in haematological indices between the groups. This study was part of a broad investigation into the metabolic effects of oral contraceptives. The effect of the oral contraceptive (OC) on haematological indices was analysed but not found to be significant. The haemoglobin concentrations were lower than normal laboratory reference values for White subjects in 12.5% of Indian, 16.5% of Black and 4.3% of Oriental control groups respectively. All the White control group were within the normal range. These findings were considered in relation to age, weight, pregnancies, smoking, alcohol consumption, nutritional status, and disorders of haemoglobin synthesis. A deficient iron intake accounted for the high incidence of low haemoglobin in the Indian group in whom low transferrin saturation and serum ferritin were observed. With the possible exception of inherited disorders of haemoglobin synthesis, none of the factors we considered could account for the low haemoglobins found in the Black group. Separate reference values for haematological indices in different ethnic populations are considered.

Adolescent↗

The evaluation of sodium valproate in the treatment of Nelson's syndrome.

It has previously been reported that sodium valproate (Epilim) lowers plasma ACTH levels in Nelson's syndrome. This report describes further experience with its use. Ten patients with Nelson's syndrome were treated with sodium valproate (600-1200 mg/day) for 5-32 weeks. Plasma ACTH was measured by cytochemical methods and RIA. Initial treatment for 5-12 weeks significantly (P less than 0.005) lowered plasma ACTH from a pretreatment mean of 2460 +/- 1870 ng/liter to 480 +/- 330 ng/liter, and the ACTH circadian rhythm was restored in two patients. On discontinuing treatment, plasma ACTH levels remained suppressed for 3 weeks and rose to pretreatment values in 5-12 weeks. Two patients' plasma ACTH levels failed to show a second response to treatment, while a third patient had a favorable second response to treatment over 32 weeks. In six patients, skin pigmentation lightened with treatment, and in one patient, a reduction in size of a pituitary microadenoma, demonstrated radiographically, occurred with treatment. gamma-Aminobutyric acid and sodium valproate were shown to be ineffective in inhibiting ACTH secretion from cultured pituitary tumor cells from a patient with Nelson's syndrome. The results show that sodium valproate is effective in some cases of Nelson's syndrome. We suggest that it reduces the hypersecretion of ACTH by enhancing gamma-aminobutyric acid function in the hypothalamus, thereby inhibiting the release of corticotropin-releasing factor.

Adrenocorticotropic Hormone↗

Effect of duration of low-dose oral contraceptive administration on carbohydrate metabolism.

Two hundred and ten healthy young women volunteered to take a combined oral contraceptive (OC) and to have glucose tolerance in insulin secretion measured in a projected 3-year study with roughly annual investigations. Although the dropout rate was high, glucose tolerance was noted to deteriorate progressively and insulin secretion to rise initially, but thereafter they remained constant. Eventually, insulin levels were lower than would have been expected from the prevailing glucose values. This combination of steroids produced marked insulin resistance to which the pancreas could respond by further insulin secretion. It is suggested that levonorgestrel is too strong a progestin for routine use in the combined OC, and it is recommended that its dose be reduced further or that weaker progestins such as norethindrone be used.

Adult↗

The effect of progestins in combined oral contraceptives on serum lipids with special reference to high-density lipoproteins.

Fasting serum lipids were measured in a group of 293 women desirous of using oral contraceptives (OCs) and 536 women who had been taking five varieties of OCS for many months before being tested. Parameters studied were serum cholesterol, triglyceride, high-density lipoprotein (HDL), the two main subfractions of HDL, namely, HDL2 and HDL3, and the ratio of HDL2 cholesterol to low-density lipoprotein (LDL) cholesterol. Studies of these five groups of women enabled us to compare the effect of varying amounts of levonorgestrel with norethindrone and to study the effects of estrogen combined with these progestins. The levonorgestrel-containing pills and the progestin-only OC significantly depressed HDL2 cholesterol levels and the ratio of HDL2 to LDL cholesterol.

Adult↗

Low density lipoprotein metabolism by cultured skin fibroblasts from atherosclerotic patients.

The aim of this study was to determine whether an abnormality in low density lipoprotein (LDL) metabolism could be demonstrated in fibroblasts cultured from normolipidaemic subjects with atherosclerosis. Seventeen male subjects aged 30-55 years with normal plasma lipid concentrations were divided into 2 groups on the basis of the presence or absence of proven coronary artery and/or peripheral vascular disease. LDL metabolism was assessed in cultured fibroblasts obtained from each of these subjects. After 6 h incubation with 125I-labelled LDL, it was found that binding, uptake and degradation of the lipoprotein were all significantly higher in cells from the atherosclerotic group of subjects than the controls. Variations in cellular LDL metabolism were also correlated with 4 risk factors for cardiovascular disease. Plasma LDL concentration in the atherosclerotic subjects was found to be inversely related to LDL binding and degradation. Subject age was inversely related to LDL degradation in both groups of subjects. No association was demonstrated in either group of subjects between LDL metabolism and glucose intolerance, or between LDL metabolism and cigarette smoking. It is concluded from these results that cellular LDL binding may constitute a factor in determining the rate of atheroma formation, which is independent of other cardiovascular risk factors.

Adult↗

Effect of treatment with sodium valproate and diazepam on plasma corticotropin in Nelson's syndrome.

Six patients with Nelson's syndrome were given sodium valproate with or without diazepam for 3 or 5 weeks. Initial high plasma adrenocorticotropic hormone (ACTH) concentrations were greatly reduced by treatment and returned to high levels when treatment was stopped. Diazepam did not add significantly to the effects of sodium valproate alone. Three patients reported a decrease in the severity and frequency of headaches while on sodium valproate. In five patients abnormal skin pigmentation was reduced. Sodium valproate is a gamma-aminobutyric acid (GABA) transaminase inhibitor and it is suggested that the drug raises GABA levels in the hypothalamus and that this is responsible for the reduction in ACTH secretion. The data are consistent with the hypothesis that Nelson's syndrome is a neuroendocrine disease caused by a deficiency in the hypothalamic GABA-ergic system.

Adrenocorticotropic Hormone↗