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Biomedical subjects

M Seed

Publications and source records attributed to M Seed.

At least 73 records · Page 4Linked to original sources

Platelet count and platelet size in healthy Africans and West Indians.

Healthy subjects of African origin were found to have lower platelet counts than simultaneously studied healthy Caucasians. A similar reduction was found in a large group of West Indian females, though not in a small group of West Indian males. It is suggested that the lower platelet counts observed in Africans and West Indians may be partly environmental and partly genetic in origin. The mean platelet volume and platelet distribution width in the Africans and West Indians showed the same relationship with the platelet count as was found in Caucasians, so that the same nomograms can be used in all ethnic groups to assess whether there is deviation from normality.

Africa↗

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↗

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↗

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↗

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↗

Normal values for peripheral blood white cell counts in women of four different ethnic origins.

Total and differential white cell counts were studied in 399 women living in the same community in Britain but drawn from four different ethnic groups. The groups were white (northern European), Indian, black (African and West Indian), and Oriental. The total white cell count and absolute neutrophil count were significantly lower in the black group than in each of the other groups. The absolute monocyte count was higher in whites than in each of the other groups. Contrary to earlier reports, the absolute eosinophil count in blacks was no higher than in whites, suggesting that the high eosinophil counts previously found had an environmental rather than a genetic cause. The eosinophil count of Indians was only marginally higher than that of whites and the difference was not significant, again suggesting that high eosinophil counts previously reported had an environmental cause. No ethnic variation was found in the absolute lymphocyte count. The lower white cell count and neutrophil count found in blacks is of considerable practical importance, and blacks should not be assessed in relation to reference ranges derived for whites. Nevertheless, the eosinophil count in healthy blacks is no higher than that of whites and counts above reference ranges for whites should be considered clinically important. The differences between white cell counts of Indians and Orientals and those of whites are minor and for practical purposes they can be assessed in relation to reference ranges derived for whites.

Adolescent↗

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↗

A DNA polymorphism adjacent to the human apolipoprotein CII gene.

We have used a cDNA clone for human apolipoprotein CII (apo CII) to detect a common DNA polymorphism with the enzyme TaqI. This polymorphism is probably caused by a single base change approximately 2000 base-pairs from the 3' end of the structural gene. In the normal population (n = 90) the frequency of the less common allele is approximately 0.44. No significant differences were observed in the allele frequency in individuals with type IIa, IIb, III, IV and V lipoprotein patterns. There does not seem to be any population association between the TaqI polymorphism and factors that predispose an individual to hyperlipidaemia.

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↗

Comparison of effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism.

Oral glucose-tolerance tests were performed and fasting serum cholesterol and triglyceride levels measured in 1628 Caucasian women taking combined oestrogen/progestagen oral contraceptives (o.c.) and 577 women not taking O.C. The former were divided into six groups according to the composition of the O.C Glucose tolerance deteriorated in all O.C. groups containing oestrane progestagens (nortestosterone-derived) or the gonane, norgestrel, but was unaltered by O.C. containing a pregnane progestagen (derived from progesterone). The greatest deterioration was with O.C. containing 75 microgram or more oestrogen, and this was associated with impairment of the early insulin response to glucose. In O.C. containing a pregnane progestagen insulin secretion was unaffected. In the remaining O.C. groups insulin secretion was increased; this was most pronounced with the O.C. containing a gonane progestagen. Serum-cholesterol was elevated only with O.C. containing 75 microgram or more oestrogen and an oestrane progestagen and tended to be lower in O.C. containing a gonane progestagen. O.C.-induced hypertriglyceridaemia was oestrogen-dose-related, and this effect was potentiated by the pregnane progestagen. The gonane progestagen antagonised oestrogen-induced hypertriglyceridaemia.

Adult↗

Influence of oral contraceptives, pyridoxine (vitamin B6), and tryptophan on carbohydrate metabolism.

Carbohydrate metabolism and vitamin-B6 status were assessed before and after pyridoxine administration in 46 women taking combined oestrogen-progestagen oral contraceptives (O.C.). 18 women had evidence of tissue depletion of vitamin B6, although all the women had abnormal tryptophan metabolism, including increased urinary xanthurenic acid (X.A.) excretion. In the women with vitamin B6 deficiency, administration of this vitamin caused elevation of fasting blood-pyruvate levels, and reduction in plasma glucose, insulin, and blood-pyruvate responses after an oral glucose load. These changes in carbohydrate metabolism were not found in the 28 non-vitamin-B6-deficient women. These results indicate that carbohydrate intolerance in women on O.C. is unlikely to be mediated by the formation of a complex of X.A. with insulin, as has formerly been proposed. Since the synthesis of the tryptophan metabolite quinolinic acid, an inhibitor of the heptaic enzyme phosphoenolpyruvate carboxykinase, may be enhanced by the administration of pyridoxine, it is suggested that this metabolite might be the important factor in the improvement of glucose tolerance in the vitamin-B6-deficient women. This conclusion is supported by the improvement in glucose tolerance observed in 6 women on O.C. and in 4 patients with glucocorticoid excess who were not vitamin-B6 deficient, when they were given tryptophan to augment the synthesis of quinolinic acid.

Adult↗