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Biomedical subjects

D M Hart

Publications and source records attributed to D M Hart.

At least 55 records · Page 3Linked to original sources

Effects of long-term Org OD 14 administration on blood coagulation in climacteric women.

98 post-menopausal women were randomly allocated to either Org OD 14 [(7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one] 2.5 mg/day or placebo. Treatment was continued for up to 6 yr. Any thromboembolic episode that occurred was recorded. Prothrombin time (PT), partial thromboplastin time (PTT), factor VII level and factor X level were measured prior to treatment and at yearly intervals. Antithrombin III level was measured in the last two yr of the study. There was one cerebrovascular accident after 3 months of placebo therapy but no other thromboembolic episodes. No significant difference was found between the effects of Org OD 14 and placebo with regard to any clotting factors at any time interval, although factor VII and factor X levels were consistently lower in the OD 14 group than in the placebo group. Antithrombin III levels measured after 5 and 6 yr were significantly higher (P less than 0.01) in the OD 14 group, suggesting a reduced risk of thrombosis in the treatment group.

Blood Coagulation↗

Lipoprotein and apoprotein levels in postmenopausal women during treatment with norethisterone.

Lipoprotein and apolipoprotein levels were monitored in 21 postmenopausal women during 6 months' treatment with norethisterone. There was no significant change in low density lipoprotein (LDL) cholesterol but apoprotein B levels rose significantly (p less than 0.001) thus increasing the apoprotein:cholesterol ratio in LDL. High density lipoprotein (HDL) cholesterol levels decreased significantly (p less than 0.001) in the first two months and did not change significantly thereafter. The HDL2 subfraction was reduced to a greater extent than the HDL3 subfraction. Apoprotein AI and AII levels were both reduced as was the apoprotein AI:AII ratio. The ratios of apoproteins AI and AII to HDL cholesterol were increased. We conclude that norethisterone has an adverse effect on the important risk factors for cardiovascular disease.

Adult↗

Organon OD 14 (tibolone) and menopausal dynamic hormone profiles.

Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.

Anabolic Agents↗

Long-term hormone implant therapy--effects on lipoproteins and steroid levels in post-menopausal women.

Lipoprotein and steroid hormone levels were measured in 61 bilaterally oophorectomised women who had been treated for 3 years with implants containing either oestradiol alone or oestradiol plus testosterone. The lipoprotein levels associated with each of the two therapy regimens were compared. In addition, lipoproteins were measured in 67 untreated bilaterally oophorectomised age-matched women and compared with those of the treated women. Despite the high oestradiol levels produced by both types of implant, the only significant finding was a reduced LDL cholesterol in the oestrogen/testosterone treated group as compared with that of the untreated group.

Adult↗

The effects of conjugated equine oestrogens with and without a cyclical progestogen on lipoproteins, and HDL subfractions in postmenopausal women.

Serum lipoprotein levels were followed for 24 weeks in 21 oophorectomised women treated with conjugated equine oestrogens (0.625 mg/day) and 21 women who had had a natural menopause and were treated with a combined preparation consisting of conjugated equine oestrogens (0.625 mg/day) with the addition of dl-norgestrel (0.15 mg/day) for the last 12 days of each treatment cycle. Conjugated equine oestrogens caused a significant (P less than 0.05) increase in triglyceride, HDL cholesterol, especially HDL2 cholesterol, and a significant decrease (P less than 0.05) in LDL cholesterol. Those subjects treated with conjugated equine oestrogens plus cyclical norgestrel showed a significant (P less than 0.05) decrease in LDL cholesterol levels only.

Cholesterol↗

Long-term hormone implant therapy--hormonal and clinical effects.

Long-term effects of hormone implants (estradiol or estradiol plus testosterone) were examined in 75 menopausal women. Both therapies relieved vasomotor symptoms with a return of significant flushing after six months, thus reimplantation was performed every six months. Estradiol levels had not returned to baseline by six months, and significant accumulation of estradiol occurred by three years. The patients given testosterone experienced a similar accumulation of testosterone. There was no significant change in mean weight, blood pressure, or liver function tests during three years. Both therapies reversed the bone biochemical changes of menopause, and in both groups there was no significant loss in bone density. Supplementation of estradiol with testosterone in implant therapy was not observed to provide additional benefit in terms of the parameters studied.

Adult↗

Effect of long term hormone replacement on plasma prolactin concentrations in women after oophorectomy.

Plasma prolactin concentrations were studied in 88 oophorectomised women who had been receiving mestranol or placebo for three to 11 years. Thirty one of them were also studied under basal conditions and by tests with thyrotrophin releasing hormone. Under basal conditions the mean prolactin concentration was higher in the oestrogen treated group but under non-rested, clinic conditions the difference was lost because of a rise in prolactin value in the placebo group only. Hence the groups showed a different prolactin response to the mild stress of clinic attendance but the same proportionate responsiveness to thyrotrophin releasing hormone. The data suggest that long term hormone replacement has no significant effect on circulating prolactin concentrations under non-rested, everyday conditions and that the prolactin stimulating effects of minor stress and oestrogen may share a similar mechanism.

Aged↗

Family history of problem drinking among young male social drinkers: reliability of the Family Tree Questionnaire.

The test-retest reliability of the Family Tree Questionnaire to detect drinking problems of family members was examined in a sample of 60 male volunteer university undergraduates. The Questionnaire was completed twice. The first occasion employed a group administration procedure, and an average of 4 months later it was readministered on an individual basis. Thus the length of time and the different administration procedures provided an extreme test of the reliability of the Questionnaire. Test-retest scores of the number of problem drinkers reported by a subject were significantly correlated for first degree and for second degree relatives. The reliability of the classification of an individual family member was also satisfactory. The Family Tree Questionnaire thus appears to be a potentially useful, reliable tool for assessing the incidence of problem drinkers within families of young male social drinkers.

Adult↗

Prevention of bone mineral loss in postmenopausal women by norethisterone.

The effect of norethisterone on bone mineral metabolism was examined in 43 postmenopausal women. A significant decline in serum calcium, phosphate, and alkaline phosphatase in urinary calcium/creatinine ratio and in tubular maximum reabsorption of phosphate was demonstrated. There was no alteration in urinary hydroxyproline/creatinine ratio. The bone mineral content measured over two years by single photon absorptiometry was compared in 20 patients receiving norethisterone and a matched control group receiving placebo. There was significant protection against bone loss in the norethisterone group.

Alkaline Phosphatase↗

Modifications of circular DNA by photoalkylation.

The effects of photoalkylation on superhelical PM2 DNA were examined. The chief product was 8-(2-hydroxy-2-propyl)guanine, formed exclusively in sequences of alternating purines and pyrimidines. Other purine damages included 8-(2-hydroxy-2-propyl)adenine and smaller quantities of two uncharacterized adenine products. DNA strand breaks were formed with increasing irradiation. A small quantity of thymine-containing photodimers was formed. Photoalkylation of poly(dG-dC):poly(dG-dC) reduced the concentration of salt required to effect inversion of the circular dichroic spectrum. This suggests that photoalkylation induces the transition of poly(dG-dC):poly(dG-dC) from the right-handed B form of DNA to the left-handed Z form.

Alkylation↗

Reduced serum free thyroxine concentration in postmenopausal women receiving oestrogen treatment.

Thyroid hormone state was assessed in a group of postmenopausal women who had received long term treatment with oestrogen. Serum concentrations of total thyroxine, triiodothyronine, and thyroxine binding globulin were raised compared with those in a control group given placebo; serum concentrations of thyroid stimulating hormone did not differ between the groups. Oestrogen treatment resulted in a significant decrease in the serum free thyroxine concentration and in the ratio of thyroxine to thyroxine binding globulin, which supports the view that oestrogen is the causative factor of the physiological reduction in free thyroid hormone during pregnancy.

Female↗

Effect of subdermal oestrogen and oestrogen/testosterone implants on calcium and phosphorus homeostasis after oophorectomy.

Various biochemical aspects of calcium metabolism were studied serially in 32 post-menopausal patients treated with subdermal implants of oestrogen, either alone or in combination with testosterone. Significant reductions in serum calcium, serum phosphate, the renal phosphate threshold (TmPO4) and the urinary calcium/creatinine ratio were observed for periods of up to 6 mth in both treatment groups as compared with baseline. The findings suggest that oestrogen replacement therapy by subdermal implant is effective in reversing the characteristic alterations in calcium metabolism which occur in the post-menopausal patient. The addition of testosterone does not appear to confer any additional benefit with respect to the parameters assessed.

Adult↗

Ten years post-menopausal hormone replacement therapy--effect on lipoproteins.

Serum lipoproteins were measured in 72 post-menopausal women, 40 of whom had been taking the synthetic oestrogen, mestranol, for a period of 10 yr and 32 of whom had been taking identical placebo tablets. Mestranol therapy was found to increase serum triglycerides, decrease low density lipoprotein (LDL) cholesterol and increase high density lipoprotein (HDL) cholesterol. The increase in HDL cholesterol was due principally to a marked increase in the cardioprotective HDL2 fraction. It is concluded that long-term mestranol therapy has a beneficial effect on serum lipoproteins which may help to protect post-menopausal women against fatal ischaemic heart disease.

Cholesterol↗

Effect on lipoproteins of Trisequens, a combined hormone preparation.

Lipoprotein concentrations were measured in 31 post-menopausal women during 1 yr of treatment with Trisequens, a natural oestrogen-progestogen preparation. Serum triglyceride, high density lipoprotein and very low density lipoprotein cholesterol concentrations did not change significantly, but low density lipoprotein cholesterol concentrations fell over the first 6 mth. After 1 yr none of the lipoprotein fractions differed significantly in concentration from pre-treatment levels.

Adult↗

Calcitonin and postmenopausal osteoporosis.

Fasting serum calcitonin levels were measured in 54 postmenopausal women who had for 10 years been taking part in a double blind trial to assess the effect of the synthetic oestrogen, mestranol, on postmenopausal bone loss. There were no differences in calcitonin levels between mestranol treated and placebo groups. Fifteen of the women were challenged with a calcium infusion to measure the secretory reserve of calcitonin. Oestrogen treatment did not increase the calcitonin response to calcium infusion. The three patients who exhibited the greatest responses were placebo treated. Bone density was measured by gamma-ray absorptiometry over the ten year period and the annual rate of change of bone density calculated. No correlation could be found between basal calcitonin level or calcitonin reserve and change in bone density. Our results indicate that postmenopausal osteoporosis is not caused by a deficiency of calcitonin and that the action of oestrogen therapy to prevent bone loss does not involve calcitonin.

Calcitonin↗