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Biomedical subjects

D M Hart

Publications and source records attributed to D M Hart.

At least 73 records · Page 4Linked to original sources

The effect of oestrogen (mestranol) on the thyrotrophin response to thyrotrophin releasing hormone in postmenopausal oophorectomised women.

The thyrotrophin (TSH) responses to thyrotrophin releasing hormone (TRH) in 16 oophorectomised postmenopausal women on long term treatment with mestranol 24 micrograms daily were compared to those in 16 oophorectomised postmenopausal women on placebo treatment. No significant difference between the groups was found in either basal TSH levels or the TSH response to TRH. It is therefore unlikely that the difference in TSH response to TRH between men and women of reproductive age is due to a direct stimulatory effect of oestrogen in women.

Castration↗

Lipoprotein levels during hormone replacement therapy by vaginal ring pessaries.

Nineteen women who had had a surgical menopause had a vaginal ring pessary containing levonorgestrel and oestradiol in situ for a period of 3 months. Fasting lipoprotein levels were measured before, and after 1 and 3 months on therapy. After 3 months total triglyceride levels were significantly lower than baseline values (P less than 0.01) as were very-low-density-lipoprotein cholesterol (P less than 0.01), low-density-lipoprotein cholesterol (P less than 0.05) and high-density-lipoprotein cholesterol (P less than 0.001) levels. These changes suggest that in this preparation the effects of the progestogen component are dominant.

Adult↗

The effects of hormone implants on serum lipoproteins and steroid hormones in bilaterally oophorectomised women.

Serum lipoproteins were measured over a period of 6 months in 14 oophorectomised women treated with oestrogen implants (50 mg oestradiol-17 beta) and 17 oophorectomised women treated with oestrogen/testosterone implants (50 mg oestradiol-17 beta, 100 mg testosterone). Both types of implant caused only minimal changes in lipoprotein metabolism. Low density lipoprotein (LDL) cholesterol decreased with both types of implant and high density lipoprotein (HDL) cholesterol rose with the oestrogen implants. HDL subfractions were also measured. The oestrogen implants caused a transient rise in HDL2 cholesterol levels at 2 months and a slower rise in HDL3 cholesterol. The oestrogen/testosterone implants had no effect on HDL fractions. The results indicate that hormone implants do not cause the profound changes in lipoproteins associated with oral hormone therapy.

Adult↗

The minimum effective dose of estrogen for prevention of postmenopausal bone loss.

In a controlled single blind study to determine the minimal effective dose of estrogen for protection against bone loss, conjugated equine estrogens in doses of 0.625 and 1.25 mg per day were equally effective in reducing bone loss in postmenopausal and oophorectomized women when bone mass was estimated by single-photon absorptiometry or radiogrammetry . Daily dose levels of less than 0.625 mg were essentially ineffective. Fifty percent response level was calculated to be 0.45 mg per day. Concomitant biochemical effects, reduction in urine calcium and hydroxyproline, were compatible with the observed effects on bone mineral.

Bone Resorption↗

Perturbations of enzymic uracil excision due to guanine modifications in DNA.

Phage PBS2 DNA, which contains uracil in place of thymine, was used as substrate for purified Bacillus subtilis uracil:DNA glycosylase. Incubation of this DNA with the ultimate carcinogen N-acetoxy-N-2-acetylaminofluorene resulted in the production of N-(deoxyguanosin-8-yl)acetylaminofluorene. A decreased Vmax resulted from the reaction of the glycosylase with this arylamidated substrate. Addition of a 2-fold excess of control PBS2 DNA following initiation of the reaction with the modified substrate showed delayed dissociation of the enzyme from the arylamidated DNA. This shows that the presence of a carcinogen-modified DNA base can reduce the capacity for uracil excision. Therefore, interference with enzymic release of uracil from DNA may be an indirect mechanism of mutagenesis by carcinogen:DNA adducts.

2-Acetylaminofluorene↗

A long-term study of the effects of norethisterone on lipoprotein metabolism in menopausal women.

Long-term effects of the androgenic progestogen norethisterone on lipoprotein metabolism were studied by measuring lipoprotein concentrations in 21 women during one year on treatment for the relief of climacteric symptoms. There were significant reductions in total serum triglyceride (p less than 0.01), very low density lipoprotein (VLDL) cholesterol (p less than 0.01) and high density lipoprotein (HDL) cholesterol (p less than 0.001) after two months on treatment, all of which were still in evidence after one year. Low density lipoprotein (LDL) cholesterol levels climbed gradually becoming significantly higher than baseline after one year on treatment (p less than 0.01). Comparison of cholesterol concentrations in HDL subfractions in the one year treated subjects with those in a control group of untreated subjects suggests that the fall in HDL cholesterol is due to reductions in both the HDL2 and HDL3 fractions. We conclude that norethisterone adversely affects the important lipoprotein risk factors for coronary heart disease.

Adult↗

Hormonal treatments of sexual unresponsiveness in postmenopausal women: a comparative study.

Forty postmenopausal women, referred for hormone replacement therapy and all of whom reported a significant concern about a decline in their sexual interest, were randomly allocated to one of two hormone implant treatment groups: either oestradiol (50 mg) alone, or oestradiol (50 mg) and testosterone (100 mg). Comparison between the two groups as a whole revealed no significant differences on any measure, both treatments being associated with a significant reduction in the severity of psychological, somatic and vasomotor symptoms, and with a significant improvement in sexual interest and responsiveness. Similar effects were also observed in patients who denied, pretreatment, any concurrent dyspareunia. Although it is not possible to identify the reasons for change, the results indicate no advantages of supplementary testosterone administration over oestradiol alone for sexually unresponsive postmenopausal women.

Adult↗

Polyglycolic acid and catgut sutures, with and without oral proteolytic enzymes, in the healing of episiotomies.

Polyglycolic acid (PGA) sutures and traditional catgut were compared in 190 patients undergoing episiotomy. Each group was also randomly allocated to a double blind comparison of therapy with oral proteolytic enzymes (Chymoral) and placebo. The combination of Chymoral and polyglycolic acid sutures was shown to reduce the level of pain, assessed subjectively, and there was a significant reduction in analgesic requirements in the Chymoral/PGA group.

Anti-Inflammatory Agents↗

Reaction of the leukocytes of melanoma patients and control donors, including pregnant women, with melanoma- and fetus-derived materials.

Using a one-stage capillary leukocyte migration inhibition assay, we examined peripheral blood leukocytes from 97 patients with malignant melanoma, 194 pregnant women, and 123 non-pregnant donors for their reactivity with materials from fetal and melanomatous tissues. As in previous studies, we found melanoma extracts selectively to inhibit melanoma patients' leukocytes. First-trimester fetal extracts also selectively inhibited melanoma patients' leukocytes, suggesting their cross-reactivity with melanoma-derived antigens. We could not localize the source of the inhibitory materials within the fetuses. We found no evidence that pregnant women were selectively immunized to fetal or melanoma extracts, regardless of their parity or the stage of their pregnancy.

Cell Migration Inhibition↗

Perturbations of enzymic uracil excision due to purine damage in DNA.

Phage PBS-2 DNA, which contains uracil in place of thymine, was selectively damaged and then used as substrate for purified Bacillus subtilis uracil-DNA glycosylase. This enzyme releases uracil from DNA in a limited processive manner. Irradiation by ultraviolet light (greater than 305 nm) in the presence of isopropanol and a free radical photoinitiator introduced covalently bound 8-(2-hydroxy-2-propyl)purines into DNA. Methylation by dimethylsulfate yielded 7-methylguanine. Apurinic sites were produced by gentle heating of methylated DNA. Rates of enzymic release of uracil from DNA varied among these three substrates. The Vmax was markedly decreased for DNA containing 8-(2-hydroxy-2-propyl)purines and apurinic sites but was unaffected by the presence of larger quantities of 7-methylguanine. This suggests that certain types of damaged DNA moieties may decrease the capacity for uracil excision. Therefore, interference with enzymic excision of this potentially mutagenic base may constitute a common mechanism of action of the reaction products of several unrelated DNA damaging agents.

Alkylating Agents↗

Assessment of synthetic steroid (Org OD 14): effect on skeletal metabolism by 24-h whole-body retention of diphosphonate.

Using a 24-h whole-body retention (WBR) of Tc99m hydroxyethylidene diphosphonate (HEDP), a sensitive measure of skeletal metabolism, 24 women receiving the synthetic steroid hormone Org OD 14 were studied. OD 14 was found to have a powerful suppressive effect on skeletal metabolism in both oophorectomized and non-oophorectomized women when compared with control subjects (P less than 0.001 and P less than 0.01, respectively). The degree of suppression was similar to that found with oestrogen therapy. While it has previously been shown that OD 14 prevents bone mineral loss (as measured by photon-absorptiometry), the present study provides further evidence as to the efficacy of this compound in suppressing skeletal metabolism.

Alkaline Phosphatase↗

Oral complaints related to climacteric symptoms in oöphorectomized women.

Numerous oral complaints have been attributed to the female climacteric including altered taste, a burning sensation and xerostomia. However, the data relating these symptoms to the climacteric require elucidation as there have been no adequately controlled studies. In the present investigation, a group of 145 oöphorectomized women were followed for one year. Approximately half were treated with oestrogen replacement and the remainder with a placebo. The results indicate that the hormone had no direct effect upon the oral symptoms but that there was a general increase in somatic complaints which appeared to be related to the degree of neurosis experienced. This is turn can be attributed to vasomotor changes which are under the control of oestrogen.

Adult↗

Prevention of spinal osteoporosis in oophorectomised women.

100 women who had taken part in a prospective controlled trial of oestrogen therapy for prevention of post-oophorectomy bone loss were reviewed after a median follow-up period of nine years. A significant reduction in height occurred among the placebo-treated group, but not in the group treated with mestranol (mean 23 x 3 micrograms/day). The placebo-treated group had a higher spine score, lower central vertebral height, and larger wedge-angle than the oestrogen group. Within each group none of these spinal morphometric changes correlated with changes in mineral content of metacarpal or radial bones as measured by photon absorptiometry or X-ray densitometry, although both peripheral and central measurements showed highly significant differences between groups. Oestrogen treatment, therefore, prevents against central, as well as peripheral, bone loss, and reduces the incidence of vertebral compression.

Body Height↗

Skeletal uptake of diphosphonate. Method for prediction of post-menopausal osteoporosis.

24-h whole-body retention (WBR) of diphosphonate (a sensitive indicator of skeletal metabolism) was measured in 37 oophorectomised women. 14 women had been prescribed oestrogen supplements and 3 of these had defaulted from therapy. For the study group there was a significant correlation between WBR and both the rate of bone loss as measured by photonabsorptiometry (r = 0.7, p ¿ 0.001) and urinary hydroxyproline (r = 0.53, p < 0.001). The oestrogen-treated group had significantly lower values for WBR and rate of bone loss than the untreated group (p < 0.01, p < 0.01 respectively) indicating suppressed skeletal metabolism. However, the highest values were found in those who had defaulted from oestrogen therapy suggesting a rebound period of accelerated skeletal metabolism and bone loss. There was a significant negative correlation between WBR and oestrogen dosage (r = 0.75, p < 0.02) suggesting that it may be possible to adjust the dosage for optimal skeletal metabolic activity. WBR of diphosphonate provides a simple and sensitive measure of skeletal metabolism which correlates well with conventional measurements of bone loss. WBR may be useful in the screening and identification of women who have increased bone turnover just after the menopause and who may subsequently be at risk of osteoporosis developing.

Aged↗