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Biomedical subjects

E Farish

Publications and source records attributed to E Farish.

At least 37 records · Page 2Linked to original sources

Prevention of bone loss by hormone replacement therapy is probably not due to stimulation of calcitonin secretion.

Weekly fasting serum calcitonin levels and biochemical indices of bone metabolism were measured in 13 postmenopausal women being given hormone replacement therapy over a period of 8 weeks. All of the biochemical indices except urinary hydroxyproline creatinine ratios fell significantly, indicating that the treatments were effective in reducing bone turnover. Calcitonin levels fell significantly and, within the individual, levels were positively correlated with adjusted calcium levels. These findings do not support the theory that estrogen conserves bone by stimulating calcitonin secretion.

Alkaline Phosphatase↗

Combined lipid-lowering and antihypertensive treatment as part of a strategy of multiple risk factor intervention.

Thirty-six patients with treated mild to moderate hypertension and hypercholesterolaemia (greater than 6.5 mmol/l) entered a 12 week study to evaluate the efficacy and patient tolerability of combined lipid-lowering and antihypertensive treatment as part of a strategy of multiple risk factor intervention. The principal effects on the plasma lipid profiles were significant reductions of 30-40% in total and LDL cholesterol. These reductions were achieved without loss of blood pressure control. There was no significant impact on HDL cholesterol or on lipoprotein Lp(a). These preliminary results suggest that substantial reductions in total and LDL cholesterol can be achieved without compromising blood pressure control which remained satisfactory at 144/82 supine and 143/80 mmHg standing. Furthermore, these changes were achieved without any problems of patient tolerability or interference with patient compliance with drug treatment. Overall, therefore, substantial reductions in CHD risk can be achieved with an acceptable combination of lipid lowering and antihypertensive treatments.

Aged↗

Effects of bilateral oophorectomy on lipoprotein metabolism.

The effects of surgical menopause on lipoprotein levels and their time course were studied in 31 premenopausal women who were undergoing hysterectomy and bilateral oophorectomy for non-malignant conditions. Lipoprotein levels were measured before oophorectomy and afterwards at 6 and 12 weeks, then at intervals of 3 months for 18 months. Low density lipoprotein (LDL) cholesterol levels rose significantly (P less than 0.05) in the 6 weeks after operation from a mean of 3.57 (SD 0.66) mmol/l to 4.21 (SD 0.84) mmol/l with no significant changes thereafter. There were no significant changes in cholesterol in the other density fractions or in triglyceride levels. High density lipoprotein (HDL) subfractions were measured in 10 of the women to assess any change in the relative amounts of cholesterol carried on HDL2 and HDL3, since the protective effect of HDL is believed to be conferred by the HDL2 fraction only. No significant change was found in either fraction. The increase in LDL cholesterol would be expected to result in an appreciable increase in the risk of developing coronary heart disease, but cannot wholly account for the increase in cardiovascular disease associated with oophorectomy.

Adult↗

Hypercholesterolaemia in treated hypertensives: a controlled trial of intensive dietary advice.

We evaluated dietary counselling by dietitians in hypercholesterolaemic hypertensives over 6 months. A total of 141 patients were randomly assigned to intensive advice or usual care. Body weight fell significantly in the intervention group, but did not in the controls. There was a modest but significant fall in total cholesterol from 7.1 to 6.8 and 7.1 to 6.9 mmol/l in the diet and the control groups, respectively (4 and 3%). A similar pattern emerged from the triglyceride measurements. Low-density lipoprotein fell in both groups, but only achieved significance (P less than 0.05) in the intervention group. High-density lipoprotein did not change. There was a more marked change in cholesterol when serum levels during the study were compared with the previous annual review. These falls occurred after selection for the study but before random allocation to groups. They are unlikely to reflect regression to the mean as the lipids were stable for 2 or more years before the study, but may reflect spontaneous changes in diet after the patients were labelled hypercholesterolaemic. Dietary advice can lower total cholesterol but the magnitude of this decrease is small. Additional approaches are likely to be required to reduce plasma cholesterol to a normal range.

Antihypertensive Agents↗

Effects of treatment with oestradiol/levonorgestrel on bone, lipoproteins and hormone status in postmenopausal women.

The aim of the study was to investigate the effects of an oestradiol/levonorgestrel regimen, administered parenterally, on bone metabolism, bone density, lipoprotein metabolism and hormone status. Twenty-five women who had undergone a surgical menopause had an oestradiol/levonorgestrel-containing vaginal ring pessary in situ for 6 months. Within the first month there were sustained changes in the biochemical indices of bone metabolism in keeping with a marked reduction in bone turnover and decrease in bone resorption. Bone mineral content in the distal forearm was measured in 14 patients and a small increase was noted in every patient. Levonorgestrel was well absorbed and the serum levels remained almost constant throughout treatment. There was a gradual increase in serum total oestradiol which became significant at 6 months. Dialysable oestradiol levels rose from 2.6% of total oestradiol at 0 time to 3.3% at 1 month with no further change thereafter. SHBG levels were 23% of pretreatment levels at 6 months. There were sustained decreases in triglyceride, VLDL and HDL cholesterol levels and a transient fall in LDL cholesterol. Total HDL, HDL2 and HDL3 cholesterol levels were reduced by 25, 40 and 21% respectively. The results suggest that levonorgestrel exerts a protective influence on bone either directly or by its effect on the proportion of oestradiol circulating in the free, physiologically active form. The effects on lipoproteins were predominately those of the progestogen component, the lipoprotein risk factors for coronary heart disease being adversely affected.

Administration, Intravaginal↗

Lipoprotein and apolipoprotein levels in postmenopausal women on continuous oestrogen/progestogen therapy.

Levels of serum lipoproteins and apolipoproteins were monitored for 48 weeks in two groups of women taking part in a double-blind trial of continuous oestrogen/progestogen with and without oestriol. There were no differences between the effects of the two treatments on the substances measured. Triglycerides did not change and there was a transient fall in very low density lipoprotein cholesterol. Low density lipoprotein cholesterol fell over the first 24 weeks but rose thereafter to pretreatment levels. There was a decrease in high density lipoprotein (HDL) cholesterol due to a transient fall in HDL2 cholesterol and a gradual decrease in HDL3 cholesterol. Consequently, the only change in lipid levels present after 48 weeks was a decrease in HDL3 cholesterol, the clinical significance of which is uncertain. There was, however, an increase in apoprotein B levels and decreases in apoprotein AI and AII levels. These alterations in apoprotein levels may be unfavourable, since apoprotein B levels have been positively correlated and apoprotein AI and AII levels negatively correlated with coronary heart disease.

Apolipoproteins↗

Changes in the bone and liver isoenzymes of alkaline phosphatase in postmenopausal women being treated with norethisterone.

The effects of norethisterone therapy on alkaline phosphatase isoenzyme activities were studied in a group of postmenopausal women. There was a significant fall in total alkaline phosphatase activity after 8 wk which was still in evidence after 24 wk. Both bone and liver alkaline phosphatase isoenzyme activities were decreased during the first 16 wk on treatment, but after 24 wk only the bone phosphatase activity was significantly lower than the pretreatment level. The other biochemical indices of bone metabolism and liver function were also measured during the study. The results indicate that bone specific alkaline phosphatase activity is a more sensitive index of bone activity than total alkaline phosphatase and that monitoring of total activity may in some instances be misleading.

Alkaline Phosphatase↗

Amiodarone therapy and glucose tolerance--a prospective trial.

It has previously been suggested that amiodarone, used widely to treat refractory cardiac arrhythmias, may induce glucose intolerance. In view of this, we have undertaken a prospective study in a group of 10 patients with normal glucose tolerance profiles requiring amiodarone therapy for control of supraventricular or ventricular dysrhythmias. The patients were followed for a total of 9 months, and glucose tolerance tests and glycosylated haemoglobin were done at 3 monthly intervals in all patients. Both fasting blood glucose levels and glucose tolerance tests were entirely within normal limits in all patients at each stage during the study. Glycosylated haemoglobin did rise significantly at 6 months, but this did not exceed the normal range in the majority of patients and the rise was not sustained at 9 months. In this prospective study therefore, there is no evidence of either glucose intolerance or a diabetogenic effect during prolonged therapy with amiodarone.

Adult↗

Effects of conjugated equine oestrogens with and without the addition of cyclical norgestrel on serum and urine electrolytes, and the biochemical indices of bone metabolism and liver function.

Serum and urine electrolytes, and biochemical indices of bone metabolism and liver function were measured in 51 post-menopausal women treated with two hormone replacement therapy regimens for 24 wk. Twenty-six of the women were treated continuously with conjugated equine oestrogens (0.625 mg/day) and the remainder were treated as above with the addition of norgestrel (0.15 mg/day) during the last 12 days of each 28-day cycle. Both treatment regimens affected electrolytes in a similar manner. The most consistent effect was a reduction in serum sodium levels and a reduction in urinary sodium/creatinine ratios. The combined regimen appeared to have a greater effect on sodium reabsorption. Both regimens decreased all the biochemical indices of bone metabolism measured, viz serum calcium (corrected for albumin), phosphate and alkaline phosphatase and urinary calcium/creatinine and hydroxyproline/creatinine ratios. The preparations used decreased the parameters by similar amounts over the 24 wk indicating that both were equally effective in reducing bone turnover. The data suggested, however, that the combined regimen had a more profound effect on bone metabolism during the early phase of treatment. The two treatment regimens had broadly the same effects on the biochemical indices of liver function, reducing albumin levels and all the liver enzymes. Judging by these indices neither regimen had a deleterious effect on liver function. We conclude that the two hormone replacement regimens have similar effects on the biochemical indices measured, but there are subtle differences between the two treatments which merit further research.

Bone and Bones↗

Exercise and platelet intracellular free calcium concentration.

1. A positive correlation between blood pressure and platelet intracellular free calcium concentration ([Ca2+]i) has been reported. We examined the effect of acute changes in blood pressure associated with exercise on platelet [Ca2+]i. 2. Twenty-one subjects had blood pressure and heart rate readings taken after 60 min rest, and subjects were then exercised on a bicycle ergometer at 120 W for 30 min. Blood pressure and heart rate readings were repeated immediately after exercise, 30 min after exercise, and then after a further hour. Blood samples were taken after each set of blood pressure and heart rate readings for catecholamine, lactate and platelet [Ca2+]i estimations. 3. There were significant increases in systolic and diastolic blood pressure, heart rate, and plasma lactate and catecholamine levels during the course of the study. There were no significant changes in platelet [Ca2+]i. 4. These results suggest that the acute blood pressure changes related to exercise are not associated with a change in platelet [Ca2+]i.

Adult↗

The effects of conjugated equine estrogens plus cyclical dydrogesterone on serum lipoproteins and apoproteins in postmenopausal women.

Serum lipoprotein and apoprotein concentrations were monitored for 24 weeks in 26 postmenopausal women treated with conjugated equine estrogens (0.625 mg/day) with the addition of dydrogesterone (10 mg/day) for the last 12 days of each 28 day cycle. The women had had no previous hormone replacement therapy. The estrogen plus dydrogesterone regimen caused significant (P less than 0.05) increases in triacylglycerol and HDL cholesterol concentrations. Both HDL2 and HDL3 cholesterol were increased. There were no other significant changes in lipoprotein concentrations. Both apoprotein AI and apoprotein AII concentrations increased significantly (P less than 0.05) over the study period. The ratios of apoprotein AI to apoprotein AII, apoprotein AI to HDL cholesterol and apoprotein AII to HDL cholesterol did not change. At the doses employed in this study, the use of dydrogesterone as a progestogen alters the effects of conjugated equine estrogens on lipoproteins and reinforces the view that the effects of a combined HRT regimen cannot be predicted from a consideration of the effects of the individual components.

Apoproteins↗

The influence of beta-adrenoceptor antagonists with and without partial agonist activity on exercise tolerance and muscle lactate production.

Epanolol is a beta-adrenoceptor antagonist with partial agonist activity, a property which could be useful in reducing the fatigue associated with beta blockers. In a double-blind, randomized, crossover study we have investigated the effects of metoprolol 100 mg b.d., epanolol 100 mg b.d., and epanolol 200 mg b.d. on blood pressure, heart rate, and exercise-induced fatigue in 10 hypertensive men. Fatigue was measured subjectively by the Borg rating scale and objectively by blood lactate concentrations. Resting and exercise heart rates were lower with metoprolol than with either dose of epanolol. Preexercise standing diastolic blood pressure was lowered by metoprolol, but there were no other treatment effects on blood pressure. Exercise-induced fatigue was not altered by any treatment, whether measured subjectively or objectively. These results do not support the hypothesis that partial agonist activity improves exercise tolerance in hypertensive patients treated with beta-adrenoceptor antagonists.

Adolescent↗

A comparison of the effects of lipoproteins of two progestogens used during cyclical hormone replacement therapy.

Lipoprotein levels were measured in 11 women who had been treated with 0.625 mg/day conjugated equine oestrogens with the addition of 0.15 mg/day DL-norgestrel for the last 12 days of each 28 day cycle for 48 wk. Treatment was then changed to an identical oestrogen regimen with dydrogesterone, 10 mg/day, as progestogen and monitoring continued for a further 24 wk. The oestrogen plus norgestrel regimen caused a significant reduction in low density lipoprotein (LDL) cholesterol levels. During the 24 wk after the change of therapy, levels of high density lipoprotein (HDL) increased significantly due to an increase in the HDL2 fraction and there was an upward trend in LDL cholesterol which did not attain statistical significance. We conclude that, when used in combination with conjugated equine oestrogens, changing from norgestrel, 0.15 mg/day, to dydrogesterone, 10 mg/day, does not lead to any significant improvement in lipoprotein profile.

Cholesterol, LDL↗

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↗

Effects of ranitidine and cimetidine on plasma lipoproteins in healthy subjects.

Serum lipoproteins were monitored in 24 healthy subjects receiving either ranitidine or cimetidine for four weeks. Ranitidine produced a significant (P less than .05) reduction in high-density lipoprotein (HDL)-cholesterol in both men and women. Cimetidine caused a nonsignificant increase in HDL-cholesterol and a reduction in LDL-cholesterol that was significant (P less than .05) only in women. As these drugs had opposite effects on HDL-cholesterol levels, the mechanism of action is unlikely to be medicated by H2-receptor blockade.

Adult↗

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↗