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Biomedical subjects

M Mälkönen

Publications and source records attributed to M Mälkönen.

At least 19 recordsLinked to original sources
PubMed1988

New natural oestradiol/cyproterone acetate oral contraceptive for pre-menopausal women.

Fifty (50) healthy ovulating women aged between 35 and 47 yr (mean age 39) were randomly allocated to one of two groups treated with biphasic formulations of either oestradiol valerate/cyproterone acetate (Group A) or oestradiol valerate/norethisterone (Group B). A double-blind design was used during the first 6 mth of treatment. In Group A, 21 out of 26 women (81%), and in Group B, 16 out of 24 (67%) completed the first year of treatment. No pregnancies occurred. The mid-cycle serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) peaks were suppressed, but there were no differences between the pretreatment serum oestradiol values and those observed during the treatment cycles. The serum progesterone values indicated that only one ovulatory cycle occurred during the first year in Group A, while there were 11 in Group B. Ultrasonic studies revealed follicular growth during treatment in both groups, most follicles becoming atretic or persistent without ovulation. No significant changes were observed in 11 coagulation factors studied in 16 women in Group A. Serum total cholesterol decreased by about 10% in both groups. In Group A bleeding became scantier and dysmenorrhoea disappeared. The incidence of spotting varied between 30% and 40%, but it is important to note that the total number of bleeding days per cycle fell. The oestradiol valerate/cyproterone acetate combination was thus found to inhibit ovulation, provide tolerable cycle control and to be free from adverse metabolic side effects.

Adult↗
PubMed1987

Clinical and lipid metabolic effects of unopposed oestrogen and two oestrogen-progestogen regimens in post-menopausal women.

No differences in the clinical effects on climacteric complaints of an unopposed oestrogen and two oestrogen-progestogen regimens were observed in a double-blind cross-over study. Only 4 out of 18 women with an intact uterus had withdrawal bleeding during oestradiol valerate (2 mg/day) treatment alone, but 14 out of 18 had regular bleeding during the two oestrogen-progestogen regimens (oestradiol/medroxyprogesterone acetate and oestradiol/levonorgestrel (LNG], each of which prevented the development of endometrial hyperplasia. High-density-lipoprotein cholesterol (HDL-CH) concentration remained 6% above the initial level and the atherogenic index (low-density-lipoprotein (LDL) cholesterol to HDL-CH ratio) improved significantly during the oestradiol/medroxyprogesterone acetate regimen, while the HDL-CH concentration fell by 20% in relation to the initial level and there was a deterioration in the atherogenic index during the oestradiol/LNG regimen. The data suggest that both of these oestradiol/progestogen combinations are clinically as effective and well-tolerated as oestradiol alone, but that combined oestradiol/medroxyprogesterone acetate causes fewer adverse lipid metabolic effects than the oestradiol/LNG combination.

Cholesterol↗
PubMed1987

Minimal doses of digoxin: a new marker for compliance to medication.

A direct and objective method of measuring compliance to medication is presented. Digoxin is used as a marker in capsules of either gemfibrozil or placebo with a minimal dose of 4.4 micrograms twice a day. Compliance is estimated by measuring the ratio of urinary digoxin to creatinine concentration. By choosing two cut-off points of this ratio patients who are taking their capsules regularly and those who have taken no capsules at all could be distinguished from others. Reduced dosage was easily detected in the marker results. During regular intake of three quarters of the dose, 53% of the samples would have classified the patient to the good compliance group. With half of the dose, 24% of samples and with a quarter of the dose, 5% of samples would have classified the subject to good compliance. Since the digoxin marker was planned for compliance measurements in the Helsinki Heart Study, a primary prevention study of coronary heart disease, it was tested under the conditions of a clinical trial. Digoxin concentrations were measured using a routine method normally applied to serum but shown to be valid for urine. The results of the urinary assays were not affected by storage at room temperature, as occurs during postal transport of samples, nor were they affected by freezing, routinely used for the storage of samples in clinical trials. The results therefore suggest that the digoxin marker represents a particularly effective method to study compliance to medication during such long-lasting clinical investigations.

Clinical Trials as Topic↗
PubMed1982

Effect of diazepam on endothelial permeability, plasma lipids and lipoproteins in cholesterol fed rabbits.

In order to investigate the effect of diazepam in reducing the incidence and severity of cholesterol induced atherosclerosis in rabbits, 3 treatment groups were compared. The control Group I received the laboratory diet alone. Group II received cholesterol (1 gm daily, given by syringe). Animals in Group III additionally received diazepam (3 mg/kg/day) orally, again by syringe. After 21 days, animals were injected with Evans blue and 3 hours later their aortas were removed and examined for permeability changes. Serum was assayed for various lipid and lipoprotein components. Cholesterol feeding produced a 10-fold increase in serum cholesterol values in Groups II and III compared to the control Group I. The aortic uptake of Evans blue was significantly increased in animals treated with cholesterol but not in those which simultaneously received diazepam. Thus, diazepam prevented the increased endothelial permeability produced by hypercholesterolaemia, but it is not yet clear whether this effect involves the central nervous system or is a consequence of some more local membrane stabilizing action.

Animals↗
PubMed1982

Plasma prekallikrein, kallikrein inhibitors, kininogen and lipids during gemfibrozil treatment in type II dyslipidaemia.

The effects of gemfibrozil on plasma prekallikrein, kallikrein inhibitors, kininogen and plasma lipids were investigated in 31 male subjects having either type IIA or IIB dyslipidaemia. During gemfibrozil use, plasma prekallikrein and kininogen were increased significantly while kallikrein inhibitors increased only slightly. Total cholesterol and triglycerides decreased while HDL cholesterol was increased. Changes in prekallikrein and HDL cholesterol were correlated, whereas no other significant correlations between changes in lipid and kinin parameters were seen. The observed changes in prekallikrein and kininogen possibly indicate a shift in the thrombo-haemorrhagic balance in favour for increased fibrinolysis. If so, the effects of gemfibrozil in prevention and management of atherosclerosis would not be solely due to correlation of the dyslipidaemia but also to protection against the accelerated coagulation tendency seen in type II dyslipidaemia.

Adult↗
PubMed1982

Studies on hypoxic dyslipidaemia. Effect of lipid modulating drugs.

Haemorrhagic anaemia, exposure to altitude and depression of cell respiration are known to increase plasma triglyceride and cholesterol levels. The common triggering mechanism in all 3 instances is oxygen deficiency but mode of action is not known. The present study was intended to investigate whether lipid lowering drugs clofibrate or gemfibrozil could counteract such hypoxic dyslipidaemia in rats induced by altitude exposure. It was unexpectedly found that in normal rats gemfibrozil elevated plasma total cholesterol with an increase in the HDL-cholesterol component whereas clofibrate caused a rise in LDL-cholesterol. Nicotinic acid had no consistent effect. In hypoxia control rats showed an increase in cholesterol and triglyceride level. Both gemfibrozil and clofibrate prevented the rise of triglycerides. Total cholesterol fell in rats treated either with gemfibrozil or clofibrate during altitude exposure, indicating that neither natural nor gemfibrozil-augmented hyper-HDL-aemia could be maintained during oxygen deficiency.

Altitude↗
PubMed1982

Kidney and liver function in rats during the edema following constriction of thoracic inferior vena cava with and without adrenalectomy or hypophysectomy.

In several animal species, constriction of the thoracic inferior vena cava (TIVCC) is known to increase proximal sodium reabsorption and inhibit natriuresis following saline loading, leading to edema. To eluicidate the role of adrenal and hypophyseal hormones in the development of edema, kidney and liver functions after TIVCC were compared in adrenalectomised or hypophysectomised rats, and in intact controls. It was found that edema (body weight increase) and kidney and liver affliction were much less pronounced after the operations. The roles of aldosterone and ADH deficiency in renal sodium and water excretion are discussed. It is concluded that adrenal and hypophyseal hormones do not initiate edema but modulate its extent. The absence of edematous changes in the liver of hypophysectomised and adrenalectomised rats deserves further attention.

Adenosine Triphosphatases↗
PubMed1981

Effects of different progestogens on lipoproteins during postmenopausal replacement therapy.

To study the effects of different types of progestogens on lipoprotein metabolism, we treated three groups of postmenopausal women (six subjects each) for three weeks with estradiol valerate, 2 mg per day, and continued the treatment with different sequential estradiol-progestogen regimens as follows: Group A received norethindrone acetate, 10 mg per day, from Day 15 to Day 24 of the cycle; Group B, medroxyprogesterone acetate, 10 mg per day; and Group C, norgestrel, 0.5 mg per day. These regimens were followed by two consecutive cycles. Total cholesterol decreased in all groups by 10 to 18 per cent from the base-line values (P < 0.05). High-density-lipoprotein (HDL) cholesterol decreased by 20 per cent from the base-line level during treatment with both the estradiol-norethindrone acetate (P < 0.05) and estradiol-norgestrel (P < 0.01) regimens, whereas estradiol with medroxyprogesterone acetate was not associated with a significant change in HDL cholesterol. Our results suggest that the androgenic progestogens of the 19-nortestosterone series reverse the beneficial effect of postmenopausal estrogen treatment on HDL cholesterol, whereas the hydroxyprogesterone derivative medroxyprogesterone acetate has no such effect.

Cholesterol↗
PubMed1981

Gemfibrozil in the treatment of dyslipidaemias in middle-aged male survivors of myocardial infarction.

The effects of gemfibrozil on serum lipids and apolipoproteins were investigated in 60 male survivors of myocardial infarction (MI) (age range 29-48 years, mean 44). Fifteen had normal serum cholesterol (less than or equal to 7.0 mmol/l) and triglyceride (less than or equal to 1.7 mmol/l) levels, but most had low levels of high density lipoprotein (HDL) cholesterol (less than 1.00 mmol/l). Ten had type II A, 27 type II B and 8 type IV hyperlipidaemia. A double-blind placebo-controlled cross-over design was used with 3-month treatment periods. Gemfibrozil was given in daily doses of 1200 mg. The drug was well tolerated and there were no drop-outs attributable to its use. In all subjects, gemfibrozil reduced the mean serum total cholesterol by 17% and triglycerides by 54% and increased HDL cholesterol by 16%. The percentage HDL cholesterol of total cholesterol increased from 14 to 19%. The changes were similar in patients with normal serum cholesterol and triglyceride values and in those with classical hyperlipidaemias. In contrast, the changes during placebo treatment corresponded to those in healthy male untreated controls who were followed simultaneously. Apoprotein A-I remained unchanged, but A-II increased by 20% during gemfibrozil treatment. It is concluded that gemfibrozil corrects effectively dyslipidaemias in male MI patients but further long-term studies are warranted.

Adult↗
PubMed1980

Effects of danazol and lynestrenol on serum lipoproteins in endometriosis.

The treatment of endometriosis with danazol or lynestrenol decreased cholesterol content of plasma high-density lipoproteins by 50% and 32%. There were simultaneous increases in low-density lipoprotein cholesterol content of 51% and 19%. We suggest that changes induced by lynestrenol are due to progestational activity, while in the case of danazol both antigonadotropic and androgenic activities are involved.

Adult↗
PubMed1978

Plasma lecithin:cholesterol acyltransferase activity in hypophysectomized rats.

Hypophysectomy in rats induces a decrease in VLDL and HDL and an increase in LDL. To investigate the importance of lecithin:cholesterol acyltransferase (LCAT) for these changes, plasma LCAT activity was determined, both according to the methods of Stokke-Norum and Glomset-Wright. Plasma LCAT activity as assessed by both these methods decreased significantly after hypophysectomy, indicating a reduction in plasma enzyme concentration. Plasma total and free cholesterol increased slightly, while the concentration of cholesteryl esters and triglycerides remained unchanged. Blood sugar and FFA decreased. The osmotic resistance of the red cells was increased, and target cells were seen. There was a decrease in blood haemoglobin and haematocrit. Serum total protein concentration, electrophoresis, and plasma ALAT activity did not change. The observed changes in lipoproteins and LCAT following hypophysectomy can be partly explained by decreased liver secretion of both LCAT and VLDL. Because of the complex relationship between lipoproteins and LCAT, no clear-cut conclusions about the association between decreased HDL and LCAT can be drawn. The precise hormonal mechanisms controlling LCAT activity and lipoprotein metabolism remain to be solved.

Animals↗
PubMed1976

A clofibrate controlled trial of gemfibrozil in the treatment of hyperlipidaemias.

The efficacy of gemfibrozil as a hypolipidaemic agent was compared with that of clofibrate in a cohort of 80 subjects, half being treated with gemfibrozil and half with clofibrate. The majority of the subjects were either of the type IIa or IIb. Both drugs proved to be effective, though there were 13 non-responders in the clofibrate group, compared with 8 in the gemfibrozil group. The mean reduction in serum cholesterol induced by clofibrate was 23% and by gemfibrozil 19%. The corresponding falls in serum triglycerides were 36% and 43%. There were no serious side effects in either group. Analysed in this way, the relative efficiencies of gemfibrozil and clofibrate seem to be indistinguishable. Further studies are being directed towards evaluation of the individual responses to both treatments.

Arteriosclerosis↗