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Biomedical subjects

J E Heikkinen

Publications and source records attributed to J E Heikkinen.

16 recordsLinked to original sources

Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other markers of bone turnover and bone mineral density.

Human serum contains two isoforms of tartrate-resistant acid phosphatase (TRACP) known as TRACP 5a and TRACP 5b with pH optima of 5.0 and 5.8, respectively. Preliminary data suggest that serum TRACP 5b is derived from osteoclasts and serum TRACP 5a from some other cells. It has been reported that heparin inhibits TRACP 5a but has no effect on the activity of TRACP 5b. Here we show that heparin has no effect on serum TRACP activity, as determined using our previously published immunoassay, suggesting that the immunoassay does not detect TRACP 5a. The change of serum TRACP 5b activity after 6 months HRT, determined by this immunoassay, correlated significantly with the changes of all markers of bone turnover determined, including serum N- and C-terminal propeptides of type I collagen and urinary-free deoxypyridinoline. Serum TRACP 5b activity was significantly elevated in patients with osteoporosis and had a significant negative correlation with bone mineral density (BMD). Serum TRACP 5a activity, determined by an immunoassay, showed no correlation with serum TRACP 5b activity, with BMD, or with any of the markers of bone turnover. These results show that serum TRACP 5b, but not 5a, reflects the bone resorption rate, and that our TRACP 5b immunoassay may be a specific method for the determination of the bone resorption rate from serum samples.

Acid Phosphatase↗

Optimizing continuous-combined hormone replacement therapy for postmenopausal women: a comparison of six different treatment regimens.

OBJECTIVE: We sought to determine the optimum estradiol valerate-medroxyprogesterone acetate regimens for efficacy and safety. STUDY DESIGN: We performed a 24-month, randomized, double-blind phase II study. Four hundred nineteen women who were postmenopausal for at least 3 years were placed in six parallel treatment groups and received 1 or 2 mg estradiol valerate with either 2.5 or 5 mg medroxyprogesterone acetate. In two groups the dose of estradiol valerate was increased from 1 to 2 mg estradiol valerate after 6 months. RESULTS: A marked improvement of climacteric symptoms was observed, and most women had no bleeding even during the first 3 months of treatment. The best bleeding pattern was achieved with 1 mg estradiol valerate and 2.5 or 5 mg medroxyprogesterone acetate, and in most groups the bleeding pattern improved over time. No cases of hyperplasia were observed. CONCLUSION: All regimens alleviated climacteric symptoms and provided excellent bleeding control, even during the early weeks of treatment. A choice of various dose combinations offers flexibility of dosing, thus enabling therapy to be tailored to the needs of individual women.

Bone Density↗

Influence of estrogen-progestin treatment on back pain and disability among slim premenopausal women with low lumbar spine bone mineral density. A 2-year placebo-controlled randomized trial.

STUDY DESIGN: A 2-year randomized controlled trial. OBJECTIVES: To examine the possible preventive or aggravating effect of estrogen-progestin treatment on the back symptoms of slim premenopausal women with low lumbar spine bone mineral density. SUMMARY OF BACKGROUND DATA: The incidence of back pain, sciatica, or both starts to increase clearly among 45-54-year-old Finnish women. METHODS: Forty-eight 39- to 49-year-old premenopausal women with a body mass index of 21 or less and a lumbar spine bone mineral density (L2-L4) of 1.1 +/- 1 g/cm3 or less compared with the normative population were recruited into the study. The women were assigned randomly to receive either estradiol-noretisteron acetate treatment or placebo. Back pain, symptoms, and disability were assessed with the Million and Oswestry questionnaires and pain drawings during the follow-up period at 0, 12, and 24 months. Inquiry also was made concerning previous back pain and sciatica history. RESULTS: There was a statistically significant decrease in nighttime back pain (P < 0.001) and the total Oswestry disability scores (P < 0.004) in the hormone-treated group compared with the control group during the follow-up, but no statistically significant differences were found in daytime back pain. At baseline, the cumulative incidence in a history of pain radiating from the buttock to the foot in this osteopenic study group was 31/48, (64.5%; 95% CI 50.5-78.6), which is much more than the predicted 20/48, (42.4%; 95% CI 39.0-45.7) at this age according to a previous population study. The cumulative incidence of at least one back pain episode 44/48, (91.7%; 95% CI 83.6-99.8) was somewhat higher in these participants than was predicted for a comparative population of women this age, 38/48 (79.2%; 95% CI 70.2-87.3). CONCLUSIONS: It seems that this regimen may have alleviating effects on nighttime back pain and functional back disability in slim osteopenic premenopausal women.

Adult↗

Influence of estrogen-progestin replacement therapy and exercise on lumbar spine mobility and low back symptoms in a healthy early postmenopausal female population: a 2-year randomized controlled trial.

The purpose of this study was to examine the influence of estrogen-progestin replacement therapy and exercise on the lumbar spine mobility and back symptoms of early postmenopausal women. The population sample consisted of 78 healthy, 49- to 55-year-old women, 0.5-5 years after menopause, who were randomized into three groups, two receiving different protocols of estradiol valerate combined with medroxyprogesterone acetate replacement therapy, and the third group a placebo. These groups were then randomized into exercise and control cases and monitored for 2 years. The mobility of the lumbar spine was measured and symptoms investigated using the Million and Oswestry pain and disability questionnaires and pain drawings at the baseline and after 1 and 2 years. During the follow-up, the mobility of the lumbar spine decreased in all six groups. The decrease was most evident in those who had been the most flexible at baseline (P < 0.0001). The decrease was less notable in the hormone replacement therapy groups than in the control group. When the replacement therapy groups were pooled together, the difference was significant at a P < 0.05 level. No difference was seen between the hormone combinations. The exercise intervention was insufficient to influence lumbar spine mobility. Only sporadic cases of back symptoms appeared and disappeared among the subjects during the follow-up, and no preventive or aggravating effects of hormone replacement therapy or the exercise program on symptoms were detected.

Disability Evaluation↗

Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss.

This study was performed to test the efficacy of short-term intravenous clodronate and etidronate in the prevention of postmenopausal bone loss. Healthy postmenopausal women, exhibiting a decreasing trend in bone mineral density, were randomized to five groups (clodronate at doses of 150, 300, and 600 mg; etidronate at a dose of 300 mg; and a placebo group) of 21-22 subjects. The drugs were administered intravenously three times with 1-week intervals, followed by regular evaluation for up to 24 months. During the first year, 300 mg of clodronate retarded bone loss significantly in the lumbar spine and femoral neck, where significant protection still persisted after 24 months. Other doses of clodronate (150 and 600 mg) were not bone protective. Etidronate (300 mg) retarded bone loss significantly in the lumbar spine up to 24 months, relative to placebo. Serum concentrations of procollagen I carboxy-terminal propeptide and urinary Ca2+ and hydroxyproline excretion decreased in all bisphosphonate groups during the first month after treatment, but the values returned later toward baseline. In the etidronate-group, serum osteocalcin concentrations also decreased significantly during the first 3 months of the study. Otherwise, no uniform serum responses to bisphosphonate-treatment were detected in circulating markers of bone formation, alkaline phosphatase, or osteocalcin. No significant differences in the serum concentrations of cross-linked carboxy-terminal telopeptide of type I collagen were detected between the groups. Patient acceptance of both bisphosphonates was excellent, and no drug-related adverse side effects were detected. These results suggest that infrequently repeated intravenous treatment with bisphosphonates may effectively counteract postmenopausal bone loss.

Absorptiometry, Photon↗

Comparison of muscle strength and bone mineral density in healthy postmenopausal women. A cross-sectional population study.

In this cross-sectional population study with 78 healthy 0.5-5 years postmenopausal, 49-55 year old females a significant simple linear correlation between lumbar spine LII-LIV bone mineral density and adjacent back extensor and flexor isometric muscle strength was found. With the stepwise multiple linear regression analyses the most significant predictors for lumbar spine LII-LIV and femoral neck bone mineral density were weight (partial R2) (R2 = 0.197, p = 0.0001; R2 = 0.157, p = 0.0009) and age (R2 = 0.056, p = 0.0205; R2 = 0.036, p = 0.0708). Height and isometric muscle strength and endurance of muscles were not significant predictors. Weight and age were the most significant predictors also for isometric muscle strength. The mobility of spine, body fat content and anaerobic threshold had no correlation on bone mineral density.

Absorptiometry, Photon↗

One year study of effects of an oestrogen-dominant oral contraceptive on serum high-density lipoprotein cholesterol, apolipoproteins A-I and A-II and hepatic microsomal function.

The effects over 1 year of an oestrogen-dominant oral contraceptive containing ethinylestradiol and levonorgestrel on serum high-density lipoprotein cholesterol, apolipoproteins A-I and A-II and liver microsomal enzyme activity assessed by antipyrine kinetics, were investigated in 21 healthy, young women. HDL cholesterol and apolipoprotein concentrations rose and hepatic microsomal enzyme activity fell during the first month of the treatment, and remained affected throughout the year. After discontinuation of treatment, the lipid and apolipoprotein concentrations and the microsomal enzyme activity returned to their pretreatment levels within 1 month. The drug, by reducing hepatic enzyme activity, may have influenced both the antipyrine elimination rate and the high-density lipoprotein concentration.

Adult↗

Pharmacokinetics of clonidine during pregnancy and nursing.

Pharmacokinetics of clonidine were examined in ten women during pregnancy, in nine during nursing, and in the newborns of these women. Clonidine crosses the placenta easily, and its concentrations were equal in maternal serum and umbilical cord serum. Amniotic fluid concentrations were up to four times that found in serum. Clonidine concentrations in milk were roughly twice that in maternal serum; in the serum of the newborns the concentrations were about half those of the mothers. All concentrations corresponded well to the doses of the drug. The neurologic examinations and assessments of serum electrolytes and blood glucose showed results parallel with those of newborns of nontreated mothers.

Amniotic Fluid↗

Life support for 10 weeks with successful fetal outcome after fatal maternal brain damage.

A 31 year old woman in whom subarachnoid and intracerebral haemorrhage occurred during the second trimester of pregnancy was sustained in intensive care with a respirator for 10 weeks. Computed tomography of the brain showed bilateral intraventricular haemorrhages. Because of drug resistant hypotonic episodes at 31 weeks' gestation caesarean section was performed, and a boy was delivered. The woman died of spontaneous cardiac arrest two days after caesarean section, and the boy showed normal development. Life support can be continued for several weeks in a modern intensive care unit after fatal insult to the brain even in a pregnant woman without affecting the fetus.

Adult↗

The effect of phenobarbital on serum hormone levels and their diurnal variations in pregnancy.

The effect of phenobarbital (PB) on serum hormones in late pregnancy was investigated. 18 pregnant women were studied before and after 2 weeks of PB treatment (100 mg per os, daily at 8 p.m.) by measuring serum estradiol, estriol, progesterone, testosterone, prolactin and cortisol concentrations. 7 pregnant women without PB therapy served as controls. Estradiol levels in the morning decreased, whereas those of estriol increased both in the morning and evening during PB treatment. The estriol/estradiol ratio increased in women on PB. PB affected the diurnal variation of hormones; the decrease in estradiol concentration between 8 a.m. and 8 p.m. was eliminated and the decrease in estriol concentration became more clear. PB did not significantly affect the serum levels of the other hormones investigated. As an enzyme-inducer PB may affect the fate of sex hormones.

Adolescent↗

Serum ferritin levels in pill and IUD users.

12 women using a low-dose combination oral contraceptive (OC) and 17 wearing a copper IUD were studied. Serum ferritin concentrations were measured before and 1, 3, and 6 months after commencing contraception. Ferritin levels in the iron-deficient range (below 50 mcg/l) were present in 5 (42%) and in 8 (47%) subjects, respectively, prior to the start of OCs or IUD insertion. The OC use induced only a temporary decrease in serum ferritin levels at the start of treatment, whereas 12 of 17 (71%) IUD users had reached iron-deficient levels by the end of the follow-up period. Thus, the use of OCs had no adverse effect on iron balance, but the monitoring of iron status and the administration of iron-replacement therapy seem to be indicated in the majority of women fitted with an IUD.

Biology↗

Phenobarbital pharmacokinetics and salivary and serum concentrations in pregnancy.

The pharmacokinetics and the ratio between salivary and serum concentrations of phenobarbital (PB) were determined in 10 women undergoing treatment in late pregnancy. An approximately 2.5-fold variation was measured in the apparent relative clearance rates of PB in the women studied. The means of the total clearance rate (0.255 L/h), the relative clearance rate (4.0 ml/h/kg of body weight), the elimination half-life (95 h), the elimination rate constant (0.0071/h), and the apparent volume of distribution (35.49 L) were within the ranges observed in nonpregnant subjects. The PB concentration in saliva was 34% of that in serum. Salivary and serum levels of PB correlated closely with each other. Serum gamma-glutamyl transpeptidase activity increased, and total bilirubin concentrations decreased during PB treatment, both of which can be linked to the PB-caused hepatic microsomal enzyme induction phenomenon. The variation in clearance rate emphasizes the importance of close monitoring of PB treatment of pregnant women. The results suggest that salivary PB measurements can be used with sufficient accuracy to predict PB concentrations in the serum and to optimize PB treatment during pregnancy.

Adolescent↗

Purification and biochemical characterization of rat skin cathepsin D.

The hemoglobin-hydrolyzing, acidic proteinase activity of rat skin was purified by using ammonium sulfate precipitation. Sephadex G-100 gel column chromatography, acid treatment, and DEAE-cellulose column chromatography, giving a purification coefficient of 182. The pH optimum, molecular size, substrate specificity, as well as inhibitor and activator sensitivity of the enzyme preparation, corresponded closely to those of cathepsin D. The enzyme activity was separated from cathepsin B1. The present status of the knowledge of skin cathespins is reviewed.

Ammonium Sulfate↗

Changes in thyroid function tests during phenobarbital treatment in late pregnancy.

The effect of phenobarbital treatment in late pregnancy on thyroid function tests was investigated in 16 women. Ten women in late pregnancy served as controls. Phenobarbital treatment for two weeks was associated with a significant decrease in serum thyroxine (T4) level and in the free thyroxine index (T3U x T4) of 18% and 16%, respectively. These changes were associated with a significant increase in serum thyrotropin concentration of 15%. gamma-Glutamyl transpeptidase activity increased, and serum bilirubin concentration decreased during phenobarbital treatment. The changes in the thyroid function test might reflect the effect of phenobarbital on thyroid hormone metabolism. The changes may have diagnostic importance in borderline cases of thyroid disease.

Adolescent↗

Nutrition during ten-week life support with successful fetal outcome in a case with fatal maternal brain damage.

A 31-year-old woman had fatal intracerebral bleeding at the beginning of the 21st week of gestation. After several days, there was evidence that the brain was dead. Combined enteral and parenteral nutrition was continued until the 32nd week of gestation when cesarean section was performed because of drug-resistant hypotension. A full-term normal 1600-g male was delivered and the later development of the child was normal. This case report demonstrates the possibility of providing nutritional requirements to the fetus even if the mother has had a fatal injury.

Adult↗