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Biomedical subjects

R Tuimala

Publications and source records attributed to R Tuimala.

At least 19 recordsLinked to original sources

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.

Apolipoprotein A-I↗

Neurologic sequelae after caesarean section.

BACKGROUND: Because pregnancy increases the sensitivity of nervous tissue to local anaesthetics, pregnant patients may be at higher risk of developing neurologic deficits after spinal block than non-pregnant patients. Therefore, we evaluated prospectively the incidence and type of neurologic symptoms after spinal anaesthesia with hyperbaric bupivacaine for caesarean section. METHODS: In this prospective follow-up study we recorded neurologic complications during anaesthesia and postoperatively until discharge from the hospital of 219 patients, who underwent caesarean section under spinal anaesthesia with hyperbaric bupivacaine (5 mg/ml, mean 13 mg). The patients filled in a questionnaire on the first and fifth postoperative days. In the case of complaints typical of neurologic symptoms they were checked first by the anaesthesiologist and, in the case of persistent symptoms, afterwards additionally by a neurologist. RESULTS: Twenty-six of 219 patients were not included in the further evaluation because of incomplete return of their questionnaires. Seventeen mothers (8.8%) complained of transient neurologic symptoms (TNSs), lasting mostly 1-2 days, in the buttocks and/or legs during the first three postoperative days. Eleven patients (5.7%) complained of postdural puncture headache. Two patients (emergency caesarean section because of protracted labour in one and elective caesarean section because of previous caesarean section in the other) complained of persisting pain or sensory abnormalities. Neither of them felt paraesthesia during lumbar puncture. CONCLUSION: Women after caesarean section under a spinal block seem to suffer more often from TNSs than non-pregnant women. The conclusions are, however, uncertain since we had no control group operated on under other than spinal anaesthesia. The persisting neurologic symptoms in two patients might also be due to the obstetric procedure itself. To find out about the validity and possible underlying causes of our results, we need randomised studies with control groups receiving epidural or general anaesthesia.

Adolescent↗

A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.

This double-blind, randomized, multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2) and 0.5 mg trimegestone (TMG) with a standard hormone replacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment of climacteric symptoms. The study was conducted over 13 cycles, each of 28 days, and involved 634 subjects, of whom 481 completed the study. The primary efficacy variable was the percentage of subjects who showed at least a 50% reduction from baseline in the mean daily number of hot flushes in cycle 3. This was observed in 98.5% of the subjects in the E2 + TMG group and 93.3% of the subjects in the E2V + NG group (95% confidence interval of the difference, -8.6, -1.9). Significant differences in favor of the E2 + TMG combination were observed in the reduction in the mean daily number and severity of hot flushes, and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment. There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerated and the incidences of adverse events were similar in the two treatment groups. Breast pain was the main adverse event, possibly related to treatment that resulted in discontinuation. The mean number of bleeding days per cycle was significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and comparable in both treatment groups. It was concluded that the E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms, and that its bleeding profile was favorable.

Double-Blind Method↗

Factors underlying changes in bone mineral during postpartum amenorrhea and lactation.

To determine the physiologic and habitual factors that may modulate changes in bone mineral density (BMD) postpartum, dual-energy X-ray absorptiometry was performed at the lumbar spine, right femoral neck and dominant distal radius immediately after delivery, after resumption of menses, and 1 year thereafter in a cohort of 41 healthy postpartum Finnish women aged 31.5 (SD 4.6) years. Mean durations of lactation and postpartum amenorrhea (PPA) were 7.7 (3.7) and 5.9 (2.9) months, respectively. After PPA, significant bone losses of 2%-4% were observed at the lumbar spine and femoral neck. Duration of PPA and different lactational variables explained (adjusted R2) from 21% to 27% of the variability in changes in BMD during PPA. A recovery to postpregnancy BMD levels was observed at the lumbar spine; in contrast BMD at the femoral neck showed only a partial recovery. The duration of unsupplemented lactation was weakly (adjusted R2 = 0.13) associated with recovery at the lumbar spine, while a long duration of total lactation also showed a weak association (adjusted R2 = 0.02) with delayed recovery at the femoral neck. In conclusion, a systematic bone loss occurs during PPA, and after resumption of menstruation BMD recovers despite continued lactation. However, the time of bony recovery back to postpregnancy level seems to be modulated slightly by lactation habits. It is obvious that the control of postpartum BMD changes is a multifactorial process that may be specific to the skeletal site of interest.

Absorptiometry, Photon↗

Why do postmenopausal women discontinue hormone replacement therapy?

OBJECTIVES: To study the prevalence and acceptance of hormone replacement therapy (HRT) in the Finnish population and to ascertain the factors leading to premature discontinuation of HRT. METHODS: A questionnaire survey was conducted among all women aged 50-60 selected from the age-sex register, 1065 women were identified and 884 (response rate 84%) agreed to participate. RESULTS: 111 women were premenopausal and 773 postmenopausal; 302 (39%) were current HRT users, 126 (16%) previous users and 345 (45%) non-users. Of the previous users 27% had used oestrogen for less than 6 months and 46% had ceased treatment within 1 year. The main reason for discontinuation was side-effects; 41% of the women had suffered from them. Fear of cancer (16%), recommendation of a physician (12%), inefficiency (4%), and advice of a friend (3%) were other causes of discontinuation. Of the current users, 20% had continuous side-effects from the treatment and 15% had been advised to discontinue the treatment. Eleven percent of current users and 11% of previous users reported not having received any information about HRT. CONCLUSIONS: in this survey, more than half of postmenopausal women had used HRT at menopause. Every third of the women had discontinued the treatment, mainly because of side-effects but also because of fear of cancer and advice of physicians.

Climacteric↗

Changes in bone mineral density during pregnancy and postpartum: prospective data on five women.

Areal bone mineral density (BMD, g/cm(2)) of five healthy women (aged 26-30 years) was measured at the lumbar spine, right femoral neck and dominant distal radius with dual-energy X-ray absorptiometry before pregnancy, immediately after delivery, 1 month after the resumption of menses and 1 year thereafter. Because of the small number of subjects, only individual changes in BMD that were greater than 2 radical2 times the short-term in vivo precision were considered as significant changes. To obtain a further perspective, the reproduction-related BMD changes were compared with twice the standard deviation (SD) of the BMD changes in healthy premenopausal women (about +/- 5%), and with the SD of the BMD in a cross-sectional sample of young healthy women. The duration of postpartum amenorrhea (PPA) and of lactation in our subjects ranged from about 2 months to 1 year and from 5 months to almost 2 years, respectively. No clear association between PPA and lactation could be seen. The magnitudes of reproduction-related BMD changes in general seemed not to differ substantially from about +/- 5% variability in BMD changes in healthy nonpregnant and nonlactating women. There was, however, some tendency toward systematic bone loss at the lumbar spine (about -3%) during pregnancy and at the femoral neck during PPA (about -5% as compared with prepregnancy data). Some individuals can yet show large, systematic bone losses comparable to 1 SD in magnitude. The site-specific reproduction-induced bone loss and consequent recovery are apparently multifactorial phenomena that may be related not only to duration and magnitude of lactation and/or duration of postpartum amenorrhea, but also to prevailing biomechanical and dietary factors, and other yet unknown individually modulated factors.

Absorptiometry, Photon↗

GnRH analogues and uterine leiomyomas. Effect of hormone replacement therapy on cell proliferation.

Cell proliferation in uterine leiomyomas treated preoperatively with either nafarelin (400 microg/day) for 3 months (7 patients) or nafarelin plus hormone (oestradiol + norethisterone) add-back therapy (6 patients) was investigated by automatic image analysis of frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. GnRHa therapy decreased cell proliferation in leiomyomas to a level corresponding to the situation previously seen in postmenopausal leiomyomas. However, there was no consistent correlation between cell proliferation and shrinkage of leiomyomal size. The hormone add-back therapy moderated the influence of GnRHa on cell proliferation and completely blocked a decrease in size of leiomyomas in our patients.

Adult↗

In the dose range of 0.5-2.0 mg/kg, acetylsalicylic acid does not affect prostacyclin production in hypertensive pregnancies.

OBJECTIVE: To determine the dose of acetylsalicylic acid (ASA), that inhibits the production of the vasoconstrictive, aggregatory thromboxane A2 while sparing the production of the vasodilatory antiaggregatory prostacyclin. DESIGN: A controlled study comparing the effects of three doses of ASA on the production of thromboxane A2 and prostacyclin. METHODS: Seven pregnant hypertensive patients and five non-pregnant healthy women received 0.5, 1.0 and 2.0 mg/kg/day of ASA, each dose for 10-12 days, the treatment periods following each other immediately. Seven normotensive pregnant women served as controls and were given no ASA. Blood and urine samples were taken at baseline and after the treatment periods to determine serum thromboxane B2 and the urinary 2.3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxaneB2, the major stable metabolites of prostacyclin and thromboxane A2, respectively. RESULTS: The urinary excretion of 11-dehydrothromboxaneB2 was significantly higher in both hypertensive (34.9+/-18.3 pg/micromol creatinine) and normotensive (39.3+/-14.4 pg/micromol creatinine) pregnant women than in non-pregnant women (14.8+/-6.4 pg/micromol creatinine). The urinary excretion of 2.3-dinor-6-ketoprostaglandinF1alpha was also higher in normotensive pregnant women (93.9+/-50.9 pg/micromol creatinine) than in non-pregnant women (18.2+/-11.3 pg/micromol creatinine). The excretion rate of 2.3-dinor-6-ketoprostaglandinF1alpha in hypertensive patients was lower than in normotensive pregnant women (44.7+/-24.2 pg/micromol creatinine). At baseline the urinary 2.3-dinor-6-ketoprostaglandin F1alpha/11-dehydrothromboxaneB2 ratio was almost the same in the hypertensive patients (1.6) and in the non-pregnant women (1.2). The ratio was 2.6 in normotensive pregnant women. In the hypertensive group, already the lowest dose of ASA inhibited urinary 11-dehydrothromboxaneB2 excretion significantly. Because none of the doses of ASA inhibited 2.3-dinor-6-ketoprostaglandinF1alpha production, the 2.3-dinor-6-ketoprostaglandinF1alpha/11-dehydrothromboxaneB2 ratio was shifted in the favor of prostacyclin at all dose levels. In the non-pregnant women, even the highest dose level of ASA failed to affect the ratio. CONCLUSION: In the dose range of 0.5-2.0 mg/kg/day, ASA has a favorable effect on the ratio of prostacyclin to thromboxane A2 in hypertensive pregnancies.

Aspirin↗

Can climacteric women self-adjust therapeutic estrogen doses using symptoms as markers?

OBJECTIVES: To investigate if disappearance of climacteric symptoms during hormone replacement therapy (HRT) also means good therapeutic level of serum estradiol. The study group comprised of 32 postmenopausal women who had frequent climacteric symptoms. METHODS: The women increased the daily treatment doses of percutaneous estradiol every 2 weeks until they felt comfortable with it. Each woman continued at that treatment dose for up to 3 months. Blood samples for estradiol assay were drawn at baseline, every time before the estradiol dosage was increased and at the end of the study. Climacteric symptoms were scored according to the Kupperman menopausal index. RESULTS: Despite the relief of climacteric symptoms, serum estradiol concentration was at a menopausal level (< 50 pg/ml) in 22% of the women. In all, 45% of the subjects showed serum estradiol remaining under 60 pg/ml, 29% of the women showed levels of 60-100 pg/ml and 26% showed serum estradiol concentration more than 100 pg/ml. CONCLUSIONS: The disappearance of climacteric symptoms during HRT does not guarantee that estrogen levels are sufficiently high for obtaining long term benefits of HRT.

Administration, Cutaneous↗

CYP1A1 activity in renal cell carcinoma and in adjacent normal renal tissue.

Cytochrome P450-isoenzyme, CYP1A1, is responsible for the metabolic activation of several precarcinogenic environmental chemicals to their carcinogenic intermediates. Microsomal CYP1A1 activity in renal cell carcinoma (RCC) and in normal renal tissue was determined by measuring spectrofluorometrically the hydroxylation rate of benzo[a]pyrene. The study included 50 patients who underwent nephrectomy for RCC. Tissue specimens were taken from renal tumours and, as a control, from macroscopic normal renal tissue adjacent to the tumours. Normal renal tissues that were adjacent to poorly differentiated grade 3 tumours and/or to metastatic RCC contained significantly higher CYP1A1 activities than renal tissues next to well-differentiated (P = 0.02) and/or organ-confined tumours (P = 0.001). In conclusion, those patients who had tumours that could be considered aggressive on the grounds of poor cell differentiation or a metastatic feature of tumour, had remarkably higher CYP1A1 activities in their kidneys than the patients with less aggressive renal tumours.

Adult↗

Activin B: detection by an immunoenzymometric assay in human serum during ovarian stimulation and late pregnancy.

A recently developed immunoenzymometric assay for activin B has been characterized further by measurement during ovarian stimulation and pregnancy. The assay is based on a monoclonal anti-peptide antibody, anti-betaB(101-115). In addition to quantitative analyses, the antibody has been used for immunohistochemical localization of the activin betaB-subunit in human term placenta. Serum samples obtained from patients suffering from tubal factor infertility who were admitted for in-vitro fertilization (IVF) treatment protocols or from patients with proven fertility who were admitted for laparoscopic tubal ligation were collected. The aim was to correlate serum activin B concentrations with other parameters during IVF and with phases of the menstrual cycle. Serum samples obtained from healthy pregnant volunteers were studied to correlate activin B concentrations with clinical parameters. During the IVF treatment protocols, activin B was detectable in all patients studied, and a significant negative correlation was observed between serum activin B and oestradiol concentrations. On the other hand, no significant difference was observed in activin B concentrations when serum samples obtained from patients at different phases of the menstrual cycle were compared, and low concentrations of activin B were observed in the samples obtained from these patients. During pregnancy, a positive correlation was observed between serum activin B concentrations and gestational age. In immunohistochemical analyses of human placental tissue obtained from healthy parturients, the activin betaB-subunit was present in trophoblast, amniotic epithelial and Hofbauer cells. The results suggest a potential clinical application in female reproductive medicine for serum activin B measurements.

Activins↗

Antibodies against copper-oxidised and malondialdehyde-modified low density lipoproteins in pre-eclampsia pregnancies.

OBJECTIVE: To measure auto-antibodies against oxidatively modified low density lipoprotein (LDL) in pre-eclamptic pregnancies using two different techniques. DESIGN: Clinical study comparing pre-eclamptic and normal pregnancies. SETTING: Tampere University Hospital, Finland. POPULATION: Twenty-one primigravidae with pre-eclampsia and 13 healthy, normotensive primigravidae as controls. METHODS: The serum titers of antibodies against both malondialdehyde-modified and copper-oxidised LDL (MDA-LDL and copper-ox LDL) were analysed and related to parameters reflecting the severity of pre-eclampsia. RESULTS: There was a positive correlation (r = 0.58) between antibodies against MDA-LDL and copper-ox LDL in women with pre-eclampsia but not in healthy pregnant controls. The antibody levels against copper-ox LDL, but not against MDA-LDL, were higher in women with pre-eclampsia than in women with a normal pregnancy (P < 0.01). While the antibody titers against copper-ox LDL did not correlate with any parameter reflecting the severity of pre-eclampsia, those against MDA-LDL showed a positive correlation with the level of diastolic blood pressure (r = 0.54) and a negative correlation with platelet count (r = -0.61) in women with pre-eclampsia. CONCLUSION: There are increased titers of serum autoantibodies against copper-oxidised LDL in pre-eclampsia, which may reflect enhanced lipid peroxidation involving circulating lipoproteins.

3,4-Methylenedioxyamphetamine↗

Patient managed clinical trial.

We describe a trial design of postmenopausal hormone therapy. Our goal was to design a trial that allows more patient management than usual, would include placebo effect in the therapy, would imitate the normal practices of health care as much as possible, and would be based on ordinary health services. We gave women a randomized recommendation to use or not use hormone therapy, invited them to two discussion groups, and sent them two questionnaires. They were asked to consult their own physician and to pay for the therapy themselves. The design worked well regarding recruitment, but compliance after 6 months was not satisfactory. The main problems were the women's aversion to randomization, the attitudes of the women's own physicians, and the difficulty in stopping the use of hormone therapy. The last-mentioned problem could be avoided by different inclusion criteria. Unless societal perception of research can be changed, most solutions to improve compliance would lead toward traditional trial designs.

Chi-Square Distribution↗

Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone versus goserelin combined with estrogen-progestogen add-back therapy in the treatment of endometriosis.

OBJECTIVE: To investigate whether the addition of low-dose estrogen-P combination hormone replacement therapy (HRT) to GnRH agonist (GnRH-a) treatment for endometriosis reduces the pharmacologic side effects of such treatment without reducing efficacy and to determine the endocrinologic changes during treatment. DESIGN: Prospective, randomized, double-blind, placebo-controlled, comparative study of two drug regimens: 3.6 mg goserelin acetate in a 28-day SC depot formulation once monthly for 6 months plus either a combination of 2 mg 17 beta-E2 and 1 mg norethisterone acetate (NET) 1 mg or matching placebo tablets once daily for 6 months. SETTING: Multicenter study in three tertiary referral centers at university teaching hospitals and two central hospitals. PATIENTS: Women with laparoscopically confirmed symptomatic endometriosis were included in the study. RESULTS: Of the total of 109 patients screened, 93 were recruited and 88 patients were randomized to either the HRT or the placebo group. Four women were withdrawn because of various medical reasons, and 76 patients were followed-up for a total of 12 months. In terms of efficacy, there was no difference between the two drug regimens for objective or subjective response. There were significantly less postmenopausal symptoms in the patients treated with goserelin plus HRT compared with those treated with goserelin plus placebo. CONCLUSION: Goserelin diminished significantly the symptoms and laparoscopic scores of endometriosis. The addition of HRT did not reduce the efficacy of goserelin but diminished the postmenopausal symptoms during treatment.

Adult↗

Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy.

A total of 153 pregnant women, of at least 287 days' menstrual age, were studied in a prospectively designed cross-sectional trial. In addition to the non-stress test, contraction stress test, sonographic estimate of amniotic fluid and grade of placental maturation, Doppler measurements of the resistance index (RI) were taken in the umbilical artery, the uteroplacental arteries in the region of placental implantation and the fetal middle cerebral artery. Data were analyzed with regard to asphyxia and otherwise complicated fetal outcome. Furthermore, a possible relationship between grade of placental maturation, Doppler flow velocity waveforms and fetal outcome was investigated. Doppler resistance indices in the umbilical artery, uteroplacental arteries in the region of placental implantation and fetal middle cerebral artery did not change significantly with increasing gestation from 41 to 43 weeks. The grade of placental maturation on ultrasound examination was not related to fetal outcome or Doppler indices in the first two vessels. In all vessels examined in this study, the majority of Doppler measurements in pregnancies with subsequent asphyxia or otherwise complicated fetal outcome were within the 95% prediction interval for patients with normal fetal outcome. None of the patients showed absent diastolic flow in the umbilical artery. With the use of a cut-off value of RI = 0.62 in the umbilical artery, asphyxia could be predicted with 37% sensitivity and 75% specificity. Oligohydramnios and antpartum cardiotocography predicted asphyxia with 16% and 8% sensitivity and 95% and 96% specificity, respectively. Sensitivity for prediction of otherwise complicated fetal outcome by umbilical artery Doppler was only 7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

Atrial natriuretic peptide and cyclic guanosine-3'5'-monophosphate in hypertensive pregnancy and during nifedipine treatment.

Atrial natriuretic peptide exhibits natriuretic, diuretic and vasodilatory properties. We compared plasma concentrations of atrial natriuretic peptide, cyclic guanosine-3',5'-monophosphate (cGMP), electrolytes and urinary excretion of cGMP and electrolytes in hypertensive pregnant women to those in normotensive pregnant and normotensive non-pregnant women. Plasma atrial natriuretic peptide concentrations in hypertensive pregnant and normotensive non-pregnant women were equal, whereas in normotensive pregnant women it was lower (P < 0.05), than in non-pregnant. Urinary cGMP excretion was higher in both normotensive and hypertensive pregnant than in non-pregnant women (P < 0.01), whereas plasma cGMP levels were similar. A five-day nifedipine treatment (10 mg t.i.d.) had no effects on any of the variables. In hypertensive pregnancy, a reduction of systolic blood pressure by nifedipine correlated with the initial plasma atrial natriuretic peptide (P < 0.05) and a decrease in diastolic blood pressure with the initial plasma cGMP concentration (P < 0.05). The results of this small material suggest that plasma atrial natriuretic peptide concentration predicts the response to nifedipine in hypertensive pregnancy. However, the atrial natriuretic peptide-cGMP system does not seem to mediate the antihypertensive effect of nifedipine, while plasma atrial natriuretic peptide remained unaltered. Increased urinary cGMP excretion in both pregnant groups but lowered plasma atrial natriuretic peptide in normotensive pregnancy suggest other factors than circulating atrial natriuretic peptide to promote renal cGMP excretion during pregnancy.

Administration, Oral↗