The role of self-rated health in the association between chronic somatic diseases and climacteric-related symptoms.

OBJECTIVES: We have previously shown an association between several chronic somatic diseases and climacteric-related symptoms. This time, we investigated whether self-rated health (SRH) contributes to this association. METHODS: The Women's Health Questionnaire was used to evaluate the climacteric-related symptoms, and existence of the diseases was investigated in 3421 women (41-54 years). In our previous study, the associations were defined with multivariable analyses. In the present study, SRH (good, moderate or bad) was included as a covariate. RESULTS: Most of the previously found associations between the diseases and the symptoms lost their significance. Accordingly, SRH played an important role in the association between the diseases and the symptoms related to the climacteric. CONCLUSIONS: SRH seems to be of significant importance regarding the relationship between the chronic somatic diseases and the symptoms related to climacteric. Most of the diseases are not associated with the climacteric-related symptoms if the disease does not deteriorate the SRH. Thus, women's own perception of their health is crucial for their symptomatology.

Variations in policies for management of the third stage of labour and the immediate management of postpartum haemorrhage in Europe.

BACKGROUND: The EUropean Project on obstetric Haemorrhage Reduction: Attitudes, Trial, and Early warning System (EUPHRATES) is a set of five linked projects, the first component of which was a survey of policies for management of the third stage of labour and immediate management of postpartum haemorrhage following vaginal birth in Europe. OBJECTIVES: The objectives were to ascertain and compare policies for management of the third stage of labour and immediate management of postpartum haemorrhage in maternity units in Europe following vaginal birth. DESIGN: Survey of policies. SETTING: The project was a European collaboration, with participants in 14 European countries. SAMPLE: All maternity units in 12 countries and in selected regions of two countries in Europe. METHODS: A postal questionnaire was sent to all or a defined sample of maternity units in each participating country. MAIN OUTCOME MEASURES: Stated policies for management of the third stage of labour and the immediate management of postpartum haemorrhage. RESULTS: Policies of using uterotonics for the management of the third stage were widespread, but policies about agents, timing, clamping and cutting the umbilical cord and the use of controlled cord traction differed widely. For immediate management of postpartum haemorrhage, policies of massaging the uterus were widespread. Policies of catheterising the bladder, bimanual compression and in the choice of drugs administered were much more variable. CONCLUSIONS: Considerable variations were observed between and within countries in policies for management of the third stage of labour. Variations were observed, but to a lesser extent, in policies for the immediate management of postpartum haemorrhage after vaginal birth. In both cases, policies about the pharmacological agents to be used varied widely.

Effects of sympatholytic therapy on insulin sensitivity indices in hypertensive postmenopausal women.

Cardiovascular risk factors are often ineffectively controlled in hypertensive postmenopausal women, and moreover, some antihypertensive drugs may increase particular risk factors such as insulin resistance. In a multicenter, multinational (Finland, Sweden, Lithuania), double-blind, prospectively randomized study hypertensive obese postmenopausal women without hormone therapy (n = 98) were randomly assigned to receive treatment with either the centrally acting agent moxonidine, 0.6 mg/day, or with the peripherally acting atenolol, 50 mg/day, for 8 weeks. In addition to blood pressure measurements, insulin sensitivity was estimated by the quantitative insulin sensitivity check index (QUICKI) and by the insulin sensitivity index (ISI-Matsuda). Subgroup analysis in insulin-resistant women (fasting P-insulin > or = 10 mU/l) and blood pressure responders (diastolic blood pressure < or = 90 mmHg and/or reduction of blood pressure > or = 10 mmHg) were also carried out. Both atenolol and moxonidine led to a significant reduction in diastolic blood pressure of 9.5 mmHg and 6.2 mmHg, respectively. Among insulin-resistant women, an increase in the insulin sensitivity assessed by ISI was improved with moxonidine treatment (p = 0.025). A decrease in insulin sensitivity assessed by QUICKI was observed with atenolol treatment in women with fasting insulin level < 10 mU/l. In patients, in whom blood pressure was reduced, an improvement in insulin sensitivity (ISI) was associated with moxonidine treatment (p = 0.019), but not with atenolol treatment. The centrally acting sympatholytic agent moxonidine did reduce blood pressure somewhat less than atenolol, but it was associated with an improved metabolic profile in terms of decreased insulin resistance both in insulin-resistant postmenopausal women and in women with a significant blood pressure response.

Recent advances in contraception.

The world population is expected to increase by 2.6 billion to 9.1 billion in 2050. This will occur, if fertility decreases from today's 2.6 children to about 2 children per woman. If fertility were to remain at the present level, 34 million persons would be added annually by mid-century and thus the world population would reach 10.6 billion by 2050. The most notable increase in the world population will occur in third world countries. Therefore immense investments are being made to develop safe, reliable and easily used contraceptive methods. It has not proven easy. Further, acceptance of the methods has been called into question. And even their distribution would be very difficult although Population Council and organizations like it have put a lot of effort into that matter also. In addition, the methods should preferably be such that they could to some extent prevent the rapid spread of sexually transmitted infections. So, the task is not easy, but every effort must be made on this question also at governmental and international political levels. It is noteworthy that this kind of approach has been given more currency since the beginning of this millennium.

Salivary testosterone in hirsutism: correlations with serum testosterone and the degree of hair growth.

Testosterone (T) concentrations in saliva and serum were measured in 53 women with various degrees of hirsutism and hyperandrogenism. The bioavailability of T was judged by comparing the correlations among the grade of hirsutism, salivary testosterone (SaT), and serum total and free T (fT) and sex hormone-binding globulin (SHBG) levels. The effect of body mass index on the correlations was also studied. The high SaT concentrations [mean, 237.6 +/- 66.7 (+/- SD) pmol/L] compared to the serum fT concentrations (mean, 29.1 +/- 11.8 pmol/L) in hirsute women may reflect the bioavailability of albumin-bound T or an ability of the salivary glands to metabolize steroids. SaT was more closely related to the T/SHBG ratio (mean, 82.5 X 10(-3) +/- 54.8), reflecting the non-SHBG-bound fraction of T, than to serum fT, which might support the former theory. SaT correlated better to the degree of hirsutism (rho = 0.45; P less than 0.01) than did any of the serum T parameters or SHBG. The correlation between SaT and hirsutism was partly dependent on the effect of body mass index. After eliminating this effect, SaT still correlated with hair growth on the total body area (rho = 0.36; P less than 0.05). On the basis of the results, SaT seems to relate to the bioavailable fraction of the hormone and, thus, appears to be an optimal method for studying hirsute women.

Placental transfer and maternal midazolam kinetics.

Midazolam was given in a single 15-mg oral dose as a sedative the evening before elective cesarean section. Twelve hours later, levels of this new benzodiazepine were measureable in the fetomaternal entity in only one of 13 cases. After 15 mg midazolam orally or 0.05 mg/kg midazolam intramuscularly 15 to 60 min before elective cesarean section, there was evident transfer of drug into the placenta, but transfer took place more slowly than with diazepam. On the basis of kinetics derived from maternal serum concentrations after oral, intramuscular, or intravenous dosing, midazolam appears to have a rapid onset and short duration of action, which was also evident from subjective assessments by the patients. There was wide interindividual variation in the gastrointestinal absorption of midazolam in full-term pregnant women. Clinically, midazolam nevertheless seemed to be very useful for nocturnal sedation before elective cesarean section; it ensures a mean duration of sleep of about 6 hr and there are virtually no detectable levels of drug in the fetomaternal entity the next morning.

Growth and development of infants surviving respiratory distress syndrome: a 2-year follow-up.

In a regional birth cohort of 5,356 live-born infants, during 12 consecutive months, 46 (0.9%) infants suffered from respiratory distress syndrome. Ten of them died before the age of 2 years. The cause of death was respiratory distress syndrome in two cases, intracerebral hemorrhage in four cases, asphyxia in one case, and congenital erythropoietic anemia in one case. Of the 36 survivors, 34 could be traced for the follow-up. Growth and development of the survivors with respiratory distress syndrome were compared with that of 3,375 term infants in the birth cohort with birth weights at the tenth percentile or above with no risk factors recognized during pregnancy, labor, delivery, or the neonatal period. Normal development was found in 85% of the survivors with respiratory distress syndrome and 99% of the control infants at the age of 2 years. Intracerebral hemorrhage and low one- and five-minute Apgar scores were associated with unfavorable outcome at 2 years in the survivors with respiratory distress syndrome. The developmental scores were significantly poorer than those of the controls at 2 years for gross motor, audiovisual, and psychosocial categories, whereas for fine motor development, the difference disappeared by the 2 years of age. The growth of the survivors with respiratory distress syndrome was satisfactory even if their heights remained below that of their control peers.

Colloid osmotic pressure of umbilical cord plasma in healthy and sick newborn infants.

Colloid osmotic pressure of umbilical cord plasma was measured in 242 healthy infants, in 34 infants with respiratory distress syndrome (RDS), in 18 infants with asphyxia, in 13 infants who were small for gestational age, in 15 infants born to mothers with diabetes mellitus, and in 18 infants born to mothers with pregnancy-induced hypertension. In healthy infants, colloid osmotic pressure correlated highly significantly with umbilical cord blood total protein level, gestational age, and birth weight. In infants with RDS, no correlation between colloid osmotic pressure and gestational age or birth weight was found. Infants with RDS and gestational age between 36 and 38 weeks had significantly lower colloid osmotic pressure than healthy infants, whereas colloid osmotic pressure of infants with RDS and gestational age between 32 and 35 weeks did not differ from that of healthy infants of corresponding gestational age. Healthy term infants delivered by cesarean section had significantly lower colloid osmotic pressure than infants delivered vaginally. Infants with asphyxia had significantly higher colloid osmotic pressure than healthy infants. Colloid osmotic pressure is related to the lung maturity of the near-term and term neonate. Infants with a colloid osmotic pressure greater than 16 mm Hg are unlikely to develop RDS.

Review of beta-lactam antibiotics in pregnancy. The need for adjustment of dosage schedules.

beta-Lactam antibiotics represent the oldest class of antibiotics used in the treatment of infections, and benzylpenicillin (penicillin G) is still the most commonly used antibiotic agent during pregnancy. There is a number of studies to suggest that the pharmacokinetics of beta-lactam antibiotics are altered during pregnancy, indicating faster elimination of these antibiotics and lowered plasma concentrations. These changes are largely related to the physiological changes taking place in the maternal body. Generally, drugs are used cautiously during pregnancy, and dosages used may sometimes be inadequate. With regards to antibiotic agents, assurance of adequate therapy by applying pharmacokinetic knowledge when dosage schedules are designed should be a major concern so that the pregnancy is protected from the hazards of infection.

Polymorphisms at the Werner locus: II. 1074Leu/Phe, 1367Cys/Arg, longevity, and atherosclerosis.

Werner syndrome (WS) is a progeroid syndrome caused by autosomal recessive null mutations at the WRN locus. The WRN gene encodes a nuclear protein of 180 kD that contains both exonuclease and helicase domains. WS patients develop various forms of arteriosclerosis, particularly atherosclerosis, and medial calcinosis. The most common cause of death in Caucasian subjects with WS is myocardial infarction. Previous studies have identified specific polymorphisms within WRN that may modulate the risk of atherosclerosis. Population studies of the 1074Leu/Phe and 1367Cys/Arg polymorphisms were undertaken to evaluate the role of WRN in atherogenesis. Frequencies of the 1074Leu/Phe polymorphisms in Finnish and Mexican populations revealed an age-dependent decline of 1074Phe/Phe genotype. In Mexican newborns, but not in Finnish newborns, the 1074Leu/Phe and 1367Cys/ Arg polymorphisms were in linkage disequilibrium. Among coronary artery disease subjects, there was a tendency for the 1074Phe allele to be associated with coronary stenosis in a gene dose-dependent manner. Furthermore, the 1367Arg/Arg genotype predicted a lower degree of coronary artery occlusion, as measured by NV50, when compared to the 1367Cys/Cys or 1367Cys/Arg genotypes. However, these tendencies did not achieve statistical significance. Samples from Mexican patients with ischemic stroke showed a trend of haplotype frequencies different from that in a control group of Mexican adults. These data support the hypothesis that WRN may mediate not only WS, but may also modulate more common age-related disorders and, perhaps, a basic aging process.

Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians.

The Werner syndrome gene (WRN) encodes a novel helicase of 1,432 amino acids. Homozygous mutations, all of which result in the truncation of the protein, lead to Werner syndrome. However, little is known about the role of WRN in "normal" aging. We have identified four missense polymorphisms and four conservative polymorphsims in WRN gene. A single study showed that a polymorphism at amino acid 1367 Cys(TTG)/ Arg(CTG) is associated with a variation in risk of myocardial infarction among a Japanese population. The 1367 Cys/Arg polymorphism was examined during aging in three different populations: Finnish, Mexican, and North American. The frequencies of 1367 Cys were higher than those of 1367 Arg in all the populations examined, though the frequencies varied among populations. The frequency of the 1367 Arg allele, thought to be protective against myocardial infarction in a Japanese population, was approximately three times higher in the North American and Finnish adult populations. When newborns and centenarians were compared within the Finnish population, no differences were observed in the proportions of 1367 Cys/Arg across age groups. Within the Finnish population, we confirmed a significant decrease of the APOE epsilon2 allele and an increase in the epsilon4 allele in newborn infants compared with centenarians. Thus, unlike the APOE polymorphism, there is no evidence of an association of this WRN polymorphism with longevity.

Ovarian-adrenal cross-talk in polycystic ovary syndrome: evidence from wedge resection.

OBJECTIVE: To determine whether the ovary influences adrenal androgen secretion in women with polycystic ovary syndrome (PCOS). DESIGN: Six PCOS-affected patients with clomiphene resistance and gonadotrophin hyperresponsivity, and six controls with regular ovulatory cycles, matched for age and body mass index. METHODS: Bilateral ovarian wedge resection was performed to induce ovulation surgically for these refractory women with PCOS. The adrenal androgen secretions were evaluated in PCOS patients before and again 6 months after this surgery, and in the controls, using an ACTH stimulation test (0.25mg synthetic ACTH(1-24)). RESULTS: Biochemically, basal levels and the maximum net increases (Delta) of 17-hydroxyprogesterone (17-OHP) and androstenedione, Delta17-OHP/Delta progesterone and Delta androstenedione/Delta17-OHP ratios in response to exogenous ACTH were significantly higher in PCOS patients before operation than those of controls. This purely ovarian surgery in women with PCOS was found to significantly reduce their basal androstenedione, testosterone and LH levels, insulin/glucose ratio, and post-corticotrophic Delta17-OHP, Delta androstenedione, Delta17-OHP/Delta progesterone and Delta androstenedione/Delta17-OHP, without obvious changes in FSH, oestradiol, sex hormone-binding globulin, Delta dehydroepiandrosterone, Delta dehydroepiandrosterone sulphate, Delta aldosterone and Delta cortisol values. CONCLUSIONS: Ovarian hyperandrogenicity from polycystic ovary may contribute to the enhanced adrenal P450c17alpha activity and subsequent Delta(4) androgen reserve revealed by the pharmacological corticotrophin stimulation in our special PCOS cases.

Uterine and umbilical flow velocity waveforms in the supine hypotensive syndrome.

Changes in central hemodynamics and uterine and umbilical artery flow velocity waveforms were studied in ten healthy women 33-41 weeks pregnant who had signs of the supine hypotensive syndrome. When changing the position from left lateral recumbency to supine, there was an initial increase in mean arterial pressure (MAP) of 13% and in maternal heart rate of 30%. After this, the MAP decreased by 19% and, simultaneously, a 26% increase (P = .002) in uterine artery systolic/diastolic (S/D) ratio was recorded. When the changes in MAP and in the uterine artery S/D ratio were compared, the response was slower and recovery faster in the uterine circulation. Two patients evidenced a transient deceleration in the fetal heart rate and a simultaneous increase in the umbilical artery S/D ratio.

The need for adjustment of dosage regimen of penicillin V during pregnancy.

OBJECTIVE: To determine whether the normal regimen of dosage of oral penicillin V is relevant during pregnancy. METHODS: Twelve pregnant and six nonpregnant women volunteered for the study. Six women were in the second trimester of pregnancy (mean +/- standard deviation 19 +/- 7 weeks' gestation) and six women were in the third trimester (35 +/- 2 weeks). All of the women took 1 x 10(6) IU phenoxymethylpenicillin orally, and multiple blood and urine samples were obtained. Assays were performed by means of a disk agar diffusion method. The results were compared by Mann-Whitney U test. RESULTS: Compared with nonpregnant women, pregnant women had smaller area under the curve values (433 +/- 93 minutes.IU/mL, P < .05 in the second trimester; 550 +/- 220 minutes.IU/mL in the third trimester) and a shorter half-life (57 +/- 56 minutes in the second trimester; 34 +/- 21 minutes, P < .05 in the third trimester). Plasma and renal clearances were faster in the pregnant women. CONCLUSION: Elimination of penicillin V is enhanced during pregnancy, necessitating either a shorter dosing interval (6-8 hours) or an increased dose with the standard dosing interval.

Growth discordancy in twin pregnancies: a risk factor not detected by measurements of biparietal diameter.

Among 460 twin pregnancies delivered at the University Central Hospital of Turku from 1970 to 1981, there were 41 (8.9%) with a weight difference of 25% or more between twins when calculated from the weight of the larger twin. The perinatal death rate in the first group (9.7%) was significantly higher (P less than .01) than the perinatal death rate (3.7%) in the group with the weight difference of less than 25%. The intrauterine mortality rate, in particular, was significantly increased (P less than .001) in the group with 25% or more difference being 6.5-fold when compared with the more difference being 6.5-fold when compared with the group with the lower weight difference. Among 271 twin pregnancies examined by ultrasound one to two weeks before delivery, there were 31 (11.4%) pairs of twins with a 3-mm or more difference in biparietal diameter, 11 (4.1%) with a 4-mm or more difference, and seven (2.6%) with a 5-mm or more difference. The sensitivity of measurements of biparietal diameter to detect the growth discordancy was 9 to 35%, the specificity 90 to 98%, and the positive predictivity 23 to 29%. This study indicates that a divergent growth pattern in twin pregnancy carries an elevated risk of intrauterine death, especially for the smaller twin. Measurement of biparietal diameter is not a method sensitive enough to detect these high-risk twin pregnancies.

The hemodynamic effects of maternal hypo- and hyperoxygenation in healthy term pregnancies.

OBJECTIVE: To evaluate the hemodynamic effects of maternal hypo- and hyperoxygenation in normal term pregnancy. METHODS: Ten healthy women between 35-41 weeks' gestation were exposed to 10% oxygen in inspired air for 10 minutes and, after a 5-minute recovery period, to a stepwise increase in oxygenation with 50 and 100% oxygen for 10 minutes. Maternal ventilation, hemodynamics, and oxygenation were assessed noninvasively, and maternal and fetal vascular responses were assessed with pulsed-wave color Doppler velocimetry. Computerized cardiotocography was used for fetal heart rate (FHR) analysis. RESULTS: Substantial maternal hypoxia was achieved and accompanied by a statistically significant rise in the maternal heart rate (from 89 +/- 11 to 104 +/- 16 beats per minute) and systolic blood pressure (from 123 +/- 13 to 131 +/- 13 mmHg). Doppler measurements demonstrated a statistically significant decline in the pulsatility index (PI) of the maternal internal carotid artery (from 1.8 +/- 0.3 to 1.5 +/- 0.4) and an increase in the uterine artery PI (from 0.60 +/- 0.12 to 0.72 +/- 0.13). Baseline FHR, heart rate variability, and Doppler velocimetry in the umbilical artery and the middle cerebral artery showed no statistically significant changes. Hyperoxia did not cause changes in the maternal circulation, but the FHR decreased significantly (from 142 +/- 12 to 133 +/- 11 beats per minute). CONCLUSION: Acute short-term hypoxia modifies the maternal circulation, suggesting redistribution of maternal blood flow, but exerts no detectable effects on the healthy fetus. Maternal hyperoxygenation induces no apparent adverse effects.

Estrogen replacement therapy and nocturnal periodic limb movements: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy on nocturnal periodic limb movements in a randomized, double-masked, placebo-controlled, crossover trial. METHODS: Seventy-one healthy postmenopausal women volunteered in answer to a newspaper announcement; 62 women completed the follow-up. Frequency of nocturnal body movements was measured with the static-charge-sensitive bed and all-night polysomnographic recordings. Serum estradiol (E2) and FSH concentrations were also measured at baseline and after each treatment period. The power of the study setup was 94%. RESULTS: Nearly half the women presented with episodes of periodic limb movements (30 of 62 women, or 48%, during placebo and 27, or 44%, during estrogen therapy). In 17 (27%) during placebo and 19 (31%) during estrogen therapy, frequency of periodic limb movements exceeded index level 5 per hour while subjects were in bed. Incidence or intensity of movements, movement durations, and movement intervals did not change with estrogen therapy. The arousal index was similar during the two treatments (medians = 1.7 for placebo and 1.3 for estrogen, P =.758). Variations in serum E2 concentration, age, and body mass index did not explain variations in movement activity. CONCLUSION: Estrogen replacement therapy in doses used to control climacteric symptoms does not alter the incidence or intensity of nocturnal periodic limb movements.

Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine.

The short-term effect of 20 mg of oral nifedipine on maternal and fetal hemodynamics was investigated in 12 women with pregnancy-induced hypertension. Within an hour after nifedipine, the mean arterial blood pressure fell by 17% and there was a slight increase in maternal heart rate. There was also a decrease in the systolic/diastolic (S/D) ratio in the flow velocity waveform in the uterine artery in seven subjects, whereas the S/D ratio was unaffected in five subjects. Lack of change in the S/D ratio was associated with a less optimal pregnancy outcome: The neonates were delivered earlier, the rate of cesarean delivery was higher, and the newborns were smaller. No changes were observed in the fetal heart rate pattern or in the umbilical or middle cerebral artery flow velocity waveforms after nifedipine in hypertensive pregnancies.

Single dose of nifedipine in normotensive pregnancy: nifedipine concentrations, hemodynamic responses, and uterine and fetal flow velocity waveforms.

The short-term effect of 20 mg of oral nifedipine on maternal and fetal hemodynamics was investigated in ten healthy, normotensive women at 38 weeks' gestation admitted to the hospital for elective cesarean delivery. Within 1 hour after nifedipine administration, mean arterial pressure had decreased by 10% and a slight increase was observed in maternal heart rate. A statistically significant (P less than .01) decrease in the systolic-diastolic ratio was found in the flow velocity waveform from the uterine artery, but no change was seen in that from the arcuate artery. No changes were observed in the fetal heart rate pattern or in umbilical or thoracic aortic flow velocity waveforms. Nifedipine concentrations in the mother had no correlation with maternal or fetal hemodynamic responses. At delivery 2.5 hours after nifedipine ingestion, the umbilical venous-maternal ratio of nifedipine concentrations was 0.76.

Flow velocity waveforms in uterine and umbilical arteries during submaximal bicycle exercise in normal pregnancy.

Eight healthy women who were not conditioned athletes, at 35-38 weeks' gestation, performed a submaximal bicycle exercise test three times for 4 minutes each with stepwise increases (73 +/- 27, 114 +/- 29, and 161 +/- 16 W) of the work load. The target heart rate at the end of the last load was 170 beats per minute. The systolic-diastolic ratios (S/Ds) of flow velocity waveforms were measured with pulsed color Doppler ultrasound in the uterine and umbilical arteries immediately after each work load and during recovery. The heart rates at the end of each load (133 +/- 3, 156 +/- 3, and 173 +/- 7 beats per minute) corresponded to an average of 70, 83, and 92% of the calculated maximum heart rate. With the subject in the sitting position on the ergometer before exercise, the S/D in the uterine artery was 1.49 +/- 0.09, increasing gradually and significantly during the exercise to the maximum of 2.04 +/- 0.06 at 1 minute of recovery. Heart rate and S/D in the uterine artery correlated significantly (r = 0.58, P less than .01). Although the mean arterial pressure increased significantly during exercise from 92 +/- 6 to 109 +/- 10 mmHg, the significant decrease of the ratio of the mean arterial blood pressure and S/D suggests that the flow in the main uterine artery may decrease during intense exercise. No changes occurred in the S/D of the umbilical artery flow velocity, but the fetal heart rate increased significantly.