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.

A randomized, double-blind, placebo-controlled, cross-over pilot study on the use of a standardized hop extract to alleviate menopausal discomforts.

OBJECTIVES: To examine the efficacy of a hop extract (standardized at 100mug 8-prenylnaringenin per day) for relief of menopausal discomforts. METHODS: A 16-week randomized, double-blind, placebo-controlled, cross-over study was conducted with 36 menopausal women. The participants were randomly allocated to either placebo or active treatment (hop extract) for a period of eight weeks after which treatments were switched for another eight weeks. The Kupperman Index (KI), the Menopause Rating Scale (MRS) and a multifactorial Visual Analogue Scale (VAS) were assessed at baseline, and after eight and sixteen weeks. RESULTS: After 8 weeks, both active treatment and placebo significantly improved all outcome measures when compared to baseline with somewhat higher average reductions for placebo than for the active treatment. After 16 weeks only the active treatment after placebo further reduced all outcome measures, whereas placebo after active treatment resulted in an increase for all outcome measures. Although, the overall estimates of treatment efficacy (active treatment-placebo) based on linear mixed models do not show a significant effect, time-specific estimates of treatment efficacy indicate significant reductions for KI (P = 0.02) and VAS (P = 0.03) and a marginally significant reduction (P = 0.06) for MRS after 16 weeks. CONCLUSIONS: Whereas the first treatment period resulted in similar reductions in menopausal discomforts in both treatment groups, results from the second treatment period suggest superiority of the standardized hop extract over placebo. Thus, phytoestrogen preparations containing this standardized hop extract may provide an interesting alternative to women seeking relief of mild vasomotor symptoms.

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.

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.

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.

Bone mineral density and lipid changes during 5 years of follow-up in a study of prevention of breast cancer with toremifene in healthy, high-risk pre- and post-menopausal women.

A double-blind, randomised, placebo-controlled pilot study was initiated to evaluate the feasibility of chemoprevention with toremifene 60 mg/day in healthy women at high risk for breast cancer. Enrolment in the study was terminated earlier than planned because of slow patient accrual, although 13% of patients continued for 5 years. The revised efficacy outcomes were change in bone mineral density (BMD) from baseline at four skeletal sites, plus effects on serum lipids. In premenopausal women there was a trend for sustained increase in BMD during toremifene therapy after year 1 in lumbar spine. In postmenopausal women, toremifene had little or no effect on BMD trends. Levels of total and low-density lipoprotein (LDL) cholesterol were largely unchanged from baseline in premenopausal women treated with toremifene but were often slightly lower than in the placebo group during follow-up. Total and LDL cholesterol levels declined slightly from baseline in the postmenopausal women and were, at several points during the first 3 years, significantly lower than in the corresponding placebo group (p < 0.01). We conclude that: (a) assessment of toremifene 60 mg/day in chemoprevention will require further clinical trials; (b) toremifene 60 mg/day has no substantive negative effects on BMD in pre- or postmenopausal women and may exert a minor favourable influence (in particular, the effects of toremifene 60 mg/day on BMD in premenopausal women may make the drug an attractive alternative to tamoxifen 20 mg/day for that patient subset); (c) lipid effects of toremifene 60 mg/day are, at minimum, neutral and may be modestly favourable for reducing cardiovascular risk.

Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women.

OBJECTIVE: Selective estrogen receptor modulators (SERMs) are drugs that exhibit both estrogen agonistic and antagonistic effects that are tissue-specific. Ospemifene (FC-1271a) is a novel SERM compound, which has been shown in animal models to have estrogen-like effects on bone and the cardiovascular system, while having antiestrogen-like effects in uterus and breast. In this study, we investigated the effects of ospemifene on the uterine endometrium, vaginal maturation index and hormonal status in healthy postmenopausal women. METHODS: The study was conducted as a double-blind, placebo-controlled phase I study, where 40 healthy postmenopausal women volunteers were randomized to receive daily oral doses of ospemifene either 25, 50, 100 or 200 mg or placebo for 12 weeks. Vaginal ultrasonography and endometrial biopsy were performed and vaginal maturation index determined at baseline and at 12 weeks' visit. Serum concentrations of estradiol, luteinizing hormone, follicle stimulating hormone (FSH), sex-hormone binding globulin (SHBG), parathyroid hormone and prolactin were determined from samples taken at baseline, at 4 days and at 4, 12, and 16 weeks' visits. Climacteric symptoms were assessed using 12 visual analogue scales (VAS) at baseline and at the end of the study. RESULTS: No clinically significant changes were seen in endometrial thickness at any dose level. Ospemifene exerted a very weak estrogenic effect on endometrial histology. On the other hand, it induced a clear estrogenic effect on vaginal epithelium. Among the endocrine parameters only FSH and SHBG showed significant dose dependent changes; FSH decreased and SHBG increased during the treatment. In general, ospemifene was well tolerated. The 25 and 50 mg doses tended to reduce climacteric symptoms, but no statistically significant differences were observed between different doses of ospemifene and placebo. The highest dose level (200 mg) induced more subjective adverse reactions, especially hot flushes, than lower doses. CONCLUSION: Our study suggests that a safe and well tolerated dose of ospemifene for potential clinical use may be between 25 and 100 mg. Further studies are needed to substantiate the results of this Phase I pilot study.

Speech sounds learned by sleeping newborns.

It is not yet clear whether humans are able to learn while they are sleeping. Here we show that full-term human newborns can be taught to discriminate between similar vowel sounds when they are fast asleep. It is possible that such sleep training soon after birth could find application in clinical or educational situations.

Climacteric vasomotor symptoms do not predict nocturnal breathing abnormalities in postmenopausal women.

OBJECTIVE: To study the association of climacteric vasomotor symptoms and nocturnal breathing abnormalities in a sample of healthy postmenopausal women. METHODS: Out of 71 postmenopausal women who took part in a large sleep study, 65 women were included into the present study. Sleep was monitored with polysomnography and nocturnal breathing with a static-charge sensitive bed and a pulse oximeter. Climacteric vasomotor symptoms were scored daily for 14 days and levels of oestradiol and FSH were measured in the serum. RESULTS: Altogether 21 (32.3%) women had some degree of breathing abnormalities during the study night. The occurrence of clinically significant sleep apnoea was low (1.5%) and of moderate type (OP-2). In contrast, increased respiratory resistance pattern, typical for partial upper airway obstruction, was frequent (16.9%). Seventy-eight per cent of the women had arterial oxyhaemoglobin desaturation events, but only in 4.6% of the women these events occurred more than 5 times/h of time in bed. Older women had more simple periodic breathing (P-1) and lower mean arterial oxyhaemoglobin saturation (SaO(2)). Body mass index (BMI) correlated with the apnoea frequency (OP-2) and inversely with the mean SaO(2). The severity of climacteric vasomotor symptoms or serum oestradiol concentration did not correlate with nocturnal breathing abnormalities. CONCLUSIONS: Nocturnal breathing abnormalities, especially partial upper airway obstruction, are common in postmenopausal women, but climacteric vasomotor symptoms do not predict their occurrence or severity. Increasing age and high BMI are important determinants of nocturnal breathing abnormalities.

Sixty thousand woman-years of experience on the levonorgestrel intrauterine system: an epidemiological survey in Finland.

OBJECTIVE: An epidemiological survey was carried out in Finland to establish the performance of the levonorgestrel intrauterine system (LNG-IUS) in a large population of women regularly using the system for contraception. STUDY DESIGN: All women who had LNG-IUS inserted between 1990 and 1993 were sent a questionnaire with questions about general health status, reproductive and contraceptive history and gynecological problems and a set of questions about their experience on the LNG-IUS. RESULTS: The women who had a LNG-IUS inserted between April 1990 and December 1993 were asked to participate in an epidemiological survey. At the insertion visit, the women were asked to fill in a questionnaire, to consent to further use of the information by signing their initials and to return the questionnaire to the manufacturer. The number of returned forms was 23,885. The names and addresses of these women were acquired from the National Register and a questionnaire with 75 questions was sent to them. Of the questionnaires, 75% were returned. Experience covered 58,600 woman-years. The mean age of the users of the LNG-IUS was 40 years. Most of them (99.3%) were parous, most often with two or three children. The cumulative 5-year Pearl index was 0.18 and there were 108 pregnancies in the study population during the use of the LNG-IUS. The continuation rates for 1, 2, 3, 4 and 5 years were 0.94, 0.87, 0.82, 0.76 and 0.65, respectively. Removal before the full 5 years was most common among the youngest age group. Bleeding disorders, infections and pain during LNG-IUS use were associated with the highest risk for discontinuation. The risk of premature removal was markedly diminished among women with totally or occasionally missed periods. CONCLUSIONS: The response rate to the survey was high and the sample studied was exceptionally large. The continuation rate of LNG-IUS was high up to 5 years. The symptoms associated with premature removal agreed with results from earlier randomized studies of the LNG-IUS.

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.

Sixty thousand woman-years of experience on the levonorgestrel intrauterine system: an epidemiological survey in Finland.

OBJECTIVE: An epidemiological survey was carried out in Finland to establish the performance of the levonorgestrel intrauterine system (LNG-IUS) in a large population of women regularly using the system for contraception. STUDY DESIGN: All women who had LNG-IUS inserted between 1990 and 1993 were sent a questionnaire with questions about general health status, reproductive and contraceptive history and gynecological problems and a set of questions about their experience on the LNG-IUS. RESULTS: The women who had a LNG-IUS inserted between April 1990 and December 1993 were asked to participate in an epidemiological survey. At the insertion visit, the women were asked to fill in a questionnaire, to consent to further use of the information by signing their initials and to return the questionnaire to the manufacturer. The number of returned forms was 23,885. The names and addresses of these women were acquired from the National Register and a questionnaire with 75 questions was sent to them. Of the questionnaires, 75% were returned. Experience covered 58,600 woman-years. The mean age of the users of the LNG-IUS was 40 years. Most of them (99.3%) were parous, most often with two or three children. The cumulative 5-year Pearl index was 0.18 and there were 108 pregnancies in the study population during the use of the LNG-IUS. The continuation rates for 1, 2, 3, 4 and 5 years were 0.94, 0.87, 0.82, 0.76 and 0.65, respectively. Removal before the full 5 years was most common among the youngest age group. Bleeding disorders, infections and pain during LNG-IUS use were associated with the highest risk for discontinuation. The risk of premature removal was markedly diminished among women with totally or occasionally missed periods. CONCLUSIONS: The response rate to the survey was high and the sample studied was exceptionally large. The continuation rate of LNG-IUS was high up to 5 years. The symptoms associated with premature removal agreed with results from earlier randomized studies of the LNG-IUS.

Pharmacokinetics of (deaminohydroxy)toremifene in humans: a new, selective estrogen-receptor modulator.

PURPOSE: New selective estrogen-receptor modulators for the treatment and prevention of osteoporosis, cardiovascular disease and breast cancer are currently the focus of intense research. (Deaminohydroxy)toremifene (Z-2-[4-(4-chloro- 1,2-diphenyl-but-1-enyl)phenoxy]ethanol; FC-1271a) has been shown to prevent bone resorption in rats while having no or weak estrogen-like effects on the uterus, which makes it a good candidate drug for osteoporosis prevention. Our purpose here was to examine the pharmacokinetics of (deaminohydroxy)toremifene in humans included in two phase-I studies. METHODS: The first was a single-dose, dose-escalation study with 28 healthy male volunteers. Doses ranged from 10 mg to 800 mg. The second study was conducted during a 12-week period with 40 healthy, post-menopausal women, who received repeated oral doses of 25-200 mg. Standard pharmacokinetic parameters were assessed. RESULTS: In the single-dose study, time to reach peak concentration (tmax) ranged from 1.3 h to 4.0 h; peak concentration (Cmax) ranged from 15 ng/ml to 445 ng/ ml; and the estimated terminal elimination half-life (mean +/- SD; t1/2) was 24.8 +/- 7.0 h. In the repeated-dose study, tmax ranged from 1.9 h to 2.6 h at 6 weeks and from 2.5 h to 2.9 h at 12 weeks. Cmax ranged from 295 ng/ml to 1,043 ng/ml at 6 weeks and from 25 ng/ml to 1211 ng/ml at 12 weeks. The average t1/2 at all dose levels was 29.7 +/- 1.5 h (overall mean +/- SD). Strong linear correlations between the dose and Cmax and between the dose and the area under the curve were observed in both studies. CONCLUSION: Our results indicate that (deaminohydroxy)toremifene has pharmacokinetics suitable for single daily dosing. The prophylactic use of this agent in women susceptible to development of osteoporosis, cardiovascular disease and breast cancer could, therefore, be tested using a once-daily dosing schedule similar to those of other hormone-replacement therapy regimens.

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.

Expression of insulin-receptor substrate-1 and -2 in ovaries from women with insulin resistance and from controls.

OBJECTIVE: To evaluate the role of insulin-receptor substrate (IRS)-1 and -2 in ovary dysfunction in women with insulin resistance. DESIGN: Immunoblotting and immunohistochemical analyses of the localization and staining intensity of IRS-1 and IRS-2 in the ovaries of women with the polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. SETTING: Department of Obstetrics and Gynecology, Turku University Central Hospital. PATIENT(S): Sections of ovary were obtained at the time of cesarean section from five volunteers without medical complications and three patients with gestational diabetes mellitus. Paraffin-embedded ovary sections were selected from those on file from the department of pathology; four were from women with a histologic diagnosis of PCOS and seven were from women with endometriosis (controls). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Protein expression of IRS in human ovary samples. RESULT(S): Immunoblotting with specific monoclonal and polyclonal antibodies showed the presence of 165-kDa and 183-kDa proteins that corresponded to the size of IRS-1 and IRS-2, respectively, in normal pregnant ovaries and human cultured follicles. Immunohistochemical staining showed that positive IRS-2 expression in antral follicles was restricted to theca internal cells in ovulatory ovaries but was distributed widely in all compartments of follicles in different stages in polycystic ovaries. Compared with follicles at a similar stage of development in ovulatory ovaries, follicles in polycystic ovaries showed decreased staining for IRS-1 in granulosa cells but increased staining for IRS-2 in theca internal cells. These features of IRS-1 and -2 expression were also noted in preantral and atretic follicles from patients with gestational diabetes mellitus compared with those who had uncomplicated pregnancy. CONCLUSION(S): This study highlights a shift of the follicular insulin signal protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestational diabetes mellitus.

Androgen excess contributes to altered growth hormone/insulin-like growth factor-1 axis in nonobese women with polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between ovarian androgen excess and impaired growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: A prospective, controlled clinical study. SETTING: Reproductive Endocrine Unit, Department of Obstetrics and Gynecology, Jinling Hospital, Nanjing University School of Clinical Medicine. PATIENT(S): Six patients with PCOS with both clomiphene resistance and gonadotropin hyperreponsiveness and six controls with regular cycles, matched for age and body mass index (BMI). INTERVENTION(S): Bilateral ovarian wedge resection (OWR) was performed to induce ovulation surgically for these refractory women with PCOS. A GH stimulation test with oral L-dopa was arranged for controls and for patients with PCOS before and again 6 months later after OWR. MAIN OUTCOME MEASURE(S): Plasma GH, IGF-1, FSH, LH, testosterone, androstenedione, estradiol, progesterone, prolactin, insulin, and glucose. RESULT(S): Basal levels and areas under the response curve of GH and GH-IGF-1 ratio to L-dopa were significantly lower in patients with PCOS before surgery than those of controls. The OWR in patients with PCOS obviously reduced their androstenedione and testosterone levels and insulin-glucose ratios, and increased the GH and GH-IGF-1 responses to L-dopa. CONCLUSION(S): Impaired somatotrophic axis caused by a defect in central dopaminergic activity may be responsible for severe anovulation in these women with PCOS, which could be reversed by removing excessive androgens with OWR.

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.

Eclampsia in Finland in 1990-1994.

BACKGROUND: Eclampsia is a serious threat to both maternal and fetal well-being. We started the present study because no recent data are available on the incidence of eclampsia and the outcome of patients with this serious disorder in Finland. METHODS: The incidence of eclampsia in Finland in 1990-1994 was studied retrospectively. The data were retrieved from the National Birth Register and the Finnish Hospital Discharge Register. Patient records were reviewed. RESULTS: Seventy-seven cases of eclampsia were found in the hospital records, which gave an eclampsia incidence of 2.4 per 10,000 deliveries (95% confidence intervals 1.9 to 2.9). Eclampsia was preceded by severe pre-eclampsia in 84% and by mild pre-eclampsia in 8% of the patients. Ten mothers suffered from severe eclampsia-related complications but, fortunately, none of the mothers died. Perinatal mortality was 5%, and 33% of the newborns were small for gestational age. CONCLUSIONS: Eclampsia is rare in Finland. Its low incidence is probably due to improved neonatal care that allows earlier deliveries before the progress of preeclampsia to eclampsia.

Climacteric symptoms and sleep quality.

OBJECTIVE: To evaluate the effect of climacteric vasomotor symptoms on sleep quality measured by self-report and polysomnography in postmenopausal women. METHODS: Seventy-one healthy postmenopausal women were recruited, of whom 63 completed the study. Each subject recorded climacteric symptoms and subjective sleep quality for 14 days. Sleep quality was evaluated objectively by all-night polysomnography using the static charge-sensitive bed. RESULTS: During polysomnography, a high frequency of climacteric vasomotor symptoms was not associated with changes in sleep latency, percentage of sleep stages, number of arousals, sleep efficiency, or total sleep time. However, a high frequency of climacteric vasomotor symptoms (range 0-8.9, r = .60, P < .001), somatic symptoms (range 0-5.0, r = .25-.44, P < .05), and mental symptoms (range 0-5.0, r = .41-.51, P < .001) was related to impaired subjective sleep quality. In stepwise regression analysis, 32% of the impairment in subjective sleep quality was explained by vasomotor symptoms (P < .001), 14% by palpitations (P < .001), and 4% by mood instability (P = .029). High body mass index predicted impaired objective sleep quality, such as prolonged latencies to stage-2 sleep (r = .27, P = .031) and slow-wave sleep (r = .51, P = .003) and decreased oxygen saturations (r = -.54, P < .001). Older women had decreased sleep efficiency (r = -.27, P = .030) and lower oxygen saturations (r = -.36, P = .004). Serum estradiol level had only a minor effect on objective sleep quality. CONCLUSION: Impaired subjective sleep quality associated with climacteric vasomotor symptoms did not manifest as abnormalities in polysomnographic sleep recordings. Body mass index and age appeared to have the strongest effect on objective sleep quality.