Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study.

OBJECTIVE: To evaluate whether parameters for calcium metabolism were associated with characteristics of polycystic ovary syndrome (PCOS). DESIGN: A prospective cohort study. METHODS: Ninety-one anovulatory, infertile women with PCOS patients underwent clomiphene citrate (CC) stimulation. Main outcome measures were parathyroid hormone (PTH); 25-hydroxyvitamin D3 (25OHD3); serum levels of calcium, phosphorus, magnesium, albumin, and total protein; the serum calcium-phosphorus product; LH; FSH; sexual hormone binding globulin; testosterone; and androstenedione. RESULTS: PTH correlated inversely with serum calcium (r=-0.235; P=0.004) and 25OHD3 (r=-0.664; P<0.001), whereas positive correlations were found between PTH and body mass index (BMI; r=0.270; P=0.010) and between PTH and testosterone (r=0.347; P=0.001). After stimulation with 50 mg CC, 57.1% (52/91) developed a follicle, whereas 26.4% (24/91) became pregnant. In a multivariate model to predict both follicle development and pregnancy, BMI and 25OHD3 deficiency were significant predictive parameters. CONCLUSIONS: 25OHD3 deficiency was an independent predictive parameter of CC stimulation outcome, in terms of follicle development and pregnancy. Our results suggest a substantial role of vitamin D in PCOS and infertility treatment in these patients.

The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents.

OBJECTIVE: To investigate possible age-related changes in associations between polymorphisms in the fat mass and obesity-associated (FTO) gene and higher body mass index (BMI). DESIGN AND SUBJECTS: Multilevel mixed regression models were used to examine associations between four FTO variants and longitudinal BMI profiles in non-Hispanic white and African American children and adolescents 8-17 years of age from two different longitudinal cohort studies, the Bogalusa Heart Study (BHS) and Project HeartBeat! (PHB). In the BHS, there were 1551 examinations of 478 African Americans and 3210 examinations of 1081 non-Hispanic whites; in PHB, there were 971 examinations of 131 African Americans and 4458 examinations of 505 non-Hispanic whites. RESULTS: In African Americans, no significant FTO associations with BMI were found. In non-Hispanic whites, linkage disequilibrium among all four variants made haplotype analysis superfluous, so we focused on the single-nucleotide polymorphism, rs9939609. In longitudinal multilevel models, the A/A genotype of rs9939609 was associated with higher BMI in non-Hispanic whites in both cohorts at all ages. A significant age-by-genotype interaction found only in the BHS cohort predicted that in those with the A/A genotype, BMI would be ∼0.7 kg m(-2) higher at age 8 and ∼1.6 kg m(-2) higher at age 17 than in those with A/T or T/T genotypes. The design of PHB limited follow-up of any single individual to 4 years, and may have reduced the ability to detect any age-by-genotype interaction in this cohort. CONCLUSIONS: The A/A genotype of rs9939609 in the FTO gene is associated with higher longitudinal BMI profiles in non-Hispanic whites from two different cohorts. The association may change with age, with the A/A genotype being associated with a larger BMI difference in late adolescence than in childhood, though this was observed only in the BHS cohort and requires verification.

Villous mucinous cystadenoma of the appendix in a postmenopausal woman.

OBJECTIVE: To present the case of a postmenopausal woman, who was suspected of having an ovarian cyst. Instead, a cystadenoma of the appendix was discovered during laparoscopy. METHODS: A 64-year-old postmenopausal nulliparous woman was admitted to our hospital because of a cystic lesion, which had been detected in the course of a routine gynecological examination. The patient underwent vaginal ultrasound, magnetic resonance tomography, and laparoscopy. RESULTS: During vaginal ultrasound, a dumbbell-shaped anechogenic cystic structure 70 x 32 x 22 mm in diameter was found in the region of the right adnexa. Magnetic resonance tomography revealed no additional information. During diagnostic laparoscopy, the cystic lesion was found to be a distended appendix. A laparoscopic appendectomy was performed. Subsequent histological analysis revealed a villous mucinous cystadenoma of the appendix with low-grade intraepithelial neoplasia. CONCLUSION: Gynecologists should routinely consider this disease in the differential diagnosis of right lower dumbbell abdominal cysts. Eleven percent to 20% of mucoceles are caused by mucinous cystadenocarcinomas, which carry the risk of peritoneal tumor implantation caused by rupture or laparoscopic resection. Therefore, it should be mandatory that a general surgeon be involved in the laparoscopic procedure and the conversion to laparotomy for resection of the structure.

Fourteen-year experience with laparoscopic ventrosuspension in patients with retroverted and retroflected uterus and pelvic pain syndromes.

BACKGROUND: In women with a retroverted uterus, who have dyspareunia, chronic pelvic pain, or dysmenorrhea, laparoscopic ventrosuspension of the uterus has been reported effective in achieving symptom relief. STUDY OBJECTIVE: To critically review our experience with our method of laparoscopic ventrosuspension. DESIGN: Cohort study (Canadian Task Force classification II-3). SETTING: Tertiary care center. PATIENTS: Sixty-three women who had undergone laparoscopic ventrosuspension for treatment of pain syndromes during 1995 through 2008. INTERVENTIONS: Laparoscopic ventrosuspension, and a questionnaire about the long-term outcome of the operation. MEASUREMENTS AND MAIN RESULTS: There were no adverse events except for 2 repeat operations within 3 postoperative days. Forty-nine women (77.8%) answered the questionnaire about long-term outcome, and in these patients, significant pain relief was achieved (p <.001). Pain levels decreased, based on a numeric rating scale, from a mean (SD) of 6.35 (1.92) to 0.97 (1.40) in patients without endometriosis, and from 6.93 (2.09) to 3.80 (2.08) in those with endometriosis. Of 34 patients without endometriosis, 1 (2.9%) stated that the operation had not led to symptom relief, compared with 4 of 15 (26.7%) with endometriosis (p = .03). CONCLUSION: Laparoscopic ventrosuspension is clearly beneficial in women with a retroverted and retroflected uterus who have pelvic pain syndromes, even in the long term.

Adrenaline: communication by electron emission. Effect of concentration and temperature. Product analysis.

BACKGROUND: Based on the recent findings about the ability of sexual hormones to emit electrons (e(aq) (-)) and to act as electron mediator, it was of interest to investigate adrenaline as an important neurotransmitter. MATERIALS AND METHODS: Highest purity adrenaline (ADR) and chemicals were used for preparation of aqueous solutions (pH ~7.4). The excitation of ADR in singlet state was achieved by irradiation of airfree aqueous solution with monochromatic UV light at λ = 254 nm. The emitted "solvated electrons" (e(aq) (-)) were scavenged by chloroethanol, where the quantum yield of Cl(-) ions, Q(Cl(-))=Q(e(aq) (-)). ADR degradation and formation of photolytic products were followed by HPLC analysis. RESULTS AND CONCLUSION: It was found that Q(e(aq) (-)) values decrease with increasing ADR concentration: for 2.5×10(-5) mol/L ADR was determined as Q(e(aq) (-))=6×10(-3), whereas for 1×10(-3) mol/L ADR was found to be 0.9×10(-3). This is explained by formation of associates in ground state, which consume a part of emitted e(aq) (-). As a main photolytic product aminochrome was determined.

Hand problems in migrant farmworkers.

PURPOSE: We estimated the self-reported prevalence of hand problems and identified factors associated with them in this cross-sectional study including 390 farmworkers representing 180 migrant farmworker families from Starr County, Texas. METHODS: A two-year cohort study (1999-2001), "Injury and Illness Surveillance in Migrant Farmworkers (MANOS), "provided the data for this study. We calculated the prevalence for the two-year follow-up period, stratified by family member and survey year. The associated work and non-work factors were identified for the entire sample using multilevel mixed-effects logistic regression analysis. RESULTS: Prevalence for hand problems was 29.0% and 17.8% for the first and second study years, respectively. Significant factors (associated odds ratios) included increasing age (1.07), female gender (3.49), duration of sleep while migrating (0.68), participation group working in both study years 1 and 2 (0.21) or year 2 only (0.14), working on average more than 11 hours per day (8.23), moving heavy objects at work (3.97), working with hand-held vibrating tools/machinery (5.16), and working in meat processing (40.48). CONCLUSIONS: The prevalence of hand problems in migrant farmworkers reported by this study was notable for mothers, fathers, and children. Further research with refined ergonomic exposure and outcome assessments for investigating hand injuries in migrant farmworkers is indicated, specifically among youth. The role of sleep in preventing symptoms should also be explored.

The creation of evidence in 'evidence-based' drug prevention: a critique of the Strengthening Families Program Plus Life Skills Training evaluation.

School-based curricula have become a mainstay of drug prevention policy in the United States and are increasing in popularity in other parts of the world. The promotion and dissemination of these interventions has been driven in large part by the creation of lists of programmes which, it is claimed, are grounded in scientific evidence demonstrating their effectiveness. Recently concerns have been raised about the data analysis and presentation practices used in evaluations of a number of programmes that appear on these lists. Here we examine a series of papers from an evaluation of an intervention that combined the Strengthening Families Program 10-14 and Life Skills Training Program, each of which is among the most widely advocated universal drug prevention programmes. The data analysis and presentation practices employed in the evaluation of this combined programme include one-tailed significance testing, alpha levels of 0.10, changes in outcome variables across publications and use of the post-test data as the baseline when assessing change over time. Taken together, these practices severely limit the claims that can be made about the results presented in the evaluation. Specifically, we believe that far from supporting the evaluators' claims concerning the rigour of the findings and their generalisability and public health significance, the results are very fragile, of little practical significance and quite possibly analysis-dependent.

A prospective, randomized, double-blind, placebo-controlled study on the influence of a hormone replacement therapy on skin aging in postmenopausal women.

BACKGROUND: There is mounting evidence that menopause affects some functions of the skin. Hormone replacement therapy (HRT) appears to limit some of the climacteric aspects of cutaneous aging. OBJECTIVE: In the light of a growing interest in the endocrinological influence of skin, we performed a study evaluating the effects of HRT on skin aging in postmenopausal women. METHODS: Forty non-hysterectomized, postmenopausal women were included in this prospective, randomized, double-blind, placebo-controlled study on the influence of oral sequential treatment with a combination of 2 mg 17beta-estradiol/10 mg dydrogesterone (Femoston) for seven 28-day cycles. Skin elasticity, skin surface lipids, skin hydration and skin thickness were measured by non-invasive methods, and both adverse-event profile and clinical-dermatological status were evaluated. RESULTS: After 7 months of HRT, skin elasticity increased significantly at the right ramus of the mandible, while skin hydration tended to improve significantly at the right upper arm (inner side); skin thickness improved significantly but skin surface lipids did not. Absolute effects did not differ significantly between HRT and placebo patients. A dermatological evaluation was largely consistent with measurement results. Safety and tolerability of HRT were positive. CONCLUSION: The results showed improvements in the parameters involved in skin aging in the HRT group as compared to baseline. While skin aging is no indication for systemic hormone supplementation, a positive effect on aging skin can be observed.

Prevention of recurrent bacterial urinary tract infections by intravesical instillation of hyaluronic acid.

OBJECTIVE: To evaluate the efficacy of vesical instillation of hyaluronic acid against recurrent urinary tract infections. METHODS: Twenty women with a history of recurrent urinary tract infections each received 9 intravesical instillations of hyaluronic acid over 6 months. Their status was assessed prospectively over 47.6 weeks and compared with a retrospective review of patient charts covering 36.2+/-6.2 weeks. RESULTS: The total numbers of urinary tract infections were 67 before and 10 after treatment (p<0.001). Thirteen patients (65%) were free of recurrences until the end of the study. One had a recurrence during treatment, and 6 (30%) during follow-up. The number of infections per year per patient was reduced from 4.99+/-0.92 to 0.56+/-0.82 (p<0.001). In women with recurrences, time to recurrence was 178.3+/-25.5 days, compared with 76.7+/-24.6 days before treatment (p<0.001). CONCLUSION: Intravesical instillation of hyaluronic acid is effective in preventing recurrent urinary tract infections.

Evaluation of the Texas 0.08 BAC law.

AIMS: The purpose of the present study was to assess the effects on alcohol-involved traffic crashes and fatalities of the 0.08 blood alcohol concentration (BAC) per se law introduced in the state of Texas in 1999. METHOD: Data pertaining to alcohol-involved traffic crashes and fatalities were extracted from two datasets: the Fatality Analysis Reporting System (FARS) compiled by the National Highway Traffic Safety Administration (for the period January 1995-September 2002), and the Texas Department of Public Safety (DPS) reports of Alcohol Related Motor Vehicle Traffic Accidents and Casualties (for the period January 1995-December 2000). The data were analysed using time-series methods (ARIMA routines). The effects of the law on all drivers were assessed, along with the effects among gender, racial, and age subgroups and crash location (urban vs rural). RESULTS: Separate time-series analyses were conducted with all alcohol-involved and fatal alcohol-involved crashes from the DPS dataset and fatal alcohol-involved crashes from the FARS dataset as the outcome variables. None of the effects for either the total sample or any of the subgroups analysed was statistically significant (this was true of both the FARS and DPS datasets). CONCLUSIONS: While there is a growing body of evidence that indicates that 0.08 BAC laws can be effective in reducing alcohol-involved traffic accidents and fatalities, the present study shows that this was not the case in Texas. Future research should move beyond the simple question of whether or not 0.08 BAC laws 'work' and instead explore in more detail the conditions, such as publicity and enforcement, under which the law does or does not contribute to a decline in alcohol-involved accidents and fatalities.

Propolis solution for the treatment of chronic vaginitis.

OBJECTIVE: To evaluate the efficacy of 5% propolis solution in recurrent vaginitis. METHOD: Fifty-four patients with recurrent vaginal infections having undergone at least one cycle of antibiotic treatment were instructed to apply a 5% aqueous propolis solution as a vaginal douche for seven days. Vaginal smears and specific symptoms were evaluated at baseline and 14 days after treatment. Long-term well-being was assessed by telephone interview six months after follow-up. RESULT: At the follow-up, the vaginal smears of 41 patients (75.9%) had improved. Forty-seven patients (87%) reported reliefs concerning at least one complaint. Associated improvement of smear and well-being was observed in 36 women (66.7%). After 6 months, 33 patients (61.1%) were satisfied with their condition without having undergone further treatment. CONCLUSION: Propolis may have a role as an alternative treatment for chronic vaginal infection.

A predictive model for endometriosis.

BACKGROUND: Aromatase is the key enzyme in the process of estrogen biosynthesis from the precursor androgen. Recently, aromatase has been found to be aberrantly expressed in eutopic endometrium of patients suffering from endometriosis. This finding has prompted speculation about the contribution of this enzyme to the prediction of this disease. METHODS: We prospectively aimed to evaluate whether endometrial biopsy, prior to laparoscopy in symptomatic women to screen for the presence of aromatase by real-time RT-PCR and immunohistochemistry, combined with select patients' characteristics, is of value to predict endometriosis. RESULTS: Of 48 consecutive symptomatic and eligible patients, 25 (52.1%) exhibited endometriosis and 23 (47.9%) were disease-free. A multiple logistic regression model revealed that 95.5% of patients whose eutopic endometrium was found to be positive for aromatase mRNA as well as immunohistochemically detected protein and who were additionally suffering from moderate to severe dysmenorrhoea (visual analogue scale score >4/10) exhibited endometriosis at laparoscopy. CONCLUSIONS: These findings provide direct evidence that screening for eutopic endometrial aromatase in combination with clinical data could be of discriminative value in the prediction of disease.

Estrogen-metabolizing gene polymorphisms and age at natural menopause in Caucasian women.

BACKGROUND: Lifestyle parameters, personal history and genetic factors are thought to affect the timing of natural menopause in humans. Based on their biological function, estrogen-metabolizing gene polymorphisms have been regarded as candidate genes for early menopause. METHODS: In the present cross-sectional, multi-centre study, we analysed nine single nucleotide polymorphisms of six estrogen-metabolizing genes [three estrogen-synthesizing genes, i.e. 17-beta-hydroxysteroid dehydrogenase type 1 (17-beta HSD), cytochrome P-450 (CYP) 17 and CYP19; and three estrogen-inactivating genes, i.e. catechol-O-methyltransferase (COMT), CYP1A1 and CYP1B1] by sequencing-on-chip-technology in 1360 Caucasian women with natural menopause. Women's lifestyle parameters, reproductive and personal histories were ascertained. RESULTS: Carriage of at least one mutant allele of the CYP1B1-4 Asn453Ser A--> G polymorphism (P = 0.004) and the number of full-term pregnancies (P < 0.001) were found to be independently associated with age at natural menopause. Women with at least one polymorphic allele of CYP1B1-4 experienced natural menopause earlier than non-carriers of the polymorphism [mean (SD) 48.6 (5.0) versus 49.4 (4.3) years]. Women with no, one, two and three or more full-term pregnancies experienced natural menopause at 48.5 (5.0), 48.8 (4.8), 49.5 (4.2) and 49.6 (4.6) years, respectively. CONCLUSION: We present the most comprehensive data on estrogen-metabolizing gene polymorphisms and timing of natural menopause to date. The number of full-term pregnancies and the CYP1B1-4 polymorphism are significant predictors of timing of natural menopause in Caucasian women.

Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women.

BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathway for hydroxylated estrogens. We hypothesize that blood 17beta-estradiol (E(2)) and estrone (E(1)) levels in postmenopausal women receiving an oral E(2) preparation are dependent on the enzyme activity of COMT. METHODS: To determine the influence of this enzyme on E(2) serum levels three groups of 12 selected from 159 healthy normotensive postmenopausal women were selected according to their codon 158 COMT genotype (COMT(HH), COMT(HL), COMT(LL)) which is known to be associated with enzyme activity. All selected women received one 2 mg tablet estradiol valerate and blood samples were taken before treatment and after 1, 3 and 48 h. RESULTS: After 3 h the serum levels of E(2) were significantly higher in women with the COMT(LL) genotype (median 69 pg/ml, range 58-91) and the COMT(HL) genotype (median 69 pg/ml, range 43-84) compared with women with the COMT(HH) genotype (median 45 pg/ml, range 15-68, P < 0.005). In a univariate analysis of variance, considering age, body weight, and COMT genotype, body weight (P = 0.034) and COMT genotype (P < 0.001) were independently related to the increase of serum E(2) levels, whereas age was not. CONCLUSIONS: Our data demonstrate that serum E(2) levels significantly correlate with the COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases such as hormone-dependent cancers, coronary heart disease and on efficacy of hormone replacement therapy.

A polymorphism of the interleukin-6 gene promoter and idiopathic recurrent miscarriage.

BACKGROUND: Cytokines have been described to play a major role in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a polymorphism of the interleukin-6 (IL-6) gene and IL-6 serum levels. METHODS: In a prospective case-control study, we studied 161 women with IRM and 124 healthy controls. Peripheral venous puncture, DNA extraction and PCR were employed to genotype women for the presence of a polymorphism at position -174 in the promoter region of IL-6. Serum IL-6 levels were assessed by a commercially available ELISA. RESULTS: Allele frequencies among women with IRM and controls were 63.4 and 58.1% respectively for allele G (wild type), and 36.6 and 41.9% respectively for allele C (mutant). No association between allele C and the occurrence of IRM was found (odds ratio 0.8; 95% confidence interval = 0.57-1.12; P = NS). IL-6 serum levels were not significantly different between genotypes and between the study and control groups. CONCLUSIONS: This is the first report on an IL-6 polymorphism in IRM. Although known to alter IL-6 expression, the IL-6 polymorphism investigated was not associated with IRM and alterations in IL-6 serum levels in a Middle-European Caucasian population.

[Ethical problems in genetics and reproduction medicine]. / Ethische Probleme in Genetik und Fortpflanzungsmedizin.

Novel knowledge in the fields of molecular biology, genetics and reproductive medicine will revolutionize medicine in the near future. Among many new therapeutical aspects arise a number ethical questions that include preimplantation diagnostics, embryonic stem cell research and gene therapy. Believing in scientific progress is often criticized but today it is primarily ignorance as well as fundamentalism that block sensible discussions. In the future it shall be of importance to differentiate between "to be alive" and "to have a life", hence yielding a new definition of the term "life". Also important is to keep in mind the difference between individual moral claims and general ethics. Without doubt, the current developments in medicine will bring about interesting consequences but the inherent dangers are recognizable as well. However, only a positive attitude will result in beneficial developments. More flexibility on all sides will be needed in the concurrent discussion process.

Endometrial nuclear receptor co-factors SRC-1 and N-CoR are increased in human endometrium during menstruation.

Steroid hormone receptor co-factors are abundantly expressed in the uterus in order to modify steroid hormone receptor action, either leading to activation or repression of transcription in the endometrium. However, the role of co-factors in remodelling of the human endometrium has not been established. We therefore endeavoured to evaluate the presence of the co-activator SRC (steroid receptor co-activator)-1 and the co-repressors N-CoR (nuclear receptor co-repressor) and steroid co-repressor SMRT (silencing mediator of retinod and thyroid) receptors in the human endometrium during the different phases of the menstrual cycle. By using a real-time RT-PCR assay, we showed that SRC-1, N-CoR and SMRT mRNA are expressed in human endometrium during all phases of the menstrual cycle, as well as in inactive endometrium. Moreover, endometrial expression of SRC-1 and N-CoR mRNA increased during menstruation when compared with the other phases of the menstrual cycle (P < 0.001). Immunohistochemistry demonstrated that SRC-1 and N-CoR stain positive in the glandular epithelium and stroma in menstrual phase endometrium. The staining was weak in proliferative and secretory endometrium and absent in inactive endometrium. Our results suggest that differential expression of endometrial steroid receptor co-factors probably play a role in the regulation of human endometrium remodelling.