Thrombophilia and antithrombotic therapy in women with recurrent spontaneous abortions

OBJECTIVE: To investigate the association between thrombophilia and recurrent spontaneous abortions (RSAs) and to evaluate the efficacy of anticoagulant treatment. STUDY DESIGN: All couples with a history of RSAs were studied by immunologic tests and determination of coagulation factors. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy were used in 29 selected cases with acquired and inherited thrombophilia. The control group included 23 women with a history of RSAs and tests positive for thrombophilia who declined to receive medication during pregnancy. RESULTS: All couples with a history of RSAs were studied by immunologic tests and determination of coagulation factors. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy were used in 29 selected cases with acquired and inherited thrombophilia. The control group included 23 women with a history of RSAs and tests positive for thrombophilia who declined to receive medication during pregnancy. CONCLUSION: All couples with RSAs require screening for thrombophilia. Low-molecular-weight heparin and low-dose aspirin daily during pregnancy appear to have a favorable effect on pregnancy outcome in selected women with RSAs and acquired or inherited thrombophilia.     

Design and analysis of trials with a partially nested design and a binary outcome measure

Where treatments are administered to groups of patients or delivered by therapists, outcomes for patients in the same group or treated by the same therapist may be more similar, leading to clustering. Trials of such treatments should take account of this effect. Where such a treatment is compared with an un‐clustered treatment, the trial has a partially nested design. This paper compares statistical methods for this design where the outcome is binary. Investigation of consistency reveals that a random coefficient model with a random effect for group or therapist is not consistent with other methods for a null treatment effect, and so this model is not recommended for this design. Small sample performance of a cluster‐adjusted test of proportions, a summary measures test and logistic generalised estimating equations and random intercept models are investigated through simulation. The expected treatment effect is biased for the logistic models. Empirical test size of two‐sided tests is raised only slightly, but there are substantial biases for one‐sided tests. Three formulae are proposed for calculating sample size and power based on (i) the difference of proportions, (ii) the log‐odds ratio or (iii) the arc‐sine transformation of proportions. Calculated power from these formulae is compared with empirical power from a simulations study. Logistic models appeared to perform better than those based on proportions with the likelihood ratio test performing best in the range of scenarios considered. For these analyses, the log‐odds ratio method of calculation of power gave an approximate lower limit for empirical power. © 2015 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.     

Exposure to Brominated Trihalomethanes in Water During Pregnancy and Micronuclei Frequency in Maternal and Cord Blood Lymphocytes

Background: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk.Objective: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes.Methods: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother–child cohort in Crete, Greece, in 2007–2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression.Results: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 μg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 μg/L = 1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 μg/L = 1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 μg/week = 3.14; 95% CI: 1.16, 8.50).Conclusions: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.Citation: Stayner LT, Pedersen M, Patelarou E, Decordier I, Vande Loock K, Chatzi L, Espinosa A, Fthenou E, Nieuwenhuijsen MJ, Gracia-Lavedan E, Stephanou EG, Kirsch-Volders M, Kogevinas M. 2014. Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes. Environ Health Perspect 122:100–106; http://dx.doi.org/10.1289/ehp.1206434     

Three peroxisome proliferator-activated receptor isotypes from each of two species of marine fish

The cloning and characterization of cDNAs and genes encoding three peroxisome proliferator-activated receptor (PPAR) isotypes from two species of marine fish, the plaice (Pleuronectes platessa) and the gilthead sea bream (Sparus aurata), are reported for the first time. Although differences in the genomic organization of the fish PPAR genes compared with their mammalian counterparts are evident, sequence alignments and phylogenetic comparisons show the fish genes to be homologs of mammalian PPARalpha, PPARbeta/delta, and PPARgamma. Like their mammalian homologs, fish PPARs bind to a variety of natural PPAR response elements (PPREs) present in the promoters of mammalian or piscine genes. In contrast, the mRNA expression pattern of PPARs in the two fish species differs from that observed in other vertebrates. Thus, PPARgamma is expressed more widely in fish tissues than in mammals, whereas PPARalpha and beta are expressed similarly in profile to mammals. Furthermore, nutritional status strongly influences the expression of all three PPAR isotypes in liver, whereas it has no effect on PPAR expression in intestinal and adipose tissues. Fish PPARalpha and beta exhibit an activation profile similar to that of the mammalian PPAR in response to a variety of activators/ligands, whereas PPARgamma is not activated by mammalian PPARgamma-specific ligands. Amino acid residues shown to be critical for ligand binding in mammalian PPARs are not conserved in fish PPARgamma and therefore, together with the distinct tissue expression profile of this receptor, suggest potential differences in the function of PPARgamma in fish compared with mammals.     

Serum CA 125 combined with transvaginal ultrasonography for ovarian cancer screening

BACKGROUND: The aim of this study was to evaluate the combination of serum CA125 and Transvaginal Ultra Sonography (TVUS) score, as a screening procedure for ovarian cancer in premenopausal and postmenopausal women. PATIENTS AND METHODS: A retrospective case-control pilot study was conducted. The files of 120 women with ovarian neoplasia detected by TVUS and increased CA125 level, within the framework of a prevention program, were reviewed. The relationship between the above tests and epithelial malignancy was investigated using the SPSS-12 program for Windows. RESULTS: The combination of CA125 value exceeding 30U/ml and a TVUS score > or = 35 had a sensitivity of 81.7% and specificity of 100% in predicting ovarian cancer. Mathematical analysis of the logistic model of our variables revealed a mathematical model that can calculate the likelihood of ovarian cancer detection, by using a combination of CA125 > or = 30U/ml and TVUS score > or = 35. CONCLUSION: By combining TVUS and CA125, an accurate prediction for the presence of ovarian cancer may be achieved. Further investigation in a larger population is warranted.     

New 1-O-acyl alpha-L-rhamnopyranosides and rhamnosylated lactones from Streptomyces sp., inhibitors of 3 alpha-hydroxysteroid-dehydrogenase (3alpha-HSD)

Chemical screening with extracts of Streptomyces sp. (strain GT 61150) resulted in the detection, isolation, and structure elucidation of two new acyl alpha-L-rhamnopyranosides (1 and 2) and three new rhamnosyllactones A, B1 and B2 (3 approximately 5). Rhamnosyllactones B1 and B2 were obtained as a 5:1 mixture. The structures were confirmed by spectroscopic analysis, especially 2D-NMR techniques. The rhamnosyltransferase of our strain is able to connect the sugar moiety to heteroaromatic carboxylic acids and enols. The metabolites 1 and 4/5 as well as previously reported acylrhamnosides 6 approximately 11 inhibit the enzyme 3alpha-hydroxysteroid-dehydrogenase (3alpha-HSD).