Genetic thrombophilic defects (Factor V Leiden, prothrombin G20210A, MTHFR C677T) in women with recurrent fetal loss

Maternal thrombophilia (inherited and acquired) has recently been identified as a major cause of thrombembolism, but it may also contribute to adverse pregnancy outcomes and recurrent pregnancy loss. To determine the association of specific inherited thrombophilias and recurrent fetal loss (RFL), three gene mutations (Factor V Leiden, prothrombin G20210A, MTHFR C677T) were investigated. The prevalence of the thrombophilic markers was compared in 156 women with history of fetal loss in different trimester of pregnancy and 80 matched controls. At least one thrombophilic defect was found in 28.2% of total study group women compared with 16.2% in controls (p=0.06; OR-2.02) and in 50% of women with RFL in third trimester (p=0.008; OR-5.15). Factor V Leiden was more common in the group of women with fetal loss in third trimester (37.5%) compared to the controls (6.2%) (p=0.002; OR-9.0). Presence of FVL was associated with a significant increased risk for RFL in second and third trimester (OR-6.25; P<0.001) and significant protection for RFL in first trimester (OR-0.16; P<0.001). Mutation prothrombin G20210A or MTHFR C677T was more common in group of women with fetal loss in first trimester compared to the controls (28.3% vs. 11.2% respectively; p=0.009; OR-3.11). The presence of either of these mutations was associated with no significant increased risk for RFL in first trimester (OR-2.5). Genetic thrombophilic defects are common in women with RFL and are associated with late fetal loss. This association is manifest by FVL rather than total number of defects involved.     

Genetic variant C677T in the MTHFR in women with recurrent early fetal loss

The aim of this study was to evaluate correlation of carrier status for thrombophilic gene mutation--C677T in the methylenetetrahydrofolate reductase (MTHFR) and recurrent early pregnancy loss. Recently inherited thrombophilia was discussed as a predisposed factor for early recurrent fetal loss (ERFL). We investigated carrier status for C677T genetic variant in 54 women with ERFL before 10 week of gestation and 67 women with one or more successful pregnancy. It was found significant prevalence of C677T genetic variant in MTHFR in women with ERFL compared with controls (p = 0.005). The significant high prevalence of C677T genetic variant in women with ERFL suggests that thrombophilia have an increased risk of early pregnancy loss and possibly, although the definition of the magnitude of risk will require prospective longitudinal studies.     

Pre-marital predictors of marital violence in the WHO World Mental Health (WMH) Surveys

Social Psychiatry and Psychiatric Epidemiology - Intimate partner violence (IPV) is a pervasive public health problem. Existing research has focused on reports from victims and few studies have...     

Association of TNF‐α polymorphisms with adult dermatomyositis and systemic lupus erythematosus in Bulgarian patients

Background Single‐nucleotide polymorphisms (SNPs) of tumor necrosis factor‐alpha (TNF‐α) have been implicated in various autoimmune diseases; however, the results are quite controversial, and there is still no widely accepted opinion about their role in the pathology of the autoimmune diseases. This is a pilot study to investigate the association of six SNPs of the TNF‐α gene with the risk of adult dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients. Materials and methods Twenty‐seven patients with DM and 27 with SLE were included in this study. Genomic DNA was extracted from the peripheral blood, and six SNPs (?1031T/C, ?863C/A, ?857C/T, ?308G/A, ?238G/A, +489G/A) were selected for investigation by polymerase chain reaction‐restriction fragment length polymorphism analysis. Results We found association between the TNF‐α?1031CC genotype and SLE (P = 0.025) and tendency for association with DM (P = 0.0876). The association appeared even stronger in the female patients with SLE (P = 0.024) and DM (P = 0.067). The TNF‐α?857GG genotype shows weak association with SLE (P = 0.097, OR 2.06, 95% CI 0.81–5.29) when analyzed for the whole group, but it appeared significantly associated with SLE in women (P = 0.048, OR 3.23, 95% CI 0.93–11.14). The ?863C allele showed association with arthritis in patients with SLE (P = 0.008). The haplotype analysis revealed a significant association between TNF ?1031C/?863C/?857C/?308G/+489G haplotype with both DM (P = 0.022) and SLE (P = 0.007) in women. Conclusions The TNF‐α polymorphisms are associated with increased relative risk mainly for SLE, particularly in women, while their role for DM is less evident and needs further analysis in an enlarged sample cohort.     

Antibodies to tumor necrosis factor alpha prevent increases in cell replication in liver due to the potent peroxisome proliferator, WY- 14,643

Several structurally dissimilar hypolipidemic drugs, plasticizers and halogenated hydrocarbons induce peroxisomes in hepatocytes, and cause hepatocellular adenoma and carcinoma in rats and mice. The mechanism by which these agents act is unknown, although recent studies have suggested a link between increased cell proliferation and hepatic cancer caused by peroxisome proliferators. Here, we demonstrate that neutralizing antibodies to tumor necrosis factor alpha (TNF alpha) block increases in protein kinase C and cell proliferation due to [4- chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,643), a hypolipidemic drug and potent peroxisome proliferator that causes tumors. WY-14,643 moderately elevated the level of TNF alpha mRNA in the liver. TNF alpha was detected immunohistochemically exclusively in Kupffer cells. These results demonstrate that WY-14,643 acts as an indirect mitogen on hepatocytes via TNF alpha. We propose that the Kupffer cell, a major source of TNF alpha in the liver, is involved in the mechanism of the mitogenic effect of WY-14,643.      

Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation

BACKGROUND: The neurobiological features of pediatric bipolar disorder (BD) are largely unknown. Children and adolescents with BD may be important to study with functional neuroimaging techniques because of their unique status of early-onset BD and high familial loading for the disorder. Neuroimaging studies of adults with BD have implicated the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in the development of this disorder. OBJECTIVES: To study children and adolescents with BD via functional magnetic resonance imaging using cognitive and affective tasks and to examine possible abnormalities in the DLPFC and ACC, as well as selected subcortical areas, in pediatric familial BD. DESIGN: We evaluated 12 male subjects aged 9 to 18 years with BD who had at least 1 parent with BD as well as 10 age- and IQ-matched healthy male controls. Stimulants were discontinued for at least 24 hours; other medications were continued. Subjects underwent functional magnetic resonance imaging at 3 T while performing a 2-back visuospatial working memory task and an affective task involving the visualization of positively, neutrally, or negatively valenced pictures. SETTING: An academic referral setting, drawing from the Bay Area of San Francisco, Calif. RESULTS: Compared with controls, for the visuospatial working memory task, subjects with BD had greater activation in several areas including the bilateral ACC, left putamen, left thalamus, left DLPFC, and right inferior frontal gyrus. Controls had greater activation in the cerebellar vermis. In viewing negatively valenced pictures, subjects with BD had greater activation in the bilateral DLPFC, inferior frontal gyrus, and right insula. Controls had greater activation in the right posterior cingulate gyrus. For positively valenced pictures, subjects with BD had greater activation in the bilateral caudate and thalamus, left middle/superior frontal gyrus, and left ACC, whereas controls had no areas of greater activation. CONCLUSIONS: Children and adolescents with BD may have underlying abnormalities in the regulation of prefrontal-subcortical circuits. Further functional magnetic resonance imaging studies of attention and mood with greater sample sizes are needed.     

The age-related changes in the incidence of 'natural' anti-sperm antibodies suggest they are not auto-/isoantibodies

PROBLEM: Establishing the age-dependent patterns of sperm antibody levels among normal humans. METHODS OF STUDY: Sera samples from 498 healthy subjects aged 0-97 years - 246 males and 252 females - were tested by the gelatin agglutination test of Kibrick, tray agglutination test of Friberg, sperm immobilization test of Isojima and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found a significant increase in the level of sperm agglutinins after 40 years, which decreased after 88 years. The antibodies detected by ELISA were the highest among prepubertal subjects and also declined with aging. No age-dependent changes were established for the sperm immobilizins. With few exceptions, there were no significant differences between male and female sera, as well as between sera of newborn and their mothers. CONCLUSIONS: These data are similar to those established for the age-dependent changes of antibodies towards exogenous antigens, suggesting that the 'naturally occurring' antibodies against human spermatozoa are not auto-/isoantibodies.     

Congenital anomalies among live-birth infants and their place in the structure of neonatal mortality--the Higher Medical Institute, Pleven (1993-97)

The aim of the study was to determine the frequency of the congenital anomalies (CA) among the live-born (LB), the structure of the neonatal mortality (NM) and the impact of congenital anomalies on it. Congenital anomalies were found in 171 (2.71%) of 11,902 infants born and hospitalized at the Clinics of Neonatology--Pleven between 1993 and 1997. 171 (14.4% o) of all LB died in 28 day after delivery. Noninfectious lung pathology and CA were responsible for respectively 28.7% and 27.5% of these deaths and were the main causes of NM. Multiple congenital anomalies and CA of cardio-vascular system were the most frequent CA that caused these deaths. The major part of the CA with genetic basis (64%) emphasizes the importance of the registration of CA and the genetic counselling for declining the NM rate.     

Modulation of human corticomuscular beta-range coherence with low-level static forces

Although corticomuscular synchronization in the beta range (15-30 Hz) was shown to occur during weak steady-state contractions, an examination of low-level forces around 10% of the maximum voluntary contraction (MVC) is still missing. We addressed this question by investigating coherence between electroencephalogram (EEG) and electromyogram (EMG) as well as cortical spectral power during a visuomotor task. Eight healthy right-handed subjects compensated isometrically static forces at a level of 4% and 16% of MVC with their right index finger. While 4% MVC was accompanied by low coherence values in the middle to high beta frequency range (25-30 Hz), a significant increase of coherence mainly confined to low beta frequencies (19-20 Hz) was observed with force of 16% MVC. Furthermore, this increase was associated with better performance, as reflected in decreased relative error in force during 16% MVC. We additionally show that periods of good motor performance within each condition were associated with higher values of EEG-EMG coherence and spectral power. In conclusion, our results suggest a role for beta-range corticomuscular coherence in effective sensorimotor integration, thus stabilizing corticospinal communication.