Maternal and neonatal health outcomes following assisted reproduction.

This study assessed the risk for maternal complications in women and neonatal outcomes in children conceived following assisted reproductive treatment as compared with spontaneously conception and also separately evaluated conventional IVF and intracytoplasmic sperm injection (ICSI). The prospective cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 who conceived spontaneously. No differences were observed in pregnancy complications (including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery) except for significantly increased risk for excess vaginal bleeding in assisted reproduction pregnancies (21.4% versus 12.9%; OR 1.67, 95% CI 1.18-2.37), which was prominent in women who reported polycystic ovary syndrome. Neonates born following assisted reproduction had increased risk for prematurity (10.6% versus 5.3%; OR 1.72, 95% CI 1.04-2.87), and IVF, but not ICSI, was associated with significantly increased risk for prematurity (OR 2.36, 95% CI 1.28-4.37) and low birthweight (OR 1.89, 95% CI 1.03-3.46). In conclusion, this study observed only an increased risk for excess vaginal bleeding as a pregnancy-associated complication in singleton pregnancies following assisted compared with spontaneous conception. However, singleton neonates born following IVF, but not ICSI, were at increased risk for prematurity.

IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.

End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.

Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.

Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.

Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study.

AIMS: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia. METHOD: A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ 2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel. RESULTS: The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042). CONCLUSIONS: We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

Psychiatric status after human fetal mesencephalic tissue transplantation in Parkinson's disease.

This report describes the prospective and systematic psychiatric assessment of nine patients who received transplantation of human fetal mesencephalic tissue into the caudate nucleus for treatment of Parkinson's disease. Unlike adrenal medullary transplantation, which often causes psychosis or delirium, this procedure appeared to have few perioperative sequelae. On longer-term follow-up, there was some statistical evidence of deterioration in psychiatric status, as manifested primarily in depressive and nonspecific emotional and behavioral symptoms. This group effect was partly attributable to the occurrence of discrete episodes of illness (major depression and panic disorder with agoraphobia) in some patients, but it was unclear whether such episodes occurred more often than would ordinarily be expected in Parkinson's disease. Differences in the neurobiological effects of fetal mesencephalic and adrenal medullary grafts may account for differences in the psychiatric sequelae of patients receiving these procedures.

General cognitive ability following unilateral and bilateral fetal ventral mesencephalic tissue transplantation for treatment of Parkinson's disease.

OBJECTIVE: To contrast the neuropsychological profiles of Parkinsonian patients, before and after fetal ventral mesencephalic tissue transplantation. DESIGN: Case series of personally examined patients. SETTING: Patients were evaluated by neurologists, neurosurgeons, and neuropsychologists as outpatients at a university hospital. PATIENTS: Fetal mesencephalic tissue was implanted in the right caudate nucleus of three patients and both nuclei of one patient. These patients were evaluated prior to surgery and at 12, 24, and 26 months postoperatively. RESULTS: Factor analysis of the test battery identified four statistically orthogonal test clusters. No statistically significant changes were identified postoperatively for clusters assessing verbal cognitive ability, nonverbal cognitive ability, and information-processing speed. An improvement of verbal memory cluster index was observed 12 months after surgery, and the improvement reached the level of statistical significance at 24 months after surgery. However, the verbal memory of all patients declined between 24 and 36 months after surgery. CONCLUSIONS: Fetal tissue transplantation to one or both caudate nuclei did not permanently arrest cognitive dysfunction. Although there is some evidence of improved cognitive ability after transplantation, it is improbable that normal cognitive function can be restored by this procedure because the impairments of cognitive ability associated with Parkinson's disease do not appear to originate solely from dopamine deficiency.

Congenital malformations in infants conceived following assisted reproductive technology in comparison with spontaneously conceived infants.

OBJECTIVE: To evaluate the risk for congenital malformations diagnosed at birth following assisted reproductive technology (ART) treatments compared with live births conceived spontaneously. METHODS: A retrospective cohort study including 9042 live births following ART and 213 288 spontaneously conceived (SC) live births during the period 1997-2004.The cohort was linked to the national live birth registry to determine the outcome of the pregnancies including congenital malformations. RESULTS: An increased adjusted risk for all congenital malformations was observed in ART compared with SC infants [2.4% versus 1.9%; ORadj = 1.45; 95% CI: 1.26, 1.68]. The increased risk was observed in singleton births [2.4% versus 1.8%; ORadj = 1.41; 95% CI: 1.14, 1.71] but not in the ART conceived multiple births [2.5% versus 2.6%.; ORadj = 1.15; 95% CI: 0.90, 1.46]. Significantly increased adjusted risks for nervous, circulatory, digestive and genital system malformations were evident in the ART singleton group compared to SC infants. In addition, increased risks were also observed in separate comparisons of IVF births versus SC [ORadj = 1.28; 95% CI: 1.00, 1.63] and ICSI births versus SC [ORadj = 1.56; 95% CI: 1.31, 1.84]. Data regarding pregnancy termination or congenital malformation diagnosed later in life were not included. CONCLUSION: Infants born following ART were at significantly increased risk for congenital malformations compared to live birth conceived spontaneously.

Mutations in the Na-Cl cotransporter reduce blood pressure in humans.

The relationship between salt homeostasis and blood pressure has remained difficult to establish from epidemiological studies of the general population. Recently, mendelian forms of hypertension have demonstrated that mutations that increase renal salt balance lead to higher blood pressure, suggesting that mutations that decrease the net salt balance might have the converse effect. Gitelman's syndrome, caused by loss of function mutations in the Na-Cl cotransporter of the distal convoluted tubule (NCCT), features inherited hypokalemic alkalosis with so-called "normal" blood pressure. We hypothesized that the mild salt wasting of Gitelman's syndrome results in reduced blood pressure and protection from hypertension. We have formally addressed this question through the study of 199 members of a large Amish kindred with Gitelman's syndrome. Through genetic testing, family members were identified as inheriting 0 (n=60), 1 (n=113), or 2 (n=26) mutations in NCCT, permitting an unbiased assessment of the clinical consequences of inheriting these mutations by comparison of the phenotypes of relatives with contrasting genotypes. The results demonstrate high penetrance of hypokalemic alkalosis, hypomagnesemia, and hypocalciuria in patients inheriting 2 mutant NCCT alleles. In addition, the NCCT genotype was a significant predictor of blood pressure, with homozygous mutant family members having significantly lower age- and gender-adjusted systolic and diastolic blood pressures than those of their wild-type relatives. Moreover, both homozygote and heterozygote subjects had significantly higher 24-hour urinary Na(+) than did wild-type subjects, reflecting a self-selected higher salt intake. Finally, heterozygous children, but not adults, had significantly lower blood pressures than those of the wild-type relatives. These findings provide formal demonstration that inherited mutations that impair renal salt handling lower blood pressure in humans.