Genome-wide haplotypic testing in a Finnish cohort identifies a novel association with low-density lipoprotein cholesterol

We performed genome-wide tests for association between haplotype clusters and each of 9 metabolic traits in a cohort of 5402 Northern Finnish individuals genotyped for 330 000 single-nucleotide polymorphisms. The metabolic traits were body mass index, C-reactive protein, diastolic blood pressure, glucose, high-density lipoprotein (HDL), insulin, low-density lipoprotein (LDL), systolic blood pressure, and triglycerides. Haplotype clusters were determined using Beagle. There were LDL-associated clusters in the chromosome 4q13.3-q21.1 region containing the albumin (ALB) and platelet factor 4 (PF4) genes. This region has not been associated with LDL in previous genome-wide association studies. The most significant haplotype cluster in this region was associated with 0.488 mmol/l higher LDL (95% CI: 0.361–0.615 mmol/l, P-value: 6.4 × 10⁻¹⁴). We also observed three previously reported associations: Chromosome 16q13 with HDL, chromosome 1p32.3-p32.2 with LDL and chromosome 19q13.31-q13.32 with LDL. The chromosome 1 and chromosome 4 LDL associations do not reach genome-wide significance in single-marker analyses of these data, illustrating the power of haplotypic association testing.     

Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Regional Assessment of Atrazine Exposure and Incidence of Breast and Ovarian Cancers in Kentucky

The association between breast and ovarian cancers with endogenous estrogen or hormonally related events has led to the hypothesis that exposures to exogenous estrogenic compounds in the environment may increase the risk of these cancers. Atrazine, the most commonly used herbicide in the United States, belongs to this group of compounds and is widely used in corn production. This study is an expansion of a previous investigation conducted in Kentucky. Using secondary data, we derived several indices of environmental exposure to atrazine and examined the association between these measures and the incidence of breast and ovarian cancer in Kentucky over a 5-year period (1993–97). Exposure indices to atrazine were derived based on public water measurements, acres of corn planted, and pounds of atrazine sold. Data on breast and ovarian cancer incidence were obtained from the Kentucky Cancer Registry by county and by the 15 Area Development Districts (ADDs) in which the 120 counties are grouped. Poisson regression analyses adjusted for education and race were conducted separately for each index of exposure and for a combined total exposure score. All exposure measures were divided in quartiles for analysis. A null association was found for breast cancer across all exposure indices, both by county and by ADD. For ovarian cancer, the data suggest an inverse association, with increasing exposure linked to decreasing incidence rates, both at the county and ADD level. The following are the rate ratios (RR) and corresponding 95% confidence intervals, for the summary exposure scores in the three upper quartiles, using the lowest quartile as baseline (RR = 1.0), and the county as the unit of analysis: 1.01 (0.83–1.21), 0.77 (0.66–0.90), and 0.76 (0.65–0.88). Due to the ecologic nature of this study and inherent limitations, it is possible that other factors may be contributing to these findings. Studies using individual-level data are recommended to elucidate the relationships between estrogenic environmental exposures and female reproductive cancers. Received: 3 April 2001/Accepted: 12 June 2001     

Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response

Gamma-linolenic acid in the form of a particular variety of evening primrose oil (Epogam) has been reported of value in the treatment of atopic eczema. Nine controlled trials of evening primrose oil were performed in eight centres. Four of the trials were parallel and five cross-over. Doctors and patients assessed the severity of eczema by scoring measures of inflammation, dryness, scaliness, pruritus and overall skin involvement. Individual symptom scores were combined to give a single global score at each assessment point. In the analysis of the parallel studies, both patient and doctor scores showed a highly significant improvement over baseline (P less than 0.0001) due to Epogam: for both scores the effect of Epogam was significantly better than placebo. Similar results were obtained on analysis of the cross-over trials, but in this case the difference between Epogam and placebo in the doctors' global score, although in favour of Epogam, failed to reach significance. The effects on itch were particularly striking. There was no placebo response to this symptom, whereas there was a substantial and highly significant response to Epogam (P less than 0.0001). When the improvements, or otherwise, in clinical condition were related to changes in plasma levels of dihomogammalinolenic and arachidoni acids, it was found that there was a positive correlation between an improvement in clinical score and a rise in the fatty acid levels.     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

A new synthesis of Rink's polymer, 4-(2′,4′-dimethoxyphenylhydroxymethyl) phenoxymethylpolystyrene

For solid-phase peptide synthesis, 2, 4-dimethoxy-4′ -hydroxybenzhydrol linker was prepared via lithium borohydride reduction of 2, 4-dimethoxy-4′-hydroxybenzophenone. The potassium salt of the linker was coupled to chloromethylpolystyrene. This method proved to be better than use of the cesium salt. This new synthesis gave a polymer with appropriate structure and a good degree of substitution.     

The impact of surgical treatment on the mental health of women with obstetric fistula

Obstetric fistula is estimated to affect 2 million women worldwide and has considerable social and psychological effects on affected individuals. In this prospective study, 51 consecutive women with obstetric fistula admitted to the Barhirdar Hamlin Fistula Centre in the north of Ethiopia were screened using the General Health Questionnaire (GHQ-28) for potential mental health disorder before and 2 weeks after fistula surgery. Prior to surgery, all women screened positive. By 2 weeks after, this had dropped to 36% ( P = 0.005). 27% of the 45 women who were cured of their incontinence screened positive, while all 6 of those with severe residual incontinence continued to screen positive. We conclude that surgical treatment of obstetric fistula results in marked improvements in mental heath.