HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation

OBJECTIVE: To test whether post-partum vitamin A supplementation can reduce incident HIV among post-partum women and identify risk factors for HIV incidence. DESIGN: Randomized, placebo-controlled trial METHODS: Between November 1997 and January 2001, 14,110 women were randomly administered 400,000 IU vitamin A or placebo within 96 h post-partum. HIV incidence was monitored among 9562 HIV-negative women. RESULTS: Cumulative incidence was 3.4% [95% confidence interval (CI), 3.0-3.8] and 6.5% (95% CI, 5.7-7.4) over 12 and 24 months post-partum, respectively. Vitamin A supplementation had no impact on incidence [hazard ratio (HR), 1.08; 95% CI, 0.85-1.38]. However, among 398 women for whom baseline serum retinol was measured, those with levels indicative of deficiency (< 0.7 micromol/l, 9.2% of those measured) were 10.4 (95% CI, 3.0-36.3) times more likely to seroconvert than women with higher concentrations. Furthermore, among women with low serum retinol, vitamin A supplementation tended to be protective against incidence (HR, 0.29; 95% CI, 0.03-2.60; P = 0.26), although not significantly so, perhaps due to limited statistical power. Severe anaemia (haemoglobin < 70 g/l) was associated with a 2.7-fold (95%CI, 1.2-6.1) greater incidence. Younger women were at higher risk of HIV infection: incidence declined by 5.7% (2.8-8.6) with each additional year of age. CONCLUSION: Among post-partum women, a single large-dose vitamin A supplementation had no effect on incidence, although low serum retinol was a risk factor for seroconversion. Further investigation is required to determine whether vitamin A supplementation of vitamin-A-deficient women or treatment of anaemic women can reduce HIV incidence.     

Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis

OBJECTIVE: To assess the strength of association between recurrent fetal loss (RFL) and presence of antiphospholipid antibodies (aPL) in women without autoimmune disease, and to examine whether magnitude of association varies according to type or titer of antibody and timing of fetal loss. METHODS: We searched Medline and Current Contents for articles published between 1975 and 2003 with terms denoting early (less than 13 weeks) and late (less than 24 weeks) RFL associated with various aPL. Published case-control, cohort, and cross-sectional studies rated moderate or strong were included in our metaanalysis. Pooled odds ratios with 95% CI were generated using the random-effects models with Cochrane Review Manager software. RESULTS: Our analysis included 25 studies. Lupus anticoagulant (LAC) was associated with late RFL (OR 7.79, 95% CI 2.30-26.45); the association of LAC was stronger than that of any other aPL. IgG anticardiolipin antibodies (aCL), when combining all titers, were associated with both early (OR 3.56, 95% CI 1.48-8.59) and late RFL (OR 3.57, 95% CI 2.26-5.65). Restricting analysis to include only women with moderate to high titers increased the strength of association (OR 4.68, 95% CI 2.96-7.40). It was not possible to extract data on isolated low IgG aCL positivity. IgM aCL were associated with late RFL (OR 5.61, 95% CI 1.26-25.03). There was no association found between early RFL and anti-Beta2-glycoprotein I antibodies (OR 2.12, 95% CI 0.69-6.53). CONCLUSION: The magnitude of the association between aPL and RFL varies according to type of aPL. More data on the relationship between recurrent fetal loss and isolated IgM aCL as well as with low titer IgG aCL would be useful. The place of testing for anti-Beta2-glycoprotein I antibodies remains to be determined.     

Urinary excretion of oxidative metabolites of bilirubin in subjects with Gilbert syndrome

BACKGROUND AND AIM: Bilirubin is a potent endogenous antioxidant substance. Recent data suggest a direct relationship exists between urinary excretion of biopyrrins, a novel group of bilirubin oxidative metabolites, and severity of oxidative stress. The aim of this study was to evaluate urinary excretion of biopyrrins in subjects with Gilbert syndrome. METHODS: The study included patients with Gilbert syndrome (n = 33) and healthy blood donors (n = 25). In all subjects complete biochemical tests were conducted along with analysis of urinary excretion of biopyrrins. Linear and logistic regression analyses were used for multiple adjustments of possible confounders/modifiers. RESULTS: As expected, high serum bilirubin levels were found in the Gilbert syndrome group as compared to controls (27.8 +/- 9.7 vs 9.9 +/- 3.0 micromol/L, P < 0.001). In contrast, urinary levels of biopyrrins were substantially lower in the Gilbert syndrome group as compared to normobilirubinemic control subjects (19.9 +/- 26.0 vs 90.2 +/- 139.1 U/g urinary creatinine, P < 0.001). The Gilbert syndrome group also had very low prevalence odds ratios for urinary biopyrrins above the median of the control values even after adjustment for possibly confounding factors (odds ratio 0.18, 95% confidence interval 0.33-0.94; P = 0.042). CONCLUSIONS: An inverse relationship was demonstrated between serum bilirubin level and urinary excretion of biopyrrins, which is presumably due to antioxidative effects of elevated serum bilirubin levels in Gilbert syndrome.     

Synovial fluid analysis with leukocyte esterase reagent strip test

To determine whether leukocyte esterase reagent strip test (LERST) analysis could help distinguish inflammatory arthritis from mechanical joint effusion. We analyzed synovial fluid (SF) from consecutive patients with a non-traumatic joint effusion during a 6-month period. Inflammatory SF was defined by white blood cell (WBC) count ≥ 2000/mm³. The LERST was performed with both semi-quantitative visual analysis (VA) and automated colorimetric reader (ACR) analysis. Leukocytes ≥ 1+ was considered a positive LERST result and WBC count was the reference. We obtained 100 SF samples (87 knees, 7 ankles, 5 hips, and 1 elbow) from 100 patients (mean ± SD age 61 ± 17 years, 59% men). The laboratory analyzed 88 SF samples (37 mechanical and 51 inflammatory). The remaining 12 SF samples were 10 hemarthrosis not allowing LERST analysis and 2 samples with coagulum not allowing WBC count. As compared with the laboratory analysis, the LERST had sensitivity and specificity 55% and 89% with VA and 47% and 92% with ACR analysis. The positive and negative predictive values were 87.5% and 59% with VA and 89% and 55% with ACR analysis. We found almost perfect agreement between VA and ACR results (kappa 0.70 [95% CI 0.50–0.90]). The WBC count increased with number of + observed after VA. Our results confirm that the LERST is able to detect inflammation in SF of native joints, thereby representing a useful and cheap tool in primary care. Its low sensitivity limits its use for ruling out inflammatory disorders.

Human homozygous R403W mutant cardiac myosin presents disproportionate enhancement of mechanical and enzymatic properties

Familial hypertrophic cardiomyopathy (FHC) is associated with mutations in 11 genes encoding sarcomeric proteins. Most families present mutations in MYBPC3 and MYH7 encoding cardiac myosin-binding protein C and beta-myosin heavy chain. The consequences of MYH7 mutations have been extensively studied at the molecular level, but controversial results have been obtained with either reduced or augmented myosin motor function depending on the type or homogeneity of myosin studied. In the present study, we took advantage of the accessibility to an explanted heart to analyze for the first time the properties of human homozygous mutant myosin. The patient exhibited eccentric hypertrophy with severely impaired ejection fraction leading to heart transplantation, and carries a homozygous mutation in MYH7 (R403W) and a heterozygous variant in MYBPC3 (V896M). In situ analysis of the left ventricular tissue showed myocyte disarray and hypertrophy plus interstitial fibrosis. In vitro motility assays showed a small, but significant increase in sliding velocity of fluorescent-labeled actin filaments over human mutant cardiac myosin-coated surface compared to control (+18%; P<0.001). Mutant myosin exhibited a large increase in maximal actin-activated ATPase activity (+114%; P<0.05) and Km for actin (+87%; P<0.05) when compared to control. These data show disproportionate enhancement of mechanical and enzymatic properties of human mutant myosin. This suggests inefficient ATP utilization and reduced mechanical efficiency in the myocardial tissue of the patient, which could play an important role in the development of FHC phenotype.     

No association of promoter variations of HMOX1 and UGT1A1 genes with liver injury in chronic hepatitis C

Background. Heme oxygenase-1 (HMOX1) and bilirubin UDP-glucuronosyltransferase (UGT1A1), both enzymes involved in bilirubin homeostasis, play an important role inoxidative stress defense.Objective. To assess the effect of promotervariations of HMOX1 and UGT1A1 genes on the progression of fibrosis in patients chronically infected with the hepatitis C virus (HCV).Material and methods. The study was performed on146 chronic HCV infection patients, plus 146 age- and sex-matched healthy subjects. The (GT)n and (TA)n dinucleotide variations in HMOX1 and UGT1A1 gene promoters, respectively, were determined by fragment analysis in all subjects.Results. No differences were found in the frequencies of each particular allele of both genes, between HCV patients and a control group (p > 0.05). Furthermore, no association was detected (p > 0.05) between either the HMOX1 or the UGT1A1 promoter variants and the individual histological stages of liver disease in the HCV positive patients. Finally, no differences in the HMOX1 and UGT1A1 genotype prevalence rates were found between pre-cirrhotic and cirrhotic patients (p > 0.05).Conclusion. Based on our data, microsatellite variations in the HMOX1 and UGT1A1 genes are not likely to protect from progression of liver disease in patients with chronic hepatitis C.     

Cyclical neutropenia and T8 lymphocyte mediated stimulation of granulopoiesis

A 33-year-old female with cyclical neutropenia and a reciprocally cycling T8 (suppressor/cytotoxic) lymphocytosis was investigated. T8 lymphocytes ranged between 1.4 and 5.6 X 10(9)/l and a significant proportion (50-75%) were preactivated (1a+). Fc gamma receptors were detected in only a minority (7-10%). Functional studies on the lymphocytes indicated that despite their phenotype, little natural killer and reduced suppressor activities were present. Anti-granulocyte antibodies were not detectable in the serum. Production of colony stimulating activity (CSA) was assessed in the patient and control subjects' lymphocytes. Using a methylcellulose marrow culture system, the CSA production by the patient's lymphocytes was markedly increased compared with the control. Monoclonal antibody cytotoxic experiments confirmed that the T8 lymphocytes were responsible. As peaks of circulating T8 lymphocytes were synchronous with granulopoietic activity in the marrow, the above findings may represent a homeostatic mechanism which is attempting to compensate for an underlying stem cell defect.