Screening for ‘window‐period’ acute HIV infection among pregnant women in rural South Africa

Objectives

The aim of this study was to evaluate the HIV‐1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the ‘window period’ of acute HIV infection (AHI) in rural South Africa.

Methods

In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV‐1 RNA pooled NAAT was performed on HIV antibody‐negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence.

Results

The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3–41.3]. Of the 467 HIV antibody‐negative samples, four (0.9%) were HIV‐1 RNA‐positive. The mean viral load in the four samples was 386 260 HIV‐1 RNA copies/mL (range 64 200–1 228 130). The HIV incidence was 11.2% per year (95% CI 0.3–22.1) and all women with AHI were ≤21 years of age.

Conclusions

Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.     

Differential affinity of vitronectin versus collagen for synthetic biodegradable scaffolds for urethroplastic applications

Cell-seeded synthetic polymer scaffolds constitute an emerging technology for urethroplastic applications. The study goal was to identify urethral proteins appropriate for cell attachment and optimize their adsorption onto two types of scaffolds: porous poly(ester urethane) with a poly(caprolactone) soft segment (PEU-PCL) and poly-(96% L/4% D)-lactic acid (P96L/4DLA). Specimens from eight men undergoing urethral reconstruction for stricture diseases were subjected to immunohistochemical analysis. Type I collagen, type IV collagen and vitronectin were detected at the interface between the epithelium and its basement membrane. Electrophoresis confirmed that polypeptide chains in the starting material were also present in fractions eluted from adsorbed scaffolds. Over a 4 week incubation assay, only vitronectin exhibited 100% retention levels for all scaffolds. The saturation point for each protein on each scaffold type was determined by titration and ELISA. The collective evidence indicates the concept that vitronectin > type IV collagen > type I collagen are preferred adsorption proteins for PEU-PCL and P96L/4DLA.     

SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure

Objective

Mutations in SCARB2 were recently described as causing action myoclonus renal failure syndrome (AMRF). We hypothesized that mutations in SCARB2 might account for unsolved cases of progressive myoclonus epilepsy (PME) without renal impairment, especially those resembling Unverricht‐Lundborg disease (ULD). Additionally, we searched for mutations in the PRICKLE1 gene, newly recognized as a cause of PME mimicking ULD.

Methods

We reviewed cases of PME referred for diagnosis over two decades in which a molecular diagnosis had not been reached. Patients were classified according to age of onset, clinical pattern, and associated neurological signs into “ULD‐like” and “not ULD‐like.” After exclusion of mutations in cystatin B (CSTB), DNA was examined for sequence variation in SCARB2 and PRICKLE1.

Results

Of 71 cases evaluated, 41 were “ULD‐like” and five had SCARB2 mutations. None of 30 “not ULD‐like” cases were positive. The five patients with SCARB2 mutations had onset between 14 and 26 years of age, with no evidence of renal failure during 5.5 to 15 years of follow‐up; four were followed until death. One living patient had slight proteinuria. A subset of 25 cases were sequenced for PRICKLE1 and no mutations were found.

Interpretation

Mutations in SCARB2 are an important cause of hitherto unsolved cases of PME resembling ULD at onset. SCARB2 should be evaluated even in the absence of renal involvement. Onset is in teenage or young adult life. Molecular diagnosis is important for counseling the patient and family, particularly as the prognosis is worse than classical ULD. Ann Neurol 2009;66:532–536     

促红细胞生成素对实验性肾性贫血的作用

促红细胞生成素(erythropoietin,EPO)是由肾细胞分泌的一种糖蛋白激素。从人胚肾细胞中诱导,经生物化学方法分离、提纯得到此品。本试验用5/6肾切除的方法造成大鼠慢性肾衰性(CRF)贫血,研究不同剂量EPO对CRF贫血的作用。结果表明EPO有显著的促进红细胞生成,改善CRF贫血状态,使其接近或达到正常水平,最佳剂量为1000 U/kg,并可预防实验性贫血,对正常鼠未见明显作用。     

Invited commentary: hormone therapy and risk of coronary heart disease why renew the focus on the early years of menopause?

After the initial report from the Women's Health Initiative estrogen-progestin trial, which found that menopausal hormone therapy was associated with an increased risk of coronary heart disease in the overall cohort (age range: 50-79 years; mean age: 63 years), researchers took a closer look at the data from this and other studies, focusing on the timing of initiation of such therapy. The results suggest that hormone therapy may have a beneficial effect on the heart if started in early menopause, when a woman's arteries are still likely to be relatively healthy, but a harmful effect if started in late menopause, when advanced atherosclerosis may be present. The implication of the timing hypothesis for clinical practice is not that recently menopausal women be given hormone therapy for coronary heart disease prevention but rather that clinicians can be reassured about cardiac risks when considering short-term use of hormone therapy for vasomotor symptom relief in such women. The reduction in vasomotor symptoms must be weighed against other risks and benefits of treatment, but coronary disease is typically not a major factor in the equation for women who are recently menopausal.     

Regrowth of the rat biliary tree after 70% partial hepatectomy is coupled to increased secretin-induced ductal secretion

BACKGROUND & AIMS: After partial hepatectomy, liver regeneration occurs with the return of hepatocyte mass to normal, Limited data exist regarding the renewal of the biliary tree after partial hepatectomy. This study tested the hypothesis that, after partial hepatectomy, the biliary tree regenerates by proliferation of the remaining cholangiocytes, leading to an increase in secretin-induced ductal bile secretion. METHODS: After 70% partial hepatectomy, cholangiocyte proliferation was assessed in situ by morphometric analysis and In vitro by measurement of 3H-thymidine incorporation. Ductal secretion was estimated by measurement of secretin receptor gene expression and adenosine 3',5'-cyclic monophosphate (cAMP) levels in vitro and by the effect of secretin on ductal bile secretion in vivo. RESULTS: DNA synthesis was undetectable in control cholangiocytes, increased and peaked at day 3 after partial hepatectomy, and returned to normal by day 28. Morphometric analysis showed regrowth of the biliary tree beginning at day 1 with restoration by day 10. The expression of secretin receptor gene and secretin-induced cAMP levels and secretin- induced bicarbonate-rich choleresis increased during the period of bile duct renewal. CONCLUSIONS: After partial hepatectomy, the increase in secretin-induced ductal bile secretion observed during bile duct renewal results from proliferation of remaining cholangiocytes. (Gastroenterology 1996 Dec;111(6):1633-44)     

Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.