Policy Perspective on Housing and HIV/AIDS

For persons battling HIV/AIDS a stable place to live may decide the length and quality of life itself. It is nearly impossible for a person on the streets to engage in a needed continuous AIDS treatment regimen when the very basic question of where that person will rest his or her head when darkness comes in just a few hours is unresolved. When danger lurks on the streets, when cold numbs the limbs, when tiredness overwhelms the mind, when fear breaks the spirit, a place to call home would make all the difference.     

Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and risk-factors for colonisation and infection

Between October 2001 and August 2002, 30 hospital patients became infected or colonised by a multiresistant (including to carbapenems) epidemic strain of Acinetobacter baumannii (AbMR) in a hospital outbreak. This study analysed the risk-factors associated with acquisition of this epidemic strain and investigated the prognosis of patients infected by AbMR, with the aim of elucidating factors which lead to mortality. A case-control study of the acquisition of AbMR in patients infected or colonised in the hospital outbreak was performed. Independent risk-factors leading to death were studied by logistic regression analysis. Multivariate analysis of the risk-factors for colonisation/infection with AbMR revealed an independent association with the presence of an arterial catheter (OR, 1.13; 95% CI, 1.03-1.25) and administration of imipenem as monotherapy (OR, 11.12; 95% CI, 2.33-53.09). Multivariate analysis of the prognostic features leading to mortality revealed a significant association with hypotension or shock (OR, 24.63; 95% CI, 1.56-387.56) at the time of bacterial isolation.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.      

Bacteroides vulgatus outer membrane antigens associated with carrageenan-induced colitis in guinea pigs.

Previous experiments with the carrageenan model for ulcerative colitis demonstrated that the inflammatory response in guinea pigs can be enhanced by immunization with Bacteroides vulgatus and subsequent feeding of this organism to experimental animals. The studies reported here show that antigens extractable from the bacterial outer membrane by EDTA are responsible for this effect. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to analyze the outer membrane proteins from various strains as well as the lipopolysaccharides (LPS) extractable by the phenol-water method. Although the observed pattern of outer membrane proteins was complex, the strains could be divided into two electrophoretic types (phenons) on the basis of immunoblotting against a panel of antisera. Cross-absorbed antisera used in immunoblotting experiments identified four outer membrane proteins uniquely associated with the phenon capable of enhancing the colitis inflammatory response. These proteins had molecular weights of 100,000, 57,000, 34,000, and 21,000 when measured in 8% to 12% acrylamide gradient sodium dodecyl sulfate gels. Other antigens identified included at least one type of smooth LPS, three types of rough LPS, and a common antigen of 30,000 molecular weight among the strains of B. vulgatus tested. The outer membrane preparations were used in animal immunization and challenge experiments, and the severity of colitis was correlated with one electrophoresis type. The potential role of membrane proteins in the enhancement of colitis is discussed.