This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal PO2 after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal PO2 concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.

SUMMARY BackgroundCertolizumab pegol is the third anti-TNF-a agent approved by the Food and Drug Administration of the United States.

To ascertain whether hepatitis C (HCV) co-infection affects the progression of HIV infection, we initiated an eight-year prospective observational study at a university hospital in Taiwan where seroprevalences of HCV antibody and HIV antibody were low. Fifty-three (12.0%) consecutive non-haemophiliac HIV-1-infected patients with HCV co-infection and 387 (88.0%) patients without HCV and hepatitis B co-infection were enrolled between June 1994 and June 2002 and observed until December 2002. Outcomes evaluated included the risk for acute hepatitis, hepatic decompensation, HIV disease progression and mortality, and changes of CD4 þ count and plasma viral load (PVL) after initiation of highly active antiretroviral therapy (HAART) at the end of the study. The baseline CD4 þ count, PVL and proportion of patients with AIDS-defining opportunistic illnesses (OI) at study entry were similar between patients with HCV co-infection and those without co-infection, but HCV-co-infected patients were older (39 versus 35 years, P ¼ 0.01) and had a higher proportion of intravenous drug use (17.0% versus 0.8%, Po0.001). After a total observation duration of 1137 patient-years (PY) (median, 791 days; range, 3-3053 days), the incidence of acute hepatitis in HCV-co-infected patients was 13.89 per 100 PY (95% confidence interval [CI], 13.31-14.49) and that in patients without co-infection was 6.39 per 100 PY (95% CI, 6.24-6.55 per 100 PY), with an adjusted odds ratio (OR) of 2.769 (95% CI, 1.652-4.640). At the end of the study, CD4 þ count increased by 137 Â 10 6 and 157 Â 10 6 /L in patients with and without HCV co-infection, respectively, (P ¼ 0.47). The proportions of achieving undetectable PVL (o400 copies/mL) after HAART was similar (76.7% versus 74.9%, P ¼ 0.79). The adjusted OR for development of new AIDS-defining OI was 1.826 (95% CI, 0.738-4.522) in HCV-co-infected patients as compared with HCVuninfected patients. The adjusted hazards ratio for death of HCV-co-infected patients when compared with those without co-infection was 0.781 (95% CI, 0.426-1.432). Our findings suggested that HCV co-infection was associated with a significantly higher risk for acute hepatitis in HIV-infected patients receiving antiretroviral therapy, but it had no adverse impact on virological, immunological and clinical responses to HAART and survival when compared with patients without HCV and HBV co-infection.

Patients with RA have similar urinary complaints when compared to controls. However, those with secondary SS have a greater severity of LUTS, a finding similar to that observed in patients with primary SS.

Objectives Our aim was to compare three different definitions of treatment failure and discuss their use as quality outcome measures for a clinical service. Methods Data for treatment‐naïve patients who attended the Melbourne Sexual Health Centre (MSHC) between 1 January 2000 and 31 December 2008 were analysed. Definition 1 was the strict Food and Drug Administration (FDA) definition of treatment failure as determined using the time to loss of virological response (TLOVR) algorithm. Definition 2 defined treatment failure as occurring in those whose viral load never fell to <400 HIV‐1 RNA copies/mL or who developed two consecutive viral loads ≥400 copies/mL on any treatment (switching or stopping treatment with a viral load <400 copies/mL was permitted). Definition 3 was the same as definition 2 except that individuals were also deemed to have failed if they stopped treatment for 6 months or longer. Results There were 310 antiretroviral‐naïve patients who started treatment in the study period. Of these, 156 [50.3%; 95% confidence interval (CI) 42.1–53.3%] experienced treatment failure under definition 1, 10 (3.2%; 95% CI 1.5–5.8%) experienced treatment failure under definition 2, and 16 (4.5%; 95% CI 2.5–7.4%) experienced treatment failure under definition 3 over the 108 months of follow‐up. The probability of failing definition 1 was statistically different from the probability of failing definition 2 or 3 (P=0.01). Conclusion There were significant differences in treatment failure for the three definitions. If definition 1 were used, the outcomes would be sufficiently common to enable clinics to be compared but would be less meaningful. If definition 2 or 3 were used, the events would be too rare to enable clinics to be compared, but it would be possible to set a benchmark level of success that clinics could aim to reach.