Undetectable viral load is associated with sexual risk taking in HIV serodiscordant gay couples in Sydney

OBJECTIVE: To determine whether reporting that the HIV-positive partner's viral load is undetectable rather than detectable is associated with unprotected anal intercourse (UAI) in HIV serodiscordant gay couples. METHOD: A cross-sectional study nested within two cohort studies, the Health in Men (HIM) cohort of HIV-negative men, from July 2001 to December 2003 and the Positive Health (PH) cohort of HIV-positive men, from February 2002 to August 2003. The study participants were 119 men in an HIV serodiscordant regular relationship of at least 6 months duration (45 HIV-negative men from HIM, 74 HIV-positive men from PH). The main outcome measure was the occurrence of UAI within the relationship in the previous 6 months. RESULTS: Eighty-two men reported no UAI and 37 reported some UAI. Of couples in which the HIV-positive partner's viral load was reported to be undetectable, 39.4% reported UAI compared with 20.8% of those where viral load was reported to be detectable (P = 0.04). In multivariate analysis, significant predictors of UAI were younger age [odds ratio (OR), 0.94; 95% confidence interval (CI), 0.87-1.00; P = 0.05], greater HIV optimism (OR, 4.98; 95% CI, 1.25-19.8; P = 0.02) and reported undetectable viral load (OR, 2.88; 95% CI, 1.13-7.37; P = 0.03). CONCLUSIONS: Most serodiscordant gay couples do not engage in any UAI. UAI within such relationships is significantly more likely to occur where the HIV-positive partner is reported to have undetectable viral load. UAI in HIV serodiscordant relationships is problematic even if viral load is undetectable because of unknown risk parameters, viral load variability and the possibility of drug-resistant strains of HIV.     

CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy

OBJECTIVE: To evaluate the safety of treatment interruption guided by CD4+ cell count in HIV-infected patients followed up prospectively. METHODS: Patients on highly active antiretroviral therapy with CD4+ cell counts > 500 x 10(6) cells/l discontinued therapy with instructions to start therapy again before their CD4+ count dropped below 200 x 10(6) cells/l. Any patients who resumed therapy would be eligible to interrupt treatment again once their CD4+ cell count increased above 500 x 10(6) cells/l. RESULTS: Data on 71 HIV infected patients is reported. Their median nadir CD4+ cell count before antiretroviral treatment was 352 x 10(6) cells/l [interquartile range (IQR), 294-445 x 10(6) cells/l]. The median CD4+ cell count at the time of first interruption was 790 x 10(6) cells/l (IQR, 657-1041 x 10(6) cells/l). The median follow-up after starting the first treatment interruption was 28.3 months (IQR, 21.4-37.0 months). During the follow-up 49 patients restarted therapy and 22 patients remain off therapy; 24 patients have interrupted therapy twice, nine patients have interrupted therapy three times and six patients four times. No AIDS-defining illnesses occurred during the follow-up. The median duration of the first interruption was 15 months (IQR, 6-26 months). The overall reduction of time on therapy was 71.1%. The duration of the first interruption and the reduction of time on therapy were related to nadir CD4+ cell count. The patients who resumed HAART rapidly regained CD4+ cells and achieved viral suppression. CONCLUSION: If carefully monitored, treatment interruptions guided by CD4+ cell count in patients with an initially high CD4+ cell counts are clinically safe, decrease exposure to the drugs and do not reduce the efficacy of therapy when this is re-started.     

Stent implantation in a central aorto-pulmonary shunt

A 5.5-week-old infant with tricuspid atresia presented with severe hypoxemia not responding to the placement of a central shunt (4 mm polytetrafluorethylene). The infant was taken to the catheterization laboratory, where an AVE stent was successfully implanted in a severe postoperative stenosis, at the pulmonary end of the anastomosis. The oxygen saturation improved significantly, however, the infant died due to renal failure. The post-mortem anatomical findings are shown.     

Early postoperative complications following liver transplantation

Liver transplantation is a highly successful treatment for patients with end-stage liver disease and acute liver failure. However, serious postoperative complications can significantly compromise patient survival. Complications can be technical, medical, or immunological in nature. The risk of developing early postoperative complications is associated with the patient's preoperative condition, the quality of the donor liver, the quality of the donor and recipient procedure, initial graft function, and perioperative anaesthesiological and intensive care management. The patient's preoperative condition can include gastrointestinal bleeding, acute renal failure, a requirement for cathecholamines or mechanical ventilation, and prolonged encephalopathy for the most detrimental risk factors for developing early postoperative complications. The necessity for prolonged mechanical ventilation or the requirement for reintubation after transplantation can significantly increase the risk of developing pneumonia, sepsis, and multiple organ dysfunction. A decrease in infectious and other complications can be achieved by early postoperative enteral nutition, including the application of probiotics.     

Usefulness of dipyridamole stress echocardiography for predicting graft patency after coronary artery bypass grafting

Noninvasive techniques often provide controversial results in patients who have coronary artery bypass grafts (CABGs). Vasodilator stress echocardiography allows semi-simultaneous imaging of CABG flow and segmental left ventricular wall motion. To assess the comparative and additive value of regional flow and function for noninvasive evaluation of graft patency status, we evaluated 110 consecutive patients who underwent CABG and who were scheduled for coronary angiography. All patients underwent stress echocardiography with dipyridamole (0.84 mg/kg) and atropine (1 mg), including wall motion analysis by 2-dimensional echocardiography and Doppler evaluation of flow reserve of each CABG. Echocardiographic findings were compared with angiographic data. Four patients had inadequate acoustic windows. The remaining 106 patients had 226 grafts performed. Stress echocardiography showed 67% sensitivity, 91% specificity, and 71% accuracy for identification of 50% to 100% stenosis in the graft or in the recipient coronary vessel. There was a fair agreement with angiography (kappa coefficient 0.60). Identification of impaired coronary bypass flow reserve (i.e., <1.9 for internal mammary grafts and <1.6 for saphenous vein grafts) by Doppler had 91% sensitivity, 88% specificity, and 89% accuracy for graft stenosis. There was good agreement with angiographic findings (kappa 0.77). The combination of the 2 techniques achieved 93% sensitivity, 93% specificity, and 93% accuracy, showing a very good agreement with the patency status of the grafts as evaluated at angiography (kappa 0.85). The combined assessment of wall motion and flow reserve in patients who underwent CABG is feasible and provides an accurate estimate of graft patency status by increasing sensitivity of stress echocardiography and specificity of Doppler flow reserve.     

Carbohydrate Deficient Transferrin in Abstaining Patients With End-Stage Liver Disease

BACKGROUND: Carbohydrate deficient transferrin (CDT), a biochemical marker of chronic alcohol consumption, is used by researchers and clinicians alike in a variety of populations. Levels of CDT may be affected by certain types of medical illnesses and conditions. Thus the interpretation of CDT results may need to be carefully examined in these populations. Because CDT is synthesized, glycosylated, and secreted by the liver, the use of CDT values in patients with liver disease has been an area of focused interest. METHODS: We evaluated the CDT values of 79 abstaining patients with end-stage liver disease. These patients were recruited from a liver transplant clinic while they were listed and waiting for transplantation. Patients were determined to be abstaining both by interview and by random blood alcohol levels in those with a diagnosis of alcoholic liver disease. The severity of the liver disease was categorized by the Child-Pugh score. Correlations were determined between CDT values and liver enzymes, and Child-Pugh scores and liver diagnosis. RESULTS: Nearly 50% of the patients had a CDT value of 2.6% or above, indicating a clinically positive value. There were strong correlations between CDT and a number of biochemical and physical variables, most importantly the Child-Pugh score (r = 0.52, p = 0.000). Specific liver diseases were not associated with absolute CDT values. However, patients with hepatitis C (HCV) had a significantly higher chance of having a clinically positive CDT compared with patients with other types of liver diseases. CONCLUSIONS: These results suggest that an elevated CDT value may not accurately represent alcohol consumption in patients with advanced liver disease. In fact, in such patients, the CDT may become a marker for the degree of liver impairment in alcoholic and nonalcoholic liver disease. CDT values should be viewed with caution in any patient with liver disease especially when the degree of cirrhosis reaches a Child-Pugh score of C (total score of 10 or above).     

17Beta-estradiol abrogates apoptosis in murine skeletal muscle cells through estrogen receptors: role of the phosphatidylinositol 3-kinase/Akt pathway

Estrogens can regulate apoptosis in various cellular systems. The present study shows that 17beta-estradiol (E2), at physiological concentrations, abrogates DNA damage, poly (ADP-ribose) polymerase cleavage, and mitochondrial cytochrome c release induced by H2O2 or etoposide in mouse skeletal muscle C2C12 cells. This protective action, which involved PI3K/Akt activation and Bcl-2 associated death agonist (BAD) phosphorylation, was inhibited by antibodies against the estrogen receptor (ER) alpha or beta isoforms, or transfecting siRNA specific for each isoform. The inhibition of the antiapoptotic action of E2 at the mitochondrial level was more pronounced when ER-beta was immunoneutralized or suppressed by mRNA silencing, whereas transfection of C2C12 cells with either ER-alpha siRNA or ER-beta siRNA blocked the activation of Akt by E2, suggesting differential involvement of ER isoforms depending on the step of the apoptotic/survival pathway evaluated. These results indicate that E2 exerts antiapoptotic effects in skeletal muscle cells which are mediated by ER-beta and ER-alpha and involve the PI3K/Akt pathway.     

17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin

Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling. RV cardiomyocyte apelin abundance increased in vivo or in vitro after treatment with E2 or ER-α agonist. Studies employing ER-α–null or ER-β–null mice, ER-α loss-of-function mutant rats, or siRNA demonstrated that ER-α is necessary for E2 to upregulate RV apelin. E2 and ER-α increased BMPR2 in pulmonary hypertension RVs and in isolated RV cardiomyocytes, associated with ER-α binding to the Bmpr2 promoter. BMPR2 is required for E2-mediated increases in apelin abundance, and both BMPR2 and apelin are necessary for E2 to exert RV-protective effects. E2 or ER-α agonist rescued monocrotaline pulmonary hypertension and restored RV apelin and BMPR2. We identified what we believe to be a novel cardioprotective E2/ER-α/BMPR2/apelin axis in the RV. Harnessing this axis may lead to novel RV-targeted therapies for PAH patients of either sex.