The rate of P aeruginosa bacteremia is falling slightly at our hospital. The emergence of the human immunodeficiency virus epidemic has had a considerable impact on both epidemiology and mortality. The presence of severe underlying disease, surgery, pneumonia, and, especially, severe sepsis are associated with a poor outcome. With the exclusion of patients with intravenous catheter-associated P aeruginosa bacteremia, the administration of an appropriate antimicrobial therapy is essential to a good outcome. Treatment with 1 active antibiotic seems to be sufficient.
Case-control studies that have investigated the association between alcoholism and alcoholinduced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2* . When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results. O ver the last few years, an increasing number of studies have provided compelling evidence for the involvement of genetically defined predisposing factors in alcoholism and alcohol-induced cirrhosis. The strongest support comes from the fact that not all subjects with a high daily intake of alcohol develop alcohol-induced liver disease. Mostly metabolized in the liver by the successive action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the rate of conversion of ingested ethanol to acetaldehyde, and of acetaldehyde to acetate, is influenced by genetic polymorphisms at both loci. ALDH2 is the most important gene that affects predisposition to alcoholism in Asian populations. Thus, the prevalence in these populations of the inactive ALDH enzymatic form encoded by the ALDH2*2 allele appears to protect against alcoholism. 1 Furthermore, alcoholics with this inactive allele may be at great risk for advanced alcoholic liver disease. [2][3][4] Regarding the ADH gene cluster, polymorphisms are also detected at the ADH2 and ADH3 loci with two alleles (referred to as *1 and *2) each. Alleles ADH2*2 and ADH3*1 encode, respectively, for the highly active  2 and ␥ 1 allozymes, 5 and a low prevalence of both alleles has been reported in alcoholic Asians-although some studies did not detect associations between ADH3 polymor-
HIV-1 elite controllers (EC) maintain undetectable viral load (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes including a proportion loosing HIV-1 control over time. In this work we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, versus persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1-infection with a longitudinal retrospective study design. Gag-specific T-cell response was assessed by intracellular poly-cytokine production quantified by flow cytometry. Viral diversity and sequence-dating were performed in proviral DNA by PCR amplification at limiting dilution in and genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity and high proinflammatory cytokines levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r=-0.8;=0.02). RANTES was a potential biomarker of transient control. This study identified, virological and immunological factors including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in a better clinical management of these individuals and in the development of future curative approaches. There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work we found differences in virological and immune factors including soluble inflammatory biomarkers between subjects with persistent control of viral replication and EC that will loss the virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose the natural control of viral replication, and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV-infection.
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