Obesity and pro-inflammatory mediators are associated with acute kidney injury in patients with A/H1N1 influenza and acute respiratory distress syndrome.

BACKGROUND: The obesity has been shown to increase the severity of A/H1N1 infection and the development of acute respiratory distress syndrome (ARDS) and organ involvement. METHODS: Circulating levels of C-peptide, insulin, glucagon, leptin, acute phase reactants (procalcitonin, C-reactive protein, tissue plasminogen activator, and serum amyloids A and P), were measured in samples from 32 critically ill patients with A/H1N1 virus infection, 17 of whom had ARDS complicated by acute kidney injury (AKI) and 15 of whom had ARDS but did not develop AKI. RESULTS: Patients with ARDS and AKI (ARDS/AKI) had higher BMI and higher levels of C-peptide, insulin, leptin, procalcitonin and serum amyloid A compared to those ARDS patient who did not develop AKI. Adjusting for confounding variables using logistic regression analysis, higher levels of C-peptide (>0.75 ng/mL) (OR=64.8, 95% CI = 2.1-1980, p = 0.0006) and BMI>30 Kg/m(2) (OR = 42.0, 95% CI = 1.2-1478, p = 0.04) were significantly associated with the development of AKI in ARDS patients. CONCLUSION: High levels of C-peptide and BMI>30 kg/m(2) were associated with the development of AKI in ARDS patients due to A/H1N1 infection. These metabolic/obesity indicators, together with the profiles of pro-inflammatory acute phase proteins, may be important links between obesity and poor outcomes in A/H1N1 09 infection.

Angiogenic and inflammatory markers in acute respiratory distress syndrome and renal injury associated to A/H1N1 virus infection.

Acute kidney injury (AKI) is often associated to acute respiratory distress syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We analyzed the serum levels of several angiogenic factors, cytokines, and chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15 ARDS patients who did not developed AKI) and in 18 healthy controls. Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI patients were detected. Adjusting by confusing variables, levels of MCP-1 ≥150 pg/mL (OR=12.0, p=0.04) and VEGF ≥225 pg/mL (OR=6.4, p=0.03) were associated with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10 were significantly associated with a higher risk of death in patients with ARDS (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over-production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and are associated to a higher risk of death.

Indoor pollution as an occupational risk factor for tuberculosis among women: a population-based, gender oriented, case-control study in Southern Mexico.

BACKGROUND: Indoor air pollution produced by biomass cooking fuels in developing countries has been associated with acute and chronic lower respiratory diseases, but has not been identified as an occupational exposure among women. OBJECTIVE: To examine the relationship between the use of biomass cooking fuels (mainly wood) and tuberculosis (TB) among women living in rural areas in Southern Mexico. METHODS: We conducted a population based case-control study in the health jurisdiction of Orizaba, Mexico. Cases were all incident female pulmonary TB patients, with Mycobacterium tuberculosis in sputum, living in communities with fewer than 15,000 inhabitants, diagnosed between March 1995 and April 2003. Woodsmoke exposure was assessed by applying a standardized questionnaire (ATS-DLD-78 questionnaire). Controls were randomly selected from sex-matched neighbors. Appropriate IRB approval was obtained. RESULTS: 42 TB cases and 84 community controls were recruited. Multivariate assessment showed that more than 20 years of exposure to smoke from biomass fuels was three times more frequent among cases than among controls [Odds ratio (OR): 3.3, 95% confidence interval (CI):1.06-10.30, p = 0.03], after controlling for age, body mass, household crowding, years of formal education and tobacco use. CONCLUSIONS: We found a strong association between the use of biomass cooking fuels and tuberculosis among women in a community-based, case-control study. Results of this study are intended to provide evidence to policy makers, community leaders and the general public on the importance of implementing gender oriented interventions that decrease the use of biomass fuels in poor communities in developing countries.

[Cytochrome P450 and NAT2 polymorphisms and drug metabolism in DOTS]. / Polimorfismos en los genes CYP450 y NAT2 y metabolismo de fármacos para el tratamiento antituberculosis estandarizado.

It has been described an increase of the frequency of Directly Observed Therapy Short-course (DOTS) failure in countries with high rates of mycobacterial drug resistance. This increase could be due to the standardized doses of DOTS results in low or insufficient dosage of drugs in plasma. Several members of cytochrome P450 enzymes superfamily could explain the variations on acetylation velocity and in drug disposition. A population with slow acetylation has a higher risk of toxicity, as that potent inhibition of cytochrome P450 (CYP450) isoforms by isoniazid (CYP2C19 y CYP3A) are dependent of INH plasmatic concentration. This inhibitory effect has been described also for CYP12, CYP2C9 and CYP2E1. INH is metabolized by N-acetyltransferase 2 (NAT2). The wide variability interethnic and intraethnic in acetylation velocity is associated with the polymorphisms of NAT2. Patients with rapid acetylation have plasmatic concentration of INH low or insufficient which induces treatment failure. The study of genotypes of P450 and NAT2 allow us to predict therapeutic and individualized dosages.

Aspectos metodológicos y éticos de la farmacogenómica en los ensayos clínicos aleatorizados / Contributions of pharmacogenomics to enhance the efficiency of randomized clinical trials

One of the greatest advances of the modern medicine has been the report of the complete sequence of the human genome. This has brought as a consequence an evolution in the design of the clinical research, in special of the randomized clinical trials (RCTs). The pharmacogenomics, a powerful tool for the prediction of pharmacological effects based on the genotype of the studied subjects, promises to be very useful next years for the development of the pharmaceutical industry. With the present integration of the pharmacogenomical methods to the investigation and development of new medicines it may start a new era in the medical prescription producing more individualized therapies, reduction of adverse events in the patients and in addition a faster development of new medicines in a more cost-effective way. Nevertheless new methodological, ethical and social challenges appear that will have to be solved simultaneously, to allow a legal use of the vast information generated by the genetic information.

Uno de los mayores avances de la medicina moderna se ha dado con el reporte en borrador de la secuencia del genoma humano. Esto ha traído como consecuencia nuevas opciones en el diseño de la investigación clínica, en especial en los ensayos clínicos aleatorizados (ECAs). La farmacogenómica que ha emergido como una herramienta poderosa para la predicción de efectos farmacológicos basados en el genotipo de los sujetos estudiados, promete ser de gran utilidad en los próximos años para el desarrollo de la industria farmacéutica. Cabe destacar que la integración actual de los métodos de la farmacogenómica a la investigación y desarrollo (I&D) de nuevos medicamentos, ofrece la perspectiva de una nueva era en la prescripción médica, con terapias más individualizadas, disminución de eventos adversos en los pacientes y además un desarrollo más rápido y costo-efectivo de nuevos medicamentos. Sin embargo, la aplicación de la farmacogenómica a la investigación clínica representa nuevas interrogantes metodológicas, éticas y sociales que tendrán que desarrollarse de igual manera, para permitir un uso legal de la información generada por los ECAs que incorporan información genética.

Tuberculosis and diabetes in southern Mexico.

OBJECTIVE: To determine the impact of diabetes on the rates of tuberculosis in a region where both diseases are prevalent. RESEARCH DESIGN AND METHODS: Data from a population-based cohort of patients with pulmonary tuberculosis undergoing clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) were linked to the 2000 National Health Survey (ENSA2000), a national probabilistic, polystage, stratified, cluster household survey of the civilian, noninstitutionalized population of Mexico. RESULTS: From March 1995 to March 2003, 581 patients with Mycobacterium tuberculosis culture and fingerprint were diagnosed, 29.6% of whom had been diagnosed previously with diabetes by a physician. According to the ENSA2000, the estimated prevalence of diabetes in the study area was 5.3% (95% CI 4.1-6.5). The estimated rates of tuberculosis for the study area were greater for patients with diabetes than for nondiabetic individuals (209.5 vs. 30.7 per 100000 person-years, P < 0.0001). CONCLUSIONS: In this setting, the rate of tuberculosis was increased 6.8-fold (95% CI 5.7-8.2, P < 0.0001) in patients with diabetes due to increases in both reactivated and recently transmitted infection. Comorbidity with diabetes may increase tuberculosis rates as much as coinfection with human immunodeficiency virus (HIV), with important implications for the allocation of health care resources.