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

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.

Differences in nocturnal basal and rhythmic prolactin secretion in untreated compared to treated HIV-infected men are associated with CD4+ T-lymphocytes.

The existence of decreased hypothalamic dopaminergic tone in HIV-infected men has been suggested. In a cross-sectional study, we determined 12 h nocturnal basal and pulsatile prolactin (PRL) release levels (by blood sampling every 10 min) and their correlation with CD4+ T cells in seven volunteer HIV-negative, healthy men (group 1), and 21 normoprolactinemic, euthyroid, HIV-infected men divided into 3 groups (each group = 7): (i) group 2, asymptomatic HIV-infected stage A1 men, untreated; (ii) group 3, AIDS stage C3 without active opportunistic infections, untreated; and (iii) group 4, previously stage C3 after at least 6 months of successful highly active antiretroviral therapy. Serum PRL was measured by radioimmunoanalysis and the results were analysed by waveform-independent deconvolution analysis. CD4+ T lymphocytes were measured by flow cytometry and viral load by a nucleic acid sequence-based amplification assay. No differences were detected in the first two groups. In the third group, however, 100% of prolactin secretion was found to be pulsatile with a shorter secretory burst duration (P = 0.04), and a greater circulating half-life and pulse amplitude (P < or = 0.04). Group 4 had the greatest basal prolactin secretion (P < or = 0.04), and a shorter secretory burst duration (P = 0.04 vs group 2), circulating half-life (P = 0.01 vs group 3) and intersecretory burst interval (P = 0.06 vs group 1). PRL approximate entropy was similar among all groups. Linear correlations existed between CD4+ T cell counts and PRL secretory burst half duration (r = 0.62, P = 0.002) and amplitude (r = -0.63, P = 0.001), and in circulating serum half-life (r = - 0.61, P = 0.002) in HIV-infected groups. Viral load showed no correlations. It is suggested that differential changes in nocturnal prolactin secretion among HIV-infected men occurred while maintaining the normal coordinate feedback and/or feedforward control within the lactotropic axis. These changes may represent an adaptative mechanism to sustain, by different means, the maximal physiologic PRL production to stimulate the highest cellular immune response and/or reconstitution in attempting to survive.

Tuberculosis-related deaths within a well-functioning DOTS control program.

To describe the molecular epidemiology of tuberculosis (TB)-related deaths in a well-managed program in a low-HIV area, we analyzed data from a cohort of 454 pulmonary TB patients recruited between March 1995 and October 2000 in southern Mexico. Patients who were sputum acid-fast bacillus smear positive underwent clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) and received treatment from the local directly observed treatment strategy (DOTS) program. After an average of 2.3 years of follow-up, death was higher for clustered cases (28.6 vs. 7%, p=0.01). Cox analysis revealed that TB-related mortality hazard ratios included treatment default (8.9), multidrug resistance (5.7), recently transmitted TB (4.1), weight loss (3.9), and having less than 6 years of formal education (2). In this community, TB is associated with high mortality rates.

Epidemiology of AIDS and tuberculosis

This article reviews literature on the epidemiology, pathogenicity, and control of HIV and Micobacterium tuberculosis coinfection. Regarding pathogenicity, immune system deterioration makes HIV-infected people more likely to develop active tuberculosis on primary or secondary exposure to the bacillus or to suffer reactivation of latent infections, and to experience considerably higher rates of extrapulmonary manifestations, relapses, and death. Regarding epidemiology, as of 1990 there were an estimated 3 million people coinfected with HIV and M. tuberculosis, with some 300 000 active tuberculosis cases and 120 000-150 000 tuberculosis deaths occurring annually among those coinfected. Over 500 000 coinfected people are thought to reside in the Americas, over 400 000 of them in Latin America. In general, the impact of coinfection is evident. Relatively high and increasing prevalences of HIV infection have been detected among tuberculosis patients around the world, and tuberculosis has become a frequent complication of AIDS cases. Moreover, there is no longer any doubt that coinfection obstructs tuberculosis prevention and control. Among other things, it effects BCG vaccination policies, suggests the need to administer preventive chemoprophylaxis to HIV-infected individuals at high risk of harboring or contracting tuberculosis infections, and complicates both detection and treatment of active tuberculosis cases. The recent proliferation of M. tuberculosis strains resistant to multiple drugs, most notably in the United States, compounds the problem... (AU)

Epidemiology of AIDS and tuberculosis

This article reviews literature on the epidemiology, pathogenicity, and control of HIV and Micobacterium tuberculosis coinfection. Regarding pathogenicity, immune system deterioration makes HIV-infected people more likely to develop active tuberculosis on primary or secondary exposure to the bacillus or to suffer reactivation of latent infections, and to experience considerably higher rates of extrapulmonary manifestations, relapses, and death. Regarding epidemiology, as of 1990 there were an estimated 3 million people coinfected with HIV and M. tuberculosis, with some 300 000 active tuberculosis cases and 120 000-150 000 tuberculosis deaths occurring annually among those coinfected. Over 500 000 coinfected people are thought to reside in the Americas, over 400 000 of them in Latin America. In general, the impact of coinfection is evident. Relatively high and increasing prevalences of HIV infection have been detected among tuberculosis patients around the world, and tuberculosis has become a frequent complication of AIDS cases. Moreover, there is no longer any doubt that coinfection obstructs tuberculosis prevention and control. Among other things, it effects BCG vaccination policies, suggests the need to administer preventive chemoprophylaxis to HIV-infected individuals at high risk of harboring or contracting tuberculosis infections, and complicates both detection and treatment of active tuberculosis cases. The recent proliferation of M. tuberculosis strains resistant to multiple drugs, most notably in the United States, compounds the problem... (AU)

Revised translation of an article entitled "Epidemiología del SIDA y la tuberculosis" that was published in Spanish in the BOSP. Vol. 116(6):546-65, 1994

Epidemiología del SIDA y la tuberculosis / Epidemiology of AIDS and tuberculosis

En este artículo, se revisan la patogenia de la coinfección por el virus de la inmunodeficiencia humana (VIH) y mycobacterium tuberculosis, sus características epidemiológicas en el mundo y especialmente en las Américas, así como las herramientas disponibles para su control. La relación entre la infección por VIH y por M. tuberculosis se hace evidente en dos situaciones: la frecuencia más alta de desarrollo de tuberculosis activa después de la primoinfección o reinfección exógena, y la reactivación del bacilo latente en el sujeto infectado por VIH al presentarse el deterioro de su sistema inmunitario. Se ha observado que las reacciones adversas a medicamentos, las recaídas y la mortalidad son más frecuentes en pacientes tuberculosos infectados por VIH que en los no infectados. El panorama en el mundo y el las Américas indica un aumento de los casos nuevos de tuberculosis y del síndrome de inmunodeficiencia adquirida (SIDA). La frecuencia de coinfectados es más alta en países y grupos humanos con alta prevalencia de infección por tuberculosis. El estudio de la coinfección puede realizarse desde tres enfoques. Primero, la estimación de la frecuencia de infección por VIH en pacientes tuberculosos. En las Américas, la prevalencia de infección por VIH en estos pacientes han sido más alta en las zonas metropolitanas del Brasil, Haití, los Estados Unidos de América y México. Segundo, la estimación de la frecuencia de tuberculosis en los casos de SIDA. En los casos de SIDA notificados anualmente en el Brasil y México se ha observado un aumento de la frecuencia de tuberculosis. La frecuencia más alta de tuberculosis en autopsias indica que la enfermedad no se diagnostica en el paciente vivo. Tercero, el estudio de la reactividad al PPD en poblaciones infectadas por VIH, cuya frecuencia varía entre 16 y 25 por ciento según el país. Por último se abordan los problemas de control de la tuberculosis en pacientes infectados por VIH o con SIDA: vacunación, quimioprofilaxis, búsqueda de casos y tratamiento

Epidemiología del SIDA y la tuberculosis / Epidemiology of AIDS and tuberculosis

En este artículo, se revisan la patogenia de la coinfección por el virus de la inmunodeficiencia humana (VIH) y mycobacterium tuberculosis, sus características epidemiológicas en el mundo y especialmente en las Américas, así como las herramientas disponibles para su control. La relación entre la infección por VIH y por M. tuberculosis se hace evidente en dos situaciones: la frecuencia más alta de desarrollo de tuberculosis activa después de la primoinfección o reinfección exógena, y la reactivación del bacilo latente en el sujeto infectado por VIH al presentarse el deterioro de su sistema inmunitario. Se ha observado que las reacciones adversas a medicamentos, las recaídas y la mortalidad son más frecuentes en pacientes tuberculosos infectados por VIH que en los no infectados. El panorama en el mundo y el las Américas indica un aumento de los casos nuevos de tuberculosis y del síndrome de inmunodeficiencia adquirida (SIDA). La frecuencia de coinfectados es más alta en países y grupos humanos con alta prevalencia de infección por tuberculosis. El estudio de la coinfección puede realizarse desde tres enfoques. Primero, la estimación de la frecuencia de infección por VIH en pacientes tuberculosos. En las Américas, la prevalencia de infección por VIH en estos pacientes han sido más alta en las zonas metropolitanas del Brasil, Haití, los Estados Unidos de América y México. Segundo, la estimación de la frecuencia de tuberculosis en los casos de SIDA. En los casos de SIDA notificados anualmente en el Brasil y México se ha observado un aumento de la frecuencia de tuberculosis. La frecuencia más alta de tuberculosis en autopsias indica que la enfermedad no se diagnostica en el paciente vivo. Tercero, el estudio de la reactividad al PPD en poblaciones infectadas por VIH, cuya frecuencia varía entre 16 y 25 por ciento según el país. Por último se abordan los problemas de control de la tuberculosis en pacientes infectados por VIH o con SIDA: vacunación, quimioprofilaxis, búsqueda de casos y tratamiento