RESUMEN
Massive loss of lamina propria CD4(+) T cells, changes in the lymphatic architecture, and altered intestinal epithelial barrier leading to microbial translocation are the common features of HIV-1 infection and are not fully restored under combined antiretroviral therapy (cART). To better understand determinants of gut mucosal restoration, we have performed phenotypic and gene expression analyses of the gut from HIV-infected patients, naive or treated with cART initiated either at the early phase of the primary infection or later during the chronic phase. We found a depletion of T helper type 22 (Th22) and interleukin-17-producing cells in naive patients. These populations, except Th22 cells, were not restored under cART. Regulatory T cells/Th17 ratio was significantly increased in HIV-infected patients and was inversely correlated to the restoration of CD4(+) T cells but not to gut HIV DNA levels. Gene profile analysis of gut mucosal distinguished two groups of patients, which fitted with the timing of cART initiation. In their majority early, but not later treated patients, exhibited conserved intestinal lymphoid structure, epithelial barrier integrity and dendritic cell maturation pathways. Our data demonstrate that early initiation of cART helps to preserve and/or restore lymphoid gut mucosal homeostasis and provide a rationale for initiating cART during the acute phase of HIV infection.
Asunto(s)
Antirretrovirales/uso terapéutico , Células Dendríticas/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Intestinos/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , ADN Viral/sangre , Células Dendríticas/inmunología , Células Dendríticas/virología , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Perfilación de la Expresión Génica , Infecciones por VIH/inmunología , VIH-1/fisiología , Humanos , Inmunidad Mucosa/efectos de los fármacos , Interleucinas/metabolismo , Intestinos/inmunología , Intestinos/virología , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/virología , Células Th17/inmunología , Células Th17/virología , Resultado del Tratamiento , Interleucina-22RESUMEN
In French Guiana, severe cases of toxoplasmosis in immunocompetent patients are associated with atypical strains of Toxoplasma gondii linked to a wild neotropical rainforest cycle and a higher genetic diversity than usually observed for T. gondii isolates from anthropized environment. This raises the question of the impact of anthropization of the natural environment, on genetic diversity and on the population structure of T. gondii. However, few data are available on strains circulating in the anthropized areas from French Guiana. Seropositive animals originating mainly from anthropized sub-urban areas and punctually from wild environment in French Guiana were analyzed for T. gondii isolation and genotyping. Thirty-three strains were obtained by bioassay in mice and compared with 18 previously reported isolates chiefly originating from the Amazon rainforest. The genotyping analysis performed with 15 microsatellite markers located on 12 different chromosomes revealed a lower genetic diversity in the anthropized environment. Results were analyzed in terms of population structure by clustering methods, Neighbor-joining trees reconstruction based on genetic distances, F(ST,) Mantel's tests and linkage disequilibrium. They clearly showed a genetic differentiation between strains associated to the anthropized environment and those associated to the wild, but with some inbreeding between them. The majority of strains from the anthropized environment were clustered into additional lineages of T. gondii that are common in the Caribbean. In conclusion the two environmental populations "wild" and "anthropized" were genetically well differentiated. The anthropization of the environment seems to be accompanied with a decreased diversity of T. gondii associated with a greater structure of the populations. We detected potential interpenetration and genetic exchanges between these two environmental populations. As a higher pathogenicity in human of "wild" genotypes has been described, the interpenetration of both environments leads to hybridization between strains that may be at risk for human health.
Asunto(s)
Variación Genética , Toxoplasma/genética , Toxoplasmosis Animal/parasitología , Toxoplasmosis/parasitología , Animales , Teorema de Bayes , Análisis por Conglomerados , Guyana Francesa , Genotipo , Humanos , Ratones , Repeticiones de Microsatélite , Modelos Genéticos , Filogenia , Filogeografía , Polimorfismo Genético , Análisis de Componente Principal , Toxoplasma/clasificación , Vida SilvestreRESUMEN
CONTEXT: Erlotinib therapy for non small-cell lung cancer (NSCLC) has mainly been evaluated in randomized trials. METHOD: OBSTAR was a multicenter, retrospective, observational study involving all patients treated with erlotinib in 18 French centers between June 2005 and September 2007. The analyses focused on the patients' characteristics, previous treatments, and treatment efficacy during a three-year follow-up period. RESULTS: 534 patients were included in this study. The median survival times were respectively 5.2 [3.7-7.4] and 4.7 [4.1-5.7] months, depending to whether erlotinib was used as second- (n=190), or ≥ third-line treatment (n=305). The disease control rate were 39.1% [30.2-48.7] and 29.9% [29.6-36.9] according to the line of treatment. Factors predictive of an objective response were gender, age, and smoking status. Factors predictive of progression were age, sex, smoking status, the line of treatment, and the number of metastases. Treatment had to be interrupted for toxicity in 8.5% of cases. CONCLUSION: This study of erlotinib therapy in 2005-2007 confirms, in the general NSCLC patient population, the results of pivotal trials.
Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/administración & dosificación , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Clorhidrato de Erlotinib , Femenino , Estudios de Seguimiento , Francia , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Quinazolinas/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Fumar , Análisis de Supervivencia , Privación de TratamientoRESUMEN
OBJECTIVES: Texture-modified food (chopped, mashed, or mixed) is often used for patients, and particularly for dependent elderly people facing swallowing disorders or dental problems. Food must be energy and protein enriched, because dilution is needed for preparation, and several meals like bread can be removed. The aim of the study was to assess the food consumption of residents in four French nursing homes depending on diet texture. DESIGN/PARTICIPANTS/MEASUREMENTS: The food consumption of 87 elderly people followed by a nutrition network, randomly taken and living in nursing homes in which texture-modified food enrichment was practiced was evaluated according to the type of texture used. RESULTS: 13.8% of residents had chopped texture and 29.9% mixed texture. There was no relationship between used food textures and nutritional status residents. Calorie consumption was below the recommended intakes for elderly nursing home residents in France, whatever the type of texture. The mixed texture had more protein than the normal one and was better balanced regarding fat intake. Protein consumption was at the lower limit of the recommended intakes. Residents in overweight were those whose food consumption relative to their weight was the lowest. CONCLUSION: It seems important to check the mode of preparation of texture-modified food in nursing homes and to assess the real energy and protein consumptions of residents receiving this food.
Asunto(s)
Trastornos de Deglución/complicaciones , Dieta , Ingestión de Alimentos/fisiología , Ingestión de Energía/fisiología , Manipulación de Alimentos/métodos , Anciano , Anciano de 80 o más Años , Proteínas en la Dieta/administración & dosificación , Femenino , Análisis de los Alimentos , Alimentos Fortificados , Francia , Hogares para Ancianos , Humanos , Masculino , Masticación/fisiología , Casas de Salud , Fenómenos Fisiológicos de la Nutrición/fisiología , Estado NutricionalRESUMEN
This study compared physical characteristics (body height [BH], body mass [BM], body fat [BF], and fat free mass [FFM]), one repetition maximum bench press (1RM (BP)), jumping explosive power (VJ), handball throwing velocity, power-load relationship of the leg and arm extensor muscles, 5- and 15-m sprint running time, and running endurance in elite (n = 16; EF) and amateur (n = 15; AF) female handball players aged 17 - 38. Results revealed that, compared to AF, EF players presented similar values in body mass and percent body fat, but higher values (p < 0.001 - 0.05) in BH (6 %), FFM (10 %), 1RM (BP) (23 %), VJ (10 %), handball throwing velocity (11 %), power-load relationship of the arm (25 %) and leg (12 %) extensors, as well as 5- and 15-m sprint (3 - 4 %) and endurance running velocities (13 %). Univariate regression analyses showed that 1RM (BP) was associated with throwing velocity (R (2) = 0.64). The higher absolute values of maximal strength and muscle power, although explained by the differences in fat free mass, will give EF an advantage to sustain certain handball game actions. The association between 1RM (BP) and throwing velocity suggests that throwing velocity values in female handball players depend more on maximal strength than on the capacity to move low loads at high velocities, during elbow extension actions.