RESUMEN
BACKGROUND: Limited evidence suggests that being flooded may increase mortality and morbidity among affected householders not just at the time of the flood but for months afterwards. The objective of this study is to explore the methods for quantifying such long-term health effects of flooding by analysis of routine mortality registrations in England and Wales. METHODS: Mortality data, geo-referenced by postcode of residence, were linked to a national database of flood events for 1994 to 2005. The ratio of mortality in the post-flood year to that in the pre-flood year within flooded postcodes was compared with that in non-flooded boundary areas (within 5 km of a flood). Further analyses compared the observed number of flood-area deaths in the year after flooding with the number expected from analysis of mortality trends stratified by region, age-group, sex, deprivation group and urban-rural status. RESULTS: Among the 319 recorded floods, there were 771 deaths in the year before flooding and 693 deaths in the year after (post-/pre-flood ratio of 0.90, 95% CI 0.82, 1.00). This ratio did not vary substantially by age, sex, population density or deprivation. A similar post-flood 'deficit' of deaths was suggested by the analyses based on observed/expected deaths. CONCLUSIONS: The observed post-flood 'deficit' of deaths is counter-intuitive and difficult to interpret because of the possible influence of population displacement caused by flooding. The bias that might arise from such displacement remains unquantified but has important implications for future studies that use place of residence as a marker of exposure.
Asunto(s)
Inundaciones/mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Inglaterra/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Inundaciones/historia , Inundaciones/estadística & datos numéricos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Sistema de Registros , Gales/epidemiología , Adulto JovenRESUMEN
During an effort to search for more potent growth hormone secretagogues, we discovered a class of compounds of which the best compound 8 was 7-fold more active in vitro than the best compound in the series we revealed before [Tata, J. R.; Lu, Z.; Jacks, T. M.; Schleim, K. D.; Cheng, K.; Wei, L.; Chan, W.-S.; Butler, B.; Tsou, N.; Leung, K.; Chiu, S.-H. L.; Hickey, G. J.; Smith, R. G.; Patchett, A. A. Bioorg. Med. Chem. Lett.1997, 7, 2319.]. Animal studies show that compound 8 can stimulate growth hormone release at the oral dose as low as 0.06 mpk. Chemistry and biological studies are discussed.
Asunto(s)
Química Farmacéutica/métodos , Hormona del Crecimiento/química , Hormona del Crecimiento/síntesis química , Administración Oral , Amidas/química , Aminas/química , Animales , Perros , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Hormona del Crecimiento/metabolismo , Indoles/farmacología , Modelos Químicos , Hipófisis/química , Hipófisis/citología , Hipófisis/efectos de los fármacos , Ratas , Compuestos de Espiro/farmacología , Relación Estructura-ActividadRESUMEN
A new series of growth hormone secretagogues have been discovered. The best compound, 26j, shows excellent ability to release growth hormone both in vitro and in vivo. The synthesis and biological activity of these compounds are discussed.