RESUMO
SETTING: University-affiliated hospital located in Porto, North Portugal, an area with a low to intermediate incidence of tuberculosis (TB). OBJECTIVE: To identify predictors and outcomes of disseminated TB (dTB). DESIGN: A cohort of patients diagnosed with TB between 2007 and 2013 was retrospectively analysed. Patients with dTB criteria were characterized and compared to single organ TB cases. Factors independently associated with dTB were determined by multivariate logistic regression analysis. RESULTS: A total of 744 patients were analysed, including 145 with dTB. Independent risk factors for dTB were pharmacological immunosuppression (OR 5.6, 95% CI 2.8-11.3), HIV infection (OR 5.1, 95% CI 3.1-8.3), chronic liver failure or cirrhosis (OR 2.3, 95% CI 1.4-4.1) and duration of symptoms (OR 2.3, 95% CI 1.4-3.8). Compared to single organ TB, the clinical presentation of dTB patients differed by the absence of haemoptysis (OR 3.2, 95% CI 1.3-8.4) and of dyspnoea (OR 1.9, 95% CI 1.2-3.1), presence of weight loss (OR 1.8, 95% CI 1.1-2.9), night sweats (OR 1.7, 95% CI 1.1-2.7) and bilateral lung involvement (OR 4.4, 95% CI 2.8-7.1). Mortality and time until culture conversion were higher for dTB patients, although not reaching statistical significance. CONCLUSION: Immunosuppressive conditions and chronic liver failure or cirrhosis were associated with increased risk of dTB. The haematogenous spread may be dependent on longer symptomatic disease and usually progresses with bilateral lung involvement.
Assuntos
Hospedeiro Imunocomprometido , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Miliar/etiologia , Adulto , Idoso , Antituberculosos/uso terapêutico , Distribuição de Qui-Quadrado , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Portugal/epidemiologia , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Estatísticas não Paramétricas , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Miliar/epidemiologiaRESUMO
Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.
Assuntos
Linfoma não Hodgkin/genética , Polimorfismo Genético , Receptor Toll-Like 9/genética , Feminino , Genética Populacional , Humanos , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease, is a fatal inherited neurodegenerative disorder. The major clinical features of this disease are vision loss, seizures and progressive cognitive and motor decline starting in childhood. Mutations in CLN3 are known to cause the disease, allowing the generation of mouse models that are powerful tools for JNCL research. In this study, we applied behavioural phenotyping protocols to test for early behavioural alterations in Cln3(Deltaex7/8) knock-in mice, a genetic model that harbours the most common disease-causing CLN3 mutation. We found delayed acquisition of developmental milestones, including negative geotaxis, grasping, wire suspension time and postural reflex in both homozygous and heterozygous Cln3(Deltaex7/8) preweaning pups. To further investigate the consequences of this neurodevelopmental delay, we studied the behaviour of juvenile mice and found that homozygous and heterozygous Cln3(Deltaex7/8) knock-in mice also exhibit deficits in exploratory activity. Moreover, when analysing motor behaviour, we observed severe motor deficits in Cln3(Deltaex7/8) homozygous mice, but only a mild impairment in motor co-ordination and ambulatory gait in Cln3(Deltaex7/8) heterozygous animals. This study reveals previously overlooked behaviour deficits in neonate and young adult Cln3(Deltaex7/8) mice indicating neurodevelopmental delay as a putative novel component of JNCL.
