RESUMO
The aim of the study was to re-assess neuropsychological profile in a group of boys with Duchenne muscular dystrophy without intellectual disability and neuropsychiatric disorder three years apart from a previous evaluation, to establish possible changes over time. We were also interested in defining more in detail correlation between genotype and neuropsychological phenotype. Thirty-three of the previous 40 subjects (mean age at follow up: 10 years and 7 months) agreed to participate in the follow up study and to perform the new assessment. The results confirm a typical neuropsychological profile, with difficulty in the manipulation of stored information, poor abstract reasoning and planning capacity and impulsiveness, supporting the involvement of a cerebellar striatal cortical network for these children. The more detailed description of subgroups of subjects, according to the real expression of Dp140, let to reveal possible genotype-neuropsychological phenotype correlations, and a more general neuropsychological impairment emerged in boys without Dp140 expression.
Assuntos
Distrofia Muscular de Duchenne/psicologia , Cerebelo , Criança , Função Executiva , Seguimentos , Genótipo , Humanos , Masculino , Distrofia Muscular de Duchenne/genética , Mutação , Testes Neuropsicológicos , FenótipoRESUMO
The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy.
Assuntos
Cognição , Função Executiva , Distrofia Muscular de Duchenne/psicologia , Criança , Humanos , Inteligência , Masculino , Memória de Curto Prazo , Testes Neuropsicológicos , Estudos ProspectivosRESUMO
BACKGROUND: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-α and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. METHODS: Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. RESULTS: The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low γ-glutamyltransferase (γ-GT) serum activities, a low pretreatment γ-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1-16.7, p < 0.001), low pretreatment γ-GT/ALT ratio (OR = 2.5, CI: 1.7-3.3, p < 0.001), age (OR = 0.96, CI: 0.94-0.98, p = 0.001) and RVR (OR = 4.18, CI: 2.85-8.65, p < 0.001) to be significantly related to treatment outcome. Patients with the IL28B rs12979860 CC genotype and a low pretreatment γ-GT/ALT ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10-71.1, p < 0.0001). CONCLUSION: The pretreatment γ-GT/ALT ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-α-based combination therapy in a nontriaged ordinary setting.
Assuntos
Alanina Transaminase/sangue , Hepacivirus/genética , Hepatite C Crônica/virologia , Interleucinas/genética , Polimorfismo Genético , RNA Viral/análise , gama-Glutamiltransferase/sangue , Adulto , Idoso , Antivirais/uso terapêutico , DNA/genética , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Humanos , Interferons , Interleucinas/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
The Elecsys hepatitis B surface antigen (HBsAg) II quantitative assay is a new quantitative electrochemiluminescence immunoassay which uses onboard dilution and a simple algorithm to determine HBsAg levels expressed in international units (IU)/ml (standardized against the World Health Organization [WHO] Second International Standard). This study evaluated its performance using routine serum samples from a wide range of HBsAg carriers and patients with chronic hepatitis B (CHB). HBsAg levels were measured in serum samples collected independently by five centers in Europe, Australia, and Asia. Serial dilution analyses were performed to assess the recommended dilution algorithm and determine the assay range free of hook effect. Assay precision was also established. Following assessment of serial dilutions (1:100 to 1:1,000,000) of the 611 samples analyzed, 70.0% and 85.6% of samples tested with analyzers incorporating 1:100 (Elecsys 2010 and cobas e 411) and 1:400 (Modular Analytics E170) onboard dilution, respectively, fell within the linear range of the assay, providing a final result on the first test. No high-dose hook effect was seen up to the maximum HBsAg serum level tested (870,000 IU/ml) using the dilution algorithm. HBsAg levels were reliably determined across all hepatitis B virus (HBV) genotypes, phases of HBV infection, and stages of disease tested. Precision was high across all analyzers (% coefficient of variation [CV], 1.4 to 9.6; HBsAg concentrations, 0.1 to 37,300 IU/ml). The Elecsys HBsAg II quantitative assay accurately and reliably quantifies HBsAg in routine clinical samples. Onboard dilution minimizes retesting and reduces the potential for error.
Assuntos
Técnicas de Laboratório Clínico/métodos , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/diagnóstico , Kit de Reagentes para Diagnóstico , Ásia , Austrália , Europa (Continente) , Humanos , Imunoensaio/métodosRESUMO
The standard test methods used to assess the efficiency of a disinfectant applied to surfaces are often based on counting the microbial survivors sampled in a liquid, but total cell removal from surfaces is seldom achieved. One might therefore wonder whether evaluations of microbial survivors in liquid-sampled cells are representative of the levels of survivors in whole populations. The present study was thus designed to determine the "damaged/undamaged" status induced by a peracetic acid disinfection for Bacillus atrophaeus spores deposited on glass coupons directly on this substrate and to compare it to the status of spores collected in liquid by a sampling procedure. The method utilized to assess the viability of both surface-associated and liquid-sampled spores included fluorescence labeling with a combination of Syto 61 and Chemchrome V6 dyes and quantifications by analyzing the images acquired by confocal laser scanning microscopy. The principal result of the study was that the viability of spores sampled in the liquid was found to be poorer than that of surface-associated spores. For example, after 2 min of peracetic acid disinfection, less than 17% ± 5% of viable cells were detected among liquid-sampled cells compared to 79% ± 5% or 47% ± 4%, respectively, when the viability was evaluated on the surface after or without the sampling procedure. Moreover, assessments of the survivors collected in the liquid phase, evaluated using the microscopic method and standard plate counts, were well correlated. Evaluations based on the determination of survivors among the liquid-sampled cells can thus overestimate the efficiency of surface disinfection procedures.
Assuntos
Bacillus/efeitos dos fármacos , Desinfetantes/farmacologia , Desinfecção/métodos , Microbiologia Ambiental , Viabilidade Microbiana/efeitos dos fármacos , Esporos/efeitos dos fármacos , Carga Bacteriana/métodos , Corantes Fluorescentes/metabolismo , Vidro , Ácido Peracético/farmacologia , Coloração e Rotulagem/métodosRESUMO
AIMS: To evaluate the impact of the mode of contamination in relation with the nature of solid substrates on the resistance of spores of Bacillus atrophaeus -selected as surrogates of Bacillus anthracis- to a disinfectant, peracetic acid. METHODS AND RESULTS: Six materials confronted in urban and military environments were selected for their different structural and physicochemical properties. In parallel, two modes of contamination were examined, i.e. deposition and immersion. Deposition was used to simulate contamination by an aerosol and immersion by an extended contact with liquids. A pronounced difference in the biocontamination levels and spatial organization of spores was observed depending on the mode of contamination and the nature of the solid substrate considered, with consequences on decontamination. Contamination by immersion led to lower efficiency of peracetic acid decontamination than contamination by deposition. Infiltration of spores into porous materials after immersion is one reason. In contrast, the deposition mode aggregates cells at the surface of materials, explaining the similar disinfecting behaviour of porous and nonporous substrates when considering this inoculation route. CONCLUSIONS: The inoculation route was shown to be as influential a parameter as material characteristics (porosity and wettability) for decontamination efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide comparative information for the decontamination of B. atrophaeus spores in function of the mode of contamination and the nature of solid substrates.
Assuntos
Bacillus anthracis/fisiologia , Desinfetantes/farmacologia , Desinfecção , Farmacorresistência Bacteriana/fisiologia , Contaminação de Equipamentos , Ácido Peracético/farmacologia , Desinfecção/métodos , Manufaturas/microbiologia , Esporos Bacterianos/fisiologiaRESUMO
The liver is the largest organ of the body. It is located between the portal and the general circulation, between the organs of the gastrointestinal tract and the heart. The main function of the liver is to take up nutrients, to store them, and to provide nutrients to the other organs. At the same time has the liver to take up potentially damaging substances like bacterial products or drugs delivered by the portal blood or microorganisms, which reach the circulation. The liver is not only an important power and sewage treatment plant of the body. In fact, the liver is probably the best example for a cheap recycling system. Both parenchymal and nonparenchymal liver cells participate in the clearance activities. The function of the liver as clearance organ, however, harbors the danger that the substances that should be degraded and/or eliminated lead to tissue damage. Thus, effective defense mechanisms are necessary. Among the nonparenchymal cells Kupffer cells, sinusoidal endothelial cells, and natural killer (NK) lymphocytes exert cellular defense functions for the whole body but also for the liver itself. Furthermore, each cell type of the liver, including the hepatocytes, possesses its own defense apparatus.
Assuntos
Hepatite/patologia , Hepatite/fisiopatologia , Regeneração Hepática , Fígado/patologia , Fígado/fisiopatologia , Animais , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Raios gama , Hepatite/etiologia , Hepatite Viral Animal/patologia , Hepatite Viral Animal/fisiopatologia , Hepatócitos/patologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/fisiopatologia , RatosRESUMO
OBJECTIVES: We studied the impact of hepatitis B virus (HBV) polymerase/reverse transcriptase (Pol/Rt) heterogeneity on adefovir rescue therapy in 34 consecutive chronic hepatitis B patients with viral breakthrough during lamivudine monotherapy. METHODS: The Pol/Rt A-F domains were directly sequenced in all patients at baseline, and 12 and 24 months. Response to therapy was evaluated at 3, 6, 12 and 24 months by quantitative HBV-DNA. RESULTS: Primary treatment failures did not occur. At 6 months 24/34 (70.6%) patients had viraemia<10(4) copies/mL [initial viral response (IVR)]; at 12 and 24 months 23 (71.9%) and 26 (81.3%) of 32 had HBV-DNA<200 copies/mL [complete viral response (CVR)]. IVR or CVR patients did not show viral breakthroughs, which occurred in one of the six remaining patients. All but three patients had baseline rtM204I/V substitutions associated with rtL180M in 23, rtL80I/V in 14, rtV173L in 4, rtT184S in 3, rtQ215S in 2 and rtA181S in 2 cases. rtA181S without rtM204I/V was found in one patient. Four of the six patients (67%) without 24 month CVR showed rtA181S or rtT184S substitutions either alone or with typical lamivudine resistance profiles. Baseline HBV-DNA levels were negatively associated with IVR (univariate analysis, P=0.023). At least one of rtA181S and rtT184S substitutions correlated negatively with IVR and CVR (univariate analysis, P=0.001) and was independently associated with absence of CVR (P = 0.016). CONCLUSIONS: Lamivudine monotherapy favours the emergence of viral quasispecies that influence the response rate to adefovir rescue therapy independently from baseline viraemia and lower the susceptibility to other nucleos(t)ide analogues.