RESUMO
The impact of the use of loop diuretics to prevent cumulative fluid balance in non-oliguric patients is uncertain. This is a retrospective study to estimate the association of time-averaging loop diuretic exposure in a large population of non-cardiac, critically ill patients with a positive fluid balance (> 5% of body weight). The exposure was loop diuretic and the main outcomes were 28-day mortality, severe acute kidney injury and successful mechanical ventilation weaning. Time-fixed and daily time-varying variables were evaluated with a marginal structural Cox model, adjusting bias for time-varying exposure and the presence of time-dependent confounders. A total of 14,896 patients were included. Patients receiving loop diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39-0.81 and baseline variables adjusted hazard ratio 0.53, 95%CI 0.45-0.62); after full adjusting, loop diuretics had no association with 28-day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74-1.54) or with reducing severe acute kidney injury occurrence during intensive care unit stay - hazard ratio 1.05 (95%CI 0.78-1.42). However, we identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35-1.89). The main results were consistent in the sub-group analysis for sepsis, oliguria and the study period (2002-2007 vs. 2008-2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant association with mortality. After adjusting for time-varying variables, the time average of loop diuretic exposure in non-cardiac, critically ill patients has no association with overall mortality or severe acute kidney injury; however, prolonged mechanical ventilation is a concern.
Assuntos
Cuidados Críticos/métodos , Diuréticos/uso terapêutico , Equilíbrio Hidroeletrolítico , Injúria Renal Aguda/prevenção & controle , Estado Terminal , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrPC) conversion into protease-resistant forms (protease-resistant PrP [PrPRes] or the scrapie form of PrP [PrPSc]) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified in vitro to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrPC mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP23-231) as the substrate and PrPSc seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP90-231), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrPC globular domain. J8 also reduced the fibrillation of mouse rPrP23-231 seeded with in vitro-produced fibrils. Furthermore, most of the compounds decreased the amount of PrPC on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrPC content on the cell surface.
Assuntos
Chalconas/farmacologia , Drogas em Investigação/farmacologia , Neurônios/efeitos dos fármacos , Oxidiazóis/farmacologia , Proteínas Priônicas/antagonistas & inibidores , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Chalconas/síntese química , Clonagem Molecular , Drogas em Investigação/síntese química , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Cinética , Camundongos , Simulação de Acoplamento Molecular , Neurônios/metabolismo , Neurônios/patologia , Oxidiazóis/síntese química , Proteínas Priônicas/química , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , TermodinâmicaRESUMO
Human bocavirus (HBoV) is a respiratory pathogen that affects young children. We screened 511 nasopharyngeal aspirates for hospital-acquired HBoV from infants hospitalised with respiratory infection from January to December 2008. Among 55 children with HBoV infection, 10 cases were hospital-acquired. Compared with the community-acquired cases, coinfection with other respiratory viruses in these patients was uncommon. HBoV should be considered for inclusion in screening protocols for nosocomial childhood respiratory infections, especially in intensive care units.
Assuntos
Infecção Hospitalar/epidemiologia , Bocavirus Humano/isolamento & purificação , Infecções por Parvoviridae/epidemiologia , Comorbidade , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/virologiaRESUMO
Comparison of the use of indirect immunofluorescence assay (IFA), immunochromatography assay (ICA-BD) and reverse transcription-polymerase chain reaction (RT-PCR) for detecting human respiratory syncytial virus (HRSV) in 306 nasopharyngeal aspirates samples (NPA) was performed in order to assess their analytical performance. By comparing the results obtained using ICA-BD with those using IFA, we found relative indices of 85.0% for sensitivity and 91.2% for specificity, and the positive (PPV) and negative (NPV) predictive values were 85.0% and 91.2%, respectively. The relative indices for sensitivity and specificity as well as the PPV and NPV for RT-PCR were 98.0%, 89.0%, 84.0% and 99.0%, respectively, when compared to the results of IFA. In addition, comparison of the results of ICA-BD and those of RT-PCR yielded relative indices of 79.5% for sensitivity and 95.4% for specificity, as well as PPV and NPV of 92.9% and 86.0%, respectively. Although RT-PCR has shown the best performance, the substantial agreement between the ICA-BD and IFA results suggests that ICA-BD, also in addition to being a rapid and facile assay, could be suitable as an alternative diagnostic screening for HRSV infection in children.
Assuntos
Cromatografia , Técnica Indireta de Fluorescência para Anticorpo , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Doença Aguda , Pré-Escolar , Cromatografia/métodos , Humanos , Líquido da Lavagem Nasal/virologia , Nasofaringe/virologia , Valor Preditivo dos Testes , RNA Viral/genética , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Sensibilidade e EspecificidadeRESUMO
Comparison of the use of indirect immunofluorescence assay (IFA), immunochromatography assay (ICA-BD) and reverse transcription-polymerase chain reaction (RT-PCR) for detecting human respiratory syncytial virus (HRSV) in 306 nasopharyngeal aspirates samples (NPA) was performed in order to assess their analytical performance. By comparing the results obtained using ICA-BD with those using IFA, we found relative indices of 85.0 percent for sensitivity and 91.2 percent for specificity, and the positive (PPV) and negative (NPV) predictive values were 85.0 percent and 91.2 percent, respectively. The relative indices for sensitivity and specificity as well as the PPV and NPV for RT-PCR were 98.0 percent, 89.0 percent, 84.0 percent and 99.0 percent, respectively, when compared to the results of IFA. In addition, comparison of the results of ICA-BD and those of RT-PCR yielded relative indices of 79.5 percent for sensitivity and 95.4 percent for specificity, as well as PPV and NPV of 92.9 percent and 86.0 percent, respectively. Although RT-PCR has shown the best performance, the substantial agreement between the ICA-BD and IFA results suggests that ICA-BD, also in addition to being a rapid and facile assay, could be suitable as an alternative diagnostic screening for HRSV infection in children.
Assuntos
Pré-Escolar , Humanos , Cromatografia , Técnica Indireta de Fluorescência para Anticorpo , Vírus Sincicial Respiratório Humano , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Vírus Respiratório Sincicial/diagnóstico , Doença Aguda , Cromatografia/métodos , Líquido da Lavagem Nasal/virologia , Nasofaringe/virologia , Valor Preditivo dos Testes , RNA Viral/genética , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Sensibilidade e EspecificidadeRESUMO
Ten out of eighty-nine strains biochemically identified as Clostridium perfringens, isolated from bovine organs, were selected by their different results showed in toxigenicity test on mice. Those and the standard strains, ATCC types A, B, C, and D, had their virulence exalted through serial intramuscular inoculation into guinea pigs. Results showed that, for toxigenic strains (6), one or two passages were enough to cause exaltation, while for the atoxigenic (4), five or six inoculations were needed. Esterase electrophoresis of standard and isolated strains, with and without exaltation, was performed. Electrophoresis analysis permits the following conclusions: strains that do not show any clinical symptoms in mice, when exalted demonstrate decreased esterase activity; on the contrary, it is increased when correlated with animal symptoms.
RESUMO
Ten out of eighty-nine strains biochemically identified as Clostridium perfringens, isolated from bovine organs, were selected by their different results showed in toxigenicity test on mice. Those and the standard strains, ATCC types A, B, C, and D, had their virulence exalted through serial intramuscular inoculation into guinea pigs. Results showed that, for toxigenic strains (6), one or two passages were enough to cause exaltation, while for the atoxigenic (4), five or six inoculations were needed. Esterase electrophoresis of standard and isolated strains, with and without exaltation, was performed. Electrophoresis analysis permits the following conclusions: strains that do not show any clinical symptoms in mice, when exalted demonstrate decreased esterase activity; on the contrary, it is increased when correlated with animal symptoms.
Assuntos
Animais , Bovinos , Bovinos , Clostridium perfringens , Eletroforese , VirulênciaRESUMO
The aim of this report is to explain the historical differences between Klippel-Trenaunay (KT), Klippel-Trenaunay-Weber (KTW), and Klippel-Trenaunay-Servelle (KTS) syndromes. Furthermore, an attempt will be made to describe the different causes, symptoms, and consequences of the pathology, largely as a consequence of venous hypertension. The significance of these syndromes within the pediatric population is highlighted.
Assuntos
Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Síndrome , Angiografia , Angiomatose/diagnóstico , Malformações Arteriovenosas/diagnóstico , Diagnóstico Diferencial , Extremidades , Feminino , Glaucoma/patologia , Hemangioma/diagnóstico , Hemangioma/patologia , Humanos , Lactente , Recém-Nascido , Perna (Membro) , Masculino , Doenças Vasculares/diagnósticoRESUMO
Eighty-nine of 144 isolates of Clostridium perfringens obtained from 187 samples of 71 bovine in several Brazilian states were submitted to esterase electrophoresis for typing. Mobilites electrophoresis, as parameter, were settled down by isolates from ATCC pattern of types A, B, C, and D. Of the 89 isolates, 43 (48.3%) were characterized as electrophoretic type A, 20 (22.5%) as D, 18 (20.2%) as C, and 3 (3.4%) as B. Five (5.6%) isolates did not identity with any type. Similarly, esterase electrophoresis enabled the typing of 94.4 % of the isolates, demonstrating to be an appropriate method for animal sample analyses.
RESUMO
Eighty-nine of 144 isolates of Clostridium perfringens abtained from 187 samples of 71 bovine in several Brazilian states were submitted to esterase electrophoresis for typing. Mobilites electrophoresis, as parameter, were settled down by isolates from ATCC pattern of types A, B, C, and D. Of the 89 isolates, 43 (48.3 per cent) were characterized as electrophoretic type A, 20 (22.5 per cent) as D, 18 (20.2 per cent) as C, and 3 (3.4 per cent) as B. Five (5.6 per cent) isolates did not identity with any type. Similarly esterase electrophoresis enabled the typing of 94.4 per cent of the isolates, demonstrating to be an appropriate method for animal sample analyses.