Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse event associated with the use of antipsychotics (AP). The objective of this study was to investigate the profile of cases of NMS and to compare our findings with those published in similar settings. A series of 18 consecutive patients with an established diagnosis of NMS was analyzed, gathering data on demography, symptoms and signs. Two thirds of all cases involved woman with a past medical history of psychiatric disorder receiving relatively high doses of AP. The signs and symptoms of NMS episodes were similar to those reported in other series and only one case had a fatal outcome, the remaining presenting complete recovery. As expected, more than two thirds of our cases were using classic AP (68%), however the clinical profile of these in comparison with those taking newer agent was similar. Newer AP also carry the potential for NMS. Key words: atypical antipsychotics, typical antipsychotics, neuroleptic malignant syndrome.Síndrome neuroléptica maligna RESUMO A síndrome neuroléptica maligna (SNM) é um evento adverso potencialmente fatal associado ao uso de antipsicóticos (AP). O objetivo deste estudo foi investigar as características clínicas de cases da SNM e comparar nossos resultados com os publicados na literatura. Uma série de 18 pacientes com diagnóstico confirmado de SNM foram analisados, associando dados demográficos, apresentação clínica, diagnóstico e tratamento. Dois terços dos casos envolveram mulheres com antecedentes psiquiátricos que recebeceram doses relativamente altas de AP. Os sinais e sintomas foram semelhantes àqueles já relatados na literatura e a maioria dos pacientes teve uma recuperação completa, exceto por um caso com desfecho fatal. Houve predomínio de pacientes que usam medicamentos neurolépticos clássicos (68%), porém não houve diferença nas manifestações destes casos em relação àqueles que usavam AP novos. AP mais novos também têm o potencial de causar SNM. Palavras-Chave: neurolépticos atípicos, neurolépticos típicos, síndrome neuroléptica maligna.
The cellular receptor for hepatitis B virus (HBV)has not yet been identified. A recent candidate is a homologue of squamous cell carcinoma antigen 1 (SCCA1), a serpin. This study confirms that transfection of SCCA1 into mammalian cells (both hepatocyte-derived and of non-hepatocyte origin) results in increased HBV binding. Furthermore, virus bound to transfected cells is protected significantly from degradation by trypsin (75% compared with 30% in untransfected cells). The possibility that HBV enters cells via the hepatic clearance system for serpin-enzyme complexes was investigated by analysis of the reactive site loop of SCCA1. Functional and deletion mutants of SCCA1 were constructed by site-directed mutagenesis and compared with the wild type construct. In no case was virus binding reduced by functional alterations or deletions within the reactive site loop. A possible role for the low density lipoprotein receptor-related protein (LRP) in binding virus was investigated. SCCA1 transfection of Huh7 cells was shown to result in up-regulation of LRP expression, reaching levels observed in total liver. However, the use of receptor-associated protein (RAP), a competitive ligand for LRP, suggests than LRP up-regulation is not responsible for enhanced virus binding to SCCA1-transfected cells.Hepatitis B virus (HBV) 1 is a member of the hepadnavirus family and exhibits extreme host and tissue specificity, being able to infect only humans and higher primates and its replication being limited almost exclusively to hepatocytes. The molecular basis of this hepatotropism remains poorly understood but may be attributable to a combination of factors, including liver-specific transcription factors required by the virus for replication, and liver-specific expression of the host cell receptor utilized during the initial stages of infection (1).The early stages of the HBV life cycle, virus binding and internalization, remain obscure, largely because of the lack of a permissive cell culture system. Many studies have made use of primary hepatocytes, but difficulties in obtaining these cells, and variability between and within batches, hamper the use of primary tissue. Moreover, primary hepatocytes lose susceptibility to HBV infection within days (2).The cellular receptor for HBV has proved elusive. , bears significant sequence homology to a serine proteinase inhibitor (serpin), squamous cell carcinoma antigen 1 (SCCA1). HBV-BP was shown to interact with the pre-S1 domain of the HBV surface protein, which is now widely accepted to be the viral ligand involved in the initial interaction with the cellular receptor (4, 5). Furthermore, transfection of HBV-BP into HepG2 cells resulted in a 2-fold increase in virus binding capacity, whereas Chinese hamster ovary cells transfected with HBV-BP showed a newly acquired susceptibility to virus binding, albeit at low levels. It was reported also that virus particles were internalized to a greater degree in cells expressing HBV-BP. These results have not yet been confirmed.The possibility tha...
IntroductionThe first 2000 days of a child’s life (during pregnancy up to age 5 years) represent a critical period, in which early interventions reduce risk associated with developmental delay, disability and intergenerational disadvantage. The risk is exacerbated by barriers to specialised early intervention for children and families. This scoping review seeks to contribute to the evidence for sustaining integrated community-based specialist care in these earliest years of a child’s life.Methods and analysisThe Joanna Briggs Institute scoping review framework will be followed. Inclusion and exclusion criteria for screening of literature is predefined, guided by the criteria of population, concept and context. The review will identify models of care delivery, and will identify quality of care outcomes that have been measured, including evidence of reliability and validity. Sources of evidence will include CINAHL, Cochrane databases, Medline, PsycINFO and Scopus.Ethics and disseminationIn a three-part study, evidence synthesis from the scoping review of the literature; mapping of existing specialist early years services in one community and a consumer consultation (Curtin University Human Research Ethics approval HRE2021-0546) in the same community will inform a model of integrated care that accounts for the context of the community it seeks to serve. Results will be disseminated by peer-reviewed publications and conference presentations, contributing to the evidence base for delivering sustainable community-based integrated care in the context of the first 2000 days. This protocol is specific to the scoping review.
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