Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biophys Chem ; 254: 106246, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31426023

RESUMO

The inhibitory effect of the flavonoid naringenin on plant and human Two-Pore Channels (TPCs) was assessed by means of electrophysiological measurements. By acting on human TPC2, naringenin, was able to dampen intracellular calcium responses to VEGF in cultured human endothelial cells and to impair angiogenic activity in VEGF-containing matrigel plugs implanted in mice. Molecular docking predicts selective binding sites for naringenin in the TPC structure, thus suggesting a specific interaction between the flavonoid and the channel.


Assuntos
Canais de Cálcio/química , Flavanonas/química , Plantas/metabolismo , Animais , Sítios de Ligação , Cálcio/química , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Colágeno/química , Combinação de Medicamentos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Flavanonas/metabolismo , Humanos , Laminina/química , Camundongos , Simulação de Acoplamento Molecular , Técnicas de Patch-Clamp , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/metabolismo , Proteoglicanas/química
3.
Epidemiol Infect ; 144(10): 2117-27, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26916674

RESUMO

We aimed to assess the performance of active surveillance for hospitalized childhood encephalitis in New South Wales (NSW) using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network to inform methodology for the nationwide Australian childhood encephalitis (ACE) study. We piloted active surveillance for suspected encephalitis from May to December 2013 at the Children's Hospital at Westmead, Sydney, NSW. Cases were ascertained using four screening methods: weekday nurse screening of admission records (PAEDS), cerebrospinal fluid (CSF) microscopy records, magnetic resonance imaging (MRI) reports, and pharmacy dispensing records. Comprehensive clinical data were prospectively collected on consented participants and subsequently reviewed by an expert panel. Cases were categorized as confirmed encephalitis or 'not encephalitis'; encephalitis cases were sub-categorized as infectious, immune-mediated or unknown. We performed an ICD-10 diagnostic code audit of hospitalizations for the pilot period. We compared case ascertainment in the four screening methods and with the ICD code audit. Forty-eight cases of suspected encephalitis were identified by one or more methods. PAEDS was the most efficient mechanism (yield 34%), followed by MRI, CSF, and pharmacy audits (yield 14%, 12%, and 7% respectively). Twenty-five cases met the criteria for confirmed encephalitis. PAEDS was the most sensitive of the mechanisms for confirmed encephalitis (92%) with a positive predictive value (PPV) of 72%. The ICD audit was moderately sensitive (64%) but poorly specific (Sp 9%, PPV 14%). Of the 25 confirmed encephalitis cases, 19 (76%) were sub-categorized as infectious, three (12%) were immune-mediated, and three (12%) were 'unknown'. We identified encephalitis cases associated with two infectious disease outbreaks (enterovirus 71, parechovirus 3). PAEDS is an efficient, sensitive and accurate surveillance mechanism for detecting cases of childhood encephalitis including those associated with emerging infectious diseases. Active surveillance significantly increases the ascertainment of encephalitis cases compared with passive approaches.


Assuntos
Encefalite/epidemiologia , Vigilância da População/métodos , Adolescente , Criança , Pré-Escolar , Encefalite/virologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , New South Wales/epidemiologia , Projetos Piloto
4.
Nat Prod Res ; 30(2): 185-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26222766

RESUMO

Digestate coming from an Anaerobic Digestion unit in a Biogas Plant, feeded on cow manure and vegetable waste from markets, has been used. About 8-35 L polyethylene transparent bags have been employed as cultivation container, outdoor. Different aliquots of digestate, alone or mixed with commercial liquid fertiliser, were employed to cultivate in batch Scenedesus dimorphus, a freshwater green microalga, in the ENEA facilities of Casaccia Research Center, near Rome, Italy. The cultivation period was June-July 2013. The average daily yields of dry microalgae biomass varied from 20 mg/L/d to 60 mg/L/d, mean 38.2 mg/L/d. Final dry biomass concentration varied from 0.18 to 1.29 g/L, mean 0.55 g/L. S. dimorphus proved to be very efficient in removing N and P from the culture medium. Another fact emerged from these trials is that S. dimorphus inner composition resulted to be variable in response to the tested different culture conditions.


Assuntos
Biocombustíveis , Fotobiorreatores , Scenedesmus/crescimento & desenvolvimento , Anaerobiose , Animais , Biomassa , Bovinos , Desenho de Equipamento , Feminino , Água Doce , Itália , Esterco , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Scenedesmus/metabolismo , Técnicas de Cultura de Tecidos/métodos
5.
Biochim Biophys Acta ; 1858(3): 607-12, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26431786

RESUMO

Plant cells possess a large intracellular compartment that animal cells do not, the central vacuole, which has been investigated for a long time. The central vacuole can occupy up to 90% of the cellular volume and, differently from intracellular organelles from animal cells such as lysosomes or endosomes, it is easy to isolate. Because of its large dimension (up to 40 µm diameter) it can be successfully studied using the classical patch-clamp technique. Following the idea that the vacuolar membrane could be used as a convenient model to characterize the functional properties of channel-forming peptides, we verified that the phytotoxic lipodepsipeptide Syringopeptin 25A from Pseudomonas syringae pv syringae was able to form ionic pores in sugar beet vacuoles and we performed a detailed biophysical analysis. Recently, we extended the use of plant vacuoles to the expression and functional characterization of animal intracellular transporters, namely rat CLC-7, and channels, i.e. human TPC2. Since endo-lysosomal transporters and channels are still largely unexplored, principally because their intracellular localization renders them difficult to study, we believe that this novel approach will prove to be a powerful system for the investigation of the molecular mechanisms of exogenous transporters and channels. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.


Assuntos
Canais de Cálcio , Proteínas de Transporte , Canais de Cloreto , Membranas Intracelulares/metabolismo , Peptídeos Cíclicos , Células Vegetais/metabolismo , Vacúolos , Animais , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Humanos , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/metabolismo , Pseudomonas syringae , Ratos , Vacúolos/genética , Vacúolos/metabolismo
6.
Cell Death Dis ; 6: e1684, 2015 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-25766323

RESUMO

Insulin release in response to glucose stimulation requires exocytosis of insulin-containing granules. Glucose stimulation of beta cells leads to focal adhesion kinase (FAK) phosphorylation, which acts on the Rho family proteins (Rho, Rac and Cdc42) that direct F-actin remodeling. This process requires docking and fusion of secretory vesicles to the release sites at the plasma membrane and is a complex mechanism that is mediated by SNAREs. This transiently disrupts the F-actin barrier and allows the redistribution of the insulin-containing granules to more peripheral regions of the ß cell, hence facilitating insulin secretion. In this manuscript, we show for the first time that BAG3 plays an important role in this process. We show that BAG3 downregulation results in increased insulin secretion in response to glucose stimulation and in disruption of the F-actin network. Moreover, we show that BAG3 binds to SNAP-25 and syntaxin-1, two components of the t-SNARE complex preventing the interaction between SNAP-25 and syntaxin-1. Upon glucose stimulation BAG3 is phosphorylated by FAK and dissociates from SNAP-25 allowing the formation of the SNARE complex, destabilization of the F-actin network and insulin release.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Reguladoras de Apoptose/biossíntese , Quinase 1 de Adesão Focal/genética , Insulina/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Proteínas Reguladoras de Apoptose/metabolismo , Feminino , Quinase 1 de Adesão Focal/metabolismo , Regulação da Expressão Gênica , Glucose/administração & dosagem , Humanos , Insulina/genética , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Fosforilação , Ligação Proteica , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Proteína 25 Associada a Sinaptossoma/genética , Sintaxina 1/metabolismo , Análise Serial de Tecidos
8.
Open Biochem J ; 7: 1-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23407460

RESUMO

Glioblastoma multiforme (GBM) is the most common malignant and resistant tumor of the central nervous system in humans and new therapeutic strategies are urgently required. Recently, we have shown that the potential chemotherapeutic polyphenol xanthohumol (XH), isolated from Humulus Lupulus, induces apoptosis of human T98G glioblastoma cells by increasing reactive oxygen species and activating MAPK pathways. Then we have found, by western blotting and microscopic analysis, that XH up-regulates cytosolic levels of ANXA1 and induces translocation of the protein on the cell membrane of T98G cells in a time-dependent manner with significant effects observed after 24 h. On the basis of the above evidence, the aim of this work was to investigate the role of intracellular and cell membrane localized ANXA1 in GBM cells. RT-PCR analysis has shown that XH up-regulates mRNA levels of ANXA1 after 16 h treatment. To demonstrate the involvement of ANXA1 in apoptosis of GBM cells we down-regulated ANXA1 expression with small interfering RNA (siRNA) and then analysed apoptosis in the presence and absence of apoptotic stimuli. Importantly, apoptosis induced by XH was reduced in siRNA-ANXA1 transfected cells where western blot analysis shows a significant reduction of ANXA1 protein levels. To investigate the role of ANXA1 expression on the cell membrane of T98G cells as potential "eat-me" signal we studied phagocytosis of apoptotic cells by human macrophages. We incubated apoptotic T98G cells with human blood monocyte derived macrophages (M=). After co-incubation period we analysed the percentage of M= phagocytosing the apoptotic cells by cytofluorimetric FACS analysis and by confocal microscopy. Our results show that XH induces phagocytosis of apoptotic T98G cells by human M= in a concentration-effect manner, a processes that is dependent on caspase mediated apoptosis. ANXA1 acts as an "eat-me" signal on the cell membrane of T98G cells, and interestingly, apoptotic siRNA-ANXA1 transfected cells are not completely ingested by M=. These results were confirmed by incubating apoptotic cells with a neutralizing anti-ANXA1 antiboby and ANXA1 membrane depletion by EDTA washing. ANXA1 was also detected in supernatants of apoptotic cells and the incubation of enriched supernatants enhanced the percentage of phagocytosis by M=. These results demonstrated that ANXA1 is involved both in the apoptosis and phagocytosis of glioblastoma cells. This study shows a possible role of ANXA1 in maintenance of brain homeostasis and may lead to novel therapeutic approaches for neuro-inflammatory diseases and chemotherapy targets in the treatment of glioblastoma multiforme.

9.
Oncogene ; 31(50): 5153-61, 2012 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-22310281

RESUMO

BAG3 is a co-chaperone of the heat shock protein (Hsp) 70, is expressed in many cell types upon cell stress, however, its expression is constitutive in many tumours. We and others have previously shown that in neoplastic cells BAG3 exerts an anti-apoptotic function thus favoring tumour progression. As a consequence we have proposed BAG3 as a target of antineoplastic therapies. Here we identify a novel role for BAG3 in regulation of neo-angiogenesis and show that its downregulation results in reduced angiogenesis therefore expanding the role of BAG3 as a therapeutical target. In brief we show that BAG3 is expressed in endothelial cells and is essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation that in turn determines increased levels of p21 and p15 and cell-cycle arrest in the G1 phase.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sistema de Sinalização das MAP Quinases , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose , Pontos de Checagem do Ciclo Celular/fisiologia , Linhagem Celular , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo , Fosfatase 6 de Especificidade Dupla/genética , Fosfatase 6 de Especificidade Dupla/metabolismo , Fase G1/fisiologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fosforilação , Ligação Proteica
10.
Mini Rev Med Chem ; 11(6): 486-91, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21561408

RESUMO

On the basis of harmine and 1-methoxy-canthin-6-one chemical structures, a series of novel 1,4-disubstituted and 1,4,9-trisubstituted ß-carbolines and tetracyclic derivatives were designed and synthesized. Cytotoxic activities of these compounds in vitro were investigated in a human tumor cell line panel. Almost all compounds demonstrated interesting cytotoxic activities in particular against prostate cancer cells PC-3 with IC50 in the low micromolar range. Compound X was found to be the most potent one with IC50 value of 8.0 µM; this suggests further studies with models of prostate cancer.


Assuntos
Antineoplásicos/síntese química , Carbolinas/química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Carbolinas/farmacocinética , Carbolinas/toxicidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos
11.
Oncogene ; 27(8): 1175-8, 2008 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-17724475

RESUMO

Heat-shock proteins (HSP) 90 exert a relevant role in the survival and response to therapy of many neoplastic cell types. Here, we show that the promoter of hsp90alpha gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-kappaB (NF-kappaB) activity. Indeed, we found that NF-kappaB factors bound to one of the two putative consensus sequences present in the hsp90alpha-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetate-stimulated expression of a luciferase reporter gene under the control of the hsp90alpha promoter. Furthermore, the downmodulation of NF-kappaB (p65) levels by a specific small interfering (si) RNA resulted in reducing the levels of endogenous HSP90alpha protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-kappaB factors and HSPs in cell defence machinery.


Assuntos
Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição RelA/fisiologia , Sequência de Bases , Linhagem Celular , Núcleo Celular/genética , Sobrevivência Celular/genética , Genes Reporter , Proteínas de Choque Térmico HSP90/biossíntese , Células HeLa , Humanos , Dados de Sequência Molecular , Regiões Promotoras Genéticas/fisiologia , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo
12.
FASEB J ; 20(9): 1498-500, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16720734

RESUMO

Annexin A1 (ANXA1) has an important role in cell-cell communication in the host defense and neuroendocrine systems. In both systems, its actions are exerted extracellularly via membrane-bound receptors on adjacent sites after translocation of the protein from the cytoplasm to the cell surface of adjacent cells. This study used molecular, microscopic, and pharmacological approaches to explore the mechanisms underlying the cellular exportation of ANXA1 in TtT/GF (pituitary folliculo-stellate) cells. LPS caused serine-phosphorylation of ANXA1 (ANXA1-S27-PO4) and translocation of the phosphorylated protein to the cell membrane. The fundamental requirement of phosphorylation for membrane translocation was confirmed by immunofluorescence microscopy on cells transfected with wild-type or mutated (S27/A) ANXA1 constructs tagged with enhanced green fluorescence protein. The trafficking of ANXA1-S27-PO4 to the cell surface was dependent on PI3-kinase and MAP-kinase. It also required HMG-coenzyme A and myristoylation. The effects of HMG-coenzyme A blockade were overcome by mevalonic acid (the product of HMG-coenzyme A) and farnesyl-pyrophosphate but not by geranyl-geranylpyrophosphate or cholesterol. Together, these results suggest that serine-27 phosphorylation is essential for the translocation of ANXA1 across the cell membrane and also identify a role for isoprenyl lipids. Such lipids could target consensus sequences in ANXA1. Alternatively, they may target other proteins in the signal transduction cascade (e.g., transporters).


Assuntos
Anexina A1/metabolismo , Membrana Celular/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Anexina A1/genética , Comunicação Celular , Linhagem Celular Tumoral , Citoplasma/metabolismo , Inibidores Enzimáticos/farmacologia , Genes Reporter , Lipopolissacarídeos/farmacologia , Ácido Mevalônico/farmacologia , Camundongos , Mutagênese Sítio-Dirigida , Fosforilação , Neoplasias Hipofisárias , Transporte Proteico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
13.
Cancer Biol Ther ; 5(6): 643-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16627980

RESUMO

We investigated the expression of annexin-1 (ANXA1) in thyroid carcinoma cell lines and in thyroid cancers with a different degree of differentiation. The highest level of ANXA1 expression examined by Western blotting was detected in the papillary carcinoma cells (NPA) and in the follicular cells (WRO). On the other hand, the most undifferentiated thyroid carcinoma cells (ARO and FRO) presented the lowest level of ANXA1 expression. In surgical tissue specimens from 32 patients with thyroid cancers, we found high immunoreactivity for ANXA1 in papillary (PTC) and follicular (FTC) thyroid cancers while in undifferentiated thyroid cancers (UTC) the expression of the protein was barely detectable. Control thyroid tissue resulted positive for ANXA1. In summary, 70% of UTC examined weakly expressed ANXA1, whereas 65% of PTC or FTC specimens tested showed high expression of the protein. Thus ANXA1 expression may correlate with the tumorigenesis suggesting that the protein may represent an effective differentiation marker in thyroid cancer.


Assuntos
Anexina A1/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Glândula Tireoide/patologia , Células Tumorais Cultivadas
15.
Arch Dis Child ; 89(2): 170-5, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14736637

RESUMO

AIMS: To determine the outcome of children with neuromuscular disease (NMD) following admission to a tertiary referral paediatric intensive care (PICU). METHODS: All children with chronic NMD whose first PICU admission was between July 1986 and June 2001 were followed up from their first PICU admission to time of study. The outcomes recorded were death in or outside of PICU, duration of PICU admission, artificial ventilation during admission and following discharge from PICU, and readmission to PICU. RESULTS: Over 15 years, 28 children were admitted on 69 occasions. Sixteen (57%) children had more than one admission. The median duration of PICU admission was 4 days (range 0.5-42). Twenty three per cent of unplanned admissions resulted in the commencement of respiratory support that was continued after discharge from the PICU. Severity of functional impairment was not associated with longer duration of stay or higher PRISM scores. Ten children (36%) died, with four (14%) deaths in the PICU. A higher proportion of children with severe limitation of function were among children that died compared to survivors. CONCLUSION: Most children with NMD admitted to the PICU recover and are discharged without the need for prolonged invasive ventilation. However, in this group of children, the use of non-invasive home based ventilation is common and they are likely to require further PICU admission.


Assuntos
Cuidados Críticos , Doenças Neuromusculares/complicações , Pediatria , Infecções Respiratórias/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação , Masculino , Doenças Neuromusculares/mortalidade , Doenças Neuromusculares/terapia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/terapia , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do Tratamento
18.
Anaesth Intensive Care ; 30(6): 786-93, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12500519

RESUMO

Despite the risk of propofol infusion syndrome, a rare but often fatal complication of propofol infusion in ventilated children and possibly adults, propofol infusion remains in use in paediatric intensive care units (PICU). This questionnaire study surveys the current pattern of use of this sedative infusion in Australian and New Zealand PICUs. Thirty-three of the 45 paediatric intensive care physicians surveyed (73%), from 12 of the 13 intensive care units, returned completed questionnaires. The majority of practitioners (82%) use propofol infusion in children in PICU, the main indication being for short-term sedation in children requiring procedures. 39% of respondents consider propofol infusion useful in ventilated children requiring longer-term sedation. 67% of paediatric intensivists use maximum infusion doses that may be considered dangerously high (> or = 10 mg/kg/h). Nineteen per cent use propofol infusion for prolonged periods (> 72 hours). A smaller proportion (15%) of respondents indicate that they may use both higher doses and prolonged periods of infusion, a practice likely to lead to a greater chance of serious adverse events. Knowledge of local protocols for the use of propofol infusion is associated with a significantly greater level of monitoring for possible adverse events. We suggest that national guidelines for the use of propofol infusion in children should be developed. These should include clear indications and contraindications to its use, a maximum dose rate and maximum period of infusion, with a ceiling placed on the cumulative dose given and clearly stated minimum monitoring requirements.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Cuidados Críticos , Hipnóticos e Sedativos/administração & dosagem , Pediatria , Propofol/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Austrália , Criança , Coleta de Dados , Uso de Medicamentos , Escolaridade , Humanos , Hipnóticos e Sedativos/efeitos adversos , Infusões Intravenosas , Unidades de Terapia Intensiva Pediátrica , Nova Zelândia , Propofol/efeitos adversos
19.
Arch Dis Child ; 87(5): 421-5, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12390920

RESUMO

AIMS: To assess the impact of two paediatric intensive care unit retrieval teams on the performance of three mortality risk scoring systems: pre-ICU PRISM, PIM, and PRISM II. METHODS: A total of 928 critically ill children retrieved for intensive care from district general hospitals in the south east of England (crude mortality 7.8%) were studied. RESULTS: Risk stratification was similar between the two retrieval teams for scores utilising data primarily prior to ICU admission (pre-ICU PRISM, PIM), despite differences in case mix. The fewer variables required for calculation of PIM resulted in complete data collection in 88% of patients, compared to pre-ICU PRISM (24%) and PRISM II (60%). Overall, all scoring systems discriminated well between survival and non-survival (area under receiver operating characteristic curve 0.83-0.87), with no differences between the two hospitals. There was a tendency towards better discrimination in all scores for children compared to infants and neonates, and a poor discrimination for respiratory disease using pre-ICU PRISM and PRISM II but not PIM. All showed suboptimal calibration, primarily as a consequence of mortality over prediction among the medium (10-30%) mortality risk bands. CONCLUSIONS: PIM appears to offer advantages over the other two scores in terms of being less affected by the retrieval process and easier to collect. Recalibration of all scoring systems is needed.


Assuntos
Cuidados Críticos , Mortalidade Hospitalar , Índice de Gravidade de Doença , Criança , Pré-Escolar , Inglaterra , Hospitais de Distrito , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Estudos Prospectivos , Medição de Risco , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA