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1.
Lancet Haematol ; 2(2): e75-81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26687612

RESUMO

BACKGROUND: Rituximab is commonly used as a treatment for primary immune thrombocytopenia to induce and maintain remission. The benefit of adding rituximab to standard-of-care treatment is uncertain. METHODS: We did a systematic review and meta-analysis of randomised controlled trials assessing the efficacy and safety of rituximab for treatment of adults with primary immune thrombocytopenia. We searched Medline, Embase, and the Cochrane database in duplicate and independently from inception up to July 31, 2014, for relevant studies. Primary outcomes were the proportion of patients achieving a complete platelet count response and a partial platelet count response (as defined in primary studies) that was maintained until the end of follow-up. We also assessed bleeding, infection, and infusion reactions. FINDINGS: Our database search returned 468 abstracts, of which five trials (with total of 463 patients) were eligible for analysis. No patients had splenectomy at the time of enrolment. Median follow-up was 6 months (IQR 6-12). Complete response (>100 × 10(9) platelets per L without rescue therapy) was more common with rituximab than with standard of care (weighted proportions: 46·8% vs 32·5%; relative risk [RR] 1·42, 95% CI 1·13-1·77; p=0·0020). Partial response was not significantly different between groups (57·6% vs 46·7%; RR 1·26, 95% CI 0·95-1·67; p=0·11). Rituximab was not associated with a reduction in bleeding (9·2% vs 5·2%; RR 1·34, 95% CI 0·63-2·87; p=0·44) or an increase in infections (20·1% vs 12·1%; RR 1·40, 95% CI 0·87-2·26; p=0·17). INTERPRETATION: Rituximab can improve complete platelet count responses by 6 months in patients with immune thrombocytopenia. Evidence for sustained responses beyond 6-12 months is limited. Clinicians must consider the goals of treatment before prescribing rituximab. FUNDING: None.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/uso terapêutico , Padrão de Cuidado , Humanos , Contagem de Plaquetas , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Resultado do Tratamento
2.
Anesth Analg ; 121(3): 709-15, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26287299

RESUMO

BACKGROUND: The incidence, severity, and duration of postoperative oxygen desaturation in the general surgical population are poorly characterized. We therefore used continuous pulse oximetry to quantify arterial oxygen saturation (SpO2) in a cross-section of patients having noncardiac surgery. METHODS: Oxygen saturation, blinded to clinicians, was recorded at 1-minute intervals in patients >45 years old for up to 48 hours after noncardiac surgery in 1250 patients from Cleveland Clinic Main Campus and 250 patients from the Juravinski Hospital. We determined (1) the cumulative minutes of raw minute-by-minute values below various hypoxemic thresholds; and (2) the contiguous duration of kernel-smoothed (sliding window) values below various hypoxemic thresholds. Finally, we compared our blinded continuous values with saturations recorded during routine nursing care. RESULTS: Eight hundred thirty-three patients had sufficient data for analyses. Twenty-one percent had ≥10 min/h with raw SpO2 values <90% averaged over the entire recording duration; 8% averaged ≥20 min/h <90%; and 8% averaged ≥5 min/h <85%. Prolonged hypoxemic episodes were common, with 37% of patients having at least 1 (smoothed) SpO2 <90% for an hour or more; 11% experienced at least 1 episode lasting ≥6 hours; and 3% had saturations <80% for at least 30 minutes. Clinical hypoxemia, according to nursing records, measured only in Cleveland Clinic patients (n = 594), occurred in 5% of the monitored patients. The nurses missed 90% of smoothed hypoxemic episodes in which saturation was <90% for at least one hour. CONCLUSIONS: Hypoxemia was common and prolonged in hospitalized patients recovering from noncardiac surgery. The SpO2 values recorded in medical records seriously underestimated the severity of postoperative hypoxemia.


Assuntos
Hipóxia/diagnóstico , Oximetria/tendências , Complicações Pós-Operatórias/diagnóstico , Idoso , Estudos Transversais , Feminino , Humanos , Hipóxia/sangue , Masculino , Pessoa de Meia-Idade , Oximetria/métodos , Complicações Pós-Operatórias/sangue , Estudos Prospectivos , Método Simples-Cego
3.
Proteomics ; 13(15): 2324-34, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23713052

RESUMO

In-depth proteomic analyses offer a systematic way to investigate protein alterations in disease and, as such, can be a powerful tool for the identification of novel biomarkers. Here, we analyzed proteomic data from a transgenic mouse model with cardiac-specific overexpression of activated calcineurin (CnA), which results in severe cardiac hypertrophy. We applied statistically filtering and false discovery rate correction methods to identify 52 proteins that were significantly different in the CnA hearts compared to controls. Subsequent informatic analysis consisted of comparison of these 52 CnA proteins to another proteomic dataset of heart failure, three available independent microarray datasets, and correlation of their expression with the human plasma and urine proteome. Following this filtering strategy, four proteins passed these selection criteria, including myosin heavy chain 7, insulin-like growth factor-binding protein 7, annexin A2, and desmin. We assessed expression levels of these proteins in mouse plasma by immunoblotting, and observed significantly different levels of expression between healthy and failing mice for all four proteins. We verified antibody cross-reactivity by examining human cardiac explant tissue by immunoblotting. Finally, we assessed protein levels in plasma samples obtained from four unaffected and four heart failure patients and demonstrated that all four proteins increased between twofold and 150-fold in heart failure. We conclude that MYH7, IGFBP7, ANXA2, and DESM are all excellent candidate plasma biomarkers of heart failure in mouse and human.


Assuntos
Anexina A2/sangue , Desmina/sangue , Insuficiência Cardíaca/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Cadeias Pesadas de Miosina/sangue , Animais , Biomarcadores/sangue , Calcineurina/genética , Calcineurina/metabolismo , Análise por Conglomerados , Bases de Dados Factuais , Modelos Animais de Doenças , Ventrículos do Coração/química , Humanos , Camundongos , Camundongos Transgênicos , Miocárdio/química , Neoplasias/metabolismo , Projetos Piloto , Proteômica
6.
Int J Nephrol ; 2011: 351672, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21660113

RESUMO

The coexistence of heart failure and renal dysfunction constitutes the "cardiorenal syndrome" which is increasingly recognized as a marker of poor prognosis. Patients with cardiorenal dysfunction constitute a large and heterogeneous group where individuals can have markedly different outcomes and disease courses. Thus, the determination of prognosis in this high risk group of patients may pose challenges for clinicians and for researchers alike. In this paper, we discuss the cardiorenal syndrome as it pertains to the patient with heart failure and considerations for further refining prognosis and outcomes in patients with heart failure and renal dysfunction. Conventional assessments of left ventricular function, renal clearance, and functional status can be complemented with identification of coexistent comorbidities, medication needs, microalbuminuria, anemia, biomarker levels, and pulmonary pressures to derive additional prognostic data that can aid management and provide future research directions for this challenging patient group.

7.
Proc Natl Acad Sci U S A ; 107(43): 18481-6, 2010 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-20937869

RESUMO

Cardiac-specific overexpression of a constitutively active form of calcineurin A (CNA) leads directly to cardiac hypertrophy in the CNA mouse model. Because cardiac hypertrophy is a prominent characteristic of many cardiomyopathies, we deduced that delineating the proteomic profile of ventricular tissue from this model might identify novel, widely applicable therapeutic targets. Proteomic analysis was carried out by subjecting fractionated cardiac samples from CNA mice and their WT littermates to gel-free liquid chromatography linked to shotgun tandem mass spectrometry. We identified 1,918 proteins with high confidence, of which 290 were differentially expressed. Microarray analysis of the same tissue provided us with alterations in the ventricular transcriptome. Because bioinformatic analyses of both the proteome and transcriptome demonstrated the up-regulation of endoplasmic reticulum stress, we validated its occurrence in adult CNA hearts through a series of immunoblots and RT-PCR analyses. Endoplasmic reticulum stress often leads to increased apoptosis, but apoptosis was minimal in CNA hearts, suggesting that activated calcineurin might protect against apoptosis. Indeed, the viability of cultured neonatal mouse cardiomyocytes (NCMs) from CNA mice was higher than WT after serum starvation, an apoptotic trigger. Proteomic data identified α-crystallin B (Cryab) as a potential mediator of this protective effect and we showed that silencing of Cryab via lentivector-mediated transduction of shRNAs in NCMs led to a significant reduction in NCM viability and loss of protection against apoptosis. The identification of Cryab as a downstream effector of calcineurin-induced protection against apoptosis will permit elucidation of its role in cardiac apoptosis and its potential as a therapeutic target.


Assuntos
Calcineurina/metabolismo , Retículo Endoplasmático/metabolismo , Miocárdio/metabolismo , Cadeia B de alfa-Cristalina/metabolismo , Animais , Apoptose/fisiologia , Calcineurina/genética , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Expressão Gênica , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Transgênicos , Miocárdio/citologia , Análise Serial de Proteínas , Proteômica , RNA Interferente Pequeno/genética , Estresse Fisiológico , Cadeia B de alfa-Cristalina/antagonistas & inibidores , Cadeia B de alfa-Cristalina/genética
8.
Curr Cardiol Rev ; 6(2): 124-33, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-21532779

RESUMO

The emergence of new platforms for the discovery of innovative therapeutics has provided a means for diagnosing cardiac disease in its early stages. Taking into consideration the global health burden of cardiac disease, clinicians require innovations in medical diagnostics that can be used for risk stratification. Proteomic based studies offer an avenue for the discovery of proteins that are differentially regulated during disease; such proteins could serve as novel biomarkers of the disease state. For instance, in clinical practice, the abundance of such biomarkers in blood could be correlated with the severity of the disease state. As such, early detection of biomarkers would enable an improvement in patient prognosis. In this review, we outline advancements in various proteomic platforms used to study the disease proteome and their applications to the field of clinical medicine. Specifically, we highlight the contributions of proteomic-based profiling experiments to the analysis of cardiovascular diseases.

9.
Expert Opin Med Diagn ; 3(2): 133-41, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23485160

RESUMO

BACKGROUND: In clinical practice, timely detection of disease and accurate diagnosis are highly important for the effective treatment of various patient populations. Biomarkers offer a new and innovative means of assessing the disease state during early, mid and late stages of progression. OBJECTIVE: Advancements in various proteomic platforms used to study the disease proteome and their applications to the field of clinical medicine are reviewed. METHODS: A literature review was done to study proteomic technology and its contribution to the discovery of cardiac biomarkers. CONCLUSION: Proteomic profiling experiments can allow for the establishment of cardiac biomarkers, which can often offer information regarding the severity of the disease state. As high-throughput evaluation of various cardiac disease proteomes continues to improve in precision, the prospect of offering medical treatment that is tailored to the individual could follow.

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