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1.
Eur Heart J Cardiovasc Imaging ; 17(4): 429-37, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26160395

RESUMO

AIMS: Despite improved outcomes and lower right ventricular failure (RVF) rates with continuous-flow left ventricular assist devices (LVADs), RVF still occurs in 20-40% of LVAD recipients and leads to worse clinical and patient-centred outcomes and higher utilization of healthcare resources. Preoperative quantification of RV function with echocardiography has only recently been considered for RVF prediction, and RV mechanics have not been prospectively evaluated. METHODS AND RESULTS: In this single-centre prospective cohort study, we plan to enroll a total of 120 LVAD candidates to evaluate standard and mechanics-based echocardiographic measures of RV function, obtained within 7 days of planned LVAD surgery, for prediction of (i) RVF within 90 days; (ii) quality of life (QoL) at 90 days; and (iii) RV function recovery at 90 days post-LVAD. Our primary hypothesis is that an RV echocardiographic score will predict RVF with clinically relevant discrimination (C >0.85) and positive and negative predictive values (>80%). Our secondary hypothesis is that the RV score will predict QoL and RV recovery by 90 days. We expect that RV mechanics will provide incremental prognostic information for these outcomes. The preliminary results of an interim analysis are encouraging. CONCLUSION: The results of this study may help improve LVAD outcomes and reduce resource utilization by facilitating shared decision-making and selection for LVAD implantation, provide insights into RV function recovery, and potentially inform reassessment of LVAD timing in patients at high risk for RVF.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Disfunção Ventricular Direita/diagnóstico por imagem , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Taxa de Sobrevida , Disfunção Ventricular Direita/fisiopatologia
2.
J Med Chem ; 52(22): 7301-9, 2009 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-19877685

RESUMO

In addition to addiction, the repeated use of (+)-methamphetamine [(+)-METH], (+)-amphetamine [(+)-AMP], or (+/-)-3,4-methylenedioxymethamphetamine ((+/-)-MDMA, commonly called ecstasy) can lead to life-threatening medical problems including cardiovascular injury, severe depression, and psychosis. Currently, there are no specific pharmacotherapies to treat these medical problems. In this study, we report the design and synthesis of two haptens, (S)-(+)-3-(9-carboxynonyloxy)methamphetamine (3a, (+)-METH MO10) and (S)-(+)-3-(5-carboxypentyloxy)methamphetamine (3b, (+)-METH MO6), and their use in generating high affinity (low K(D) value) monoclonal antibodies (mAbs) against (+)-METH, (+)-AMP, and/or (+)-MDMA. On the basis of results from the determination of mAb K(D) values and ligand specificity, the mAbs generated from hapten 3a showed the greatest promise for generating active and passive immunotherapies for treating overdose or addiction from (+)-METH-like stimulants.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Descoberta de Drogas , Haptenos/química , Haptenos/imunologia , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias/imunologia , Animais , Proteínas de Transporte/metabolismo , Bovinos , Linhagem Celular , Feminino , Haptenos/metabolismo , Imunização , Camundongos , Ovalbumina/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Especificidade por Substrato
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