Assuntos
Materia Medica/normas , Medicina Baseada em Evidências , Humanos , Legislação de Medicamentos , Marketing de Serviços de Saúde/legislação & jurisprudência , Marketing de Serviços de Saúde/normas , Segurança do Paciente , Rotulagem de Produtos/legislação & jurisprudência , Rotulagem de Produtos/normas , Opinião Pública , Controle de QualidadeRESUMO
Previous contributions to Quarterly Journal of Medicine have drawn attention to the work of FEAM, the Federation of European Academies of Medicine, in collaboration with others, in exploring and explaining the issues that will ensure an appropriate European Union (EU) policy framework for health research and innovation. In this article, we present a proposal for an archive of important research conducted in the EU that will act as a resource for illustrating and guiding the development of the necessary regulatory framework.
Assuntos
Pesquisa Biomédica/organização & administração , Academias e Institutos , Pesquisa Biomédica/legislação & jurisprudência , União Europeia , Política de Saúde , HumanosAssuntos
Pesquisa Biomédica/legislação & jurisprudência , Segurança Computacional/legislação & jurisprudência , Confidencialidade/legislação & jurisprudência , Prontuários Médicos/legislação & jurisprudência , Pesquisa Biomédica/normas , Europa (Continente) , União Europeia , Controle de Formulários e Registros/legislação & jurisprudência , Registros de Saúde Pessoal , HumanosAssuntos
Ensaios Clínicos como Assunto/legislação & jurisprudência , Aprovação de Drogas/legislação & jurisprudência , Garantia da Qualidade dos Cuidados de Saúde/normas , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos como Assunto/normas , União Europeia , Humanos , Garantia da Qualidade dos Cuidados de Saúde/legislação & jurisprudênciaAssuntos
Obstrução das Vias Respiratórias/induzido quimicamente , Albuterol/efeitos adversos , Broncodilatadores/efeitos adversos , Complicações Intraoperatórias/induzido quimicamente , Obstrução das Vias Respiratórias/fisiopatologia , Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Criança , Epilepsia/cirurgia , Feminino , Humanos , Histerectomia , Complicações Intraoperatórias/fisiopatologia , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Respiração com Pressão PositivaAssuntos
Bases de Dados de Ácidos Nucleicos , Atenção à Saúde , Privacidade Genética , Pesquisa em Genética , Genética Médica , Genética Populacional , Pesquisa , Alocação de Recursos , Medicina Estatal , Bioética , Confidencialidade , Bases de Dados Factuais , Humanos , Consentimento Livre e Esclarecido , Informática Médica , Sistemas Computadorizados de Registros Médicos , Setor Privado , Setor Público , Sujeitos da Pesquisa , Controle Social Formal , Medicina Estatal/organização & administração , Reino Unido , Estados UnidosRESUMO
This paper explores, mainly from the UK perspective, some of the issues relating to the current, and potential, impact of advances in genetics and molecular biology on the education and research training of healthcare professionals. We start by describing some of the expectations for progress in the use of genomic technologies and genetic data in healthcare delivery and the need for policy development to ensure timely translation of advances in science and technology into improved patient care. We review briefly the likely evolution of clinical genetics service provision to build the requisite scientific basis in primary care and explore how user needs could be addressed. Strategic issues for the future medical curriculum are introduced and linked with the concerns about the current status of clinical academic research. The issues for research training, career progression, nurturing of research 'at the bedside', definition of the research agenda and weaknesses in both academic infrastructure and support costs are reviewed in the context of the urgent imperative for medicine to harness the accelerating pace of progress in genomics.
Assuntos
Educação Médica/organização & administração , Genética Médica/educação , Currículo , Humanos , PesquisaRESUMO
Anistreplase is a thrombolytic agent comprising a complex of streptokinase, lys-plasminogen, and a p-anisoyl group, which temporarily protects the catalytic center of the enzyme complex. Streptokinase was previously shown to reduce infarct size (IS) in dogs with a fibrin-rich clot in the left anterior descending coronary artery (LAD) without necessarily producing reperfusion. Therefore, we hypothesized that IS in this model would be reduced by anistreplase. In addition, we studied the effect of tissue-type plasminogen activator (t-PA) on IS, testing our hypothesis in anesthetized dogs in which thrombin (100 U) and calcium (50 microliters, 0.05 M) were sequentially injected into the LAD to form a thrombus, anistreplase [0.01, 0.05, or 0.10 U/kg intravenous (i.v.) bolus], t-PA (0.1, 0.5, 2, or 8 micrograms/kg/min infusion for 60 min) or vehicle (VEH) was administered 55 min later. Anistreplase (0.05 or 0.10 U/kg) significantly (p < 0.05) reduced clot weight (VEH 22 +/- 3 mg; anistreplase 0.05 U/kg, 13 +/- 4 mg; anistreplase 0.10 U/kg, 0.7 +/- 0.6 mg), increased incidence of reperfusion (VEH 0%; anistreplase 0.05 U/kg, 42%; anistreplase 0.10 U/kg, 100%) and reduced IS (VEH 23 +/- 3%; anistreplase, 0.05 U/kg, 14 +/- 2%; anistreplase 0.10 U/kg, 15 +/- 2%). t-PA reduced thrombin weight (VEH 26 +/- 3 mg; 2 micrograms/kg/min t-PA 12 +/- 4; 8 micrograms/kg/min t-PA 2 +/- 2 mg) and increased incidence of reperfusion (VEH 0%; 2 micrograms/kg/min 75%; 8 micrograms/kg/min 100%), but IS was not altered (VEH 19 +/- 3%; 0.1 microgram/kg/min 18 +/- 3%; 0.5 microgram/kg/min 23 +/- 2%; 2 micrograms/kg/min 16 +/- 5%; 8 micrograms/kg/min: 19 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anistreplase/farmacologia , Fibrinolíticos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Anestesia , Animais , Anistreplase/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Fibrinolíticos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Hemostáticos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miocárdio/enzimologia , Peroxidase/metabolismo , Ativador de Plasminogênio Tecidual/farmacologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Despite major advances in redesigning and producing proteins through recombinant DNA technology, many therapeutic proteins are still produced by extraction from biological tissues or fluids, or from nonrecombinant microorganisms. Modification of such proteins, to improve potency and bioavailability and reduce immunogenicity, can only be carried out post-translationally by chemical-derivatization methods. Genetic- and chemical-modification methods are not mutually exclusive, however, and may be combined to optimize protein-engineering strategies, because chemical modification can introduce structural changes that are not encoded by DNA into both recombinant, and nonrecombinant proteins.
Assuntos
Proteínas/isolamento & purificação , Proteínas/uso terapêutico , Alérgenos/química , Alérgenos/isolamento & purificação , Animais , Sítios de Ligação , Biotecnologia , Humanos , Polímeros/síntese química , Polímeros/química , Proteínas/química , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/uso terapêuticoAssuntos
Trombose Coronária/tratamento farmacológico , Fibrinólise , Fibrinolíticos/uso terapêutico , Trombose/tratamento farmacológico , Animais , Trombose Coronária/prevenção & controle , Fibrina/metabolismo , Humanos , Modelos Biológicos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Ativadores de Plasminogênio/fisiologia , Ativadores de Plasminogênio/uso terapêutico , Trombose/prevenção & controleRESUMO
Antistreptokinase antibodies present in patients as a result of previous streptococcal infections might theoretically influence the thrombolytic response to streptokinase or anistreplase. The potential influence of antibody, measured as antigen binding to immunoglobulin G, was investigated in a randomized, double-blind, multicenter patency comparison of intravenous streptokinase (1.5 million units/60 minutes) and intravenous anistreplase (30 units/2 to 5 minutes) in patients with acute myocardial infarction. Antibody results were evaluated in 333 patients (from a total study population of 370 patients) less than 76 years of age with ECG evidence of ST segment elevation who could be treated within 4 hours of the onset of symptoms. Variations in pretreatment circulating levels of antibody did not influence angiographically defined early coronary patency rates (Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, measured at a mean of 140 minutes after therapy was begun) for either streptokinase or anistreplase. Similarly the lytic response represented by systemic plasminogen activation and measured as changes in plasma plasminogen and fibrinogen levels after dosing (at mean times of 90 minutes and 24 hours) was not correlated with baseline antibody levels. Furthermore, pretreatment antibody was not a risk factor for poor outcome in response to streptokinase or anistreplase (reocclusion within 24 hours, in-hospital death, or stroke) and did not correlate with hypotension or allergic-type reactions recorded as adverse events. In conclusion, within the population limits defined by the inclusion and exclusion criteria of the study (patients were excluded if they had received streptokinase or anistreplase within the previous 6 months), pretreatment antistreptokinase immunoglobulin G is not a significant determinant of the efficacy response to streptokinase or anistreplase.
Assuntos
Anistreplase/uso terapêutico , Imunoglobulina G/imunologia , Infarto do Miocárdio/tratamento farmacológico , Estreptoquinase/imunologia , Estreptoquinase/uso terapêutico , Terapia Trombolítica , Vasos Coronários/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Masculino , Infarto do Miocárdio/epidemiologia , Resultado do Tratamento , Grau de Desobstrução Vascular/efeitos dos fármacosRESUMO
OBJECTIVE: To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction. DESIGN: Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay). SETTING: Cardiology department in a general hospital. PATIENTS: 128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion. RESULTS: Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18). CONCLUSION: Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.
Assuntos
Anistreplase/imunologia , Anticorpos/análise , Imunoglobulina G/análise , Infarto do Miocárdio/imunologia , Estreptoquinase/imunologia , Terapia Trombolítica , Adulto , Idoso , Anistreplase/uso terapêutico , Formação de Anticorpos/imunologia , Método Duplo-Cego , Resistência a Medicamentos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Estudos Prospectivos , Estreptoquinase/uso terapêutico , Fatores de TempoAssuntos
Fibrinólise/efeitos dos fármacos , Heparina/farmacologia , Ativadores de Plasminogênio/efeitos dos fármacos , Animais , Heparina/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/tratamento farmacológico , Ativadores de Plasminogênio/metabolismo , Trombose/sangue , Trombose/tratamento farmacológicoAssuntos
Diabetes Mellitus/tratamento farmacológico , Fibrinólise/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Complicações do Diabetes , Diabetes Mellitus/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations. 2. The two agents were found to have similar volumes of distribution (5.68 and 5.90 l), but SK was cleared significantly more rapidly than anistreplase, resulting in a shorter terminal phase half-life (0.61 vs 1.16 h) and a shorter mean residence time (0.76 vs 1.55 h).