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1.
Front Chem ; 12: 1386055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911992

RESUMO

A promising pollution control technology is cold plasma driven chemical processing. The plasma is a pulsed electric gas discharge inside a near atmospheric-pressure-temperature reactor. The system is energized by a continuous stream of very short high-voltage pulses. The exhaust gas to be treated flows through the reactor. The methods applied involve the development of robust cold plasma systems, industrial applications and measuring technologies. Tests of the systems were performed at many industrial sites and involved control of airborne VOC (volatile organic compound) and odor. Electrical, chemical and odor measuring data were collected with state-of-the-art methods. To explain the test data an approximate solution of global reaction kinetics of pulsed plasma chemistry was developed. It involves the Lambert function and, for convenience, a simple approximation of it. The latter shows that the amount of removal, in good approximation, is a function of a single variable. This variable is electric plasma power divided by gas flow divided by input concentration. In the results sections we show that in some cases up to 99% of volatile pollution can be removed at an acceptable energy requirement. In the final sections we look into future efficiency enhancements by implementation of (sub)nanosecond pulsed plasma and solid state high-voltage technology and by integration with catalyst technology.

2.
Virchows Arch ; 483(1): 105-110, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36241730

RESUMO

Clonality assessment by the detection of immunoglobulin (IG) gene rearrangements is an important method to determine whether two concurrent or subsequent lymphoid malignancies in one patient are clonally related. Here, we report the detailed clonality analysis in a patient with a diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) followed by a histiocytic sarcoma (HS), in which we were able to study clonal evolution by applying next generation sequencing (NGS) to identify IG rearrangements and gene mutations. Using the sequence information of the NGS-based IG clonality analysis, multiple related subclones could be distinguished in the PAX5 P80R-mutated B-ALL. Notably, only one of these subclones evolved into HS after acquiring a RAF1 mutation. This case demonstrates that NGS-based IG clonality assessment and mutation analysis provide clear added value for clonal comparison and thereby improves clinicobiological understanding.


Assuntos
Linfoma de Burkitt , Sarcoma Histiocítico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Sarcoma Histiocítico/genética , Sarcoma Histiocítico/patologia , Imunoglobulinas/genética , Rearranjo Gênico , Linfoma de Burkitt/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Fator de Transcrição PAX5/genética
3.
Clin Genet ; 93(1): 111-118, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28671271

RESUMO

Mitochondrial respiratory chain complex I consists of 44 different subunits and contains 3 functional modules: the Q-, the N- and the P-module. NDUFA9 is a Q-module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. So far, a single patient carrying an NDUFA9 variant with a severe neonatally fatal phenotype has been reported. Via exome sequencing, we identified a novel homozygous NDUFA9 missense variant in another patient with a milder phenotype including childhood-onset progressive generalized dystonia and axonal peripheral neuropathy. We performed complex I assembly analysis using primary skin fibroblasts of both patients. Reduced complex I abundance and an accumulation of Q-module subassemblies were present in both patients but more pronounced in the severe clinical phenotype patient. The latter displayed additional accumulation of P-module subassemblies, which was not present in the milder-phenotype patient. Lentiviral complementation of both patient fibroblast cell lines with wild-type NDUFA9 rescued complex I deficiency and the assembly defects. Our report further characterizes the phenotypic spectrum of NDUFA9 deficiency and demonstrates that the severity of the clinical phenotype correlates with the severity of the effects of the different NDUFA9 variants on complex I assembly.


Assuntos
Complexo I de Transporte de Elétrons/genética , Proteínas Mitocondriais/genética , Mutação Puntual , Células Cultivadas , Complexo I de Transporte de Elétrons/metabolismo , Evolução Fatal , Células HEK293 , Humanos , Recém-Nascido , Masculino , Proteínas Mitocondriais/metabolismo , Sequenciamento do Exoma/métodos
4.
Ann Hematol ; 95(3): 417-23, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26732883

RESUMO

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4-257 months). Median age at diagnosis was 43 years (range 1-87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21-74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome.


Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Vigilância da População , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Doença de Hodgkin/terapia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Vigilância da População/métodos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
Neth J Med ; 67(11): 394-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20009116

RESUMO

Glycogenic hepatopathy (GH) is a rare cause of serum transaminase elevations in type 1 diabetes mellitus (DM). We describe a 29-year-old woman with a history of poorly controlled type 1 DM who presented with hepatomegaly and severe transaminase flares. Liver histology confirmed GH, with glycogen accumulation due to severe fluctuations in both glucose and insulin. GH can be regarded as an adult variant of Mauriac's syndrome. Despite severe laboratory abnormalities, it does not cause liver cirrhosis. Treatment consists of improving glycaemic control.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Diabetes Mellitus Tipo 1/complicações , Hepatopatias/etiologia , Hepatopatias/metabolismo , Glicogênio Hepático/metabolismo , Adulto , Biópsia , Causalidade , Diabetes Mellitus Tipo 1/prevenção & controle , Diagnóstico Diferencial , Fígado Gorduroso Alcoólico/etiologia , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Testes de Função Hepática , Prognóstico , Doenças Raras
6.
Osteoporos Int ; 20(10): 1705-13, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19238308

RESUMO

SUMMARY: Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. INTRODUCTION: Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. METHODS: A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. RESULTS: The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. CONCLUSION: Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.


Assuntos
Antidepressivos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Quadril/induzido quimicamente , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/efeitos adversos , Esquema de Medicação , Métodos Epidemiológicos , Feminino , Fraturas do Fêmur/epidemiologia , Fraturas do Quadril/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Adulto Jovem
7.
J Med Genet ; 45(3): 129-33, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17954552

RESUMO

PURPOSE: To identify the biochemical and molecular genetic defect in a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder. METHODS: Measurement of the mitochondrial energy-generating system (MEGS) capacity in muscle and enzyme analysis in muscle and fibroblasts were performed. Relevant parts of the mitochondrial DNA were analysed by sequencing. Transmitochondrial cybrids were obtained by fusion of 143B206 TK(-) rho zero cells with patient-derived enucleated fibroblasts. Immunoblotting techniques were applied to study the complex V assembly. RESULTS: A homoplasmic nonsense mutation m.8529G-->A (p.Trp55X) was found in the mitochondrial ATP8 gene in the patient's fibroblasts and muscle tissue. Reduced complex V activity was measured in the patient's fibroblasts and muscle tissue, and was confirmed in cybrid clones containing patient-derived mitochondrial DNA. Immunoblotting after blue native polyacrylamide gel electrophoresis showed a lack of holocomplex V and increased amounts of mitochondrial ATP synthase subcomplexes. An in-gel activity assay of ATP hydrolysis showed activity of free F(1)-ATPase in the patient's muscle tissue and in the cybrid clones. CONCLUSION: We describe the first pathogenic mutation in the mitochondrial ATP8 gene, resulting in an improper assembly and reduced activity of the complex V holoenzyme.


Assuntos
Cardiomiopatia Hipertrófica/enzimologia , Cardiomiopatia Hipertrófica/genética , Códon sem Sentido , Genes Mitocondriais , ATPases Mitocondriais Próton-Translocadoras/deficiência , ATPases Mitocondriais Próton-Translocadoras/genética , Doenças do Sistema Nervoso/enzimologia , Doenças do Sistema Nervoso/genética , Adolescente , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA/genética , Humanos , Células Híbridas , Masculino , Doenças Mitocondriais/enzimologia , Doenças Mitocondriais/genética , ATPases Mitocondriais Próton-Translocadoras/química , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
8.
Heart ; 91(4): 507-12, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15772214

RESUMO

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the additional one year costs at 166. CONCLUSIONS: The one year data from RAVEL suggest an attractive balance between costs and effects for sirolimus eluting stents in the treatment of single native de novo coronary lesions. The cost effectiveness of drug eluting stents in more complex lesion subsets remains to be determined.


Assuntos
Estenose Coronária/terapia , Imunossupressores/administração & dosagem , Sirolimo/administração & dosagem , Stents/economia , Angiografia Coronária/economia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/economia , Reestenose Coronária/prevenção & controle , Estenose Coronária/economia , Análise Custo-Benefício , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Metais , Países Baixos , Sirolimo/uso terapêutico , Propriedades de Superfície
9.
Eur Heart J ; 24(1): 77-85, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12559939

RESUMO

AIMS: Treatment with the glycoprotein IIb/IIIa receptor antagonist abciximab before and during coronary intervention in refractory unstable angina improves early outcome. We collected 4-year follow-up data to assess whether this benefit is sustained. Additionally, we investigated the predictive value of baseline troponin T and CRP for long-term cardiovascular events. METHODS AND RESULTS: Of 1265 patients enrolled in the CAPTURE trial follow-up was available in 94% of the patients alive after 6 months (median 48 months). Survival was similar in both groups. Both elevated troponin T and CRP were associated with impaired outcome, independently of other established risk factors, but with a different time course. Elevated troponin was associated with increased procedure related risk, and elevated CRP with increased risk for subsequent events. Lower rates of the composite end-point of death or myocardial infarction with abciximab vs. placebo were sustained during long-term follow up: 15.7% vs 17.2% at 4 years (P=ns), particularly in patients with elevated troponin T: 16.9% with abciximab vs 28.4% with placebo: P=0.015. Elevated CRP was not associated with specific benefit of abciximab. CONCLUSION: Troponin T as a marker of thrombosis and CRP as a marker of inflammation are independent predictors of impaired outcome at 4 years follow-up. The initial benefit from abciximab with regard to death and myocardial infarction was preserved at 4 years. No specific benefit with abciximab was observed for patients with elevated CRP, suggesting that a chronic inflammatory process is not affected by abciximab. In contrast the benefit of treatment in patients with elevated troponin T implies that the acute thrombotic process in refractory unstable angina is treated effectively.


Assuntos
Angina Instável/terapia , Angioplastia Coronária com Balão/métodos , Anticorpos Monoclonais/uso terapêutico , Proteína C-Reativa/metabolismo , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Troponina T/metabolismo , Abciximab , Angina Instável/sangue , Angina Instável/tratamento farmacológico , Doença Crônica , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Valor Preditivo dos Testes , Análise de Sobrevida , Resultado do Tratamento
10.
Eur Heart J ; 23(19): 1529-37, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12242073

RESUMO

In order to study the safety of 'rescue' strategies in the treatment of patients with failed thrombolysis, all 548 patients admitted with evolving myocardial infarction to the Thoraxcenter, Rotterdam, from January 1997 until April 1999 were reviewed. Of these patients, 49% had received thrombolysis. Of patients treated with thrombolysis and not referred from other hospitals (n = 154) 36% received rescue therapy for failed thrombolysis. Three rescue therapies were used after failed thrombolysis: percutaneous coronary intervention (74%), retreatment with thrombolysis (39%) and platelet glycoprotein (GP) IIb/IIIa receptor blockers (53%), often in combination. Platelet GP IIb/IIIa receptor blockers were administered in 64% of patients treated with rescue percutaneous coronary intervention. Major bleeding occurred in 14% of all thrombolysis treated patients, and in 30% of patients who received multiple rescue therapies. Bleeding was related to heparin usage and platelet GP IIb/IIIa receptor blockers, as was the insertion of catheters for percutaneous coronary intervention or intra-aortic balloon pumps. Major bleeding resulted in one death due to a ruptured ventricle, one haemorrhagic stroke, and three cases of tamponade for which surgery was needed. Four of these patients had received combination rescue therapy. Rescue therapy is a widely used strategy for failed thrombolysis, but is associated with a high bleeding rate. Alternative reperfusion strategies to avoid failed thrombolysis should be considered in high risk patients.


Assuntos
Infarto do Miocárdio/terapia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/uso terapêutico , Terapia Trombolítica , Angioplastia Coronária com Balão , Terapia Combinada , Feminino , Fibrinolíticos/uso terapêutico , Ventrículos do Coração/patologia , Ventrículos do Coração/cirurgia , Hemorragia/etiologia , Hemorragia/mortalidade , Hemorragia/terapia , Heparina/uso terapêutico , Humanos , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Países Baixos/epidemiologia , Reoperação , Reperfusão , Estudos Retrospectivos , Análise de Sobrevida , Ativador de Plasminogênio Tecidual/uso terapêutico , Falha de Tratamento
11.
Eur Heart J ; 22(22): 2125-30, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11686669

RESUMO

AIMS: Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis. METHODS AND RESULTS: Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents. CONCLUSION: Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia.


Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Reestenose Coronária/prevenção & controle , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos de Coortes , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/etiologia , Creatina Quinase/sangue , Creatina Quinase Forma MB , Segurança de Equipamentos , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/instrumentação , Ultrassonografia de Intervenção
12.
J Psychosom Res ; 51(3): 469-77, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11602216

RESUMO

OBJECTIVE: To examine the independent prognostic value of the four subscales of the Heart Patients Psychological Questionnaire (HPPQ) on mortality in male and female patients 10 years following percutaneous transluminal coronary angioplasty (PTCA). METHODS: The HPPQ, which measures well-being, feelings of being disabled, despondency, and social inhibition, was administered to 356 patients (23% women) post-PTCA. The patients were followed for a median of 10 years. Clinical and demographic variables were sampled from medical records. RESULTS: During the follow-up period, 104 patients (29%) had died. Women scored significantly worse on all psychological subscales compared with men. Fifty-nine (72%) women and 92 (34%) men had a score indicating at least mild to moderate feelings of being disabled. Men scoring high on feelings of being disabled were at increased risk of mortality compared with men having a low score, adjusted for other cardiac risk factors (chi(2)=7; P=.008). No differences were found between women with low or high scores on feelings of being disabled (relative risk (RR): 1.2; 95% confidence interval (CI): 0.5-3.3). None of the other HPPQ subscales were related to mortality. CONCLUSION: Feelings of being disabled measured at least 1 year after hospital discharge is a significant predictor of mortality in men 10 years post-PTCA, but not in women. This finding adds to the increasing knowledge that psychosocial variables influence morbidity and mortality in cardiac patients.


Assuntos
Angioplastia Coronária com Balão/psicologia , Atitude Frente a Saúde , Doença das Coronárias/psicologia , Autoimagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/mortalidade , Doença das Coronárias/mortalidade , Doença das Coronárias/cirurgia , Fadiga/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Países Baixos/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Estudos de Amostragem , Fatores Sexuais , Inquéritos e Questionários , Análise de Sobrevida
13.
Am Heart J ; 142(1): 43-50, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11431655

RESUMO

BACKGROUND: Despite the significant survival benefit associated with successful reperfusion therapy for acute myocardial infarction, global indices of outcome left ventricular function, such as ejection fraction, have often demonstrated little or no improvement. Although these measurements are confounded by numerous clinical, physiologic, and angiographic variables, no comprehensive analysis of this issue in a large series of patients is available. We used the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) database to better understand this phenomenon by determining independent predictors of left ventricular function and their interplay with regard to outcome ventricular function and improvement in function during the initial postinfarction week. METHODS: Ninety-minute and 5- to 7-day posttreatment global and regional indices derived from left ventriculograms were analyzed from a population of 676 patients. These observations were combined with clinical data to describe independent determinants of ventricular function outcome. RESULTS: Clinical factors predictive of global and regional ventricular function as well as improvement in function between 90 minutes and 5 to 7 days included time to treatment, early infarct-related artery flow grade, and body mass index. These same factors contribute significantly to compensatory hyperkinesis of the noninfarct zone, which is critical to maintenance of global ventricular function during this time period. CONCLUSIONS: The ventricular function benefits of early complete reperfusion after myocardial infarction are readily demonstrable after adjustment for multiple covariables and include (1) maintenance of global ventricular function and (2) prevention or delay in ventricular dilatation.


Assuntos
Índice de Massa Corporal , Infarto do Miocárdio/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Velocidade do Fluxo Sanguíneo , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica , Valor Preditivo dos Testes , Análise de Regressão , Estatísticas não Paramétricas , Terapia Trombolítica , Resultado do Tratamento , Grau de Desobstrução Vascular , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Ventriculografia de Primeira Passagem
14.
Eur Heart J ; 22(11): 934-41, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11428817

RESUMO

AIMS: This study reports the clinical outcome, up to 17 years, of the first 856 consecutive patients treated by coronary angioplasty at a single centre and attempts to identify a subgroup of patients at low risk of adverse events. METHODS AND RESULTS: Follow-up status was established via hospital and general practitioner records and the civil registry. Median follow-up was 16 years. The overall 5-, 10-, 15- and 17-year survival was 90%, 78%, 64% and 58%, respectively and corresponding event-free survival was 53%, 33%, 22% and 19%. After 32% of patients had experienced a major adverse cardiac event in the first year, the annual coronary re-intervention incidence thereafter and, even beyond year 10, remained at 2%--3%. Using multivariable Cox regression, significant independent predictors of mortality were advanced age, diabetes, multivessel disease and impaired left ventricular function at the time of PTCA. A subgroup of 26% of the patients with none of these risk factors had a survival rate similar to the general Dutch population matched for age and gender (at 5 years: 96%, at 10 years: 89% and at 15 years: 83%). CONCLUSION: Although the majority of patients (>80%) experienced a further cardiac event during the 17 years after their first angioplasty procedure, in those non-diabetics under 60 years with single-vessel disease and good left ventricular function, prognosis was similar to the general population.


Assuntos
Angioplastia Coronária com Balão , Adulto , Idoso , Angina Pectoris/terapia , Angioplastia Coronária com Balão/mortalidade , Intervalos de Confiança , Ponte de Artéria Coronária/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Recidiva , Fatores de Risco , Análise de Sobrevida , Tempo , Resultado do Tratamento
15.
N Engl J Med ; 344(15): 1117-24, 2001 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-11297702

RESUMO

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be $2,973 per patient. CONCLUSION: As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.


Assuntos
Angioplastia Coronária com Balão , Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Doença das Coronárias/terapia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/economia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/prevenção & controle , Ponte de Artéria Coronária/economia , Doença das Coronárias/mortalidade , Análise Custo-Benefício , Creatina Quinase/sangue , Creatina Quinase Forma MB , Complicações do Diabetes , Intervalo Livre de Doença , Feminino , Custos Hospitalares , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Qualidade de Vida , Recidiva , Stents/economia , Resultado do Tratamento
16.
Heart ; 85(4): 444-50, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11250974

RESUMO

OBJECTIVE: Lefradafiban is the orally active prodrug of fradafiban, a glycoprotein IIb/IIIa receptor antagonist. The present phase II study aimed to determine the dose of lefradafiban that provides 80% blockade of the glycoprotein IIb/IIIa receptors by fradafiban, and to study the pharmacodynamics and safety of different doses in patients with stable angina undergoing angioplasty. DESIGN: A double blind, placebo controlled, dose finding study. SETTING: Four academic and community hospitals in the Netherlands. PATIENTS: 64 patients with stable coronary artery disease undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTIONS: 30 mg, 45 mg, and 60 mg of lefradafiban three times daily or placebo was given for 48 hours. MAIN OUTCOME MEASURES: The primary safety end point was the occurrence of bleeding, classified as major, minor, or insignificant according to the thrombolysis in myocardial infarction (TIMI) criteria. Efficacy indices included per cent fibrinogen receptor occupancy (FRO), ex vivo platelet aggregation, and plasma concentrations of fradafiban. RESULTS: Administration of lefradafiban 30, 45, and 60 mg three times daily resulted in a dose dependent increase in median FRO levels of 71%, 85%, and 88%, respectively. Inhibition of platelet aggregation was closely related to FRO. There were no major bleeding events. The 60 mg lefradafiban group had a high (71%) incidence of minor and insignificant bleeding. The incidence of bleeding was 44% in the 30 mg and 45 mg groups, compared with 9% in placebo patients. Puncture site bleeding was the most common event. The odds of bleeding increased by 3% for every 1% increase in FRO. CONCLUSIONS: Lefradafiban is an effective oral glycoprotein IIb/IIIa receptor blocker. The clinical effectiveness of doses up to 45 mg three times daily should be investigated.


Assuntos
Angioplastia Coronária com Balão , Compostos de Bifenilo/administração & dosagem , Doença das Coronárias/terapia , Inibidores da Agregação Plaquetária/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Pró-Fármacos/administração & dosagem , Pirrolidinas/administração & dosagem , Administração Oral , Idoso , Área Sob a Curva , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/sangue , Compostos de Bifenilo/farmacocinética , Método Duplo-Cego , Feminino , Hemorragia , Hemostasia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinética , Pirrolidinas/efeitos adversos , Pirrolidinas/sangue , Pirrolidinas/farmacocinética , Risco
17.
Heart ; 85(1): 73-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11119468

RESUMO

OBJECTIVE: To assess the mechanism of restenosis after balloon angioplasty. DESIGN: Prospective study. PATIENTS: 13 patients treated with balloon angioplasty. INTERVENTIONS: 111 coronary subsegments (2 mm each) were analysed after balloon angioplasty and at a six month follow up using three dimensional intravascular ultrasound (IVUS). MAIN OUTCOME MEASURES: Qualitative and quantitative IVUS analysis. Total vessel (external elastic membrane), plaque, and lumen volume were measured in each 2 mm subsegment. Delta values were calculated (follow up - postprocedure). Remodelling was defined as any (positive or negative) change in total vessel volume. RESULTS: Positive remodelling was observed in 52 subsegments while negative remodelling occurred in 44. Remodelling, plaque type, and dissection were heterogeneously distributed along the coronary segments. Plaque composition was not associated with changes in IVUS indices, whereas dissected subsegments had a greater increase in total vessel volume than those without dissection (1.7 mm(3) v -0.33 mm(3), p = 0.04). Change in total vessel volume was correlated with changes in lumen (p < 0.05, r = 0.56) and plaque volumes (p < 0.05, r = 0.64). The site with maximum lumen loss was not the same site as the minimum lumen area at follow up in the majority (n = 10) of the vessels. In the multivariate model, residual plaque burden had an influence on negative remodelling (p = 0.001, 95% confidence interval (CI) -0.391 to -0.108), whereas dissection had an effect on total vessel increase (p = 0.002, 95% CI 1.168 to 4.969). CONCLUSIONS: The mechanism of lumen renarrowing after balloon angioplasty appears to be determined by unfavourable remodelling. However, different patterns of remodelling may occur in individual injured coronary segments, which highlights the complexity and influence of local factors in the restenotic process.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/terapia , Estudos de Coortes , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/lesões , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Modelos Cardiovasculares , Análise Multivariada , Estudos Prospectivos , Recidiva , Análise de Regressão , Ultrassonografia de Intervenção
18.
Neth Heart J ; 9(1): 3-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25696687

RESUMO

OBJECTIVE: To evaluate the relationship between the completeness of revascularisation by percutaneous coronary intervention and the one-year occurrence of adverse cardiac events in patients with multivessel disease. PATIENTS: Patients with stable or unstable angina pectoris, or with exercise-induced ischaemia, were enrolled in the Coronary Angioplasty versus Bypass Revascularisation Investigation (CABRI). METHODS: In CABRI, patients were randomised to coronary bypass grafting (CABG; n=513) or angioplasty (PTCA; n=541). Revascularisation in patients randomised to PTCA was defined as complete if no lesions with a diameter stenosis <50% remained post-procedure. Patients with complete revascularisation were distinguished from those with one, two, and three or more remaining lesions, respectively. Differences in baseline characteristics and in the one-year occurrence of death, myocardial infarction, (re)CABG, and (re)PTCA between these subgroups were evaluated. Comparisons were made with patients randomised to CABG. RESULTS: Complete revascularisation was obtained in 148 patients randomised to PTCA (27%). In 147 (27%) cases one lesion remained, while there were 122 (23%) and 119 (22%) patients with two and three or more remaining lesions, respectively. Five (1%) patients could not be classified. The one-year rates of either death or MI were 9.5%, 5.4%, 8.2%, and 12.6% in the respective PTCA subgroups (p=0.225), and 6.2% in patients randomised to CABG (comparison with three or more remaining lesions after PTCA: p=0.017). The percentages of repeat interventions during one-year follow-up were 29.7%, 29.3%, 39.3%, and 51.3% (p<0.001), much higher than after CABG (3.5%; p<0.001). CONCLUSION: Complete revascularisation by PTCA in multivessel coronary disease did not result in a lower death or MI rate compared with incomplete revascularisation. Overall the patient's prognosis after PTCA is similar to CABG, but patients with three or more remaining lesions after PTCA had a worse prognosis than CABG patients.

19.
Neth J Med ; 55(4): 184-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10555435

RESUMO

BACKGROUND: The occurrence of a corneal arcus before the age of 60 years has been associated with the presence of atherosclerosis and the occurrence of hypercholesterolemia. The aim of this observational study was to assess the correlation between the presence of a corneal arcus and the severity of coronary artery disease. METHODS: A consecutive group of 200 Caucasian patients aged 40-60 years were studied. All patients were scheduled for diagnostic coronary angiography in a tertiary referral center. RESULTS: The severity of coronary disease was assessed by coronary angiography. A corneal arcus was observed in 38% of the patients. The prevalence of multivessel disease on a coronary angiogram was significantly higher in the group of patients with corneal arcus (p < 0.02). Patients with a corneal arcus compared to patients without a corneal arcus were slightly older (p < 0.05). Corrected for age, patients with an arcus has a relative risk for multivessel disease of 3.3 (CI 1.1-12.1, p < 0.05). CONCLUSION: In Caucasian patients with symptoms of coronary disease, the presence of a corneal arcus below 60 years of age indicates a high risk for multivessel coronary atherosclerosis.


Assuntos
Arco Senil/etiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Adulto , Fatores Etários , Arco Senil/diagnóstico , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
20.
Catheter Cardiovasc Interv ; 48(2): 207-10, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10506782

RESUMO

The clinical course and angiographic follow-up of a woman with spontaneous coronary dissections in all three coronary arteries during the third trimester of pregnancy is described. Mother and child survived and subsequent clinical course was uneventful. At 6-month follow-up, dissections in the right and circumflex coronary artery had healed completely. At the site of the dissection in the LAD, an aneurysm had formed. This is to our knowledge the first report of antepartum and antemortem diagnosis of pregnancy related coronary dissections in all three coronary arteries. Cathet. Cardiovasc. Intervent. 48:207-210, 1999.


Assuntos
Dissecção Aórtica/diagnóstico , Aneurisma Coronário/diagnóstico , Complicações Cardiovasculares na Gravidez/diagnóstico , Adulto , Dissecção Aórtica/terapia , Cesárea , Aneurisma Coronário/terapia , Angiografia Coronária , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Remissão Espontânea , Ruptura Espontânea , Ultrassonografia de Intervenção
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