RESUMO
AIM: Balloon aortic valvuloplasty (BAV) has reemerged with transcatheter valve therapy. Cylindrical balloons have been the device of choice despite limitations. An hour glass shaped balloon may permit enhanced fixation and broader leaflet opening without annular compromise. METHODS: We report our initial BAV experience using the V8 balloon (InterValve Inc.) in 20 consecutive patients compared to 20 patients from a 403-patient BAV database using cylindrical balloons. Patients were propensity matched on a 1:1 basis by age, gender, left ventricular ejection fraction (LVEF), baseline aortic valve area (AVA) and Society of Thoracic Surgery (STS) mortality risk score. End points included change in AVA and aortic insufficiency (AI) by echocardiography. New atrioventricular conduction defects (AVCD), need for post procedure pacemaker were documented. Major adverse events (MAE) included procedure related death, emergency surgery or stroke. RESULTS: V8 and cylindrical balloon groups were similar across age, gender, LVEF, AVA and STS score. The change in AVA from baseline to post-procedure strongly trended towards being larger in the V8 group than cylindrical balloon group (mean [SD]; 0.30±0.23 cm2 vs. 0.17±0.21 cm2; P=0.063). There were no differences in outcomes for degree of AI, AVCD, need for pacemaker or MAE. CONCLUSION: Preliminary findings in this small experience suggest an advantage for enhancing AVA when using the V8 compared with cylindrical balloons. Additionally, there was no evidence of increased AI, AVCD or MAE.
Assuntos
Estenose da Valva Aórtica/terapia , Valvuloplastia com Balão/métodos , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/patologia , Valvuloplastia com Balão/efeitos adversos , Valvuloplastia com Balão/instrumentação , Ecocardiografia , Desenho de Equipamento , Humanos , Masculino , Pontuação de Propensão , Índice de Gravidade de Doença , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
OBJECTIVE: Estrogen-based hormone therapy (HT) attenuates abdominal fat gain after menopause, but whether HT improves abdominal fat loss during weight loss is unknown. It was hypothesized that HT or a selective estrogen receptor modulator (raloxifene) would augment reductions in abdominal visceral fat during weight loss when compared to placebo, potentially increasing improvements in glucose tolerance and lipid profile. METHODS: Healthy postmenopausal women (n = 119; age 50-70 yr) underwent a 6-month weight-loss (primarily exercise) intervention with randomization to raloxifene (60 mg/d), HT (conjugated estrogens, 0.625 mg/d), or placebo. Outcomes were change in total and abdominal (visceral and subcutaneous) fat mass, lipid profile, and fasting and post-challenge glucose and insulin. RESULTS: Neither HT nor raloxifene augmented loss of total or abdominal fat mass during exercise-induced weight loss when compared with placebo. Weight loss-induced improvements in risk factors were similar among the three groups, except for a greater reduction in fasted glucose in the HT group (difference in change [95%CI] from placebo; -0.40 [-0.76, -0.05]) and greater reductions in LDL (-0.36 [-0.63, -0.09]) and increases in HDL (0.15 [0.07, 0.24]) in both treatment groups. CONCLUSIONS: Postmenopausal HT and raloxifene did not increase abdominal fat loss during weight loss, but did improve some cardiometabolic outcomes.
Assuntos
Adiposidade/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Estrogênios/farmacologia , Obesidade/metabolismo , Cloridrato de Raloxifeno/farmacologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Idoso , Glicemia/metabolismo , Composição Corporal/efeitos dos fármacos , Metabolismo Energético , Estrogênios/uso terapêutico , Exercício Físico , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Pessoa de Meia-Idade , Obesidade/prevenção & controle , Obesidade/terapia , Pós-Menopausa/sangue , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
The aim of this study was to determine whether estrogen and/or raloxifene help to conserve bone mineral density (BMD) during moderate weight loss. Postmenopausal women (n = 68) participated in a 6-month weight loss program that consisted primarily of supervised exercise training. Another 26 women were studied over 6 months of weight stability. All participants were randomized to three treatment arms: placebo, raloxifene (60 mg/d), or hormone therapy (HT; conjugated estrogens, 0.625 mg/d; trimonthly medroxyprogesterone acetate, 5 mg/d for 13 d, for women with a uterus). Changes in body weight (mean +/- se) averaged 0.8 +/- 0.5 kg in the weight-stable group and -4.1 +/- 0.4 kg in the weight loss group. Across all measured skeletal sites, average changes in BMD in weight stable women were -0.6 +/- 1.1% (n = 7), 0.9 +/- 0.6% (n = 9), and 3.0 +/- 0.7% (n = 10) in the placebo, raloxifene, and HT groups, respectively; comparable BMD changes in the weight loss groups were -1.5 +/- 0.5% (n = 22), -0.5 +/- 0.5% (n = 23), and 1.1 +/- 0.4% (n = 23). There were no significant interactions between weight loss and drug treatment on changes in BMD, but there were significant main effects of weight loss on lumbar spine (P = 0.022), total hip (P = 0.010), and trochanter BMD (P < 0.001). These findings suggest that weight loss, even when modest in magnitude and induced by exercise training, causes a reduction in BMD, particularly in women not taking raloxifene or HT. It is not known whether reductions in BMD of this magnitude increase the risk for osteoporotic fracture.
Assuntos
Densidade Óssea/efeitos dos fármacos , Estrogênios/farmacologia , Exercício Físico , Cloridrato de Raloxifeno/farmacologia , Redução de Peso , Idoso , Composição Corporal , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
To test the hypothesis that estrogens alter insulin action, we evaluated the effects of intravenous conjugated estrogens (CE) on insulin-stimulated steady-state glucose infusion rate (SSGIR) and suppression of plasma glycerol in postmenopausal women (mean +/- SD; 56 +/- 4 yr; n = 12) not using hormone replacement. SSGIR and glycerol were measured during a two-stage (8 and 40 mU. m-2. min-1) hyperinsulinemic euglycemic clamp on 2 days, with or without a 2.5-mg intravenous CE bolus. Serum estradiol concentrations were increased approximately 200% on the estrogen (EST) compared with the control (CON) days. Serum insulin was reduced (P < 0.01) during stage 2 of the clamp for EST (63.3 +/- 12.8 micro U/ml) vs. CON (78.2 +/- 15.8 micro U/ml). Mean SSGIR and plasma glycerol did not differ between CON and EST days. With adjustment for differences in insulin concentration between conditions, stage 2 glucose disposals were significantly higher (8.63 vs. 7.20 mg. kg-1. min-1) and plasma glycerol concentrations were significantly lower (29.4 vs. 35.0 micro mol/l) for EST vs. CON. Our findings suggest that acute CE administration increases insulin clearance and action in postmenopausal women.
Assuntos
Estrogênios Conjugados (USP)/administração & dosagem , Insulina/sangue , Insulina/farmacologia , Pós-Menopausa , Composição Corporal , Estradiol/sangue , Feminino , Glucose/administração & dosagem , Técnica Clamp de Glucose , Glicerol/sangue , Humanos , Hiperinsulinismo , Injeções Intravenosas , Cinética , Pessoa de Meia-IdadeRESUMO
Early diagnosis and improved treatment are leading to the potential for increased reproductive capability in homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency, but information about reproductive outcome and risk of thromboembolism in pregnancy is limited. To provide further information, clinical and biochemical information was obtained on women with maternal homocystinuria, on their pregnancies and on the offspring. This information included blood sulphur amino acids and total homocysteine, CbetaS gene mutations and developmental and cognitive scores in the offspring. The study involved 15 pregnancies in 11 women, of whom 5 were pyridoxine-nonresponsive and 6 were pyridoxine-responsive. Complications of pregnancy included pre-eclampsia at term in two pregnancies and superficial venous thrombosis of the leg in a third pregnancy. One pregnancy was terminated and two pregnancies resulted in first-trimester spontaneous abortions. The remaining 12 pregnancies produced live-born infants with normal or above-normal birth measurements. One offspring has multiple congenital anomalies that include colobomas of the iris and choroid, neural tube defect and undescended testes. He is also mentally retarded and autistic. A second offspring has Beckwith-Wiedemann syndrome. The remaining 10 offspring were normal at birth and have remained normal. There was no relationship between the severity of the biochemical abnormalities or the therapies during pregnancy to either the pregnancy complications or the offspring outcomes. The infrequent occurrences of pregnancy complications, offspring abnormalities and maternal thromboembolic events in this series suggest that pregnancy and outcome in maternal homocystinuria are usually normal. Nevertheless, a cautious approach would include careful monitoring of these pregnancies with attention to metabolic therapy and possibly anticoagulation.
Assuntos
Cistationina beta-Sintase/deficiência , Cistationina beta-Sintase/genética , Homocistinúria/complicações , Reprodução/genética , Adolescente , Adulto , Aminoácidos/sangue , Aminoácidos Sulfúricos/metabolismo , Criança , Pré-Escolar , Análise Mutacional de DNA , Parto Obstétrico , Resistência a Medicamentos , Feminino , Homocistina/sangue , Homocistinúria/etiologia , Homocistinúria/genética , Humanos , Recém-Nascido , Estado Nutricional , Gravidez , Resultado da Gravidez , Piridoxina/metabolismo , Piridoxina/uso terapêutico , Reprodução/fisiologiaRESUMO
To compare the efficacy of self-expanding (SE) and balloon-expandable (BE) stents in native coronary arteries, we randomly assigned 1,096 patients with new and restenotic lesions to receive either device. Baseline demographics and coronary angiographic characteristics were similar in the 2 groups. The incidence of major adverse cardiac events including death, myocardial infarction, bypass surgery, and repeat intervention was similar for both groups at 1 month (2.9% vs 3.1% for SE vs BE, respectively) and at 9 months (19.3% vs 20.1%, SE vs BE respectively). In a subgroup of patients who underwent follow-up angiography (n = 250), the binary restenosis rates (24.2% vs 18.7%, p = 0.30), late loss (0.98 vs 94 mm, p = 0.60), and loss index (0.55 vs 55, p = 0.95) were not significantly different for both groups. In 62 patients who underwent intravascular ultrasound examination (IVUS), there was a trend toward a lower incidence of edge tears in the SE group (6% vs 23%, p = 0.06). Follow-up IVUS analysis showed that the minimum stent area of the SE stent increased by 33% at 6 months, whereas no change occurred in the BE stents; this was accompanied by a greater degree of intimal proliferation in the SE stents compared with BE stents (3.1 +/- 2.0 vs 1.7 +/- 1.7 mm(2)). Thus, the SE stents had similar clinical and angiographic outcomes in patients with lesions in native coronary arteries.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Stents , Doença das Coronárias/diagnóstico por imagem , Estudos Cross-Over , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Pressão , Estudos Prospectivos , UltrassonografiaRESUMO
BACKGROUND: Electron-beam CT (EBCT) quantification of coronary artery calcification (CAC) allows noninvasive assessment of coronary atherosclerosis. We undertook a follow-up study to determine whether CAC extent, measured at the time of angiography by EBCT, predicted future hard cardiac events, comprising cardiac death and nonfatal myocardial infarction (MI). We also assessed the potential of selected coronary artery disease (CAD) risk factors, prior CAD event history (MI or revascularization), and angiographic findings (number of diseased vessels and overall disease burden) to predict subsequent hard events. METHODS AND RESULTS: Two hundred eighty-eight patients who underwent contemporaneous coronary angiography and EBCT scanning were contacted after a mean of 6.9 years. Vital status and history of MI during follow-up were determined. Cox proportional hazards models were used to compare the predictive ability of CAC extent with selected CAD risk factors, CAD event history, and angiographic findings. Median CAC score was 160 (range 0 to 7633). The 22 patients who experienced hard events during follow-up were older and had more extensive CAC and angiographic disease (P<0.05). Only 1 of 87 patients with CAC score <20 experienced a subsequent hard event during follow-up. Event-free survival was significantly higher for patients with CAC scores <100 than for those with scores >/=100 (relative risk 3.20; 95% CI 1.17 to 8.71). When a stepwise multivariable model was used, only age and CAC extent predicted hard events (risk ratios 1.72 and 1.88, respectively; P<0.05). CONCLUSIONS: In patients undergoing angiography, CAC extent on EBCT is highly predictive of future hard cardiac events and adds valuable prognostic information.
Assuntos
Calcinose/diagnóstico por imagem , Doença das Coronárias/diagnóstico por imagem , Vasos Coronários/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Fatores de Risco , Análise de Sobrevida , Fatores de TempoRESUMO
AIM: sudden coronary death (SCD) in older individuals is generally associated with extensive coronary atherosclerosis, although it may be the first manifestation of ischaemic heart disease. In younger age-groups, SCD may occur in the presence of less severe disease. We sought to (1) examine the extent of coronary atherosclerosis in young victims of SCD compared with age- and sex-matched controls, (2) analyse the composition of atherosclerotic plaques in these patients, (3) identify the predominant mechanism of SCD, and (4) evaluate the possibility of detecting this mechanism on the basis of morphologic plaque features, in particular presence and amount of lipid accumulation and calcific deposits. METHODS AND RESULTS: coronary arteries were obtained at autopsy from 28 victims of SCD under age 50 with no prior clinical manifestation of ischaemic heart disease (IHD) and no myocardial scar formation and from 16 age- and sex-matched subjects dying of noncardiac causes out of hospital. Sections of all available major coronary arteries were cut in 5-mm intervals to yield a total of 1357 histologic sections, which were analysed using digitised planimetry. Victims of SCD had significantly more major coronary arteries per subject with luminal area narrowing > or = 75% than controls (on average, 2.1 vs. 0.2). Plaque area per histologic section was 5.1 +/- 2.1 mm(2) in SCD cases and 2.0 +/- 0.9 mm(2) in controls (P < 0.001). The major constituent of all plaques was fibrous tissue. Lipid core area per section was 0.49 +/- 0.59 mm(2) in SCD cases and 0.004 +/- 0.01 mm(2) in controls (P < 0.001), and calcified plaque area was 0.18 +/- 0.19 mm(2) in SCD cases and 0.02 +/- 0.05 mm(2) in controls (P < 0.001), both defining significant differences between SCD cases and controls. Arterial thrombosis, most often with underlying plaque rupture was the mechanism of SCD in > 80% of the cases. Considering histologic sections with > or = 50 and with > or = 75% area stenosis, plaque rupture was independently predicted by lipid core area. Calcific deposits were a frequent feature of plaque rupture but were only associated with it in univariate analysis. CONCLUSIONS: the extent and severity of coronary atherosclerosis in young victims of SCD as the first manifestation of IHD was substantially greater than in age-and sex-matched controls and comparable with that previously reported in SCD cases with a broader age range. Lipid core and calcified plaque areas provided for excellent separation between the two groups, which may have implications for identifying persons at increased risk for SCD by non invasive visualisation and assessment of the coronary arteries.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Morte Súbita Cardíaca/epidemiologia , Adulto , Índice de Massa Corporal , Calcinose/epidemiologia , Calcinose/patologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/patologia , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Vasos Coronários/química , Vasos Coronários/patologia , Feminino , Fibrose , Humanos , Hiperplasia , Lipídeos/análise , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ruptura EspontâneaRESUMO
Studies of metabolic processes have been enhanced by our understanding of the relationships among obesity, body fat distribution, insulin sensitivity and islet beta-cell function. Thus, we have learned that although insulin resistance is usually associated with obesity, even lean subjects can be insulin resistant due to the accumulation of visceral fat. Insulin sensitivity and beta-cell function are also intimately linked. The hyperbolic relationship between these two parameters explains why insulin-resistant individuals have markedly enhanced insulin responses, whereas subjects who are insulin sensitive exhibit very low responses. Failure to take into account this relationship will lead to erroneous conclusions. By accounting for this important interaction, it has been clearly demonstrated that subjects at high risk of developing type 2 diabetes (older individuals, women with a history of gestational diabetes or polycystic ovary syndrome, subjects with impaired glucose tolerance and first-degree relatives of individuals with type 2 diabetes) have impaired beta-cell function. Furthermore, the progression from normal glucose tolerance to impaired glucose tolerance and type 2 diabetes is associated with declining insulin secretion.
Assuntos
Tecido Adiposo/anatomia & histologia , Diabetes Mellitus/fisiopatologia , Diabetes Gestacional/fisiopatologia , Insulina/sangue , Ilhotas Pancreáticas/fisiopatologia , Composição Corporal , Índice de Massa Corporal , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Obesidade/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , GravidezAssuntos
Síndromes de Imunodeficiência/complicações , Terapia de Imunossupressão/efeitos adversos , Neoplasias/etiologia , Adulto , Animais , Linfócitos B/virologia , Criança , Suscetibilidade a Doenças , Infecções por Vírus Epstein-Barr/imunologia , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/imunologia , Predisposição Genética para Doença , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/congênito , Síndromes de Imunodeficiência/genética , Vigilância Imunológica , Recém-Nascido , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/virologia , Camundongos , Camundongos Knockout , Modelos Animais , Neoplasias/epidemiologia , Neoplasias/imunologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/imunologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/imunologiaRESUMO
BACKGROUND AND AIM OF THE STUDY: Elevated serum serotonin is associated with carcinoid heart disease, the hallmark of which is valvular thickening. Yet, the mechanistic role of serotonin in carcinoid heart disease is poorly understood. We postulated that serotonin has a direct mitogenic effect on cardiac valvular subendocardial cells, and that this effect is mediated by serotonin receptors. METHODS: The dose-dependent proliferative effects of serotonin (10(-8) to 10(-4)M) on cultured porcine aortic valve cells via a [3H]thymidine assay were determined in vitro. Serotonin receptor antagonist studies in culture were also performed using methiotepin, a 5HT1b antagonist, and ketanserin, a 5HT2 receptor antagonist, to determine the mechanism of serotonin action. The ex-vivo proliferation level in human carcinoid (n = 26) and normal valves (n = 10) was compared using proliferating cell nuclear antigen (PCNA) staining, a marker for proliferation. Identification and localization of specific 5HT receptor was assessed by immunostaining for serotonin receptors in the valves. RESULTS: Serotonin increased valvular proliferation in vitro in a dose-dependent manner (10-fold increase) (p <0.001), and this mitogenic effect was inhibited by methiotepin but not ketanserin. In human carcinoid heart valves the level of proliferation was 35-fold higher than in normal human valves (p <0.001). 5HT1b receptors were found only in the carcinoid valves, and not in the normal valves. CONCLUSION: Serotonin is a powerful mitogen for valvular subendocardial cells. The mitogenic effect is at least partly mediated via 5HT1b receptors. Subendothelial cell proliferation is significantly elevated in human carcinoid valves in vivo. The data suggest a mechanism whereby serotonin may contribute to valvular proliferation in carcinoid heart disease.
Assuntos
Doença Cardíaca Carcinoide/fisiopatologia , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Endocárdio/efeitos dos fármacos , Endocárdio/fisiopatologia , Sequestradores de Radicais Livres/farmacologia , Valvas Cardíacas/efeitos dos fármacos , Valvas Cardíacas/fisiopatologia , Receptores de Serotonina/efeitos dos fármacos , Serotonina/farmacologia , Animais , Doença Cardíaca Carcinoide/patologia , Relação Dose-Resposta a Droga , Endocárdio/patologia , Valvas Cardíacas/patologia , Humanos , Técnicas In Vitro , Ketanserina/farmacologia , Metiotepina/farmacologia , Receptores de Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , SuínosRESUMO
Vasculogenesis and angiogenesis are the processes responsible for the development of the circulatory system during embryonic and adult life. Vasculogenesis occurs during embryogenesis while angiogenesis refers to blood vessel formation from any preexisting vasculature. Postnatal angiogenesis resumes during reproduction, wound healing, and ischemia. Excess blood vessel formation may contribute to initiating and maintaining many diseases such as chronic inflammatory disorders, tumor growth, restenosis, and atherosclerosis. In contrast. insufficient blood vessel formation is responsible for tissue ischemia, as in coronary artery disease. An increasing number of patients with advanced coronary artery disease remain symptomatic despite maximal interventional, surgical or medical treatment. Ideally, they would benefit most from additional arterial blood supply to ischemic areas of myocardium. Therapeutic angiogenesis, the ability to induce the growth of new blood vessels, is one of the most intriguing new frontiers in interventional cardiology for this growing patient group. Several approaches are currently undergoing intensive experimental investigations or have already entered early clinical trials involving either local angiogenic peptide administration or the transfection of angiogenic genes. Gene therapy for therapeutic myocardial angiogenesis is the most promising synthesis of two emerging technologies. In the following article, we will review the fundamental pathophysiological concepts of gene-based angiogenic therapy, the technical approaches and delivery systems, and the results of the first clinical trials. We will also discuss the controversies and unresolved issues of this new revascularization therapy.
Assuntos
Doença da Artéria Coronariana/terapia , Circulação Coronária , Terapia Genética/tendências , Neovascularização Fisiológica/genética , HumanosRESUMO
Increased plasma fibrinogen concentration is an independent risk factor for cardiovascular disease. Fibrinogen is the main coagulation protein in plasma, a determinant of blood viscosity, and can act as a cofactor for platelet aggregation. In this study of middle-aged men and women, we examined the association between plasma fibrinogen concentration and coronary artery calcification (CAC), a marker of preclinical coronary atherosclerosis. Two hundred twenty-eight participants were selected from the community-based Epidemiology of Coronary Artery Calcification Study, in which CAC was measured noninvasively by electron beam computed tomography. One hundred fourteen participants (57 men) were selected because they had high quantities of CAC; the remaining 114 participants (57 men) were selected because they had no detectable CAC. Logistic regression models were used to investigate the association between plasma fibrinogen concentration and high quantity of CAC. In men, an increase of 1 standard deviation in fibrinogen concentration was associated with a statistically significant odds ratio of 1.6 (95% CI 1.1 to 2.5) for a high quantity of CAC. In women, the corresponding odds ratio was 2.5 (95% CI 1.6 to 4.1). Inferences from sex-specific bivariate logistic models for odds ratios adjusted individually for each coronary risk factor and C-reactive protein were similar to those from the univariate models. In women, there was also a significant interaction between fibrinogen concentration and age. According to the models, younger women with high plasma fibrinogen were more likely to have high quantities of CAC than were younger women with low plasma fibrinogen. The strength of this association was diminished in older women.
Assuntos
Calcinose/metabolismo , Doença das Coronárias/metabolismo , Fibrinogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Electron beam CT (EBCT) is an accurate, noninvasive method to detect and quantify coronary artery calcification, a marker of coronary artery disease (CAD). This investigation examined the accuracy of EBCT to detect obstructive CAD (> or =50% stenosis) and determined the optimal strata for quantity of coronary artery calcification to facilitate clinical decision-making. METHODS AND RESULTS: Clinical research patients (n=213) were examined with coronary angiography and EBCT (angiography group), and 765 research participants were examined with only EBCT (nonangiography group). Of the angiography group, 53% had obstructive CAD. After adjustment for verification bias, the estimated sensitivity and specificity for calcium score > or =1 were 97.0% and 72.4%, respectively. Likelihood ratios for strata of calcium score associated with obstructive CAD were calculated in each sex and 2 age groups. Among those > or =50 years old, the same 4 strata of EBCT calcium scores were identified in each sex; likelihood ratios ranged from 0.03 (calcium score 0) to 12.85 (calcium score > or =200). The same 3 strata EBCT calcium scores were identified in each sex among those <50 years old; likelihood ratios ranged from 0.13 (calcium score 0) to 190 (calcium score > or =100). CONCLUSIONS: A calcium score > or =200 among those > or =50 years old and calcium score > or =100 among those <50 years old provided strong evidence that patients of either sex had obstructive CAD. A calcium score of 0 provided strong evidence that patients > or =50 years old did not have obstructive CAD.
Assuntos
Angiografia Coronária , Doença das Coronárias/diagnóstico , Adulto , Calcinose , Cálcio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios XRESUMO
During the 1950s work on bone marrow transplantation for patients with aplastic anemia led to the search for means other than total body irradiation to prevent rejection of the bone marrow allograft. At the same time, it had become clear that lymphocyte proliferation was a prominent feature of the immune response against all kinds of antigens, including skin allografts. These two factors led us to test various chemical agents known to block the proliferation of leukemic lymphocytes for their ability to inhibit the immune response against soluble antigens and skin allografts. One compound, the antileukemic drug 6-mercaptopurine, was effective in both test systems. This drug and its sister compound azathioprine (which is mercaptopurine with an imidizaole ring instead of a sulfhydryl group on carbon 6) were soon applied to human allografting and the treatment of autoimmune diseases.
Assuntos
Terapia de Imunossupressão/história , Imunologia de Transplantes , Previsões , História do Século XX , Tolerância Imunológica , Imunossupressores/história , Imunossupressores/uso terapêutico , Transplante de Órgãos/história , Estados UnidosRESUMO
The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three-decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contributions of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here in six tables and annotated with references.
Assuntos
Transplante de Órgãos/história , Imunologia de Transplantes , Animais , História do Século XX , Humanos , Los Angeles , Transplante de Órgãos/tendências , UniversidadesRESUMO
BACKGROUND: Epidemiological studies have demonstrated that hyperfibrinogenemia is an independent risk factor for cerebrovascular atherosclerosis. However, the underlying mechanisms are poorly understood. We studied whether hyperfibrinogenemia could modify the histological composition of atherosclerotic plaque and precipitate carotid thrombosis resulting from rupture of the plaque. METHODS AND RESULTS: We studied the histological composition of 71 carotid atherosclerotic plaques from patients who had undergone surgical endarterectomy after a first episode of transient ischemic attack. Patients were divided into 3 groups corresponding to the tertiles of plasma fibrinogen values. Hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, and smoking habit were also assessed. At the histological analysis, plaques of patients in the highest tertile of fibrinogen (>407 mg/dL) were characterized by a high incidence of thrombosis (66.7% of cases) compared with plaques of subjects in the lower (21.7%) (P=0.002) and middle (29. 2%) (P=0.009) tertiles. Plaque rupture was significantly associated with high fibrinogen levels (54.2%, P=0.003). Multivariate logistic regression indicated that hyperfibrinogenemia was an independent risk factor for a decrease in cap thickness (P=0.0005), macrophage foam cell infiltration of the cap (P=0.003), and thrombosis (P=0. 003). When the presence of other risk factors was accounted for, hyperfibrinogenemia remained an independent predictor of carotid thrombosis with an odds ratio of 5.83, compared with other risk factors. CONCLUSIONS: The results of the present study add to the evidence that hyperfibrinogenemia, independently of other risk factors, is associated with a specific histological composition of carotid atherosclerotic plaques that predisposes them to rupture and thrombosis.
Assuntos
Arteriosclerose/sangue , Arteriosclerose/complicações , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Fibrinogênio/análise , Ataque Isquêmico Transitório/complicações , Idoso , Arteriosclerose/patologia , Doenças das Artérias Carótidas/patologia , Feminino , Humanos , Trombose Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de RiscoRESUMO
OBJECTIVES: The study was done to test the ability to predict the extent of angiographically determined coronary artery disease (CAD) by quantification of coronary calcium using electron-beam computed tomography (EBCT) and to compare it with more conventional parameters for delineating the angiographic extent of CAD, that is, cardiovascular risk factors and radionuclide single-photon emission computed tomography (SPECT). BACKGROUND: The angiographic extent of CAD is a powerful predictor of subsequent events. Use of EBCT may be able to define it by virtue of its ability to determine plaque burden. METHODS: We examined 308 patients presenting with suspected but not previously known CAD who underwent selective coronary angiography. As measures of the angiographic extent of CAD, coronary artery greater even 20 (CAGE > or =20) and CAGE > or =50 scores represented the total number of coronary segments with > or =20% or > or =50% stenoses, respectively. The EBCT-derived total calcium scores were obtained in 291 patients, risk factors as defined by the National Cholesterol Education Program in 239 patients, and SPECT scans in 136 patients. RESULTS: Using multiple linear regression analysis, total calcium scores were better independent predictors of both CAGE > or =20 and CAGE > or =50 scores than either a SPECT-derived radionuclide perfusion score or the risk factors age, male gender and ratio of total/high-density lipoprotein (HDL) cholesterol. The association between EBCT and angiographic scores remained highly significant after excluding the influence of all interrelated risk factors and SPECT variables (r = 0.65; p < 0.001 for CAGE > or =20 scores, r = 0.50; p < 0.001 for CAGE > or =50 scores). CONCLUSIONS: Coronary calcium predicts the angiographic extent of CAD in symptomatic patients and provides independent and incremental information to the more conventional clinical parameters derived from SPECT or risk assessment.