191 resultados para Enzyme Prodrug Therapy


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OBJECTIVE: Detect of cardiac alterations in children with AIDS and compare their evolution with the administration of only one anti-retroviral and the recent cases who received drugs in combination. METHODS: We prospectively studied 47 children in 3 groups: group 1, 20 cases treated only with zidovudine; group 2, 10 patients treated initially with zidovudine and later with a combination of drugs and in group 3, 17 patients, who receiced two or three since the beginning. In all patients it was done chest X-ray, EKG and echocardiography every 6 months and after death complete pathological study. RESULTS: Among the 45 patients cases 26 (57%) were index cases. Malnutrition, diarrhea tachycardia, signs of congestive heart failure, pericardial effusion, abnormal ventricular repolarization and arrhythmias were more frequent in group 1. Echocardiographic abnormalities were present in 10 (50%) children of group 1. They were less frequent in the others two groups. In regard to the outcome in group 1, two patients had worsening of sings of cardiomyopaty and 4 died. Cardiac dysfunction in all cases of group 2 and 3 improved with the medication. CONCLUSION:- The children who received combination and their cardiac alterations had more favorable outcome than those who received only one drug.

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OBJECTIVE: To assess the major causes of surgical morbidity and mortality in patients with infective endocarditis operated upon in a regional cardiology center. METHODS: Thirty-four patients underwent surgical treatment for infective endocarditis. Their ages ranged from 20 to 68 years (mean of 40.6) and 79% were males. Their NYHA functional classes were as follows: IV - 19 (55.8%) patients; III - 12 (35.2%) patients; II - 3 (8.8%) patients. Blood cultures were positive in only 32% of the cases. Eight patients had already undergone previous cardiac surgery, whose major indication (82.3%) was heart failure refractory to clinical treatment. RESULTS: Four (11.7%) patients died at the hospital. Follow-up was complete in 26 (86%) patients. Five (14.7%) patients died later, 12, 36, 48, 60, and 89 months after hospital discharge. Of the 21 patients being currently followed up, 1 is in NYHA functional class III, and 5 in NYHA functional class II. CONCLUSION: A high degree of clinical suspicion, at an early diagnosis, and indication of surgical treatment prior to deterioration of left ventricular function and installation of generalized sepsis may improve prognosis.

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A sixty-four-year-old male patient was studied who had acute coronary syndrome with ST segment elevation experienced bilateral hemarthrosis of the knees after administration of streptokinase and acetylsalicylic acid.

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OBJECTIVE: To assess the short- and long-term results of the use of streptokinase (SK) for the treatment of thromboses in cardiac valvular prostheses. METHODS: Seventeen patients with cardiac prosthetic thrombosis diagnosed by clinical, echocardiographic, and radioscopic findings underwent fibrinolytic treatment with a streptokinase bolus of 250,000 U followed by 100.000 U/hour. Short- and long-term results were assessed by radioscopy and echocardiography. RESULTS: Of the 17 patients, 12 had mechanical double-disk prostheses (4 aortic, 6 mitral, 2 tricuspid), 4 had single-disk prostheses (2 aortic, 1 mitral, and 1 tricuspid), and 1 had a tricuspid bioprosthesis. The success rate was 64.8%, the partial success rate was 17.6%, and the nonsuccess rate was 17.6%. All patients with a double-disk prosthesis responded, completely or partially, to the treatment. None of the patients with a single-disk prosthesis had complete resolution of the thrombosis. The time of streptokinase infusion ranged from 6 to 80 hours (mean of 56 h). The mortality rate due to the use of streptokinase was 5.8% and was secondary to cerebral bleeding. During streptokinase infusion, 3 (17.6%) embolic episodes occurred as follows: 1 cerebral, 1 peripheral, and 1 coronary. The rethrombosis index was 33% in a mean follow-up of 42 months. CONCLUSION: The use of fibrinolytic agents was effective and relatively safe in patients with primary thrombosis of a double-disk prosthesis. A fatal hemorrhagic complication occurred in 1 (5.8%) patient, and embolic complications occurred in 3 (17.6%) patients. In a mean 42-month follow-up, 67% of the patients were free from rethrombosis.

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Background: The effects of modern therapy on functional recovery after acute myocardial infarction (AMI) are unknown.Objectives:To evaluate the predictors of systolic functional recovery after anterior wall AMI in patients undergoing modern therapy (reperfusion, aggressive platelet antiaggregant therapy, angiotensin-converting enzyme inhibitors and beta-blockers).Methods:A total of 94 consecutive patients with AMI with ST-segment elevation were enrolled. Echocardiograms were performed during the in-hospital phase and after 6 months. Systolic dysfunction was defined as ejection fraction value < 50%.Results:In the initial echocardiogram, 64% of patients had systolic dysfunction. Patients with ventricular dysfunction had greater infarct size, assessed by the measurement of total and isoenzyme MB creatine kinase enzymes, than patients without dysfunction. Additionally, 24.5% of patients that initially had systolic dysfunction showed recovery within 6 months after AMI. Patients who recovered ventricular function had smaller infarct sizes, but larger values of ejection fraction and E-wave deceleration time than patients without recovery. At the multivariate analysis, it can be observed that infarct size was the only independent predictor of functional recovery after 6 months of AMI when adjusted for age, gender, ejection fraction and E-wave deceleration time.Conclusion: In spite of aggressive treatment, systolic ventricular dysfunction remains a frequent event after the anterior wall myocardial infarction. Additionally, 25% of patients show functional recovery. Finally, infarct size was the only significant predictor of functional recovery after six months of acute myocardial infarction.

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Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

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Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

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Background: End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes. Objective: To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis. Methods: Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study. Results: The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor. Conclusions: The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.

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Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

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Background:Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events.Objective:To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days.Methods:Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira) or Fisher's exact test (Armitage) were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of <10% were submitted to multiple logistic regression model.Results:A total of 457 patients with a mean age of 62.1 years, of whom 63.7% were males, were included. Risk factors such as hypertension (85.3%) and dyslipidemia (75.9%) were the most prevalent, with 35% of diabetics. In the evaluation of events at 180 days, there were 28 deaths (6.2%). The statistical analysis showed that the variables that interfered with troponin elevation (> 0.5 ng / mL) were high blood glucose at admission (p = 0.0034) and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016). The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482). The C-statistics for this model was 0.77.Conclusion:This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this reduction could lead to fewer severe clinical events such as death and re-infarction at 180 days.

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AbstractBackground:Despite the increased evidence of the important role of matrix metalloproteinases (MMP-9 and MMP‑2) in the pathophysiology of hypertension, the profile of these molecules in resistant hypertension (RHTN) remains unknown.Objectives:To compare the plasma levels of MMP-9 and MMP-2 and of their tissue inhibitors (TIMP-1 and TIMP-2, respectively), as well as their MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, between patients with controlled RHTN (CRHTN, n=41) and uncontrolled RHTN (UCRHTN, n=35). In addition, the association of those parameters with clinical characteristics, office blood pressure (BP) and arterial stiffness (determined by pulse wave velocity) was evaluate in those subgroups.Methods:This study included 76 individuals diagnosed with RHTN and submitted to physical examination, electrocardiogram, and laboratory tests to assess biochemical parameters.Results:Similar values of MMP-9, MMP-2, TIMP-1, TIMP-2, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were found in the UCRHTN and CRHTN subgroups (P>0.05). A significant correlation was found between diastolic BP (DBP) and MMP-9/TIMP-1 ratio (r=0.37; P=0.02) and DPB and MMP-2 (r=-0.40; P=0.02) in the UCRHTN subgroup. On the other hand, no correlation was observed in the CRHTN subgroup. Logistic regression models demonstrated that MMP-9, MMP-2, TIMP-1, TIMP-2 and their ratios were not associated with the lack of BP control.Conclusion:These findings suggest that neither MMP-2 nor MMP-9 affect BP control in RHTN subjects.

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AbstractIntroduction:Cardiac allograft vasculopathy (CAV) is a major limitation for long-term survival of patients undergoing heart transplantation (HT). Some immunosuppressants can reduce the risk of CAV.Objectives:The primary objective was to evaluate the variation in the volumetric growth of the intimal layer measured by intracoronary ultrasound (IVUS) after 1 year in patients who received basiliximab compared with that in a control group.Methods:Thirteen patients treated at a single center between 2007 and 2009 were analyzed retrospectively. Evaluations were performed with IVUS, measuring the volume of a coronary segment within the first 30 days and 1 year after HT. Vasculopathy was characterized by the volume of the intima of the vessel.Results:Thirteen patients included (7 in the basiliximab group and 6 in the control group). On IVUS assessment, the control group was found to have greater vessel volume (120–185.43 mm3 vs. 127.77–131.32 mm3; p = 0.051). Intimal layer growth (i.e., CAV) was also higher in the control group (27.30–49.15 mm3 [∆80%] vs. 20.23–26.69 mm3[∆33%]; p = 0.015). Univariate regression analysis revealed that plaque volume and prior atherosclerosis of the donor were not related to intima growth (r = 0.15, p = 0.96), whereas positive remodeling was directly proportional to the volumetric growth of the intima (r = 0.85, p < 0.001).Conclusion:Routine induction therapy with basiliximab was associated with reduced growth of the intima of the vessel during the first year after HT.

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Background:Polypharmacy is a significant economic burden.Objective:We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients.Methods:We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost.Results:The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05‑340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively.Conclusion:RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.

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AbstractBackground:30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes.Objective:This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx) at different stages of cardiac resynchronization therapy (CRT).Methods:Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC) III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves.Results:The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD), ejection fraction < 25% and use of high doses of diuretics (HDD) increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping.Conclusion:We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.