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Biomedical subjects

Charles Mady

Publications and source records attributed to Charles Mady.

At least 19 recordsLinked to original sources
PubMed2006

Lack of association of tumor necrosis factor-alpha polymorphisms with Chagas disease in Brazilian patients.

One third of Trypanosoma cruzi-infected individuals develop chronic Chagas disease cardiomyopathy (CCC) while the majority remains asymptomatic (ASY). About 30% of CCC patients develop heart failure due to end-stage inflammatory dilated cardiomyopathy. Increased production of tumor necrosis factor (TNF)-alpha has been described in all clinical forms of Chagas disease, and the highest levels are detected in CCC patients with severe ventricular dysfunction. Genetic susceptibility may play a role in the clinical outcome of Chagas disease. We investigated TNF as a candidate gene for susceptibility to development and/or progression of CCC. We analyzed the TNFa microsatellite and the -308 TNF promoter polymorphisms, in 166 CCC compared to 80 ASY geographically and age-matched patients in an association study. To analyze the association of TNF polymorphisms with progression of the cardiomyopathy, CCC patients were also grouped in three categories according to degree of left ventricular (LV) dysfunction into severe (n=57), mild to moderate (n=21) and absent (n=88). Our results show no significant differences either between CCC and ASY patients, or among CCC patients according to severity of cardiomyopathy with respect to TNFa or -308 TNF promoter polymorphisms. These results indicate that TNF polymorphisms are associated neither to CCC development nor to progression to more severe forms of cardiomyopathy in Brazilian Chagas disease patients.

Brazil↗
PubMed2006

[Venous endothelial dysfunction in Chagas' disease patients without heart failure].

OBJECTIVE: To analyze the venous endothelial function in Chagas' disease patients without heart failure. METHODS: The Chagas' disease Group (G1) was composed by 14 women and 2 men aged 46 +/- 2.7 and the Control Group (G0) by 7 women and 1 man matched by age, weight and height. Dorsal Hand Vein Compliance Technique was used to evaluate the venous endothelial function. Crescent doses of phenylephrine were infused to get a 70% pre-constriction of the vein; after that, acetylcholine and sodium nitroprusside were respectively administrated to analyze the endothelium-dependent and -independent venodilation. RESULTS: No significant systemic hemodynamic changes were observed in both groups during the experiment. The necessary phenylephrine dose to reach 70% pre-constriction of the vein was significantly higher in the G1 (1116 +/- 668.2 ng/ml) compared to G0 (103 +/- 28 ng/ml) p = 0.05. The endothelium-dependent venous dilation was significantly lower in G1 (65.5 +/- 8%) compared to G0 (137 +/- 20%) p = 0.009. No difference was observed in the endothelium-independent venous dilatation between groups. CONCLUSION: Patients with Chagas' disease without heart failure presented venous endothelial dysfunction.

Acetylcholine↗
PubMed2006

The monocyte chemoattractant protein-1 gene polymorphism is associated with cardiomyopathy in human chagas disease.

BACKGROUND: Only a subset of individuals infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC). Familial aggregation of CCC in areas of endemicity indicates that susceptibility may be genetic, which may be a plausible explanation for why only one-third of T. cruzi-infected individuals develop CCC. The monocyte chemoattractant protein-1 (CCL2/MCP-1) has been shown to enhance the uptake of T. cruzi in murine macrophages and to up-regulate the inducible nitric oxide synthase/nitric oxide system, with a consequent increased production of nitric oxide that controls the replication of the parasite. METHODS: We assessed CCL2 variants at position -2518A/G, which are known to influence transcriptional activity, by polymerase chain reaction and restriction fragment-length polymorphism in 245 individuals, all of whom were infected with T. cruzi. One hundred sixty-nine patients had CCC, and 76 were asymptomatic. RESULTS: Genotype distributions differed between the CCC and asymptomatic groups (chi2 = 9.4; P = .009), with an excess of genotypes with the A allele (AA + AG) in the CCC group. Among patients with CCC, 5% were homozygous for the G allele, compared with 16% of the asymptomatic subjects (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.7-11; P = .001). A similar trend was observed when individuals heterozygous for the G allele were compared with individuals homozygous for the G allele between the CCC and asymptomatic groups (OR, 2.7; 95% CI, 0.97-7.2; P = .026). The A allele seems to confer susceptibility to CCC (OR, 1.9; 95% CI, 1.3-2.9; P = .001). CONCLUSIONS: The CCL2 variant correlated with a low transcriptional level behaves as a genetic modifier of clinical outcome for T. cruzi infection, and subjects with the CCL2 -2518AA genotype have a 4-fold greater risk of developing CCC than do those without this genotype.

Aged↗
PubMed2006

Aortic distensibility measured by pulse-wave velocity is not modified in patients with Chagas' disease.

BACKGROUND: Experimental studies demonstrate that infection with trypanosoma cruzi causes vasculitis. The inflammatory lesion process could hypothetically lead to decreased distensibility of large and small arteries in advanced Chagas' disease. We tested this hypothesis. METHODS AND RESULTS: We evaluated carotid-femoral pulse-wave velocity (PWV) in 53 Chagas' disease patients compared with 31 healthy volunteers (control group). The 53 patients were classified into 3 groups: 1) 16 with indeterminate form of Chagas' disease; 2) 18 with Chagas' disease, electrocardiographic abnormalities, and normal systolic function; 3) 19 with Chagas' disease, systolic dysfunction, and mild-to-moderate congestive heart failure. No difference was noted between the 4 groups regarding carotid-femoral PWV (8.4 +/- 1.1 vs 8.2 +/- 1.5 vs 8.2 +/- 1.4 vs 8.7 +/- 1.6 m/s, P = 0.6) or pulse pressure (39.5 +/- 7.6 vs 39.3 +/- 8.1 vs 39.5 +/- 7.4 vs 39.7 +/- 6.9 mm Hg, P = 0.9). A positive, significant, similar correlation occurred between PWV and age in patients with Chagas' disease (r = 0.42, P = 0.002), in controls (r = 0.48, P = 0.006), and also between PWV and systolic blood pressure in both groups (patients with Chagas' disease, r = 0.38, P = 0.005; healthy subjects, r = 0.36, P = 0.043). CONCLUSION: Carotid femoral pulse-wave velocity is not modified in patients with Chagas' disease, suggesting that elastic properties of large arteries are not affected in this disorder.

Adult↗
PubMed2006

BAT1, a putative anti-inflammatory gene, is associated with chronic Chagas cardiomyopathy.

BACKGROUND: It is not understood why only a subset of individuals infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC). Patients with CCC display high levels of circulating proinflammatory cytokines. Heart-infiltrating lymphocytes from patients with CCC also express proinflammatory cytokines (tumor necrosis factor- alpha and interferon- gamma ) that are detectable in biopsy samples and surgical heart-tissue samples. BAT1, a putative anti-inflammatory gene, presents functional polymorphisms in its promoter region that influence its transcriptional level. METHODS: We assessed, by polymerase chain reaction restriction fragment-length polymorphism analysis, BAT1 variants in the promoter region at positions -22C/G and -348C/T in 154 patients with CCC and in 76 T. cruzi-infected but asymptomatic (ASY) patients. RESULTS: Of the patients with CCC, 16% were homozygous for the -22C allele, compared with 4% of the ASY patients (P=.004; odds ratio [OR], 4.7 [95% confidence interval {CI}, 1.4-16]). A similar trend was observed for the -348C homozygotes (P=.01; OR, 1.9 [95% CI, 1.0-3.5]). Susceptibility to CCC was conferred by the C variants at nt -22 (P=.003; OR, 1.8 [95% CI, 1.2-2.8]) and at nt -348 (P=.02; OR, 1.7 [95% CI, 1.0-2.8]). CONCLUSIONS: BAT1 variants previously associated with reduced expression of HLA-B-associated transcript 1 are predictive of the development of CCC. These variants may be less efficient in down-regulating inflammatory responses and may contribute to the elevated production of proinflammatory cytokines in patients with CCC.

Brazil↗
PubMed2006

[NT pro-BNP levels in pericardial diseases and how they are used as complementary evaluation method of diastolic restriction. Initial experience: 25 cases].

OBJECTIVE: To determine whether NT pro-BNP levels are high in patients reporting pericardial diseases, as well as to investigate how they relate to diastolic dysfunction echocardiographic measures. METHODS: Twenty-five patients were split into two groups: 1) pericardial effusion (PE): 15 patients; 2) constrictive pericarditis (CP): 10 patients. A control group was made up with 30 individuals reporting no heart disease. Pericardial effusion was evaluated by bidimensional echocardiogram, with restriction evaluated by pulsed Doppler of mitral flow. CP diagnosis was confirmed by MRI. NT pro-BNP levels were measured by immunoassay and detected by electrochemiluminescence. RESULTS: From the 15 PD patients, 14 reported relevant PD, and only 1, moderate PD. Log NT pro-BNP was shown to be higher in PD (p < 0.05), with log mean of 2.31 pg/ml and CP (p < 0.05), with log mean of 2.67 pg/ml, when compared to control group, log mean of 1.32 pg/ml. No difference was reported between PD and CP (p = 0.149). The NT pro-BNP log showed to be correlated to peak velocity of the E wave (r = 0.845; p = 0.001) and with E/A (r = 0.717; p = 0.003). CONCLUSION: NT pro-BNP is shown to have increased in pericardial diseases, and is associated to diastolic dysfunction. It may serve as an additional method in quantifying restriction.

Adolescent↗
PubMed2006

Holt-Oram syndrome presenting as agenesis of the left pericardium.

We report on a case of a 60-year-old man with progressive heart failure, mitral and aortic valve insufficiency and bilateral asymmetrical skeletal upper-limb deformities. Central to the suspicion of Holt-Oram syndrome in this patient was the surgical finding of agenesis of the left pericardium. A Holt-Oram syndrome diagnostic was confirmed through molecular analysis of the TBX5 gene. A new amino acid substitution at position 61 of the TBX5 gene was identified and confirmed the clinical diagnosis of Holt-Oram syndrome. The clinical presentation of the present case broadens the clinical spectrum of Holt-Oram syndrome and point out the importance of Tbx 5 in pericardium development. It is still an unstudied issue whether TBX5 mutations may also be present in other clinical presentations where absence of the pericardium is a feature.

Abnormalities, Multiple↗
PubMed2006

Long-term survival of a patient with isolated noncompaction of the ventricular myocardium.

Isolated noncompaction of the myocardium (INCM) is a rare, congenital, unclassified cardiomyopathy. It is caused by a disorder in endomyocardial morphogenesis in the absence of other structural disease. INCM is characterized by numerous prominent trabeculations and deep intertrabecular recesses in the myocardium. Frequently, INCM is associated with an increased incidence of heart failure, arrhythmias, and cardioembolic events with high morbidity and mortality. We describe a 28-year-old woman experiencing symptoms of heart failure since she was 4 years old. She had been intensively investigated and misdiagnosed as having dilated, restrictive, and apical hypertrophic cardiomyopathies. Cardiac magnetic resonance and echocardiography recently revealed the actual diagnosis of INCM. The patient is alive and well, taking vasodilators and warfarin. Herein, we describe the long-term follow-up of this patient and demonstrate that some patients have a favorable prognosis. In addition, the improvement in noninvasive cardiac imaging has revealed a higher prevalence of INCM, previously undetected.

Anticoagulants↗
PubMed2006

Usefulness of a new proposed tissue Doppler imaging global function index in hypertrophic cardiomyopathy.

BACKGROUND: A global function index (GFI) derived from tissue Doppler imaging (TDI) has been proposed to improve the diagnosis of hypertrophic cardiomyopathy (HCM). We aimed to evaluate the usefulness of this index in a large selected HCM population. METHODS: GFI =[E/Ea]/Sa, was calculated at mitral annulus lateral and septal borders in 164 HCM patients and in 40 healthy volunteers. Group comparisons and correlations between GFI and other variables were performed. RESULTS: Of the 164 patients, 69 (42%) had a peak gradient >30 mmHg in the left ventricle outflow tract (LVOT). GFI (lateral or septal) was not normally distributed. There were differences among controls, obstructive HCM, and nonobstructive HCM (P < 0.0001), but significant overlap of GFI values were observed between groups. GFI was correlated to septal thickness (r = 0.44; P < 0.0001), left atrial diameter (r = 0.52; P < 0.0001), and LVOT gradient (r = 0.58; P < 0.0001). CONCLUSION: In a selected HCM population, GFI was limited by its asymmetrical distribution and significant overlap of values between groups. Further studies are necessary to verify the reliability of GFI in the clinical practice and its position among other tissue Doppler indices.

Adolescent↗
PubMed2006

Relationship between outflow obstruction and left ventricular functional impairment in hypertrophic cardiomyopathy: a Doppler echocardiographic study.

Left ventricular outflow tract (LVOT) obstruction is predictive of a worse outcome in hypertrophic cardiomyopathy (HCM). In a detailed Doppler echocardiographic study of 178 selected HCM patients, the group of patients (n = 73) with the obstructive form (resting peak gradient > or = 30 mmHg) presented more hypertrophy and poorer systolic and diastolic left ventricular (LV) functions than the HCM group (n = 105) without obstruction. LVOT peak gradient was positively correlated with hypertrophy (P < 0.0001) and negatively to tissue Doppler mitral annulus systolic (P = 0.0001) and early diastolic (P < 0.0001) velocities. The gradient significantly correlated with E/Ea ratio (r = 0.67; P < 0.0001). By multiple regression, LVOT gradient was related to E/Ea, LV maximal thickness and left atrial size. In comparison with patients without obstruction, patients with obstruction presented greater hypertrophy (P < 0.0001), lower systolic and early diastolic mitral annulus velocities (both P < 0.0001), higher E/Ea ratio (P < 0.0001) and higher global function index (P < 0.0001). In HCM, beyond the effects on hypertrophy, LVOT obstruction is an independent determinant of LV functional abnormalities.

Adolescent↗
PubMed2006

Effects of metoprolol tartrate therapy in patients with heart failure.

OBJECTIVE: To study the effects of metoprolol tartrate therapy in patients with heart failure. METHODS: Fifty patients (36 males) aged 52+/-14.8 yrs, with functional class II to IV heart failure (HF) and left ventricular ejection fraction (LVFE) < 45%, assessed by radionuclide ventriculography, were evaluated in a retrospective study. Metoprolol tartrate was added to the usual therapy, with a starting dose of 12.5 mg, which was increased weekly to a maximum of 200 mg/day, according to patients tolerance. Clinical evaluation, electrocardiogram, Doppler echocardiogram, 24-h Holter monitoring and radionuclide ventriculography were carried out in the pre-treatment phase and repeated three and six months after the start of therapy. RESULTS: At the end of six months, there was functional class (NYHA) improvement with a reduction from 3.04+/-0.11 to 1.66+/-0.06(p<0.001). Ejection fraction increased from 29.84+1.61% to 38.56+/-1.95% (p< 0.001). The left ventricular diastolic diameter showed a reduction from 67.70+/-1.31 mm to 63.96+/-1.29 mm (p<0.001), and the left ventricular systolic diameter showed a reduction from 54.80+/-1.67 mm to 48.58+/-1.38 (p<0.001). There was no alteration in noradrenaline levels during the six-month follow-up period (p>0.05). Cardiac frequency decreased from 78.84+/-1.68 to 67.48+/-1.86 b.p.m. (p<0.001). CONCLUSION: The adding of metoprolol tartrate to the usual heart failure therapy is followed by an increase of ejection fraction, functional class improvement, and decrease of ventricular diameters and cardiac frequency. These results suggest anti-remodeling effects in patients with HF who utilize metoprolol tartrate in addition to the usual therapy.

Adolescent↗
PubMed2006

Hypertrophic cardiomyopathy: the importance of arrhythmic events in patients at risk for sudden cardiac death.

OBJECTIVE: To evaluate, in patients with hypertrophic cardiomyopathy and risk for SCD who underwent implantable cardioverter-defibrillator (ICD) implantation: a- the occurrence of arrhythmic events; b- the occurrence of clinical events and their correlation with arrhythmic events; c- the occurrence of ICD shock therapy and clinical and functional correlations; d- clinical and functional predictors of prognosis. METHODS: Twenty six patients with hypertrophic cardiomyopathy and risk factors for SCD undergoing ICD implantation from May, 2000 to January, 2004 (mean follow-up = 20 months) were studied. Fourteen patients (53.8%) were females and the mean age was 42.7 years. ICD was indicated for primary prevention of sudden cardiac death in 16 patients (61.5%), and for secondary prevention in 10 patients (38.5%). Twenty patients (76.9%) presented syncope prior to ICD implantation; half of them were related to ventricular fibrillation or sustained ventricular tachycardia, 15 (57.7%) had a history of familial sudden death, 12 patients (46.2%) had nonsustained ventricular tachycardia on the 24-hour Holter monitoring, and five (19.2%) had an interventricular septal thickness greater than 30 mm. RESULTS: Four shock therapies were recorded by the ICD in potentially lethal arrhythmias (three patients with sustained ventricular tachycardia and one patient with ventricular fibrillation) during the follow-up. One death occurred, probably due to a thromboembolic stroke. Four patients had recurrence of syncope with no arrhythmic event recorded by the ICD. The statistical analysis showed a significant difference in early ICD shock therapy in patients whose interventricular septal thickness was greater than 30 mm. CONCLUSION: 1- occurrence of arrhythmic events in 50% of the patients; most of them (62%) were ventricular tachycardia, whether sustained (31%) or nonsustained (31%); in the remaining patients paroxysmal supraventricular tachycardia was observed. 2- recurrent syncope in the minority of the patients (16%), however not associated with the presence of arrhythmic events. 3- the presence of an interventricular septal thickness greater than 30 mm in the echocardiogram was associated with early shock therapy (p = 0.003). 4- absence of clinical or functional predictors.

Adolescent↗
PubMed2006

Aldosterone antagonism in an inflammatory state: evidence for myocardial protection.

INTRODUCTION: Chagas' disease is one of the most important causes of dilated cardiomyopathy in South and Central America. It is an inflammatory cardiomyopathy. We wanted to investigate whether it could have the same response to aldosterone antagonism as demonstrated before in other dilated cardiomyopathies. OBJECTIVE: To evaluate the role of spironolactone in myocardial remodelling in a Chagas cardiomyopathy model. MATERIAL AND METHODS: We studied 60 Sirius Hamsters divided into: control (C) infected (Inf) and Inf plus spironolactone (Infsp, 40 mg/kg/day) groups, for 11 months. Echocardiography with colour doppler was performed. Left ventricular end diastolic diameter (LVEDD), fractional shortening (FS) and corrected isovolumic relaxation time (IRT) were evaluated, as well as interstitial collagen volume fraction (ICVF) and myocardial inflammation. RESULT: The results demonstrated that survival was improved by use of spironolactone in the chronic phase (p<0.04). Body weight (BW) was C:190 g, Inf:167 g*, Infsp:198 g (*p<0.05, compared to C and Infsp), LVEDD/BW was C:0.31, Inf: 0.35*, Infsp: 0.29 (*p<0.05, compared to C and Infsp), FS was C:38, Inf: 35.5, Infsp: 38 (with no statistical difference) and IRT was C: 23 msec, Inf: 26 msec*, Infsp: 22 msec (p<0.05, compared to C and Infsp). ICVF (%) was attenuated at LV (C: 0.34+/-0.1, Inf: 1.75+/-0.7*, Infsp: 0.95+/-0.2*; *p<0.05, p<0.05). CONCLUSION: Spironolactone attenuated the myocardial remodelling in Chagas cardiomyopathy, reduced mortality during the chronic phase and reduced inflammatory infiltration.

Aldosterone↗
PubMed2005

TNF gene polymorphisms are associated with reduced survival in severe Chagas' disease cardiomyopathy patients.

Chronic Chagas' disease cardiomyopathy (CCC) is the most important clinical outcome of infection by the parasite Trypanosoma cruzi, affecting 18 million individuals in Latin America. One-third of CCC patients develop heart failure due to end-stage dilated cardiomyopathy, and their survival is reduced by 50% compared to patients with other cardiomyopathies. Genetic susceptibility may play a role in the differential survival of severe CCC patients. Given the role of TNF-alpha in the progression of heart failure, and the increased TNF-alpha plasma and heart tissue levels observed in these patients, we chose TNF as a candidate gene for increased mortality in severe CCC patients. We typed the TNFa microsatellite and the -308 TNF promoter polymorphism and then analyzed the survival curves of 42 patients with severe ventricular dysfunction (left ventricular ejection fraction<or=40%) according to the presence of the TNF2 promoter allele or the TNFa2 microsatellite allele, both previously associated with high TNF-alpha production. Multivariate regression analysis (Cox proportional hazards model) revealed the TNF genotype and age of onset of severe CCC as independent predictors of mortality in severe CCC. We showed that patients positive for TNF2 or TNFa2 alleles display a significantly shorter survival time compared to those carrying other alleles; the median survival times were 2.9 and 8 months, respectively (HR(adj)=2.28, p=0.020). We have identified for the first time a genetic factor related to reduced survival in severe Chagas' disease cardiomyopathy. The association of TNF genotype with earlier death in CCC should be taken into account when planning therapeutic intervention.

Adult↗
PubMed2005

Effect of Losartan on left ventricular diastolic function in patients with nonobstructive hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HC), diastolic dysfunction of the left ventricle is a prominent feature caused by myocardial hypertrophy and fibrosis. Angiotensin II has trophic and profibrotic effects on the heart, and the blockade of angiotensin II receptors reverses hypertrophy and fibrosis in human cardiac diseases and in animal HC. This study investigated the short-term (6 months) effects of losartan 100 mg/day in 20 patients with nonobstructive HC, with an emphasis on left ventricular (LV) diastolic dysfunction, compared with 10 patients with HC who were not treated. At the final evaluation, significant changes were observed in the losartan group: a left atrial diameter decrease (p<0.0001), a tissue Doppler early (Ea) mitral annulus diastolic velocity increase (p=0.003) and an E/Ea ratio decrease (p=0.0002), and a significant decrease in plasma levels of the aminoterminal fragment of pro-brain natriuretic peptide (NT-pro-BNP) from a median of 860 to 606 pg/ml (p=0.001). A significant correlation was found between percentage changes in NT-pro-BNP and the E/Ea ratio from baseline to 6 months (r=0.61, p=0.002). In the 2 groups, echocardiographic LV wall and cavity measures did not change. In conclusion, in selected patients with nonobstructive HC, losartan during a 6-month period improved LV diastolic function.

Adolescent↗
PubMed2005

[Cardiac papillary fibroelastoma. Experience of an institution].

Primary intracardiac tumors are rare, with prevalence between 0.0017% and 0.19% from non-selected autopsy studies. Approximately 75% are benign and almost half of them are myxomas. The remaining tumors are divided among rhabdomyomas, lipomas and fibroelastomas. Myxomas are the most common intracardiac tumors in adult age and rhabdomyomas the most common among pediatric population. Papillary fibroelastoma (PFE) is a relative rare benign heart tumor, corresponding to approximately 8% of intracardiac tumors. They most commonly manifested in cardiac valves. In the past, they either consisted of necropsy findings or were found in surgical procedures at random. In vivo diagnosis was sporadic. With the improvement of echocardiography techniques, PFE has been more frequently diagnosed. They are usually described as a movable, pedunculate, well-delimited mass and with predilection for valve endocardium. Therapeutic proposal, when they are pedunculate, is surgical resection, preventing cerebral, pulmonary, coronary or peripheral embolic phenomena. Five cases diagnosed in our institution, in the period from August 1995 to June 2004, will be presented.

Adult↗