Torres O.A.,Institute Parasitologia y Biomedicina Lopez Neyra |
Calzada J.E.,Instituto Conmemorativo Gorgas Of Estudios Of La Salud Icges |
Beraun Y.,Institute Parasitologia y Biomedicina Lopez Neyra |
Morillo C.A.,Fundacion Cardiovascular de Colombia |
And 3 more authors.
Infection, Genetics and Evolution | Year: 2010
Genetic susceptibility to Trypanosoma cruzi infection and the development of cardiomyopathy is complex, heterogeneous, and likely involves several genes. Previous studies have implicated cytokine and chemokine genes in susceptibility to Chagas disease. Here we investigated the association between the interferon-gamma gene (IFNG) +874T/A polymorphism and Chagas disease, focusing on susceptibility and severity. This study included 236 chagasic patients (asymptomatic, n=116; cardiomyopathic, n=120) and 282 healthy controls from a Colombian population where T. cruzi is highly endemic. Individuals were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) of the IFNG gene by amplification refractory mutational system PCR (ARMS-PCR). Moreover, clinical manifestations of Chagas in patients were analyzed. We found a significant difference in the distribution of the IFNG +874 "A" allele between patients and healthy controls (P=0.003; OR = 1.46, 95% CI, 1.13-1.89). The frequency of the IFNG +874 genotype A/A, which is associated with reduced production of interferon-gamma, was increased in the patients relative to controls (38.1% vs. 26.6%). We compared the frequencies of IFNG alleles and genotypes between asymptomatic patients and those with chagasic cardiomyopathy and found no significant difference. Our data suggest that the IFNG +874T/A genetic polymorphism may be involved in susceptibility but not in the progression of Chagas disease in this Colombian population. © 2010 Elsevier B.V. Source
Bojan M.,Necker Enfants Malades University Hospital |
Basto Duarte M.C.,Fundacion Cardiovascular de Colombia |
Ermak N.,Necker Enfants Malades University Hospital |
Lopez-Lopez V.,Necker Enfants Malades University Hospital |
And 2 more authors.
Critical Care | Year: 2016
Background: Uncertainties about the pathophysiological processes resulting in cardiac surgery-related acute kidney injury (AKI) in infants concern the relative impact of the most prominent risk factors, the clinical relevance of changes in glomerular filtration rate vs tubular injury, and the usefulness of available diagnostic tools. Structural equation modelling could allow for the assessment of these complex relationships. Methods: A structural model was specified using data from a prospective observational cohort of 200 patients <1year of age undergoing cardiopulmonary bypass surgery. It included four latent variables: AKI, modelled as a construct of perioperative creatinine variation, of oliguria and of urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations; the cardiopulmonary bypass characteristics; the occurrence of a post-operative low cardiac output syndrome and the post-operative outcome. Results: The model showed a good fit, and all path coefficients were statistically significant. The bypass was the most prominent risk factor, with a path coefficient of 0.820 (95% CI 0.527-0.979), translating to a 67.2% explanation for the risk of AKI. A strong relationships was found between AKI and early uNGAL excretion, and between AKI and the post-operative outcome, with path coefficients of 0.611 (95% CI 0.347-0.777) and 0.741 (95% CI 0.610-0.988), respectively. The path coefficient between AKI and a >50% increase in serum creatinine was smaller, with a path coefficient of 0.443 (95% CI 0.273-0.596), and was intermediate for oliguria, defined as urine output <0.5mlkg-1 h-1, with a path coefficient of 0.495 (95% CI 0.250-0.864). A path coefficient of -0.229 (95% CI -0.319 to 0.060) suggested that the risk of AKI during the first year of life did not increase with younger age at surgery. Conclusions: These findings suggest that cardiac surgery-related AKI in infants is a translation of tubular injury, predominately driven by the cardiopulmonary bypass, and linked to early uNGAL excretion and to post-operative outcome. Trial registration: ClinicalTrials.gov identifier NCT01219998. Registered 11 October 2010. © 2016 The Author(s). Source
Morillo C.A.,Hamilton Health Sciences |
Avezum A.,Instituto Dante Pazzanese Of Cardiologia |
Sosa-Estani S.,Instituto Nacional Of Parasitologia |
Rassi A.,Hospital do Cora..o Anis Rassi |
And 14 more authors.
New England Journal of Medicine | Year: 2015
BACKGROUND The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven. METHODS We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event. RESULTS The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P = 0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P = 0.16 for interaction). CONCLUSIONS Trypanocidal therapy with benznidazole in patients with established Chagas' cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.). © 2015 Massachusetts Medical Society. All rights reserved. Source
Gamboa-Delgado E.M.,Fundacion Cardiovascular de Colombia |
Rodriguez-Ramirez S.,Instituto Nacional Of Salud Publica
Revista Facultad de Medicina | Year: 2014
Ethical considerations must be taken into account in studies involving people. The evaluation of programmes using randomised designs requires careful consideration regarding their enrolment, intervention allocation and follow/up phases. From the outset, special emphasis must be placed on equity during the enrolment phase concerning the inclusion of subjects participating in such studies, gaining/giving their informed consent and confidentiality. The allocation intervention phase should consider the control group’s deprivation of benefits, their assignation by random draw and equity regarding the distribution of benefits. Special consideration should be paid to adverse events during the follow-up phase and participants’ remuneration. The ethical implications of randomising individuals benefitting from programmes require extensive analysis, the organisation of consensus and ethical guidelines being disseminated for researchers and evaluators. © 2014, Universidad Nacional de Colombia. All rights reserved. Source
Reyes L.M.,University of Alberta |
Garcia R.G.,Fundacion Cardiovascular de Colombia |
Ruiz S.L.,Fundacion Cardiovascular de Colombia |
Broadhurst D.,University of Alberta |
And 3 more authors.
Growth Factors | Year: 2012
Background: An imbalance between anti-angiogenic factors (e.g. soluble vascular endothelial growth factor receptor-1 (s-FLT1) and soluble endoglin (s-Eng)) and pro-angiogenic factors (e.g. placental growth factor (PlGF)) as well as increased oxidized low-density lipoprotein (ox-LDL) concentrations have been associated with preeclampsia (PE). Risk factors associated with the development of PE, however, are known to be different between developed and developing countries. The aim of the study was to determine the levels of s-FLT1, s-Eng, PIGF, and ox-LDL in women with PE from a developing country. Methods: A multi-center casecontrol study was conducted. One hundred and forty three women with PE were matched by age and parity with 143 healthy pregnant women without cardiovascular or endocrine diseases. Before delivery, blood samples were taken and serum was stored until analysis. Results: Women with PE had lower concentrations of PIGF (p < 0.0001) and higher concentrations of s-Eng (p = 0.001) than healthy pregnant women. There were no differences between the groups regarding ox-LDL or s-FLT1. Women with early onset PE had higher s-FLT1 concentrations (p = 0.0004) and lower PIGF concentrations (p < 0.0001) than their healthy pregnant controls. Women with late onset PE had higher concentrations of s-Eng (p = 0.005). Women with severe PE had higher concentrations of s-Eng (p = 0.0008) and ox-LDL (p = 0.01), and lower concentrations of PIGF (p < 0.0001). Conclusions: Women with PE from a developing country demonstrated an angiogenic imbalance and an increased rate of LDL oxidation. Findings from this study support the theory that PE is a multifactorial disease, and understanding differences in these subpopulations may provide a better target to approach future therapies. © 2012 Informa UK, Ltd. Source