RESUMEN

Heart disease is a major cause of death worldwide. Chronic Chagas cardiomyopathy (CCC) caused by infection with Trypanosoma cruzi leading to high mortality in adults, and rheumatic heart disease (RHD), resulting from infection by Streptococcus pyogenes affecting mainly children and young adults, are amongst the deadliest heart diseases in low-middle income countries. Despite distinct etiology, the pathology associated with both diseases is a consequence of inflammation. Here we compare systemic immune profile in patients with these cardiopathies, to identify particular and common characteristics in these infectious heart diseases. We evaluated the expression of 27 soluble factors, employing single and multivariate analysis combined with machine-learning approaches. We observed that, while RHD and CCC display higher levels of circulating mediators than healthy individuals, CCC is associated with stronger immune activation as compared to RHD. Despite distinct etiologies, univariate analysis showed that expression of TNF, IL-17, IFN-gamma, IL-4, CCL4, CCL3, CXCL8, CCL11, CCL2, PDGF-BB were similar between CCC and RHD, consistent with their inflammatory nature. Network analysis revealed common inflammatory pathways between CCC and RHD, while highlighting the broader reach of the inflammatory response in CCC. The final multivariate model showed a 100% discrimination power for the combination of the cytokines IL-12p70, IL-1Ra, IL-4, and IL-7 between CCC and RHD groups. Thus, while clear immunological distinctions were identified between CCC and RHD, similarities indicate shared inflammatory pathways in these infectious heart diseases. These results contribute to understanding the pathogenesis of CCC and RHD and may impact the design of immune-based therapies for these and other inflammatory cardiopathies that may also share immunological characteristics.

Asunto(s)

Cardiomiopatía Chagásica/sangre , Cardiomiopatía Chagásica/inmunología , Quimiocinas/sangre , Citocinas/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Adulto , Anciano , Análisis por Conglomerados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mapas de Interacción de Proteínas , Cardiopatía Reumática/sangre , Cardiopatía Reumática/inmunología , Solubilidad

RESUMEN

BACKGROUND: Rheumatic heart disease (RHD) is associated with inflammation that damages cardiac valves, often requiring surgical interventions. The underlying mechanisms involved in the disease progression are not completely understood. This study aimed to evaluate cytokine plasma levels in patients with RHD as possible markers of disease severity. METHODS AND RESULTS: Eighty-nine patients with RHD, age of 41 years ±11.5 years, were prospectively enrolled. RHD severity was defined as valve dysfunction that required invasive intervention, either valve repair or replacement. Peripheral blood samples were collected from all patients for cytokine measurements. The patients were followed up to look at adverse clinical events defined as either the need for valve intervention or death. At baseline, 64 (71.9%) patients had previously undergone valve intervention, whereas 25 patients had stable clinical presentation. Patients with severe RHD displayed higher levels of inflammatory cytokines than patients with stable disease. Cluster analysis showed segregation of severe and stable RHD based on IL-6/TNF-α and IL-6/IL-17A, respectively. IL-6 and TNF-α expression were positively correlated in severe but not in stable RHD patients. During a median follow-up of 23 months, 16 patients (18%) had an adverse outcome. IL-10 at baseline (HR 1.24, 95% CI 1.08-1.43, p = 0.003), and IL-4 (HR 1.12, 95% CI 1.01-1.24, p = 0.041) were predictors of events during the follow-up. CONCLUSIONS: High levels of cytokines are associated with severity of RHD. The co-regulated expression of IL-6 and TNF-α is associated with severe valve dysfunction, whereas high IL-10 and IL-4 levels predicted subsequently adverse outcome.

Asunto(s)

Citocinas/sangre , Cardiopatía Reumática/sangre , Adulto , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inflamación/sangre , Interleucina-6/sangre , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangre

RESUMEN

Rheumatic fever (RF) and its subsequent progression to rheumatic heart disease (RHD) are chronic inflammatory disorders prevalent in children and adolescents in underdeveloped countries, and a contributing factor for high morbidity and mortality rates worldwide. Their primary cause is oropharynx infection by Streptococcus pyogenes, whose acetylated residues are recognized by ficolin-1. This is the only membrane-bound, as well as soluble activator molecule of the complement lectin pathway (LP). Although LP genetic polymorphisms are associated with RF, FCN1 gene's role remains unknown. To understand this role, we haplotyped five FCN1 promoter polymorphisms by sequence-specific amplification in 193 patients (138 with RHD and 55, RF only) and 193 controls, measuring ficolin-1 serum concentrations in 78 patients and 86 controls, using enzyme-linked immunosorbent assay (ELISA). Patients presented lower ficolin-1 serum levels (p < 0.0001), but did not differ according to cardiac commitment. Control's genotype distribution was in the Hardy-Weinberg equilibrium. Four alleles (rs2989727: c.-1981A, rs10120023: c.-542A, rs10117466: c.-144A, and rs10858293: c.33T), all associated with increased FCN1 gene expression in whole blood or adipose subcutaneous tissue (p = 0.000001), were also associated with increased protection against the disease. They occur within the *3C2 haplotype, associated with an increased protection against RF (OR = 0.41, p < 0.0001) and with higher ficolin-1 levels in patient serum (p = 0.03). In addition, major alleles of these same polymorphisms comprehend the most primitive *1 haplotype, associated with increased susceptibility to RF (OR = 1.76, p < 0.0001). Nevertheless, instead of having a clear-cut protective role, the minor c.-1981A and c.-144A alleles were also associated with additive susceptibility to valvar stenosis and mitral insufficiency (OR = 3.75, p = 0.009 and OR = 3.37, p = 0.027, respectively). All associations were independent of age, sex or ethnicity. Thus, minor FCN1 promoter variants may play a protective role against RF, by encouraging bacteria elimination as well as increasing gene expression and protein levels. On the other hand, they may also predispose the patients to RHD symptoms, by probably contributing to chronic inflammation and tissue injury, thus emphasizing the dual importance of ficolin-1 in both conditions.

Asunto(s)

Lectinas/genética , Estenosis de la Válvula Mitral/genética , Cardiopatía Reumática/genética , Streptococcus pyogenes/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Haplotipos/genética , Haplotipos/inmunología , Humanos , Lectinas/sangre , Lectinas/inmunología , Lectinas/metabolismo , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/sangre , Estenosis de la Válvula Mitral/inmunología , Estenosis de la Válvula Mitral/microbiología , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Cardiopatía Reumática/sangre , Cardiopatía Reumática/inmunología , Cardiopatía Reumática/microbiología , Adulto Joven , Ficolinas

RESUMEN

Abstract Objective: The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). Methods: Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. Results: During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6 ± 0.48 g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. Conclusion: The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis.

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Resumo Objetivo: Definir os preditores da cardite crônica em pacientes com cardite reumática aguda (CRA). Métodos: Os pacientes diagnosticados com CRA entre maio de 2010 e maio de 2011 foram incluídos no estudo. Foram feitos os testes de ecocardiografia, eletrocardiograma, uma análise do subgrupo de linfócitos, provas de fase aguda, níveis de albumina plasmática, antiestreptolisina-O (ASO) na manifestação inicial. As avaliações ecocardiográficas foram repetidas no 6º mês de acompanhamento. Os pacientes foram divididos em dois grupos de acordo com a persistência da patologia valvular no 6º mês como Grupo 1 e Grupo 2 e todos os parâmetros clínicos e laboratoriais na internação foram comparados entre dois grupos de comprometimento valvular. Resultados: Durante o período do estudo de um ano, 22 pacientes apresentaram doença valvular; 17 (77,2%) apresentaram regressão da patologia valvular. Houve desaparecimento de regurgitação moderada inicial em oito pacientes (36,3%). Entre sete (31,8%) pacientes com regurgitação moderada inicialmente, a regurgitação desapareceu em três e quatro apresentaram melhoria para regurgitação leve. Dois pacientes com regurgitação grave inicialmente apresentaram melhoria para regurgitação moderada (9,1%). Em cinco (22,8%) pacientes o grau de regurgitação (regurgitação moderada em um [4,6%] e regurgitação grave em quatro [18,2]) continuou inalterado. O nível de albumina foi significativamente menor no diagnóstico no Grupo 2 (2,6 ± 0,48 gr/dL). A análise do subgrupo de linfócitos mostrou uma redução significativa no percentual de CD8 e um aumento significativo no percentual de CD19 no Grupo 2 em comparação com o Grupo 1. Conclusão: O nível de albumina no sangue e o percentual de linfócitos CD8 e CD19 (+) no diagnóstico podem ajudar a prever risco de doença valvular crônica em pacientes com cardite reumática aguda.

Asunto(s)

Humanos , Masculino , Femenino , Niño , Adolescente , Insuficiencia de la Válvula Aórtica/diagnóstico , Cardiopatía Reumática/diagnóstico , Albúmina Sérica/análisis , Antígenos CD19/inmunología , Insuficiencia de la Válvula Mitral/diagnóstico , Miocarditis/diagnóstico , Insuficiencia de la Válvula Aórtica/clasificación , Cardiopatía Reumática/sangre , Ecocardiografía Doppler , Enfermedad Aguda , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Estudios de Seguimiento , Linfocitos T CD8-positivos/inmunología , Electrocardiografía , Insuficiencia de la Válvula Mitral/clasificación , Miocarditis/sangre , Antiestreptolisina/sangre

RESUMEN

OBJECTIVE: The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). METHODS: Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. RESULTS: During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6±0.48g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. CONCLUSION: The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis.

Asunto(s)

Antígenos CD19/inmunología , Insuficiencia de la Válvula Aórtica/diagnóstico , Insuficiencia de la Válvula Mitral/diagnóstico , Miocarditis/diagnóstico , Cardiopatía Reumática/diagnóstico , Albúmina Sérica/análisis , Enfermedad Aguda , Adolescente , Antiestreptolisina/sangre , Insuficiencia de la Válvula Aórtica/clasificación , Linfocitos T CD8-positivos/inmunología , Niño , Ecocardiografía Doppler , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Insuficiencia de la Válvula Mitral/clasificación , Miocarditis/sangre , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Cardiopatía Reumática/sangre

RESUMEN

MASP-2 is a key protein of the lectin pathway of complement system. Several MASP2 polymorphisms were associated with MASP-2 serum levels or functional activity. Here we investigated a possible association between MASP2 polymorphisms and MASP-2 serum levels with the susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD). We haplotyped 11 MASP2 polymorphisms with multiplex sequence-specific PCR in 145 patients with history of RF from south Brazil (103 with RHD and 42 without cardiac lesion [RFo]) and 342 healthy controls. MASP-2 levels were determined by ELISA. The low MASP-2 producing p.377A and p.439H variants were negatively associated with RF (P=0.02, OR=0.36) and RHD (P=0.01, OR=0.25). In contrast, haplotypes that share the intron 9 - exon 12 g.1961795C, p.371D, p.377V and p.439R polymorphisms increased the susceptibility to RHD (P=0.02, OR=4.9). MASP-2 levels were associated with MASP2 haplotypes and were lower in patients (P<0.0001), which may reflect protein consumption due to complement activation. MASP2 gene polymorphisms and protein levels seem to play an important role in the development of RF and establishment of RHD.

Asunto(s)

Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/genética , Fiebre Reumática/genética , Cardiopatía Reumática/genética , Adolescente , Adulto , Secuencia de Bases , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos/genética , Humanos , Masculino , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/metabolismo , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Fiebre Reumática/sangre , Cardiopatía Reumática/sangre , Análisis de Secuencia de ADN , Adulto Joven

RESUMEN

OBJECTIVE: To evaluate the immunological profile and gene expression of endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated from a reference service in cardiovascular surgery. METHODS: This was a quantitative, observational and cross-sectional study. Thirty-five subjects (divided into four groups) participated in the study, 25 patients with chronic rheumatic heart disease and ten control subjects. The mean age of the sample studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were female. Inflammatory cytokines (TNF-α, IL-4 and IL-10) were measured and ten mitral valves of patients who underwent first valve replacement were collected for determination of gene expression of endothelin-1 by real time PCR. RESULTS: Among the groups studied (patients vs. controls), there was a statistically significant difference in IL-10 levels (P=0.002), and no differences in other cytokines. Expression of endothelin-1 was observed in 70% of samples. Quantitatively, average of ET-1 expression was 62.85±25.63%. CONCLUSION: Inflammatory cytokine IL-10 participates in the maintenance of chronicity of rheumatic fever in patients who underwent valve replacement and those who are undergoing medical treatment. The expression of endothelin-1 in heart valve lesions in patients undergoing mitral valve replacement confirms its association with inflammatory activity in rheumatic fever.

Asunto(s)

Endotelina-1/genética , Enfermedades de las Válvulas Cardíacas/genética , Interleucina-10/genética , Cardiopatía Reumática/genética , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Endotelina-1/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Enfermedades de las Válvulas Cardíacas/sangre , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Interleucina-10/sangre , Interleucina-4/sangre , Interleucina-4/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Cardiopatía Reumática/sangre , Cardiopatía Reumática/cirugía , Espectrofotometría , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Adulto Joven

RESUMEN

Objective: To evaluate the immunological profile and gene expression of endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated from a reference service in cardiovascular surgery. Methods: This was a quantitative, observational and cross-sectional study. Thirty-five subjects (divided into four groups) participated in the study, 25 patients with chronic rheumatic heart disease and ten control subjects. The mean age of the sample studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were female. Inflammatory cytokines (TNF-α, IL-4 and IL-10) were measured and ten mitral valves of patients who underwent first valve replacement were collected for determination of gene expression of endothelin-1 by real time PCR. Results: Among the groups studied (patients vs. controls), there was a statistically significant difference in IL-10 levels (P=0.002), and no differences in other cytokines. Expression of endothelin-1 was observed in 70% of samples. Quantitatively, average of ET-1 expression was 62.85±25.63%. Conclusion: Inflammatory cytokine IL-10 participates in the maintenance of chronicity of rheumatic fever in patients who underwent valve replacement and those who are undergoing medical treatment. The expression of endothelin-1 in heart valve lesions in patients undergoing mitral valve replacement confirms its association with inflammatory activity in rheumatic fever. .

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Objetivo: Avaliar o perfil imunológico e a expressão gênica de endotelina-1 em valvas mitrais de pacientes com febre reumática, originados de um serviço de referência em cirurgia cardiovascular. Métodos: Este foi um estudo quantitativo, observacional e transversal. Trinta e cinco indivíduos (divididos em quatro grupos) participaram do estudo, 25 deles com doença cardíaca reumática crônica, além de 10 controles. A média de idade da amostra estudada foi de 34,5 anos. Dezessete (48,58%) dos indivíduos eram homens, e 18 (51,42%) eram mulheres. Foram medidas algumas citocinas inflamatórias (TNF-α, IL-4 e IL-10) e coletadas 10 valvas mitrais de pacientes que se submeteram a primeira troca valvar para determinação da expressão gênica de endotelina-1 pelo PCR real-time. Resultados: Entre os grupos estudados (pacientes e controles), observou-se diferença estatisticamente significante em relação aos níveis de IL-10 (P=0,002), sem diferenças nas outras citocinas. Em relação à endotelina-1, foi observada sua expressão em 70% das amostras. Quantitativamente, a expressão média de endotelina-1 foi de 62,85±25,63%. Conclusão: A citocina inflamatória IL-10 participa da manutenção da cronicidade da febre reumática em pacientes que se submeteram a troca valvar e naqueles que estão em tratamento médico. A expressão de endotelina-1 nas lesões em valvas cardíacas de pacientes que foram submetidos à troca valvar mitral confirma sua relação com a atividade inflamatória na febre reumática. .

Asunto(s)

Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Endotelina-1/genética , Enfermedades de las Válvulas Cardíacas/genética , /genética , Cardiopatía Reumática/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Endotelina-1/sangre , Expresión Génica , Implantación de Prótesis de Válvulas Cardíacas , Enfermedades de las Válvulas Cardíacas/sangre , Enfermedades de las Válvulas Cardíacas/cirugía , /sangre , /genética , /sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Cardiopatía Reumática/sangre , Cardiopatía Reumática/cirugía , Espectrofotometría , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética

RESUMEN

Chronic rheumatic valve disease (CRVD) is a late sequel of Rheumatic Fever (RF) which appears in approximately 30% of RF patients, leading to valve injury. Advanced Oxidation Protein Products (AOPP) and high sensitive C-Reactive Protein (hs-CRP) plasma levels were measured in patients with CRVD in order to evaluate the presence of oxidative stress and systemic inflammation. A total of 90 patients (70 female, 20 male, mean age 46.01 +/- 11.72 years, range 24-69 years) with CRVD, who have or have not undergone valve replacement due to rheumatic etiology, and 46 healthy subjects (27 female, 19 male, mean age 41.89 +/- 9.02 years range 28-60 years) were studied. Levels of AOPP were measured by the determination of optical density (OD) at 340 nm under acidic conditions and hs-CRP by enhanced immunonephelometric assays. Significantly elevated levels of AOPP and hs-CRP were observed in CRVD patients when compared to the controls (AOPP 212.62 +/- 34.14 umol/l vs. 126.97 +/- 27.74 umol/l p < 0.00006 and for hs-CRP 5.40 +/- 1.98 mg/l vs. 2.66 +/- 1.36 mg/l p < 0.05). In addition, high levels of AOPP were associated to the presence of prosthetic valve and time after surgery (p < 0.0008 and p < 0.005, respectively). No correlation was observed between the levels of AOPP and hs-CRP with age, sex and degree of mitral valve stenosis. No correlation was found between AOPP and hs-CRP plasma values. These results suggest the involvement of oxidative stress and systemic inflammation in the pathogenesis of CRVD.

Asunto(s)

Proteína C-Reactiva/metabolismo , Mediadores de Inflamación/sangre , Estenosis de la Válvula Mitral/sangre , Estrés Oxidativo , Cardiopatía Reumática/sangre , Adulto , Anciano , Brasil/epidemiología , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/fisiopatología , Estenosis de la Válvula Mitral/cirugía , Cardiopatía Reumática/fisiopatología , Cardiopatía Reumática/cirugía , Resultado del Tratamiento

RESUMEN

Although mannose-binding lectin (MBL) is known to be involved in the primary defense against microorganisms, there are emerging lines of evidence for an active proinflammatory role for MBL in different chronic diseases. In this study we determined the circulating levels of MBL in patients with rheumatic heart disease (RHD). A total of 100 patients (77 women, 23 men; mean age 45.8 +/- 11 years, range 19-76 years) with chronic RHD, and a previous diagnosis of rheumatic fever, were studied. Transthoracic echocardiography was performed in all patients to evaluate valvular heart disease. Ninety-nine healthy individuals matched for age, sex and ethnic origin were included as controls. MBL concentration was measured by enzyme-linked immunosorbent assay and C3 and C4 levels by turbidimetry. MBL levels were significantly higher in patients with RHD than in healthy subjects (mean +/- SEM: 3036.2 +/- 298.9 ng/ml versus 1942.6 +/- 185.5 ng/ml, P <0.003). In addition, MBL deficiency was more prevalent in controls (17.1%) than in patients (9% P <0.09). Concentrations of C4 were within the normal range (22.7 +/- 0.8 mg/dl, normal: 10.0-40.0 mg/dl), while C3 concentrations were found to be elevated (109.2 +/- 3.6 mg/dl, normal: 50.0-90.0 mg/dl). No correlation was observed between serum MBL levels and valve area or the type of surgical procedure. The significantly elevated circulating MBL levels in patients with RHD together with the greater prevalence of MBL deficiency in controls suggest that MBL may cause undesirable complement activation contributing to the pathogenesis of RHD.

Asunto(s)

Lectina de Unión a Manosa/sangre , Cardiopatía Reumática/sangre , Adulto , Anciano , Complemento C3/análisis , Complemento C4/análisis , Femenino , Humanos , Masculino , Lectina de Unión a Manosa/deficiencia , Lectina de Unión a Manosa/inmunología , Persona de Mediana Edad , Cardiopatía Reumática/inmunología , Cardiopatía Reumática/cirugía

RESUMEN

PURPOSE: To study the clinical features of a group of patients with fatal acute rheumatic fever (ARF). PATIENTS AND METHODS: Thirteen patients with ARF, the ages ranged between 4.5 and 25 (mean 14) years. Eight patients were male. Patients were studied in two groups: group A of those 14 year-old or younger (8 cases), and group B of those older than 15 years (5 cases). RESULTS: Clinical presentation was fever and severe heart failure in all patients. In group A, it was the first attack of ARF in 5 patients. The time elapsed between beginning of symptoms and hospital admission ranged between 10 and 90 (mean 40) days. Mitral insufficiency occurred in all patients. The blood leukocyte count was greater than 10000 per mm3 in six cases. Atrioventricular block occurred in one case. Valvular vegetations were detected on echocardiogram in 4 cases. Two patients received antibiotic therapy. Surgical treatment of the valvular heart disease was carried on in one patient. In group B, it was the first ARF attack in 2 cases, the time elapsed between beginning of the symptoms and hospital admission ranged between 4 and 60 (mean 21) days. Leukocyte count greater than 10000 por mm3 occurred in 4 cases. Atrioventricular block was diagnosed in one case. Valvular vegetations on echocardiogram were detected in 2 patients. In two cases, the treatment was antibiotic therapy. Three patients were operated on. CONCLUSION: ARF may still be fatal, even in the first attack or in patients in the third decade of life. Other diagnoses are frequently considered, due to the intense clinical and laboratorial manifestations.

Asunto(s)

Cardiopatía Reumática/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Tiempo de Internación , Recuento de Leucocitos , Masculino , Cardiopatía Reumática/sangre , Cardiopatía Reumática/patología , Cardiopatía Reumática/terapia

RESUMEN

Casuística e Métodos - Teze portadores de DR ativa fatal, de idades entre 4,5 e 25 (média de 14) anos, oito (61,5%) do sexo masculino, com diagnóstico confirmado pela necrópsia. Constituiram-se: grupo A: idade até 15 anos (8 casos), e grupo B: idade superior a 15 anos (5 casos). Resultados - O quadro clínico principal foi febre associada a insuficiência cardíaca grave em todos os casos. No grupo A, foi o primeiro surto reumático em 5 casos e o tempo decorrido entre o início dos sintomas e a hospitalizaçäo variou de 10 a 90 (média de 40) dias; insuficiência mitral ocorreu em todos os casos, em seis a taxa de leucócitos foi superior a 10000 por mm3 e em sete a taxa de mucocproteínas foi superior a 8 mg/dl; bloqueio atrioventricular de 1§ grau ocorreu em um caso; vegetaçöes valvares ao ecocardiograma foram reconhecidas em 5 casos. Dois casos receberam antibiotioterapia, cinco prednisona e depois antibióticos, e um antibióticos e depois prednisona; tratamento cirúrgico da disfunçäo valvar foi realizado em um paciente. No grupo B, foi o primeiro surto reumático em dois casos, o tempo decorrido entre o início dos sintomas e a hospitalizaçäo variou de 4 a 60 (média de 21) dias; em quatro casos a taxa de leucócitos fou superior a 10000 por mm3 e a taxa de mucoproteiína foi superior a 8 mg/dl em 2 casos; bloqueio atrioventricular foi diagnosticado em um caso; Vegetaçöes valvares foram reconhecidas ao ecocardiograma em dois casos; em dois casos foi aplicada antibioticoterapia e em três foi indicado o tratamento cirúrgico. Conclusäo - A DR ativa pode ter evoluçäo fatal mesmo no primeiro surto ou já na terceira década da vida. Outros diagnósticos säo freqüentemente cogitados, em funçäo de manifestaçöes clínicas e laboratoriais muito intensas

Asunto(s)

Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Cardiopatía Reumática/patología , Cardiopatía Reumática/complicaciones , Cardiopatía Reumática/sangre , Cardiopatía Reumática/terapia , Enfermedad Aguda , Insuficiencia Cardíaca/complicaciones , Tiempo de Internación , Recuento de Leucocitos