Minipuberty and Sexual Dimorphism in the Infant Human Thymus.

AIRE expression in thymus is downregulated by estrogen after puberty, what probably renders women more susceptible to autoimmune disorders. Here we investigated the effects of minipuberty on male and female infant human thymic tissue in order to verify if this initial transient increase in sex hormones - along the first six months of life - could affect thymic transcriptional network regulation and AIRE expression. Gene co-expression network analysis for differentially expressed genes and miRNA-target analysis revealed sex differences in thymic tissue during minipuberty, but such differences were not detected in the thymic tissue of infants aged 7-18 months, i.e. the non-puberty group. AIRE expression was essentially the same in both sexes in minipuberty and in non-puberty groups, as assessed by genomic and immunohistochemical assays. However, AIRE-interactors networks showed several differences in all groups regarding gene-gene expression correlation. Therefore, minipuberty and genomic mechanisms interact in shaping thymic sexual dimorphism along the first six months of life.

Double Root Switch Repair for Taussig-Bing Anomaly.

The double root switch was used to repair a Taussig-Bing anomaly in a two-month-old child. The surgery was performed with translocation of the aortic root to the left ventricular outflow tract and the pulmonary root to the right ventricular outflow tract, after closure of the ventricular septal defect with a patch that ultimately directed flow from the left ventricle to the aorta. This surgical approach has the theoretical advantage of reducing the likelihood of subneopulmonary obstruction, left ventricular outflow obstruction, neoaortic dilatation, and regurgitation and therefore has the potential to minimize the mortality and morbidity related to reintervention and reoperation.

Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants.

Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue--obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT)--and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the "canonical" way of thymus functioning. Conversely, DS networks represent a "non-canonical" way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes.

[The role of echocardiography as an isolated method for indicating surgery in patients with congenital heart disease]. / O papel do ecocardiograma como método isolado na indicação cirúrgica de pacientes portadores de cardiopatia congênita.

OBJECTIVE: To determine the diagnostic accuracy of echocardiography for indicating surgery without catheterization in patients with congenital heart disease through a prospective analysis and comparison of the echocardiographic diagnosis with the intraoperative findings, or invasive study, or both. METHODS: From February 2000 to January 2001, 493 patients with congenital heart diseases indicated for surgery were followed up. They underwent echocardiography with color-flow mapping for a therapeutic decision. The results were compared with the findings of surgery or catheterization, or both, when the latter were performed for diagnostic reasons. RESULTS: Of the patients studied, 94.3% (465 cases) underwent congenital heart disease correction based only on echocardiographic findings, without a diagnostic catheterization. The invasive study was performed for diagnostic reasons in 28 (5.6%) patients, the surgical treatment was performed in more than 95% of the patients, and therapeutic catheterization was performed in 3.6%. The echocardiographic findings were confirmed in 464 (94.1%) patients, which showed the high accuracy of the method. False-positive findings occurred in 8 (1.6%) patients, and false-negative findings in 39 (7.9%). According to surgeons, no diagnostic error led to complications or adversely affected the surgical results. CONCLUSION: Echocardiography proved to be a sensitive and safe method for indicating surgery, making catheterization, often, unnecessary. The invasive study was restricted to diagnostic or therapeutic uses.

Mixed type total anomalous pulmonary venous connection: early results and surgical techniques.

INTRODUCTION: The mixed total anomalous pulmonary connection is a rare type of congenital cardiopathy. The occurrence of multiple connections of the pulmonary veins has important implication in the diagnosis and surgical planning. These types of total anomalous pulmonary venous connection (TAPVC) and the infracardiac have higher surgical mortality. METHODS: Between December 1994 and July 2013, a total of 58 children underwent surgical treatment of TAPVC. Twenty-five (43.1%) patients had supracardiac connection, 15 (25.8%) patients had intracardiac type, 12 (20.6%) patients had a mixed type, and 6 (10.3%) patients had an infracardiac type. In children with mixed TAPVC, four (33.3%) patients had type I, five (41.6%) patients had type II, and three (25.0%) patients had type III. The diagnosis of TAPVC was performed in all patients using Doppler echocardiography, and they underwent cardiopulmonary bypass with aorta-bicaval cannulation and lately we use mild hypothermia with normal flow. The drainage channels were ligated in all patients. RESULTS: The immediate surgical results were as follows: one (16.6%) death in the infracardiac group, four (16.0%) deaths in the supracardiac group, one (8.3%) death in the mixed group, and no death in the cardiac group (no statistical difference, P = .488). CONCLUSION: In this series of patients, the mixed TAPVC could be corrected only with preoperative two-dimensional Doppler echocardiography with good immediate results, and we believe that the use of computed angiotomography combined with three-dimensional reconstruction may improve the surgical outcome mainly in the mixed and infracardiac group of TAPVC.

Double root switch: a complete anatomical correction for transposition of the great arteries.

We report the cases of two neonates with transposition of the great arteries, whose surgical correction consisted of translocation of the aortic root with the aortic valve and coronary arteries to the left ventricle and translocation of the pulmonary root with the pulmonary valve to the right ventricle. We believe that the aortic translocation may reduce the likelihood of dilatation of the neoaorta, aortic regurgitation, and changes in the endothelium of coronary arteries which have occasionally been seen following arterial switch operations.

New technique: aortic and pulmonary translocation with preservation of pulmonary valve.

We applied successfully, a new surgical technique, in two children with transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction, that utilized aortic translocation with the aortic valve and the coronary arteries to the left ventricle, after correction of left outflow tract obstruction and correction of the ventricular septal defect, associated to pulmonary root translocation to the right ventricle, conserving integrally the pulmonary valve.

Balloon atrial septostomy guided by echocardiography in a neonatal intensive care unit.

BACKGROUND: The bedside two-dimensional echocardiography (2-D ECHO) has been successfully used to guide the balloon atrial septostomy, speeding up the procedure and preventing the risks of transportation to the hemodynamics laboratory. OBJECTIVE: To assess the results of the bedside balloon atrial septostomy in cyanotic neonates. METHODS: Between January/1997 and July/2008, 102 atrioseptostomies by balloon catheter guided by echocardiography were carried out and saturation levels, defect diameter, oxygen saturation, clinical-laboratory response and complications related to the procedure were evaluated. RESULTS: Of 102 cases of bedside Rashkind septostomy, 98 met the inclusion criteria, with 90 neonates in Group A (Rashkind procedure in the preoperative phase) and 8 in Group B (procedure at the postoperative phase). There was a predominance of the male sex (75%), mean age was 8.3 ± 9.3 days and the mean weight was 3,100 ± 1,100 g; the transposition of the great arteries was the most frequent congenital heart disease (n = 74). When comparing the levels of saturation pre and post-procedure (65.9 ± 19.5% and 86 ± 9.7%) and the diameter of the interatrial septal defect pre and post-procedure (2.3 ± 1.0 mm and 5.5 ± 1.3 mm) there was a statistically significant difference (p < 0.001). When comparing the levels of saturation and the diameter of the interatrial septal defect between the group of survivors vs non-survivor, there was no statistically significant difference (p > 0.05). CONCLUSION: The balloon atrial septostomy guided by the echocardiography reduces the risks by allowing the effective palliative procedure to be carried out promptly in cyanotic neonates, in addition to presenting lower hospital costs.

Biointegration and growth of porcine valved pulmonary conduits in a sheep model.

As there is currently no suitable valved pulmonary conduit for small children, porcine conduits treated by the L-Hydro process were implanted into 9 newborn lambs to investigate growth potential. Of the 8 survivors, 7 were kept alive for 12 months after implantation. The diameter of the conduit and gradient across the valve were evaluated at surgery and at 3 and 9 months postoperatively using bidirectional echocardiographic and angiographic methods. After sacrifice, histological and radiological analyses were performed. The mean weight of the animals was 4.2 +/- 1.1 kg at implantation and 43.1 +/- 6.2 kg at sacrifice. There was a significant increase in mean valve area from 139.9 +/- 18.0 mm2 at implantation to 443.5 +/- 89.2 mm2 at 12 months. Pre-sacrifice angiography showed no transvalvular gradient, and radiographic analysis did not reveal significant conduit wall or leaflet calcification in any of the animals. Histological examination of the grafts demonstrated total integration, with native-like intact valve leaflets. Thus functional evaluation, echocardiography, and histology demonstrated growth of the grafts with completely endothelialized and apparently normal pulmonary valve leaflets without calcification.

New technique: Norwood operation with regional cerebral and coronary perfusion.

OBJECTIVE: To assess the immediate result of the modified Norwood procedure with new technique of anterograde regional cerebral perfusion (ARCeP) and retrograde regional coronary perfusion (RRCoP) in substitution of profound hypothermia and circulatory arrest in children with hypoplastic left heart syndrome (HLHS) with extremely hypoplastic ascending aorta (HA). METHODS: In the period of December of 2006 to February 2008 the modified Norwood procedure with tube between the right ventricle and pulmonary arteries or Sano shunt was performed in eight children with HLHS and with ascending aorta diameter less than 3 mm, (four male and four female) with median age of 9.2 days (ranging from 1 to 29 days) and median weigh of 3.3 kg (ranging from 2.7 to 3.8 kg). We used cardiopulmonary bypass and hypothermia at 25 masculineC with two venous cannulas and suture with a polytetrafluoroethylene graft sutured to the innominate artery as an arterial line and used to ARCeP. The RRCoP was performed by a deviation in the arterial line and placement of a catheter in the ascending aorta. The immediate surgical results and the clinical neurological manifestation were assessed. RESULTS: The immediate surgical results revealed mortality of 25% and there were absence of neurological injury at clinical examination. CONCLUSIONS: The modified Norwood procedure can be accomplished with ARCeP and RRCoP in children with HLHS with HA with satisfactory immediate surgical result and without neurological complications.

Nova técnica: translocação aórtica e pulmonar com preservação da valva pulmonar / New technique: aortic and pulmonary translocation with preservation of pulmonary valve

Realizamos com sucesso novo procedimento cirúrgico, em duas crianças portadoras de transposição das grandes artérias associada a comunicação interventricular e obstrução da via de saída do ventrículo esquerdo. A cirurgia consiste na realização de translocação aórtica com a valva aórtica e as artérias coronárias para o ventrículo esquerdo, após a ampliação da via de saída desse ventrículo e da comunicação interventricular com pericárdio autólogo fixado em glutaraldeído, associada à translocação do tronco pulmonar para o ventrículo direito, conservando integralmente a valva pulmonar.

We applied successfully, a new surgical technique, in two children with transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction, that utilized aortic translocation with the aortic valve and the coronary arteries to the left ventricle, after correction of left outflow tract obstruction and correction of the ventricular septal defect, associated to pulmonary root translocation to the right ventricle, conserving integrally the pulmonary valve.

Atriosseptostomia por cateter balão guiada pela ecocardiografia em unidade de terapia intensiva neonatal / Balloon atrial septostomy guided by echocardiography in a neonatal intensive care unit

FUNDAMENTO: A ecocardiografia bidimensional à beira do leito tem sido utilizada com sucesso para guiar a atriosseptostomia com cateter balão, agilizando o procedimento e evitando os riscos do transporte para o laboratório de hemodinâmica. OBJETIVO: Avaliar os resultados da atriosseptostomia com cateter balão à beira do leito em neonatos cianóticos. MÉTODOS: Entre jan/1997 e jul/2008, foram realizados 102 procedimentos de atriosseptostomia com cateter balão guiados pela ecocardiografia, sendo avaliados níveis de saturação, diâmetro da comunicação, saturação de oxigênio, resposta clínico-laboratorial e complicações relacionadas ao procedimento. RESULTADOS: De um total de 102 casos de Rashkind realizados à beira do leito, 98 preencheram os critérios de inclusão, sendo 90 neonatos do Grupo A (procedimento de Rashkind em fase pré-operatória) e 8 do Grupo B (procedimento em fase pós-operatória). Houve predomínio do sexo masculino (75 por cento), a idade média foi de 8,3 ± 9,3 dias, o peso médio foi de 3.100 ± 1.100 g e a transposição das grandes artérias foi a cardiopatia congênita mais frequente (n = 74). Comparando-se os valores das saturações pré e pós-procedimento (65,9 ± 19,5 por cento e 86 ± 9,7 por cento) e o diâmetro da comunicação interatrial pré e pós-procedimento (2,3 ± 1,0 mm e 5,5 ± 1,3 mm) houve diferença estatisticamente significativa (p < 0,001). Comparando-se os valores das saturações e o diâmetro da comunicação interatrial nos grupos de sobreviventes e não sobreviventes não houve diferença estatisticamente significativa (p > 0,05). CONCLUSÃO: A atriosseptostomia com cateter guiada pela ecocardiografia reduz os riscos por possibilitar a efetiva paliação sem perda de tempo em neonatos cianóticos, além de apresentar menores custos hospitalares.

BACKGROUND: The bedside two-dimensional echocardiography (2-D ECHO) has been successfully used to guide the balloon atrial septostomy, speeding up the procedure and preventing the risks of transportation to the hemodynamics laboratory. OBJECTIVE: To assess the results of the bedside balloon atrial septostomy in cyanotic neonates. METHODS: Between January/1997 and July/2008, 102 atrioseptostomies by balloon catheter guided by echocardiography were carried out and saturation levels, defect diameter, oxygen saturation, clinical-laboratory response and complications related to the procedure were evaluated. RESULTS: Of 102 cases of bedside Rashkind septostomy, 98 met the inclusion criteria, with 90 neonates in Group A (Rashkind procedure in the preoperative phase) and 8 in Group B (procedure at the postoperative phase). There was a predominance of the male sex (75 percent), mean age was 8.3 ± 9.3 days and the mean weight was 3,100 ± 1,100 g; the transposition of the great arteries was the most frequent congenital heart disease (n = 74). When comparing the levels of saturation pre and post-procedure (65.9 ± 19.5 percent and 86 ± 9.7 percent) and the diameter of the interatrial septal defect pre and post-procedure (2.3 ± 1.0 mm and 5.5 ± 1.3 mm) there was a statistically significant difference (p < 0.001). When comparing the levels of saturation and the diameter of the interatrial septal defect between the group of survivors vs non-survivor, there was no statistically significant difference (p > 0.05). CONCLUSION: The balloon atrial septostomy guided by the echocardiography reduces the risks by allowing the effective palliative procedure to be carried out promptly in cyanotic neonates, in addition to presenting lower hospital costs.

Nova técnica: operação de Norwood com perfusão regional cerebral e coronariana / New technique: Norwood operation with regional cerebral and coronary perfusion

Objetivo: Avaliar o resultado imediato da operação de Norwood modificado com nova técnica de perfusão regional cerebral (PRCeA) anterógrada associado a perfusão regional coronariana (PRCoR) retrógrada em substituição à parada circulatória total com hipotermia profunda em crianças portadoras da Síndrome da Hipoplasia do Coração Esquerdo (SHCE) com aorta ascendente extremamente hipoplásica (AH). Métodos: No período de dezembro de 2006 a fevereiro de 2008, a operação de Norwood modificado com tubo entre o ventrículo direito e as artérias pulmonares ou shunt tipo Sano foi realizada em oito crianças portadoras de SHCE e aorta ascendente com diâmetro inferior a 3 mm, (quatro do sexo masculino e quatro do sexo feminino) com idade média de 9,2 dias (variando de 1 a 29 dias) e peso médio de 3,3 kg (variando de 2,7 a 3,8 kg). Utilizada CEC e hipotermia a 25ºC com duas cânulas venosas e anastomose de um enxerto de politetrafluoretileno com a artéria inominada utilizado como linha arterial e para PRCeA. A PRCoR foi realizada por meio de um desvio na linha arterial e colocação de um cateter na aorta ascendente. Foram analisados o resultado cirúrgico imediato e a presença de alterações neurológicas nesse período. Resultados: O resultado cirúrgico imediato revelou mortalidade de 25 por cento e ausência de comprometimento neurológico ao exame clínico. Conclusão: A operação de Norwood modificado pode ser realizada com PRCeA e PRCoR em crianças com SHCE e AH com resultado cirúrgico imediato satisfatório e ausência de complicações neurológicas.

Objective: To assess the immediate result of the modified Norwood procedure with new technique of anterograde regional cerebral perfusion (ARCeP) and retrograde regional coronary perfusion (RRCoP) in substitution of profound hypothermia and circulatory arrest in children with hypoplastic left heart syndrome (HLHS) with extremely hypoplastic ascending aorta (HA). Methods: In the period of December of 2006 to February 2008 the modified Norwood procedure with tube between the right ventricle and pulmonary arteries or Sano shunt was performed in eight children with HLHS and with ascending aorta diameter less than 3 mm, (four male and four female) with median age of 9.2 days (ranging from 1 to 29 days) and median weigh of 3.3 kg (ranging from 2.7 to 3.8 kg). We used cardiopulmonary bypass and hypothermia at 25ºC with two venous cannulas and suture with a polytetrafluoroethylene graft sutured to the innominate artery as an arterial line and used to ARCeP. The RRCoP was performed by a deviation in the arterial line and placement of a catheter in the ascending aorta. The immediate surgical results and the clinical neurological manifestation were assessed. Results: The immediate surgical results revealed mortality of 25 percent and there were absence of neurological injury at clinical examination. Conclusions: The modified Norwood procedure can be accomplished with ARCeP and RRCoP in children with HLHS with HA with satisfactory immediate surgical result and without neurological complications.

Quando indicar e quando não indicar a cirurgia de duplo switch / Double switch for congenitally corrected transposition of the great arteries: when indicate or not

A transposição congenitamente corrigida das grandes artérias (ccTGA) é uma cardiopa-tia pouco frequente e complexa, em que os ventrículos e suas respectivas válvulas estão inapropriadamente conectados com os átrios e na qual as grandes artérias estão trans-postas. Na ccTGA, os efeitos da inversão ventricular estão fisiologicamente corrigidos pela presença da transposição das grandes artérias, isto é, o retorno venoso sistêmico é ejetado para o tronco pulmonar e o retorno venoso pulmonar é ejetado para a aorta. A maioria dos casos apresenta defeitos associados, como comunicação interventricular, obstrução da via de saída do ventrículo morfologicamente esquerdo, anomalias da valva atrioventricular morfologicamente direita e a localização anormal do tecido de condução atrioventricular. A sobrevida é determinada pelos defeitos associados e mesmo na ccTGA isolada há menor expectativa de sobrevida, podendo ser melhorada pelo duplo switch, chamado de correção anatômica. O switch arterial, juntamente com o switch atrial e a correção dos defeitos associados existentes para que o ventrículo esquerdo fique conectado à circulação sistêmica, é a proposta atual de tratamento destes pacientes e tem excelentes resultados. É essencial o entendimento dos reais benefícios deste tra-tamento e sua aplicabilidade frente ao tratamento convencional chamado de correção fisiológica. A indicação do double switch ainda é muito tímida em nosso país e é ne-cessário que haja confiança na técnica cirúrgica. Devemos raciocinar em termos de lon-gevidade e qualidade de vida para escolher a melhor tática para estes pacientes. Neste trabalho, são enumeradas e discutidas as possibilidades cirúrgicas para o tratamento da ccTGAe seus resultados.

O papel do ecocardiograma como método isolado na indicação cirúrgica de pacientes portadores de cardiopatia congênita / The role of echocardiography as an isolated method for indicating surgery in patients with congenital heart disease

OBJETIVO: Determinar a acurácia diagnóstica do ecocardiograma, analisando prospectivamente, o valor do método na indicação cirúrgica sem cateterismo em portadores de cardiopatia congênita, através da comparação do diagnóstico ecocardiográfico com os achados intra-operatórios e/ou do estudo invasivo. MÉTODOS: De fevereiro/2000 a janeiro/2001, foram acompanhados 493 pacientes cardiopatas congênitos com indicação cirúrgica, submetidos a ecocardiograma com mapeamento de fluxo em cores para decisão terapêutica. Os resultados foram comparados aos achados cirúrgicos e/ou de cateterismo quando realizado para complementação diagnóstica. RESULTADOS: Dos pacientes estudados, 94,3 por cento (465 casos) foram submetidos à correção da cardiopatia congênita apenas com o ecocardiograma e sem cateterismo diagnóstico. O estudo invasivo foi realizado para complementação diagnóstica em 28 (5,6 por cento) casos, o tratamento cirúrgico realizado em mais de 95 por cento dos casos e o cateterismo terapêutico em 3,6 por cento. Os achados do ecocardiograma se confirmaram em 464 (94,1 por cento) dos casos, demonstrando uma alta acurácia do método. Ocorreram 8 (1,6 por cento) casos de falso positivos e 39 (7,9 por cento) casos de falso negativos. Segundo os cirurgiões, nenhum dos erros diagnósticos levaram a complicações ou afetaram os resultados cirúrgicos adversamente. CONCLUSAO: O ecocardiograma se mostrou método sensível e seguro para indicação cirúrgica, dispensando, muitas vezes, a realização de estudo invasivo, ficando este, restrito aos casos de complementação diagnóstica ou terapêutica.

Tratamento cirúrgico da tétrade de Fallot associada a coronária anômala / Surgical treatment of tetralogy of Fallot associated with anomalous coronary vessel

A presença de artéria coronária anômala cruzando a via de saída do ventrículo direito associada a tétrade de Fallot, tem grande importância quando da realizaçäo do tratamento cirúrgico, já que a secçäo inadvertida dessa artéria, é acompanhada de um alto índice de mortalidade. No período de 1977 a 1987, foram operados 475 pacientes portadores de tétrade de Fallot, 14 dos quais apresentavam coronária anômal (3%); três tinham idade inferior a um ano; 11 eram do sexo masculino. O diagnóstico foi realizado na sala de operaçäo em 13 pacientes. Doze tinham a coronária descendente anterior originando-se da coronária direita e dois eram portadores de coronária esquerda única. Durante o tratamento cirúrgico dois pacientes sofreraram secçäo da coronária anômala sendo em um interposto enxerto de veia safena homólogo e anastomose término-terminal em outro. Nos restantes realizou-se ventriculotomia transversa (um caso), dissecçäo paliativa (um caso), colocaçäo de tubo valvulado entre ventrículo direito e tronco da pulmonar (um caso), correçäo via átrio-pulmonar (sete casos). Näo houve mortalidade imediata e no seguimento tardio (média de três anos) houve um óbito. Os autores sugerem, sempre que a anatomia pirmitir, a correçäo via átri-pulmonar, nos casos de associaçäo de coronária anômala e tétrade de Fallot

Tratamento cirúrgico de drenagem anômala total de veias pulmonares em veia cava superior direita / Surgical Treatment of Total Anomalous Pulmonory Venous Drainage into the Right Superior Vena Cava

This report describes a 2-month-old boy with diagnosis of total anomalous pulmonary venous obstruction and marked hypertension established by cross-sectioned echocardiography and catheterization with angiography. Successful surgical correction was performed with profound hypothermia and circulatory arrest. The risk factors and the high operative mortality associated with this type of anomaly are analyzed

Criança de 2 meses de idade, com diagnóstico de drenagem anômala total de veias pulmonares para veia cava superior direita com drenagem obstrativa e hipertensão pulmonar severa, estabelecido através de ecocardiografia e exame hemodinâmico. Realizada correção cirúrgica com sucesso através de hipotermia profunda e parada circulatória total. Os fotores de risco e a alta mortalidade cirúrgica associada a este tipo de anomalias são analisados