Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome

The voltage-dependent K+ channel responsible for the slowly activating delayed K+ current IKs is composed of pore-forming KCNQ1 and regulatory KCNE1 subunits, which are mutated in familial forms of cardiac long QT syndrome. Because KCNQ1 and KCNE1 genes also are expressed in epithelial tissues, such as the kidneys and the intestine, we have investigated the adaptation of KCNE1-deficient mice to different K+ and Na+ intakes. On a normal K+ diet, homozygous kcne1−/− mice exhibit signs of chronic volume depletion associated with fecal Na+ and K+ wasting and have lower plasma K+ concentration and higher levels of aldosterone than wild-type mice. Although plasma aldosterone can be suppressed by low K+ diets or stimulated by low Na+ diets, a high K+ diet provokes a tremendous increase of plasma aldosterone levels in kcne1−/− mice as compared with wild-type mice (7.1-fold vs. 1.8-fold) despite lower plasma K+ in kcne1−/− mice. This exacerbated aldosterone production in kcne1−/− mice is accompanied by an abnormally high plasma renin concentration, which could partly explain the hyperaldosteronism. In addition, we found that KCNE1 and KCNQ1 mRNAs are expressed in the zona glomerulosa of adrenal glands where IKs may directly participate in the control of aldosterone production by plasma K+. These results, which show that KCNE1 and IKs are involved in K+ homeostasis, might have important implications for patients with IKs-related long QT syndrome, because hypokalemia is a well known risk factor for the occurrence of torsades de pointes ventricular arrhythmia.

Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to epithelial cells of the developing embryonic lung of transgenic mice disrupting normal pulmonary morphogenesis during the pseudoglandular stage of development. By embryonic day 15.5(E15.5), lungs of transgenic surfactant protein C (SP-C)-KGF mice resembled those of humans with pulmonary cystadenoma. Lungs were cystic, filling the thoracic cavity, and were composed of numerous dilated saccules lined with glycogen-containing columnar epithelial cells. The normal distribution of SP-C proprotein in the distal regions of respiratory tubules was disrupted. Columnar epithelial cells lining the papillary structures stained variably and weakly for this distal respiratory cell marker. Mesenchymal components were preserved in the transgenic mouse lungs, yet the architectural relationship of the epithelium to the mesenchyme was altered. SP-C-KGF transgenic mice failed to survive gestation to term, dying before E17.5. Culturing mouse fetal lung explants in the presence of recombinant human KGF also disrupted branching morphogenesis and resulted in similar cystic malformation of the lung. Thus, it appears that precise temporal and spatial expression of KGF is likely to play a crucial role in the control of branching morphogenesis during fetal lung development.

Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21.

Cerebral cavernous malformation is a common disease of the brain vasculature of unknown cause characterized by dilated thin-walled sinusoidal vessels (caverns); these lesions cause varying clinical presentations which include headache, seizure, and hemorrhagic stroke. This disorder is frequently familial, with autosomal dominant inheritance. Using a general linkage approach in two extended cavernous malformation kindreds, we have identified linkage of this trait to chromosome 7q11.2-q21. Multipoint linkage analysis yields a peak logarithm of odds (lod) score of 6.88 with zero recombination with locus D7S669 and localizes the gene to a 7-cM region in the interval between loci ELN and D7S802.

Marcadores prognósticos em recém-nascidos portadores de mielomeningocele

Introdução: Pacientes com mielomeningocele apresentam elevada mortalidade e desenvolvem déficits neurológicos que ocorrem, primariamente, pelo desenvolvimento anormal da medula e de raízes nervosas e, secundariamente, por complicações adquiridas no período pós-natal. O desafio no cuidado desses pacientes é o reconhecimento precoce dos recém-nascidos de risco para evolução desfavorável a fim de estabelecer estratégias terapêuticas individualizadas. Objetivo: Este estudo tem como objetivo identificar marcadores prognósticos de curto prazo para recém-nascidos com mielomeningocele. As características anatômicas do defeito medular e da sua correção neurocirúrgica foram analisadas para esta finalidade. Métodos: Foi realizado um estudo de coorte retrospectiva com 70 pacientes com mielomeningocele em topografia torácica, lombar ou sacral nascidos entre janeiro de 2007 a dezembro de 2013 no Centro Neonatal do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Pacientes com infecção congênita, anomalias cromossômicas e outras malformações maiores não relacionadas à mielomeningocele foram excluídos da análise. As características anatômicas da mielomeningocele e a sua correção neurocirúrgica foram analisadas quanto aos seguintes desfechos: reanimação neonatal, tempo de internação, necessidade de derivação ventricular, deiscência da ferida operatória, infecção da ferida operatória, infecção do sistema nervoso central e sepse. Para a análise bivariada dos desfechos qualitativos com os fatores de interesse foram empregados testes do qui-quadrado e exato de Fisher. Para a análise do desfecho quantitativo, tempo de internação hospitalar, foram empregados testes de Mann-Whitney. Foram estimados os riscos relativos e os respectivos intervalos com 95% de confiança. Foram desenvolvidos modelos de regressão linear múltipla para os desfechos quantitativos e regressão de Poisson para os desfechos qualitativos. Resultados: Durante o período do estudo 12.559 recém-nascidos foram admitidos no Centro Neonatal do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Oitenta pacientes foram diagnosticados com mielomeningocele, com incidência de 6,4 casos para cada 1.000 nascidos vivos. Dez pacientes foram excluídos da análise devido à mielomeningocele em topografia cervical (n = 1), à cardiopatia congênita (n = 4), à trissomia do cromossomo 13 (n = 1), à onfalocele (n = 3) e à encefalocele (n = 1). Ocorreram três óbitos (4,28%). Mielomeningocele extensa foi associada a infecção do sistema nervoso central, a complicação de ferida operatória e a maior tempo de internação hospitalar. Os pacientes com mielomeningocele em topografia torácica apresentaram tempo de internação, em média, 39 dias maior que aqueles com defeito em topografia lombar ou sacral. Houve maior necessidade de reanimação em sala de parto entre os pacientes com macrocrania ao nascer. A correção cirúrgica realizada após 48 horas de vida aumentou em 5,7 vezes o risco de infecção do sistema nervoso central. Entre os pacientes operados nas primeiras 48 horas de vida não foi observado benefício adicional na correção cirúrgica realizada em \"tempo zero\". A ausência de hidrocefalia antenatal foi um marcador de bom prognóstico. Nestes pacientes, a combinação dos desfechos necessidade de derivação ventricular, complicações infecciosas, complicações de ferida operatória e reanimação em sala de parto foi 70% menos frequente. Conclusão: Este estudo permitiu identificar marcadores prognósticos de curto prazo em recém-nascidos com mielomeningocele. Os defeitos medulares extensos e a correção cirúrgica após 48 horas de vida influenciaram negativamente na evolução de curto prazo. As lesões extensas foram associadas a maiores taxas de infecção do sistema nervoso central, a complicações de ferida operatória e a internação hospitalar prolongada. A correção cirúrgica realizada após 48 horas de vida aumentou significativamente a ocorrência de infecção do sistema nervoso central. Ausência de hidrocefalia antenatal foi associada a menor número de complicações nos primeiros dias de vida

Aid decision algorithms to estimate the risk in congenital heart surgery

Background and objective: In this paper, we have tested the suitability of using different artificial intelligence-based algorithms for decision support when classifying the risk of congenital heart surgery. In this sense, classification of those surgical risks provides enormous benefits as the a priori estimation of surgical outcomes depending on either the type of disease or the type of repair, and other elements that influence the final result. This preventive estimation may help to avoid future complications, or even death. Methods: We have evaluated four machine learning algorithms to achieve our objective: multilayer perceptron, self-organizing map, radial basis function networks and decision trees. The architectures implemented have the aim of classifying among three types of surgical risk: low complexity, medium complexity and high complexity. Results: Accuracy outcomes achieved range between 80% and 99%, being the multilayer perceptron method the one that offered a higher hit ratio. Conclusions: According to the results, it is feasible to develop a clinical decision support system using the evaluated algorithms. Such system would help cardiology specialists, paediatricians and surgeons to forecast the level of risk related to a congenital heart disease surgery.

Complex Congenital Heart Disease: The Influence of Prenatal Diagnosis

INTRODUCTION: Complex congenital heart disease is a group of severe conditions. Prenatal diagnosis has implications on morbidity and mortality for most severe conditions. The purpose of this work was to evaluate the influence of prenatal diagnosis and distance of residence and birth place to a reference center, on immediate morbidity and early mortality of complex congenital heart disease. MATERIAL AND METHODS: Retrospective study of complex congenital heart disease patients of our Hospital, born between 2007 and 2012. RESULTS: There were 126 patients born with complex congenital heart disease. In 95%, pregnancy was followed since the first trimester, with prenatal diagnosis in 42%. There was a statistically significant relation between birth place and prenatal diagnosis. Transposition of great arteries was the most frequent complex congenital heart disease (45.2%), followed by pulmonary atresia with ventricular septal defect (17.5%) and hypoplastic left ventricle (9.5%). Eighty-two patients (65.1%) had prostaglandin infusion and 38 (30.2%)were ventilated before an intervention. Surgery took place in the neonatal period in 73%. Actuarial survival rate at 30 days, 12 and 24 months was 85%, 80% and 75%, respectively. There was no statistically significant relation between prenatal diagnosis and mortality. DISCUSSION: Most patients with complex congenital heart disease did not have prenatal diagnosis. All cases with prenatal diagnosis were born in a tertiary center. Prenatal diagnosis did not influence significantly neonatal mortality, as already described in other studies with heterogeneous complex heart disease. CONCLUSION: prenatal diagnosis of complex congenital heart disease allowed an adequate referral. Most patients with complex congenital heart disease were not diagnosed prenatally. This data should be considered when planning prenatal diagnosis of congenital heart disease.

The physical, psycho-social, and vocational progress in congenital paraplegia due to spina bifida cystica

Bibliography: leaves 122-127.

The early diagnosis of congenital abnormalities /

Includes index.

A practical treatise on the ætiology, pathology, and treatment of the congenital malformations of the rectum and anus.

Spine title: Congenital malformations of the rectum & anus.