RESUMO
With the shift from SNP arrays to high-throughput sequencing, most researchers studying diseases in consanguineous families do not rely on linkage analysis any longer, but simply search for deleterious variants which are homozygous in all patients. AutozygosityMapper allows the fast and convenient identification of disease mutations in patients from consanguineous pedigrees by focussing on homozygous segments shared by all patients. Users can upload multi-sample VCF files, including WGS data, without any pre-processing. Genome-wide runs of homozygosity and the underlying genotypes are presented in graphical interfaces. AutozygosityMapper extends the functions of its predecessor, HomozygosityMapper, to the search for autozygous regions, in which all patients share the same homozygous genotype. We provide export of VCF files containing only the variants found in homozygous regions, this usually reduces the number of variants by two orders of magnitude. These regions can also directly be analysed with our disease mutation identification tool MutationDistiller. The application comes with simple and intuitive graphical interfaces for data upload, analysis, and results. We kept the structure of HomozygosityMapper so that previous users will find it easy to switch. With AutozygosityMapper, we provide a fast web-based way to identify disease mutations in consanguineous families. AutozygosityMapper is freely available at https://www.genecascade.org/AutozygosityMapper/.
Assuntos
Consanguinidade , Análise Mutacional de DNA , Humanos , Genótipo , Homozigoto , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único , Análise Mutacional de DNA/métodosRESUMO
Traditionally, to map environmental features using remote sensing, practitioners will use training data to develop models on various satellite data sets using a number of classification approaches and use test data to select a single 'best performer' from which the final map is made. We use a combination of an omission/commission plot to evaluate various results and compile a probability map based on consistently strong performing models across a range of standard accuracy measures. We suggest that this easy-to-use approach can be applied in any study using remote sensing to map natural features for management action. We demonstrate this approach using optical remote sensing products of different spatial and spectral resolution to map the endemic and threatened flora of quartz patches in the Knersvlakte, South Africa. Quartz patches can be mapped using either SPOT 5 (used due to its relatively fine spatial resolution) or Landsat8 imagery (used because it is freely accessible and has higher spectral resolution). Of the variety of classification algorithms available, we tested maximum likelihood and support vector machine, and applied these to raw spectral data, the first three PCA summaries of the data, and the standard normalised difference vegetation index. We found that there is no 'one size fits all' solution to the choice of a 'best fit' model (i.e. combination of classification algorithm or data sets), which is in agreement with the literature that classifier performance will vary with data properties. We feel this lends support to our suggestion that rather than the identification of a 'single best' model and a map based on this result alone, a probability map based on the range of consistently top performing models provides a rigorous solution to environmental mapping.
Assuntos
Monitoramento Ambiental/métodos , Tecnologia de Sensoriamento Remoto/métodos , Algoritmos , Análise por Conglomerados , Conservação dos Recursos Naturais/métodos , Meio Ambiente , Geografia , Funções Verossimilhança , Probabilidade , Reprodutibilidade dos Testes , África do SulRESUMO
Premature constriction or closure of the ductus arteriosus can occur during fetal life. It is a rare phenomenon and has been described secondary to medication or structural lesions or as idiopathic constriction. Premature closure of the ductus arteriosus can lead to progressive right heart dysfunction with tricuspid regurgitation, congestive heart failure, fetal hydrops, and intrauterine death. This series describes diagnosis of fetal ductus arteriosus constriction of unknown etiology in 3 cases, prenatal management, and outcomes. Constriction of the ductus arteriosus can be diagnosed prenatally with careful interrogation of the ductal arch using pulsed Doppler sonography and complete fetal echocardiography. Close monitoring is mandatory to rule out development of right heart failure and to determine the intervention time.
Assuntos
Canal Arterial/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/patologia , Diagnóstico Diferencial , Canal Arterial/patologia , Ecocardiografia , Feminino , Doenças Fetais/patologia , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da GravidezRESUMO
OBJECTIVES: Transcatheter stent placement carries the risk of cardiovascular aneurysm or rupture. Covered stent implantation reduces these risks. The recently marketed Advanta V12 large-diameter-covered stent is pre-mounted and requires 9 (8)-11 Fr delivery systems. The aim was to report on the early results of the treatment of various cardiovascular obstructions by the implantation of a new polytetrafluoroethylene-covered stent (V12). METHODS: Graft stents on balloons with a diameter (12, 14, 16 millimetres) sufficient to anchor the stent in various obstructions (congenital aortic coarctation, n = 5; obstruction after ascending aorta repair, n = 2; pulmonary arteries, n = 5; inferior caval vein, n = 1; atretic superior caval vein, n = 1; pulmonary vein obstruction, n = 1; and right ventricular outflow tract, n = 1) were implanted using the smallest available delivery system. Secondary dilation with larger-diameter balloons was performed when the residual pressure was gradient, the stent-vessel wall relationship or stent re-coiling due to different reasons needed a re-intervention by pure ballooning or second stent placement. RESULTS: All 16 patients aged 5-46 years underwent V12 implantation. The variability of the treated lesions and the need for additional interventions were responsible for large ranges in fluoroscopy time between 7.3 to 48.2 minutes (median 17.3). Considering the additional procedures, the V12 stent achieved the desired result in all cases. There were no major complications. At short-term median follow-up of 2 months, all patients are alive and well with no evidence of stent failing. CONCLUSION: These initial results show that the covered Advanta V12 large-diameter stent is safe and effective in the immediate treatment of various cardiovascular obstructions. Long-term follow-up is required.
Assuntos
Coartação Aórtica/cirurgia , Pneumopatia Veno-Oclusiva/cirurgia , Stents , Obstrução do Fluxo Ventricular Externo/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Interrupted aortic arch (IAA) is a rare but serious anomaly. Prenatal diagnosis is challenging and published data are limited. The aim of the study was to review the data of fetuses and neonates diagnosed with IAA during a 16-year period at Children's Hospital Giessen. METHODS: Retrospective ascertainment of 8 fetuses and 20 neonates with a confirmed diagnosis of IAA from 1994 to 2010 by reviewing the hospital database of the cardiovascular program of the prenatal and pediatric cardiology clinics at the University Hospital Giessen. RESULTS: Eighteen cases with IAA type B and 10 cases with IAA type A were found. After 2005, prenatal diagnosis was achieved in 8 cases and postnatal imaging confirmed IAA in all 8 neonates. Twenty-nine percent of individuals had a chromosomal anomaly, with microdeletion 22q11.2 being the most common abnormality (n = 6, 21%). In 46% (13/28) other complex cardiac anomalies were present. Mortality after surgery was 18%. Long-term morbidity and mortality was due to neurological impairment in the presence of microdeletion 22q11.2 and the need of surgical or catheter re-intervention. CONCLUSION: Despite the difficulties and challenges in diagnosis, the prenatal detection rate of IAA is increasing. Associated complex cardiac and chromosomal abnormalities influence the outcome of patients with IAA and are important issues of parental counseling.
Assuntos
Doenças da Aorta/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Doenças da Aorta/diagnóstico , Doenças da Aorta/genética , Aberrações Cromossômicas , Ecocardiografia/métodos , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Humanos , Prognóstico , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodosRESUMO
INTRODUCTION: Ductal stenting for pulmonary blood supply in newborns with cyanotic congenital heart disease (CHD) might be a low risk and safe alternative to the surgical aorto-to-pulmonary artery (AP) shunt in dual-source lung perfusion. Ductal stenting in truly duct-dependent pulmonary circulation has not been evaluated. METHODS: Prospective interventional and clinical follow-up trial. Ductal stenting based on variable access sites, a 2-wire technique when crossing a tortuous ductus, and use of premounted coronary stents. Primary outcome measures were procedural success and complication rates presented as early and mid-term results. RESULTS: From 2003-2009, 58 duct-dependent newborns underwent ductal stenting; 27 of them were truly duct dependent, 20 had pulmonary atresia (PA)/ventricular septum defect or complex CHD, 4 had PA/intact ventricular septum, 2 had PA with Ebstein anomaly, and 1 had PA with tricuspid atresia. Ductal stenting was performed without procedure-related mortality; 3 of 27 required an acute surgical AP-shunt (stent migration in 1, acute duct obstruction in 2). During mid-term follow-up, 4 of 24 needed an AP-shunt and two others stent redilation. Three patients died prior to follow-up surgery (1 unexpectedly at home and 2 due to syndromatic disease). Fifteen patients received staged univentricular palliation, 8 had a biventricular repair, and 1 is awaiting follow-up operation. CONCLUSION: Ductal stenting is a feasible, safe, and effective palliation in newborns with truly duct-dependent pulmonary circulation irrespective of duct morphology. Vasucular access from various locations is important for technical success rate. Ductal stenting is a minimally invasive procedure to achieve adequate pulmonary artery growth for subsequent palliative or corrective surgery.
Assuntos
Cateterismo Cardíaco/métodos , Permeabilidade do Canal Arterial/terapia , Stents , Anomalia de Ebstein/terapia , Ecocardiografia , Humanos , Recém-Nascido , Estudos Prospectivos , Artéria Pulmonar/cirurgia , Atresia Pulmonar/terapia , Circulação Pulmonar , Retratamento , Resultado do TratamentoRESUMO
OBJECTIVE: Fetal cardiac intervention (FCI) has been performed at our center in selected fetuses with complex congenital heart disease since 2000. Most interventions are performed in fetuses with a ductus arteriosus (DA)-dependent circulation. Indomethacin promotes closure of the DA in newborns and in fetal life, a potentially life threatening complication in fetuses with ductus-dependent congenital heart disease. METHODS: We reviewed our experience with FCI with a focus on the frequency, features, and clinical course of ductal constriction. Fetuses undergoing FCI receive comprehensive pre- and postoperative cardiac and cerebral ultrasound evaluation, approximately 24 hours before and after the procedure, including imaging of DA flow and Doppler assessment of the umbilical artery and vein, ductus venosus, and, since 2004, the middle cerebral artery. RESULTS: Among 113 fetuses that underwent FCI, 24 of which were older than 28 0/7 weeks gestation, 2 were found to have DA constriction due to indomethacin therapy within 24 hours of intervention. Both of these were 30-week fetuses with hypoplastic left heart syndrome and restrictive or intact atrial septum. The DA was stenotic by spectral and color Doppler, and middle cerebral and umbilical artery pulsatility indexes were depressed. After discontinuation of indomethacin, the Doppler indices improved or normalized. CONCLUSION: Close echocardiographic monitoring of fetal Doppler flow velocities is very important after fetal intervention and indomethacin treatment, as the consequences of DA constriction in a fetus with hypoplastic left heart syndrome are potentially lethal. Sonographic evaluation should include measurement of cerebral and umbilical arterial flow velocities as well as color and spectral Doppler interrogation of the DA.
Assuntos
Canal Arterial/efeitos dos fármacos , Terapias Fetais , Síndrome do Coração Esquerdo Hipoplásico/terapia , Indometacina/efeitos adversos , Tocolíticos/efeitos adversos , Septo Interatrial/diagnóstico por imagem , Septo Interatrial/fisiopatologia , Cateterismo , Constrição Patológica/induzido quimicamente , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/epidemiologia , Canal Arterial/diagnóstico por imagem , Feminino , Humanos , Indometacina/uso terapêutico , Gravidez , Tocolíticos/uso terapêutico , UltrassonografiaRESUMO
OBJECTIVES: Our aims were to estimate the prevalence of increased nuchal translucency in fetuses with a normal karyotype that were subsequently diagnosed with congenital cardiac disease on fetal echocardiography, and to assess whether there is a link between increased nuchal translucency and specific congenital cardiac malformations. METHODS: We reviewed all patients referred to King's College Hospital and the Evelina Children's Hospital in London for fetal echocardiography between January 1998 and December 2007. We investigated the proportion of chromosomally normal fetuses with congenitally malformed hearts in which nuchal thickness was increased, both overall and with specific defects. RESULTS: We identified 2133 fetuses with congenital cardiac disease by prenatal echocardiography. Of those, 707 were excluded due to abnormal karyotype, and 690 were excluded due to unknown karyotype. The remaining 736 were eligible for inclusion. Among 481 fetuses with documented congenital cardiac disease and normal chromosomes, making up 23% of the overall cohort, 224 had increased nuchal thickness defined as equal or greater than 2.5 millimetres, this being 0.47 of the inclusive cohort, with 95% confidence intervals from 0.42 to 0.51. These proportions were significantly higher than the expected proportion of the normal population, which was 0.05 (p < 0.001). The only diagnosis for which the proportion of fetuses with nuchal translucency measurement equal or greater than 2.5 millimetres was higher than the others was atrioventricular septal defect, with 0.62 of this cohort having abnormal values, with 95% confidence intervals from 0.47 to 0.77 (p = 0.038). CONCLUSION: We found that nearly half of prenatally diagnosed fetuses with congenitally malformed hearts, when examined ultrasonically in the first or early-second trimester, had increased nuchal thickness. We recommend, therefore, referral of all fetuses with increased nuchal translucency for fetal echocardiography.
Assuntos
Doenças Fetais/diagnóstico por imagem , Cardiopatias/congênito , Cardiopatias/diagnóstico por imagem , Medição da Translucência Nucal , Cardiopatias/epidemiologia , Humanos , Cariotipagem , PrevalênciaAssuntos
Anormalidades Múltiplas/diagnóstico por imagem , Apêndice Atrial/anormalidades , Apêndice Atrial/diagnóstico por imagem , Ventrículos do Coração/anormalidades , Ventrículos do Coração/diagnóstico por imagem , Síndrome de Heterotaxia/diagnóstico por imagem , Ultrassonografia Pré-Natal , Feminino , Humanos , GravidezRESUMO
Isolated ventricular non-compaction (IVNC) is a rare congenital cardiomyopathy characterized by arrest in endomyocardial morphogenesis. Presenting features in children include systolic and diastolic ventricular dysfunction, cardiac arrhythmias, and thromboembolism. End-stage cardiac failure necessitating cardiac transplantation is described in adults. We report the unique case of a 5-year-old boy with IVNC and end-stage heart failure who underwent cardiac transplantation. Diagnostic echocardiographic features, gross cardiac morphology, and histopathologic findings are illustrated.
Assuntos
Cardiomiopatias/congênito , Cardiomiopatias/cirurgia , Cardiopatias Congênitas/cirurgia , Transplante de Coração , Pré-Escolar , Endocárdio/anormalidades , Endocárdio/embriologia , Coração/embriologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , MiocárdioRESUMO
Spontaneous healing with no or only very mild ichthyosis distinguishes the "self-healing collodion baby" from other congenital ichthyoses. In two self-healing collodion baby siblings with markedly diminished epidermal transglutaminase 1 activity we found the compound heterozygous transglutaminase 1 mutations G278R and D490G. Molecular modeling and biochemical assays of mutant proteins under elevated hydrostatic pressure suggest significantly reduced activity in G278R and a chelation of water molecules in D490G that locks the mutated enzyme in an inactive trans conformation in utero. After birth these water molecules are removed and the enzyme is predicted to isomerize back to a partially active cis form, explaining the dramatic improvement of this skin condition.
Assuntos
Ictiose/genética , Doenças do Recém-Nascido/genética , Mutação Puntual , Pele/enzimologia , Transglutaminases/genética , Pré-Escolar , Feminino , Humanos , Ictiose/patologia , Recém-Nascido , Doenças do Recém-Nascido/patologia , Modelos Químicos , Fenótipo , Estrutura Terciária de Proteína , Pele/patologia , Transglutaminases/química , Transglutaminases/metabolismoRESUMO
OBJECTIVE: The aim of this study was to examine the accuracy in predicting pathway location in children with Wolff-Parkinson-White syndrome for each of seven published algorithms. PATIENTS AND INTERVENTIONS: ECGs from 100 consecutive children with Wolff-Parkinson-White syndrome undergoing electrophysiological study were analysed by six investigators using seven published algorithms, six of which had been developed in adult patients. MAIN OUTCOME MEASURES: Accuracy and concordance of predictions were adjusted for the number of pathway locations. RESULTS: Accessory pathways were left-sided in 49, septal in 20 and right-sided in 31 children. Overall accuracy of prediction was 30-49% for the exact location and 61-68% including adjacent locations. Concordance between investigators varied between 41% and 86%. No algorithm was better at predicting septal pathways (accuracy 5-35%, improving to 40-78% including adjacent locations), but one was significantly worse. Predictive accuracy was 24-53% for the exact location of right-sided pathways (50-71% including adjacent locations) and 32-55% for the exact location of left-sided pathways (58-73% including adjacent locations). CONCLUSIONS: All algorithms were less accurate in our hands than in other authors' own assessment. None performed well in identifying midseptal or right anteroseptal accessory pathway locations.
Assuntos
Feixe Acessório Atrioventricular/diagnóstico , Algoritmos , Cateterismo Cardíaco/métodos , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Síndrome de Wolff-Parkinson-White/diagnóstico , Feixe Acessório Atrioventricular/complicações , Feixe Acessório Atrioventricular/fisiopatologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Síndrome de Wolff-Parkinson-White/etiologia , Síndrome de Wolff-Parkinson-White/fisiopatologiaRESUMO
Dilation of the ascending aorta (AA) is common in patients with a bicuspid aortic valve. The natural history of the aortic root and AA and the risk factors for dilation have not been characterized in patients with congenital aortic stenosis (AS) treated with balloon valvuloplasty during childhood. The present study was performed to determine the prevalence of aortic dilation in patients with congenital AS before and up to 20 years after balloon valvuloplasty performed during childhood. In patients who underwent balloon valvuloplasty for AS at age ≤ 18 years from 1984 to 2005, the aortic diameter measurements before intervention and at 5-year intervals afterward were recorded and the Z scores calculated. Among 156 patients (median age 1.5 years at valvuloplasty), the AA Z scores were significantly larger than normal before intervention (median Z score 1.5) and at all follow-up points (all p <0.001). Using mixed modeling, with time as a categorical variable (before intervention, 5-year window, 10-year window, and so forth), the mean AA Z score was greater at all postvalvuloplasty points than before the intervention, with mean Z score increases of 1.20 at 5 years and 2.11 at 20 years (p <0.001). Moderate or greater aortic regurgitation early after valvuloplasty was associated with greater AA Z scores than mild or less aortic regurgitation, with a progressive difference over time. More significant residual AS after valvuloplasty was associated with lower AA Z scores over time. In conclusion, AA dilation is common in children with congenital AS and continues to progress over many years after balloon valvuloplasty.
Assuntos
Aorta/fisiopatologia , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/terapia , Cateterismo/métodos , Adolescente , Distribuição por Idade , Estenose da Valva Aórtica/congênito , Estenose da Valva Aórtica/diagnóstico por imagem , Cateterismo/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Dilatação Patológica/epidemiologia , Dilatação Patológica/etiologia , Dilatação Patológica/fisiopatologia , Ecocardiografia Doppler/métodos , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Resultado do TratamentoRESUMO
OBJECTIVES: We report our analysis of conventional surgery and the cone procedure for Ebstein's malformation (EM) of the tricuspid valve at a single institution. Previous conventional surgery for EM, including use of bioprosthetic valves, has inherent problems especially in pediatrics. The newer cone procedure aims to construct a funnel-like valve out of native leaflets, obviating problems with artificial valves. METHODS: This is a retrospective cohort study to examine short-term outcomes of both surgeries for EM. RESULTS: Nineteen patients (our initial cohort) had the cone procedure, and 13 had conventional tricuspid valve repair or replacement. No early deaths occurred in either group. Three cone and one conventional repair patients required reoperation. Two of 19 patients in the cone and one of 13 in the conventional group died suddenly >30 days after operation, assumed secondary to dysrhythmias. At discharge, by two-dimensional echocardiography, the cone group had 85% reduction in tricuspid valve regurgitation (TVR), and the conventional group had 56% reduction, P= .004. This decrease of TVR persisted to a greater extent in the cone group. DISCUSSION: Short-term results for the cone procedure are similar to conventional surgery. The cone procedure uses autologous tissue; hypothetically, early favorable improvement in reduction of TVR should persist.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Anomalia de Ebstein/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Adolescente , Adulto , Boston , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Anuloplastia da Valva Cardíaca , Criança , Pré-Escolar , Anomalia de Ebstein/complicações , Anomalia de Ebstein/diagnóstico por imagem , Anomalia de Ebstein/mortalidade , Implante de Prótese de Valva Cardíaca , Humanos , Lactente , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/anormalidades , Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/mortalidade , Ultrassonografia , Adulto JovemRESUMO
Patients with truncus arteriosus often require pulmonary arterial (PA) and/or right ventricular outflow tract (RVOT) reintervention within the first year of repair. However, little is known about the risk factors for early reintervention on the PAs or RVOT in this population. The objective of the present retrospective cohort study was to determine the risk factors for early PA or RVOT reintervention after repair of truncus arteriosus in neonates and young infants. Of 156 patients ascertained (median age at repair 14 days; 143 early survivors), reinterventions on the RVOT and/or PAs were performed in 109. The first reintervention was catheter therapy in 73 patients (conduit dilation/stenting in 29, PA dilation/stenting in 31, both in 13) and conduit reoperation in 36 patients. The freedom from any RVOT or PA reintervention was 68 ± 4% at 1 year and 48 ± 5% at 2 years. The factors associated with early reintervention (shorter 1-year freedom from reintervention) on univariate analysis were repair quartile, neonatal repair, smaller weight at repair, and smaller implanted conduit size. On multivariable analysis, only smaller conduit size remained significant (multivariable hazard ratio 0.66/mm, range 0.53 to 0.83; p <0.001). The freedom from conduit reoperation was 92 ± 3% at 1 year and 76 ± 4% at 2 years. Overall, the left and right PA sizes were modestly larger than normal by the 1-sample t test, and PA Z scores and the PA area index were not associated with the risk of reintervention. Early reintervention for PA and/or RVOT conduit obstruction is common after neonatal and early infant repair of truncus arteriosus using homograft conduits. A smaller conduit size was associated with early RVOT/PA reintervention. The branch PA size was normal before surgery, suggesting that the PA stenosis in these patients resulted from factors other than intrinsic stenosis or hypoplasia.
Assuntos
Anormalidades Múltiplas/cirurgia , Prótese Vascular , Artéria Pulmonar/cirurgia , Reoperação/estatística & dados numéricos , Persistência do Tronco Arterial/cirurgia , Obstrução do Fluxo Ventricular Externo/cirurgia , Ecocardiografia , Seguimentos , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Persistência do Tronco Arterial/diagnóstico por imagem , Persistência do Tronco Arterial/fisiopatologia , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/fisiopatologiaRESUMO
Our study addressed the question of whether surface properties of modern standard gel prostheses may have a measurable impact on the fibrogenic properties of cultured human dermal fibroblasts. Fibroblasts were isolated from breast implants by using the explant culture technique and incubated either on smooth or on textured silicone elastomere surfaces. Fibroblast growth was observed 4 weeks following incubation. Expression of transforming growth factor (TGF)-ß1 was measured after cell culture. Incubated fibroblasts on textured surfaces showed a fivefold lower growth rate during all experiments. TGF-ß1 expression was lowered in smooth surface fibroblasts compared with textured surface cultures. Our results show that smooth and textured silicone surfaces of modified gel breast implants have a different impact on the fibroproliferative properties of dermal fibroblasts. These preliminary results seem promising and we aim to further perform qualitative and quantitative analyses of the inflammatory processes in the environment of the implant and their link to the TGF-ß pathway.
Assuntos
Implantes de Mama , Fibroblastos/metabolismo , Silicones , Células Cultivadas , Fibrose/metabolismo , Géis , Humanos , Microscopia Eletrônica de Varredura , RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/citologia , Propriedades de Superfície , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVES: The objective of this article is to review anatomic, physiologic, and clinical features of fetuses and neonates with severe mitral regurgitation (MR) in conjunction with aortic stenosis (AS) and left ventricular (LV) and left atrial (LA) dilation and to present preliminary results of pre-natal intervention for this condition. BACKGROUND: Severe fetal valvar AS with an abnormal mitral valve (MV) and MR can lead to left heart dilation, with consequent compression of the right ventricle (RV); hydrops and low cardiac output are often associated. METHODS: This is a retrospective review of fetuses diagnosed with AS, severe MR, and LA dilation (2002 to 2009) and neonates with the same combination of abnormalities (1988 to 2009). RESULTS: Fourteen fetuses and 7 neonates were investigated. Eleven fetuses had severe hydrops; all had polyhydramnios and a structurally abnormal MV, abnormal MV inflow pattern, restrictive/intact atrial septum, retrograde flow in the transverse aortic arch, and compression of the right heart. The mean indexed RV output was 326 ± 160 ml/kg/min, lower than the normal average fetal combined ventricular output of 550 ± 150 ml/kg/min. Ten fetuses underwent pre-natal cardiac intervention: aortic valvuloplasty (n = 8) and/or atrial septal dilation/stenting (n = 5). Seven of these, and 11 overall, were live born. Nine patients died (median age 6 days), and 2 patients are currently alive. All 7 patients diagnosed in the neonatal period died (median age 1 day). CONCLUSIONS: Aortic stenosis associated with significant MR in the fetus can cause severe LA and LV enlargement, leading to low cardiac output and hydrops. Despite the potential advantages of early pre-natal diagnosis and both fetal and neonatal interventions, this rare complex of anomalies carries a poor prognosis.
Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Hidropisia Fetal/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/terapia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hidropisia Fetal/terapia , Recém-Nascido , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/terapia , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Systematic evaluation of left ventricular (LV) endocardial fibroelastosis (EFE) in the fetus has not been reported. The role of EFE in the pre- and postnatal evolution of hypoplastic left heart disease, and the implications of EFE for outcomes after prenatal intervention for fetal aortic stenosis with evolving hypoplastic left heart syndrome have also not been determined. A 4-point grading system (0-3) was devised for the assessment of fetal LV echogenicity, which was presumed to be due to EFE. Two reviewers independently graded EFE on the preintervention echocardiograms of fetuses treated with in utero aortic valvuloplasty for evolving hypoplastic left heart syndrome from 2000 to 2008. Intra- and interobserver reproducibility was determined for the EFE grade and characterization of related echocardiographic features. The relations among EFE severity, other left heart anatomic and physiologic variables, and postintervention outcomes were analyzed. The assessment and grading of EFE was possible for both observers in all 74 fetuses studied. By consensus, the EFE severity was grade 1 in 31 patients, grade 2 in 32, and grade 3 in 11. Fetuses with mild (grade 1) EFE had significantly greater maximum instantaneous aortic stenosis gradients (e.g., higher LV pressures) and less globular LV geometry than patients with grade 2 or 3 EFE on preintervention echocardiogram. The severity of EFE was not associated with the size of the aortic valve or LV. From preintervention to late gestation, the time-indexed change in LV end-diastolic volume was significantly greater in fetuses with grade 1 EFE than those with more severe EFE. Incorporation of EFE severity into our previously published threshold score improved the sensitivity and positive predictive value for the postnatal biventricular outcomes. In conclusion, echocardiographic grading of EFE is possible, with reasonable intra- and interobserver reliability in midgestation fetuses with evolving hypoplastic left heart syndrome. EFE severity corresponded to some indexes of left heart size, geometry, and function and with the probability of a biventricular outcome postnatally. Additional experience and external validation of the EFE grading scoring system are necessary.
Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Fibroelastose Endocárdica/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Estenose da Valva Aórtica/embriologia , Estenose da Valva Aórtica/terapia , Cateterismo Cardíaco/métodos , Cateterismo/métodos , Diagnóstico Diferencial , Fibroelastose Endocárdica/embriologia , Feminino , Doenças Fetais/terapia , Seguimentos , Idade Gestacional , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico por imagem , Síndrome do Coração Esquerdo Hipoplásico/embriologia , Síndrome do Coração Esquerdo Hipoplásico/terapia , Gravidez , Curva ROC , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To determine the frequency of prenatal detection among liveborn patients with an interrupted aortic arch (IAA), the accuracy of prenatal diagnosis, and the anatomic features associated with IAA in the fetus. The prenatal diagnosis of an IAA is challenging. The data on the features and outcomes of fetal IAA are limited. This was a retrospective review of the fetuses and neonates diagnosed with IAA at the Children's Hospital Boston. From 1988 to 2009, 26 fetuses were diagnosed with an IAA. Of these, 21 were live born, and 5 pregnancies were terminated. Of these 21 patients, 18 were confirmed to have an IAA after birth and 3 had severe aortic coarctation. Of the 56 patients diagnosed with an IAA as neonates, 3 had a prenatal echocardiogram that did not include the correct diagnosis. Among the liveborn patients with a postnatally confirmed IAA, 24% were diagnosed prenatally, which increased from 11% during the first 7-year period to 43% more recently. Also, 15% of the prenatally diagnosed patients with IAA had a family history of structural or genetic anomalies. In fetuses with an IAA, echocardiographic Z-scores for the aortic valve and ascending aorta were significantly lower than in normal fetuses, but the left ventricular dimensions were normal. Aortopulmonary diameter ratios were abnormally low. In conclusion, although the identification of IAA on a prenatal echocardiogram can be challenging, a number of anatomic features can facilitate the diagnosis. In particular, a low aortopulmonary diameter ratio in the absence of a ventricular size discrepancy should prompt consideration of this diagnosis. Despite the diagnostic challenges, the frequency of prenatal diagnosis of the IAA is increasing.