Background: We reviewed our experience using the Amplatzer septal occluder (AGA Medical, Golden Valley, MN) to close large, secundum-type atrial septal defects (ASDs) in children. Methods: Between June 2002 and December 2005, 52 patients (mean age 13.5 ¡Ó 8.7 years) underwent transcatheter closure of large (≥25 mm), secundum ASDs by using the Amplatzer septal occluder (ASO). Groups 1 and 2 included patients with a retroaortic rim of <5 mm (n = 39) or ≥5 mm(n = 13), respectively. All procedures were performed with general anesthesia and transesophageal echocardiographic guidance except for 10 patients, which involved local anesthesia and 3-dimensional transthoracic echocardiography. Successful device implantations, device sizes, approaches, complications, and closure rates were assessed. Results: Device implantation was successful in 50 patients (96.1%), with no difference between groups (95% vs 100%, P > 0.05). In 2 patients, implantation failed because of embolism or deployment failure. Devices were larger in group 1 than in group 2 (29.7 ¡Ó 3.9 vs 26.7 ¡Ó 3.0 mm, P =0.04). The right upper pulmonary-vein approach was more common in group 1 than in group 2 (P = .0001). Complications and closure rates did not differ between the groups (P > .05). Conclusions: Transcatheter closure of large, secundum ASD by using the ASO device was feasible, and complication rates were low. A deficient retroaortic rim did not preclude successful device implantation; however, a large device may be needed to close large ASD. Close long-term follow-up is necessary to determine the safety of transcatheter closure of large ASDs in children.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Made available in DSpace on 2014-06-12T18:28:36Z (GMT). No. of bitstreams: 2 arquivo7943_1.pdf: 588119 bytes, checksum: e8cc7c0faea91e5e61cd0397f2cb04cc (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2003 / A cardiomiopatia hipertrófica (CMH) é uma doença genética de caráter autossômico dominante em cerca de 50% dos casos e é a principal causa de morte súbita (MS) de origem cardíaca em pessoas abaixo dos 35 anos de idade, especialmente nos atletas. Nos últimos anos pesquisas têm sido realizadas visando a identificação de marcadores de risco para MS. O eletrocardiograma de alta resolução (ECGAR) é um método não invasivo que baseia-se no registro dos potenciais tardios (PT). Vários investigadores têm demonstrado que o registro destes potenciais em pacientes acometidos de infarto do miocárdio pode estar relacionado a maior probabilidade para o desenvolvimento de arritmias ventriculares e MS. O valor deste exame na estratificação de risco de outras cardiopatias não está bem estabelecido. O presente estudo tem por finalidade verificar a associação da presença dos PT com marcadores de malignidade em um grupo de pacientes (pct.) portadores de cardiomiopatia hipertrófica familiar (CMH). Entre março de 2001 e dezembro de 2002, 32 pct. foram selecionados através do ecocardiograma transtorácico, dos quais 22 foram incluídos e interrogados sobre MS familiar e ocorrência de síncope. O Holter de 24h foi realizado para a pesquisa de arritmias ventriculares complexas e o ECGAR para a pesquisa de PT. A idade variou de sete a 54 anos, com média 25,6 ± 14,7 anos, sendo 12 pct. do sexo feminino (55%). Hipertrofia septal assimétrica predominou em 16 pct. (73%). Do ponto de vista hemodinâmico apenas três apresentavam obstrução (14%). História familiar de CMH foi relatada por 14 pct. (64%); MS súbita familiar foi referida por 12 (55%) e síncope por cinco (23%). Arritmias ventriculares complexas foram detectadas em três pct. (14%) e PT em cinco (23%). Foi analisado, então, se a presença dos PT 8 estava associada a MS familiar, síncope e arritmias ventriculares complexas. O teste estatístico utilizado foi o exato de Fisher, sendo considerado significante p&#8804; 0,05. Os resultados do presente estudo não mostraram associação estatística de PT com MS familiar (p=1,00), síncope (p=0,54) nem com arritmias ventriculares complexas (p=1,00). Neste estudo, a presença dos PT não contribuiu na estratificação de risco dos portadores de CMH e não foram associados a outros marcadores prognósticos já estabelecidos

The combination of bone morphogenetic protein 7 (BMP7) and neurotrophins (e.g. brain-derived neurotrophic factor, BDNF) protects septal neurons during hypoglycemic stress. I investigated the signaling mechanisms underlying this synergistic protection. BMP7 (5 nM) increased phosphorylation and nuclear translocation of BMP-responsive Smads 1/5/8 within 30 min in cultures of rat embryonic septal neurons. BDNF (100 ng/ml) enhanced the BMP7-induced increase in phospho-Smad levels in both nucleus and cytoplasm; this effect was more pronounced after a hypoglycemic stress. BDNF increased both Akt and Erk phosphorylation, but pharmacological blockade of these kinase pathways (with wortmannin and U0126, respectively) did not reduce the Smad phosphorylation produced by the BMP7+BDNF combination. Inhibitors of casein kinase II (CK2) activity reduced the (BMP7 + BDNF)-induced Smad phosphorylation, and this trophic factor combination increased CK2 activity in hypoglycemic cultures. These findings suggest that BDNF can increase BMP-dependent Smad phosphorylation via a mechanism requiring CK2. Preliminary results indicate that a cytoplasmic component robustly inhibits CK2. Protection of septal cholinergic neurons during a hypoglycemic stress is inhibited by a CK2 inhibitor and by a Phosphatidylinositol 3-kinase inhibitor, indicating that increases in CK2 activity and in Smad phosphorylation are only part on the protective mechanisms.

To identify genes related to the heart developments, a total of 92 CHD families from Kaohsiung Veteran General Hospital, including 290 individuals with 95 affected, were genotyped in this study. Among these CHDs families, 54 were diagnosed as VSDs, accounted for 56.8% of all CHDs. Ten highly polymorphic markers, D22S420, D22S427, D22S1638, D22S941, D22S1648, D22S944, D22S1623, D22S264, D22S303 and D22S315, from centromere to the HSA22q telomere, covering HSA22q11 were genotyped by using a semi-quantitative fluorescent PCR. LOH at loci on 22q11 have been identified in 31 VSDs affected individuals. Candidate genes in HSA22q11 region was identified by bioinformatic methods firstly based on Ensembl (EMBL-EBI and the Sanger Institute), Genome browser (UCSU) and Map viewer (NCBI), and then FatiGO Data mining with Gene Ontology and Swiss-Prot annotations. In order to narrow down more specific cardiac development-related candidate genes within HSA22q11, TUBA8, DGCR2, DGCR14, CLTCL1, HIRA, TBX1 and GNB1L, from the centromere to telomere, were further subjected to dosage analyses by quantitative PCR. Results indicated the most frequent LOH region was localized on D22S1648. There are 48.3% and 38.7% of 31 VSDs patients with one copy deletion in TUBA8 and HIRA, respectively. Two VSDs patients were deleted in all seven candidate genes. Furthermore, there are one CAVC and one VSD patient were deleted in five consecutive genes, TUBA8, DGCR2, DGCR14, CLTCL1 and HIRA.

Objective. Congenital heart disease (CHDs) in Taiwan cause twice as many children die each year comparing with childhood cancers. Prevalent CHDs are ventricular septal defects (VSDs) which accounted for ~40% Taiwanese population averagely. Studies on heart development-related genes on the human genome will provide valuable information for early diagnosis/prevention in eugenics and the development of therapeutic strategies. Methods. A total of 239 CHD families from Kaohsiung Veteran General Hospital, including 713 individuals with 245 affected, participated in this study. Among these CHDs families, 83 were diagnosed as VSDs, accounted for 34.7% of all CHDs. We initiated using a semi-quantitative fluorescent PCR method applying ten highly polymorphic markers that located within 22q11, genotyping analysis for deletion or loss of heterozygosity. In those cases that are identified as chromosome 22q11-independent VSDs, cardiac development-related candidate genes TBX5, CSX and JAG1 analyses were performed by Single-Strand Conformation Polymorphisms (SSCPs) and Temporal Temperature Gradient Gel Electrophoresis (TTGE) analyses to identify whether any genomic mutation/deletion exists. Results. So far, there are twenty-five VSD affected individuals have been identified as loss of heterozygosity (LOH) at loci D22S264, D22S303, D22S420, D22S427,D22S941, D22S944, D22S1638 and D22S1648. Candidate gene approaches will therefore be carried out within chromosome 22q11 subregion in these individuals. Conclusions. The frequency of CHD necessitating intervention in patients referred for cardiovascular evaluation after diagnosis of a chromosome 22q11 deletion. Routine screening for CHDs, including VSD and other imaging studied to identify the any microdeletion(s) or LOH.

No description available.

Afhandling-Copenhagen. / Includes bibliographical references.

Afhandling-Copenhagen. / Includes bibliography.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.