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At least 217 records · Page 12Linked to original sources
PubMed1982

Conduction defects, ventricular arrhythmias, and late death after surgical closure of ventricular septal defect.

One hundred and eighty-seven patients who had surgical closure of a ventricular septal defect between 1958 and 1975 were followed for up to 21 years. there were 17 late sudden deaths of which eight occurred in completely fit patients while nine were already under medical care. In an attempt to elucidate possible risk factors and reoperative and serial postoperative electrocardiograms of all patients were studied. Fifty-one unselected healthy follow-up patients agreed to 24 hour ambulatory monitoring. Progressive exercise testing (Bruce protocol) was carried out on 31 of them and an additional seven patients. There was a significant correlation between recorded ventricular arrhythmias and conduction defects, particularly progressive conduction defects. Transient complete heart block carried a bad prognosis and grade 3-4b ventricular arrhythmias were a major risk factor and recorded in 10 of the 17 patients who died. Long-term postoperative electrocardiographic follow-up is recommended and 24 hour ambulatory monitoring and exercise testing complement the findings of the resting electrocardiogram. The long-term treatment of survivors found to have ventricular arrhythmias must be considered.

Adolescent↗
PubMed2006

Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects.

BACKGROUND: Congenital cardiovascular diseases are the most common form of birth defects in humans. A substantial portion of these defects has been associated with inappropriate induction, migration, differentiation and patterning of pluripotent cardiac neural crest stem cells. While TGF-beta-superfamily signaling has been strongly implicated in neural crest cell development, the detailed molecular signaling mechanisms in vivo are still poorly understood. RESULTS: We deleted the TGF-beta type I receptor Alk5 specifically in the mouse neural crest cell lineage. Failure in signaling via ALK5 leads to severe cardiovascular and pharyngeal defects, including inappropriate remodeling of pharyngeal arch arteries, abnormal aortic sac development, failure in pharyngeal organ migration and persistent truncus arteriosus. While ALK5 is not required for neural crest cell migration, our results demonstrate that it plays an important role in the survival of post-migratory cardiac neural crest cells. CONCLUSION: Our results demonstrate that ALK5-mediated signaling in neural crest cells plays an essential cell-autonomous role in the pharyngeal and cardiac outflow tract development.

Activin Receptors, Type I↗
PubMed2004

An N-terminal WT1 mutation (P181S) in an XY patient with ambiguous genitalia, normal testosterone production, absence of kidney disease and associated heart defect: enlarging the phenotypic spectrum of WT1 defects.

OBJECTIVE: This study reports the clinical and molecular data of an XY patient with a very unusual phenotype due to a Wilms' tumor-suppressor (WT1) gene mutation. The genotype-phenotype relationship of different WT1 mutations is then discussed. PATIENT: The patient presented at birth with micropenis, severe hypospadias and cryptorchidism. Normal androgen production and an absence of clinical response to a testosterone treatment trial suggested partial androgen resistance. Eventually, female sex of rearing was chosen. At the beginning of puberty, normal male androgen production occurred, and subsequent gonadectomy did not show gonadal dysgenesis. It is notable that the patient, now 20 years of age, has not developed kidney disease. In addition to the genital malformation, the patient displayed an associated congenital heart defect, consisting of a coarctation of the aorta and a patent ductus arteriosis (PDA). RESULTS: No mutations were detected in the androgen receptor or 5alpha-reductase genes. Direct sequencing of the WT1 gene identified a heterozygous proline to serine substitution at position 181 (P181S). The same heterozygous mutation was found in the mother. Interestingly, the mother shows no signs of kidney disease at her present age of 49. CONCLUSION: This is the first germline missense mutation in the N-terminal part of WT1 identified in a patient with the very particular phenotype of ambiguous genitalia with absence of gonadal dysgenesis and kidney disease. The possible molecular mechanisms leading to the patient's phenotype are considered. The high frequency of PDA in newborns and the absence of heart abnormalities in XX females carrying the P181S mutation, however, suggest that the heart defect was most likely a coincidental association. This case enlarges the clinical spectrum of WT1 defects and may provide new insights into the complex functions of WT1 in genital and kidney development.

Aortic Coarctation↗
PubMed1992

[A case of incomplete endocardial cushion defect with mirror-image dextrocardia, IVC defect and azygos connection].

A case of incomplete endocardial cushion defect associated with mirror-image dextrocardia, IVC defect and azygos connection is reported. Intracardiac defect was corrected under moderate hypothermia with cardiopulmonary bypass. Three venous drainage cannulas were necessary to be indwelled into SVC, hepatic vein and right common iliac vein to maintain adequate venous drainage for extra-corporeal circulation. Thus, anomaly of venous system, which is commonly associated with mirror-image dextrocardia, must be recognized correctly and prepared before intracardiac correction.

Azygos Vein↗
PubMed1989

[Surgical treatment of residual defects following closure of secundum atrial septal defect].

Among 1485 patients with secundum atrial septal defect repaired from May, 1958 through May, 1986, 6 and 1 additional patient were readmitted to our hospital with symptomatic recurrence. In all but 1, their systolic murmur persisted. Cardiothoracic ratio and pulmonary plethora remained unaltered. A residual defect in all of the 7 patients was confirmed by right heart catheterization. They were reoperated upon under cardiopulmonary bypass. There was no early mortality, nor late death. The major postoperative complications include: hemothorax in 2 cases; temporary atrial fibrillation in 1. This article analysis the common causes of residual defect and discussed methods of diagnosis, treatment and prognosis.

Adolescent↗
PubMed1979

[Evolution of lesser circulation hypertension in patients with congenital heart defects based on the example of an interventricular septal defect].

The results of direct pressure measurement in pulmonary circulation in 452 patients with ventricular septal defect (216 males and 236 females), whose age ranged from 12 months to 37 years, were analysed. The findings of diagnostic catheterization of the heart in 150 practically healthy persons 12 months to 40 years of age were used to elaborate the normal values of pressure in pulmonary circulation. The results of pressure measurement in pulmonary circulation repeated at intervals of 1 to 6 years in 46 patients with ventricular septal defect, 18 months to 23 years of age, were analysed. Reverse evolution of pressure in pulmonary circulation after surgical rehabilitation was followed up in 85 patients in 1, 2, 3, 5, and 7 years after the operation. At the age of 12 months to 7 years, systolic pressure in the right ventricle and pulmonary artery comes down to a possible minimum due to expenditure of the adaptational reserve. In large ventricular septal defects, however, the organism proves incapable of reducing the pressure in the early and first periods of childhood as a rule, and so the pressure increases throughout life.

Adolescent↗
PubMed1981

[Interventricular defect with discrete aortic stenosis below the defect].

"Discrete" (fixed) subaortic stenosis associated with ventricular septal defect (VSD) is a rare but important anomaly. Two types of left ventricular outflow tract obstruction should be distinguished on the basis of its relation with the VSD, depending on whether the stenosis is above or below the defect. The four cases presented here are all in the latter category. Usually the patients belonging in the former category are associated with severe anomalies of the aortic arch. The diagnosis was made by clinical examination and by means of non invasive techniques, ecg, chest x-rays and ecocardiograms in all but one patient (the case "3"), in whom a subpulmonary stenosis (SPS) was associated. The final diagnosis was established by catheterization, which demonstrated the pressure gradient on the withdrawal curve from the apical part of the left ventricle to the aorta, and by contrastography. Three of four patients underwent total correction and are in good condition from 6 to 18 months after surgery, one of these cases had also SPS. In the remaining case, we thought the operation was not indicated on the basis of small size of VSD, of mild pressure gradient, and mild aortic valvular insufficiency (case "4"). The surgical approach to resect the "fixed" obstruction and to closure the VSD was carried out through a right atriotomy in two patients, and through a right ventriculotomy in the patient with SPS. The trans-aortic approach has to be discarded because it affords limited exposure of both defects and could increase the risk of damage of conducting tissue. A careful evaluation of aortic and left ventricular pressure, in association with angled angiography is highly recommended in the study of VSD.

Aortic Stenosis, Subvalvular↗
PubMed1981

Birth defects related to bendectin use in pregnancy. I. Oral clefts and cardiac defects.

The risk of birth defects previously associated with Bendectin use in early pregnancy were evaluated in a case-control study of malformed infants whose mothers were interviewed in three regional centers; 98 infants with isolated cleft palate (CP), 221 with cleft lip with or without cleft palate (CL +/- CP), and 122 with selected heart defects (HD) were compared with 970 other malformed infants who served as controls. Relative risk estimates (with their 95% confidence limits) for first-trimester exposure to Bendectin were as follows: CP, 0.9 (0.5 to 1.5); CL +/- CP, 0.6 (0.4 to 0.8); and HD, 1.0 (0.6 to 1.6). Allowance for a large number of potentially confounding factors did not materially influence the risk estimates. These findings suggest that early in utero exposure to Bendectin does not appreciably increase the risk of oral clefts or selected cardiac defects.

Antiemetics↗
PubMed1997

[Catheter treatment of congenital heart defects. Arterial septal defects and open ductus arteriosus].

The results of new methods for catheter treatment of congenital heart defects are presented. Between 1989 and 1996 closure of a patent ductus arteriosus was performed in 66 instances on 63 patients, eight of which were with coils. Three patients were treated twice, one with an additional umbrella, two with coils. The overall complete closure rate for umbrellas was 75%, after two ducts, which were initially totally occluded, recanalized. In six more patients the procedure was either aborted or indication was not present. All six ducts treated with coils as the first procedure were completely closed. One of two patients who had residual leak after previous umbrella treatment achieved complete closure after subsequent coil implantation. Closure of atrial septal defects in the oval fossa was performed using the Amplatzer septal occluder in seven children. Complete closure was achieved in all of them. There have been no complications, in particular there have been no cases of embolization in any of the groups. The results seem to indicate that coil occlusion of a persistently patent duct may be at least as good as the umbrella in terms of complete closure. So far both methods have been safe, but experience with coils is limited. The closure of atrial septal defects shows encouraging results. We will continue to offer this treatment as an alternative to open heart surgery in carefully selected patients.

Adolescent↗
PubMed1986

Doppler evaluation of atrial septal defect, ventricular septal defect, and complex malformations.

The Doppler approaches, accuracy, pitfalls and quantitation of atrial and ventricular shunts are reviewed. For both levels of shunting, Doppler demonstration of flow through the septum confirms the diagnosis and directional flow information may provide physiologic information. Shunt sizes may be measured directly by Doppler, and should be reflected by chamber dimensions and volumes. The flow disturbances present in complex malformations such as Ebstein's malformation, transposition of the great arteries with ventricular septal defect, atrial shunting before and after balloon atrial septostomy, total anomalous pulmonary venous return, closely related high velocity flows and coarctation are described. A sequential approach to each anomaly allows one to evaluate each, even if multiple defects are combined in a given patient.

Aortic Coarctation↗
PubMed1989

Comparison of cardiovascular adjustments to exercise in adolescents 8 to 15 years of age after correction of tetralogy of fallot, ventricular septal defect or atrial septal defect.

Surgical correction of tetralogy of Fallot (TF) has generally been associated with a reduced maximal exercise tolerance, possibly related to the ventriculotomy inherent to the intracardiac repair procedure. This study documents the exercise hemodynamics of a group of patients operated on for TF who showed similar clinical and functional characteristics, and compares these responses to those of age-matched patients operated on for an isolated ventricular septal defect (VSD) or atrial septal defect (ASD) in an attempt to better understand the role of the ventriculotomy in the exercise limitation. Thirty patients, ages 12 to 19 years, operated on before 5 years of age for complete repair of TF (n = 13), VSD (n = 7) or ASD (n = 10) and 10 age-matched control subjects underwent a progressive maximal cycling test to determine the maximal oxygen uptake (VO2 max), and completed submaximal cycling at intensities of 33 and 66% VO2 max, respectively, to determine the cardiac output (CO2-rebreathing). No significant differences in VO2 max were observed (TF = 37.6 +/- 10; VDS = 34.0 +/- 9.2; ASD = 36.5 +/- 7; controls = 41.3 +/- 6.0 ml/kg/min). The maximal heart rate, however, remained lower in all patient groups in comparison with control subjects (p less than or equal to 0.05) (TF = 178 +/- 14; VSD = 172 +/- 17; ASD = 179 +/- 16; controls = 191 +/- 12 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2001

[A case of central nervous system anomalies (agenesis of corpus callosum, colpocephaly, hydrocephalus, congenital dermal sinus) associated with congenital heart disease(double-outlet right ventricle, complete endocardial cushion defect, atrial septal defect, pulmonary arterial stenosis, patent ductus arteriosus)].

A case of central nervous system anomalies(agenesis of corpus callosum, colpocephaly, hydrocephalus, congenital dermal sinus) associated with congenital heart disease(double-outlet right ventricle, complete endocardial cushion defect, atrial septal defect, pulmonary arterial stenosis, patent ductus arteriosus) is reported. Female patient had been already diagnosed as hydrocephalus during pregnancy and ventricular drainage was performed soon after the delivery. Prostaglandin E 1 was also applied for heart disease, but saturation of O2 decreased to 80% on arterial blood gas analysis. Blalock-Taussig operation and ligation of ductus arteriosus was done 41 days after the delivery and ventricle-peritoneal shunt was also made for the progressive hydrocephalus on the same day. Chromosome analysis showed no abnormality. The genesis of this complicated brain and heart anomaly is discussed from the viewpoint of neural crest cell abnormality.

Abnormalities, Multiple↗
PubMed2000

Approximately 150 nucleotides from the 5' end of an influenza A segment 1 defective virion RNA are needed for genome stability during passage of defective virus in infected cells.

Defective influenza A virus RNAs analyzed in two studies so far possess at least 80-90 nucleotides from the 5' end of the virion RNA segment and more typically around 200 nucleotides, whereas the 3' sequence could be as short as 25 nucleotides (P. A. Jennings et al., Cell 34, 619-627; 1983; S. D. Duhaut and N. J. Dimmock, Virology 247, 241-253, 1998). To determine the biological significance of the highly conserved 5' sequence, we constructed plasmids that expressed a naturally occurring defective segment 1 RNA from A/equine/Newmarket/7339/79 (EQV, H3N8) or modified RNAs with lesser amounts of the 5' end. These had terminal 5' sequences of 220 nucleotides (POLI-220), 150 nucleotides (POLI-150), 80 nucleotides (POLI-80), and 30 nucleotides (POLI-30). Their remaining sequence came from the 3' end of virion RNA, and all were exactly 445 nucleotides in length. After transfection with one of the RNA-expressing POLI plasmids and plasmids encoding PB1, PB2, PA, and NP proteins, Vero cells were infected with a helper influenza virus of one of three different subtypes (the parental H3N8, an H2N2, or an H1N1 virus). Progeny infectious and presumptive progeny defective virus in the resulting tissue culture fluids were then passaged serially to new cultures up to 10 times. We found that POLI-220 and POLI-150 RNAs proved stable on passage and POLI-80 RNA was detected intermittently, while POLI-30 was not detected beyond passage three. Data were essentially reproducible with the three helper viruses and in two cell lines. It thus appears that the terminal 5' 150 nucleotides are necessary for influenza virion RNA molecules to be replicated and packaged consistently in cell culture. The possible functional significance of the 5' sequence is discussed.

Animals↗
PubMed1986

Defective bile acid transport in an animal model of defective debrisoquine hydroxylation.

Bile acid transport in female DA (dark Aguti) rats, a model for debrisoquine hydroxylation deficiency in man, was investigated. Compared to hydroxylation competent male DA and Sprague-Dawley rats of either sex, the female DA rat had a significantly lower taurocholate maximal secretory rate in vivo. Studies in the perfused liver showed this to be due to a decreased extraction efficiency during exogenous taurocholate loading. To characterize further the defect, taurocholate uptake velocity into isolated hepatocytes was studied. This showed a decreased maximal uptake velocity in the female DA rat (P less than 0.02). Whether this defect in bile acid uptake is related to the defective debrisoquine hydroxylation, remains to be established.

Animals↗
PubMed1986

Two yeast mutants defective in endocytosis are defective in pheromone response.

We have purified biosynthetically labeled alpha-factor secreted from transformed yeast alpha cells. This alpha-factor binds specifically to a cells and is internalized by a time-, temperature-, and energy-dependent process. alpha-factor is internalized in an intact form and then rapidly degraded. Two yeast mutants defective in the accumulation of an endocytotic marker, lucifer yellow CH, in the vacuole have been isolated. end1 accumulates invaginations of the plasma membrane, and end2, an internal membrane-bound organelle. One of these mutants, end1, is defective for internalization of alpha-factor. Both of these mutants are defective in pheromone response.

Cell Membrane↗
PubMed2005

Persistent vascular defects in lung allografts attributed to defective endogenous endothelial progenitors.

BACKGROUND: A major pathological finding in human newborns with pulmonary hypoplasia and congenital diaphragmatic hernia is the presence of vascular abnormalities in lungs. Vasculogenesis/angiogenesis are crucial to lung development. To study lung alveolar development, including microvascular formation in fetal lung implants, Schwarz et al. [1] developed a subcutaneous allograft model. We adopted their model to assess the influence of neovascularization or the "host-graft vascular development" on hypoplastic lung structure and growth. MATERIALS AND METHODS: Normal and hypoplastic lungs at pseudoglandular stage were implanted subcutaneously under the dorsolateral fold of immunocompromised nude mice (athymic, nu/nu). Lung allografts were removed and assessed at 2, 4, 6, and 8 weeks postimplantation. RESULTS: Neovascularization of implanted lungs from subcutaneous vasculature of nude mice resulted in varying degrees of maturation of implanted normal and hypoplastic lungs. By 4 weeks, implanted normal lungs contained Type 2-like cells and by 7 to 8 weeks, Type 2 and Type 1-like cells, air spaces had enlarged, and surfactant secretion was observed. Despite some differentiation and maturation of hypoplastic lungs, there was more mesenchymal tissue, no secondary septa, and smaller air spaces compared to normal lungs. CONCLUSIONS: (a) Neovascularization or host-graft vascular development occurs in both normal and hypoplastic lung allografts. (b) Development and maturation of implanted normal and hypoplastic lungs follow the establishment of the vascular connections between the host and grafts. (c) The host-graft vascular connections do not improve the growth of normal or hypoplastic lungs. (d) Neovascularization failed to overcome the embryonic defects in vascular formation and the pulmonary vasculogenesis remained defective in hypoplastic lung allografts, which may be attributed to the defective endogenous endothelial progenitor cells.

Animals↗
PubMed2002

Palmitoylation-defective asialoglycoprotein receptors are normal in their cellular distribution and ability to bind ligand, but are defective in ligand uptake and degradation.

The hepatic asialoglycoprotein receptor (ASGP-R) is an endocytic recycling receptor that mediates the endocytosis of desialylated glycoproteins. The human ASGP-R is composed of two homologous subunits, H1 and H2, and the cytoplasmic Cys residues in both subunits are palmitoylated. To study the effects of palmitoylation on ASGP-R activity and function, we generated four types of stably transfected cell lines in SK-Hep-1 hepatoma cells, expressing wild-type, or partially or completely palmitoylation-defective ASGP-Rs containing Cys-to-Ser mutations in either one or both subunits. Scatchard analysis showed that all four stable cell lines expressed a similar number of binding sites for asialo-orosomucoid, with comparable dissociation constants of approximately 1-3nM. Immunofluorescence confocal microscopy indicated a normal distribution of the palmitoylation-defective H1 and H2 subunits compared to the wild-type. However, cell lines expressing palmitoylation-defective ASGP-Rs had markedly reduced rates of ligand uptake and degradation compared to cells expressing wild-type ASGP-Rs. We conclude that failure to palmitoylate Cys residues in either or both subunits of human ASGP-Rs results in very inefficient uptake and degradation of ligands.

Asialoglycoprotein Receptor↗
PubMed1989

Defective regulation of epithelial Cl- permeability and protein secretion in cystic fibrosis: the putative basic defect.

The search for a basic functional defect in CF appears to be converging on a defect in the regulation of epithelial Cl- permeability and perhaps protein secretion. Fundamental issues that remain unresolved include (1) the identity of the CF gene, (2) the precise role played by the CF gene product in regulating Cl- permeability and protein secretion, and (3) the identities and properties of alternate pathways for regulating Cl- permeability and protein secretion that are not compromised in CF. The first issue should be resolved in the near future as molecular genetic approaches are used to pinpoint the location of the CF locus on chromosome 7. The second issue is more complex and will require the development of generally useful assays of Cl- permeability and protein secretion that can be used to assess the abilities of candidate CF gene products to complement, or correct, the functional defect in CF cells. Characterizing the precise function of the CF gene product may be difficult if the regulatory pathways that control these cellular processes are complex (ie, involve multiple regulatory steps and second messengers) or if the CF gene is a regulatory gene (rather than a structural gene) that represses or induces the synthesis of proteins involved in modulating Cl- permeability and protein synthesis. The third issue relates to the development of therapeutic strategies for treating CF patients that involve elevating epithelial Cl- permeability or modulating protein secretion by pharmacologically activating regulatory pathways that are unaffected in CF. In this regard, it is important to note that the stimulation of the Cl- permeabilities of airway epithelial cells by Ca2+-mediated secretagogues appears not to be compromised in CF. Pharmacological manipulation of this or other regulatory pathways may provide a means to activate the Cl- permeabilities of CF affected cells.

Chlorides↗