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The repair of an ostium secundum atrial septal defects (ASDs) by an open heart operation is a safe procedure associated with low mortality and morbidity. Transcatheter closure of ASDs is a less invasive method of repairing ASDs and may also be the procedure of first choice in residual postsurgical ASD.
The impact of device size choice on closure results was analyzed in 138 (101 females, 37 males; age 0.5-84.0 years) consecutive patients who underwent transcatheter closure of the secundum atrial septal defect (ASD) using the Amplatzer septal occluder (ASO). The balloon stretched diameter (SD) of ASD was 19.5 +/- 7.2 mm in 123 patients with single defects, and 20.4 +/- 6.6 mm for the largest defects in 15 patients with multiple ASDs. The difference (delta) between ASO size chosen for closure and the stretched diameter of the defect was calculated and divided into groups: A (delta < -2 mm); B (delta -2.0 to -0.1 mm); C (delta = 0); D (delta 0.1-2.0 mm) and E (delta > 2 mm). The results demonstrated that immediate and 24-hour complete closure rates were significantly higher in patients in groups C and D (P < 0.001). However, at 6-month follow-up, the complete closure rates were similar in patients of groups A-D, while patients of group E had a lower closure rate of 75%. The complication rates were similar in all groups. In conclusion, a choice of a device size identical to or within 2 mm larger than the SD of the defect should be used to maximize the closure rates of ASD using the ASO.
Various transcatheter devices and methods to close congenital heart defects are currently available. Devices have been designed specifically for atrial septal defect (ASD), patent foramen ovale (PFO), and ventricular septal defect (VSD) closure. The trend in interventional treatment of intracardiac shunts shows toward defect-specific systems. The PFO is a tunnel defect requiring occluders that adapt to its length while common ASD strongly vary in their diameter, making a large scale of device sizes indispensable. VSDs are predominantly sealed by coils or tissue-adapted devices like muscular or perimembranous occluders. Since VSDs may occur with an aneurysm (VSA), a multi-perforated septum, an instable myocardial situation (postinfarction) or a high interventricular pressure gradient, closure of these defects is regarded sometimes as complicated. But during the last 30 years (since King and Mills implanted the first double-umbrella occluding system) several studies have proven procedure efficacy and safety of both ASD and VSD closure. This article reviews a large scale of studies and includes our single center data on 1,609 PFO, ASD, and VSD patients.
The clinical, electrocardiographic, radiographic, and two-dimensional, M-mode and Doppler echocardiographic findings of five cases of canine ostium secundum type atrial septal defect (ASD) are described. The atrial septal anomaly was associated with other congenital cardiac abnormalities in two dogs: ventricular septal defect in one case and tricuspid dysplasia in the other. ASD was found in addition to dilated cardiomyopathy and suspected atrial thrombosis in one geriatric dog, but was the only cardiac abnormality detected in the remaining two dogs. Colour Doppler imaging facilitated the diagnosis of ASD in all subjects. The long-term prognosis for dogs with isolated and small-sized ASD is usually good, but can be compromised by the presence of concurrent congenital or acquired cardiac diseases.
The ability of Legionella pneumophila to cause Legionnaires' disease is dependent on its capacity to survive in the intracellular environment of its host cells. Furthermore, outbreaks of this disease have been associated with contaminated water sources where L. pneumophila survives as a parasite of protozoa. In this study, we determined the effect of nutritional auxotrophy on the ability of L. pneumophila to survive in the intracellular environment of its host cells. We generated a diaminopimelic acid (DAP) auxotroph (AA400) of L. pneumophila by disruption of the aspartate-beta-semialdehyde (asd) gene. The ability of AA400 to survive within macrophages and protozoa was found to be defective. This defect was due solely to the asd disruption since complementation of the mutant with the wild-type asd gene restored its capacity for intracellular survival. Furthermore, the defect was not completely complemented by DAP supplementation to the culture media. Thus, our results suggest that disruption of the asd gene may prove to be useful in the design of attenuated vaccines against Legionnaires' disease.
Pseudomonas putida KT2440, a paradigm organism in biodegradation and a good competitive colonizer of the maize rhizosphere, was the subject of studies undertaken to establish the genetic determinants important for its rhizospheric lifestyle. By using in vivo expression technology (IVET) to positively select single cell survival, we identified 28 rap genes (root-activated promoters) preferentially expressed in the maize rhizosphere. The IVET system had two components: a mutant affected in aspartate-beta-semialdehyde dehydrogenase (asd), which was unable to survive in the rhizosphere, and plasmid pOR1, which carries a promoter-less asd gene. pOR1-borne transcriptional fusions of the rap promoters to the essential gene asd, which were integrated into the chromosome at the original position of the corresponding rap gene, were active and allowed growth of the asd strain in the rhizosphere. The fact that five of the rap genes identified in the course of this work had been formerly characterized as being related to root colonization reinforced the IVET approach. Up to nine rap genes encoded proteins either of unknown function or that had been assigned an unspecific role based on conservation of the protein family domains. Rhizosphere-induced fusions included genes with probable functions in the cell envelope, chemotaxis and motility, transport, secretion, DNA metabolism and defense mechanism, regulation, energy metabolism, stress, detoxification, and protein synthesis.
AIM: To quantitatively examine the influence of study methodology and population characteristics on prevalence estimates of autism spectrum disorders. METHODS: Electronic databases and bibliographies were searched and identified papers evaluated against inclusion criteria. Two groups of studies estimated the prevalence of typical autism and all autism spectrum disorders (ASD). The extent of variation among studies and overall prevalence were estimated using meta-analysis. The influence of methodological factors and population characteristics on estimated prevalence was investigated using meta-regression and summarised as odds ratios (OR). RESULTS: Forty studies met inclusion criteria, of which 37 estimated the prevalence of typical autism, and 23 the prevalence of all ASD. A high degree of heterogeneity among studies was observed. The overall random effects estimate of prevalence across studies of typical autism was 7.1 per 10,000 (95% CI 1.6 to 30.6) and of all ASD was 20.0 per 10,000 (95% CI 4.9 to 82.1). Diagnostic criteria used (ICD-10 or DSM-IV versus other; OR = 3.36, 95% CI 2.07 to 5.46), age of the children screened (OR = 0.91 per year, 95% CI 0.83 to 0.99), and study location (e.g. Japan versus North America; OR = 3.60, 95% CI 1.73 to 7.46) were all significantly associated with prevalence of typical autism. Diagnostic criteria, age of the sample, and urban or rural location were associated with estimated prevalence of all ASD. CONCLUSIONS: Sixty one per cent of the variation in prevalence estimates of typical autism was explained by these models. Diagnostic criteria used, age of children screened, and study location may be acting as proxies for other study characteristics and require further investigation.
Although it is a common congenital cardiac lesion, secundum atrial septal defect (ASD) rarely presents in infancy. Its natural history in the first two decades of life is generally benign. Reports of symptomatic ASD in early childhood stress the place of conservative management, and recommend that the operation should be deferred until school age. Few accounts of the indications for surgery in infancy exist. We present our experience of 6 patients who failed to respond adequately to conservative treatment and required operation for intractable heart failure due to isolated secundum ASD in the first year of life. As their presentation and physical signs were not typical of ASD seen in later childhood, they presented problems both of diagnosis and management.
OBJECTIVES: To estimate the incidence of adult Still's disease (ASD) and to specify, if possible, associated factors. METHODS: A retrospective study of the populations of the Brittany and Loire regions in west France was made from 1 January 1982 to 31 December 1991. All internal medicine and rheumatology practitioners of these regions were consulted. RESULTS: Sixty-two (62) cases were reported (93% response). The disease incidence calculated over five years was 0.16 per 100,000 inhabitants in the study population. There was no sex bias (sex ratio 1.06 in ASD v 1.05 in the overall population. The mean age of the study population was 36 years, with two peaks of distribution at 15-25 and 36-45 years. A history of allergy was present in 23% of patients (n = 14). In two patients, it was possible to correlate an environmental allergen to exacerbation of ASD. CONCLUSION: The yearly incidence of ASD was estimated to be 0.16 per 100,000 inhabitants. However, it was not possible to incriminate any infectious, toxic, or genetic factors in exacerbation of the disease.
OBJECTIVES: To determine the effects of atrial septal defects (ASD) and their closure on systolic and diastolic right and left ventricular function; and by comparing surgical closure with transcatheter device closure, to establish differences attributable to cardiopulmonary bypass. DESIGN: Cross sectionally guided M mode echocardiographic ventricular long axis function was measured prospectively before and within one week after ASD closure by device in 17 patients and by surgery in 12 patients, and compared with 18 normal subjects. RESULTS: All indices of right ventricular function were impaired after surgery: mean total excursion, -1.89 cm (95% confidence interval (CI), -2.18 to -1.59); peak shortening rate, -9.09 cm/s (-10.82 to -7.35); peak lengthening rate, -9.26 cm/s (-11.09 to -7.43). Total excursion and peak lengthening rate were preserved after device closure, at -0.12 cm (-0.28 to 0.05) and 0.01 cm/s (-2.29 to 2.31), respectively. Left ventricular free wall function was unchanged after closure by either method, while all septal measurements were reduced after closure by either method (changes ranging from -3.51 to -0.32; 95% CI ranging from -4.90 to -0.13). CONCLUSIONS: Left ventricular free wall function is unaffected by ASD closure, whereas septal function is impaired, irrespective of the method of closure. Right ventricular function, both systolic and diastolic, is impaired by cardiopulmonary bypass but preserved after device closure. These findings support the transcatheter approach to ASD closure in anatomically suitable defects.
OBJECTIVE: To compare effectiveness, complications, and cost of Amplatzer with surgical atrial septal defect (ASD) closure. DESIGN: Prospective study. SETTING: Tertiary cardiac referral centre. PATIENTS: 43 consecutive patients (excluding non-UK residents) aged between 2.1 and 56.8 years (median 7) undergoing ASD closure. MAIN OUTCOME MEASURES: Procedural success, complications, regression of right ventricular dilatation (up to one year postprocedure), cost, inpatient stay, and home convalescent time. RESULTS: Amplatzer ASD closure was successful in 24 of 27 (89%) patients. Surgical closure was successful in all 19 cases. Cardiac complications affecting management occurred in three (11%) of the Amplatzer group (two procedural failures, one device embolisation) and 4 of 19 (21%) surgical patients (one pericardial pain, one global pericardial effusion requiring drainage, and one patient with anaemia requiring haematinics in addition to an incidental pericardial effusion and one further incidental pericardial effusion) (p = NS). There were complications that did not affect management in a further 5 of 19 surgical patients. There was no significant difference in regression of right ventricular dilatation by six months postprocedure (median right ventricular end diastolic diameter decrease: Amplatzer group 17.5%, surgical group 15.1%; median cardiothoracic ratio decrease: Amplatzer 7.9%, surgical 7.5%). Both hospital stay and home convalescent times were significantly shorter after Amplatzer closure (median hospital stay: Amplatzer one day, surgery six days; median convalescent time: Amplatzer two weeks, surgery 5.5 weeks). Median cost was similar for both groups (Amplatzer pound5375, surgical pound5412). CONCLUSIONS: Amplatzer ASD closure has a lower chance of success with a single procedure than surgery. Overall, there were more complications in the surgical group but the majority of these were minor and did not require any change in management. Resolution of right ventricular dilatation over the study period was similar for both techniques. Time spent in hospital and away from work or school was shorter for the Amplatzer group. The cost of both techniques was similar.
AIM: To investigate the role of pulmonary arterial hypertension (PAH) in adult patients born with a cardiac septal defect, by assessing its prevalence and its relation with patient characteristics and outcome. METHODS AND RESULTS: From the database of the Euro Heart Survey on adult congenital heart disease (a retrospective cohort study with a 5-year follow-up), the relevant data on all 1877 patients with an atrial septal defect (ASD), a ventricular septal defect (VSD), or a cyanotic defect were analysed. Most patients (83%) attended a specialised centre. There were 896 patients with an ASD (377 closed, 504 open without and 15 with Eisenmenger's syndrome), 710 with a VSD (275, 352 and 83, respectively), 133 with Eisenmenger's syndrome owing to another defect and 138 remaining patients with cyanosis. PAH was present in 531 (28%) patients, or in 34% of patients with an open ASD and 28% of patients with an open VSD, and 12% and 13% of patients with a closed defect, respectively. Mortality was highest in patients with Eisenmenger's syndrome (20.6%). In case of an open defect, PAH entailed an eightfold increased probability of functional limitations (New York Heart Association class >1), with a further sixfold increase when Eisenmenger's syndrome was present. Also, in patients with persisting PAH despite defect closure, functional limitations were more common. In patients with ASD, the prevalence of right ventricular dysfunction increased with systolic pulmonary artery pressure (OR = 1.073 per mm Hg; p<0.001). Major bleeding events were more prevalent in patients with cyanosis with than without Eisenmenger's syndrome (17% vs 3%; p<0.001). CONCLUSION: In this selected population of adults with congenital heart disease, PAH was common and predisposed to more symptoms and further clinical deterioration, even among patients with previous defect closure and patients who had not developed Eisenmenger's physiology.
OBJECTIVE: To examine the effects of pulmonary hypertension on left ventricular diastolic function and to relate the findings to possible mechanisms of interdependence between the right and left sides of the heart in ventricular disease. DESIGN: A retrospective and prospective analysis of echocardiographic and Doppler studies. SETTING: A tertiary referral centre for both cardiac and pulmonary disease. PATIENTS: 29 patients with pulmonary hypertension (12 primary pulmonary hypertension, 10 pulmonary fibrosis, five atrial septal defect (ASD), and two scleroderma) were compared with a control group of 10 patients with an enlarged right ventricle but normal pulmonary artery pressure (six ASD, one after ASD closure, one ASD and pulmonary valvotomy, one tricuspid valve endocarditis and repair, and one pulmonary fibrosis). None had clinical or echocardiographic evidence of intrinsic left ventricular disease. MAIN OUTCOME MEASURES: M mode echocardiographic measurements were made of septal thickness, and left and right ventricular internal cavity dimensions. Doppler derived right ventricular to right atrial pressure drop, and time intervals were measured, as were isovolumic relaxation time, and Doppler left ventricular filling characteristics. RESULTS: The peak right ventricular to right atrial pressure gradient was (mean (SD)) 60 (16) mm Hg in pulmonary hypertensive patients, and 18 (5) mm Hg in controls. The time intervals P2 to the end of the tricuspid regurgitation, and P2 to the start of tricuspid flow were both prolonged in patients with pulmonary hypertension compared with controls (115 (60) and 120 (40) v 40 (15) and 45 (10) ms, p values less than 0.001). Pulmonary hypertensive patients commonly had a dominant A wave on the transmitral Doppler (23/29); however, all the controls had a dominant E wave. Isovolumic relaxation time of the left ventricle was prolonged in pulmonary hypertensive patients compared with controls, measured as both A2 to mitral valve opening (80 (25) v 50 (15) ms) and as A2 to the start of mitral flow (105 (30) v 60 (15) ms, p values less than 0.001). The delay from mitral valve opening to the start of transmitral flow was longer in patients with pulmonary hypertension (30 (15) ms) compared with controls (10 (10) ms, p less than 0.001). At the time of mitral opening there was a right ventricular to right atrial gradient of 12 (10) mm Hg in pulmonary hypertensive patients, but this was negligible in controls (0.4 (0.3) mm Hg, p less than 0.001). CONCLUSIONS: Prolonged decline of right ventricular tension, the direct result of severe pulmonary hypertension, may appear as prolonged tricuspid regurgitation. It persists until after mitral valve opening on the left side of the heart, where events during isovolumic relaxation are disorganised, and subsequent filling is impaired. These effects are likely to be mediated through the interventricular septum, and this right-left ventricular asynchrony may represent a hitherto unrecognised mode of ventricular interaction.
OBJECTIVE: To compare outcome in patients with medically treated secundum atrial septal defect (ASD) first diagnosed after the age of 25 with the long-term outcome in a similar group of patients after surgical closure. DESIGN: A historical, prospective, unrandomised study. SETTING: A tertiary referral centre. PATIENTS: All patients with ASD followed up since 1955 who fulfilled the entry criteria and had reached a current age of over 45 years--that is, 34 medical and 48 surgical patients with a mean follow up of 25 years. MAIN OUTCOME MEASURES: Survival, symptoms, and complications. RESULTS: There was no difference in survival or symptoms between the two groups and no difference in the incidence of new arrhythmias, stroke or other embolic phenomena, or cardiac failure. No patient in either group developed progressive pulmonary vascular disease. CONCLUSION: Outcome in adults with ASD was not improved by surgical closure. Because progressive pulmonary vascular disease did not develop in any of these patients its prevention is not a reason for advising closure of ASD in adults.
Administration of a specific combination of anti-aminopeptidase A (APA) mAb (ASD-37/41) in mice induces an acute albuminuria which is independent of angiotensin II, a well-known substrate of APA. In the present experiments, we examined whether binding of the mAb initiated changes in the podocytic expression of cytoskeleton (-associated), adhesion and slit-diaphragm proteins in relation to the time course of albuminuria. In addition, we measured ultrastructurally the extent of foot process retraction (the number of foot processes per microm GBM) and the width of the slit pore between the podocytes by morphometric methods. An injection of the mAb combination ASD-37/41 induced a massive but transient albuminuria that started at 6 h, and peaked at 8 h, after which it declined. However, even at day 7 after injection of the mAbs some albuminuria was present. Injection of the combination ASD-3/41 or saline did not induce an albuminuria. Notably, we observed changes in the staining of CD2AP and podocin, two slit-pore-associated proteins that coincided with the start of the albuminuria. Nephrin staining was reduced and podocytic actin staining became more granular only at a time albuminuria was declining (24 h). The number of foot processes per microm GBM was already decreased at 4 h with a further reduction thereafter. The width of the slit pore was unchanged at the time of peak albuminuria and gradually decreased thereafter. At day 7, podocytic foot process effacement was even more prominent although albuminuria was only slightly abnormal. Expression of CD2AP was still granular. We observed however a change toward normal in the expression of podocin. Injection of saline or ASD-3/41 had no effect on the expression of podocytic proteins, the number of foot processes or width of the slit pore. Our data show that the onset of albuminuria in the anti-APA model is related to alterations in CD2AP and podocin, proteins that are important for maintaining slit-diaphragm structure and podocytic function. Extended studies at day 7 demonstrated uncoupling of albuminuria, podocytic foot process effacement and CD2AP staining. Changes in podocin more closely paralleled changes in albuminuria.
Autism spectrum disorders (ASD) are thought to be present right from birth, even if a minority of children displays a normal course during infancy followed by a regression during the second year of life. However, established criteria are not yet available to differentiate these different courses of ASD, and data coming from different sources have not yet been organized into a clear definition. The aim of this study was to elucidate the time of onset, as well as type, frequency and stability of symptoms during the first year of life in ASD. The behavioral summarized evaluation scale, applied to 40 home movies of children later diagnosed as having ASD, showed that most of the subjects (87.5%) display symptoms within the first year of life, when only a small group (12.5%) is completely symptom free. A group of more rated symptoms was found, constituting a typical pattern characterized by being withdrawn, and displaying poor social initiative, hypoactivity, and lack of emotional modulation. The importance of these findings is discussed in relation to early diagnosis and treatment.
Anti-siphon devices (ASD) were initially bench tested at flow rates between 10 and 50 cm3/h and with the distal catheter height between 0 and -60 cm. There was a small increase in pressure with increased flow rate in the horizontal position (p less than 0.001). The inflow pressure initially dropped with the distal catheter height at -20 cm; it then rose progressively with distal catheter heights of -40 and -60 cm (p less than 0.001). To determine the effect of ambient pressure the devices were placed in a barometric chamber at pressures between -200 and +200 mm H2O. Positive pressures caused a linear increase in inflow pressure; negative chamber pressure reduced the anti-siphon effect. Eight ASDs were implanted subcutaneously in piglets and tested in situ weekly for 4 weeks. Implantation caused a mean increase in inflow pressure of 93.5 mm H2O 7 days after implantation (p less than 0.001) and which persisted for 4 weeks. Incision of the capsule surrounding the ASD at the end of 4 weeks caused a drop in pressure. The capsule consisted of an outer layer of collagen fibres with an inner layer of histiocytes. Subcutaneous implantation of ASDs causes an increase in the ambient pressure of the device which significantly increases their resistance to flow.
The aim of the present study was to determine which of the anterior or posterior efferents of the suprachiasmatic nucleus (SCN) predominantly act for the maintenance of estrous cycle in female rats. A small knife (0.8 mm in radius) was used for anterior (ASD), posterior (PSD) and complete suprachiasmatic deafferentations (CSD). The rats subjected to CSD were divided into two groups, the first group bearing lesions on the medial preoptic nucleus (MPN; group CSD-MPN-L) and the other group bearing no lesions on the MPN (group CSD). For reference, anterior hypothalamic deafferentation (AHD) was carried out using a large knife (2.0 mm in radius). All rats with AHD or CSD-MPN-L and some of CSD rats showed persistent estrus, but all animals with ASD or PSD resumed regular estrous cycles after transient irregular periods. Ovaries of AHD, CSD and CSD-MPN-L rats contained very few, if any, corpora lutea, while the number of corpora lutea in ASD or PSD rats was not significantly different from that of sham-operated controls. Immunohistochemical examination revealed that in AHD rats LHRH immunoreactivity in the median eminence was markedly reduced as compared with that of sham-operated controls. In contrast, in ASD, PSD, CSD and CSD-MPN-L rats, the LHRH immunoreactivity in the median eminence was similar to that of sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)