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[Coronary sinus atrial septal defect diagnosed by cyanosis after operation of ventricular septal defect].

We have experienced a case of coronary sinus atrial septal defect (ASD) with ventricular septal defect (VSD). Cardiac catheterization revealed a step-up of oxygen saturation in right ventricle, L-R shunt 70.3%, R-L shunt 6.9% and pulmonary hypertension (PH). Since diagnosis of coronary sinus ASD was difficult, the operation was performed under diagnosis of VSD. Although the operation was success, cyanosis appeared after the operation. Contrast echocardiography using subcostal 4 chamber view showed coronary sinus ASD with a large Thebesian valve and the right-to-left shunt of the ASD. The Thebesian valve seemed to lead the venous return flow to the left atrium. Coronary sinus ASD was closed using a Xenomedica patch.

Cyanosis↗

Percutaneous closure of secundum atrial septal defect in adults a single center experience with the amplatzer septal occluder.

Percutaneous closure of atrial septal defects (ASD) is increasingly performed in pediatric and adult patients. This study reports a single-center experience with the use of the Amplatzer Septal Occluder for percutaneous ASD closure in adults. One hundred and seventeen consecutive patients were prospectively included in the database. The procedure was successful in 106 patients (90.6%). The mean age was 50 years. Eighty-four percent of the patients had a Qp:Qs > 1.5. Other indications included a history of thromboembolism, decreased exercise tolerance, atrial arrhythmias, evidence of pulmonary hypertension or right heart overload. Mean procedure time was 44 minutes, and mean fluoroscopy time was 13 minutes. The mean defect diameter was 17.2 mm (range, 5 30 mm). There was no residual shunting at the end of the procedure in 75% of the patients. Shunting was minimal in all but 2 of the remaining 25 patients (1.8%). No major complications were observed at a mean follow-up of 19 months. Patients in whom the procedure failed had larger defects (mean, 25.0 mm versus 18.3 mm; p < 0.001), larger right ventricles (44.1 mm versus 38.2 mm; p = 0.03) and more significant shunting (Qp:Qs, 3.5 versus 2.1; p < 0.001). New York Heart Association functional class improved in all but 1 patient. Percutaneous ASD closure using ASO is safe and mid-term results compare favorably with those reported with surgical ASD closure. It can therefore be recommended as the first line of treatment in adult patients with secundum ASD.

Adult↗

Indolyl-3-acryloylglycine (IAG) is a putative diagnostic urinary marker for autism spectrum disorders.

BACKGROUND: Autism is a heterogeneous pervasive developmental disorder with a poorly defined aetiology and pathophysiology. There are indications that the incidence of the disease is rising but still no definitive diagnostic biochemical markers have been isolated. Here we have addressed the hypothesis that urinary levels of trans -indolyl-3-acryloylglycine (IAG) are abnormal in patients diagnosed with autism spectrum disorders (ASD) compared to age-matched controls. MATERIAL/METHODS: Urine samples were collected on an opportunistic basis and analysed for IAG concentration (normalised against creatinine content to account for changes in urinary volume) using reversed phase HPLC with UV detection. RESULTS: Statistical analysis (Mann-Whitney tests) showed highly significant increases (p=0.0002) in the levels of urinary IAG in the ASD group (median 942 microV per mmol/L of creatinine [interquartile range 521-1729], n=22) compared to asymptomatic controls (331 [163-456], n=18). Detailed retrospective analysis showed that gender (boys 625 microV per mmol/L of creatinine [294-1133], n=29; girls 460 [282-1193], n=11: P=0.79) and age (control donor median 10 years [8-14], n=15; ASD median 9 years [7-11] n=22: P=0.54) were not significantly correlated with IAG levels in this non-blinded volunteer study. CONCLUSIONS: Our results strongly suggest that urinary titres of IAG may constitute an objective diagnostic indicator for ASD. Mechanisms for the involvement of IAG in ASD are discussed together with future strategies to address its specificity.

Adolescent↗

Atrial septal closure in adults: surgery versus amplatzer--comparison of results.

OBJECTIVE: To compare the efficacy, safety and morbidity of surgical versus percutaneous atrial septal defect (ASD) closure. POPULATION AND METHODS: We studied all cases of ASD closure (surgical or percutaneous) performed in our hospital during the last 5 years. We analyzed the clinical and echocardiographic characteristics of both groups and compared the success rate of the procedure, events, days of hospital stay and evolution during the 1st year. RESULTS: 63 patients (pts) with ostium secundum ASD were treated in our hospital in the last 5 years; 25 (60% female) underwent surgery (A) while 38 (68% female) underwent percutaneous closure with an Amplatzer device (B); mean age was 38 (13-67) and 40 years (15-72), respectively. Dyspnea and fatigue were the most frequent symptoms in both groups (57% A; 29% B), while the most frequent signs were fixed splitting of S2 (78% A; 88% B) and systolic murmur at the left sternal border (82% A; 87% B). Previous ECG presented incomplete right bundle branch block in 63% of both groups. The size of the ASDs, as well as Qp:Qs, were greater in the surgical group: 24.6 (5-50) vs. 18.97 mm and 3.1 (1.5-6.5) vs. 2.7 (1.2-5.2) respectively. Right cardiac chambers were enlarged in 92% of pts in A vs. 84% in B. Paradoxical interventricular septal motion (PSM) was present in 78% of pts in A and 67% in B. The success rate (100%) was similar in both groups but immediate minor events were more frequent in A (28 vs. 13%). Duration of hospital stay was longer in A: 5.4 days (3-9) vs. 1.5 days (1-4). Normalization of right cardiac chamber diameter was faster in B: 73% in the 1st control echocardiogram (at 0-64 days, mean 29) vs. 60% in A, performed at a later stage (45-455 days after the procedure, mean 155). At the time of reassessment PSM was still present in all the pts of group A and in only 10% of B (p < 0.0001). CONCLUSIONS: The success rate of ASD closure is 100% with both procedures and complications are rare. The percutaneous technique, however, permits a shorter hospital stay, involves less morbidity, and, despite sample limitations, seems to be associated with faster anatomical recovery. Therefore, in our opinion, surgical treatment should be reserved for those cases in which closure with an Amplatzer device is not technically or anatomically possible.

Adolescent↗

The amplatzer [corrected] septal occluder as a standard for therapy of secundum-type [corrected] atrial septal defect.

Atrial septal defect (ASD) accounts for 5-10% of congenital heart malformations. An uncorrected ASD may lead to congestive heart failure, severe pulmonary hypertension, or paradoxical arterial embolism with stroke. Transthoracic echocardiography is often diagnostic in the pediatric population, but transesophageal echocardiography may be required in adults. Closure of an ASD traditionally has been performed surgically, but the most common type (secundum ASD) can now be closed with a percutaneously deployed device. We briefly describe the types of ASDs and their diagnosis. Results of percutaneous closure in 74 children and adults are then presented.

Adult↗

[Early haemodynamic changes after transcatheter closure of atrial septal defect].

OBJECTIVE: To evaluate the outcomes of transcatheter closure of secundum atrial septal defect (ASD) using the Amplatzer Septal Occluder (ASO). METHODS: Between December 2000 and December 2002, 27 adult patients (20 females, 7 males) with a mean age of 41.1 +/- 13.3 (range 18-62) years were enrolled for an attempt at ASD closure with the ASO device. All patients had an isolated secundum ASD with a large left-to-right shunt (ratio of pulmonary to systemic blood flow or Qp:Qs >1.5:1). Transthoracic color Doppler echocardiographic examination was performed on all patients before procedure, 24 hours, 1 and 6 months after surgery. Clinical observation (NYHA class) was performed 1 and 6 months after surgery. RESULTS: The ASO device was successfully implanted in all patients (procedure time 19-63 minutes, median 43 minutes, fluoroscopy time 4-40 minutes, median 12.6 minutes), with only 3 patients with a trivial residual shunt. The defect echo diameter was 14.2 +/- 4.3 (7-24). At one month of follow-up transthoracic echocardiography showed that the device was correctly positioned in all cases and no predictors for a residual shunt were identified. Residual trivial shunt in one month follow-up was shaded in 3 patients. Paradoxical septal motion abnormalities normalized in all patients. The right ventricular dimension evaluated by 2D echocardiography decreased in 20 pts (74.1%), mean 5.0 +/- 3.4 mm (range 1.5-8), the right atrium dimension decreased in 21 pts (77.8%), mean 8.65 +/- 4.3 mm (range 2-20) and the left atrium dimension decreased in 15 pts (55.6%), mean 6.36 +/- 3 mm (range 2-21). We didn't find correlations between ratio of left-to-right shunt before ASD closure and the decrease of right heart dimension as well as the decrease of pulmonary artery systolic pressure. CONCLUSIONS: Transcatheter closure of secundum ASD using the ASO is a safe and effective procedure, with excellent short-term follow-up results. During one month observation it caused partial normalization of echocardiographic parameters.

Adult↗

[Early results of atrial septal defect closure with the Amplatzer Septal Occluder are impacted by tricuspid insufficiency].

OBJECTIVE: Our study reports the results of a comparison of transcatheter closure of secundum atrial septal defect (ASD) using the Amplatzer Septal Occluder (ASO) in patients with and without tricuspid insufficiency. METHODS: Consecutive 27 adult patients (20 females, 7 males) with a mean age of 41.1 +/- 13.3 (range 18-62) years having an ASD II and a transcatheter closure between December 2000 and December 2002 were analyzed. All the patients had an isolated secundum ASD with a significant left-to-right shunt (ratio of pulmonary to systemic blood flow or Qp:Qs >1.5:1). Patients were divided in two groups: group I--without tricuspid abnormalities (8 patients, 29.6%), group II--patients with tricuspid insufficiency I-III stage, (19 patients, 70.4%). Transthoracic color Doppler echocardiographic study was performed in all patients before discharge and was repeated one month after discharge. RESULTS: The mean age, the diameter of defect, the degree of left-to-right shunt, the diameter of implanted device were comparable in both groups. Before implantation the dimension of right heart cavities differed between groups. The right ventricular dimension was larger in group II (mean 36.2 mm vs. 29.1 mm; p<0.009), the right atrium diameter was larger in group II (46.2 mm vs. 24.3 mm; p<0.007). Pulmonary artery systolic pressure before the procedure was higher in group II (36.6 mmHg vs. 20.43 mmHg; p<0.006). The ASO device was successfully implanted in all the patients. At one month follow-up septal motion abnormalities normalized in all patients in both groups. The mean decrease of right atrium diameter in group I was 6.2 mm (range 1.5-12 mm) compared to 9.6 mm (range 2-20) in group II, (p<0.001), the mean decrease of right ventricular diameter in group I was 5.8 mm (range 2-8 mm) compared to 3.1 mm (range 1-5.9) in group II, (p<0.006). CONCLUSIONS: Short-term follow-up demonstrated excellent results of ASD closure in both groups. In one month follow-up the decrease of right cavities dimensions was significantly higher in the patients without tricuspid abnormalities. The pulmonary artery systolic pressure before ASD closure was significantly higher in the patients with tricuspid abnormality.

Adult↗

[Percutaneous transcatheter closure for secundum atrial septal defect].

OBJECTIVE: To evaluate the effect of transcatheter closure treatment for secundum atrial septal defect(ASD). METHODS: ASD was established by transthoracic echocardiogram (TTE) and transvenous cardiac catheterization. A balloon catheter was inserted at ASD and was inflated to measure the ASD stretched diameter. Then, a long sheath was inserted to the left atrium (LA) from the right atrium( RA), Thereafter a proper auto-expanded atrial septal occluder (ASO) was inserted to the tip of the sheath. Under the fluoroscopic and TTE guidance, the ASO was expanded. Once the position of ASO was optimal, it was released. RESULTS: From May 1999 to July 2002, 32 patients were treated with this method. Among them, 28 patients (87.5%) obtained satisfactory results. At the end of the operation, TTE could not find out any residual shunt. Before discharging the patients, TTE showed the diameter of the right atrium and the right ventricle were decreased from (39.4 +/- 5.8) mm to (33.7 +/- 4.2) mm and from (45.3 +/- 6.8) mm to (37.1 +/- 4.5) mm respectively (P < 0.001 for both). The operation failed in 4 patients (12.5%). Two patients did not get proper ASO for them in the early period of our work. ASO slipped off from the defects in another 2 patients during the operation. There were no other complications. CONCLUSION: Tanscatheter closure is suitable for most patients with ASD. It is safe and less invasive with few complications.

Adolescent↗

Transcatheter closure of interatrial communications with Amplatzer device: results, unfulfilled attempts and special considerations in children and adolescents.

OBJECTIVE: We report our clinical experience with the Amplatzer device in transcatheter closure of 80 atrial septal defects (ASD) in children. METHODS: Among 99 patients (mean age: 7.2+/-3.8 years) with ASD selected by transthoracic echocardiography, procedures were performed in 80 patients under general anesthesia with fluoroscopic and transesophageal echocardiographic (TEE) guidance. Optimal device size was selected after stretched balloon sizing of the ASD's. The patients were discharged at 24 hours after an evaluation with X-ray, electrocardiography and echocardiography. RESULTS: The mean follow-up period (FUP) was 38+/-14 months. Mean ASD size was 11.5+/-3.7 mm at TEE (stretched size: 17.6+/-3.9 mm). The mean size of the device was 18.6+/-4.0 mm. Procedure and fluoroscopy time were 52.1+/-17.8 minutes and 11.0+/-4.9 minutes, respectively. Immediately after the procedure 35 patients (43.8%) had residual shunts. Trivial shunt remained in only 2 of them (2.5%) after FUP. None of the patients had major complications. Minor and transient rhythm abnormalities were observed in 5 patients and trivial mitral regurgitation was seen in 6 patients. CONCLUSION: Amplatzer is an effective and safe device for transcatheter closure of ASD especially in pediatric patients.

Adolescent↗

[Influence of age-related complications on clinical outcome in patients with surgical repair of atrial septal defect].

BACKGROUND: The influence of perioperative characteristics on postoperative outcome has been obscure in the adult patients with atrial septal defect (ASD). This study was designed to investigate whether perioperative patient profiles and complications will contribute to postoperative outcome following surgical closure of ASD in adult patients. METHODS: Subjects were 39 (17 male and 22 female) ASD patients, aged 16 to 69 years (mean 53 +/- 15) who were scheduled for surgical repair of isolated secundum ASD between 1999 to 2003. All patients were evaluated for circulatory characteristics using echocardiography and cardiac catheterization. Postoperative complications were evaluated by examining duration of postoperative oxygen requirement, postoperative duration until first ambulation, intubation and hospital stay after surgery. RESULTS: In elderly group (over 50 years of age), preoperative %FEV1.0, preoperative oxygen index and creatinine clearance were lower compared with those of younger group (under 50 years of age) (P=0.0309, P= 0.0341 and P= 0.0112, respectively). Moreover, elderly group showed longer duration of oxygen requirement compared with younger group (3 +/- 5 days and 2 +/- 1 days; P=0.0273). Age and change of the left ventricular diastolic diameter (LVDd) affected the incidence of postoperative arrhythmia (P=0.0195 and P=0.0204). Preoperative oxygen index and %VC affected long term intubation (P=0.0201 and P=0.0363). TAP, smoking and pulmonary hypertension affected long term oxygen supply (P=0.0070, 0.0349 and 0.0355). Only %VC affected postoperative duration until first ambulation (P = 0.0219). Delirium and postoperative oxygen index affected the length of hospitalization (P=0.0072 and 0.0188). CONCLUSIONS: Respiratory function was important in short-term outcomes in the patients with ASD. In addition, preoperative small LVDd was a useful predictor for postoperative atrial fibrillation.

Adolescent↗

[Cardiopulmonary exercise test in the evaluation of exercise capacity in patients with Ebstein anomaly and patent ostium secundum atrial septal defect aged over 30 years].

UNLABELLED: There are few data available on applying the cardiopulmonary exercise test for evaluation of cardiac exercise capacity in adult patients with congenital heart diseases. The aim of the study was to perform this test in adults with Ebstein anomaly and patients with patent ASD II (atrial septal defect) and determination of potential relationships between these parameters and echocardiographically assessed hemodynamic indices. MATERIAL AND METHODS: Twenty patients with Ebstein anomaly mean aged 40.3 +/- 12.3 years were studied. Control group consisted of 19 individuals at mean age of 39.9 years. Echocardiography was performed for the evaluation of severity of the disease. Additionally, 36 patients with ASD II were included, mean age 44.7 +/- 8.2 years. The control group consisted of 25 individuals at mean age of 45.6 years. Maximum exercise treadmill test was carried out and resting and exercise spirometry. RESULTS: Ebstein anomaly. Maximum oxygen uptake, minute ventilation, maximum heart rate and blood pressure at peak exercise were significantly lower in study patients than in control group. VE/VCO2 was increased. No differences were observed between groups with respect to spirometric parameters. Oxygen uptake decreased along with the severity of the disease. ASD II. Maximum oxygen uptake, minute ventilation, maximum heart rate and blood pressure at peak exercise and spirometric parameters were significantly lower in study patients than in control group. Significant negative correlations were shown for VO2 (maximum oxygen uptake) and Qp:Qs (pulmonary to systemic flow ratio) (p = 0.004), maximum heart rate - HRmax and HRmax% and RV (end-diastolic right ventricular diameter) (p = 0.02 i p = 0.01), RV and systolic pressure at peak exercise (p = 0.03), obstruction marker FEV1 and RV (p = 0.04) and between RVSP (right ventricular end-systolic pressure) (p = 0.01). Negative correlation was observed between RQ (respiratory quotient) and RVSP (p = 0.004), and positive correlation between HRmax and VO2 (p = 0.005). CONCLUSIONS: The exercise capacity of adults with Ebstein anomaly and those with patent ASD II is significantly reduced. It decreases along with the echocardiographic severity of the disease in Ebstein anomaly patients and it seems to result from the right ventricular volume overload in patients with patent ASD II.

Abnormalities, Multiple↗

[Good practice guidelines for the treatment of autistic spectrum disorders].

INTRODUCTION: Due to the inexistence of an aetiology-based intervention for autistic spectrum disorders (ASD) families and professionals are exposed to diverse and sometimes conflictive recommendations when they have to decide the most adequate alternative for treatment. AIM: To elaborate treatment guidelines agreed by consensus at the ASD Study Group of the (National) Institute of Health Carlos III. DEVELOPMENT: Information about treatment of ASD was searched and gathered through available evidence based medical (EBM) databases. The data generated was complemented with practice parameters published elsewhere, reports from prestigious international institutions, focus oriented searches in PubMed and, finally, the opinion and experience of a multidisciplinary Study Group with extensive experience in treating ASD in Spain. Most popular treatment methods were reviewed as well as the common elements to be considered in successful support programs. CONCLUSION: No simple treatment algorithm can be produced at this time, and the level of available evidence based recommendations are in the weaker degrees of EBM classifications. Nevertheless, there is widespread agreement to stress that education, with special incidence in the development of communication and social competence, with the addition of community support are the main means of treatment. They can be complemented, depending on individual needs, with medication, behavioural approaches and cognitive-behavioural therapy for associated psychological problems in persons with higher cognitive level. Support to families and community empowerment are essential elements for the quality of life of persons with ASD.

Autistic Disorder↗

A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders.

BACKGROUND: A medical hypothesis has suggested that some autism spectrum disorders (ASDs) may result from interactions between the methionine cycle-transsulfuration and androgen pathways following exposure to mercury. METHODS: The IRB of the Institute for Chronic Illnesses approved the present study. A novel treatment was utilized combining LUPRON (leuprolide acetate, TAP Pharmaceuticals, Inc.) and CHEMET (meso-2, 3-dimercaptosuccinic acid--DMSA, McNeil Consumer Products Company) on 11 consecutive children with ASDs. RESULTS: A significant (p<0.01) overall improvement from the 70-79th percentile of severity (median baseline score=87) at baseline to the 40-49th percentile of severity (median end of study period score=63) at the end of the study was observed for patients treated for a median of approximately 4 months. Significant improvements in sociability, cognitive awareness, behavior, and clinical symptoms/behaviors of hyperandrogenemia were also observed. Significant decreases in blood androgens and increases in urinary heavy metal concentrations were observed. Minimal drug adverse effects were found. CONCLUSION: This study provides the first clinical evidence for the benefit that combined anti-androgen and anti-heavy metal therapy may have on some children with ASDs. Additional studies should examine androgen and heavy metal mechanisms of action in ASDs, and future ASD treatment protocols should consider androgens and heavy metals.

Adolescent↗

[Non-surgical repair of atrial septal defect by "buttoned" double disk device in children. First results in 3 children].

Transcatheter closure of ostium secundum atrial septal defect (ASD) with a "buttoned" double-disk device was attempted in 5 children aged 14 months to 12 years, with success in 3 cases. The diameter of the ASD was 15 to 20 mm. The occluding devices were chosen with sizes 12-15 mm greater than those of the ASDs. There were no operative complications: the ASD was practically completely occluded in 2 children and left a very small shunt in a third case. Those three patients are doing well, 8 to 9 months after the procedure. In the other two cases, the device fell into the right atrium and had to be removed surgically without any complications. The "buttoned" double-disk device seems to be relatively simple and easy to insert through an 8F catheter. Additional technical improvements should enable more complete occlusion of ASD and easier retrieval by the transvenous route when incorrectly inserted. Further experimental and clinical studies are required to assess the results and to compare them with those of the other teams.

Cardiac Catheterization↗

[The role of transesophageal echocardiography in atrial septal defect detected in adults].

UNLABELLED: To assess the value of combined transesophageal echocardiography (TE) and transthoracic echocardiography (TTE) in the preoperative evaluation of atrial septal defect (ASD) 59 consecutive patients (aged 15-62, mean 38 yrs) with clinically or echocardiographically suspected ASD underwent TE and complete noninvasive hemodynamic study by TTE. ASD was found by TE in 48: fossa ovalis (FO) type in 36, sinus venosus (SV) type in 11 and primum type in 1. For FO and SV defect the sensitivity of clinical judgement was 83 and 0%, the specificity 39 and 100% resp., the sensitivity of TTE was 78 and 9%, the specificity 78 and 100%. The most frequently associated anomaly by TE was mitral valve prolapse (25%). SV defect was always associated with anomalous right upper pulmonary venous drainage, and left superior vena cava was found in 27% of SV defects. There was significant correlation between Qp/Qs measured by TTE and by catheterization (r = 0.64), but the Qp/Qs was not related to defect size. An excellent correlation was found between pulmonary artery systolic pressure measured by CW Doppler and catheterization (r = 0.98). IN CONCLUSION: 1) TTE combined with TE is reliable in the preoperative assessment of ASD in adults, 2) TE is not necessary if there are unequivocal clinical and TTE signs of an FO defect with significant left-to-right shunt, 3) TE is indicated in patients with signs of right ventricular overload or pulmonary hypertension if an ASD cannot be ruled out by TTE, 4) catheterization is necessary if all 4 pulmonary veins cannot be visualized by TE.

Adolescent↗

[Successful surgical treatment of incomplete type IB2 cor triatriatum (absent left innominate vein) with coronary sinus atrial septal defect].

The combination of type IB2 cor triatriatum and coronary sinus ASD is very rare in congenital heart condition. Up to present, only one case of IB2 cor triatriatum and thirteen cases of coronary sinus ASD were reported in Japan. In this combination, we have presented the first successful surgical treatment for type IB2 cor triatriatum (Lucas-Schmidt's classification), absent left innominate vein and coronary sinus ASD. The patient was a 52-year-old female admitted with chronic dyspnea. Echocardiography and cardiac catheterization revealed ASD, severe mitral regurgitation, cor triatriatum, left SVC connected to left atrium (accessory chamber) and absent coronary sinus. Under cardiopulmonary bypass she underwent surgical treatment which consisted of a resection of the intra-left-atrial diaphragm, closure of ASD with patch, mitral valve replacement with Omnicarbon #29 valve and ligation of left SVC. Her postoperative course was uneventful.

Brachiocephalic Veins↗

[Congenital heart disease with right ventricular overloading in the elderly].

This study was undertaken to characterize the clinical pictures of long-standing overload of the right ventricle and to investigate its hemodynamics. 1. Myocardial cell injury of the right ventricle was studied. Histopathological examinations were performed by biopsy in patients with atrial septal defect (ASD). Cell diameter was more widely distributed in the disease compared to the control. The range of distribution was more markedly scattered in ASD with congestive heart failure. Change in the ultra-fine structure was also more remarkable in ASD with than without pump failure. 2. ASD with impending myocardial infarction was discussed as an example of associated acquired disease. 3. The occurrence of pulmonary hypertension could be monitored with recently developed color Doppler method. A representative case of ASD and pulmonary hypertension was presented and discussed. 4. Right ventricular overloading associated with arrhythmias was presented. The effects of arrhythmias on Ebstein's anomaly and Uhl disease were examined. In these anomalies, development of pump failure and life-threatening arrhythmias were serious problems in managing old patients. In summary, histo-pathological examinations, monitoring of pulmonary artery pressure by Doppler echocardiography and management of arrhythmias were necessary to evaluate prognosis of congenital heart disease in the elderly.

Adult↗

The covalent tagging of the cell surface insulin receptor in intact cells with the generation of an insulin-free, functional receptor. A new approach to the study of receptor dynamics.

A new method is described in which the cell surface insulin receptor can be radioactively tagged in a specific manner with a small insulin-free probe. After protecting the amino groups of insulin essential for binding and bio-activity, insulin is coupled to the heterobifunctional, cleavable cross-linking reagent SASD (sulfosuccinimidyl 2-(p-azidosalicylamido)-1,3'-dithiopropionate), via displacement of the N-hydroxysuccinimide moiety of SASD. Removal of the protecting groups results in the formation of 2-(p-azidosalicylamido)-1,3'-dithiopropionate (ASD)-insulin with insulin receptor binding activity equivalent to unmodified insulin. Iodination of ASD-insulin results in the incorporation of 125I into both the azidohydroxybenzoyl moiety of SASD and a tyrosine residue of insulin. Following binding of 125I-ASD-insulin to intact monolayers of 3T3-C2 cells, radiolabel is incorporated exclusively into a 135-kDa protein in a manner dependent upon the length of exposure of the cells to short wavelength ultraviolet light. This protein corresponds in molecular weight to the alpha subunit of the insulin receptor. Labeling of this protein can be inhibited by excess unlabeled insulin. Reduction of the disulfide bond of ASD with 10 mM glutathione causes the release of the 125I-insulin portion of the reagent from the receptor complex, with the iodinated photoactivated end of ASD covalently attached to the receptor. Insulin receptor labeled in this manner retains its ability to bind insulin. General metabolic processes of the intact cells do not appear to be perturbed by this labeling procedure, and the cellular processing of the insulin receptor does not appear to be modified by the covalent labeling of the receptor protein. This procedure therefore provides a way to specifically label the cell surface insulin receptor in a manner which does not perturb the normal functioning of the labeled cell and equally importantly, does not perturb the normal cellular processing of the insulin receptor itself.

Amino Acids↗