Evaluation of recent research grant applications to the National Institutes of Health in the area of pediatric nephrology

To assess the National Institutes of Health extramural activity in the area of pediatric nephrology research, the rate of submission of grant applications to the National Institutes of Health and available indicators of the quality of these applications were analyzed. This was accomplished by utilizing the grant application files of the Division of Research Grants' Statistics and Analysis Branch with the help of the Reports, Analysis and Presentation Section. Applications reviewed during the period 1980-1983 (May 1980 to January 1984 Council dates) were evaluated, and data from the 10 Study Sections most frequently involved with the review of nephrology applications were tabulated. Results showed that the number of pediatric nephrology applications submitted was quite low, whereas the approval rate was good for those that were submitted.     

Infants with apparent life threatening events. Cardiac rhythm and conduction

The role of cardiac dysrhythmias in the pathogenesis of Sudden Infant Death Syndrome (SIDS) is uncertain, but there have been several reports of infants with Apparent Life Threatening Events (ALTE) due to significant dysrhythmias. To further characterize the cardiac rhythm and conduction of these "at-risk for SIDS" infants, we performed 24-hour continuous (Holter) electrocardiograms on 100 full term, healthy infants with ALTE. Sixty-two patients (62%) had one or more dysrhythmias on Holter monitor. Twenty-five patients (25%) had premature ventricular depolarizations (PVD), including five with couplets. Thirty (30%) had QTc greater than 2 SD above the mean, and, of these, 40 percent had PVD's. Fifteen (15%) had premature atrial depolarizations and 39 (39%) had evidence of moderate or marked sinus node irregularity. There was no prexcitation, supraventricular tachycardia, ventricular tachycardia, or atrioventricular block. Two patients with marked sinus node dysfunction were treated with propantheline and did well. All patients were monitored at home, with no deaths or clinically significant dysrhythmias on follow-up (1-32 months (mean = 18]. In summary, when Holter monitoring was performed, a high incidence of dysrhythmia was found in infants with ALTE. Most dysrhythmias were clinically insignificant. The incidence of ventricular dysrhythmias and long QTc are consistent with previously advanced theories of cardiac electrical instability in some of these patients, but no patient with ventricular dysrhythmias required therapy. The incidence of sinus node dysfunction requiring therapy was 2 percent. Although Holter monitoring of infants with ALTE only infrequently determines therapy, it may provide data linking theories of cardiac etiology of SIDS with actual clinical events.     

Unusual roentgenographic presentation of a congenital cystic malformation of the lung

We describe here an infant with a large, solitary, fluid-filled lung cyst and hyperinflation of adjacent lung tissue in the same lobe. The combination of a fluid-filled cyst and ectatic emphysema in the same lobe suggests bronchial collapse and airway obstruction as a contributory mechanism for this unusual roentgenographic presentation of a congenital cystic malformation of the lung.This investigation was supported in part by a grant (RR-81) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health and by Grant HD-00049 from the National Institutes of Health     

Transseptal left heart catheterization: Experience with a new technique in 520 pediatric and adult patients

Summary A new technique for transseptal left heart catheterization utilizing the Transseptal Introducer Set® in 520 patients is described in detail. The age range of these patients was 3 months to 40 years with 30% of the patients less than 2 years old and 28% less than 10 kilograms in weight. The safety and advantages of the technique are emphasized. The introducer set and new technique make transseptal left heart catheterization a safe, versatile, and dependable approach to all areas of the left heart, particularly in infants and children with complex congenital heart lesions.Supported in part by grant HL-07190 from the National Institutes of Health, United States Public Health Service and by grant RR-00188 from General Clinical Research Branch, National Institutes of Health.Presented in part at 52nd Scientific Session of American Heart Association, November 12–15, 1979.     

Comparison of the cardiovascular action of isoproterenol,dopamine, and dobutamine in the neonatal and mature dog

Summary To determine if there are age-related differences of cardiovascular responses to isoproterenol, dopamine hydrochloride, and dobutamine hydrochloride, we recorded cardiac output, renal artery blood flow, central aortic blood pressure, and heart rate in 11 anesthetized puppies ranging in age from 0 to 10 days and in five adult dogs during incremental infusion of isoproterenol (0.05 to 1.25μg/kg/min), dopamine (2 to 50μg/kg/min), and dobutamine (2 to 50μg/kg/min). Isoproterenol decreased systemic arterial mean blood pressure and renal blood flow more in adult dogs than in puppies. Cardiac output was increased in both age groups, but the increase was more marked in adults than in puppies. Heart rate increased similarly in puppies and adults. Dopamine increased systemic arterial mean blood pressure, heart rate, renal blood flow, and cardiac output in both puppies and adult dogs, but the increase of cardiac output was more marked in adult dogs than in puppies. Dobutamine significantly increased systemic arterial mean blood pressure, cardiac output, and renal blood flow in adult dogs but not in puppies. Heart rate increased in both groups of dogs. This study demonstrates age-related differences in the response of the cardiovascular system of anesthetized dogs to isoproterenol, dopamine, and dobutamine. This material was developed by the Section of Myocardial Biology of the National Heart and Blood Vessel Research and Demonstration Center, Baylor College of Medicine, a grant-supported research project of the National Heart, Lung, and Blood Institute, National Institutes of Health, grant HL 17269 and contract HV-52998. Supported in part by grant HL-5756 from the National Institutes of Health. Dr. Driscoll is recipient of Young Investigator's Award 1-R23 H622309-01 from the National Heart, Lung, and Blood Institute. Dr. Gillette is recipient of National Institutes of Health Research Career Development Award HL00571. Presented at the Scientific Sessions of the American Academy of Pediatrics, Section of Cardiology, New York, New York, November 1977     

Paradoxical relationship between mitral valve prolapse and left ventricular function in Marfan's syndrome

Summary A child with Marfan's syndrome had cardiac failure during infancy. Aortic sinus aneurysms, mitral prolapse with severe regurgitation, and atrial septal defect were present. After myocardial infarction at age 4 years, the mitral prolapse became less and the regurgitation disappeared. After recovery of left ventricular function, mitral regurgitation reappeared. The unusual relationship between mitral valve and left ventricular function could be related to redundant chordae and leaflet. Myocardial infarction occurs in Marfan's syndrome even during childhood.Supported by grant RR-305 from the General Clinic Research Centers Program of the Division of Research Resources, National Institutes of Health, Bethesda, Maryland     

Congenital aortico-left atrial tunnel

Summary A newborn baby with heart failure had ventricular septal defect and aorto-left atrial communication. Aortography demonstrated a large funnel-shaped vessel originating from a dilated left aortic sinus and opening into the base of the left atrial appendage. Open heart surgery was unsuccessful. Histological examination (750 serial sections) of the vessel including the adjoining aorta and left atrial appendage showed no evidence of coronary artery structures. To our knowledge, this represents the first case of congenital aortico-left atrial tunnel.Supported in part by grant RR-305 from the General Clinical Research Centers Program of the Division of Research Resources and by grant HE-07605-17 from the National Heart Institute, National Institutes of Health, Bethesda, MarylandDr. Lev is a Career Investigator and Educator of the Chicago Heart Association.     

Cardiac Dysrhythmias in Pediatric Patients Before and 1 Year After Transcatheter Closure of Atrial Septal Defects Using the Amplatzer Septal Occluder

To prospectively assess the incidence of cardiac dysrhythmias before and after closure of atrial septal defects (ASDs) using the Amplatzer septal occluder (ASO), 24-hour Holter electrocardiograms (ECGs) were performed before and 1 year after the procedure in 23 pediatric patients (9 male and 14 female). Patients' ages ranged from 2 to 15 years (mean, 7.1 years). All had an ASD of the secundum type that was completely closed (n = 22) or had a small residual shunt (n = 1). No preexisting dysrhythmia was present in 22 patients; atrioventricular nodal reentrant tachycardia had been diagnosed in 1 patient. During the observation period, no clinical dysrhythmia occurred. Analysis of the Holter ECGs before the intervention showed regular sinus rhythm in 20 patients and sinus rhythm with intermittent atrial rhythm in 3 patients. Atrial premature complexes (APCs) were detected in 1 patient, and a ventricular couplet was present in 1 patient. The Holter ECG 1 year after the intervention showed sinus rhythm in 18 patients and sinus rhythm with intermittent atrial rhythm in 5 patients. APCs were still observed in 1 patient and seen for the first time in 1 patient; 1 patient and rare ventricular premature complexes. In conclusion, cardiac dysrhythmias on Holter ECG in pediatric patients before and 1 year after transcatheter ASD closure with the ASO device are rare and benign. Regular Holter monitoring seems to be useful in detecting late dysrhythmias.     

Dysrhythmias after the modified Fontan procedure

Summary The cardiac rhythm before and after the modified Fontan procedure was reviewed in 24 patients. Transient atrial dysrhythmias were common in the immediate postoperative period. Late postoperative premature atrial contractions were detected by ambulatory monitoring in 20 of 23 patients; eight (34.8%) had supraventricular tachycardia. Late ventricular dysrhythmia was detected in 18 of 23 patients: ten had low-grade ventricular dysrhythmias and eight (34.8%) had multiform premature ventricular contractions. Five of the latter had couplets and one of these five plus another had ventricular tachycardia. Seven patients with supraventricular tachycardia and five patients with ventricular dysrhythmia required antiarrhythmic medication. Asymptomatic bradycardia was detected in five patients (21.7%). One patient had intermittent second-degree atrioventricular block. No specific risk factors predicted dysrhythmias. Thus, cardiac dysrhythmias were common in patients after the modified Fontan procedure, but were well tolerated in most patients. No sudden deaths or syncopal episodes have occurred during a mean follow-up of 5 years. One patient's death was related to severe left ventricular dysfunction. Permanent pacing has not been required in any patient.     

Intestinal tuberculosis in a child in an affluent society

A rare case of intestinal tuberculosis occurring in a child in an affluent society is described. The radiographic appearances of the terminal ileum resembled those previously stated to be pathognomonic of Crohn's Disease.Academic Trainee in Diagnostic Radiology. Supported by grant GM 1707 of the National Institute of General Medical Sciences, National Institutes of Health, USPHS.     

Demonstration of vestibular implantation of ectopic ureters on an excretory urogram

The authors describe a patient in whom they demonstrated ectopic vestibular ureteral implantation on excretory urography. They indicate that this simple rechnique should be fully exploited before doing vaginograms or other more exotic examinations.Academic Trainee in Diagnostic Radiology. Supported by grant GM 1707 of the National Institute of General Medical Sciences, National Institutes of Health, USPHS.     

Sleep phase and gastro-oesophageal reflux in infants at possible risk of SIDS.

The association between gastro-oesophageal reflux and sleep state in 24 infants with confirmed or suspected gastro-oesophageal reflux was studied by monitoring both the pH in the lower oesophagus and polygraphic tracings made during sleep at night. Gastro-oesophageal reflux during the night was confirmed in 20 infants. Three hundred and sixteen precipitous drops of more than one unit of pH were recorded during the studies, 186 during periods of wakefulness. Of 130 drops in pH during sleep, 62 (48%) began during active sleep and 62 during indeterminate sleep. Of the latter, 56 (90%) were associated with brief gross body movements. Only five of the drops in pH (4%) began during quiet sleep. Gastro-oesophageal reflux stopped during active sleep on 56 occasions (43%), in indeterminate sleep in 62 (47%), and in quiet sleep in 12 (9%). Episodes of gastro-oesophageal reflux starting or ending in quiet sleep were uncommon. The occurrence of gastro-oesophageal reflux during active sleep may partly explain why reflux during sleep is a risk factor for pulmonary disease.     

Inducible polymorphous ventricular tachycardia following Mustard operation for transposition of the great arteries

Summary A 22-year-old woman with chronic atrial tachycardia following Mustard's operation for transposition of the great arteries presented with dizziness and ventricular tachycardia documented with dynamic 24-h electrocardiogram. During intracardiac electrophysiology study, programmed ventricular extrastimulation induced polymorphous ventricular tachycardia (torsades de pointes). This was prevented by intravenous administration of procainamide. We postulate that polymorphous ventricular tachycardia is a possible cause of death in patients with Mustard's operation. Postoperative electrophysiologic study may define those patients at risk to develop this potentially fatal arrhythmia.This work was supported in part by Institutional Training grant HL 07387 and research grants HL 18794 and HL 23566 from the National Institutes of Health, Bethesda, Maryland, and a grant from the Bane Estate, Chicago, Illinois.     

Growth hormone secretory patterns in children with short stature

To assess whether growth-retarded children with a stimulated growth hormone (GH) level greater than 10 ng/mL have an abnormality in spontaneous GH secretion, we measured GH levels every half hour for 24 hours in 50 children 2.7 to 17 years of age. Growth rate was subnormal in all. Mean 24-hour GH concentration ranged from 1.2 to 7.7 ng/mL, and was significantly greater in pubertal than in prepubertal children (P less than 0.01). In both groups, GH concentration during sleep was significantly greater than during wakeful hours (P less than 0.0005); 24-hour GH concentration correlated significantly with sleep-induced GH peak. A decrease in 24-hour GH concentration and sleep-induced GH peak were noted in four pubertal children with stimulated GH less than 15 ng/mL. A progressive and significant increase in somatomedin C (SmC) level was noted with increasing age and sexual development. No correlations were found between 24-hour GH concentration and rate of growth, age, or bone age. Serum SmC values correlated significantly with age and bone age (P less than 0.01), and with 24-hour GH concentration only in prepubertal children (P less than 0.05). A strong correlation between SmC and growth rate was noted only in pubertal children (P less than 0.01). Growth velocity increased significantly during GH therapy regardless of the 24-hour GH concentration. Our results indicate that in children with growth retardation there is a wide variation in 24-hour GH concentration and a significant increase in GH concentration during puberty; the GH concentration during nocturnal sleep, rather than an entire 24-hour GH concentration, can be used for evaluation; during puberty the SmC level reflects sexual development more than GH reserve; and GH therapy appears to increase growth velocity in both non-GH-deficient and partially GH-deficient short children.     

Recurrent Kawasaki disease

Summary This case report describes a boy who had Kawasaki disease (KD) at age 12 months and had a recurrence one year later. The coronary arteries were normal following the initial episode; however, during the second episode he developed coronary aneurysms. Gallium-67 radionuclide imaging, echocardiography, and angiography were used to diagnose the coronary abnormalities.This work was supported in part by grant RR-00188 from the General Clinical Research Branch of the National Institutes of Health, Bethesda, Maryland.     

Ventricular dysrhythmias in children with Marfan's syndrome

A teenager with Marfan's syndrome required resuscitation and was found to have multiform premature ventricular contractions and ventricular tachycardia. Of 24 children with Marfan's syndrome, eight (33.3%) were found to have ventricular dysrhythmias, including three with ventricular tachycardia. Six of these eight patients had mitral valve prolapse, and five had prolonged QT or QTU intervals corrected for heart rate. However, only two patients had severe mitral regurgitation, five had only mild heart disease, and one had no detectable heart lesion. The role of mitral valve prolapse and/or delayed repolarization in the development of ventricular dysrhythmia was explored. Delayed repolarization, especially when combined with mitral valve prolapse, is associated with occurrence of ventricular dysrhythmia. Serious ventricular dysrhythmia can occur in children with Marfan's syndrome with or without substantial valve disease, and the dysrhythmia appears to progress with age.     

Cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy

To assess the incidence and prognostic significance of cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy, the clinical course of 59 patients was retrospectively reviewed over a period of 27 years. Dilated cardiomyopathy (DCM) was diagnosed in 28 patients and hypertrophic cardiomyopathy (HCM) in 31 patients. The mean age at the time of diagnosis was 2.8±0.7 years in DCM patients and 6.7±0.8 years in HCM patients. Mean follow-up time after diagnosis of cardiomyopathy was 4.1±1.0 years in DCM patients and 6.6±0.8 years in HCM patients. Clinically significant cardiac dysrhythmias were found in 17 of 59 patients (29%): 7 of 28 patients (25%) with DCM and 10 of 31 patients (32%) with HCM. The initial diagnosis of a cardiac dysrhythmia was made by standard electrocardiography in 12 of 17 patients (71%) and by 24-hour Holter monitoring in 5 of 17 patients (29%). Ventricular dysrhythmias were present in 5 of 7 patients with dilated cardiomyopathy and in 5 of 10 patients with hypertrophic cardiomyopathy. During the follow-up time, death occurred in 18 of 59 patients (31%): 8 of 59 patients (14%) died from congestive heart failure and 10 of 59 patients (17%) died suddenly. Among the sudden deaths were 4 of 28 patients (14%) with dilated cardiomyopathy and 6 of 31 patients (19%) with hypertrophic cardiomyopathy. Cardiac dysrhythmias had been documented in 6 of the 10 patients dying suddenly (3 of 4 patients with DCM and 3 of 6 patients with HCM). It is concluded that (1) cardiac dysrhythmias are not a rare finding in children with idiopathic dilated or hypertrophic cardiomyopathy, and (2) their occurrence is not a predictor for sudden death.     

Developmental delay in infants with congenital heart disease

Summary The mental and motor development of 173 infants with congenital heart disease was assessed by means of the Bayley Scales of Infant Development and clinical neurological examinations. The relationship between age, sex, congestive heart failure, hypoxemia, hospitalization, and test results was evaluated. The presence of congestive heart failure was found to be significantly associated with both mental and motor developmental delay. Hypoxemia and hospitalization were associated with delayed motor development. Developmental delay could be recognized as early as 2 months of age. Supported in part by training grant HL 05855 and program project grant HL 10436 from the National Institutes of Health, Bethesda, Maryland     

Study of the conduction system in a population of patients with sudden infant death syndrome

Summary The conduction system of 23 infant hearts, 15 of sudden infant death syndrome (SIDS) and eight of those dying from known cause, was serially sectioned. A left-sided His bundle was found more commonly in (SIDS) (eight of 15) than in the controls (two of eight). Taking into account a previous study in which a left-sided His bundle was found in only four of 32 hearts from all age groups, this is statistically significant and may be a factor promoting SIDS.This research was aided by grant HL-30558-02 from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.     

Cardiac dysrhythmias after transcatheter closure of ASD with Amplatzer device

Transcatheter closure of atrial septal defect (ASD) has been used as an alternative to open heart surgery. Although transcatheter closure of ASD with the Amplatzer septal occluder is a safe and feasible method in pediatric patients, there is little published data on arrhythmia analysis following transcatheter device closure of secundum ASD. We evaluated cardiac dysrhythmias with 24-hour ambulatory electrocardiographic (ECG) monitoring after transcatheter closure of ASD with Amplatzer device. A total of 85 consecutive patients with ASD underwent transcatheter closure of secundum ASD with Amplatzer device between October 1998 and December 2003. The study involved 65 of these patients assessed by 24-hour ambulatory ECG monitoring. Seven patients were evaluated a second time by 24-hour monitorization. During the procedure, transient complete atrioventricular (AV) block was seen in two patients. One of them returned to normal sinus rhythm in catheterization lab and the other returned to normal sinus rhythm in two hours. Transient junctional rhythm was observed in another patient during the device placement. Twenty-four hour ambulatory ECG monitoring was performed on all patients after a mean four-month period (1-12 months). Holter recordings demonstrated rare supraventricular extrasystole in two patients, rare ventricular premature beats in two patients, and intermittent sinus arrest with sinus pause lasting <1.5 seconds in one patient, for a total of five patients (7.6%). In conclusion, dysrhythmias after transcatheter device closure of secundum ASD with Amplatzer device are rare and benign. We need further long-term follow-up to evaluate late dysrhythmias after the transcatheter device closure of secundum ASD.