William A. Neal

An Alternative Method for Repair of Partial Anomalous Pulmonary Venous Connection to the Superior Vena Cava

The surgical management of 15 patients with partial anomalous pulmonary venous connection (PAPVC) to the high superior vena cava (SVC) is described. This new technique redirects the anomalous pulmonary venous flow into the left atrium through the cardiac end of the SVC, transected and oversewn above the anomalous pulmonary vein or veins, by coaptation of the atrial septal defect (or of the surgically created septal defect in patients with an intact atrial septum) to the intracardiac orifice of the SVC. Normal SVC-right atrial flow is reconstituted by atriocavoplasty to the cephalad portion of the transected SVC. A 31-year-old woman with severe pulmonary hypertension died early in the series; this was the only death. Surviving patients enjoy full activity. Except for one symptomatic SVC obstruction due to technical error (since relieved), this technique has achieved total correction of these congenital defects with marked reduction in the undesirable postoperative sequelae often associated with other methods of repair.

Effects of an exercise intervention using Dance Dance Revolution on endothelial function and other risk factors in overweight children.

OBJECTIVE To determine whether an exercise intervention using an active video game (Dance Dance Revolution [DDR]) is effective in improving endothelial dysfunction (EDF) and other risk factors in overweight children. DESIGN Thirty-five children (Body mass index > or = 85(th) percentile, mean age 10.21+/-1.67 years, 17 females) with EDF were assessed for flow-mediated dilation (FMD), lipids, insulin, glucose, NO(2)+NO(3), asymmetric dimethylarginine, symmetric dimethylarginine, l-arginine, height, weight, aerobic fitness, and blood pressure. In a subsample, tumor necrosis factor alpha, interleukin-6, C-reactive protein, and adiponectin were also assessed. Subjects were randomly assigned to 12-weeks of aerobic exercise (EX) using DDR or to a non-exercising delayed-treatment control group (DTC). RESULTS EX had significant improvements in FMD ( 5.56+/-5.04% compared with 0.263+/-4.54%, p=0.008), exercise time on the graded exercise test (53.59+/-91.54 compared with -12.83+/-68.10 seconds, p=0.025), mean arterial pressure (MAP) (-5.62+/-7.03 compared with -1.44+/-2.16 mmHg, p=0.05), weight (0.91+/-1.53 compared with 2.43+/-1.80 kg, p=0.017) and peak VO(2) (2.38+/-3.91 compared with -1.23+/-3.18 mg/kg/min, p=0.005) compared with the DTC. Thirteen EX subjects achieved normal EDF while ten did not. These groups differed at baseline with regard to total cholesterol (TC) and low-density lipoprotein (LDL). CONCLUSION Twelve weeks of DDR-use improved FMD, aerobic fitness, and MAP in overweight children. Improvements occurred without changes in inflammatory markers or nitric oxide production. The results document the need to explore relationships between obesity, endothelial function, inflammation, lipids, exercise intensity, and gender in a larger sample of overweight children.

Metabolic Abnormalities in Children with Asthma

RATIONALE Childhood asthma and obesity have reached epidemic proportions worldwide, and the latter is also contributing to increasing rates of related metabolic disorders, such as diabetes. Yet, the relationship between asthma, obesity, and abnormal lipid and glucose metabolism is not well understood, nor has it been adequately explored in children. OBJECTIVES To analyze the relationship between asthma diagnosis and body mass in children across the entire range of weight percentile categories, and to test the hypothesis that early derangement in lipid and glucose metabolism is independently associated with increased risk for asthma. METHODS Cross-sectional analysis of a representative sample of public school children from a statewide community-based screening program, including a total of 17,994 children, 4 to 12 years old, living in predominantly rural West Virginia, and enrolled in kindergarten, second, or fifth grade classrooms. MEASUREMENTS AND MAIN RESULTS We analyzed demographics; family history; smoke exposure; parent-reported asthma diagnosis; body mass index; evidence of acanthosis nigricans as a marker for developing insulin resistance; and fasting serum lipid profile including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Regardless of their body mass index percentile, children diagnosed with asthma were more likely than children without asthma to have higher triglyceride levels and acanthosis nigricans after controlling for sex differences and smoke exposure. CONCLUSIONS This study provides the first set of community-based data linking asthma, body mass, and metabolic variables in children. In particular, these findings uniquely describe a statistically significant association between asthma and abnormal lipid and glucose metabolism beyond body mass index associations.

Universal versus targeted blood cholesterol screening among youth: The CARDIAC project.

OBJECTIVES: The goal was to determine the sensitivity and specificity of family history in identifying children with severe or genetic hyperlipidemias in a rural, predominantly white population. METHODS: A total of 20266 fifth-grade children in West Virginia, from the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project, who completed a family history and fasting lipid profile were used in analyses. The relationship between hyperlipidemia and family history was determined, and the use of family history to predict the need for pharmacologic treatment among children with dyslipidemia was evaluated. RESULTS: A total of 71.4% of children met the National Cholesterol Education Program (NCEP) guidelines for cholesterol screening on the basis of positive family history. Of those, 1204 (8.3%) were considered to have dyslipidemia (low-density lipoprotein ≥130 mg/dL), and 1.2% of these children with dyslipidemia warranted possible pharmacologic treatment (low-density lipoprotein ≥160 mg/dL). Of the 28.6% who did not have a positive family history (did not meet NCEP guidelines), 548 (9.5%) had dyslipidemia, 1.7% of whom warranted pharmacologic treatment. Sensitivity and specificity data demonstrated that family history does not provide a strong indication as to whether pharmacologic treatment may be warranted. CONCLUSIONS: Results indicate that the use of family history to determine the need for cholesterol screening in children would have (1) missed many with moderate dyslipidemia and (2) failed to detect a substantial number with likely genetic dyslipidemias that would require pharmacologic treatment. The use of universal cholesterol screening would identify all children with severe dyslipidemia, allowing for proper intervention and follow-up and leading to the prevention of future atherosclerotic disease.

Patent ductus arteriosus complicating respiratory distress syndrome

PDA was diagnosed in 76 (19%) of 396 patients with RDS. Evidence of excessive pulmonary blood flow and CHF developed in 15 (20%). CHF was not recognized prior to 10 days of age in any patient. All 15 with CHF were initially managed medically. Seven improved; three died of other causes. Five patients who failed medical management were surgically treated; all survived operation, but only two were improved.

Comparative Study of Clinical Evaluation of Heart Murmurs by General Pediatricians and Pediatric Cardiologists

In a study to compare the clinical diagnostic skills of academic general pediatricians and academic pediatric cardiologists in the evaluation of heart murmurs, a total of 128 patients (aged 1 month to 18 years) newly referred to a university pediatric cardiology clinic were evaluated by one of three general pediatricians and one of four pediatric cardiologists. The murmurs were clinically classified as innocent, pathologic, or possibly pathologic. The classification was revised after the review of electrocardiogram (EKG) and chest radiograph (CXR), if indicated. The definitive diagnosis was ascertained by echocardiography (94 normal, 34 abnormal). The general pediatricians identified as many pathologic heart murmurs as the pediatric cardiologists (27/34 vs. 29/34), with no difference in sensitivity, 79% vs. 85% (p=0.53). The similarity in sensitivity could be because the general pediatricians were more cautious in the classification of heart murmurs and had classified more innocent heart murmurs as pathologic than the pediatric cardiologists (13/39 vs. 3/23), 41% vs. 13% (p=0.02). The pediatric cardiologists correctly identified more innocent murmurs than general pediatricians (52/94 vs.72/94), with a better specificity, 55% vs. 76% (p=0.001); however, the accuracy of prediction of innocence was similar for both groups (52/59 vs. 72/77), 88% vs. 93% (p=0.36). The revision of diagnosis with review of EKG and CXR was more often misleading than helpful for either group. Academic general pediatricians would identify most of the pathologic murmurs and are no more likely than an academic pediatric cardiologist to misclassify a pathologic heart murmur as innocent. Clin Pediatr. 1999;38:511-518

Luminol-dependent chemiluminescence analysis of opsonophagocytic dysfunctions

Abstract The use of luminol as a means of amplifying the native chemiluminescence responses of phagocytosing human polymorphonuclear leukocytes was studied. Parameters examined included the effects of luminol, leukocyte and particle (opsonized zymosan) concentration on luminol-dependent chemiluminescence response. The results indicate that all of the parameters studied influence the luminol-dependent chemiluminescence assay system and that, on the basis of experiments designed to assess both opsonic and phagocytosis defects, this system appears to reflect the same or similar metabolic events as does native chemiluminescence. The luminol-dependent chemiluminescence assay represents a significant improvement of the phagocyte chemiluminescence assay in that greater sensitivity is possible, and may therefore have clinical utility as a means of evaluating phagocytic function.

Treatment Gaps in Adults with Heterozygous Familial Hypercholesterolemia in the United States: Data from the CASCADE-FH Registry

Background— Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. Methods and Results— We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received >1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C <100 mg/dL and 41% achieved a ≥50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08–2.82) and hypertension (2.48; 1.92–3.21). Factors associated with a ≥50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86–28.86) and use of >1 LDL-lowering medication (1.80; 1.34–2.41). Conclusions— FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors.

Assessing BMI in West Virginia Schools: Parent Perspectives and the Influence of Context

West Virginia is a state at the forefront of the obesity epidemic and one that is experiencing immense health and economic costs as a result. The childhood obesity research discussed in this article was conducted over the past 10 years through 4 projects that range from a school-based cardiovascular risk screening program to an evaluation of state legislation targeting childhood obesity via modifications in the school environment. In the course of these projects, we have collected BMI and other health indices on students, provided feedback to students and their parents, and assessed the obesity and health-related beliefs of West Virginians through individual and focus-group interviews and questionnaires. Our work has been accomplished by using an active-consent process, and BMI has typically been only 1 component of the comprehensive health data we collect and feedback we provide. Collaboration with state and local partners and regular dissemination of our findings have been key elements of the approach taken. The research and policy implications of our findings and approach are discussed.

Metabolic syndrome in fifth grade children with acanthosis nigricans: results from the CARDIAC project

BackgroundA number of cardiovascular disease (CVD) risk factors have been linked to obesity and associated negative health outcomes in children. However, no consistent definition of metabolic syndrome exists for children. In addition, research is needed to systematically examine the prevalence of metabolic syndrome in high-risk children, including those with insulin resistance. This study explores several definitions of metabolic syndrome and determines the prevalence of metabolic syndrome in a large sample of children with acanthosis nigricans (AN).MethodsThe study used results from a large-scale screening of fifth-grade students in West Virginia to explore the prevalence of metabolic syndrome among 676 male and female participants who had mild to severe AN.ResultsIn this high-risk sample of students who had AN, 49% met the criteria, i.e., three risk factors including insulin resistance, high body-mass index, and elevated blood pressure or dyslipidemia, when tested for metabolic syndrome. Children with AN who were classified as obese or morbidly obese were at significantly increased odds of having metabolic syndrome.ConclusionsResults are discussed in terms of systematically defining metabolic syndrome for high-risk children, as well as public health and clinical interventions targeting children who are overweight or obese. The presence of AN and morbid obesity might be easily observed markers for metabolic syndrome.