A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents.

Introduction: Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation (SI) across adolescence.

Methods: Mega-analysis of pooled genetically informative data on SI was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N = 19 313 pairs) between ages 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the United States, Europe, and Australia.

Results: Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of SI across developed countries.

Hoarseness as the initial clinical presentation of anomalous left coronary artery from the pulmonary artery.

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital anomaly that, if left untreated, will most often result in severe myocardial ischemia and significant morbidity and mortality. We report an unusual presentation of this defect in a 2-month-old infant who had an initial complaint of a "hoarse cry." We theorize that impingement of the recurrent laryngeal nerve due to dilatation of the pulmonary artery was the most likely etiology of the patient's symptoms.

Autoregulation of cerebral blood flow in fetuses with congenital heart disease: the brain sparing effect.

Fetuses with congenital heart disease (CHD) have circulatory abnormalities that may compromise cerebral oxygen delivery. We believe that some CHD fetuses with decreased cerebral oxygen supply have autoregulation of blood flow that enhances cerebral perfusion (brain sparing). We hypothesize that cerebral autoregulation occurs in CHD fetuses, and the degree of autoregulation is dependent on the specific CHD and correlates with intrauterine head circumferences.

Balloon dilation of discrete subaortic stenosis associated with other cardiac defects in children.

Balloon dilation (BD) is reported as an effective treatment for isolated discrete thin membranous subaortic stenosis (SAS). We asked if BD of SAS with associated cardiac defects: 1) is effective; 2) creates or worsens mitral insufficiency in the presence of valvar membrane attachment; and 3) creates or worsens aortic insufficiency. BD was performed on 13 patients (9 females, 4 males with a mean age of 5.

Childhood passive smoking, race, and coronary artery disease risk: the MCV Twin Study. Medical College of Virginia.

Background: Children with long-term exposure to passive cigarette smoke may be at elevated risk for the development of premature coronary artery disease (CAD).

Objective: To examine how CAD risk factors, exposure to passive smoking, sex, and race are related in pubertal children and to determine if there is an identifiable childhood risk profile (i.e.

Models for the longitudinal genetic analysis of same-age twins: application to HDL cholesterol.

Models are presented for the analysis of longitudinal data from same-age twins which permit the exploration of a remarkably diverse array of alternative explanations for continuity and change during development. Data of this type permit the detection of new sources of genetic or environmental covariation during development that are not expressed at earlier ages and, because they include the effects of age-specific genes, the resulting heritability estimates are more reliable than those obtained from relatives who differ in age. The proposed models were applied to measurements of HDL cholesterol obtained on 81 pairs of monozygotic (MZ) twins and 69 dizygotic (DZ) pairs at 11, 12.

Tracking of left ventricular mass in children: race and sex comparisons: the MCV Twin Study. Medical College of Virginia.

Background: Increased left ventricular (LV) mass is a predictor of cardiovascular disease in adults. The mechanism(s) for these observations are not fully understood.

Methods And Results: We repeatedly studied a biracial sample of children from ages 11 through 17 years.

Age changes in the causes of individual differences in conservatism.

Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780 dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores derived from a 28-item social attitude inventory.

Genetic regulation of hemodynamic variables during dynamic exercise. The MCV twin study.

Background: Both resting and exercise levels of blood pressure in individuals have been used as predictors of adult hypertension. One possible mechanism underlying the relation between childhood resting and exercise blood pressure and future blood pressure is a set of genes expressed in childhood that persists to regulate adult blood pressure.

Methods And Results: To investigate the genetic relation of blood pressure and heart rate during both rest and exercise, we asked: (1) Are the genes that regulate resting hemodynamic variables the same genes that regulate these variables during exercise? (2) How much of the variance in exercise hemodynamic variables is genetic and how much is environmental? (3) Do the genetic and environmental influences on hemodynamic responses change with increasing levels of exercise? To determine how genetic and environmental effects expressed at rest influenced responses during dynamic exercise, a genetic analysis was conducted by fitting a series of models to the covariance matrices with the use of the LISREL VII program.

Advances in preventive cardiology.

Since the publication of the Report of the Expert Panel on Blood Cholesterol in Children in 1991, both multi-institutional and office-practice-based studies have attested to its diet recommendations' safety and efficacy in modestly lowering blood cholesterol. Normal growth was preserved. Investigators have found no aberrations of either macro- or micronutrients.

Modulation of atrial repolarization by site of pacing in the isolated rabbit heart.

Background: Single-site or multisite atrial pacing may reduce the incidence of atrial fibrillation in humans. The therapeutic mechanisms may include synchronization of atrial repolarization (repolarization "memory") and/or decreased dispersion of atrial repolarization. These responses have not been well documented in intact atria.

Genetic influences on ambulatory blood pressure patterns. The Medical College of Virginia Twin Study.

The genetic influence of ambulatory blood pressure and heart rate was examined in 38 pairs of monozygotic twins, 17 pairs of same-sex dizygotic twins, and 11 pairs of opposite-sex dizygotic twins, all aged 15 or 17 years. The data were analyzed taking into consideration that the response was multivariate (24-h values) instead of the usual univariate response. The results demonstrated the heritability of ambulatory blood pressure and heart rate.

New perspectives in childhood blood pressure.

Ambulatory blood pressure monitoring is a new technique available to the pediatric cardiologist, and several studies have investigated its usefulness. Investigators are now providing data for both normal values and reproducibility. Other authors have examined the effects of hypertension in mothers upon their offspring, which include small birthweight and possible developmental delay.

Altered blood pressure reactivity in adolescent diabetics.

Objective: We examined hemodynamic responses to a variety of physiologic stimuli in 14 normotensive adolescents with type I diabetes and 45 healthy controls to determine whether structural vascular changes contribute to a reduced vasodilator capacity in adolescent diabetics. We asked, in adolescents with type I diabetes: (1) Are structural vascular changes present? (2) Are changes in the systemic vascular bed reflected in abnormal blood pressure regulation? and (3) Is abnormal vascular reactivity associated with either diabetes duration or control?

Methodology: Diabetic subjects were outpatients treated at the Medical College of Virginia, ages 13 to 18 years. Diabetes duration averaged 7.

Hypertension and atherosclerosis in children.

This article reviews important advances in the understanding and treatment of hypercholesterolemia and persistently high blood pressure in children. Two plant sterols, sitosterol and sitostanol, have been tested in prepubertal and adolescent children with hypercholesterolemia and appear promising. The advantages and disadvantages of family history in screening algorithms for atherosclerotic disease are discussed.

Cardiovascular reactivity in isometric exercise and mental arithmetic in children.

In children, we studied noninvasively the cardiovascular stress responses, including changes over time of systolic blood pressure (SBP), heart rate (HR), and stroke volume (SV) in isometric handgrip (IHG) and mental arithmetic. Specifically, we asked whether 1) these cardiovascular stress responses were different for the two stress conditions in children, 2) these responses differed in boys and girls, and 3) the anthropometric variables related to these stress responses. SV differed significantly between IHG and mental arithmetic over the entire stress period.

Investigation of the influences of puberty, genetics, and environment on the composition of subgingival periodontal floras.

The classical twin model was utilized in this study in an attempt to determine the importance of host genetics to the composition of the subgingival flora. Simultaneously, the effect of puberty on the flora composition was assessed. The compositions of the floras were significantly different at ages 11 and 14 in the same people, indicating that transition to an adult flora composition may be initiated during puberty.

Univariate genetic analysis of oxygen transport regulation in children: the Medical College of Virginia Twin Study.

We investigated the relative contributions of genetic, individual environmental, and shared environmental effects on 2,3-diphosphoglycerate (DPG) regulation in preadolescent children. In a population of 165 early pubescent boy and girl twin pairs (11.4 y old), of whom 63 were passive smokers, we asked: 1) Are there differences in the control of DPG levels between early pubertal boys and girls? 2) If present, are these differences influenced by exposure to passive cigarette smoke? Non-passive-smoking boys and girls had similar DPG levels.

Common fragile site expression in lymphocytes from an individual mosaic for trisomy 8.

During the course of a survey of fragile site expression in lymphocytes from twins one member of a dizygotic pair was found to be mosaic for trisomy 8. One hundred fifty metaphases from this individual were analyzed (100 treated with aphidicolin and 50 untreated); 43% were 46,XY and 57% 46,XY,+8. No differences were observed between the treated and control cultures in either the proportions of normal and trisomic metaphases or the overall or specific fragile site expression in the normal and trisomic cells.

Genetic factors that predispose the child to develop hypertension.

Familial aggregation, population, and twin studies all point to important genetic influences on the level of blood pressure in childhood and adolescence. Whether a major gene effect operates during childhood has not been determined. The investigation of polygenic paths leads to the study of variables such as ion transport and reactivity paths that appear to be under strong genetic influences.