Stephen J. Chanock

Cardiovascular manifestations of human immunodeficiency virus infection in infants and children

Thirty-one pediatric patients with human immunodeficiency virus infection were prospectively evaluated using 2-dimensional and M-mode echocardiography, Doppler cardiography, electrocardiography and Holter monitoring. Left ventricular shape, wall motion and valve morphology were evaluated with 2-dimensional echocardiography. Valve function was assessed using Doppler cardiography. Left ventricular performance was evaluated with shortening fraction, afterload with end-systolic wall stress and contractility with the end-systolic wall stress and rate-corrected velocity of shortening relation. Although left ventricular performance, afterload and contractility varied widely, 2 patterns of left ventricular function abnormalities were noted. Hyperdynamic left ventricular performance, generally with enhanced contractility and reduced afterload, was the most common echocardiographic finding (63%). Diminished contractility was noted in 8 patients (26%), including 4 patients with symptomatic dilated cardiomyopathy. Serial echocardiographic evaluation revealed changes from the original level (elevated, normal or depressed) of left ventricular function, afterload or contractility in 89%. Pericardial effusion without tamponade was seen in 8 patients (26%). Mononuclear pericarditis, myocarditis and inflammation of the intracardiac conduction tissue as well as peripheral nerve were seen in autopsy specimens, yet histologic or culture evidence of myocardial infection with opportunistic organisms was lacking. High grade atrial (1 patient) and ventricular (3 patients) ectopy, as well as second-degree atrioventricular block, were observed. Cardiac abnormalities, detectable by noninvasive methods but often clinically inapparent, appear to be common in children with human immunodeficiency virus infection and may cause symptoms or even death.(ABSTRACT TRUNCATED AT 250 WORDS)

Scanning the horizon: What is the future of genome-wide association studies in accelerating discoveries in cancer etiology and prevention?

Genome-wide association studies using recently developed large scale single nucleotide polymorphism platforms are beginning to be performed, and results reported. Initial indications are that these studies are capable of discovering loci associated with relative risks too modest to have been detectable through family-based linkage studies. However, as these studies initially test 500,000 or more polymorphisms in a first series of cases and controls, the need for robust replication in one, or preferably, several independent studies is paramount to winnow out the true positive results from the large number of expected false positives. We discuss the need for the formation of consortia to conduct these multi-stage studies, and stress the importance of full disclosure of allele frequencies in cases and controls from these studies in order to facilitate joint analyses across datasets to speed discovery of reproducible associations, and to explore more complex associations such as gene-gene interactions. Desirable characteristics of studies in which genome-wide association studies will be most informative are discussed. The validation of genetic variants that alter risk of specific cancers may be relevant to screening, the identification of high risk persons for risk-reducing interventions, and the discovery of new biological mechanisms that may provide insight into cancer causes and preventive strategies.