Alopecia areata: genetic complexity underlies clinical heterogeneity.

Alopecia areata is a complex, non-scarring hair loss disease that affects approximately 1-2% of the population. The etiology of AA is unknown, although both genetic factors and environmental agents are thought to contribute to the immune disregulation leading to the final pathways of disease. Here, we examine the complex interplay of genetic and non-genetic factors that, no doubt, underpin the wide-ranging clinical expression of AA. We further discuss emerging strategies and tools that promise to better define the genetic basis of disease and reveal novel targets for next generation therapies.

Effect of cardiac resynchronization therapy on diastolic dysfunction as assessed by transthoracic two-dimensional Doppler echocardiography.

Cardiac resynchronization therapy (CRT) in patients with left ventricular systolic dysfunction and electrical dyssynchrony has been shown to improve morbidity and mortality. Improvement in diastolic dysfunction may contribute to these results. In this retrospective study, the authors assessed the effect of CRT on the E/A ratio and mitral valve deceleration time, which are commonly utilized parameters of left ventricular diastolic function. In 13 patients (aged 62 +/- 11.3 years), the E/A ratio increased from 1.17 +/- 0.58 to 1.49 +/- 0.66 (p = nonsignificant) and the mitral valve deceleration time increased from 178.48+/-57.71 milliseconds to 227.70 +/- 76.18 milliseconds (p = 0.054) post-CRT. In patients without mitral regurgitation, there was a significant increase in E/A ratio, from 1.22 +/- 0.4 to 1.86 +/- 0.47 (p = 0.025), but no significant change in the mitral valve deceleration time post-CRT was observed. These data suggest improvement in diastolic dysfunction as assessed by routine two-dimensional echocardiography in patients who receive CRT devices.

Clinical applications of DNA microarray analysis.

Microarray technology provides a revolutionary macro-genetic and bioinformatic-rich platform for understanding human diseases. DNA microarrays facilitate the study of complex diseases, enabling several observations simultaneously that can become foundations for newer hypotheses-shifting us towards a non-reductionist approach to biological phenomenon. This appears of particular value for scientific and clinical dissection of tumor pathologies. Despite the tremendous potential presented by microarray technology for the investigation of disease, concrete insights and advances that translate to the clinical setting are only recently beginning to be tapped. Here, we discuss specific examples of how microarray technology is being integrated into our ever-evolving approach to clinical disease. We focus on molecular strategies for (a) disease classification, (b) disease outcome, and (c) disease mechanisms.

Alopecia areata: autoimmune basis of hair loss.

Alopecia areata (AA) is a heterogeneous disease characterized by nonscarring hair loss on the scalp or any hair-bearing surface. A wide range of clinical presentations can occur -- from a single patch of hair loss to complete loss of hair on the scalp (alopecia totalis) or the entire body (alopecia universalis). Particularly in severe or chronic cases, AA may cause considerable psychological and emotional distress for affected individuals. The estimated lifetime risk of developing AA is 1.7%. While the precise etiology of this common disorder has not been elucidated, a substantial body of evidence suggests that AA is an organ-specific, autoimmune disease, targeted to hair follicles. However, the antigenic target(s), mechanisms, and consequences of autoimmune attack in AA have yet to be determined. Here, we critically explore the evidence supporting the hypothesis that AA is an autoimmune disease and propose specific pathways by which self-directed immune responses are generated.