Cardiac involvement in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated with a hypercoagulable state and fetal loss and with other clinical manifestations including cardiac involvement. Cardiac manifestations of APS are valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. Antiphospholipid antibodies (aPLs) may have a role in the accelerated atherosclerotic arterial disease observed in APS, related to their ability to induce endothelial activation. aPLs have been incriminated in the pathogenesis of heart valve lesions in APS patients. Markers of endothelial cell activation are up-regulated with prominent deposition of aPL in heart valves, suggesting aPL deposition initiates an inflammatory process that recruits complement leading to the valve lesion. Autoantibody-mediated endothelial cell activation probably plays a role in sustaining a proadhesive, proinflammatory, and procoagulant phenotype. The heterogeneity of APS clinical manifestations is likely linked to the varied effects that aPL can induce on endothelial cells and to the different functions that endothelial cells display depending on the anatomic localization.

Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report.

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.

Contrast-dependent responses in the human visual system: childhood through adulthood.

Visual evoked potentials (VEPs) to temporal modulation of spatial patterns, recorded from humans ranging in age from 4-42 years, demonstrated that contrast-dependent responses exist in early childhood and change dramatically throughout childhood. Bright or dark isolated-check stimuli were used to emphasize contributions from ON or OFF pathways to the VEP. (ON and OFF pathways constitute one major pair of parallel subsystems, which process brightness [positive-contrast] and darkness [negative-contrast] information, respectively.) The developmental effects observed for each pathway were similar in magnitude and time course, suggesting maturation of a common physiological mechanism dependent on spatial contrast. Children's responses were more variable and larger than those of adults, and exhibited a relative phase lag. In addition, we recorded transient VEPs to a conventional contrast-reversing checkerboard pattern. The latency of the major positive wave (P100) was found to decrease, while the latency of the initial positive wave (P60) was found to increase, with increasing age. We propose a vector-summation model, which posits a relative decrease in cortical excitation with increasing age, to explain our major findings.