Echocardiographic prevalence of mitral and/or aortic regurgitation in patients exposed to either fenfluramine-phentermine combination or to dexfenfluramine.

We evaluated the prevalence of valvular regurgitation in patients who have taken anorectic medications. Two-dimensional echocardiograms with color flow Doppler were recorded in 200 consecutive patients referred to a major metropolitan hospital for evaluation of cardiac function because of a history of anorectic medication use. Each patient filled out a questionnaire at the time of the visit or through telephone contact. Each echocardiogram was reviewed by 2 observers. The degree of valvular regurgitation was graded by a consensus of both observers. Significant valvular regurgitation was defined as at least moderate mitral regurgitation (MR) or at least mild aortic regurgitation (AR), as recommended by the Food and Drug Administration and Centers for Disease Control and Prevention. For all patients having taken anorectic drugs, there was a 5% prevalence of at least moderate MR, a 12% prevalence of at least mild AR, and a 16% prevalence of significant MR and/or AR. Patients with significant AR and/or MR were older than those without significant valvular regurgitation (49+/-12 vs 44+/-11 years, p = 0.03). Patients with significant MR and/or AR had a longer exposure duration (8 vs 6 months, p = 0.049) to anorectic drugs. There was no difference in weight loss between those with and without significant regurgitation (p = NS). The 2 largest subgroups were patients who took the fenfluramine-phentermine combination (n = 127) and those who took dexfenfluramine alone (n = 42). The prevalence of significant MR and AR was 5% and 9% for the fenfluramine-phentermine group and 0% and 14% for the dexfenfluramine group, respectively. There was also a high subthreshold level of MR and AR in these patients.

Immunolocalization of the amyloid precursor protein within the senile plaque.

The isolation and sequencing of three transcripts for the precursor of the cerebral amyloid of Alzheimer disease have greatly facilitated understanding the relationship of the amyloid precursor protein (APP) to its 42 amino acid residue fragment (beta-protein or A4) which composes amyloid fibrils. In this study, we have used the 695 amino acid residue sequence described by Kang and co-workers to prepare antisera to synthetic peptides corresponding to various regions of APP in order to identify localized concentrations of this protein in cerebral cortex in cases of Alzheimer disease. We found that antisera to APP regions outside those of the amyloidogenic beta protein recognize diffuse non-congophilic plaques. While these antisera did not recognize the congophilic senile plaque core, they did recognize a halo surrounding them. Interestingly, cell processes were often identified in this halo region. In contrast, those antisera raised to sequences contained within beta-protein recognized both congophilic amyloid cores as well as non-congophilic diffuse plaques. Our findings suggest that accumulation of APP precedes development of and probably defines the senile plaque and the site of APP processing.