Danna Jennings

Estimating the half-lives of PCB congeners in former capacitor workers measured over a 28-year interval

To date, most estimates of the half-life of polychlorinated biphenyls (PCBs) in humans have been based on relatively short follow-up periods. To address this issue, we determined the half-lives of PCB congeners of occupational origin in the serum of former capacitor workers as part of a study conducted in 2003–2006 — approximately 28 years after their last occupational exposure. A total of 241 persons from a source population of 6798 former capacitor workers were interviewed and asked to donate a blood sample for serum PCB congener analysis. A subgroup of 45 participants also had serum archived from 1976 and reanalyzed for the same 27 PCB congeners by the same laboratory. Our estimates of the half-lives of the congeners among these 45 persons were longer than those reported by Wolff et al. (1992), due primarily to the much longer interval between exposure and determination of serum PCB concentrations. Half-lives were significantly greater for the heavy versus light occupational congeners, for women versus men and for those with low versus high initial exposure. Current serum total PCB concentrations, expressed as the geometric mean of wet weight data, averaged 6.7 ng/g for the entire 241-person cohort, which represents a 10-fold decrease from values reported in the late 1970s, but is still nearly twice the average for persons of similar age residing in the same area, but without occupational exposure. In addition, current serum PCB concentrations remained significantly and positively associated with earlier occupational exposure, but were not associated with fresh water fish consumption. In general, the results support a consistent and long-duration trend of increased PCB body burden in this cohort of former capacitor workers compared with non-occupationally exposed individuals. The results may aid in further understanding the toxicological/epidemiological consequences of exposure to PCBs in humans.

Molecular PET imaging in multicenter Alzheimer’s therapeutic trials: current trends and implementation strategies

Current therapeutic approaches for Alzheimer’s disease (AD) have evolved to target specific molecular biological, metabolic and neuropathologic hallmarks of the disease. Since these approaches are hypothesized to be most effective at the earliest stages of the degenerative process, the ability to accurately detect and monitor progression of AD pathology and metabolic changes in vivo may accelerate the discovery and development of disease-modifying drugs. The use of molecular imaging biomarkers can not only enhance diagnostic accuracy and facilitate patient selection/stratification, but can also serve as key outcomes for clinical trials. In this review, we discuss emerging trends in the use of PET in AD drug development and provide a roadmap for harnessing its promise in multicenter clinical trials.