The long-term goal of the proposed research is to ameliorate the harmful effects of increased lead (Pb) absorption in children. To this end, we will continue to assess the biochemical and functional consequences of moderate body burdens of Pb in young children within a comprehensive clinical research program focused on the effects of chelation treatment. Our multidisciplinary approach focuses on the relationships between body burden of Pb and three types of outcomes. Body Pb burden is being measured in three ways: 1) blood Pb concentrations, an index of recent exposure; 2) urinary Pb excretion during CaNa2 EDTA testing, an index of mobilzable Pb stores; and 3) L x-ray fluorescence determination of bone Pb, a direct, non-invasive and quantitative measure of bone Pb that has accumulated over time. The outcome measures are those which are affected by lead burden. these include: 1) biochemical abnormalities -- erythrocyte protoporphyrin levels (EP) in whole blood and 1,25- dihydroxyvitamin D (1,25-(OH)2D) and osteocalcin concentrations in serum; 2) central nervous system dysfunction as indexed by auditory and somatosensory evoked potentials; and 3) behavioral deficits as reflected by global measures of intelligence in addition to specific measures of attention and reaction time. A pre-/post-treatment design is permitting us to describe the effects of treatment on multiple outcomes over time, to make inferences about the effects of moderate Pb toxicity on children's brain function and behavior, and to explore different means by which Pb exerts its toxic effects.
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