The long-term goal of the proposed research is to ameliorate the harmful effects in children of absorbing moderate amounts of lead (Pb). In order to do this, we wish 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. Because of our multidisciplinary approach, we are concerned with the relationships between body burden of Pb and three type of outcomes. Body Pb burden is measured in three ways: 1) blood Pb concentrations, an index of recent exposure; 2) urinary Pb excretion during CaNa2EDTA provocative testing, an index of mobilizable Pb stores; and 3) x-ray fluorescence measurement of bone Pb, direct measurement of bone Pb that has accumulated over time. The outcome measures, that is, those affected by lead burden, include 1) biochemical abnormalities -- erythrocyte protoporphyrin levels (EP) in whole blood and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations in serum; 2) central nervous system dysfunction as indexed by auditory and somatosensory evoked potentials; and 3) behavioral deficits as indexed by global measures of intelligence as well as specific measures of attention and reaction time. A pre-/post-treatment design will allow 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 may exert its effects.
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