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The past, present and future of childhood lead poisoning. Two Thousand Years of Lead Poisoning 1st Century AD. Dioscerides: Lead makes the mind give way 1763. Benjamin Franklin:Lead in painters, printers and tinkers 1830 Charles Dickens: Uncommercial Traveler
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Two Thousand Years of Lead Poisoning • 1st Century AD. Dioscerides: Lead makes the mind give way • 1763. Benjamin Franklin:Lead in painters, printers and tinkers • 1830 Charles Dickens: Uncommercial Traveler • 1892. Brisbane Australia: Childhood lead poisoning described • 1943. Randolph Byers: Long term effects • 1991. PHS Strategic Plan • 1993: NAS Report
Five Phases of Lead Toxicology • There is no such thing as childhood lead poisoning. (1892)
J Lockhart Gibson Gibson
Five Phases of Lead Toxicology • It exists, but if it doesn’t kill you, it doesn’t touch you (1943)
Byers Byers
Five Phases of Lead Toxicology • There are long term effects, but only in children with severe symptoms (1979) • Silent lead exposure has long term consequences • Lead exposure is associated with antisocial behavior
Flaws in Early Studies • Inadequate exposure markers • Screening or group measures of outcome • Inadequate control of confounders • Potential selection bias
Responses to Design Issues • Replaced blood with dentine • Tested 3500 teeth from 2500 subjects in primary school • Measured 40 covariates; adjusted for those that were associated with exposure
Newer Studies • Lanphear et al.Cognitive deficits associated with blood lead concentrations <10 microg/dL in US children and adolescents.Public Health Rep. 2000 • Canfield et al Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.NEJM 2003 • Bellinger and Needleman Intellectual impairment and blood lead levels NEJM 2003
Clues to the Lead/Delinquency link Race Urban residence Low IQ ADHD Moffit’s studies
Case-Control Study • 195 adjudicated delinquents, 155 controls • Bone lead levels • Cases 11ppm±32ppm • Controls 1.5 ± 32ppm • 10 variates controlled in the analysis • Odds ratio 4.0 ( 1.4-11.1) • Population attributable risk: 11%-38%
The Nature of Aging • A reduction in molecular fidelity over time exceeding the organism’s repair capability • Due to the inherent thermodynamic instability of complex molecules
Processes Associated with the Aging Process • DNA mutations • ROS damage • Mitochondrial damage • Shortening of telomeres
Toxic Expressions of Lead • Mutations: Klug’s findings • Mitochondrial damage • ALAD and mitochondria • Heme deficiency and neuronal decay
Lead and Telomerase • Sheng Wu Hua Xue Yu Sheng WU Wu Li Xue Bao( Shanghai) 2002 34: 240-4
Risk factors Common to Alzheimer’s and Lead • Race • Urbanization • Autopsy findings: Niklowitz • Apoptosis • Fetal exposure and later disease
Reasons for Persistence of Lead Poisoning • Belief that it is a poor black problem • Belief that it is a problem of poor child rearing • Belief that the problem has been solved • Lack of interest by academic pediatrics • Efforts of lead industry to disguise the problem • Belief that we cannot afford to solve the problem
When a thing was new, people said: • “It’s not true.” • When it was shown to be true, people said: • “It’s not important.” • And when its importance could no longer be denied, people said:“Anyway, it’s not new.” • William James