PON1 lactonase activity and its association with cardiovascular disease.

BACKGROUND: Paraoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates. MATERIALS AND METHODS: Activity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls. An ordered logistic-regression analysis of PON1 phenotypes was performed in the CVD group with respect to the control group. RESULTS AND CONCLUSIONS: Logistic-regression analysis showed that CC-108 genotype was associated with CRF and CVD. The CVD group had the lowest activities of PON1. The LACase might be a better biomarker for CVD (OR, 0.52; 95% CI, 0.44-0.61) followed by CMPAse (OR, 0.82; 95% CI, 0.77-0.86), AREase (OR, 0.98; 95% CI, 0.97-0.99) and PONase (OR, 0.99, 95% CI, 0.99-0.99). Logistic regression of PON1 phenotypes by haplotypes showed that LACase activity was not influenced by the polymorphisms and that it could be a new potential biomarker in the development of CVD. Larger scale longitudinal studies are required.

AKRs expression in peripheral blood lymphocytes from smokers: the role of body mass index.

Aldo-keto reductases (AKRs) metabolize a wide range of substrates, including polycyclic aromatic hydrocarbons (PAHs), generating metabolites (o-quinones) and reactive oxygen species (ROS), which are capable of initiating and promoting carcinogenesis. Exposure to PAHs, their metabolites, and ROS further increase AKRs isoform expression that may amplify oxidative damage. Human AKR enzymes are highly polymorphic, and allelic variants may contribute to different AKRs expression in individuals. Despite the importance of AKRs in PAHs metabolism, there are no studies that evaluate, in general human populations, the effect of PAHs on AKRs expression in peripheral blood lymphocytes (PBLs). The aim of this study was to determine the effect of tobacco smoke exposure, and AKR1A1*2 and AKR1C3*2 polymorphisms, on AKR1A1 and AKR1C1-AKR1C3 messenger RNA (mRNA) levels in PBLs from smokers. In the smoker group, there is a statistically significant positive association between AKR1A1, AKR1C1, and AKR1C3 mRNA induction and urine cotinine levels in individuals with a body mass index (BMI) less than 25. However, AKR1A1*2 and AKR1C3*2 alleles did not influence AKR1A1 and AKR1C1-AKR1C3 mRNA levels. These results suggest that AKRs induction by PAHs in smokers' PBLs is associated with BMI; therefore, the role of adipose tissue accumulation in PAHs' effects needs further investigation.

Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight.

BACKGROUND: Although there is evidence from animal studies of impaired reproductive function by exposure to organophosphates (OP), the effects on birth weight have not been sufficiently evaluated in epidemiological studies. Paraoxonase (PON1) detoxifies organophosphates by cleavage of active oxons. Some PON1 gene polymorphisms could reduce the enzyme activity and increase susceptibility to OP toxicity. OBJECTIVE: To assess the association between maternal exposure to floriculture during pregnancy and the risk of low birth weight (<2500 g) in their offspring, as well as to evaluate the interaction between this exposure and maternal genotype for PON1 Q192R polymorphisms. MATERIALS AND METHODS: A cross sectional study was carried out in two Mexican states (States of Mexico and Morelos) with high frequencies of greenhouse activity. We interviewed and collected blood samples from 264 females (floriculturists or partners of floricultural workers) who became pregnant during the 10 years prior to the interview. The questionnaire measured socioeconomic characteristics, tobacco and alcohol consumption, diseases and occupational and reproductive history. We also applied a food frequency questionnaire. Information was obtained pertaining to 467 pregnancies. DNA was extracted from white cells, and PON1 genotype was determined by Restriction Fragment Length Polymorphism for Q192R polymorphisms. Results were analyzed with generalized estimating equations models. RESULTS: After adjusting for potential confounders, we detected a statistically significant interaction between maternal exposure to flower growing work during pregnancy and PON1 Q192R polymorphisms on risk of low birth weight. The risk of having a baby with LBW is nearly six times higher if a mother is a floriculture worker during pregnancy and has PON1 192RR genotype (OR 5.93, 95% CI 1.28, 27.5). CONCLUSION: These results suggest that the interaction between maternal floriculture work during pregnancy and 192RR PON1 genotype increases the probability of having children with LBW.

Short communication: impact of climate variability on the incidence of dengue in Mexico.

We evaluated the impact of weather variables and climatic indicators associated with the incidence of dengue in two municipalities of the state of Veracruz, Mexico, from 1995 to 2003. A retrospective ecological study was conducted, using time-series analysis in which we compiled the weekly reported cases of dengue and the weather and climatic parameters: temperature, rainfall and sea-surface temperature (SST), the latter as an El Niño Southern Oscillation indicator. We statistically evaluated the data with autogressive models. The models' predictive abilities were evaluated using data collected from 1995 to 2002 and were validated with those observed for 2003. Each degree Centigrade increase in SST was followed by an increase in the number of dengue cases: 46% in San Andrés Tuxtla (P = 0.001) 16 weeks later and 42% in Veracruz 20 weeks later (P = 0.002). Increases in weekly minimum temperature and rainfall were also significant factors in the increase in the reported cases of dengue. We recommend future studies using the same method, involving larger populations with different geographic location, climate and weather. We also recommend strengthening environmental, health and entomological surveillance systems to improve preparedness and emergency responses.

Evaluation of BacT/ALERT plastic culture bottles for use in testing pooled whole blood-derived leukoreduced platelet-rich plasma platelets with a single contaminated unit.

BACKGROUND: In certain countries, whole blood-derived platelet (PLT)-rich plasma PLTs can only be pooled within 4 hours of transfusion. One prerequisite for prestorage pooling is the ability to detect low levels of bacteria from a single unit (approx. 10 colony-forming units [CFUs]/mL) once pooled (10/6 approx. 2 CFUs/mL). This study evaluated the BacT/ALERT (bioMérieux) for detection of bacteria in 1 unit of a 6-unit pool. STUDY DESIGN AND METHODS: Bacillus cereus, Clostridium perfringens, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into single PLT units (target, 10 and 100 CFUs/mL; mean recovered, 5 and 92 CFUs/mL) and then pooled with 5 sterile units. Four milliliters was inoculated into both plastic aerobic and anaerobic bottles, and 0.5 mL was plated (10 sets). RESULTS: All cases were detected when the single unit had at least 6 CFUs per mL. With B. cereus (< or =2 CFUs/mL), all bottles were reactive. With K. pneumoniae and S. viridans (< or =3 CFUs/mL), all samples were detected with a two-bottle set, but not all bottles were reactive. With S. marcescens (< 2 CFUs/mL), only 7 of the 10 sets were reactive. With C. perfringens (0.2 CFUs/mL), only 3 of 10 samples were detected in the anaerobic bottles. CONCLUSIONS: This study evaluates the use of the BacT/ALERT system for detection of bacteria in PLT pools. Overall, the BacT/ALERT detected all contaminated pooled PLTs when the single inoculated unit had a calculated or recovered concentration at least 3 CFUs per mL with 10 different species of bacteria. Low recovered concentrations (< or =2 CFUs/mL) were, in some cases, only detected with a two-bottle set.

Validation of BacT/ALERT plastic culture bottles for use in testing of whole-blood-derived leukoreduced platelet-rich-plasma-derived platelets.

BACKGROUND: Bacterial detection of platelet (PLT)-rich-plasma (PRP)-derived PLTs presents unique challenges for countries that do not allow pooling before storage. This study validated the BacT/ALERT for use in testing pooled PRP-derived PLTs with nine contaminating organisms. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into two PRP-derived PLT pools (target, 10 and 100 colony-forming units [CFUs]/mL; actual recovered concentrations, 5 and 90 CFUs/mL). Four milliliters of each postbacterial inoculation sample was inoculated into both plastic aerobic and anaerobic bottles and 0.5 mL was plated onto blood agar. RESULTS: All organisms (excluding P. acnes) were detected in 8.2 to 22.0 and 7.6 to 20.3 hours (10 and 100 CFUs/mL, respectively) and the mean time to detection was 15.0 and 13.1 hours (10 and 100 CFUs/mL, respective). P. acnes was detected with the anaerobic bottles in a mean of 74.9 and 64.3 hours (10 and 100 CFUs/mL, respectively). With E. cloacae, E. coli, K. pneumoniae, S. marcescens, and S. viridans detection with the anaerobic bottles was faster or equivalent to the detection with the aerobic bottles. This was most notable with S. viridans where the anaerobic bottle was reactive on average 21.6 and 10.8 hours (10 and 100 CFUs/mL, respectively) faster than the aerobic bottle. CONCLUSIONS: This study validates the use of the BacT/ALERT system for the detection of bacteria in PRP-derived PLTs in a pooled format. Overall, the use of the BacT/ALERT system allowed the detection of pooled PRP-derived PLTs inoculated with nine bacteria at 10 and 100 CFUs per mL in 7.6 to 22.0 hours (excluding P. acnes).

Evaluation of a new generation of plastic culture bottles with an automated microbial detection system for nine common contaminating organisms found in PLT components.

BACKGROUND: A microbial detection system (BacT/ALERT 3D, bioMérieux [formerly Organon Teknika]) has previously been validated with a variety of bacterial contaminants in PLTs. The recovery of nine organisms seeded into PLTs with new plastic culture bottles was studied in comparison to the current glass bottles. The use of plastic instead of glass would be expected to reduce the risk of injury. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into Day 2 (>24 hr <48 hr) apheresis PLT units to 10 and 100 CFUs per mL. Replicate samples (4 mL) were inoculated into both current- and new-generation standard aerobic and anaerobic bottles. RESULTS: All organisms (with the exception of P. acnes) were detected in a mean time of 9.3 to 18.9 hours (10 CFUs/mL) or 8.7 to 18.2 hours (100 CFUs/mL). In aggregate (with the exception of P. acnes), the plastic and glass aerobic bottles had a mean difference in detection of 1.2 hours (p < 0.0001), and the plastic and glass anaerobic bottles had a mean difference of 3.3 hours (p < 0.0001). In all cases, the mean detection time was superior or clinically comparable (within 0.1 hr) with the new plastic bottles. P. acnes (an anaerobic organism) was detected with the new and current anaerobic bottles in a mean of 72.8 and 90.4 hours (10 CFUs/mL) or 64.0 and 80.8 hours (100 CFUs/mL), respectively. The narrower bottle neck and smaller inoculation septum present with the new-generation plastic bottles were inoculated with comparable ease to that of the glass bottles. CONCLUSIONS: These data demonstrate that the new plastic bottles are clinically comparable or superior to the current glass standard aerobic and anaerobic culture bottles.

Monitoring of apheresis platelet bacterial contamination with an automated liquid culture system: a university experience.

BACKGROUND: With 4 million platelet units transfused per year in the United States and with the current estimate of bacteria contamination rate in PLT units, it would be expected that 2000 to 4000 bacterially contaminated units are transfused and associated with 333 to 1000 cases of clinical sepsis. STUDY DESIGN AND METHODS: Apheresis platelets were sampled on Day 2 of storage (collection day=Day 0) and issue (or following outdate, Days 6-8) using a sterile connection device (SCD) to attach a sampling bag. Using aseptic technique and a laminar flow hood, bottles were inoculated and placed onto an automated liquid culture system (BacT/ALERT 3D Microbial Detection System) for 7 days. RESULTS: A total of 2397 apheresis PLT units were sampled. A triple apheresis collection was reactive within 14 hours of the Day 2 sampling (aerobic bottles) and the bags were removed from inventory. Staphylococcus epidermidis was identified in all three contaminated bags. Two double-apheresis collections were found to be contaminated with Proprionibacterium sp. after 6 days of incubation but had been transfused to four patients without discernible clinical sequelae. There was one false-positive aerobic bottle and one false-positive anaerobic result due to inadvertent contamination of a bottle. Thus, the overall true-positive rate was 7 of 2397 apheresis units (0.29%) with a true-positive rate for aerobic organisms of 0.13% and an anaerobic true-positive rate of 0.17%. The false-positive rate was 2 out of 4794 samplings (0.04%) or 2 out of 9588 bottles (0.02%). CONCLUSION: This preliminary data suggests that the use of a SCD, aseptic technique, and a laminar flow hood is associated with a low rate of contamination. In no case did an issue (or outdate) detect contamination that was not detected by the Day 2 culture. Additional surveillance is necessary before we can conclude that a Day 2 sterile culture is truly predictive of an issue (or outdate) sterile culture. Bacterial culture surveillance of PLTs would be expected to save lives and may facilitate an extension in PLT storage.

Evaluation of a new generation of culture bottle using an automated bacterial culture system for detecting nine common contaminating organisms found in platelet components.

BACKGROUND: An automated bacterial culture system (BacT/ALERT 3D, bioMérieux) has been previously validated with a variety of bacteria in platelets. The recovery of bacteria in platelets using a new generation of culture bottles that do not require venting and that use a liquid emulsion sensor was studied. STUDY DESIGN AND METHODS: Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes isolates were inoculated into Day 2 platelets to concentrations of 10 and 100 CFU per mL. Samples were then studied with current and new aerobic, anaerobic, and pediatric bottles. RESULTS: All organisms, except P. acnes, were detected in a mean time of 9.2 to 20.4 (10 CFU/mL) or 8.7 to 18.6 (100 CFU/mL) hours. P. acnes was detected in a mean time of 69.2 (10 CFU/mL) or 66.0 (100 CFU/mL) hours. The 10-fold increase in inoculum was associated with a mean 9.2 percent difference in detection time. The aerobic, anaerobic, and pediatric bottles had a mean difference in detection time (hours) between the current and new bottles of 0.10 (p=0.61), 0.4 (p=0.38), and 1.0 (p < 0.001), respectively. CONCLUSION: No difference in detection time between the current and new aerobic and anaerobic bottles was demonstrated. The new pediatric bottles had a small but significant delay in detection.

Spatial distribution of EEG theta activity as a function of lifetime lead exposure in 9-year-old children.

The relationship between low-level childhood lead exposure and developmental retardation has been proposed but the existing evidence is weak. We examined the EEG of 42 children participating in the Mexico City Prospective Lead Study to determine if relative theta power and distribution across the scalp was related to history of lifetime lead exposure as measured by sequential blood lead concentration of the mother during pregnancy and the child after delivery. EEG was recorded from scalp electrodes placed according to the 10-20 system during eyes-closed. Theta activity (4-7 Hz) was filtered with a fast Fourier transform (FFT) and relative power calculated. The expected distribution of theta was found, with the greatest relative power centrally located and lesser amounts at frontal, occipital, and lateral derivations. Multiple regression models of theta at each electrode showed that increasing postnatal blood lead from 6 to 96 months was related to increasing relative theta power adjusted for age, sex and fetal suffering at delivery, in occipital derivations. The most significant increases in theta power were associated with blood lead levels (geometric mean = 10.3 microg/dl) measured between 54 and 72 months. Spatially weighted regression demonstrated that there was a significant antero-posterior gradient in lead-induced increase in relative theta power associated with postnatal blood lead levels at 54-72 months and 78-96 months. The greatest lead effect on both occipital relative theta power and the antero-posterior gradient of theta power was found with lead at an age during which relative theta power reaches its developmental maximum and starts to decrease. Results suggest that 54-72 months represent a critical period during which lead can exert lasting effects on the developmental pattern of theta activity. Occipital derivation of the largest effects of lead on theta activity may also be related to other lead-related developmental deficits.

Lead levels in blood bank blood.

Although blood bank blood is usually screened for dangerous pathogens, the presence of toxic metals in blood has received little attention. Population blood lead levels have been declining in the United States, but occasional high outliers in blood lead concentration can be found--even when mean levels of blood lead are low. We sampled 999 consecutive blood bank bags from the King/Drew Medical Center, used between December 1999 and February 2000. The geometric mean blood lead level was 1.0 microg/dl (0.048 micromol/l), but 0.5% of the samples had lead levels that exceeded 10 microg/dl, and 2 samples had lead levels that exceeded 30 microg/dl. The 2 samples with the highest lead levels could have presented an additional risk to infants if they were used for blood replacement. Therefore, even in countries with generally low population blood lead levels, blood bank blood should be screened for lead concentration prior to use with infants.

Neonatal lead poisoning from maternal pica behavior during pregnancy.

Lead toxicity has gained increasing attention in the public media because of its ubiquitous distribution in the environment and the potentially serious medical complications that it can induce, particularly in children. We present a case of an asymptomatic Hispanic woman who exhibited a unique form of pica during her pregnancy. By serendipity, she agreed to enroll into a lead screening study at our medical center when she presented to deliver her child. Her blood lead level was 119.4 microg/dL at delivery, and simultaneous measurement of the neonate's cord blood lead level was 113.6 microg/dL. The infant underwent an exchange transfusion, and the mother was treated with oral 2,3-dimercaptosuccinic acid. Both demonstrated dramatic biochemical improvement.

The lead content of blood serum.

Serum lead concentrations measured by stable isotope dilution with a thermal ionization mass spectrometer and blood lead concentrations measured by graphite furnace atomic absorption spectrophotometry are reported for 73 women of child bearing age resident in Los Angeles, California. The two quantities are related by the line y=0.00030+0.00241x (r=0.83), where y is serum lead concentration and x is blood lead concentration, both being expressed in units of microg/L. The linearity of the relationship appears to hold to a blood lead concentration of at least 60 microg Pb/L. The slope of the line indicates that lead in serum is 0.24% of that in whole blood in contrast to recent reports of between 0.32 and 0.35% determined by inductively coupled plasma (ICP) mass spectrometry with bismuth used as an internal standard. The discrepancy stems from the ICP mass spectrometer-generated curves not passing through the origin.

Use of V4R in patients who sustain blunt chest trauma.

OBJECTIVE: In blunt chest trauma, the right ventricle is more vulnerable than the left. The purpose of this study was to determine whether recording V4R in patients with blunt chest trauma would provide additional useful information to that already obtained from the standard 12-lead electrocardiogram (ECG). METHODS: Forty-five patients with blunt chest trauma and 40 unmatched control subjects without blunt chest trauma had standard 12-lead ECG and right precordial leads recorded. The ECGs were read blindly by three physicians. RESULTS: Patients with chest trauma were distinguishable from controls on the basis of the left-sided ECGs (odds ratio, 2.9; 95% confidence interval, 1.71-4.90). This was not the case using V4R (odds ratio, 1.23; 95% confidence interval, 0.59-2.0). CONCLUSION: Patients with a significant mechanism and physical findings of blunt chest trauma were more likely than controls to have an abnormal ECG. They were not more likely to have abnormalities in V4R. We recommend that a 12-lead ECG, but not V4R, be routinely obtained on these patients.

The effects of retained lead bullets on body lead burden.

BACKGROUND: Numerous case reports have demonstrated that lead poisoning with potentially fatal consequences can result from retained lead projectiles after firearm injuries. To assess the impact of retained projectiles on subsequent lead exposure in the population, one cannot rely on self-selected cases presenting with symptoms of lead intoxication. This preliminary study seeks to identify increased lead burden and identify risk factors of elevated blood lead levels for individuals with retained lead bullets. METHODS: Forty-eight patients were originally recruited from gunshot victims presenting for care at the King/Drew Medical Center in Los Angeles, California. An initial blood level was measured for all recruited patients and repeated for the 28 participants available for follow-up, 1 week to 8 months later. Medical history, including a history of prior firearm injuries and other retained projectiles, was taken, along with a screening and risk factor questionnaire to determine other sources of lead (occupational/recreational) to which the patient might have been, or is at present, exposed. The participants also had K-shell x-ray fluorescence determinations of bone lead in the tibia and calcaneus in order to determine past lead exposures not revealed by medical history and risk factor questionnaire. Multivariate models of blood level were made using risk factor and bone lead concentration data. RESULTS: We demonstrated that blood lead tends to increase with time after injury in patients with projectile retention, and that the increase in significant part depended on the presence of a bone fracture caused by the gunshot. CONCLUSION: We encountered evidence suggesting that the amount of blood lead increase in time after injury is also dependent on the tibia lead concentration. There were too few cases in the study to fully test the effects of bullet location, or the interaction of bullet location with bone fracture or bullet fragmentation.

Seasonal variation in bone lead contribution to blood lead during pregnancy.

Population blood lead level (PbB) often shows seasonal variation, frequently being higher in summer and lower in winter. As vitamin D metabolites also show seasonal variability, and the metabolites are associated with bone metabolism, some authors have posited a role for bone lead release in seasonal PbB changes. We made third trimester and postdelivery PbB measurements on 414 immigrant women (98% Latina) in Los Angeles. We measured in vivo tibia and calcaneus (heel) lead concentration postdelivery via K-shell X-ray fluorescence. We saw evidence of seasonal variation in prenatal PbB, but not postnatal PbB. PbB was highest in spring and lowest in autumn. Tibia lead concentration was associated with prenatal PbB, as reported before. The contribution of tibia lead to prenatal PbB varied seasonally, with the greatest contribution occurring in the winter quarter and the least in the summer quarter. The temporal pattern of bone lead contribution to PbB follows the seasonal alteration of insolation. There was no seasonal component in prenatal PbB associated with calcaneus lead, nor were there seasonal variations in either calcaneus or tibia lead contributions to postnatal PbB. Bone turnover in the third trimester of pregnancy may be higher in winter months than in summer months, resulting in greater fetal lead exposure in spring than at other times of the year.

One approach for doublet deconvolution to improve reliability in spectra analysis for in vivo lead measurement.

Calculation of lead concentration from K-series X-ray fluorescent studies uses a robust normalization technique based on the amplitude or area of the elastic signal. Parameter estimation of the elastic signal can be affected by the overlap of the Kbeta2 line, especially for concentrations greater than 40 ppm where the Kbeta2 amplitude can be greater than 1% of the elastic signal. We tested the combination of estimation by method of least moduli and doublet deconvolution. We found that the estimation of the area of the elastic signal is more robust to changes in the low-energy end of the region of interest with the combined method than with method of least-squares estimation and singlet processing. We recommend use of the combined method for creation of calibration curves at concentrations greater than or equal to 40 ppm.

How to calculate lead concentration and concentration uncertainty in XRF in vivo bone lead analysis.

The authors provide a substantial correction for calculating estimates of lead concentration and uncertainty for in vivo X-ray fluorescent bone analysis with Cd-109 source. Based on general principles, they provide mathematical techniques for propagation of uncertainties in XRF analysis. They give additional considerations for lowering the detection limit and improving spectral data quality.

Temporal pattern in the effect of postnatal blood lead level on intellectual development of young children.

To determine the temporal pattern of the effect of postnatal blood lead level on the General Cognitive Index (GCI) of the McCarthy Scales of Children's Abilities, we used data from 112 children of the Mexico City Prospective Lead Study with complete evaluations from 36 to 60 months of age at 6-month intervals. We measured blood lead level every 6 months from 6 to 54 months. We controlled for 5-min Apgar, birth weight, birth order, sex, socioeconomic level, maternal IQ, and maximum maternal educational level in a repeated measures ANCOVA using child blood lead level grouped by 6-18 month (geometric mean 10.1 microg/dl, range 3.5-37.0 microg/dl), 24-36 month (geometric mean 9.7 microg/dl, range 3.0-42.7 microg/dl), and 42-54 month (geometric mean 8.4 microg/dl, range 2.5-44.8 microg/dl) averages. There were significant interactions between the 6-18 month blood lead level and age with GCI as the endpoint and between 24-36 month blood lead level and age. The regression coefficient of blood lead at 6-18 months became more negative with age until 48 months, when the rate of decline moderated (linear polynomial contrast p=0. 047). The regression coefficient of blood lead at 24-36 months with CGI became more negative as well from 36 to 48 months but then started decreasing toward zero from 48 to 60 months (quadratic polynomial contrast p=0.019). Significant between-subjects lead effects on GCI were found for 24-36 month blood lead level at 48 months (p=0.021) and at 54 months (p=0.073). The greatest effect (at 48 months) was a 5.8-point GCI decrease with each natural log unit increase in blood lead. Significant between-subjects lead effects on GCI were found for 42-54 month blood lead level at 54 months (p=0. 040) and at 60 months (p=0.060). The effect of postnatal blood lead level on GCI reaches its maximum approximately 1-3 years later, and then becomes less evident. Four to five years of age appears to be a critical period for the manifestation of the earlier postnatal blood lead level effects.