Correlating agricultural use of organophosphates with outdoor air concentrations: a particular concern for children

For the organophosphate pesticide chlorpyrifos, median inhalation noncancer, acute children's exposures in agricultural communities are elevated above reference doses; for diazinon, similar exposures are nearly elevated. We used multivariate linear regression analysis to examine the temporal and spatial associations between agricultural use and measured air concentrations of chlorpyrifos, chlorpyrifos oxon, diazinon, and malathion. Agricultural use within a 3-mile radius on the monitoring day and use on the 2-4 prior days were significantly associated with air concentrations (p < 0.01) for all analytes except malathion; chlorpyrifos oxon showed the strongest association (p < 0.0001). In the final models, which included weather parameters, the proportion of variance (r2, adjusted for the number of model variables) for all analytes ranged from 0.28 (p < 0.01) for malathion to 0.65 (p < 0.0001) for diazinon. Recent cellular, animal, and human evidence of toxicity, particularly in newborns, supports the public health concern indicated by initial risk estimates. Agricultural applications of organophosphates and their oxon products may have substantial volatization and off-field movement and are a probable source of exposures of public health concern.     

Association of housing disrepair indicators with cockroach and rodent infestations in a cohort of pregnant Latina women and their children

Health burdens associated with poor housing and indoor pest infestations are likely to affect young children in particular, who spend most of their time indoors at home. We completed environmental assessments in 644 homes of pregnant Latina women and their children living in the Salinas Valley, California. High residential densities were common, with 39% of homes housing > 1.5 persons per room. Housing disrepair was also common: 58% of homes had peeling paint, 43% had mold, 25% had water damage, and 11% had rotting wood. Evidence of cockroaches and rodents was present in 60% and 32% of homes, respectively. Compared with representative national survey data from the U.S. Department of Housing and Urban Development, homes in our sample were more likely to have rodents, peeling paint, leaks under sinks, and much higher residential densities. The odds of rodent infestations in homes increased in the presence of peeling paint [odds ratio (OR) 2.1; 95% confidence interval (CI), 1.5-3.1], water damage (OR 1.9; 95% CI, 1.2-2.7), and mold (OR 1.5; 95% CI, 1.0-2.1). The odds of cockroach infestation increased in the presence of peeling paint (OR 3.8; 95% CI, 2.7-5.6), water damage (OR 1.9; 95% CI, 1.2-2.9), or high residential density (OR 2.1; 95% CI, 1.2-3.8). Homes that were less clean than average were more prone to both types of infestations. Pesticides were stored or used in 51% of households, partly to control roach and rodent infestations. These data indicate that adverse housing conditions are common in this community and increase the likelihood of pest infestations and home pesticide use. Interventions to improve housing and promote children's health and safety in this population are needed.     

Characterizing exposures to nonpersistent pesticides during pregnancy and early childhood in the National Children's Study: a review of monitoring and measurement methodologies

The National Children's Study is a proposed longitudinal cohort study to evaluate the relationships between children's health and the environment. Enrollment is estimated to begin in September 2005, and 100,000 children will be followed from preconception or early pregnancy until adulthood. Among multiple health outcomes, the study is proposing to investigate whether pre- and/or postnatal exposures to nonpersistent pesticides increase the risk of poor performance on neurobehavioral and cognitive exams during infancy and early childhood. Characterization of exposures will be challenging. Nonpersistent pesticides include many chemicals with biologic half-lives on the order of hours or days. Exposures can occur through multiple pathways (e.g., food and residential or agriculture pesticide use) and by multiple routes (inhalation, ingestion, dermal). Effects may depend on the developmental stage when exposure occurs. Sequential sampling is likely to be required and may involve a combination of environmental and biologic monitoring as well as collection of questionnaire data. In this article we review measurements that can be used to characterize exposures. These include biologic markers, personal and indoor air sampling techniques, collection of dust, surface and dermal wipe samples, and dietary assessment tools. Criteria for sample selection will necessitate evaluation of the time frame of exposure captured by the measurement in relationship to critical windows of susceptibility, the cost and validity of the measurements, participant burden, and variability in exposure routes across populations and at different age periods.     

A novel molecule (frakefamide) with peripheral opioid properties: the effects on resting ventilation compared with morphine and placebo

In animal models frakefamide (FF) is a potent analgesic that acts as a peripheral active mu-selective receptor agonist. In this double-blind, randomized, double dummy four-way crossover study in 12 healthy male subjects, we investigated the effects on resting ventilation of FF and 2 dose levels of morphine compared with placebo. Each drug was infused for 6 h. The subjects received 1.22 mg/kg FF, 0.43 mg/kg morphine (M-large), and 0.11 mg/kg morphine (M-small). Sodium chloride 9 mg/mL was used as placebo. Ventilation was measured by pneumotachography and inline capnography. Blood was collected and plasma concentrations of FF and morphine and its metabolites were analyzed. Within 15 min after administration of FF all subjects complained of a transient myalgia, which disappeared within 30 min. At target measurement (335 min), there were no differences in tidal volume among the groups. Respiratory rates were, however, slower in the two M-groups (P < 0.05 in M-small and P < 0.001 in M-large) compared with FF and placebo. Minute volume was significantly less in the M-large group compared with the FF (P < 0.01) and placebo (P < 0.01) groups. This difference was reflected by an elevated ETco(2) in the M-large group (P < 0.01). We conclude that, during resting ventilation, FF, unlike morphine, did not cause central respiratory depression. This suggests that FF has only peripheral mu-opioid agonist activity in humans.     

Age-related increase in wall stress of the human abdominal aorta: an in vivo study

BACKGROUND: The regulation of wall stress in the abdominal aorta (AA) of humans might be of specific interest, because the AA is the most common site for aneurysm formation in which wall stress seems to be an important pathophysiological factor. We studied the age-related changes in wall stress of the AA in healthy subjects, with the common carotid artery (CCA) as a comparison. METHODS: A total of 111 healthy subjects were examined with B-mode ultrasonography to determine the lumen diameter and intima-media thickness (IMT) in the AA and the CCA. RESULTS: Aortic IMT was affected by age in men and by both age and lumen diameter in women. Carotid IMT was affected by age and pulse pressure in both men and women. Wall stress was higher in the AA than in the CCA (P < .001), and men had higher wall stress than women in both the AA (P < .001) and the CCA (P < .05). Furthermore, wall stress was constant during life in the CCA of men and women and in the AA of women. In the male aorta, however, wall stress increased with age (P < 0.01). CONCLUSIONS: Arterial diameters increase with age, and a compensatory thickening of the arterial wall prevents the circumferential wall stress from increasing. However, this compensatory response is insufficient in the male AA and results in an increase in stress with age. These findings might explain the propensity for aneurysms to develop in the AA of men.     

New and unusual O alleles at the ABO locus are implicated in unexpected blood group phenotypes

BACKGROUND: In the ABO blood group system mutations in the A gene may lead to weak A subgroups owing to a dysfunctional 3-alpha-N-acetylgalactosaminyltransferase. STUDY DESIGN AND METHODS: Blood and DNA were investigated to correlate weak A phenotypes with genotype, and an overrepresentation of the infrequent O2 allele was observed. Consequently, 57 available O2 alleles were examined in detail. RESULTS: Two new O2 alleles were identified having mutations resulting in Gly229Asp with or without Arg217Cys. A recently described O2 variant (488C>T; Thr163Met) was also found. Surprisingly, both the original and the variant O2 alleles were associated with either O or Aweak phenotypes. Three novel O alleles surfaced in six other samples with suspected A subgroups. These were A1-like alleles having nonsense mutations causing premature truncation at codons 56, 107, or 181. A second example of the rare O3 allele was also identified. A newly described O1 allele having 768C>A was found to be the third most frequent O allele among Swedish donors. Of the five novel O alleles, three were incorrectly interpreted as A1 following routine ABO genotyping. CONCLUSION: Apparent O alleles lacking 261delG may cause weak A expression on red blood cells and/or inhibit anti-A production. A hypothesis that exchange of genetic material between principally dissimilar O alleles during mitosis ("autologous chimerism") restores glycosyltransferase activity in some cells would explain this interesting phenomenon.