Biomedical subjects

Andrew M Geller

Publications and source records attributed to Andrew M Geller.

7 recordsLinked to original sources

PubMed2006

Induction of asthma and the environment: what we know and need to know.

The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop "Environmental Influences on the Induction and Incidence of Asthma" to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment.

Adolescent↗

PubMed2005

Repeated spike exposure to the insecticide chlorpyrifos interferes with the recovery of visual sensitivity in rats.

Reports from Japan and India and data submissions to the US EPA indicate that exposure to cholinesterase (ChE)-inhibiting organophosphorous insecticides (OP) can produce ocular toxicity, in particular long-lasting changes in retinal physiology and anatomy. We have examined the effects of a 1 year dietary exposure to the OP chlorpyrifos (CPF) on retinal structure and function. Adult male Long-Evans rats were fed CPF in their diet at the rate of 0, 1 (low), or 5 (high) mg/kg body weight/day. In addition, half of each feeding group received an oral (spike) dose of CPF in corn oil (45 mg/kg) or corn oil (VEH) alone every 2 months, resulting in six exposure groups: Control-VEH, Control-CPF, Low-VEH, Low-CPF, High-VEH, and High-CPF. Dark-adapted electroretinograms (ERG) were measured 3-5 months (n= 15-18/group) after the completion of dosing. There were no significant differences between dose or spike groups in a-wave, b-wave, or oscillatory potential amplitudes or implicit times. In addition, the time course of dark adaptation were measured in a subset of these rats (6-8/group) eight months after the completion of dosing by determining the flash intensity needed to elicit a 40 microV b-wave at selected intervals after bleaching 90% of the photopigment. Rats receiving the episodic oral spike of CPF showed a slowed recovery of dark-adapted sensitivity compared to rats receiving the corn oil VEH across chronic dosing conditions. No effects were seen on retinal morphology. This result suggests that episodic high dose exposures to CPF may result in altered retinal function. This effect, akin to effects seen in aging humans and humans exposed to other ChE-inhibiting compounds, may reflect alterations in the photoreceptors and retinal pigment epithelium (RPE) complex necessary for regenerating photopigment.

Animals↗

PubMed2005

Epilepsy and medication effects on the pattern visual evoked potential.

Visual disruption in patients diagnosed with epilepsy may be attributable to either the disease itself or to the anti-epileptic drugs prescribed to control the seizures. Effects on visual function may be due to perturbations of the GABAergic neurotransmitter system, since deficits in GABAergic cortical interneurons have been hypothesized to underlie some forms of epilepsy, some anti-epileptic medications increase cortical GABA levels, and GABAergic neural circuitry plays an important role in mediating the responses of cells in the visual cortex and retina. This paper characterizes the effects of epilepsy and epilepsy medications on the visual evoked response to patterned stimuli. Steady-state visual evoked potentials (VEP) evoked by onset-offset modulation of high-contrast sine-wave stimuli were measured in 24 control and 54 epileptic patients. Comparisons of VEP spectral amplitude as a function of spatial frequency were made between controls, complex partial, and generalized epilepsy groups. The effects of the GABA-active medication valproate were compared to those of carbamezepine. The amplitude of the fundamental (F1) component of the VEP was found to be sensitive to epilepsy type. Test subjects with generalized epilepsy had F1 spatial frequency-amplitude functions with peaks shifted to lower spatial frequencies relative to controls and test subjects with complex partial epilepsy. This shift may be due to reduced intracortical inhibition in the subjects with generalized epilepsy. The second harmonic component (F2) response was sensitive to medication effects. Complex partial epilepsy patients on VPA therapies showed reduced F2 response amplitude across spatial frequencies, consistent with previous findings that showed the F2 response is sensitive to GABA-ergic effects on transient components of the VEP.

Adult↗

PubMed2005

Human neurobehavioral effects of long-term exposure to styrene: a meta-analysis.

Many reports in the literature suggest that long-term exposure to styrene may exert a variety of effects on the nervous system, including increased choice reaction time and decreased performance of color discrimination and color arrangement tasks. Sufficient information exists to perform a meta-analysis of these observations quantifying the relationships between exposure (estimated from biomarkers) and effects on two measures of central nervous system function: reaction time and color vision. To perform the meta-analysis, we pooled data into a single database for each end point. End-point data were transformed to a common metric of effect magnitude (percentage of baseline). We estimated styrene concentration from biomarkers of exposure and fitted linear least-squares equations to the pooled data to produce dose-effect relationships. Statistically significant relationships were demonstrated between cumulative styrene exposure and increased choice reaction time as well as increased color confusion index. Eight work-years of exposure to 20 ppm styrene was estimated to produce a 6.5% increase in choice reaction time, which has been shown to significantly increase the probability of automobile accidents. The same exposure history was predicted to increase the color confusion index as much as 1.7 additional years of age in men.

Accidents, Traffic↗

PubMed2005

Aging and the environment: a research framework.

The rapid growth in the number of older Americans has many implications for public health, including the need to better understand the risks posed to older adults by environmental exposures. Biologic capacity declines with normal aging; this may be exacerbated in individuals with pre-existing health conditions. This decline can result in compromised pharmacokinetic and pharmacodynamic responses to environmental exposures encountered in daily activities. In recognition of this issue, the U.S. Environmental Protection Agency (EPA) is developing a research agenda on the environment and older adults. The U.S. EPA proposes to apply an environmental public health paradigm to better understand the relationships between external pollution sources --> human exposures --> internal dose --> early biologic effect --> adverse health effects for older adults. The initial challenge will be using information about aging-related changes in exposure, pharmacokinetic, and pharmacodynamic factors to identify susceptible subgroups within the diverse population of older adults. These changes may interact with specific diseases of aging or medications used to treat these conditions. Constructs such as "frailty" may help to capture some of the diversity in the older adult population. Data are needed regarding a) behavior/activity patterns and exposure to the pollutants in the microenvironments of older adults; b) changes in absorption, distribution, metabolism, and excretion with aging; c) alterations in reserve capacity that alter the body's ability to compensate for the effects of environmental exposures; and d) strategies for effective communication of risk and risk reduction methods to older individuals and communities. This article summarizes the U.S. EPA's development of a framework to address and prioritize the exposure, health effects, and risk communications concerns for the U.S. EPA's evolving research program on older adults as a susceptible subpopulation.

Aged↗

PubMed2002

Apartment residents' and day care workers' exposures to tetrachloroethylene and deficits in visual contrast sensitivity.

Tetrachloroethylene (also called perchloroethylene, or perc), a volatile organic compound, has been the predominant solvent used by the dry-cleaning industry for many years. The U.S. Environmental Protection Agency (EPA) classified perc as a hazardous air pollutant because of its potential adverse impact on human health. Several occupational studies have indicated that chronic, airborne perc exposure adversely affects neurobehavioral functions in workers, particularly visual color discrimination and tasks dependent on rapid visual-information processing. A 1995 study by Altmann and colleagues extended these findings, indicating that environmental perc exposure at a mean level of 4,980 microg/m(3) (median=1,360 microg/m(3)) alters neurobehavioral functions in residents living near dry-cleaning facilities. Although the U.S. EPA has not yet set a reference concentration guideline level for environmental exposure to airborne perc, the New York State Department of Health set an air quality guideline of 100 microg/m(3). In the current residential study, we investigated the potential for perc exposure and neurologic effects, using a battery of visual-system function tests, among healthy members of six families living in two apartment buildings in New York City that contained dry-cleaning facilities on the ground floors. In addition, a day care investigation assessed the potential for perc exposure and effects among workers at a day care center located in the same one-story building as a dry-cleaning facility. Results from the residential study showed a mean exposure level of 778 microg/m(3) perc in indoor air for a mean of 5.8 years, and that perc levels in breath, blood, and urine were 1-2 orders of magnitude in excess of background values. Group-mean visual contrast sensitivity (VCS), a measure of the ability to detect visual patterns, was significantly reduced in the 17 exposed study participants relative to unexposed matched-control participants. The groups did not differ in visual acuity, suggesting that the VCS deficit was of neurologic origin. Healthy workers in the day care investigation were chronically exposed to airborne perc at a mean of 2,150 microg/m(3) for a mean of 4.0 years. Again, group-mean VCS, measured 6 weeks after exposure cessation, was significantly reduced in the nine exposed workers relative to matched controls, and the groups did not differ significantly in visual acuity. These results suggested that chronic, environmental exposure to airborne perc adversely affects neurobehavioral function in healthy individuals. Further research is needed to assess the susceptibility of the young and elderly to perc-induced effects, to determine whether persistent solvent-induced VCS deficits are a risk factor for the development of neurologic disease, and to identify the no observable adverse effect level for chronic, environmental, perc exposure in humans.

Adolescent↗

PubMed2002

Increased ERG a- and b-wave amplitudes in 7- to 10-year-old children resulting from prenatal lead exposure.

PURPOSE: To determine the dose-response relationship between blood lead concentration ([PbB]) and scotopic ERG amplitude in 7- to 10-year-old children with lifetime lead exposure. METHODS: Full-field flash scotopic ERGs were recorded over a 4-log-unit range in 45 dark-adapted children with normal visual acuity. [PbB] was measured throughout pregnancy and postnatal development, and the subjects' [PbB] levels were grouped at each age by tertiles. RESULTS: The median [PbB] during pregnancy was, from lowest to highest tertile, 2.5 to 5.0, 7.5 to 9.0, and 14.0 to 16.5 microg/dL, and after birth was 4.0 to 8.0, 6.0 to 14.5, and 7.5 to 21.0 microg/dL. Only maternal [PbB] at 12 weeks of pregnancy showed a significant dose-response relationship with the ERG measures, so that with increasing [PbB] there were significant increases in leading-edge a-wave amplitude, peak a-wave amplitude, and b-wave amplitude and sensitivity, with no changes in implicit times. Data analyses showed that children whose mothers had [PbB] of 10.5 microg/dL or more at 12 weeks of pregnancy had relatively increased a- and b-waves. CONCLUSIONS: Lead exposure during the first trimester of pregnancy produces dose-dependent increases in scotopic a- and b-wave amplitudes in 7- to 10-year-old children. The results suggest that the increases in a- and b-wave amplitudes originate from rods; however, the increased b-wave amplitude and sensitivity may also originate in the inner retina. These alterations occurred at maternal [PbB] at or below currently accepted safe levels. These novel findings reveal that the developing retina is a sensitive target for lead and suggest that lead-exposed children be examined for possible future visual system deficits.

Child↗