It is known that ouabain, a selective inhibitor of Na/K-ATPase, can cause not only activation of signal cascades, which regulate the cell viability, but also can cause free radical accumulation, which can evoke the oxidative stress. We have shown that nanomolar concentrations of ouabain result in the temporary increase in the level of intracellular free radicals but the millimolar concentration of ouabain induces a stable intracellular accumulation of free radicals in rat thymocytes. The increasing level of free radicals resulting from both low and high concentrations of ouabain can be attenuated by the antioxidant, carnosine. Moreover the long-term incubation with ouabain leads to the cell death by necrosis and apoptosis. Ouabain-mediated apoptosis and necrosis were also abolished by carnosine.
Na/K-ATPase; free radicals; ouabain; carnosine; thymocytes
Anniston, Alabama, is the site of a former Monsanto plant where polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971. Residents of Anniston are known to have elevated levels of PCBs. The objective of the study was to test the hypothesis that levels of the various lipid components (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are differentially associated with concentrations of total PCBs and total pesticides, and further that different congeners, congener groups and different pesticides do not have identical associations in serum samples obtained from Anniston residents in a cross-sectional study.
Fasting serum samples were obtained from 575 residents of Anniston who were not on any lipid-lowering medication and were analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol, LDL and HDL cholesterol and triglyceride concentrations. Associations between toxicant concentrations and lipid levels were determined using multiple linear regression analysis.
We observed that elevated serum concentrations of lipids were associated with elevated serum concentrations of ΣPCBs and summed pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption, smoking and exercising status. The strongest associations were seen for PCB congeners with three, four, or at least eight substituted chlorines. Mono-ortho substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and tetra-ortho congeners 199, 196–203, 206 and 209 each were significantly associated with total lipids, total cholesterol and triglycerides. Serum concentrations of HCB and chlordane also had strong associations with lipid components.
Increased concentrations of PCBs and organochlorine pesticides are associated with elevations in total serum lipids, total cholesterol and triglycerides, but the patterns are different for different groups of PCBs and different pesticides. These observations show selective effects of different organochlorines on serum concentrations of different groups of lipids. This elevation in concentrations of serum lipids may be the basis for the increased incidence of cardiovascular disease found in persons with elevated exposures to PCBs and chlorinated pesticides.
Cholesterol; Triglycerides; Persistent organic pollutants; LDL cholesterol; HDL cholesterol; Hexachlorobenzene; DDT; PCBs
Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation.
We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia.
Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC.
Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27–0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure.
The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.
Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.
Traumatic Brain Injury (TBI); Functional magnetic resonance imaging (fMRI); DTI; Cognitive Function
This article synthesizes discussion of collaborative research results, interventions and policy engagement for St Lawrence Island (SLI), Alaska, during the years 2000–2012.
As part of on-going community-based participatory research (CBPR) studies on SLI, 5 discrete exposure-assessment projects were conducted: (a) a biomonitoring study of human blood serum; (b–d) 3 investigations of levels of contaminants in environmental media at an abandoned military site at Northeast Cape – using sediment cores and plants, semi-permeable membrane devices and blackfish, respectively; and (e) a study of traditional foods.
Blood serum in residents of SLI showed elevated levels of polychlorinated biphenyls (PCBs) with higher levels among those exposed to the military site at Northeast Cape, an important traditional subsistence-use area. Environmental studies at the military site demonstrated that the site is a continuing source of PCBs to a major watershed, and that clean-up operations at the military site generated PCB-contaminated dust on plants in the region. Important traditional foods eaten by the people of SLI showed elevated concentrations of PCBs, which are primarily derived from the long-range transport of persistent pollutants that are transported by atmospheric and marine currents from more southerly latitudes to the north.
An important task for all CBPR projects is to conduct intervention strategies as needed in response to research results. Because of the findings of the CBPR projects on SLI, the CBPR team and the people of the Island are actively engaging in interventions to ensure cleanup of the formerly used military sites; reform chemicals policy on a national level; and eliminate persistent pollutants internationally. The goal is to make the Island and other northern/Arctic communities safe for themselves and future generations.
As part of the CBPR projects conducted from 2000 to 2012, a series of exposure assessments demonstrate that the leaders of SLI have reason to be concerned about the health of people due to the presence of carcinogenic chemicals as measured in biomonitoring and environmental samples and important traditional foods.
community-based participatory research; Yupik; persistent organic pollutants; polychlorinated biphenyls; environmental health; military toxics
Background: Indigenous American communities face disproportionate health burdens and environmental health risks compared with the average North American population. These health impacts are issues of both environmental and reproductive justice.
Objectives: In this commentary, we review five indigenous communities in various stages of environmental health research and discuss the intersection of environmental health and reproductive justice issues in these communities as well as the limitations of legal recourse.
Discussion: The health disparities impacting life expectancy and reproductive capabilities in indigenous communities are due to a combination of social, economic, and environmental factors. The system of federal environmental and Indian law is insufficient to protect indigenous communities from environmental contamination. Many communities are interested in developing appropriate research partnerships in order to discern the full impact of environmental contamination and prevent further damage.
Conclusions: Continued research involving collaborative partnerships among scientific researchers, community members, and health care providers is needed to determine the impacts of this contamination and to develop approaches for remediation and policy interventions.
Alaska Natives; environmental justice; First Nations; Native Americans; reproductive justice
Background: Air pollution is known to cause respiratory disease. Unlike motor vehicle sources, fuel-fired power plants are stationary.
Objective: Using hospitalization data, we examined whether living near a fuel-fired power plant increases the likelihood of hospitalization for respiratory disease.
Methods: Rates of hospitalization for asthma, acute respiratory infection (ARI), and chronic obstructive pulmonary disease (COPD) were estimated using hospitalization data for 1993–2008 from New York State in relation to data for residences near fuel-fired power plants. We also explored data for residential proximity to hazardous waste sites.
Results: After adjusting for age, sex, race, median household income, and rural/urban residence, there were significant 11%, 15%, and 17% increases in estimated rates of hospitalization for asthma, ARI, and COPD, respectively, among individuals > 10 years of age living in a ZIP code containing a fuel-fired power plant compared with one that had no power plant. Living in a ZIP code with a fuel-fired power plant was not significantly associated with hospitalization for asthma or ARI among children < 10 years of age. Living in a ZIP code with a hazardous waste site was associated with hospitalization for all outcomes in both age groups, and joint effect estimates were approximately additive for living in a ZIP code that contained a fuel-fired power plant and a hazardous waste site.
Conclusions: Our results are consistent with the hypothesis that exposure to air pollution from fuel-fired power plants and volatile compounds coming from hazardous waste sites increases the risk of hospitalization for respiratory diseases.
asthma; COPD; particulates; respiratory infection; SO2
Use of nurse practitioners and physician assistants ("affiliates") is increasing significantly in the intensive care unit (ICU). Despite this, few data exist on how affiliates allocate their time in the ICU. The purpose of this study was to understand the allocation of affiliate time into patient-care and non-patient-care activity, further dividing the time devoted to patient care into billable service and equally important but nonbillable care.
We conducted a quasi experimental study in seven ICUs in an academic hospital and a hybrid academic/community hospital. After a period of self-reporting, a one-time monetary incentive of $2,500 was offered to 39 affiliates in each ICU in which every affiliate documented greater than 75% of their time devoted to patient care over a 6-month period in an effort to understand how affiliates allocated their time throughout a shift. Documentation included billable time (critical care, evaluation and management, procedures) and a new category ("zero charge time"), which facilitated record keeping of other patient-care activities.
At baseline, no ICUs had documentation of 75% patient-care time by all of its affiliates. In the 6 months in which reporting was tied to a group incentive, six of seven ICUs had every affiliate document greater than 75% of their time. Individual time documentation increased from 53% to 84%. Zero-charge time accounted for an average of 21% of each shift. The most common reason was rounding, which accounted for nearly half of all zero-charge time. Sign out, chart review, and teaching were the next most common zero-charge activities. Documentation of time spent on billable activities also increased from 53% of an affiliate's shift to 63%. Time documentation was similar regardless of during which shift an affiliate worked.
Approximately two thirds of an affiliate's shift is spent providing billable services to patients. Greater than 20% of each shift is spent providing equally important but not reimbursable patient care. Understanding how affiliates spend their time and what proportion of time is spent in billable activities can be used to plan the financial impact of staffing ICUs with affiliates.
Background: Beneficial effects of fish consumption on early cognitive development and cardiovascular health have been attributed to the omega-3 fatty acids in fish and fish oils, but toxic chemicals in fish may adversely affect these health outcomes. Risk–benefit assessments of fish consumption have frequently focused on methylmercury and omega-3 fatty acids, not persistent pollutants such as polychlorinated biphenyls, and none have evaluated Great Lakes fish consumption.
Objectives: The risks and benefits of fish consumption have been established primarily for marine fish. Here, we examine whether sufficient data are available to evaluate the risks and benefits of eating freshwater fish from the Great Lakes.
Methods: We used a scoping review to integrate information from multiple state, provincial, and federal agency sources regarding the contaminants and omega-3 fatty acids in Great Lakes fish and fish consumers, consumption rates and fish consumption advisories, and health effects of contaminants and omega-3 fatty acids.
Data synthesis: Great Lakes fish contain persistent contaminants—many of which have documented adverse health effects —that accumulate in humans consuming them. In contrast, data are sparse on omega-3 fatty acids in the fish and their consumers. Moreover, few studies have documented the social and cultural benefits of Great Lakes fish consumption, particularly for subsistence fishers and native communities. At this time, federal and state/provincial governments provide fish consumption advisories based solely on risk.
Conclusions: Our knowledge of Great Lakes fish has critical gaps, particularly regarding the benefits of consumption. A risk–benefit analysis requires more information than is currently available on the concentration of omega-3 fatty acids in Great Lakes fish and their absorption by fish eaters in addition to more information on the social, cultural, and health consequences of changes in the amount of fish consumed.
dioxin; fish consumption; Great Lakes; methylmercury; omega-3 fatty acids; PCBs; risk assessment
Evidence is emerging that exposure to persistent organic pollutants (POP) is a risk factor for atherosclerosis-related diseases and for diabetes mellitus (DM). We hypothesized that residential proximity to sources of POP will be associated with an increase in hospitalization rates for ischemic stroke (IS) with comorbid DM (IS-DM).
We examined IS-DM hospitalization rates in the New York State (exclusive of New York City) during a 12-year period. POP exposure status was assessed based on residency in a zip code containing or abutting environmental sources of POP. Adjusted relative risks (RR) of IS-DM hospitalization were estimated by multivariate Poisson regression.
A statistically significant 10% increase in IS-DM hospitalization rates was observed in populations environmentally exposed to POP (adjusted RR 1.10, 95% confidence interval, CI, 1.01–1.20; p = 0.031). IS-DM hospitalization rates were also higher in males (adjusted RR 1.34, 95% CI 1.30–1.39; p < 0.001), in blacks (adjusted RR 4.54, 95% CI 4.16–4.94; p < 0.001) and in older age groups (p for trend <0.001).
Residential proximity to sources of POP is associated with an increase in RR of IS-DM hospitalization. Our findings support the hypothesis of POP being a risk factor for IS. Further studies are warranted.
Ischemic stroke, epidemiology; Risk factors; Diabetes mellitus; Environmental factors
Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) may be effective in treating depression. Parental verbal abuse has been linked to decreased fractional anisotropy (FA) of white matter and reduced FA correlated with depression and anxiety scores. Utilizing a nonhuman primate model of mood and anxiety disorders following disrupted mother-infant attachment, we examined whether adverse rearing conditions lead to white matter impairment of the ALIC.
We examined white matter integrity using Diffusion Tensor Imaging (DTI) on a 3T-MRI. Twenty-one adult male Bonnet macaques participated in this study: 12 were reared under adverse [variable foraging demand (VFD)] conditions whereas 9 were reared under normative conditions. We examined ALIC, posterior limb of the internal capsule (PLIC) and occipital white matter.
VFD rearing was associated with significant reductions in FA in the ALIC with no changes evident in the PLIC or occipital cortex white matter.
Adverse rearing in monkeys persistently impaired frontal white matter tract integrity, a novel substrate for understanding affective susceptibility.
Diffusion tensor imaging; fractional anisotropy; white matter integrity; variable foraging demand
Fish is a valuable source of nutrition, and many people would benefit from eating fish regularly. But some people eat a lot of fish, every day or several meals per week, and thus can run a significant risk of overexposure to methylmercury. Current advice regarding methylmercury from fish consumption is targeted to protect the developing brain and nervous system but adverse health effects are increasingly associated with adult chronic low-level methylmercury exposure. Manifestations of methylmercury poisoning are variable and may be difficult to detect unless one considers this specific diagnosis and does an appropriate test (blood or hair analysis). We provide information to physicians to recognize and prevent overexposure to methylmercury from fish and seafood consumption. Physicians are urged to ask patients if they eat fish: how often, how much, and what kinds. People who eat fish frequently (once a week or more often) and pregnant women are advised to choose low mercury fish.
Background: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown.
Objectives: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers.
Methods: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure.
Results: Solvent-exposed workers’ performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices—areas serving working memory function and attention—was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers.
Conclusions: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work.
brain function; fMRI; solvent exposure
The effects of low concentrations of aluminum chloride on thymocytes and lymphocytes acutely dissociated from young mice were studied using flow cytometry with a DNA-binding dye. We demonstrate a rapid and dose-dependent injury in murine thymocytes and lymphocytes resulting from exposure to aluminum, as indicated by an increase in the entry into the cell of the DNA-binding dye, propidium iodine. A 60-minute exposure to 10 μM AlCl3 caused damage of about 5% of thymocytes, while 50% were injured after 10 minutes at 20 μM. Nearly all thymocytes showed evidence of damage at 30 μM AlCl3 after only 5 minutes of incubation. In lymphocytes, injury was observed at 15 μM AlCl3 and less than 50% of cells were injured after a 60-minute exposure to 20 μM. Injury only rarely proceeded to rapid cell death and was associated with cell swelling. These results suggest that aluminum has cytotoxic effects on cells of the immune system.
Studies suggest that environmental exposure to persistent organic pollutants (POPs) may be an emerging risk factor for ischemic heart disease, including acute myocardial infarction (AMI). However, some studies indicate that exposure to POPs may also be a risk factor for hypertension, a well-established risk factor for AMI. To investigate effect of POPs on the environmental burden of cardiovascular disease, a study of AMI with comorbid hypertension in populations environmentally exposed to persistent organic pollutants, based on the zip code of residence, was conducted. Data on hospital discharges for AMI with comorbid hypertension were obtained from the New York Statewide Planning and Research Cooperative System for 1993–2004. Patients residing in zip codes containing or abutting POPs contaminated sites were considered environmentally exposed. Relative risks (RR) — with corresponding 95% confidence intervals (95% CI) — of hospitalization for AMI with comorbid hypertension were estimated by Poisson regression, adjusting for known confounders. Adjusted hospitalization rates for AMI with comorbid hypertension were 12.4% higher in populations residing in proximity to a POPs site (adjusted RR = 1.124, 95% CI 1.025–1.233, p < 0.05), compared to not in proximity to a POPs site. Also, hospitalization rates for AMI with comorbid hypertension were higher in males than in females (adjusted RR = 2.157, 95% CI 2.100–2.215, p < 0.05), in African Americans than in Caucasians (adjusted RR = 1.631, 95% CI 1.483–1.794, p < 0.05), and in older age groups (p for trend <0.05). These findings are consistent with the established effects of non-modifiable risk factors and serve as indirect quality indicators for our model. In conclusion, our results support the hypothesis that environmental exposure to POPs increases the burden of cardiovascular disease in exposed populations.
myocardial infarction; hypertension; hazardous waste; persistent organic pollutants
Residents of Anniston, Alabama, live near a Monsanto plant that manufactured polychlorinated biphenyls (PCBs) from 1929 to 1971 and are relatively heavily exposed.
The goal of this study was to determine the relationship, if any, between blood pressure and levels of total serum PCBs, several PCB groups with common actions or structure, 35 individual PCB congeners, and nine chlorinated pesticides.
Linear regression analysis was used to determine the relationships between blood pressure and serum levels of the various contaminants after adjustment for age, body mass index, sex, race, smoking, and exercise in 394 Anniston residents who were not taking antihypertensive medication.
Other than age, total serum PCB concentration was the strongest determinant of blood pressure of the covariates studied. We found the strongest associations for those PCB congeners that had multiple ortho chlorines. We found the associations over the full range of blood pressure as well as in those subjects whose blood pressure was in the normal range. The chlorinated pesticides showed no consistent relationship to blood pressure.
In this cross-sectional study, serum concentrations of PCBs, especially those congeners with multiple ortho chlorines, were strongly associated with both systolic and diastolic blood pressure.
Ah receptor; Anniston; Alabama; body mass index; hypertension; linear regression
Evidence from cell studies indicates that persistent organic pollutants (POP) can induce insulin resistance, an essential component of the metabolic syndrome (MetS). We hypothesized that residential proximity to environmental sources of POP would be associated with the MetS in the population. The present study examined the association between residency in a zip code containing or abutting environmental sources of POP and MetS-related hospitalization rates. Hospitalization data were obtained from the New York Statewide Planning and Research Cooperative System. Relative risks (RR) were calculated as hospitalization rate ratios. Adjusted RR and their 95% confidence intervals (CI) were estimated by multivariable Poisson regression. A higher proportion of African Americans resided in POP zip codes compared to Caucasians (25.9% and 24.3%, respectively, p < 0.01). Residence in POP zip codes was associated with a statistically significant 39.2% increase in MetS-related hospitalization rates, adjusted for race, gender, and age (adjusted RR = 1.392, 95% CI: 1.032–1.879, p = 0.030). Increase in age was independently associated with higher MetS-related hospitalization rates (p for trend < 0.001). Our findings contribute to the body of evidence supporting the hypothesis of POP constituting an environmental risk factor for the MetS. Further studies investigating exposure to POP and insulin resistance are warranted.
persistent organic pollutants; metabolic syndrome; hazardous waste sites; residential proximity
Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) and chlorinated pesticides, have been shown to have many adverse human health effects. These contaminants therefore may pose a risk to Alaska Natives that follow a traditional diet high in marine mammals and fish, in which POPs bioaccumulate.
Methods and Findings
This study examined the levels of PCBs and three pesticides [p, p′-DDE, mirex, and hexachlorobenzene (HCB)] in muscle tissue from nine fish species from several locations around the Aleutian Islands of Alaska. The highest median PCB level was found in rock sole (Lepidopsetta bilineata, 285 ppb, wet weight), while the lowest level was found in rock greenling (Hexagrammos lagocephalus, 104 ppb, wet weight). Lipid adjusted PCB values were also calculated and significant interspecies differences were found. Again, rock sole had the highest level (68,536 ppb, lipid weight). Concerning the PCB congener patterns, the more highly chlorinated congeners were most common as would be expected due to their greater persistence. Among the pesticides, p, p′-DDE generally dominated, and the highest level was found in sockeye salmon (Oncorhynchus nerka, 6.9 ppb, wet weight). The methodology developed by U.S. Environmental Protection Agency (USEPA) was used to calculate risk-based consumption limits for the analyzed fish species. For cancer health endpoints for PCBs, all species would trigger strict advisories of between two and six meals per year, depending upon species. For noncancer effects by PCBs, advisories of between seven and twenty-two meals per year were triggered. None of the pesticides triggered consumption limits.
The fish analyzed, mainly from Adak, contain significant concentrations of POPs, in particular PCBs, which raises the question whether these fish are safe to eat, particularly for sensitive populations. However when assessing any risk of the traditional diet, one must also consider the many health and cultural benefits from eating fish.
Waste Crankcase Oil (WCO), the oil that is removed from motor engines during an oil change, is frequently discarded into the environment, resulting in pollution of both aquatic and terrestrial ecosystems. In some developing countries, this common hazardous material is not properly managed. In Uganda little is known about its generation, utilization, and disposal. These factors were investigated using in-depth interviews of a sample of mechanics from 379 motor repair garages and 109 fuel stations in the Kampala district. Most garages (94%) and fuel stations (96%) in the study area offered oil-changing services. On average, each garage produced 62 litres, and each fuel station produced 134 litres of WCO per week. In garages 35% was sold, 16% poured on the ground, 18% taken by vehicle owners and 31% given away for free. At fuel stations, 49% was picked by private collectors, 27% sold, 4% poured on the ground, 2% burnt, 13% taken by vehicle owners, and 6% given away for free. Uses of WCO included coating roofing timber and fencing posts, use in timber cutting, marking play grounds, and pest control in animals. Its disposal involved burning, and pouring in the environment. Lack of policy and information for proper handling of WCO contributed to the poor management of WCO exhibited.
Waste crankcase oil; generation; disposal; garage; fuel station
Perchloroethylene (PERC) is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994–2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.
White matter abnormalities have been detected using diffusion tensor imaging (DTI) in a variety of locations in the brains of patients with schizophrenia. Studies that included first-episode patients report less severe or no abnormalities but more pronounced deficits in chronic patients. Here we investigated these abnormalities in a very large group of schizophrenia that had both large ranges in age and in duration of illness. A highly reproducible DTI-tractography technique was used to quantify the fractional anisotropy of the genu and splenium of the corpus callosum as well as the bilateral pyramidal tracts. We found a decline in fractional anisotropy that correlated with the duration of illness in the genu and splenium of the corpus callosum but not in the pyramidal tracts. The findings suggest that there are white matter tract-specific degenerative mechanisms that may be present at the point of illness onset and that progress throughout the illness.
Diffusion Tensor Imaging; Schizophrenia; Fiber Tracking
Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems.
We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population.
We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately.
Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05–0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06–0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women.
Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men.
DDE; endocrine disruption; hexachlorobenzene mirex; Native Americans
Studying the impact of environmental exposures is important in children because they are more vulnerable to adverse effects on growth, development, and health. Assessing exposure in children is difficult, and measuring biomarkers is potentially useful. Research measuring biomarkers in children raises a number of ethical issues, some of which relate to children as research subjects and some of which are specific to biomarker research.
As an international group with experience in pediatric research, biomarkers, and the ethics of research in children, we highlight the ethical issues of undertaking biomarker research in children in these environments.
Significant issues include undertaking research in vulnerable communities, especially in developing countries; managing community expectations; obtaining appropriate consent to conduct the research; the potential conflicts of obtaining permission from an ethics review board in an economically developed country to perform research in a community that may have different cultural values; returning research results to participants and communities when the researchers are uncertain of how to interpret the results; and the conflicting ethical obligations of maintaining participant confidentiality when information about harm or illegal activities mandate reporting to authorities.
None of these challenges are insurmountable and all deserve discussion. Pediatric biomarker research is necessary for advancing child health.
biobanks; biomarkers; children; environmental exposure; genetics; infants; informed consent; research ethics
Animal studies have suggested that the reduction in stroke risk observed with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) therapy is owing to an increase in basal cerebral blood flow (CBF). The purpose of the study was to determine if statin therapy was associated with increased CBF in humans with cerebrovascular atherosclerotic disease. Quantitative measurements of CBF were obtained on study entry in 97 patients with carotid artery occlusion enrolled in a prospective study of cerebral hemodynamics and stroke risk. This study represents a post hoc analysis of CBF measurements based on whether patients were receiving statin therapy at the time of CBF measurement. Global and regional CBF (including hemispheric, basal ganglia, and arterial borderzones), and baseline clinical, epidemiologic, and laboratory stroke risk factors were compared between the two groups. Nineteen of the 97 patients were on a statin agent on study entry. The statin group was younger, had significantly lower LDL levels and included more women. Statin therapy was not associated with higher baseline values of CBF in global or regional analyses. Mean middle cerebral artery territory CBF (±s.d.) ipsilateral to the occluded carotid artery was 37.6±12.7 mL/100 g min for the statin group (n = 19) compared with 38.6±12.7 mL/100 g min for the nonstatin group (n = 78). Contralateral values were 42.9±13.5 and 44.2±13.3 mL/100 g min for the statin and nonstatin groups, respectively. We conclude that the stroke risk reduction observed with statin therapy in humans likely involves mechanisms other than an increased basal CBF.
atherosclerosis; CBF measurements; cerebral hemodynamics; cerebrovascular disease