Prospective cohort study of respiratory effects at ages 14 to 26 following early life exposure to arsenic in drinking water.

Background: We previously reported chronic respiratory effects in children who were then 7-17 years of age in Matlab, Bangladesh. One group of children had been exposed to high concentrations of arsenic in drinking water in utero and early childhood (average 436 µg/L), and the other group of children were never known to have been exposed to >10 µg/L. The exposed children, both males and females, had marked increases in chronic respiratory symptoms.

Age at Exposure to Arsenic in Water and Mortality 30-40 Years After Exposure Cessation.

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure.

Obesity and increased susceptibility to arsenic-related type 2 diabetes in Northern Chile.

Background: The prevalence of type 2 diabetes (T2D) has nearly doubled since 1980. Elevated body mass index (BMI) is the leading risk factor for T2D, mediated by inflammation and oxidative stress. Arsenic shares similar pathogenic processes, and may contribute to hyperglycemia and β-cell dysfunction.

Lung, Bladder, and Kidney Cancer Mortality 40 Years After Arsenic Exposure Reduction.

Background: Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction.

Methods: We previously identified high mortality rates in Region II up to the year 2000.

Maternal perchlorate exposure in pregnancy and altered birth outcomes.

Background: At high medicinal doses perchlorate is known to decrease the production of thyroid hormone, a critical factor for fetal development. In a large and uniquely exposed cohort of pregnant women, we recently identified associations between environmental perchlorate exposures and decreased maternal thyroid hormone during pregnancy. Here, we investigate whether perchlorate might be associated with birthweight or preterm birth in the offspring of these women.

2,4-dichlorophenoxyacetic acid (2,4-D) and risk of non-Hodgkin lymphoma: a meta-analysis accounting for exposure levels.

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most commonly used selective herbicides in the world. A number of epidemiology studies have found an association between 2,4-D exposure and non-Hodgkin lymphoma (NHL) but these results are inconsistent and controversial. A previous meta-analysis found no clear association overall but did not specifically examine high-exposure groups.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile.

Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited.

Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60μg/L; and Arica, with long-term water concentrations ≤10μg/L.

Results: Compared to adults never exposed >10μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.

Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California.

Background: Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring.

Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life.

Background: Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer.

Rapid reduction in breast cancer mortality with inorganic arsenic in drinking water.

Background: Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970.

Methods: We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations.

Elevated lung cancer in younger adults and low concentrations of arsenic in water.

Arsenic concentrations greater than 100 µg/L in drinking water are a known cause of cancer, but the risks associated with lower concentrations are less well understood. The unusual geology and good information on past exposure found in northern Chile are key advantages for investigating the potential long-term effects of arsenic. We performed a case-control study of lung cancer from 2007 to 2010 in areas of northern Chile that had a wide range of arsenic concentrations in drinking water.

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

Background: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer.

Methods: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data.

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile.

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.

Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh.

Background: Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited.

Methods: This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7-17 years.

Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer.

Background: Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer.

Methods: We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern Chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust.

Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed Northern Chile.

Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response.

Drinking water arsenic in northern chile: high cancer risks 40 years after exposure cessation.

Background: Millions of people worldwide are exposed to arsenic-contaminated water. In the largest city in northern Chile (Antofagasta), more than 250,000 people were exposed to high arsenic drinking water concentrations from 1958 until 1970 when a water treatment plant was installed. Because of its unique geology, limited water sources, and good historical records, lifetime exposure and long-term latency patterns can be assessed in this area with better accuracy than in other arsenic-exposed areas worldwide.

Mortality in young adults following in utero and childhood exposure to arsenic in drinking water.

Background: Beginning in 1958, the city of Antofagasta in northern Chile was exposed to high arsenic concentrations (870 µg/L) when it switched water sources. The exposure abruptly stopped in 1970 when an arsenic-removal plant commenced operations. A unique exposure scenario like this--with an abrupt start, clear end, and large population (125,000 in 1970), all with essentially the same exposure--is rare in environmental epidemiology.

Ischemia-reperfusion injury in rat steatotic liver is dependent on NFκB P65 activation.

Background: Steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly, contributing to increased primary graft nonfunction following transplantation. Activation of nuclear factor kappa-B (NFκB) following I/R injury plays a crucial role in activation of pro-inflammatory responses leading to injury.

Methods: We evaluated the role of NFκB in steatotic liver injury by using an orthotopic liver transplant (OLT) model in Zucker rats (lean to lean or obese to lean) to define the mechanisms of steatotic liver injury.

Creatinine, diet, micronutrients, and arsenic methylation in West Bengal, India.

Background: Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic.

Objectives: We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data.

Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis.

Arsenic in drinking water causes increased mortality from several cancers, ischemic heart disease, bronchiectasis, and other diseases. This paper presents the first evidence relating arsenic exposure to pulmonary tuberculosis, by estimating mortality rate ratios for Region II of Chile compared with Region V for the years 1958-2000. The authors compared mortality rate ratios with time patterns of arsenic exposure, which increased abruptly in 1958 in Region II and then declined starting in 1971.

Kidney cancer mortality: fifty-year latency patterns related to arsenic exposure.

Background: Arsenic in drinking water is associated with kidney cancer. Beginning in 1958, a region of Chile experienced a rapid onset of high arsenic exposure in drinking water, followed by sharp declines when water treatment plants were installed in 1971.

Methods: For the years 1950-1970, we obtained mortality data from death certificates for an exposed region and an unexposed region in Chile.

Low-level population exposure to inorganic arsenic in the United States and diabetes mellitus: a reanalysis.

Background: Although studies have reported associations between high concentrations of ingested inorganic arsenic and diabetes mellitus, there is no evidence of this association at low exposures. However, a well-publicized study (JAMA. 2008;300:814-822) recently produced an extraordinary finding of a more than 3-fold increase in diabetes at low concentrations of urinary arsenic.

Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile.

Arsenic in drinking water is an established cause of lung, bladder, and skin cancers in adults and may also cause adult kidney and liver cancers. Some evidence for these effects originated from region II of Chile, which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water.

Incidence of residual choledocholithiasis detected by intraoperative cholangiography at the time of laparoscopic cholecystectomy in patients having undergone preoperative ERCP.

Introduction: The purpose of this study is to determine the incidence of residual common bile duct (CBD) stones after preoperative ERCP for choledocholithiasis and to evaluate the utility of routine intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) in this patient population.

Methods: All patients who underwent preoperative ERCP and interval LC with IOC from 5/96 to 12/05 were reviewed under an Institutional Review Board (IRB)-approved protocol. Data collected included all radiologic imaging, laboratory values, clinical and pathologic diagnoses, and results of preoperative ERCP and LC with IOC.