Faculty Bibliography

Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions

Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies

Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes, including premalignant and malignant skin tumors, total mortality, pregnancy outcomes, and children's cognitive development. In this paper, we provide descriptions of the study methods including study design, study population, data collection, response rates, and exposure and outcome assessments. We also present characteristics of the study participants including the distribution of exposure and the prevalence of skin lesion at baseline recruitment. A total of 11,746 married men and women between 18 and 75 years of age participated in the study at baseline (a response rate of 98%) and completed a full questionnaire interview that included a food frequency questionnaire, with a response rate of 98%. Among the 98% of the participants who completed the clinical evaluation, over 90% provided blood samples and spot urine samples. Higher educational status, male gender, and presence of premalignant skin lesions were associated with an increased likelihood of providing blood and urine samples. Older participants were less likely to donate a blood sample. About one-third of the participants consumed water from a well with As concentration in each of three groups: >100 mug/l, 25-100 mug/l, and <25 mug/l. Average urinary As concentrations were 140 and 136 mug/l for males and females, respectively. HEALS has several unique features, including a prospective study design, comprehensive assessments of both past and future changes in As exposure at the individual level, a large repository of biological samples, and a full dose range of As exposures in the study population. HEALS is a valuable resource for examining novel research questions on the health effects of As exposure.Journal of Exposure Analysis and Environmental Epidemiology advance online publication, 14 September 2005; doi:10.1038/sj.jea.7500449

We conducted a population-based prevalence survey in Araihazar, Bangladesh, to describe the distribution of arsenic exposure in a rural Bangladeshi population and to assess the population's awareness to this problem as well as to possible remediation options. Water samples from 5,967 contiguous tube wells in a defined geographic area were tested using laboratory-based methods. Additionally, for each well, the owner/caretaker (or a close relative) was interviewed regarding his or her awareness of the health consequences of As exposure. Arsenic exposure data and demographic characteristics for the 65,876 users of these wells were also collected from the 5,967 respondents. Among the 65,876 residents, more than half (54%) regularly consumed well water with an As concentration > or = 50 microg/L--above the acceptable government standard in Bangladesh. Respondents were 15-92 years of age, with an average age of 42 years, and 43% were male. Presence of awareness was significantly related to male sex, nonlabor head of household occupation, better housing, and having had the well tested for As concentration. Most respondents (92%) expressed a willingness to take steps to reduce their exposure, with switching to a safe well the most favored option (46.2%). Willingness to reduce exposure was positively related to awareness of the health risks of As. However, the association between awareness and switching to a safe well [odds ratio (OR) = 1.25; 95% confidence interval (CI), 1.01-1.54] was no stronger than the associations between awareness and using surface water (with or without treatments) (OR = 1.54; 95% CI, 1.22-1.95) or using an existing well after treatment or increasing the depth (OR = 1.34; 95% CI, 1.08-1.67). These findings suggest that health education programs may need to target individuals with lower socioeconomic status and that well switching should be encouraged with more appropriate health education. Increasing knowledge of the health consequences of As may be an important element in facilitating remediation

OBJECTIVE: We sought to determine whether supplementation of vitamin E (alpha-tocopherol), selenium (L-selenomethionine), or their combination improves arsenical skin lesions. METHODS: A 2 x 2 randomized, placebo-controlled, double-blind trial among 121 men and women chronically exposed to arsenic in drinking water was conducted in rural Bangladesh. Participants were randomized to one of four treatment arms: vitamin E, selenium, vitamin E and selenium (combination), or placebo and were treated for 6 months. RESULTS: At baseline, the average skin lesion scores were 2.23, 2.26, and 2.63 and at follow-up, the average skin lesion scores went down to 2.00, 2.06, and 2.47 in those receiving vitamin E, selenium, and the combination, respectively. CONCLUSIONS: Supplementation with vitamin E and selenium, either alone or in combination, slightly improved skin lesion status, although the improvement was not statistically significant

EphA4 signaling has recently been implicated in the regulation of synapse formation and plasticity. In this study, we show that ankyrin repeat-rich membrane spanning (ARMS; also known as a kinase D-interacting substrate of 220 kD), a substrate for ephrin and neurotrophin receptors, was expressed in developing muscle and was concentrated at the neuromuscular junction (NMJ). Using yeast two-hybrid screening, we identified a PDZ (PSD-95, Dlg, ZO-1) domain protein, alpha-syntrophin, as an ARMS-interacting protein in muscle. Overexpression of alpha-syntrophin induced ARMS clustering in a PDZ domain-dependent manner. Coexpression of ARMS enhanced EphA4 signaling, which was further augmented by the presence of alpha-syntrophin. Moreover, the ephrin-A1-induced tyrosine phosphorylation of EphA4 was reduced in C2C12 myotubes after the blockade of ARMS and alpha-syntrophin expression by RNA interference. Finally, alpha-syntrophin-null mice exhibited a disrupted localization of ARMS and EphA4 at the NMJ and a reduced expression of ARMS in muscle. Altogether, our findings suggest that ARMS may play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EphA4

BACKGROUND: Several case reports and series report an association between celiac disease and inflammatory bowel disease (IBD); however, there is no current data assessing this association. We therefore studied the occurrence of these conditions in a cohort of patients with celiac disease seen at a referral center. METHODS: A database of patients with celiac disease seen between 1981 and 2002 was analyzed. Only biopsy-proven adults were included. Patients who had endoscopic and pathologic evidence of IBD were identified, and their pathology was reviewed. Age- and sex-adjusted prevalence rate ratios were determined by comparing results with population-based prevalence data. RESULTS: Among 455 patients with celiac disease, IBD was identified in 10 (5 had ulcerative colitis and 5 had Crohn's disease). This represented an age- and sex-adjusted prevalence rate ratio for ulcerative colitis of 3.56 (95% confidence interval, 1.48-8.56) and for Crohn's disease of 8.49 (95% confidence interval, 3.53-20.42). CONCLUSION: Within our cohort of patients with celiac disease, IBD was significantly more common than in the general population