Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke.

BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.

Retrospective Pathological Studies of Splenic Lesions in Domestic Hamsters (Phodopus spp.).

Fifteen splenic biopsy specimens from a total of 212 biopsy specimens and necropsy cases of domestic hamsters (Phodopus spp.) from the Division of Wild (Exotic) Animal Medicine, Veterinary Medical Teaching Hospital, National Chung Hsing University, Taiwan, collected between 2010 and 2017, were studied retrospectively. The incidence of lesions in the spleen was 7.1% (15/212). The mean age of affected hamsters was 16.6 months and females were affected more than males. The lesions consisted of 10 neoplasms and five non-neoplastic lesions. The most common tumours were histiocytic sarcoma (HS), lymphoma, malignant fibrous histiocytoma (MFH) and hemangiosarcoma. Immunohistochemistry revealed the HSs and MFHs to express lysozyme. The lymphomas were negative for CD20; however, one case was positive for CD3 and another was positive for CD79a. The hemangiosarcoma expressed von Willebrand factor. The non-neoplastic lesions were all fibrotic nodules and these were all identified in ageing female hamsters. The nodules consisted of collagen fibres identified with Masson's trichrome stain, and they were related to repair of trauma in the spleen.

Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph node metastasis from papillary thyroid carcinoma.

OBJECTIVES: Ultrasound-guided aspiration cytology (US-FNAC) was previously used to diagnose lymph node metastasis of papillary thyroid carcinoma (PTC). Combined US-FNAC with nodal thyroglobulin (LN-FNA-Tg) significantly improved the diagnostic rate. However, diagnostic accuracy depends on proper node selection. Therefore, it is crucial to choose the nodes with reliable sonographic features to guide clinician for confirmation. DESIGN AND SETTING: Retrospective cohort study was carried out in one medical centre from 2011 to 2014. PARTICIPANTS: A total of 148 patients with PTC, being treated by total thyroidectomy and radioiodine, were assessed for potential nodal metastases by ultrasound. MAIN OUTCOME MEASURES: Lymph nodes with cystic content, peripheral hypervascularity, calcification, hyperechoic content, the absence of hilum and Solbiati index < 2 indicated risk of malignancy. US-FNAC and LN-FNA-Tg were both performed. Positive nodal metastasis was further confirmed by dissection. Risk impact of these sonographic features on LN-FNA-Tg to diagnose nodal metastasis was tested by logistic regression analysis based on the significance in both univariate and multivariate models. RESULTS: Overall, 49 lymph nodes were documented as recurrent nodal metastasis. LN-FNA-Tg greater than serum thyroglobulin and higher than 1 ng/mL achieved 100% of diagnostic rate for recurrent nodal metastasis. The malignant sonographic features that significantly cohered with positive LN-FNA-Tg were cystic and hyperechoic content and lack hilum, in sequence. CONCLUSIONS: LN-FNA-Tg is an excellent tool to quantitatively diagnose nodal metastasis. To achieve ideal diagnosis, the most reliable sonographic features were cystic content, hyperechoic content and the absence of hilum in lymph nodes, but not calcification or Solbiati index < 2.

Phylogenetic Analysis of the Spike (S) Gene of the New Variants of Porcine Epidemic Diarrhoea Virus in Taiwan.

New variants of porcine epidemic diarrhoea virus (PEDV), which emerged in Taiwan in late 2013, have caused a high morbidity and mortality in neonatal piglets. To investigate the molecular characteristics of the spike (S) gene of the emerging Taiwan PEDV strains for a better understanding of the genetic diversity and relationship among the Taiwan new variants and the global PEDVs, full-length S genes of PEDVs from nine 1-7 day-old piglets from three pig farms in the central and southern Taiwan were sequenced and analysed. The result of phylogenetic analysis of the S gene showed that all the Taiwan PEDV strains were closely related to the non-S INDEL strains from US, Canada and China, suggesting a common ancestor for these strains. As compared with the historic PEDVs and CV777-based vaccine strains, the nine Taiwan PEDV variants shared almost the same genetic signatures as the global non-S INDEL strains, including a series of insertions, deletions and mutations in the amino terminal as well as identical mutations in the neutralizing epitopes of the S gene. The high similarity of the S protein among the Taiwan and the globally emerged non-S INDEL PEDV strains suggests that the Taiwan new variants may share similar pathogenesis and immunogenicity as the global outbreak variants. The development of a novel vaccine based on the Taiwan or the global non-S INDEL strains may be contributive to the control of the current global porcine epidemic diarrhoea outbreaks.

Efficacy of phenytoin, valproic acid, carbamazepine and new antiepileptic drugs on control of late-onset post-stroke epilepsy in Taiwan.

BACKGROUND AND PURPOSE: To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post-stroke epilepsy. METHODS: This nationwide cohort study was conducted by using data from 2004 to 2008 on new occurrence of post-stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan-Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs. RESULTS: In all, 3622 late-onset post-stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person-months based on ER visits [95% confidence interval (CI) 0.95-1.15] and hospitalizations (95% CI 0.62-0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person-months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42-0.74; P < 0.001), 0.37 (95% CI 0.18-0.75; P = 0.006) and 0.28 (95% CI 0.15-0.52; P < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results. CONCLUSIONS: This large nationwide, population-based study demonstrated that late-onset post-stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization.

Newly diagnosed gastroesophageal reflux disease increased the risk of acute exacerbation of chronic obstructive pulmonary disease during the first year following diagnosis--a nationwide population-based cohort study.

BACKGROUND: While prior studies have demonstrated that chronic obstructive pulmonary disease (COPD) is associated with gastroesophageal reflux disease (GERD), and that GERD is associated with acute exacerbations of COPD (AECOPD), no study to date has been able to establish temporality in this relationship. The purpose of this cohort study was to explore the impact of a new diagnosis of GERD on the risk of subsequent AECOPD. METHODS: We used a retrospective population-based cohort design to analyse the data of 1976 COPD subjects with GERD as an exposure cohort and 3936 COPD subjects without GERD as a comparison group. We individually tracked each subject in this study for 12 months and identified those subjects who experienced an episode of AECOPD. Hazard ratios (HR) were calculated using Cox proportional hazards regression analysis. RESULTS: The incidence of AECOPD was 4.08 and 2.79 per 100 person-year in individuals with and without GERD, respectively (p = 0.012). Following adjustment for sex, age, ischaemic heart disease, heart failure, atrial fibrillation, hypertension, osteoporosis, anxiety, diabetes mellitus, angina, stroke, anaemia, dementia, occupational category, monthly insurance premium, number of OPD visits and COPD severity. The stepwise Cox regression analysis revealed that GERD was independently associated with an increased risk of AECOPD (HR = 1.48, 95% CI = 1.10-1.99). CONCLUSION: This study demonstrated that GERD is an independent risk factor for AECOPD. Caution should be exercised when assessing GERD symptoms in patients with COPD.

Central nervous system infections and stroke -- a population-based analysis.

BACKGROUND: Chronic central nervous system (CNS) infections have been found to associate with cerebrovascular complications. Acute CNS infections are more common than chronic CNS infections, but whether they could increase the risk of vascular diseases has not been studied. METHODS: The study cohort comprised all adult patients with diagnoses of CNS infections from Taiwan National Health Insurance Research Database during 2000-2009 (n = 533). The comparison group were matched by age, sex, urbanization, diagnostic year, and vascular risk factors of cases (cases and controls = 1:5). Patients were tracked for at least 1 year. Kaplan-Meier analysis was used to compare the risk of stroke and acute myocardial infarction (AMI) after adjusting censoring subjects. RESULTS: After adjusting the patients demographic characteristics and comorbidities, the risk of patients with CNS infections developing stroke was 2.75-3.44 times greater than their comparison group. More than 70% of the stroke events were occurring within 1 year after CNS infections. The risk of AMI was not found as we compared patients with and without CNS infections. CONCLUSIONS: The population-based cohort study suggested that adult patients with CNS infections have higher risk to develop stroke but not AMI, and the risk is marked within a year after infections.

Pre-ICH warfarin use, not antiplatelets, increased case fatality in spontaneous ICH patients.

BACKGROUND AND PURPOSE: Anticoagulant and antiplatelets for prevention of ischaemic stroke and cardiovascular diseases may increase the risk of intracerebral hemorrhage (ICH). This study aimed to investigate the influence of pre-ICH use of anticoagulant and antiplatelets on ICH patients. METHODS: Consecutive patients with acute spontaneous ICH registered in a single-center stroke registry during 2001 to 2010 were analyzed and categorized according to their pre-ICH use of warfarin (Group I), antiplatelets (Group II), or neither (Group III). Survival analysis and the Cox proportional hazard model were used to compare between the three groups and the predictors. RESULTS: Of 2021 ICH patients (male, 63.3%; mean age, 62.6 ± 14.4 years) included, there were 94 (4.7%) in Group I, 232 (11.4%) in Group II, and 1695 (83.9%) in Group III. Warfarin users had larger hematoma volume, more intraventricular extension, higher frequencies of lobar ICH, and higher case fatality than non-warfarin users (Groups II and III). The Cox proportional hazard model showed increased 6-month case fatality in pre-ICH warfarin users (adjusted hazard ratio 2.75, 95% confidence interval 2.04-3.72, P < 0.001), but not in pre-ICH antiplatelet users (adjusted hazard ratio 0.95, 95% confidence interval 0.72-1.26). CONCLUSIONS: Intracerebral hemorrhage patients with prior warfarin use, but not antiplatelet use, had significantly higher case fatality at 6 months.

B lymphocyte-induced maturation protein 1 (BLIMP-1) attenuates autoimmune diabetes in NOD mice by suppressing Th1 and Th17 cells.

AIMS/HYPOTHESIS: Recent reports indicate that B lymphocyte-induced maturation protein 1 (BLIMP-1), encoded by the Prdm1 gene, expands its control over T cells and is associated with susceptibility to colitis in mice with T cell-specific BLIMP-1 deficiency. In this study, we aimed to investigate the potential role of BLIMP-1 in regulating autoimmune diabetes and T helper type 17 (Th17) cells. METHODS: We generated T cell-specific Blimp1 (also known as Prdm1) transgenic (Tg) or conditional knockout (CKO) NOD mice, in which Blimp1 is overexpressed or deleted in T cells, respectively. By side-by-side analysing these Tg or CKO mice, we further dissected the potential mechanisms of BLIMP-1-mediated modulation on autoimmune diabetes. RESULTS: Overproduction of BLIMP-1 in T cells significantly attenuated insulitis and the incidence of diabetes in NOD mice. Consistent with these results, the diabetogenic effect of splenocytes was remarkably impaired in Blimp1 Tg mice. Moreover, overproduction of BLIMP-1 repressed the proliferation and activation of lymphocytes and enhanced the function of regulatory T cells (Tregs) in NOD mice. In contrast, mice lacking BLIMP-1 in T cells markedly increased Th1 and Th17 cells, and developed highly proliferative and activated lymphocytes. Strikingly, overexpansion of Th1 and Th17 cells in CKO mice was significantly reduced by introducing a Blimp1 transgene, reinforcing the emerging role of BLIMP-1 in autoimmunity. CONCLUSIONS/INTERPRETATION: We conclude that BLIMP-1 orchestrates a T cell-specific modulation of autoimmunity by affecting lymphocyte proliferation and activation, Th1 and Th17 cell differentiation, and Treg function. Our results provide a theoretical basis for developing BLIMP-1-manipulated therapies for autoimmune diabetes.

Oral administration recombinant porcine epidermal growth factor enhances the jejunal digestive enzyme genes expression and activity of early-weaned piglets.

This study attempted to determine ingested porcine epidermal growth factor (pEGF) on the gastrointestinal tract development of early-weaned piglets. Thirty-two piglets (14-day weaned) were randomly allotted to supplemented with 0 (control), 0.5, 1.0, or 1.5 mg pEGF/kg diet. Each treatment consisted of four replicates with two pigs per pen for a 14 days experimental period. Piglets were sacrificed and gastrointestinal tract samples were collected to measure mucosa morphology, mRNA expression and activities of digestive enzymes in the gastrointestinal tract of piglets at the end of the experiment. Diets supplemented with pEGF failed to influence growth performance but tended to increase jejunal mucosa weight (p < 0.09) and protein content (p < 0.07). Piglets supplemental pEGF induced incrementally the gastric pepsin activity (p < 0.05) and stimulated jejunal alkaline phosphatase (ALP) and lactase activities accompanied with the increase of jejunal ALP and maltase mRNA expression. No effect of pEGF on the activities of all enzymes in ileum except the stimulation of ileal aminopeptide N mRNA expression. These results reveal that dietary pEGF supplementation might enhance gene expression and activities of digestive enzymes in the stomach and jejunum of piglets.

Association among hypogonadism, quality of life and erectile dysfunction in middle-aged and aged male in Taiwan.

The association between hypogonadism, quality of life (QoL), and erectile dysfunction (ED) among the middle-aged and aged male in Taiwan is evaluated. A total of 680 study subjects aged >or=40 years old were recruited from Northern (n=276), Middle (n=238), and Southern (n=202) Taiwan, respectively. ED was diagnosed by score of International Index of Erectile Function (IIEF-5). Taiwan version questionnaire for QoL includes domain 1 (physical domain), domain 2 (psychological domain), domain 3 (social relationship domain), and domain 4 (environmental domain) was used to measure QoL. Blood hormones, including FSH, LH, Prolactin, SHBG, total testosterone (TT), calculated free testosterone (cFT), and bioavailable testosterone (Bio-T), were determined. Logistic regression analysis was used to estimate crude and multivariate-adjusted odds ratio of risk factors and its 95% confidence interval. A significantly inverse association between concentration of serum cFT and Bio-T, and severity of ED was observed. Scores of QoL of Domain 1-4 were significantly decreased with the increament of severity of ED. Significant correlations were found between IIEF scores and four domains of QoL, respectively. After adjustment for age, cFT and Bio-T, study subjects with ED (IIEF

Plasma-transforming growth factor-alpha expression in residents of an arseniasis area in Taiwan.

Epidemiological studies have demonstrated an association between long-term exposure to inorganic arsenic and the related adverse effects such as cancers, skin lesions, and vascular diseases. Although several hypotheses have been proposed for the mechanism of arsenic-induced pathogenesis, it remains imperfectly understood. Recent studies have suggested that alterations in growth signal transduction pathways, particularly involving transforming growth factor-alpha (TGF-alpha), may be important. Immunoassays were used to determine the plasma levels of TGF-alpha and epidermal growth factor receptor (EGFR), which is the receptor for TGF-alpha, in residents of an arseniasis area of Taiwan in relation to their estimated cumulative arsenic exposure from drinking water. No relationship between arsenic exposure and EGFR was found. However, among the high cumulative exposure group (>6 ppm-years), levels of plasma TGF-alpha (25.5+/-38.2 pg ml-1) and the proportion of individuals with TGF-alpha over-expression (29.4%) were significantly higher (p<0.05) than normal, healthy unexposed controls (8.1+/-5.6 pg ml-1, 8.6%, respectively). There was a significant linear trend between cumulative arsenic exposure and the prevalence of plasma TGF-alpha over-expression after adjusting for age and sex (p=0.019). The results suggest that plasma TGF-alpha expression may be a useful biomarker when detecting adverse effects on arsenic exposed population.

Infrared thermography to mass-screen suspected SARS patients with fever.

Fever greater than 38 degrees C is a cardinal sign of patients with the severe acute respiratory syndromes (SARS). To reduce the risk of nosocomial cross infections, screening all patients and visitors who visit hospitals and clinics for fever at the entrance of every hospital building has become a standard protocol in Taiwan during the SARS epidemic from mid-April to mid-June 2003. We used a digital infrared thermal imaging (DITI) system (Telesis Spectrum 9000 MB) to conduct mass screening of patients and visitors who entered the hospital to identify those with fever. The DITI system has two components: a sensor head and a PC imaging workstation. The sensor head is an optic-mechanical device which consists of imagining optics for focusing the infrared source information on the infrared detector. The infrared images are further converted into electrical signals, which are then processed for real-time display on the monitor. During the period from April 13 to May 12 2003, 72,327 outpatients and visitors entered Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan. A total of 305 febrile patients (0.42%) was detected by infrared thermography. Among them, three probable SARS patients were identified after thorough studies including contact history, laboratory tests and radiology examinations. The findings suggests that infrared thermography was an effective and reliable tool ideal for mass-screening patients with fever in the initial phase of screening for SARS patients at a busy hospital which sees approximately 3,000 outpatients every weekday during the SARS epidemic.

Orally administrable enterotoxigenic Escherichia coli vaccine encapsulated by ethylcellulose powder dispersion.

To overcome the limitations of injection administration to vaccinate neonatal piglets against diarrheal disease, an oral vaccine needs to be developed. Enteric microspheres of oral vaccines were developed by a co-spray drying process based on formalin-inactivated enterotoxigenic Escherichia coli antigens with various encapsulating materials. The encapsulating efficiencies of ECN7m, ECN14m and ECN22m (vaccine microsphere formulations) tested by extraction procedure are high, more than 85%. To assess enteric characteristics, an in vitro dissolution test was performed with microspheres. Formulations with ethylcellulose ECN14m and ECN22m allow controlled release in a neutral or basic environment and resisted acid damage. In all cases, 95% of the E. coli protein was released within 2 h at pH 6.8-7, but there was no release at pH 1.5-2. However, ECN7m was less acid-resistant and had lower release at low pH. In animal immunization tests, oral immunization with microspheres of formulations ECN14 and ECN22m effectively evoked both systemic IgG and mucosal IgA responses against E. coli whole cell antigens in mice. In the mice challenge test, orally administrable ECNm14 (12 mg) or ECN22m (12.6 mg) vaccine (i.e., encapsulating 3.0x10(9) cfu inactive bacterial mass) provided good protection from infection in animals.

Seroepidemiologic survey of Dirofilaria immitis infection among domestic dogs in Taipei City and mountain aboriginal districts in Taiwan (1998-1999).

To estimate the seroprevalence of Dirofilaria immitis infection in domestic dogs in Taiwan, we utilized a commercial ELISA kit (Snap, IDEXX, USA) for detecting circulating antigens released by adult female worms. Serum specimens of 664 domestic dogs sampled from Taipei City in northern Taiwan and 14 mountain aboriginal districts in eastern Taiwan were screened for D. immitis antigens. Multivariate-adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated by multiple logistic regression analysis. A total of 89 subjects were antigen-positive, giving a seroprevalence of 13.4%, of which the seroprevalence in Taipei City and mountain aboriginal districts were 13.8 and 12.1%, respectively. The mean overall seropositive rates were 6.3% in 1-3-year-old age group, 14.1% in 3-6-year-old age group and 23.7% in the > or =6-year-old age group. The older the age, the higher the seroprevalence (OR=4.6, 95% CI=2.4-9.0 for the > or =6-year-old age group versus 1-3-year-old age group, P<0.001) for all the dogs in the present study. Moreover, seroprevalence was not different between female and male dogs in either Taipei City or mountain aboriginal districts (P>0.05). Also, no significant difference in seroprevalence among dogs between the two geographical areas was found (P>0.05). In the logistic regression analysis, the seroprevalence of D. immitis remained significantly increased with age after multivariate adjustment in the present study. To our knowledge, this is the first report on the status of D. immitis infection in domestic dogs in Taipei City and mountain aboriginal districts in Taiwan to date.

Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan.

Arsenic is a notorious environmental toxicant known as both a carcinogen and an atherogen in human beings, but the pathogenic mechanisms are not completely understood. In cell culture studies, trivalent arsenic enhanced oxidative stress in a variety of mammalian cells, and this association may be closely associated with the development of arsenic-related diseases. To investigate the effect of arsenic exposure on oxidative stress in humans, we conducted a population study to determine the relationships of blood arsenic to reactive oxidants and antioxidant capacity at the individual level. We recruited 64 study subjects ages 42-75 years from residents of the Lanyang Basin on the northeast coast of Taiwan, where arsenic content in well water varies from 0 to > or = 3,000 microg/L. We used a chemiluminescence method, with lucigenin as an amplifier for measuring superoxide, to measure the plasma level of reactive oxidants. We used the azino-diethyl-benzthiazoline sulphate method to determine the antioxidant capacity level in plasma of each study subject. We determined arsenic concentration in whole blood by hydride formation with an atomic absorption spectrophotometer. The average arsenic concentration in whole blood of study subjects was 9.60 +/- 9.96 microg/L (+/- SD) with a range from 0 to 46.50 microg/L. The level of arsenic concentration in whole blood of study subjects showed a positive association with the level of reactive oxidants in plasma (r = +0.41, p = 0.001) and an inverse relationship with the level of plasma antioxidant capacity (r = -0.30, p = 0.014). However, we found no significant association (p = 0.266) between levels of plasma reactive oxidants and antioxidant capacity. Our results also show that the lower the primary arsenic methylation capability, the lower the level of plasma antioxidant capacity (p = 0.029). These results suggest that ingestion of arsenic-contaminated well water may cause deleterious effects by increasing the level of reactive oxidants and decreasing the level of antioxidant capacity in plasma of individuals. Persistent oxidative stress in peripheral blood may be a mechanism underlying the carcinogenesis and atherosclerosis induced by long-term arsenic exposure.

Incidence of transitional cell carcinoma and arsenic in drinking water: a follow-up study of 8,102 residents in an arseniasis-endemic area in northeastern Taiwan.

A significant association between ingested arsenic and bladder cancer has been reported in an arseniasis-endemic area in southwestern Taiwan, where many households share only a few wells in their villages. In another arseniasis-endemic area in northeastern Taiwan, each household has its own well for obtaining drinking water. In 1991-1994, the authors examined risk of transitional cell carcinoma (TCC) in relation to ingested arsenic in a cohort of 8,102 residents in northeastern Taiwan. Estimation of each study subject's individual exposure to inorganic arsenic was based on the arsenic concentration in his or her own well water, which was determined by hydride generation combined with atomic absorption spectrometry. Information on duration of consumption of the well water was obtained through standardized questionnaire interviews. The occurrence of urinary tract cancers was ascertained by follow-up interview and by data linkage with community hospital records, the national death certification profile, and the cancer registry profile. Cox proportional hazards regression analysis was used to estimate multivariate-adjusted relative risks and 95% confidence intervals. There was a significantly increased incidence of urinary cancers for the study cohort compared with the general population in Taiwan (standardized incidence ratio = 2.05; 95% confidence interval (CI): 1.22, 3.24). A significant dose-response relation between risk of cancers of the urinary organs, especially TCC, and indices of arsenic exposure was observed after adjustment for age, sex, and cigarette smoking. The multivariate-adjusted relative risks of developing TCC were 1.9, 8.2, and 15.3 for arsenic concentrations of 10.1-50.0, 50.1-100, and >100 microg/liter, respectively, compared with the referent level of < or =10.0 microg/liter.

Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan.

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.

Genetic polymorphisms of N-acetyltransferase 1 and 2 and risk of cigarette smoking-related bladder cancer.

Aromatic amines from cigarette smoking or occupational exposure, recognized risk factors for bladder cancer, are metabolized by N-acetyltransferases (NAT). This study examined the association of (NAT) 1 and 2 genotypes with the risk of smoking-related bladder cancer. A total of 74 pathologically confirmed bladder cancer patients and 184 controls were serially recruited from the National Taiwan University Hospital. History of cigarette smoking and other risk factors for bladder cancer was obtained through standardized questionnaire interview. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT1 and NAT2 by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods. Allele frequency distributions of NAT1 and NAT2 were similar between cases and controls. There was a significant dose-response relationship between the risk of bladder cancer and the quantity and duration of cigarette smoking. The biological gradients were significant among subjects carrying NAT1*10 allele or NAT2 slow acetylators, but not among NAT2 rapid acetylators without NAT1*10 allele. The results are consistent with the hypothesis that NAT1 and NAT2 might modulate the susceptibility to bladder cancer associated with cigarette smoking.

Low serum carotene level and increased risk of ischemic heart disease related to long-term arsenic exposure.

To elucidate the association between arsenic-related ischemic heart disease (ISHD) and serum antioxidant micronutrient level, residents aged 30 or older living in arseniasis-hyperendemic villages in Taiwan were recruited in a community-based health survey. A structured questionnaire was used to obtain a history of long-term exposure to arsenic through consuming artesian well water and fasting serum samples were also collected at the recruitment. A total of 74 patients affected with ISHD, who were diagnosed through both electrocardiography and Rose questionnaire interview, and 193 age-sex-matched healthy controls were selected for the examination of serum levels of micronutrients by high performance liquid chromatography (HPLC). There was a significant biological gradient between the risk of ISHD and the duration of consuming high-arsenic artesian well water. A significant reverse dose-response relationship with arsenic-related ISHD was observed for serum level of alpha- and beta-carotene, but not for serum levels of retinol, lycopene and alpha-tocopherol. Multivariate analysis showed a synergistic interaction on arsenic-related ISHD between duration of consuming artesian well water and low serum carotene level. An increased risk of arsenic-related ISHD was also associated with hypertension and elevated body mass index, but not with serum lipid profile, cigarette smoking and alcohol drinking. The findings seem to suggest that arsenic-related ISHD has a pathogenic mechanism which is at least partially different from that of ISHD unrelated to long-term exposure to arsenic.