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Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers.

Objective: To investigate the association between regular coffee consumption and the prevalence of coronary artery calcium (CAC) in a large sample of young and middle-aged asymptomatic men and women., Methods: This cross-sectional study included 25 138 men and women (mean age 41.3 years) without clinically evident cardiovascular disease who underwent a health screening examination that included a validated food frequency questionnaire and a multidetector CT to determine CAC scores. We used robust Tobit regression analyses to estimate the CAC score ratios associated with different levels of coffee consumption compared with no coffee consumption and adjusted for potential confounders., Results: The prevalence of detectable CAC (CAC score >0) was 13.4% (n=3364), including 11.3% prevalence for CAC scores 1-100 (n=2832), and 2.1% prevalence for CAC scores >100 (n=532). The mean ±SD consumption of coffee was 1.8±1.5 cups/day. The multivariate-adjusted CAC score ratios (95% CIs) comparing coffee drinkers of <1, 1-<3, 3-<5, and ≥5 cups/day to non-coffee drinkers were 0.77 (0.49 to 1.19), 0.66 (0.43 to 1.02), 0.59 (0.38 to 0.93), and 0.81 (0.46 to 1.43), respectively (p for quadratic trend=0.02). The association was similar in subgroups defined by age, sex, smoking status, alcohol consumption, status of obesity, diabetes, hypertension, and hypercholesterolaemia., Conclusions: In this large sample of men and women apparently free of clinically evident cardiovascular disease, moderate coffee consumption was associated with a lower prevalence of subclinical coronary atherosclerosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Gatifloxacin, a fluoroquinolone antibiotic, has been reported to produce several adverse reactions. In the present investigation, gatifloxacin administered at the dose rate of 10 and 20 mg kg(-1) body weight per day, respectively, for 21 consecutive days, was evaluated for its potential to induce antioxidant status alterations and retinal damage in rabbits. A significant alteration in the antioxidant status of rabbits particularly in the high-dose group was observed which is indicated by decreased activity of superoxide dismutase and levels of blood glutathione with a concomitant increase in the activity of catalase, glutathione peroxidase, and glutathione S-transferase enzymes. The activity of glutathione reductase differed nonsignificantly between groups throughout the study period. The levels of malondialdehyde were elevated in the high-dose group. The histopathological examination of eyeball tunics revealed clumping of nuclei of the retinal outer nuclear layer in the gatifloxacin-treated groups. The results from this study indicate that repeated gatifloxacin administration produces a dose-dependent oxidative stress and retinopathy., (© The Author(s) 2014.)

Recent findings have shown that the rs1042714 (Gln27Glu) single-nucleotide polymorphism (SNP) on the β2-adrenoceptor gene may predispose to obesity. The findings from other studies carried on different populations, however, have been inconsistent. The authors investigated the association between the rs1042714 SNP with obesity-related parameters. DNA of 672 Malaysian Malays was analyzed using real-time polymerase chain reaction. Univariate and multivariate linear regression analyses revealed significant associations between rs1042714 and diastolic blood pressure in the pooled Malaysian Malay subjects under additive and recessive models. After gender stratification, however, a significant association was found between the rs1042714 and triglyceride and the rs1042714 and log-transformed high-density lipoprotein cholesterol levels in Malaysian Malay men. No significant association was found between the SNP and log-transformed body mass index. This polymorphism may have an important role in the development of obesity-related traits in Malaysian Malays. Gender is an effect modifier for the effect of the rs1042714 polymorphism on obesity-related traits in Malaysian Malays., (© 2011 APJPH.)

In the present investigation, ameliorative effect of selenium on carbendazim induced oral sub chronic toxicity in bucks was assessed by studying various indices of antioxidant defense system. Bucks were randomly divided into four groups of four animals each. Group I served as control, Group II was orally drenched carbendazim at the dose rate of 50mg/kg body weight for 90 consecutive days. Group III was orally administered selenium in the form of sodium selenite at the dose rate of 0.05mg/kg body weight for 90 consecutive days. Group IV was orally administered carbendazim along with selenium at the same dosages as Group II and III. Prolonged administration of carbendazim produced oxidative stress in goat bucks as evidenced by increase in lipid peroxidation and decline in total antioxidant capacity. The increase in the activity of antioxidant enzymes was not sufficient to prevent pesticide induced oxidative stress. Selenium supplementation provides some amelioration against this effect. Further study is needed to prove ameliorative potential of this antioxidant against carbendazim induced toxicity in goat bucks., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Aim: With an increasing burden on overstretched colonoscopy services, a simple risk score for significant pathology in symptomatic patients may aid in the prioritization of patients., Methods: A derivative study of a risk score model for colonic neoplasia (colorectal carcinoma [CRC] and advanced adenoma) and CRC alone was conducted in symptomatic adults referred for an index colonoscopy. The accuracy of the final model was assessed by the area under the curve (AUC) of the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit statistic., Results: A total of 1013 subjects (mean age 59.9 ± 13.7 years, 52.3% females) from a multi-ethnic Asian background (Chinese 56%, Malay 20.4%, Indian 21.5%) were recruited. Colonic neoplasia and CRC were identified in 175 (17.3%) and 114 (11.3%) cases, respectively. Risk scores were assigned to individual factors identified in a logistic regression model of both demographic (age, gender, ethnicity, education level, smoking history, Aspirin use) and clinical symptoms (change in bowel habit, bloody stool, weight loss, appetite loss, lethargy). The risk score for each patient was the sum of their individual risk factors. The AUC of the risk score for colonic neoplasia and CRC was 0.76 (Hosmer-Lemeshow goodness-of-fit statistic of P = 0.745) and 0.83 (Hosmer-Lemeshow goodness-of-fit statistic of P = 0.982), respectively., Conclusion: A simple risk score for colonic neoplasia and CRC may be able to prioritize colonoscopy referrals in symptomatic subjects from a multi-ethnic background. A further study to validate this scoring system is required., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored., Methods: We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation., Results: After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD., Conclusions: In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.

Purpose: To examine the longitudinal association between age and intraocular pressure (IOP) in a large sample of Korean men and women., Methods: We conducted a prospective cohort study of 274,064 young and middle-aged Korean adults with normal fundoscopic findings, following them from January 1, 2002, to February 28, 2010. Health exams were scheduled annually or biennially. At each visit, IOP was measured in both eyes using automated noncontact tonometers. The longitudinal change in IOP with age was evaluated using three-level mixed models for longitudinal paired-eye data, accounting for correlations between paired eyes and repeated measurements over time., Results: In fully adjusted models, the average longitudinal change in IOP per 1-year increase in age was -0.065 mm Hg (95% confidence interval [CI] -0.068 to -0.063), with marked sex differences (P < 0.001). In men, the average annual IOP change was -0.093 mm Hg (95% CI -0.096 to -0.091) throughout follow-up. In women, the average annual IOP change was -0.006 mm Hg (95% CI -0.010 to -0.003), with a relatively flat association in the age range of 30 to 59 years and more marked annual decreases at younger and older ages., Conclusions: Intraocular pressure was inversely associated with age in a large cohort of Korean adults attending health-screening visits. For men, this inverse association was observed throughout the entire age range, while for women it was evident only in younger (<30 years of age) and older (≥60 years of age) women, with no association in women aged 30 to 59. Further research is needed to better understand the underlying mechanisms and to reconsider cutoffs for defining high IOP by age and sex groups in Asian populations., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Objective: Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC)., Approach and Results: We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone., Conclusions: In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification., (© 2014 American Heart Association, Inc.)

Objective: The aim of this study was to examine an impact of body mass index (BMI) and weight change on the risk of diabetes according to metabolic health status., Methods: Cohort study of 34,999 Korean men and women 30-59 years of age free of diabetes at baseline were followed-up annually or biennially for an average of 5.1 years. Being metabolically healthy was defined as not having any metabolic syndrome component., Results: During 176,878.6 person-years of follow-up, 889 participants developed diabetes (incidence rate 5.0 per 1000 person-years). Compared to metabolically healthy normal-weight individuals, the adjusted hazard ratios for diabetes in metabolically unhealthy obese and in metabolically healthy obese were 13.7 (95% confidence interval [CI] 9.8-19.0) and 2.7 (95% CI: 1.7-4.3), respectively. The aHR (95% CI) for incident diabetes for weight changes of <-0.9, 0.5 to 2.0, and ≥2.1 kg compared to a weight change of -0.9 to 0.4 kg (reference) were 0.80 (0.66-0.97), 0.99 (0.82-1.20), and 1.24 (1.02-1.49), respectively (P-trend<0.001)., Conclusions: In this large cohort of young and middle age Koreans, metabolic health status, obesity, and weight change were all independently associated with increased incidence of diabetes over 5 years of follow-up., (Copyright © 2014 The Obesity Society.)

A genome-wide association study showed that the tagging single nucleotide polymorphism (SNP) rs7566605 in the insulin-induced gene 2 (INSIG2) was associated with obesity. Attempts to replicate this result in different populations have produced inconsistent findings. We aimed to study the association between the rs7566605 SNP with obesity and other metabolic parameters in Malaysian Malays. Anthropometric and obesity-related metabolic parameters and DNA samples were collected. We genotyped the rs7566605 polymorphism in 672 subjects using real-time polymerase chain reaction. No significant associations were found between the rs7566605 tagging SNP of INSIG2 with obesity or other metabolic parameters in the Malaysian Malay population. The INSIG2 rs7566605 SNP may not play a role in the development of obesity-related metabolic traits in Malaysian Malays.

Background & Aims: Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location., Methods: In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma., Results: Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P = .04) for fasting glucose, 1.07 (0.99-1.15; P = .10) for insulin, 1.09 (1.02-1.18, P = .02) for HOMA, 1.09 (1.01-1.17; P = .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P = .08), 1.10 (0.98-1.24; P = .12), 1.15 (1.02-1.29; P = .02), 1.14 (1.01-1.28; P = .03), and 1.20 (1.05-1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P = .11), 1.23 (0.87-1.75; P = .24), 1.30 (0.92-1.85; P = .14), 1.13 (0.79-1.61; P = .50), and 1.67 (1.15-2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P < .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P = .002). Associations were similar for adenomas located in the distal versus proximal colon., Conclusions: Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Prolonged antibiotic and antiinflammatory therapy for complicated infections exposes the body to xenobiotics that can produce several adverse effects for which oxidative damage is the proposed underlying mechanism. In this context, we evaluated the effect of pazufloxacin, a fluoroquinolone antimicrobial, and meloxicam, a nonsteroidal antiinflammatory drug, on antioxidant parameters and lipid peroxidation in rabbits after oral administration for 21 d. Reduced glutathione levels were significantly decreased in rabbits (n = 4 per group) given pazufloxacin, meloxicam, or their combination. In addition, glutathione peroxidase activity was induced in the rabbits treated with pazufloxacin only. Administration of pazufloxacin and meloxicam, as single agents as well as in combination, produced significant lipid peroxidation compared with levels in untreated controls. In conclusion, both pazufloxacin and meloxicam potentially can induce oxidative damage in rabbits.

Context: Hyperthyroidism and hypothyroidism, both overt and subclinical, are associated with all-cause and cardiovascular mortality. The association between thyroid hormones and mortality in euthyroid individuals, however, is unclear., Objective: To examine the prospective association between thyroid hormones levels within normal ranges and mortality endpoints., Setting and Design: A prospective cohort study of 212 456 middle-aged South Korean men and women who had normal thyroid hormone levels and no history of thyroid disease at baseline from January 1, 2002 to December 31, 2009. Free T4 (FT4), free T3 (FT3), and TSH levels were measured by RIA. Vital status and cause of death ascertainment were based on linkage to the National Death Index death certificate records., Results: After a median follow-up of 4.3 years, 730 participants died (335 deaths from cancer and 112 cardiovascular-related deaths). FT4 was inversely associated with all-cause mortality (HR = 0.77, 95% confidence interval 0.63-0.95, comparing the highest vs lowest quartile of FT4; P for linear trend = .01), and FT3 was inversely associated cancer mortality (HR = 0.62, 95% confidence interval 0.45-0.85; P for linear trend = .001). TSH was not associated with mortality endpoints., Conclusions: In a large cohort of euthyroid men and women, FT4 and FT3 levels within the normal range were inversely associated with the risk of all-cause mortality and cancer mortality, particularly liver cancer mortality.

Objectives: The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women., Background: The risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial., Methods: We conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5., Results: MHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups., Conclusions: MHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity., Methods: The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform., Results: The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09-2.05, p = 0.012; and OR 1.51, 95 % CI 1.09-2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10-2.17, p = 0.013; and OR 1.56, 95 % CI 1.10-2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01-2.21, p = 0.044; and OR 1.52, 95 % CI 1.03-2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28-5.43, p = 0.009; and OR 4.35, 95 % CI 1.93-9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41-12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08-2.85, p = 0.04)., Conclusion: This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.

Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene have been linked with obesity and with adiponectin levels in various populations. Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261 SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity parameters and adiponectin levels were measured in 574 subjects. Genotyping was performed using real-time polymerase chain reaction and Sequenom MassARRAY. A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no significant association was found between allelic frequencies of ADIPOQ rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes of the ADIPOQ gene were not associated with obesity. We confirmed the previously reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs are not important modulators of adiponectin levels in this population.

Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.

Background: Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans., Methods: Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009., Results: Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The prevalence of adenomas increased annually in both men and women., Conclusions: In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries., Impact: Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed., (©2014 AACR.)

Background: Although laparoscopic surgeries are associated with reduced surgical stress response and shortened post-operative recovery, intense pain and high analgesia requirements in the immediate post-operative period are often the chief complaints., Aim: The aim of this study was to evaluate the effect of pre-emptive intraperitoneal local anaesthetic drugs on post-operative pain management and metabolic stress response in laparoscopic appendicectomy., Method: The method used was a randomized double-blinded placebo-controlled study. Patients with clinical diagnosis of acute appendicitis who fulfil the criteria, were taken into this study. Primary outcomes investigated were consumption of patient-controlled analgesia during the immediate post-operative period (first 6 h) and subsequent 18 h as well as serum cortisol sampling., Results: Total of 120 patients were recruited into three different treatment groups (placebo, ropivacaine, levobupivacaine). In order to maintain visual analogue score of 0-1 during the immediate post-operative period, patients in the placebo group required significantly (P < 0.001) higher dose of analgesia (morphine/mg) - 11 mg (8.3-15.5) as compared with ropivacaine - 4 mg (3.0-6.0) and levobupivacaine - 3.5 mg (2.0-5.0). The immediate post-operative serum cortisol showed a significant increase in serum cortisol in the placebo group (P = 0.001) as compared with ropivacaine and levobupivacaine groups., Conclusion: Pre-emptive intraperitoneal local anaesthesia in laparoscopy surgery is a safe, non-invasive procedure that can benefit patients by reducing the immediate post-operative pain intensity and metabolic stress response of the body., (© 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.)

This study validated the use of mutant prevention concentration (MPC) and pharmacokinetic and pharmacodynamic (PK-PD) modeling approach for optimization of dose regimen of enrofloxacin to contain the emergence of Pasteurella multocida resistance. The PK and PD characteristics of enrofloxacin were investigated in buffalo calves after intramuscular administration at a dose rate of 12 mg/kg. The concentration of enrofloxacin and ciprofloxacin in serum were determined by high-performance liquid chromatography. The serum peak concentration (Cmax), terminal half-life (t1/2K10), volume of distribution (Vd(area)/F) and mean residence time (MRT) of enrofloxacin were 1.89 ± 0.35 μg/ml, 5.14 ± 0.66 h, 5.59 ± 0.99 l/kg/h and 8.52 ± 1.29 h, respectively. The percent metabolite conversion ratio of ciprofloxacin to enrofloxacin was 79. The binding of enrofloxacin to plasma proteins was 11%. The MIC, MBC and MPC for enrofloxacin against P. multocida were 0.05, 0.06 μg/ml and 1.50 μg/ml.In vitro and ex-vivo bactericidal activity of enrofloxacin was concentration dependent. Modeling of ex-vivo growth inhibition data to the sigmoid Emax equation provided AUC24h/MIC values to produce bacteriostatic (19 h), bactericidal (43 h) and bacterial eradication (64 h). PK-PD data in conjunction with MPC and MIC90 data predicted dosage schedules for enrofloxacin that may achieve optimum efficacy in respect of bacteriological and clinical cure and minimize the risk of emergence of resistance., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Information on the impact of cecal insertion time on colorectal neoplasm detection is limited. Our objective was to determine the association between cecal insertion time and colorectal neoplasm detection rate in colonoscopy screening., Methods: We performed a cross-sectional study of 12,679 consecutive subjects aged 40-79 years undergoing screening colonoscopy in routine health check-ups at the Center for Health Promotion of the Samsung Medical Center from December 2007 to June 2009. Fixed effects logistic regression conditioning on colonoscopist was used to eliminate confounding due to differences in technical ability and other characteristics across colonoscopists., Results: The mean cecal insertion time was 5.9 (SD, 4.4 minutes). We identified 4,249 (33.5%) participants with colorectal neoplasms, of whom 1,956 had small single adenomas (<5 mm), 595 had medium single adenomas (5-9 mm), and 1,699 had multiple adenomas or advanced colorectal neoplasms. The overall rates of colorectal neoplasm detection by quartiles of cecal insertion time were 36.8%, 33.4%, 32.7%, and 31.0%, respectively (p trend <0.001).The odds for small single colorectal adenoma detection was 16% lower (adjusted OR 0.84; 95% CI 0.71 to 0.99) in the fourth compared to the first quartile of insertion time (p trend 0.005). Insertion time was not associated with the detection rate of single adenomas ≥5 mm, multiple adenomas or advanced colorectal neoplasms., Conclusion: Shorter insertion times were associated with increased rates of detection of small colorectal adenomas <5 mm. Cecal insertion time may be clinically relevant as missed small colorectal adenomas may progress to more advanced lesions.

Background and Aim: Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD., Methods: A total of 144 biopsy-proven NAFLD and 198 controls were genotyped using the Sequenom MassARRAY platform., Results: We observed a significant association between the LEPR rs1137100 and rs1137101 with susceptibility to NAFLD (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.18-2.28, P = 0.003; and OR 1.61, 95% CI 1.11-2.34, P = 0.013, respectively) and to non-alcoholic steatohepatitis (OR 1.49, 95% CI 1.05-2.12, P = 0.026; and OR 1.57, 95% CI 1.05-2.35, P = 0.029, respectively). The LEPR rs1137100 is also associated with simple steatosis (OR 2.27, 95% CI 1.27-4.08, P = 0.006). Analysis of gene-gene interaction revealed a strong interaction between the LEPR and PNPLA3 genes (empirical P = 0.001). The joint effect of LEPR and PNPLA3 greatly exacerbated the risk of NAFLD (OR 3.73, 95% CI 1.84-7.55, P < 0.0001). The G allele of rs1137100 is associated with lower fibrosis score (OR 0.47, 95% CI 0.28-0.78, P = 0.001)., Conclusions: We report an association between variants of LEPR rs1137100 and rs1137101 with risk of NAFLD. This study suggests that rs1137100, specifically the G allele, is associated with a less severe form of liver disease in patients with NAFLD. The interaction between LEPR and PNPLA3 genes showed increased risk of NAFLD compared to either gene alone., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Epidermal growth factor receptor (EGFR) mutation status is an important predictor of the efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy in patients with non-small cell lung cancer (NSCLC). We evaluated the real impact of EGFR mutation status on chemotherapy patterns of NSCLC patients., Patients and Methods: This is a retrospective cohort study of consecutive advanced NSCLC patients attended at the Samsung Medical Centre in Seoul, Korea, from January 2007 through July 2010. EGFR mutation was analyzed by direct sequencing testing., Results: Among 1164 patients treated during the study period, 166 (14.3%) were EGFR mutation positive, 275 (23.6%) were mutation negative, and 723 (62.1%) had mutation status unknown. Overall, 605 (52%) received TKI therapy as a first-, second-, or third-line therapy. The proportions of patients receiving TKI therapy among those with positive, negative and unknown EGFR mutation status were 88.0, 46.5, and 45.8%, respectively. After adjustment for other factors, patients with a positive EGFR mutation status (odds ratio [OR] 7.88, 95% CI 4.58, 13.57), and those who were female (OR 2.83, 95% CI 2.04, 3.92) or had poor performance status (OR 1.58, 95% CI 1.13, 2.22) were significantly more likely to receive TKI treatment. Furthermore, the temporal relationship between EGFR mutation reporting and initiation of TKI therapy significantly differed by EGFR mutation status., Conclusion: EGFR mutation status significantly affected the chemotherapy patterns in advanced NSCLC. More widespread EGFR testing and the use of faster and more sensitive mutation tests will result in more timely and appropriate use of TKI therapy in advanced NSCLC., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: There is suggestive but sparse evidence that dyslipidemia is associated with colorectal neoplasms. We investigated the association of serum lipid and apolipoprotein concentrations with the prevalence of colorectal adenomas., Methods: Cross-sectional study of 19,281 consecutive participants aged 40-79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009., Results: We identified 5,958 participants with colorectal adenomas (30.9%), including 5,504 (28.5%) with non-advanced adenomas and 454 (2.4%) with advanced adenomas. The adjusted relative prevalence ratios (aRPRs) comparing the fourth with the first quartiles of serum triglycerides were 1.35 (95% confidence interval (CI) 1.20-1.52; P trend<0.001) for non-advanced adenomas and 1.45 (95% CI 1.02-2.06; P trend=0.005) for advanced adenomas. Higher levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 (ApoA-1) were significantly associated with 12% (Q4 vs. Q1 aRPR 1.12; 95% CI 1.00-1.26; P trend=0.049) and 17% (Q4 vs. Q1 aRPR 1.17; 95% CI 1.04-1.31; P trend=0.004) higher prevalence of non-advanced adenoma. There was also a non-significant association between higher levels of low-density lipoprotein (LDL) cholesterol (Q4 vs. Q1 aRPR 1.22; 95% CI 0.91-1.66; P trend= 0.12) and apolipoprotein B (ApoB) (Q4 vs. Q1 aRPR 1.32; 95% CI 0.94-1.83; P trend=0.07) with higher prevalence of advanced adenoma. There was no association between total cholesterol levels with colorectal adenoma., Conclusions: In this large cross-sectional study, higher levels of serum triglycerides were significantly associated with an increasing prevalence of both non-advanced and advanced colorectal adenomas, while higher levels of ApoA-1 and HDL cholesterol were significantly associated with an increasing prevalence of non-advanced adenomas.

Several method parameters have been refined for application of CIEF methods to provide optimal capillary robustness and performance longevity while maintaining desired analytical output for the ever increasing characterization scrutiny of protein reagents used in clinical assay formulations. Demonstrated here are significant modifications to the existing protocols in order to attain a robust, reproducible method that achieves as much as a 20-fold increase in the number of consecutive runs before capillary degradation. Not only is it a concern for the rudimentary analysis of acidic and basic components of the isoform profile for monoclonal antibodies, but a comprehensive identification of each individual isoform to obtain a characteristic fingerprint is necessary for minor distinguishable properties between multiple proteins in unambiguous identification. In order to maintain the integrity of these modifications, extensive studies were conducted on an implemented system suitability standard protein with specifically defined parameters indicating either sufficient or poor separation performance., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea., Methods: Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records., Results: This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma., Conclusions: In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.

Background: Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe., Aim: This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays., Methods: The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY® iPLEX platform. Anthropometric and blood lipid profiles were measured., Results: MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters., Conclusions: The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.

Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.

The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.

Introduction: The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country., Methods: In 2004, we conducted a national cross-sectional population-based study using a stratified two-stage cluster sampling design (N = 17,211). Metabolic syndrome was defined according to the International Diabetes Federation/National Heart, Lung and Blood Institute/American Heart Association (IDF/NHLBI/AHA-2009) criteria. Multivariate models were used to study the independent association between ethnicity and the prevalence of the metabolic syndrome., Results: The overall mean age was 36.9 years, and 50.0% participants were female. The ethnic distribution was 57.0% Malay, 28.5% Chinese, 8.9% Indian and 5.0% Indigenous Sarawakians. The overall prevalence of the metabolic syndrome was 27.5%, with a prevalence of central obesity, raised triglycerides, low high density lipoprotein cholesterol, raised blood pressure and raised fasting glucose of 36.9%, 29.3%, 37.2%, 38.0% and 29.1%, respectively. Among those <40 years, the adjusted prevalence ratios for metabolic syndrome for ethnic Chinese, Indians, and Indigenous Sarawakians compared to ethnic Malay were 0.81 (95% CI 0.67 to 0.96), 1.42 (95% CI 1.19 to 1.69) and 1.37 (95% CI 1.08 to 1.73), respectively. Among those aged ≥40 years, the corresponding prevalence ratios were 0.86 (95% CI 0.79 to 0.92), 1.25 (95% CI 1.15 to 1.36), and 0.94 (95% CI 0.80, 1.11). The P-value for the interaction of ethnicity by age was 0.001., Conclusions: The overall prevalence of metabolic syndrome in Malaysia was high, with marked differences across ethnicities. Ethnic Chinese had the lowest prevalence of metabolic syndrome, while ethnic Indians had the highest. Indigenous Sarawakians showed a marked increase in metabolic syndrome at young ages.

Background: Breast cancer is the most common cancer among women in Malaysia. Of the total cancer cases registered in the National Cancer Registry for 2006, 3,525 were female breast cancer cases. The overall age standardized rate was 39.3 per 100,000 population in 2006. An estimated 30%-40% were diagnosed in the late stages and this had resulted in poor survival rates. The purpose of the study was to determine the factors and barriers related to mammography screening uptake among hospital personnel., Methods: This mixed method explanatory study was carried out on a universal sampling of 707 female personnel aged 40 and above, from June 2007 until November 2007. The study was conducted at University Malaya Medical Centre, a tertiary hospital in Kuala Lumpur. Pre-tested self-administered questionnaires were mailed to eligible personnel., Results: The prevalence of mammography screening uptake was 80.3% (95%CI: 76.8%,83.5%) among 534 respondents. Personnel who had physician recommendation had significantly higher odds of mammography screening uptake compared to those who did not have recommendation, adjusted odds ratio of 21.25 (95%CI:12.71,36.56). Reported barriers can be grouped into several themes; negative perception of the procedure like embarrassment due to the presence of male technicians/radiographers; low confidence with radiologist/radiographers in detecting abnormality; lack of coping skills in dealing with expected results and pain during procedure., Conclusions: The findings of this study highlighted that 20% of personnel did not undertake mammography screening although there is no cost incurred and the procedure is fully accessible to them. Opportunistic recommendation by physician and concerns on the procedure should be addressed.

Objectives: The clinical impact of seasonal influenza is understudied in tropical countries. The aim of this study was to describe the clinical features and seasonal pattern of influenza in children hospitalized in Malaysia, and to identify predictors of severe disease., Methods: Children hospitalized with community-acquired, laboratory-confirmed influenza at a teaching hospital in Kuala Lumpur, Malaysia during 2002-2007 were identified retrospectively. Clinical data were collected, and predictors of severe disease were identified by multivariate logistic regression. All influenza cases from 1982 to 2007 were also analyzed for seasonal patterns., Results: A total of 132 children were included in the study, 48 (36.4%) of whom had underlying medical conditions. The mean age was 2.5 years and 116 (87.9%) were <5 years old. The most common presenting features were fever or history of fever, cough, rhinitis, vomiting, and pharyngitis. Severe influenza was seen in 16 patients (12.1%; nine previously healthy), including 12 (9.1%; eight previously healthy) requiring intensive care. There were three (2.3%) deaths. Severe disease was associated with age <12 months, female sex, and absence of rhinitis on admission. Influenza was seen year-round, with peaks in November-January and May-July., Conclusions: Seasonal influenza has a considerable impact on children hospitalized in Malaysia, in both the healthy and those with underlying medical conditions., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies., Methodology: A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA)., Results: Thirty six patients (mean age 59.8 +/- 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6%) with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50%) patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 +/- 1.6 vs 26.3 +/- 3.5 kg/m2, p < 0.0001; MAMC 19.4 +/- 1.5 vs 24.5 +/- 3.6 cm, p = 0.002) and females (BMI 19.4 +/- 2.7 vs 28.9 +/- 4.3, p = 0.001; MAMC 18.0 +/- 0.9 vs 28.1 +/- 3.6, p < 0.0001), but not with visceral proteins. The SGA demonstrated a trend towards more malnutrition in Child-Pugh C compared to Child-Pugh B liver cirrhosis (40% grade C vs 25% grade C, p = 0.48). Alcoholic cirrhosis had a higher proportion of SGA grade C (41.7%) compared to viral (26.7%) and cryptogenic (28.6%) cirrhosis, but this was not statistically significant., Conclusion: Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis.

Background: The role of ethnicity in the development of dyspepsia remains uncertain., Aims: To examine the epidemiology of dyspepsia in a multi-ethnic Asian population and its impact on health-related quality of life (HRQOL)., Methods: A cross-sectional survey was conducted in a representative urban population in Kuala Lumpur, Malaysia., Results: A total of 2039 adults (mean +/- s.d. age: 40.5 +/- 11.8 years, males 44.2%, ethnicity: Malays 45.3%, Chinese 38.0% and Indians 13.1%, tertiary education level 62%, professional employment 47.7% and median monthly income USD 850.00) were interviewed. Dyspepsia was prevalent in 496 (24.3%) adults. Independent predictors for dyspepsia, explored by logistic regression, were identified as: Malay (OR 2.17, 95% CI = 1.57-2.99) and Indian (OR 1.59, 95% CI = 1.03-2.45) ethnicity, heavy chilli intake (OR 2.35, 95% CI = 1.15-4.80), use of regular analgesia (OR 3.51, 95% CI = 2.54-4.87) and chronic illness (OR 1.67, 95% CI = 1.22-2.28). HRQOL was assessed with the EQ-5D and significantly lower scores were noted in dyspeptics compared with healthy controls (0.85 +/- 0.17 vs. 0.95 +/- 0.12, P < 0.0001)., Conclusion: Ethnicity, in addition to recognized epidemiological factors, is a risk factor for dyspepsia in an urban multi-racial Asian population.

The purpose of this study was to determine the association between different ethnic groups and the prevalence, awareness, and control of diabetes in Malaysia. A population-based cross-sectional study using multistage sampling was conducted in Malaysia. Diabetes is defined as having a fasting blood glucose > or =7 mmol/L or a self-reported diabetic on treatment. Among the 7683 respondents aged > or =30 years, the prevalence of diabetes mellitus was 15.2% (95% CI = 14.1, 16.4). Multivariate analysis showed that compared with Malays, Chinese had lower odds (adjusted odds ratio [aOR] 0.71; 95% CI = 0.56, 0.91) and Indians had higher odds of having diabetes (aOR 1.54; 95% CI = 1.20, 1.98). The odds of diabetes increased with age, family history of diabetes, body mass index, and lower education levels. Among those with diabetes mellitus, 45.0% were aware and 42.7% were under treatment. Among treated diabetics, 25.1% had their fasting blood sugar under control. There is a significant association between prevalence of diabetes and different ethnic groups.

Objectives: The epidemiology and impact of dyspepsia in rural Asia remains uncertain. We aimed to determine the prevalence epidemiology and impact of dyspepsia in a rural Malaysian community., Methods: A door-to-door survey was conducted in a representative rural population in Malaysia. Dyspepsia was defined according to the Rome II criteria, and health-related quality of life (HRQOL) was assessed using the Euroqol (EQ-5D) instrument., Results: Of 2,260 adults, 2,000 (88.5%) completed the survey. The mean age of respondents was 40.4+/-15.3 years, 62.7% were women, 79.0% were ethnic Malays, 8.4% had been educated up to the tertiary level, 49.7% were unemployed, and 63.4% resided in village-type housing with 49.1% having >8 residents per household. Dyspepsia was prevalent in 292 (14.6%) adults, and they had lower mean EQ-5D utility scores compared with healthy controls (0.91+/-0.17 vs. 0.97+/-0.08, P<0.0001). Dyspepsia was found to be associated with female gender (15.8 vs. 12.7% males, P=0.058), Chinese ethnicity (19.7 vs. 14.2% non-Chinese), higher education levels, medium-range incomes (19.1% medium range vs. 13.3% low range), non-village-type housing (16.3 vs. 13.5% village-type house, P=0.08), nonsmokers (18.7 vs. 13.7%, P=0.015), non-tea drinkers (19.5 vs. 12.3%, P<0.0001), regular analgesia intake (27 vs. 12.7%, P<0.0001), and adults with chronic illness (26.6 vs. 11.1%, P<0.0001). Logistic regression analysis showed that higher levels of education, i.e., secondary (odds ratio (OR) 2.13, 95% confidence interval (CI)=1.15-3.93) and tertiary (2.70, 95% CI=1.30-5.62) education, non-village housing (OR 1.36, 95% CI=1.02-1.80), regular analgesia (OR 2.22, 95% CI=1.60-3.09), and chronic illness (OR 2.83, 95% CI=2.12-3.77) were independent risk factors for dyspepsia. Conversely, regular tea drinking (OR 0.59) seemed to have an inverse relationship., Conclusions: Dyspepsia in rural Malaysians is associated with a lower HRQOL. Epidemiological risk factors include a higher socioeconomic status, regular analgesic consumption, and chronic illness.

Background: Locoregional recurrence after mastectomy for breast cancer may predict distant recurrence and mortality. This study examined the pattern and rates of post-mastectomy locoregional recurrence (PMLRR), survival outcome and prognostic factors for isolated PMLRR (ILR) in a breast cancer cohort in University of Malaya Medical Center (UMMC)., Methods: We studied 522 patients who underwent mastectomy between 1998 and 2002 and followed them up until 2008. We defined PMLRR as recurrence to the axilla, supraclavicular nodes and or chest wall. ILR was defined as PMLRR occurring as an isolated event. Prognostic factors for locoregional recurrence were determined using the Cox proportional hazards regression model., Results: The overall PMLRR rate was 16.4%. ILR developed in 42 of 522 patients (8.0%). Within this subgroup, 25 (59.5%) remained disease free after treatment while 17 (40.5%) suffered disease progression. Univariate analyses identified race, age, size, stage, margin involvement, lymph node involvement, grade, lymphovascular invasion and ER status as probable prognostic factors for ILR. Cox regression resulted in only stage III disease and margin involvement as independent prognostic factors. The hazard of ILR was 2.5 times higher when the margins were involved compared to when they were clear (aHRR 2.5; 95% CI 1.3 to 5.0). Similarly, compared with stage I those with Stage II (aHRR 2.1; 95%CI 0.6 to 6.8) and stage III (aHRR 4.6; 95%CI 1.4 to 15.9) had worse prognosis for ILR., Conclusion: Margin involvement and stage III disease were identified to be independent prognostic factors for ILR. Close follow-up of high risk patients and prompt treatment of locoregional recurrence were recommended.

Background: Locally advanced breast cancer (LABC) is characterized by the presence of a large primary tumour (>5 cm) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. These cancers are classified as stage IIIA and IIIB according to the AJCC Staging System. Treatment of choice involves combinations of surgery, chemotherapy, radiotherapy and/or hormonal therapy. Current guidelines recommend primary surgery or neoadjuvant therapy followed by surgery. The primary objective of this study was to compare the outcome of LABC patients subjected to neoadjuvant chemotherapy before surgery and those who underwent surgery as the primary treatment and to determine prognostic predictors. Secondary objectives were to evaluate the response after neoadjuvant therapy and to determine the treatment compliance rate., Methods: This retrospective study of Stage III breast cancer patients was conducted over a 5 year period from 1998 to 2002. The survival data were obtained from the National Registry of Births and Deaths with the end-point of the study in April 2006. The Kaplan Meier method was applied for survival analysis. Cox regression analysis by stepwise selection was performed to identify important prognostic factors., Results: Out of a 155 evaluable patients, 74 (47.7%) had primary surgery, 62 (40%) had neoadjuvant chemotherapy, 10 patients (6.5%) were given Tamoxifen as the primary treatment, while 9 patients (5.8%) defaulted any form of treatment. After neoadjuvant chemotherapy, 9 patients defaulted further treatment, leaving 53 evaluable patients. Out of these 53 evaluable patients, 5 patients (9.4%) had complete pathological response, 5 (9.4%) a complete clinical response, and 26 (49.1%) had partial response after neoadjuvant chemotherapy. The 5-year survival in the primary surgery group was 56.7 % compared to 44.7% in the neoadjuvant chemotherapy group (p<0.01). The important prognostic factors were race, size of tumour, nodal status, estrogen receptor status and response to neoadjuvant chemotherapy., Conclusion: Patients who had primary surgery had better survival than those who underwent neoadjuvant chemotherapy, which may be due to bias in the selection of patients for neoadjuvant chemotherapy. Out of a total of 155 patients, 25.1% defaulted part of the treatment, or did not receive optimal treatment, emphasizing the importance of psychosocial support and counselling for this group of patients.

Background: Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population., Methods: We conducted a retrospective review of the medical records of 152 women with breast cancer who underwent genetic testing for BRCA mutations. The patients self-reported ethnicity, age at onset, and clinical stage at diagnosis and tumor pathology were reviewed., Results: A total of 31 patients carried germline deleterious mutations (16 BRCA1, 15 BRCA2). We found that tumors in BRCA1 carriers were more likely to be estrogen receptor (ER)-negative and progesterone receptor (PR)-negative. HER2 was more likely to be negative in both BRCA1 and BRCA2 subjects compared with non-BRCA subjects. We found a strong association between triple-negative status and BRCA1 carriers. In addition, tumors in BRCA1 carriers were more likely to be higher grade than those in BRCA2 and non-BRCA carriers; but the difference was not statistically significant., Conclusions: These results suggest that tumors associated with BRCA1 mutations are distinct from those of BRCA2-associated and non-BRCA-associated breast cancers, and that the tumors associated with BRCA2 mutations are similar to the non-BRCA-associated breast cancers. Further studies are required to determine if the prognosis is different in each of these groups and the best management strategy for each group.

Acceptability rates of human papillomavirus (HPV) vaccination by 362 Malaysian mothers were 65.7% and 55.8% for daughters and sons, respectively. Younger mothers, and those who knew someone with cancer, were more willing to vaccinate their daughters. If the vaccine was routine and cost free, acceptability rate was 97.8%.

Ofloxacin, a quinolone, is an extensively used, well-tolerated antibacterial agent but has been reported to induce photosensitivity at low incidences. In the present investigation, the possible role of oxidative stress in ofloxacin-induced retinopathy in rabbits was evaluated. It was observed that ofloxacin at a dose rate of 10 and 20 mg/rabbit, twice daily for 21 consecutive days, resulted in significant elevation in the extent of lipid peroxidation and depletion of the blood glutathione levels. Marked alterations were also observed in various parameters of the glutathione-redox cycle. There was significant increase in the enzymic activity of glutathione peroxidase and glutathione reductase, whereas a significant decrease was observed in the activities of superoxide dismutase, catalase, and glutathione-S-transferase enzymes. Histopathological studies revealed retinal damage especially in the pigmented cell layer. Degenerative changes in liver and kidneys were also observed. Liver showed focal areas of necrosis, dilation of sinusoids, and cellular infiltration, whereas in kidneys, there was glomerular and tubular degeneration, suggesting impaired renal functioning.

The effect of long-term administration of sodium selenite on leucocyte indices of peripheral blood of calves was determined. Nine calves, 9-12 months old, with an average body weight of 104kg were divided into three groups. Calves of groups 2 and 3 were administered with sodium selenite at 0.1 and 0.25mg/kg body weight for 98 consecutive days. The clinical signs characteristic of selenosis viz. alopecia, cracking of hooves, intradigital lesions and discoloration of hard palate, started appearing from 45 to 60 days onwards with high dose, whereas only subtle indications of toxicosis were observed in the low-dose group. The prolonged administration of sodium selenite produced a progressive and dose-dependent decline in the circulating leucocyte count with concomitant decline in the circulating neutrophil count. There was a high negative correlation (0.94) between blood selenium levels and neutrophils. Granulocyte/agranulocyte ratio was also significantly reduced in the treated animals. Evaluation of bone marrow smears revealed a decline in the myeloid to erythroid ratio. In addition, there was also maturation arrest of neutrophils at promyelocyte or myelocyte level as shown by differential granulocyte count in the bone marrow. The results indicated that host's immune response may be adversely affected., (Copyright © 2007 Elsevier B.V. All rights reserved.)

Study Design: A cross-sectional study was conducted in all states of Malaysia to determine the prevalence, awareness, treatment and control of hypertension. A stratified two-stage cluster sampling design with proportional allocation was used., Methods: Trained nurses obtained two blood pressure measurements from each subject. Hypertension was defined as mean systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg, or a self-reported diagnosis of hypertension and taking antihypertensive medication. All data were analysed using Stata 9.2 software and took the complex survey design into account. A two-sided P-value of <0.05 was considered to be statistically significant., Results: The overall prevalence of hypertension for subjects aged 15 years was 27.8% (95% confidence interval (CI) 26.9-28.8). The prevalence of hypertension was significantly higher in males (29.6%, 95% CI 28.3-31.0) compared with females (26.0%, 95% CI 25.0-27.1). Multivariate logistic regression showed that the odds of having hypertension increased with increasing age, in males, in subjects with a family history of hypertension, with increasing body mass index, in non-smokers and with decreasing levels of education. Only 34.6% of the subjects with hypertension were aware of their hypertensive status, and 32.4 were taking antihypertensive medication. Amongst the latter group, only 26.8% had their blood pressure under control. The prevalence of hypertension amongst those aged 30 years has increased from 32.9% in 1996 to 40.5% in 2004., Conclusion: In Malaysia, the prevalence of hypertension is high, but levels of awareness, treatment and control are low. There is an urgent need for a comprehensive integrated population-based intervention programme to ameliorate the growing problem of hypertension in Malaysians.

Overweight and obesity place children and adolescents at increased risk of significant health problems, both during their early life and adult life. A cross sectional study was carried out to determine the prevalence of overweight among secondary school students aged 13-17 years in the Klang district and to determine the association between overweight and age, sex, ethnicity, religion and blood pressure. Random cluster proportionate to size sampling technique was used to select the respondents. Weight was recorded using TANITA model HD-309 and height was measured using SECA Body meter Model 208. A mercury sphygmomanometer was used to measure blood pressure manually. Statistical analysis was carried out using SPSS version 13. Out of the 3,333 respondents, 11.4% were found to be at risk of overweight and 8.2% were overweight. The prevalence of overweight was significantly higher in the males (10.6%) as compared to females (6.0%). Prevalence of overweight was highest in Malays (10.7%) followed by the Indians (7.1%) and the Chinese (5.9%). Prevalence of 'risk of overweight' was highest in the Indians (13.7%) followed by Chinese (12.0%) and Malays (9.8%). There was a moderate direct significant relationship between overweight and systolic blood pressure (r=0.5, r2=0.25, p<0.001) and also diastolic blood pressure (r=0.42, r2=0.18, p<0.001). The relationship between BMI and overweight was very weak (r=0.11, r2=0.01 and df=3331, p<0.001). In conclusion the prevalence of overweight among the secondary school students is high and there is a need for a comprehensive integrated population-based intervention program.

Unlabelled: A population-based cross-sectional study was conducted in all states of Malaysia with the aim to determine the prevalence of obesity among Malaysians aged fifteen years and above and factors associated. A stratified two-stage cluster sampling design with proportional allocation was used. Trained interviewers using a standardized protocol obtained the weight and height measurements and other relevant information. Subjects with a body mass index >= 30 kg/m2 were labelled as obese. The results show that the overall national prevalence of obesity among Malaysians aged 15 years old and above was 11.7% (95% CI = 11.1 - 12.4%). The prevalence of obesity was significantly higher in females (13.8%) as compared to 9.6% in males (p< 0.0001). Prevalence of obesity was highest amongst the Malays (13.6%) and Indians (13.5%) followed by the indigenous group of "Sarawak Bumiputra" (10.8%) and the Chinese (8.5%). The indigenous group of "Sabah Bumiputra" had the lowest prevalence of 7.3%. These differences are statistically significant (p< 0.0001). Logistic regression analysis results show that there was a significant association between obesity and age, gender, ethnicity urban/rural status and smoking status. The prevalence of obesity amongst those aged >= 18 years old has markedly increased by 280% since the last National Health and Morbidity Survey in 1996., Conclusion: The overall prevalence of obesity in Malaysia is very high as compared to 1996. There is an urgent need for a comprehensive integrated population-based intervention program to ameliorate the growing problem of obesity in Malaysians.

Anemia is the most prevalent nutritional deficiency during pregnancy. Except for a study conducted 10 years ago in Kelantan, Malaysia's available statistics are based on isolated small urban maternity hospital studies from the 1980s. There was therefore, a need for a large study at national level to estimate the magnitude of the problem in the country as well as to understand its epidemiology. This multi-center, cross-sectional study was conducted from February to March 2005, to assess the prevalence of anemia. Multistage stratified random sampling technique was used and 59 Ministry of Health (MOH) primary health care clinics were selected. Our final dataset consisted of 1,072 antenatal mothers from 56 clinics. The overall prevalence of anemia in this population was 35 % (SE 0.02) if the cut off level is 11 g/dL and 11 % (SE 0.03) if the cut-off level is 10 g/dL. The majority was of the mild type. The prevalence was higher in the teenage group, Indians followed by Malays and Chinese being the least, grandmultiparas, the third trimester and from urban residence. After multiple linear regression analysis, only gestational age remained significant. These findings are useful for our Maternal Health program planners and implementers to target and evaluate interventions. Work is in progress for outcomes and cost-effectiveness studies to best tackle this problem. In conclusion, the prevalence of anemia is 35% and mostly of the mild type and more prevalent in the Indian and Malays.

We adapted the English International Index of Erectile Function (IIEF) into Malay. This was difficult as many sex-related terms do not exist in colloquial Malay. In the pretest, there was no difficulty with comprehension and all subjects judged the Malay IIEF equivalent to the English IIEF. After slight modification, a final instrument was evaluated in two studies. Study A included 136 subjects. It showed that the instrument had good reliability and discriminant validity. The factor structure of the English IIEF was not reproducible. Study B included 26 ED subjects who underwent oral sildenafil therapy. The Malay IIEF was sensitive to treatment response. The area under the ROC curve of the Malay IIEF-5 was 0.86; the optimal cutoff score has a sensitivity of 85% and specificity of 75%. The results suggest that the Malay IIEF requires more work, but the Malay IIEF-5 has acceptable measurement properties to recommend its use in clinical practice and research.

The present investigation reports the effect of sodium selenite-induced sub-chronic toxicity in crossbred cow calves on various antioxidant enzymes. Sodium selenite (0.25 mg/kg for 16 w) resulted in characteristic signs of sub-chronic selenosis, ie alopecia, cracking and enlargement of hooves, interdigital lesions, ring formation on the coronet region, and gangrene at tip of the tail. The sodium selenite resulted in significant rise of blood selenium levels and concurrent increase in erythrocytic glutathione peroxidase (GPx) activity. Blood selenium levels and GPx activity had a high positive correlation (r = 0.97). Blood glutathione levels were lowered from 211.1 +/- 13.4 to 95.56 +/- 11.8 microg/ml. Selenosis caused oxidative stress as evidenced by a 3-fold increase in lipid peroxidation: activities of glutathione-S-transferase, glutathione reductase, superoxide dismutase and catalase were significantly increased. These findings support the hypothesis that the pro-oxidant attributes of selenium play important roles in its toxicity.