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1.  Influence of the Flushing Response in the Relationship between Alcohol Consumption and Cardiovascular Disease Risk 
Korean Journal of Family Medicine  2014;35(6):295-302.
The purpose of this study was to examine the relationship between cardiovascular disease risk and alcohol consumption according to facial flushing after drinking among Korean men.
The subjects were 1,817 Korean men (non-drinker group, 283 men; drinking-related facial flushing group, 662 men; non-flushing group, 872 men) >30 years who had undergone comprehensive health examinations at the health promotion center of a Chungnam National University Hospital between 2007 and 2009. Alcohol consumption and alcohol-related facial flushing were assessed through a questionnaire. Cardiovascular disease risk was investigated based on the 2008 Framingham Heart Study. With the non-drinker group as reference, logistic regression was used to analyze the relationship between weekly alcohol intake and cardiovascular disease risk within 10 years for the flushing and non-flushing groups, with adjustment for confounding factors such as body mass index, diastolic blood pressure, low density lipoprotein cholesterol, triglycerides, and exercise patterns.
Individuals in the non-flushing group with alcohol consumption of ≤4 standard drinks (1 standard drink = 14 g of alcohol) per week had significantly lower moderate or high cardiovascular disease risk than individuals in the nondrinker group (adjusted odds ratio, 0.51; 95% confidence interval, 0.37 to 0.71). However, no significant relationship between the drinking amount and cardiovascular disease risk was observed in the flushing group.
Cardiovascular disease risk is likely lowered by alcohol consumption among non-flushers, and the relationship between the drinking amount and cardiovascular disease risk may differ according to facial flushing after drinking, representing an individual's vulnerability.
PMCID: PMC4242907  PMID: 25426277
Alcohol; Flushing; Cardiovascular Diseases; Risk
2.  Diabetes and Depressive Symptoms in Korean Women: The Fifth Korean National Health and Nutrition Examination Survey (2010-2011) 
Korean Journal of Family Medicine  2014;35(3):127-135.
The purpose of this study was to investigate the association between diabetes and depressive symptoms among Korean women.
We performed an analysis of data for 6,572 women aged 30 or over obtained from the Fifth Korean National Health and Nutrition Examination Survey conducted in 2010 to 2011. We examined the presence of depressive symptoms and the treatment of depression according to diabetes status.
The presence of depressive symptoms was observed in 22.6% of subjects with diabetes. In the multiple logistic regression model, diabetes was associated with an increased risk of depressive symptoms (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.20 to 1.21) but the treatment of depression among diabetics was less common (OR, 0.54; 95% CI, 0.54 to 0.55). Uncontrolled diabetes (glycosylated hemoglobin ≥ 7%) was associated with an increased risk of depressive symptoms (OR, 1.71; 95% CI, 1.69 to 1.73) among diabetics.
Physicians should manage individuals with diabetes in consideration of the presence of depressive symptoms, especially in those with uncontrolled diabetes.
PMCID: PMC4040430  PMID: 24921031
Diabetes Mellitus; Depression; Women
3.  Reliability and Validity of Alcohol Use Disorder dentification Test-Korean Revised Version for Screening At-risk Drinking and Alcohol Use Disorders 
There needs to be an amendment to the Korean version of the Alcohol Use Disorder Identification Test (AUDIT) with regards to the recent change in percent alcohol by volume (ABV) Korean liquor. This study was performed to suggest a cutoff value, reliability and validity of AUDIT-Korean revised version (AUDIT-KR), which reflect the change of the ABV of Korean alcohol.
The subjects were 435 peoples (210 males and 225 females), who visited the Chungnam National University Hospital for a comprehensive medical examination. The respondents completed the AUDIT-KR. At-risk drinking and alcohol use disorders had been evaluated by diagnostic interview. The Cronbach's alpha value, the receiver operating characteristic curve, the appropriate cutoff value, sensitivity and specificity of the AUDIT-KR were evaluated.
There were 190 at-risk drinkers (111 males and 79 females), and 66 people with alcohol use disorders (48 males and 18 females). The cutoff value of the AUDIT-KR for at-risk drinking was 3 points (sensitivity 93.69% and specificity 78.79%) for males and 3 points (sensitivity 92.40% and specificity 78.08%) for females. The cutoff value for alcohol use disorders was 10 points (sensitivity 100.00% and specificity 89.51%) for males and 8 points (sensitivity 100.00% and specificity 93.71%) for females. Cronbach's alpha of the AUDIT-KR was 0.885.
The above results suggest that the AUDIT-KR shows a high reliability and validity in identifying at-risk drinking and alcohol use disorders.
PMCID: PMC3912263  PMID: 24501664
Alcohols; Questionnaires; Drinking
4.  The Role of Paternal Drinking Problems in the Psychological Characteristics of High School Students 
Korean Journal of Family Medicine  2013;34(6):377-384.
It has been reported that children with parental drinking problems are at increased risk of drinking problems or psychiatric diseases in adulthood. The present study was conducted to examine the psychiatric characteristics of high school students according to paternal drinking problems.
The subjects were 950 high school students (390 male and 560 female). The paternal drinking problems were assessed by using the Father-Short Michigan Alcoholism Screening Test. The Alcohol Use Disorders Identification Test, Beck's depression inventory, and Beck's anxiety inventory were used to evaluate the drinking behavior, depression, and anxiety of high school students.
While male students with paternal drinking problems showed significantly increased risk of anxiety (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.05 to 4.63), female students with paternal drinking problems showed significantly increased risk of depression (OR, 1.84; 95% CI, 1.24 to 2.74) according to the results of logistic regression analysis with adjustments for participants' age, whether they live together with parents, their religion, club activities, and smoking habits on the basis of students without paternal drinking problems.
The above results suggest that paternal drinking problems lead to unstable mentalities in both male and female students, and that a family physician should address the mental state of teenagers with paternal drinking problems during clinical encounters.
PMCID: PMC3856279  PMID: 24340159
Fathers; Students; Alcohol; Depression; Anxiety
5.  Effect of Alcohol Consumption on Risk of Hyperhomocysteinemia Based on Alcohol-Related Facial Flushing Response 
Korean Journal of Family Medicine  2013;34(4):250-257.
This study examined the relationship between alcohol consumption and hyperhomocysteinemia based on facial flushing caused by drinking.
Among male patients aged ≥ 18 years who visited Health Promotion Center of Chungnam National University Hospital in Daejeon from January 2008 to December 2010, 948 males (182 nondrinkers, 348 subjects with drinking-related facial flushing, and 418 subjects without drinking-related facial flushing) were selected. After adjusting for confounding factors such as age, body mass index, hypertension, diabetes, smoking, triglycerides, high density lipoprotein cholesterol, and gamma-glutamyl transpeptidase, a multiple logistic regression analysis was performed to assess the risk of hyperhomocysteinemia in the nonfacial flushing and facial flushing groups compared with the nondrinkers.
After adjusting for confounding factors, risk of hyperhomocysteinemia was significantly lower in the group with a weekly alcohol consumption of < 8 standard drinks (1 drink = 14 g alcohol) in the nonfacial flushing group (<4 drinks: odds ratio [OR], 0.27; 95% confidence interval [CI], 0.10 to 0.74; 4≤, <8 drinks: OR, 0.21; 95% CI, 0.06 to 0.73). Risk of hyperhomocysteinemia was significantly lower in the group with a weekly alcohol consumption < 4 drinks in the facial flushing group (OR, 0.30; 95% CI, 0.13 to 0.68).
Our results suggest that the risk of hyperhomocysteinemia is likely lowered by alcohol consumption based on drinking quantity, as lowering the risk of hyperhomocysteinemia differs depending on vulnerability associated with facial flushing.
PMCID: PMC3726792  PMID: 23904954
Homocysteine; Flushing; Alcohol Drinking
6.  Utility of the Alcohol Consumption Questions in the Alcohol Use Disorders Identification Test for Screening At-Risk Drinking and Alcohol Use Disorders among Korean College Students 
Korean Journal of Family Medicine  2013;34(4):272-280.
This study evaluated the utility of the Alcohol Use Disorders Identification Test Alcohol Consumption Questions (AUDIT-C) in screening at-risk drinking and alcohol use disorders among Korean college students.
For the 387 students who visited Chungnam National University student health center, drinking state and alcohol use disorders were assessed through diagnostic interviews. In addition, Alcohol Use Disorders Identification Test (AUDIT), AUDIT-C, and cut down, annoyed, guilty, eye-opener (CAGE) were applied. The utility of the questionnaires for the interview results were compared.
The areas under the receiver operating characteristic curves (AUROCs) of AUDIT-C for screening at-risk drinking were 0.927 in the male and 0.921 in the female participants. The AUROCs of AUDIT and CAGE were 0.906 and 0.643, respectively, in the male, and 0.898 and 0.657, respectively, in the female participants. The optimal screening scores of at-risk drinking in AUDIT-C were ≥6 in the male and ≥4 in the female participants; and in AUDIT and CAGE, ≥8 and ≥1, respectively, in the male, and ≥5 and ≥1 in the female participants. The AUROCs of AUDIT-C in screening alcohol use disorders were 0.902 in the male and 0.939 in the female participants. In the AUDIT and CAGE, the AUROCs were 0.936 and 0.712, respectively, in the male, and 0.960 and 0.844, respectively, in the female participants. The optimal screening scores of alcohol use disorders in AUDIT-C were ≥7 in the male and ≥6 in the female participants; and in AUDIT and CAGE, ≥10 and ≥1, respectively, in the male, and ≥8 and ≥1 in the female participants.
AUDIT-C is considered useful in screening at-risk drinking and alcohol use disorders among college students.
PMCID: PMC3726795  PMID: 23904957
Universities; Students; Alcohol; Mass Screening
7.  Association of Abdominal Aortic Calcification with Lifestyle and Risk Factors of Cardiovascular Disease 
Korean Journal of Family Medicine  2013;34(3):213-220.
Abdominal aortic calcification (AAC) is a marker of subclinical atherosclerotic disease and an independent predictor of subsequent vascular morbidity and mortality. This study was conducted to investigate the association of AAC with lifestyle and risk factors of cardiovascular disease.
The results of the abdominal computed tomography of 380 patients who visited Chungnam National University Hospital for a health checkup from January 1, 2008 to December 31, 2009 were reviewed. A six-point scale was used in grading the overall severity of the calcification in three areas of the abdominal aorta, including the area superior to the renal artery, the upper-half area inferior to the renal artery, and the lower-half area inferior to the renal artery, in addition to the common iliac artery. The association of the AAC severity with the age, lifestyle factors, and risk factors of cardiovascular disease was analyzed via multiple linear regression analysis.
In the male subjects, the age, presence of dyslipidemia and smoking were positively related to AAC, but exercising was negatively related to AAC (total R2 = 0.563). In the female subjects, the age and presence of diabetes mellitus, hypertension, and dyslipidemia were positively related to AAC, but exercising was negatively related to AAC (total R2 = 0.547).
AAC was related to both the male and female subjects' age, presence of dyslipidemia, and exercising, to smoking in the male subjects and to the presence of diabetes mellitus and hypertension in the female subjects.
PMCID: PMC3667229  PMID: 23730489
Aorta; Calcification; Atherosclerosis; Life Style
8.  Relationships between the Level of Alcohol Consumption and Abnormality in Biomarkers According to Facial Flushing in Korean Male Drinkers 
Korean Journal of Family Medicine  2013;34(2):123-130.
This research investigated the association between facial flushing after drinking and alcohol-induced biomarker abnormalities.
This retrospective study included 374 male drinkers who visited the department of Family Medicine of Chungnam National University Hospital between January and December of 2010. The participants were classified into two groups: the flushing group (n = 107) and the non-flushing group (n = 267). The biomarkers assessed were % carbohydrate-deficient transferrin (CDT) and gamma glutamyl transferase (rGTP). The upper limits of %CDT and rGTP were set as 2.47 and 50, respectively. The receiver operating characteristic (ROC) curve was used to obtain the cut-off value for the amount of drinking that caused abnormal %CDT and rGTP levels in the two groups. The sensitivity and specificity of the cut-off drinking amount for %CDT and rGTP abnormalities were analyzed in each group.
In the flushing group, the cut-off value for alcohol-induced %CDT abnormality was 3.38 drinks (1 drink: 14 g of alcohol) per week, with sensitivity of 77.8% and specificity of 70.4%. In the non-flushing group, the cut-off value was 11.25 drinks per week, with sensitivity of 62.2% and specificity of 69.6%. The cut-off value for the amount of alcohol that induced rGTP abnormality was 3.38 drinks per week in the flushing group, with sensitivity of 68.0% and specificity of 76.8%, whereas it was 8.75 drinks in the non-flushing group, with sensitivity of 71.1% and specificity of 66.7%. The area under the ROC of the drinking level was 0.726 in the flushing group and 0.684 in the non-flushing group for %CDT. For rGTP, the value was 0.738 in the flushing group and 0.718 in the non-flushing group.
The weekly drinking amount required to induce biomarker abnormalities was lower in the flushers than in the non-flushers.
PMCID: PMC3611100  PMID: 23560211
Flushing; Alcohol; Biological Markers; Drinking
9.  Nomogram for Predicting the Benefit of Adjuvant Chemoradiotherapy for Resected Gallbladder Cancer 
Journal of Clinical Oncology  2011;29(35):4627-4632.
Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer.
Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT.
A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser–based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary.
A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT.
PMCID: PMC3236647  PMID: 22067404
10.  Usefulness of Alcohol-screening Instruments in Detecting Problem Drinking among Elderly Male Drinkers 
Korean Journal of Family Medicine  2012;33(3):126-133.
In Korea, few studies have been performed on screening instruments for the detection of at-risk drinking and alcohol use disorders in the elderly. This study evaluated the validity of three screening instruments in elderly male drinkers.
The subjects were 242 Korean men aged ≥ 65 years. Face-to-face interviews were used to identify at-risk drinking and alcohol use disorders. At-risk drinking was defined according to the criteria for heavy or binge drinking of the National Institute on Alcohol Abuse and Alcoholism. Alcohol use disorder was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV-text revision. The Alcohol Use Disorder Identification Test (AUDIT), Short Michigan Alcoholism Screening Test-geriatric version (SMAST-G), and cut down, annoyed, guilty, eye-opener (CAGE) questionnaire were used as the alcohol-screening instruments. Based on the diagnostic interview results, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of the instruments were compared.
For identification of at-risk drinking, the AUDIT AUROC demonstrated greater diagnostic power than did those of SMAST-G and CAGE (both P < 0.001). In screening for alcohol use disorders, the AUDIT AUROC was also significantly higher than those of SMAST-G and CAGE (both P < 0.001). The sensitivity and specificity of screening for at-risk drinking with an AUDIT score ≥ 7 were 77.3% and 85.1%, respectively, whereas those for the alcohol use disorders with an AUDIT score ≥ 11 were 91.3% and 90.8%, respectively.
The results suggest that the AUDIT is the most effective tool in identifying problem drinkers among elderly male drinkers.
PMCID: PMC3391637  PMID: 22787534
Alcohol; Mass Screening; Aged; Alcoholism
11.  Effects of Brief Advice from Family Physicians on the Readiness to Change of Korean Male At-risk Drinkers 
Korean Journal of Family Medicine  2012;33(3):157-165.
This study examined the effects of the method of delivery of brief advice on the readiness to change in at-risk drinkers.
The participants were 103 at-risk male drinkers who visited Chungnam National University Hospital for general health examinations. Baseline data on drinking behavior, readiness to change drinking behavior, and sociodemographic characteristics were obtained from a questionnaire. Family physicians gave two minutes of advice by telephone or in-person. The brief advice comprised a simple statement that the patient's drinking exceeded the recommended limits and could lead to alcohol-related problems. It also included advice to moderate one's drinking. One month later, the readiness to change was assessed again by telephone. The improvement in the readiness to change according to each method of delivery was investigated.
Initially, among the 58-patient in-person advice group, 12 patients were in the precontemplation stage, 38 in the contemplation stage, and 8 in the action stage. One month after the advice was given to the patients, the distribution had changed significantly (P < 0.001) to 1, 21, and 36 patients, respectively. Among the 45-patient telephone advice group, 7 patients were in the precontemplation stage, 32 patients were in the contemplation stage, and 6 patients were in the action stage before the advice. The distribution had changed significantly (P < 0.001) to 1, 17, and 27 patients, respectively, 1 month after the advice.
These results suggest that brief advice by family physicians is effective in improving the readiness to change of at-risk drinkers, regardless of the delivery method.
PMCID: PMC3391641  PMID: 22787538
Drinking; Counseling; Physicians; Telephone; Attitude
12.  Brief Insight-enhancement Intervention among Patients with Alcohol Dependence 
Patients' insight has a critical role in the recovery from problematic behavior. The aim of this study was to evaluate the effects of a brief intervention to promote insight among alcohol-dependent patients. A total of 41 alcohol-dependent patients (30 males, 11 females) in an insight-deficient state who had been admitted to a community-based alcohol treatment center, were randomized into two groups based on their admission order: an intervention group (IG) (n = 20) and a control group (CG) (n = 21). Patients in both the IG and CG participated in an identical treatment program with one exception: patients in the IG were required to undergo five sessions of brief individual intervention focusing on insight enhancement. Changes in insight state were assessed after the intervention. The IG exhibited significant (P < 0.05) changes in the distribution of insight level, while the CG did not exhibit any significant changes in the distribution of insight level. The insight score after intervention was significantly (P < 0.05) greater for the IG than the CG with adjustment for the baseline characteristics. The results suggest that a brief individual intervention focused on insight enhancement may be an effective tool to improve insight among alcohol-dependent patients.
PMCID: PMC3012834  PMID: 21218023
Insight; Brief Intervention; Alcohol Dependence; Individual Counseling; Patient Education
13.  Carbohydrate-deficient Transferrin as a Marker of Heavy Drinking in Korean Males 
Journal of Korean Medical Science  2007;22(4):652-655.
This study was performed to evaluate the usefulness of carbohydrate-deficient transferrin (CDT) as a marker of heavy drinking in Korean males. The subjects (143 Korean males) were classified into 2 groups according to the amount of drinking, moderate drinkers (72 individuals) who drank 14 drinks or less per week and heavy drinkers (71 individuals) who drank more than 14 drinks per week. Using %CDT, gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as clinical markers for heavy drinking, sensitivity, specificity, positive and negative predictive values were investigated. Sensitivities of %CDT, GGT, AST, and ALT were 83.1%, 67.6%, 52.1% and 46.5%, respectively. Specificities were 63.9%, 45.8%, 72.2%, and 54.2%, respectively. Positive predictive values were 69.4%, 55.2%, 64.9%, and 50.0% respectively. Negative predictive values were 79.3%, 58.9%, 60.5%, and 50.6% respectively. The areas under the receiver operating characteristic curve (95% confidence interval) for %CDT, GGT, AST, and ALT were 0.823 (0.755-0.891), 0.578 (0.484-0.673), 0.622 (0.528-0.717), and 0.516 (0.420-0.613), respectively. CDT is considered as the most reliable marker for detecting heavy drinking in Korean males.
PMCID: PMC2693814  PMID: 17728504
Drinking; Carbohydrate-deficient Transferrin; Diagnosis
14.  The Readiness to Change and Insight in Alcohol dependent Patients 
Journal of Korean Medical Science  2007;22(3):453-458.
This study was performed to investigate the effect of insight on the readiness to change in alcoholism. The subjects were 131 Korean male patients with alcohol dependence who were being hospitalized in a community-based alcohol treatment center. The patients' readiness to change was classified into precontemplation, contemplation, and action stage through the readiness to change questionnaire. The state of the patients' insight was measured through the Hanil alcohol insight scale. Fourteen patients (10.7%) were in the stage of precontemplation, 65 (49.6%) in contemplation and 52 (39.7%) in action stage. The insight score of the patients in precontemplation stage was significantly lower (p<0.001) than that of others. On the basis of the precontemplation stage, multinomial logistic regression analysis for the control of the differences in the patients' characteristics among each stage of the readiness to change showed that the possibility of contemplation and action stage went up 1.231 (p<0.01) and 1.249 (p<0.01) times higher as the insight score increased.
PMCID: PMC2693637  PMID: 17596653
Alcoholism; Motivation; Awareness; Readiness to Change
15.  The Role of Alcoholics' Insight in Abstinence from Alcohol in Male Korean Alcohol Dependents 
Journal of Korean Medical Science  2007;22(1):132-137.
This study was performed to examine the relationship between the abstinence results of alcohol dependents after discharge and the level of insight at the time of discharge. 117 male Korean alcohol dependents discharged from a community-based alcohol treatment center were followed up to determine the initial months of abstinence on a successive basis (IMA), total months of abstinence during 12-month period (TMA), and complete abstinence for one full year after discharge. Analyses of abstinence results with adjustment for the differences in baseline characteristics were performed for subjects' insight levels (poor, fair and good). The mean IMA of patients with good insight was significantly (p<0.01) longer than that of patients with poor insight and TMA of patients with good insight was significantly (p<0.001) longer than that of others. Using patients with good insight as the reference, patients with poor insight showed an adjusted odds ratio (OR) of 0.07 (95% confidence interval [CI]=0.01-0.75, p<0.05) for complete abstinence for one full year after discharge and patients with fair insight, adjusted OR of 0.17 (95% CI=0.03-0.81, p<0.05). These results suggest that alcohol dependents' insight could be regarded as a factor related with abstinence.
PMCID: PMC2693550  PMID: 17297266
Insight; Alcoholism; Alcohol Dependence; Abstinence
16.  A coronary heart disease prediction model: the Korean Heart Study 
BMJ Open  2014;4(5):e005025.
The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score.
A prospective cohort study within a national insurance system.
18 health promotion centres nationwide between 1996 and 2001 in Korea.
268 315 Koreans between the ages of 30 and 74 years without CHD at baseline.
Outcome measure
Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI).
The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort.
The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.
PMCID: PMC4039825  PMID: 24848088
17.  Physicochemical Characterization of Simulated Welding Fume from a Spark Discharge System 
This study introduces spark discharge system (SDS) as a way to simulate welding fumes. The SDS was developed using welding rods as electrodes with an optional coagulation chamber. The size, morphology, composition, and concentration of the fume produced and the concentration of ozone (O3) and nitrogen oxides (NOX) were characterized. The number median diameter (NMD) and total number concentration (TNC) of fresh fume particles were ranged 10–23 nm and 3.1×107–6×107 particles/cm3, respectively. For fresh fume particles, the total mass concentration (TMC) measured gravimetrically ranged 85–760 μg/m3. The size distribution was stable over a period of 12 h. The NMD and TNC of aged fume particles were ranged 81–154 nm and 1.5×106–2.7×106 particles/cm3, respectively. The composition of the aged fume particles was dominated by Fe and O with an estimated stoichiometry between that of Fe2O3 and Fe3O4. Concentrations of O3 and NOX were ranged 0.07–2.2 ppm and 1–20 ppm, respectively. These results indicate that the SDS is capable of producing stable fumes over a long-period that are similar to actual welding fumes. This system may be useful in toxicological studies and evaluation of instrumentation.
PMCID: PMC4119574  PMID: 25097299
18.  Toxicity Assessment of Air-delivered Particle-bound Polybrominated Diphenyl Ethers 
Toxicology  2014;317:31-39.
Human exposure to polybrominated diphenyl ether (PBDE) can occur via ingestion of indoor dust, inhalation of PBDE-contaminated air and dust-bound PBDEs. However, few studies have examined the pulmonary toxicity of particle-bound PBDEs, mainly due to the lack of an appropriate particle-cell exposure system. In this study we developed an in vitro exposure system capable of generating particle-bound PBDEs mimicking dusts containing PBDE congeners (BDEs 35, 47, 99) and delivering them directly onto lung cells grown at an air-liquid interface (ALI). The silica particles and particle-coated with PBDEs ranged in diameter from 4.3 to 4.5 μm and were delivered to cells with no apparent aggregation. This experimental set up demonstrated high reproducibility and sensitivity for dosing control and distribution of particles. ALI exposure of cells to PBDE-bound particles significantly decreased cell viability and induced reactive oxygen species generation in A549 and NCI-H358 cells. In male Sprague-Dawley rats exposed via intratracheal insufflation (0.6 mg/rat), particle-bound PBDE exposures induced inflammatory responses with increased recruitment of neutrophils to the lungs compared to sham-exposed rats. The present study clearly indicates the potential of our exposure system for studying the toxicity of particle-bound compounds.
PMCID: PMC3975599  PMID: 24451063
Particle-bound PBDEs; Lung cells; Air-liquid interface; In vitro toxicity testing; Cytotoxicity
19.  Expansive marker analysis replicating the association of glaucoma susceptibility with human chromosome loci 1q43 and 10p12.31 
Three human chromosome loci (1q43, 10p12.31, and 12q21.31) were recently associated with the susceptibility to primary open-angle glaucoma (POAG) in a Japanese population; however, this was not replicated in three subsequent studies using South Indian, Afro-Caribbean, and Chinese populations. To identify genetic markers that are robustly associated across ethnic populations, numerous markers in addition to the six in the three reported loci were examined in this study. A total of 31 single-nucleotide polymorphism (SNP) markers were genotyped for 1115 Korean participants, and many neighboring SNPs were imputed using the Korean HapMap Project genotype data. Each SNP was statistically tested for association with POAG susceptibility by comparisons among 211 POAG patients with 904 unaffected controls. A strong and statistically significant association was found with a previously unreported SNP, rs7098387 (odds ratio, OR=2.0 (1.4–3.0), P=0.00038) at the 10p12.31 locus (where 11 SNPs were typed and 38 imputed) in contrast to the reported rs7081455, which was too poorly correlated with newly associated rs7098387 (r2=0.003, D′=0.40) to show association. Additionally, a modest association was observed with the reported rs693421 (OR=1.4 (1.1–1.7), P=0.0082) and several other SNPs located within and around ZP4 at the 1q43 locus (10 SNPs typed and 14 imputed). However, no association was observed with the reported rs7961953 SNP or any other SNPs at the 12q21.31 locus, upstream of TMTC2 (10 SNPs typed and 29 imputed). Accordingly, POAG susceptibility association was replicated using rs7098387 (C) rather than rs7081455 (T) at the 10p12.31 locus and additionally with rs693421 (T) at the 1q43 locus.
PMCID: PMC3925277  PMID: 23838595
primary open-angle glaucoma; single-nucleotide polymorphism; replicative association study; 1q43; 10p12.31
20.  Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk 
Molecular Vision  2015;21:548-554.
The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma.
Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data.
Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis.
The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG.
PMCID: PMC4431411  PMID: 26015768
21.  Vitamin D Status and Response to Initial Vitamin D Supplementation in Korean Women with Osteoporosis 
Journal of Bone Metabolism  2014;21(4):257-262.
The aim of this study is to evaluate whether the optimal vitamin D level is achieved after taking recommended dose in vitamin D deficient patients.
This was a retrospective study. Women (n=52) first diagnosed with osteoporosis were recruited in outpatient clinic. They were recommended to be exposed to sun light for more than 30 min a day. Subjects were divided into 3 groups according to serum 25-hydroxy-vitamin D3 (25-[OH]D3) status: deficiency (less than 20 ng/mL), insufficiency (20-30 ng/mL) and sufficiency (30 ng/mL or more). Insufficient and sufficient patients received the recommended dose (1,000 IU/day) but deficient patients received recommended or double dose (1,800-2,000 IU/day). We compared 25-(OH)D levels at baseline and after vitamin D supplementation for 3 months.
Median (interquartile range) serum 25-(OH)D concentration at baseline was 15.10 (13.30-16.97) ng/mL and the proportion of deficient, insufficient and sufficient groups were 69.2%, 23.1%, and 7.7% respectively. The optimal 25-(OH)D level (30 ng/mL or more) was achieved in 83.3% of insufficient patients with the recommended dose and was did in 55.6% of deficient patients with recommended dose (P=0.117). However, 88.9% of the deficient patient with double dose achieved optimal level (P=0.030).
About 44% of vitamin D deficient patients did not attain the optimal level of serum 25-(OH)D despite recommended daily intake of vitamin D to 1,000 IU in patients with osteoporosis. Follow-up of serum 25-(OH)D levels may be required for vitamin D supplementation in vitamin D deficient patients with osteoporosis.
PMCID: PMC4255046  PMID: 25489574
25-hydroxyvitamin D3; Osteoporosis; Vitamin D; Women
22.  Intracranial Stenting for Severe Symptomatic Stenosis: Self-Expandable versus Balloon-Expandable Stents 
Interventional Neuroradiology  2013;19(3):276-282.
Intracranial atherosclerosis against optimal medical treatment requires reperfusion therapy to improve the clinical outcome. We compared outcomes between self-expandable stent (SES) and/or balloon-expandable stent (BES) and present the potential advantages of using each stent.
During the same time frame before and after Wingspan introduction to our institute, 115 consecutive patients underwent intracranial stenting for symptomatic severe intracranial stenosis against optimal medical treatment using BES alone (n = 71) vs. BES or SES (n = 44). We analyzed 15 factors including outcome related to an adverse event (AE), modified Rankin Scale (mRS) and restenosis at six months and retrospectively compared the potential advantages of using each stent.
BES or SES groups had a significantly lower AE rate (2.3%) than the BES only group (14%) (P = 0.049) revealing mRS of ≤ 2 in all patients at six months compared to 93% of the patients in the BES group. Analysis of BES or SES subgroups revealed that BES was associated with less residual stenosis after stenting than SES (18 vs. 32%; P < 0.001).
Both SES and BES can improve the clinical outcome of intracranial stenting especially with a selective choice of SES or BES. Further study is needed to analyse the difference in long-term outcome and the restenosis rate between SES and BES.
PMCID: PMC3806001  PMID: 24070075
intracranial stenosis, stenting, outcome
23.  A Study Design to Evaluate Association between Smoking and Intracranial Atherosclerotic Stenosis 
Neurointervention  2014;9(2):89-93.
Smoking is a well known risk factor for stroke. The cerebral arteries may be uniquely susceptible to the atherosclerotic effects of smoking, such that it has a different risk profile for stroke compared with other atherosclerosis risk factors. It remains uncertain whether smoking is associated specifically with intracranial (IC) or extracranial (EC) atherosclerotic cerebrovascular disease. The aim of this study design will be to evaluate the association between smoking and severe IC stenosis, adjusting for other atherosclerosis risk factors, particularly age distribution.
Study design
This is a retrospective cohort study design. Participants are patients (n=1714) with severe atherosclerotic stenosis undergoing cerebral catheter angiography because of stroke or transient ischaemic attack. All atherosclerotic steno-occlusive lesions are described in terms of location (anterior versus posterior circulation, IC versus EC, or intradural versus extradural). The atherosclerotic or stroke risk factors for analysis include age, gender, smoking history, number of lesions (single versus multiple), cardiac disease, diabetes mellitus, hypertension, family history, dyslipidemia, history of previous stroke, alcohol intake, metabolic syndrome and body mass index. Statistical analysis includes univariate analysis followed by multivariate logistic regression. The relationship between IC atherosclerotic stenosis and smoking will be assessed. Differences in risk factor distribution is analysed according to age at intervals of 10 years. Significant risk factors associated with IC atherosclerotic stenosis will also be assessed by multivariate logistic regression analysis.
This is an analytical study design that intends to measure the association between IC or EC atherosclerotic stenosis and smoking and other risk factors. We anticipate that it will have the power to detect any relationship between smoking and IC atherosclerotic lesions especially in younger patients.
PMCID: PMC4239414  PMID: 25426304
Smoking; Stenosis; Atherosclerosis; Risk Factors
24.  Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models 
Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses.
Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured.
An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals.
Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route.
PMCID: PMC3994238  PMID: 24684892
Zinc oxide nanoparticles; Dissolution; Inhalation; Murine model; Pulmonary response; Toxicity
25.  Validation of an in vitro exposure system for toxicity assessment of air-delivered nanomaterials 
To overcome the limitations of in vitro exposure of submerged lung cells to nanoparticles (NPs), we validated an integrated low flow system capable of generating and depositing airborne NPs directly onto cells at an air–liquid interface (ALI). The in vitro exposure system was shown to provide uniform and controlled dosing of particles with 70.3% efficiency to epithelial cells grown on transwells. This system delivered a continuous airborne exposure of NPs to lung cells without loss of cell viability in repeated 4 h exposure periods. We sequentially exposed cells to air-delivered copper (Cu) NPs in vitro to compare toxicity results to our prior in vivo inhalation studies. The evaluation of cellular dosimetry indicated that a large amount of Cu was taken up, dissolved and released into the basolateral medium (62% of total mass). Exposure to Cu NPs decreased cell viability to 73% (p < 0.01) and significantly (p < 0.05) elevated levels of lactate dehydrogenase, intracellular reactive oxygen species and interleukin-8 that mirrored our findings from subacute in vivo inhalation studies in mice. Our results show that this exposure system is useful for screening of NP toxicity in a manner that represents cellular responses of the pulmonary epithelium in vivo.
PMCID: PMC3950355  PMID: 22981796
Nanoparticles; Lung cells; Air–liquid interface; Deposition efficiency; Spatial uniformity; Cellular dose

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