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1.  Nationwide Survey of Patient Knowledge and Attitudes towards Human Experimentation Using Stem Cells or Bee Venom Acupuncture for Parkinson’s Disease 
Journal of Movement Disorders  2014;7(2):84-91.
Objective
Stem cell treatment is a well-recognized experimental treatment among patients with Parkinson’s disease (PD), for which there are high expectations of a positive impact. Acupuncture with bee venom is one of the most popular complementary and alternative treatments for PD. Patient knowledge and attitudes towards these experimental treatments are unknown.
Methods
Using a 12-item questionnaire, a nationwide survey was conducted of 963 PD patients and 267 caregivers in 44 Korean Movement Disorders Society member hospitals from April 2013 to June 2013. The survey was performed by trained interviewers using conventional methods.
Results
Regarding questions on experimental treatments using stem cells or bee venom acupuncture, 5.1–17.7% of PD patients answered questions on safety, efficacy, and evidence-based practice incorrectly; however, more than half responded that they did not know the correct answer. Although safety and efficacy have not been established, 55.5% of PD patients responded that they were willing to receive stem cell treatment. With regard to participating in experimental treatments, there was a strong correlation between stem cell treatment and bee venom acupuncture (p < 0.0001, odds ratio = 5.226, 95% confidence interval 3.919–6.969). Younger age, higher education, and a longer duration of PD were all associated with a correct understanding of experimental treatments.
Conclusions
Our data suggest that relatively few PD patients correctly understand the safety and efficacy of experimental treatments and that PD patients are greatly interested in new treatments. We hope that our data will be used to educate or to plan educational programs for PD patients and caregivers.
doi:10.14802/jmd.14012
PMCID: PMC4213536  PMID: 25360232
Parkinson’s disease; Survey; Experimental treatment; Stem cell; Complementary alternative medicine
2.  Topical Prostaglandin Analogue Drugs Inhibit Adipocyte Differentiation 
Purpose
To investigate the effects of topical prostaglandin analogue drugs on the differentiation of adipocytes.
Methods
Differentiation of 3T3-L1 preadipocytes was induced with isobutylmethylxanthine, dexamethasone, and insulin. 3T3-L1 cells were exposed to 0.008, 0.08, 0.2 µM of latanoprost and travoprost. Reverse transcription polymerase chain reaction for mRNA expression of lipoprotein lipase and peroxisome proliferator-activated receptor γ 2 (PPARγ2), and glycerol-3-phosphate dehydrogenase (G3PDH) assays were performed to examine the effects on early and late differentiation, respectively. Also, glycerol assays were done to evaluate the effect of prostaglandin analogues on lipolysis after differentiation.
Results
Both prostaglandin analogues inhibited differentiation of preadipocytes. Topical prostaglandin analogues significantly decreased G3PDH activity, a marker of late differentiation. However, topical prostaglandin analogues did not change mRNA expressions of lipoprotein lipase and PPARγ2, markers of early differentiation. The activities of the early markers of differentiation were not changed significantly before and after growth arrest. Compared to latanoprost, travoprost decreased G3PDH activity more significantly (p < 0.05). Both prostaglandin analogues did not affect the lipolysis of differentiated adipocytes (p > 0.05).
Conclusions
Prostaglandin analogues display an inhibitory effect on the differentiation of adipocytes when the cells start to differentiate especially in the late stage of differentiation. Thus, commercial topical prostaglandin analogues may decrease the fat contents of eyelids.
doi:10.3341/kjo.2014.28.3.257
PMCID: PMC4038732  PMID: 24882960
Adipocytes; Differentiation; Eyelids; Prostaglandin
3.  The Efficacy of Exercise Programs for Parkinson's Disease: Tai Chi versus Combined Exercise 
Background and Purpose
Exercise is recommended for every patient with Parkinson's disease (PD). The effectiveness of two different forms of exercise for PD, Tai Chi and combined stretching-strengthening exercise, was compared.
Methods
Patients with mild-to-moderate PD were recruited to join either the combined stretching-strengthening exercise group (n=7), the Tai Chi group (n=9), or the control (nonintervention) group (n=7). Exercise was performed three times a week over a period of 8 weeks. The Tai Chi exercise was led by certified instructors based on a Tai-Chi-for-arthritis program. The combined stretching-strengthening exercise comprised folk dancing, stepping, and elastic-band exercises. The subjects' functional fitness, parkinsonian symptoms, quality of life (QoL), and depression were evaluated.
Results
Both exercise groups yielded better results in their overall functional fitness after the intervention. However, no improvement with exercise was found for parkinsonian symptoms, as evaluated using the Unified Parkinson's Disease Rating Scale. With respect to the domains of QoL, the combined stretching-strengthening exercise group fared better in the social domain of QoL, and the Tai Chi group fared better in the emotional domain, while QoL and depression worsened in the control group. The postintervention QoL was improved relative to the control condition only for the Tai Chi group. Although the exercise interventions did not have any effect on depression, the control group was associated with a significant deterioration.
Conclusions
Exercise improved the functional fitness and QoL of PD patients, with Tai Chi yielding better results in QoL and favorable results in functional fitness. These findings suggest that Tai Chi could be a good exercise strategy for patients with PD.
doi:10.3988/jcn.2013.9.4.237
PMCID: PMC3840134  PMID: 24285965
Parkinson's disease; exercise; Tai Chi; quality of life
4.  Usefulness of Forward-Viewing Endoscope for Endoscopic Retrograde Cholangiopancreatography in Patients with Billroth II Gastrectomy 
Clinical Endoscopy  2012;45(4):397-403.
Background/Aims
Patients undergoing Billroth II (B II) gastrectomy are at higher risk of perforation during endoscopic retrograde cholangiopancreatography (ERCP). We assessed the success rate and safety of forward-viewing endoscopic biliary intervention in patients with B II gastrectomy.
Methods
A total of 2,280 ERCP procedures were performed in our institution between October 2008 and June 2011. Of these, forward-viewing endoscopic biliary intervention was performed in 46 patients (38 men and 8 women with B II gastrectomy). Wire-guided selective cannulations of the common bile duct using a standard catheter and guide wire were performed in all patients.
Results
The success rate of afferent loop entrance was 42 out of 46 patients (91.3%) and of biliary cannulation after the approach of the papilla was 42 out of 42 patients (100%). No serious complications were encountered, except for one case of small perforation due to endoscopic sphincterotomy site injury.
Conclusions
When a biliary endoscopist has less experience and patient volume is low, ERCP with a forward-viewing endoscope is preferred because of its ease and safety in all patients with prior B II gastrectomies. Also, forward-viewing endoscope can be used to improve the success rate of biliary intervention in B II patients.
doi:10.5946/ce.2012.45.4.397
PMCID: PMC3521942  PMID: 23251888
Billroth II gastrectomy; Endoscopic retrograde cholangiopancreatography; Forward-viewing endoscope
5.  Effect of Advanced Glycation End Products on Oxidative Stress and Senescence of Trabecular Meshwork Cells 
Purpose
To investigate the effect of advanced glycation end products (AGE) on oxidative stress and cellular senescence in cultured human trabecular meshwork cells (HTMC).
Methods
Primarily cultured HTMC were exposed to 0, 10, 50, 100, 200 µg/mL of glycated bovine serum albumin (G-BSA) for 5 days. Also co-exposed were L-arginine, sepiapterin, and antioxidant N-acetylcysteine (NAC). Cellular survival and production of nitric oxide (NO), superoxide, and reactive oxygen species were assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay, Griess assay, cytochrome c assay, and dichlorofluorescin diacetate assay, respectively. Senescence-associated β-galactosidase staining was performed to quantify the degree of cellular senescence.
Results
G-BSA decreased cellular survival, NO production, and increased superoxide production significantly in a dose-dependent manner. The effects of G-BSA were abolished with co-exposure of L-arginine, sepiapterin, and NAC. G-BSA enhanced cellular senescence accompanied by increased production of reactive oxygen species. G-BSA-induced cellular senescence was suppressed by application of L-arginine, sepiapterin, and NAC.
Conclusions
AGE enhances cellular senescence of HTMC accompanied with increased oxidative stress. AGE-induced oxidative stress and cellular senescence could be delayed by application of anti-oxidants.
doi:10.3341/kjo.2012.26.2.123
PMCID: PMC3325617  PMID: 22511839
Advanced glycation end products; Aging; Antioxidants; Oxidative stress; Trabecular meshwork cells
6.  Prehospital Notification from the Emergency Medical Service Reduces the Transfer and Intra-Hospital Processing Times for Acute Stroke Patients 
Background and Purpose
There is little information available about the effects of Emergency Medical Service (EMS) hospital notification on transfer and intrahospital processing times in cases of acute ischemic stroke.
Methods
This study retrospectively investigated the real transfer and imaging processing times for cases of suspected acute stroke (AS) with EMS notification of a requirement for intravenous (IV) tissue-type plasminogen activator (t-PA) and for cases without notification. Also we compared the intra-hospital processing times for receiving t-PA between patients with and without EMS prehospital notification.
Results
Between December 2008 and August 2009, the EMS transported 102 patients with suspected AS to our stroke center. During the same period, 33 patients received IV t-PA without prehospital notification from the EMS. The mean real transfer time after the EMS call was 56.0±32.0 min. Patients with a transfer distance of more than 40 km could not be transported to our center within 60 min. Among the 102 patients, 55 were transferred via the EMS to our emergency room for IV t-PA. The positive predictive value for stroke (90.9% vs. 68.1%, p=0.005) was much higher and the real transfer time was much faster in patients with an EMS t-PA call (47.7±23.1 min, p=0.004) than in those without one (56.3±32.4 min). The door-to-imaging time (17.8±11.0 min vs. 26.9±11.5 min, p=0.01) and door-to-needle time (29.7±9.6 min vs. 42.1±18.1 min, p=0.01) were significantly shorter in the 18 patients for whom there was prehospital notification and who ultimately received t-PA than in those for whom there was no prehospital notification.
Conclusions
Our results indicate that prehospital notification could enable the rapid dispatch of AS patients needing IV t-PA to a stroke centre. In addition, it could reduce intrahospital delays, particularly, imaging processing times.
doi:10.3988/jcn.2010.6.3.138
PMCID: PMC2950918  PMID: 20944814
stroke; thrombolysis; prehospital notification; stroke care system
7.  A Case of Gerstmann-Sträussler-Scheinker Disease 
Background
Gerstmann-Sträussler-Scheinker disease (GSS) is a type of human transmissible spongiform encephalopathy (TSE) that is determined genetically.
Case Report
A 46-year-old woman presented with a slowly progressive ataxic gait and cognitive decline. She was alert but did not cooperate well due to severe dementia and dysarthria. High signal intensities in the cerebral cortices were evident in MRI, especially in diffusion-weighted images (DWI). A prion protein gene (PRNP) analysis revealed a P102L (proline-to-leucine) mutation in codon 102.
Conclusions
This is the first reported case of GSS (confirmed by PRNP analysis) in Korea. Distinctive MRI findings are also presented.
doi:10.3988/jcn.2010.6.1.46
PMCID: PMC2851297  PMID: 20386644
Gerstmann-Sträussler-Scheinker disease; transmissible spongiform encephalopathy; diffusion-weighted imaging
8.  Cognitive Impairment in Parkinson's Disease without Dementia: Subtypes and Influences of Age 
Background and Purpose
Cognitive impairments are common in Parkinson's disease (PD), although the severity of these impairments does not significantly impair the patient's daily activities. The aim of this study was to determine the frequency of mild cognitive impairment (MCI) of Parkinson's disease (PDMCI) and its subtypes in nondemented PD patients. We also evaluated the influence of age on the pattern of subtypes of PDMCI.
Methods
A total of 141 consecutive, nondemented PD patients underwent a comprehensive neuropsychological assessment covering the five cognitive domains: attention, language, visuospatial, memory, and executive functions. PDMCI was defined as impaired performance in at least one of these five cognitive domains. The influence of age on the distribution of subtypes of PDMCI was assessed by comparing patients in two groups dichotomized according to their age at assessment (younger vs. older).
Results
Fifty-seven (40.4%) of the nondemented PD patients had an impairment in at least one domain, and were therefore considered as having PDMCI. The age at assessment and age at disease onset were significantly higher in the PDMCI patients. The amnestic type of PDMCI was the most frequent, followed by the visuospatial, linguistic, executive, and attention types in that order. The frequency of PDMCI was higher for all subtypes in the older group; the domain that was influenced the most by age was executive function.
Conclusions
MCI was common in PD and the subtypes were diverse. Age was found to be an important risk factor for the development of PDMCI, particularly for the executive subtype. These results indicate that the concept of MCI should be introduced in PD.
doi:10.3988/jcn.2009.5.3.133
PMCID: PMC2760718  PMID: 19826564
Parkinson's disease; mild cognitive impairment; Parkinson's disease dementia
9.  Non-Motor Off Symptoms in Parkinson's Disease 
Journal of Korean Medical Science  2009;24(2):311-314.
The aim of this study is to elucidate the clinical spectrum and frequency of non-motor symptoms during off periods (NMOS) in Parkinson's disease (PD) patients with motor fluctuation. We compared clinical characteristics between PD patients with motor symptoms only (M-off) and those with both motor and non-motor symptoms (NM-off) during off periods. The association of NMOS with parkinsonian clinical characteristics was also investigated. Sixty-seven consecutive PD patients of both M-off and NM-off groups were included in this study. We reviewed medical records, interviewed the patients, and administered a structured questionnaire. NMOS is classified into three categories: autonomic, neuropsychiatric and sensory. The frequency of NMOS and their individual manifestations were assessed. Of 67 patients with off symptoms, 20 were M-off group and 47 NM-off group. Among NMOS, diffuse pain was the most common manifestation, followed by anxiety and sweating. There were no significant differences between M-off and NM-off groups with regard to age, duration of disease and treatment, interval between onset of parkinsonian symptoms and off symptoms and off periods. Patients taking higher dosage of levodopa had fewer NMOS. NMOS is frequent in PD. Comprehensive recognition of NMOS can avoid unnecessary tests and is important for optimal treatment in PD.
doi:10.3346/jkms.2009.24.2.311
PMCID: PMC2672134  PMID: 19399276
Parkinson Disease; Non-Motor Off; Motor Fluctuation
10.  Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey 
AIM: To investigate prevalence of Clonorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea.
METHODS: Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire.
RESULTS: Of 3080 patients with gastrointestinal diseases, 396 (12.9%) had clonorchiasis and 1140 patients (37.2%) had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 (20.9%) patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than non-infected patients [34/396 (8.6%) vs 145/2684 (5.4%), P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation (P = 0.008). Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis.
CONCLUSION: Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.
doi:10.3748/wjg.15.86
PMCID: PMC2653299  PMID: 19115472
Clonorchis sinensis; Epidemiology; Cholangiocarcinoma; Korea; Multicenter study; Clonorchiasis
11.  Insulin Enhances Nitric Oxide Production in Trabecular Meshwork Cells via De Novo Pathway for Tetrahydrobiopterin Synthesis 
Purpose
To investigate the effect of insulin on the production of nitric oxide (NO) in the trabecular meshwork (TM) cells and the enzymatic synthetic pathway of tetrahydrobiopterin (BH4) synthesis.
Methods
Primarily cultured human TM cells were exposed to 1, 10, and 100 µg/ml of insulin and 0, 1, 10, 100 and 1000 nM dexamethasone for 3 days. To evaluate the enzymatic pathway of BH4 synthesis, 10 µM dexamethasone, 5 mM diaminopyrimidinone, 100 µM ascorbic acid, 100 µM sepiapterin, or 10 µM methotrexate were also co-administered respectively. Cellular survival and NO production were measured with MTT and Griess assay.
Results
Insulin enhanced NO production in a dose-dependent manner significantly (p<0.05) without affecting cell viability, whereas dexamethasone inhibited NO production. With co-exposure of insulin, diaminopyrimidinone and sepiapterin inhibited insulin-induced NO production. Ascorbic acid increased NO production independent of insulin and methotrexate did not affect to the action of insulin in NO production.
Conclusions
Insulin increases NO production in TM cells via de novo synthetic pathway for BH4 synthesis. Insulin could be involved in the regulation of trabecular outflow by enhancing NO production in TM cells.
doi:10.3341/kjo.2007.21.1.39
PMCID: PMC2629692  PMID: 17460431
Dexamethasone; Insulin; Nitric oxide; Tetrahydrobiopterin; Trabecular meshwork cell
12.  Adenocarcinoma Originating From a Completely Isolated Duplication Cyst of the Mesentery in an Adult 
Intestinal Research  2014;12(4):328-332.
Alimentary tract duplications are uncommon congenital abnormalities that usually have an anatomical connection with some part of the gastrointestinal tract and have a common blood supply with the adjacent segment of intestine. A completely isolated duplication cyst (CIDC) is a very rare type of gastrointestinal duplication that does not communicate with the normal bowel segment and possesses its own exclusive blood supply. Only 5 CIDC cases in adults have been reported in the English medical literature. Additionally, only 1 case of mucinous cystadenoma from an infected CIDC of the ileum has been reported. This report describes a 52-year-old male patient with a peritoneal CIDC, which upon curative excision was found to have given rise to an adenocarcinoma. The latter was lined internally with malignant glandular cells and contained a smooth muscular outer layer as determined by microscopic examination of the tissue. We believe that this is the first reported case of an adenocarcinoma originating from a CIDC in an adult.
doi:10.5217/ir.2014.12.4.328
PMCID: PMC4214961  PMID: 25374500
Adenocarcinoma; Completely isolated duplication cyst; Duplication cyst; Enteric duplications; Enterogenous cyst
14.  Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea 
Journal of Korean Medical Science  2014;29(4):494-501.
The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).
Graphical Abstract
doi:10.3346/jkms.2014.29.4.494
PMCID: PMC3991791  PMID: 24753695
Oral Cholera Vaccine; Safety; Immunogenicity; Vibriocidal Assay, Seroconversion Rate
15.  Peroxisome Proliferator-Activated Receptor Gamma/Signal Transducers and Activators of Transcription 5A Pathway Plays a Key Factor in Adipogenesis of Human Bone Marrow-Derived Stromal Cells and 3T3-L1 Preadipocytes 
Stem Cells and Development  2011;21(3):465-475.
Adipogenesis is largely dependent on the signal transducers and activators of transcription (STAT) pathway. However, the molecular mechanism of the STAT pathway in the adipogenesis of human bone marrow-derived stromal cells (hBMSCs) remains not well understood. The purpose of this research was to characterize the transcriptional regulation involved in expression of STAT5A and STAT5B during adipogenesis in hBMSCs and 3T3-L1 cells. The expression of STAT5A and STAT5B increases with the onset of adipogenesis in hBMSCs and 3T3-L1 cells. The PPAR response elements regulatory element of STAT5A exists at a promoter region ranging from −346 to −101, and the CCAAT/enhancer-binding protein (C/EBP) regulatory element is located at −196 to −118 of the STAT5B promoter. C/EBPβ and C/EBPα bound to the STAT5B promoter region, whereas peroxisome proliferator-activated receptor γ (PPARγ) bound to STAT5A. RNA interference of STAT5A completely blocked differentiation, whereas the inhibition of STAT5B only partially blocked differentiation. We propose that C/EBPα, C/EBPβ, and PPARγ control adipogenesis by regulating STAT5B and STAT5A and that STAT5A is necessary, whereas STAT5B plays a supplementary role during adipogenesis. Further, the regulation of PPARγ-STAT5 by C/EBPβ signaling seems to be the crucial adipogenesis pathway-initiating cascade of the various adipogenic genes.
doi:10.1089/scd.2010.0591
PMCID: PMC3272248  PMID: 21542777
16.  Predictive factors affecting cecal intubation failure in colonoscopy trainees 
Background
Successful cecal intubation (SCI) is not only a quality indicator but also an important marker in a colonoscopy trainee’s progress. We conducted this study to determine factors predicting SCI in colonoscopy trainees, and to compare these factors before and after trainees achieve technical competence.
Methods
Design of this study was a cross-sectional studies of two time series design for one year at a single center. From March 2011 to February 2012, a total 2,050 subjects who underwent colonoscopy by four first-year gastrointestinal fellows were enrolled at Christian hospital, Wonju, Republic of Korea. Four gastrointestinal fellows have filled out the colonoscopic documentation. Main outcome measurement was predictive factors affecting cecal intubation failure and learning curves.
Results
Colonoscopy was successfully completed to the cecum in 1,720 patients (83.9%). Success rates gradually increased as trainees performed more colonoscopies: the rate of SCI was 62% in the first 50 cases, and grew to 93% by the 250th case. Logistic regression analysis of factors affecting cecal intubation failure showed that female gender, low BMI (BMI < 18.5 kg/m2), poor bowel preparation, and past history of stomach surgery were more often associated with cecal intubation failure, particularly before the trainees achieved technical competence.
Conclusion
Several patient characteristics were identified that may predict difficulty of cecal intubation in colonoscopy trainees. Particularly, low BMI, inadequate bowel cleansing, and previous stomach operation were predictors of cecal intubation failure before the trainees have reached technical competency. The results could be informative so that trainees enhance the success rate regarding better colonoscopy training programs.
doi:10.1186/1472-6920-13-5
PMCID: PMC3560110  PMID: 23331720
17.  Translation and Validation of the Korean Version of the 39-Item Parkinson's Disease Questionnaire 
Background and Purpose
The importance of health-related quality of life (HrQoL) has been increasingly emphasized when assessing and providing treatment to patients with chronic, progressive, degenerative disorders. The 39-item Parkinson's disease questionnaire (PDQ-39) is the most widely used patient-reporting scale to assess HrQoL in Parkinson's disease (PD). This study evaluated the validity and reliability of the translated Korean version of the PDQ-39 (K-PDQ-39).
Methods
One hundred and two participants with PD from 10 movement disorder clinics at university-affiliated hospitals in South Korea completed the K-PDQ-39. All of the participants were also tested using the Unified Parkinson's Disease Rating Scale (UPDRS), Korean version of the Mini-Mental State Examination (K-MMSE), Korean version of the Montgomery-Asberg Depression Scale (K-MADS), Epworth Sleepiness Scale (ESS) and non-motor symptoms scale (NMSS). Retests of the K-PDQ-39 were performed over time intervals from 10 to 14 days in order to assess test-retest reliability.
Results
Each K-PDQ-39 domain showed correlations with the summary index scores (rS=0.559-0.793, p<0.001). Six out of eight domains met the acceptable standard of reliability (Cronbach's α coefficient ≥0.70). The Guttman split-half coefficient value of the K-PDQ-39 summary index, which is an indicator of test-retest reliability, was 0.919 (p<0.001). All of the clinical variables examined except for age, comprising disease duration, levodopa equivalent dose, modified Hoehn and Yahr stage (H&Y stage), UPDRS part I, II and III, mood status (K-MADS), cognition (K-MMSE), daytime sleepiness (ESS) and (NMSS) showed strong correlations with the K-PDQ-39 summary index (p<0.01).
Conclusions
The K-PDQ-39 has been validated for use in the Korean-speaking PD population. The questionnaire is a valid and reliable assessment tool for assessing the HrQoL of Korean PD patients.
doi:10.3988/jcn.2013.9.1.26
PMCID: PMC3543906  PMID: 23346157
Parkinson's disease; quality of life; validation
18.  Krüppel-Like Factor KLF8 Plays a Critical Role in Adipocyte Differentiation 
PLoS ONE  2012;7(12):e52474.
KLF8 (Krüppel-like factor 8) is a zinc-finger transcription factor known to play an essential role in the regulation of the cell cycle, apoptosis, and differentiation. However, its physiological roles and functions in adipogenesis remain unclear. In the present study, we show that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3-L1 preadipocytes, we found that KLF8 expression was induced during differentiation, which was followed by expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Adipocyte differentiation was significantly attenuated by the addition of siRNA against KLF8, whereas overexpression of KLF8 resulted in enhanced differentiation. Furthermore, luciferase reporter assays demonstrated that overexpression of KLF8 induced PPARγ2 and C/EBPα promoter activity, suggesting that KLF8 is an upstream regulator of PPARγ and C/EBPα. The KLF8 binding sites were localized by site mutation analysis to −191 region in C/EBPα promoter and −303 region in PPARγ promoter, respectively. Taken together, these data reveal that KLF8 is a key component of the transcription factor network that controls terminal differentiation during adipogenesis.
doi:10.1371/journal.pone.0052474
PMCID: PMC3528641  PMID: 23285057
19.  Toxic Encephalopathy 
Safety and Health at Work  2012;3(4):243-256.
This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure.
doi:10.5491/SHAW.2012.3.4.243
PMCID: PMC3521923  PMID: 23251840
Occupational diseases; Nervous system diseases; Toxic encephalopathy
20.  Validation of the Korean-Version of the Nonmotor Symptoms Scale for Parkinson's Disease 
Background and Purpose
Non-motor symptoms are common in Parkinson's disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD.
Methods
In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinson's Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinson's Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient.
Results
The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbach's α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearman's rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001).
Conclusions
The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients.
doi:10.3988/jcn.2012.8.4.276
PMCID: PMC3540287  PMID: 23323136
Parkinson's disease; non-motor symptoms scale; validation
21.  Genetics of Parkinson’s Disease - A Clinical Perspective 
Journal of Movement Disorders  2012;5(2):33-41.
Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogenesis of Parkinson’s disease (PD). Genes found to be associated with PD through investigating genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some environmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for general clinicians managing PD patients.
doi:10.14802/jmd.12009
PMCID: PMC4027661  PMID: 24868412
Parkinson’s disease; Genetics
22.  Elevated Levels of α-Synuclein Oligomer in the Cerebrospinal Fluid of Drug-Naïve Patients with Parkinson's Disease 
Background and Purpose
The detection of α-synuclein in the body fluids of patients with synucleinopathy has yielded promising but inconclusive results, in part because of conformational changes of α-synuclein in response to environmental conditions. The aim of this study was to determine the feasibility of using α-synuclein as a biological marker for Parkinson's disease (PD).
Methods
Twenty-three drug-naïve patients with PD (age 62.4±12.7 years, mean±SD; 11 males) and 29 age- and sex-matched neurologic control subjects (age 60.1±16.2 years; 16 males) were recruited. The levels of oligomeric and total α-synuclein in the cerebrospinal fluid (CSF) and plasma were measured using two simultaneous enzyme-linked immunosorbent assays.
Results
The level of α-synuclein oligomer in the CSF of PD patients was significantly higher in PD patients than in neurological controls, but other findings (plasma α-synuclein oligomer and total α-synuclein in CSF and plasma) did not differ significantly between the two groups. When the control subjects were divided into a symptomatic control group (11 patients who complained of parkinsonian symptoms and were diagnosed with hydrocephalus and drug-induced or vascular parkinsonism) and a neurologic control group (10 normal subjects and 8 patients with diabetic ophthalmoplegia), the level of α-synuclein oligomer in the CSF was still significantly higher in PD patients than in both of the control subgroups.
Conclusions
These findings provide further evidence for a pathogenic role of the α-synuclein oligomer and suggest that CSF levels of α-synuclein oligomer can be a reliable marker for PD.
doi:10.3988/jcn.2011.7.4.215
PMCID: PMC3259496  PMID: 22259618
Parkinson's disease; cerebrospinal fluid; alpha-synuclein; enzyme-linked immunosorbent assay
23.  Clinical Outcomes and Risk Factors of Rebleeding Following Endoscopic Therapy for Nonvariceal Upper Gastrointestinal Hemorrhage 
Clinical Endoscopy  2011;44(2):93-100.
Background/Aims
Rebleeding after endoscopic therapy for non-variceal upper gastrointestinal hemorrhage (NGIH) is the most important predictive factor of mortality. We evaluated the risk factors of rebleeding in patients undergoing endoscopic therapy for the NGIH.
Methods
Between January 2003 and January 2007, 554 bleeding events in 487 patients who underwent endoscopic therapy for NGIH were retrospectively enrolled. We reviewed the clinicoendoscopical characteristics of patients with rebleeding and compared them with those of patients without rebleeding.
Results
The incidence of rebleeding was 21.7% (n=120). In the multivariate analysis, initial hemoglobin level ≤9 g/dL (p=0.002; odds ratio [OR], 2.433), inexperienced endoscopist with less than 2 years of experience in therapeutic endoscopy (p=0.001; OR, 2.418), the need for more 15 cc of epinephrine (p=0.001; OR, 2.570), injection therapy compared to thermal and injection therapy (p=0.001; OR, 2.840), and comorbidity with chronic renal disease (p=0.004; OR, 2.908) or liver cirrhosis (p=0.010; OR, 2.870) were risk factors for rebleeding following endoscopic therapy.
Conclusions
Together with patients with low hemoglobin level at presentation, chronic renal disease, liver cirrhosis, the need for more 15 cc of epinephrine, or therapy done by inexperienced endoscopist were risk factors for the development of rebleeding.
doi:10.5946/ce.2011.44.2.93
PMCID: PMC3363058  PMID: 22741119
Gastrointestinal hemorrhage; Risk factors; Endoscopy; Therapy
24.  Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease 
BMC Neurology  2011;11:100.
Background
A recent trial involving predominantly Caucasian subjects with Parkinson Disease (PD) showed switching overnight from an oral dopaminergic agonist to the rotigotine patch was well tolerated without loss of efficacy. However, no such data have been generated for Korean patients.
Methods
This open-label multicenter trial investigated PD patients whose symptoms were not satisfactorily controlled by ropinirole, at a total daily dose of 3 mg to 12 mg, taken as monotherapy or as an adjunct to levodopa. Switching treatment from oral ropinirole to transdermal rotigotine was carried out overnight, with a dosage ratio of 1.5:1. After a 28-day treatment period, the safety and tolerability of switching was evaluated. Due to the exploratory nature of this trial, the effects of rotigotine on motor and nonmotor symptoms of PD were analyzed in a descriptive manner.
Results
Of the 116 subjects who received at least one treatment, 99 (85%) completed the 28-day trial period. Dose adjustments were required for 11 subjects who completed the treatment period. A total of 76 treatment-emergent adverse events (AEs) occurred in 45 subjects. No subject experienced a serious AE. Thirteen subjects discontinued rotigotine prematurely due to AEs. Efficacy results suggested improvements in both motor and nonmotor symptoms and quality of life after switching. Fifty-two subjects (46%) agreed that they preferred using the patch over oral medications, while 31 (28%) disagreed.
Conclusions
Switching treatment overnight from oral ropinirole to transdermal rotigotine patch, using a dosage ratio of 1.5:1, was well tolerated in Korean patients with no loss of efficacy.
Trial registration
This trial is registered with the ClincalTrails.gov Registry (NCT00593606).
doi:10.1186/1471-2377-11-100
PMCID: PMC3166898  PMID: 21831297
25.  Fulminant Epstein-Barr Virus-associated T-cell Lymphoproliferative Disorder in an Immunocompetent Middle-aged Man Presenting with Chronic Diarrhea and Gastrointestinal Bleeding 
Journal of Korean Medical Science  2011;26(8):1103-1107.
The World Health Organization (WHO) recently defined systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPD) of childhood as a life-threatening illness. However, this rare disease has not been extensively studied. Here we report a case of systemic EBV-positive T-cell LPD in a previously healthy middle-aged man with a chief complaint of chronic diarrhea. The initial colon biopsy showed focal infiltration of EBV-positive small lymphocytes without any atypia. However, the disease rapidly progressed and the patient required a total colectomy due to severe gastrointestinal bleeding. Three and half months after admission, the patient died from a complication of disseminated intravascular coagulation. The resected colon showed diffuse infiltration of EBV-positive atypical lymphocytes with ischemic change. Most atypical lymphocytes were CD3+ or CD5+. The monoclonality of EBV was demonstrated by sequence variation analysis of the latent membrane protein 1 (LMP1) gene in the colectomy specimen as well as in the initial biopsy.
doi:10.3346/jkms.2011.26.8.1103
PMCID: PMC3154349  PMID: 21860564
Epstein-Bar Virus Infections; Lymphoproliferatife Disorders; Atypical T-cell Proliferation

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