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1.  Analysis of Anesthesia-related Medical Disputes in the 2009-2014 Period Using the Korean Society of Anesthesiologists Database 
Journal of Korean Medical Science  2015;30(2):207-213.
Using the Korean Society of Anesthesiologists database of anesthesia-related medical disputes (July 2009-June 2014), causative mechanisms and injury patterns were analyzed. In total, 105 cases were analyzed. Most patients were aged < 60 yr (82.9%) and were classified as American Society of Anesthesiologists physical status ≤ II (90.5%). In 42.9% of all cases, the injuries were determined to be 'avoidable' if the appropriate standard of care had been applied. Sedation was the sec most common type of anesthesia (37.1% of all cases), following by general anesthesia. Most sedation cases (27/39, 69.2%) showed a common lack of vigilance: no pre-procedural testing (82.1%), absence of anesthesia record (89.7%), and non-use of intra-procedural monitoring (15.4%). Most sedation (92.3%) was provided simultaneously by the non-anesthesiologists who performed the procedures. After the resulting injuries were grouped into four categories (temporary, permanent/minor, permanent/major, and death), their causative mechanisms were analyzed in cases with permanent injuries (n=20) and death (n=82). A 'respiratory events' was the leading causative mechanism (56/102, 54.9%). Of these, the most common specific mechanism was hypoxia secondary to airway obstruction or respiratory depression (n=31). The sec most common damaging event was a 'cardiovascular events' (26/102, 25.5%), in which myocardial infarction was the most common specific mechanism (n=12). Our database analysis demonstrated several typical injury profiles (a lack of vigilance in seemingly safe procedures or sedation, non-compliance with the airway management guidelines, and the prevalence of myocardial infarction) and can be helpful to improve patient safety.
doi:10.3346/jkms.2015.30.2.207
PMCID: PMC4310949  PMID: 25653494
Adverse Effects; Injuries; Legislation; Malpractice
2.  Screening for Abdominal Aortic Aneurysm during Transthoracic Echocardiography in Patients with Significant Coronary Artery Disease 
Yonsei Medical Journal  2014;56(1):38-44.
Purpose
Coronary artery disease (CAD) shares several risk factors with abdominal aortic aneurysm (AAA). We evaluated the prevalence during transthoracic echocardiography (TTE) and risk factors of AAA in patients with CAD.
Materials and Methods
A total of 1300 CAD patients were screened from August 2009 to May 2010, and measurement of abdominal aorta size was feasible in 920 patients (71%) at the end of routine TTE. An AAA was defined as having a maximal diameter of ≥30 mm.
Results
Of the 920 patients, 22 (2.4% of the study population) were diagnosed with AAA; of these AAA patients, 86% were male, and 82% were over 65 years-old. Abdominal aortic size was weakly correlated with aortic root diameter (r=0.22, p<0.01). Although the proportions of male gender, hypertension, and dyslipidemia were higher in AAA patients, such differences were not statistically significant. Advanced age [odds ratio (OR)=1.07; 95% confidence interval (CI): 1.01-1.12; p<0.01], smoking (OR=3.44; 95% CI: 1.18-10.04; p=0.02), and peripheral arterial disease (OR=5.88; 95% CI: 1.38-25.05; p=0.01) were found to be associated with AAA.
Conclusion
Although prevalence of AAA is very low in the Asian population, the prevalence of AAA in Asian CAD patients is higher than the general population. Therefore, opportunistic examination of the abdominal aorta during routine TTE could be effective, especially for male CAD patients over 65 years with a history of smoking or peripheral arterial disease.
doi:10.3349/ymj.2015.56.1.38
PMCID: PMC4276776  PMID: 25510745
Abdominal aortic aneurysm; screening; coronary artery disease; transthoracic echocardiography
3.  Aggravation of Hepatopulmonary Syndrome after Sildenafil Treatment in a Patient with Coexisting Portopulmonary Hypertension 
Korean Circulation Journal  2015;45(1):77-80.
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are complications of portal hypertension and cirrhosis. Their pathophysiological mechanisms clearly differ. HPS is characterized by a defect in arterial oxygenation induced by pulmonary vascular dilatation. In contrast, PPHTN is predominantly due to excessive pulmonary vasoconstriction and vascular remodeling, but is rarely associated with hypoxia. We report a case of a patient who had both HPS and PPHTN at the time of presentation. HPS was aggravated after sildenafil administration for the treatment of PPHTN. We demonstrated increased amount of intrapulmonay shunt after sildenafil challenge by using agitated saline contrast transthoracic echocardiography.
doi:10.4070/kcj.2015.45.1.77
PMCID: PMC4310984  PMID: 25653708
Hepatopulmonary syndrome; Pulmonary arterial hypertension; Sildenafil
4.  Determinants of Brachial-Ankle Pulse Wave Velocity and Carotid-Femoral Pulse Wave Velocity in Healthy Koreans 
Journal of Korean Medical Science  2014;29(6):798-804.
The aim of this study was to determine the normal value of brachial-ankle pulse wave velocity (baPWV) and carotid-femoral pulse wave velocity (cfPWV) according to age group, gender, and the presence of cardiovascular risk factors in healthy Koreans, and to investigate the association between PWV and risk factors such as prehypertension, dyslipidemia, smoking, and obesity. We measured an arterial stiffness in 110 normal subjects who were 20 to 69 yr-old with no evidence of cardiovascular disease, cerebrovascular accident or diabetes mellitus. The mean values of baPWV and cfPWV were 12.6 (±2.27) m/sec (13.1±1.85 in men, 12.1±2.51 in women; P=0.019) and 8.70 (±1.99) m/sec (9.34±2.13 in men, 8.15±1.69 in women; P=0.001), respectively. The distribution of baPWV (P<0.001) and cfPWV (P=0.006) by age group and gender showed an increase in the mean value with age. Men had higher baPWV and cfPWV than women (P<0.001). There was a difference in baPWV and cfPWV by age group on prehypertension, dyslipidemia, current smoking, or obesity (P<0.001). In multiple linear regression, age and prehypertension were highly associated with baPWV and cfPWV after adjustment for confounding factors (P<0.001). The present study showed that baPWV and cfPWV are associated with age, gender, and prehypertension in healthy Koreans.
Graphical Abstract
doi:10.3346/jkms.2014.29.6.798
PMCID: PMC4055813  PMID: 24932081
Prehypertension; Gender Identity; Age Groups; Ankle Brachial Index; Carotid-Femoral; Pulse Wave Analysis
5.  Clinical Utility of Coronary CT Angiography with Stress Perfusion CT in Preoperative Cardiac Risk Evaluation 
Korean Circulation Journal  2014;44(3):170-176.
Background and Objectives
Vascular surgery carries high operative risk. Recently developed cardiac computed tomography (CT) provides excellent imaging of coronary artery disease (CAD), as well as myocardial perfusions. We investigated the role of stress perfusion CT with coronary computed tomography angiography (CCTA) using 128-slice dual source CT (DSCT) in preoperative cardiac risk evaluation.
Subjects and Methods
Patients scheduled for vascular surgery were admitted and underwent the adenosine stress perfusion CT with CCTA using DSCT. Patients who presented with unstable angina, recent myocardial infarction, decompensated heart failure, or renal failure were excluded. Stress perfusion CT was first acquired using sequential mode during adenosine infusion, after which, scanning for CT angiography was followed by helical mode. Perioperative events were followed up for 1 month.
Results
Ninety-one patients completed the study. Most patients (94.5%) had coronary atherosclerosis, with 36 (39.6%) patients had more than 50% coronary artery stenosis. Perfusion defects with significant stenosis were found in 12 cases (13.2%). Revascularization after DSCT was rarely performed. Four patients (4.4%) experienced cardiac events in the perioperative period: two experienced heart failure and two had non-fatal myocardial infarction.
Conclusion
We cannot conclude that the stress perfusion CT, with CCTA using DSCT, plays a significant role in preoperative risk evaluation from this study. However, the coronary atherosclerosis and the significant CAD were commonly found. The perfusion defects with significant lesions were found in only small fraction of the patients, and did not contribute to perioperative myocardial infarction or heart failure.
doi:10.4070/kcj.2014.44.3.170
PMCID: PMC4037639  PMID: 24876858
Vascular surgical procedure; Coronary artery disease; Multidetector computed tomography; Myocardial perfusion imaging
6.  Immunoglobulin G4 Non-Related Sclerosing Disease with Intracardiac Mass Mimicking Mitral Stenosis: Case Report 
Journal of Korean Medical Science  2013;28(12):1830-1834.
The cardiovascular system may be one of the target organs of both immunoglobulin G4 related and non-related systemic multifocal fibrosclerosis. We present a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis on echocardiography. For a more detailed differential diagnosis, we used multimodal imaging techniques. After surgical biopsy around the abdominal aortic area in the retroperitoneum, histological examination revealed IgG4 non-related systemic multifocal fibrosclerosis. We describe the multimodal imaging used to diagnose IgG4 non-related systemic multifocal fibrosclerosis and a positive response to steroid treatment. There have been no previous case reports of IgG4 non-related systemic multifocal fibrosclerosis with intracardiac involvement. Here, we report a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis.
doi:10.3346/jkms.2013.28.12.1830
PMCID: PMC3857383  PMID: 24339717
Immunoglobulin G4 Non-Related Sclerosing Disease; Periaortitis; Left Atrium Mass; Mitral Valve Stenosis
7.  Comparison of Cardiovascular Risk Factors for Peripheral Artery Disease and Coronary Artery Disease in the Korean Population 
Korean Circulation Journal  2013;43(5):316-328.
Background and Objectives
The objective of this study was to analyze and compare risk factors for peripheral artery disease (PAD) and coronary artery disease (CAD).
Subjects and Methods
The sample included 7936 Korean patients aged ≥20 years who were hospitalized from 1994 to 2004. Of the 7936 subjects, PAD (n=415), CAD (n=3686), and normal controls (Control) (n=3835) were examined at the Health Promotion Center, Samsung Medical Center.
Results
The mean age (years) of PAD subjects was 64.4 (±9.3), while CAD subjects was 61.2 (±9.9), and Control subjects was 59.9 (±9.1) (p<0.01). The proportion of males was 90.6% for PAD, 71.4% for CAD, and 75.5% for Control subjects (p<0.01). The adjusted odds ratios (ORs) for hypertension, diabetes mellitus, hypercholesterolemia, smoking, metabolic syndrome and chronic kidney disease were significantly higher in subjects with PAD or CAD compared to those in Control. However, the ORs for high density lipoprotein, being overweight, and being obese were significantly lower in PAD subjects compared to those in Control.
Conclusion
We found that cardiovascular risk factors were in fact risk factors for both PAD and CAD.
doi:10.4070/kcj.2013.43.5.316
PMCID: PMC3675306  PMID: 23755078
Peripheral artery disease; Coronary artery disease; Risk factors
8.  Dose fentanyl injection for blunting the hemodynamic response to intubation increase the risk of reflex bradycardia during major abdominal surgery? 
Korean Journal of Anesthesiology  2012;63(5):402-408.
Background
Although supplemental fentanyl has been widely used to blunt the hemodynamic responses to laryngoscopic intubation, its residual vagotonic effect may increase the risk of reflex bradycardia. We compared the incidence and severity of significant reflex bradycardia after a bolus injection of equivalent doses of fentanyl and remifentanil (control drug).
Methods
In this prospective, randomized, double-blind study, 220 adult patients undergoing major abdominal surgery were randomly assigned to receive fentanyl (1.5 µg/kg) or remifentanil (1.5 µg/kg). No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to < 50 beats per minute (bpm) or to 50-59 bpm associated with a systolic arterial pressure < 70 mmHg in connection with surgical maneuvers. If bradycardia or hypotension developed, atropine or ephedrine was administered following a predefined treatment protocol.
Results
In total, 188 subjects (remifentanil, 95; fentanyl, 93) were included. The proportion of subjects with symptomatic reflex bradycardia in the fentanyl group was similar to that in the remifentanil group (30.1% vs. 28.4%, respectively). Atropine and/or ephedrine were needed similarly in both groups. The differences between the group of 55 patients who presented with symptomatic reflex bradycardia were not statistically significant with respect to the lowest heart rate, anesthetic depth-related data (bispectral index and end-tidal sevoflurane concentration), or the proportion of causative surgical maneuvers.
Conclusions
Fentanyl (1.5 µg/kg) administered intravenously during anesthetic induction is unlikely to increase the incidence and severity of significant reflex bradycardia in patients undergoing major abdominal surgery.
doi:10.4097/kjae.2012.63.5.402
PMCID: PMC3506848  PMID: 23198032
Bradycardia; Fentanyl; Reflex; Surgical procedures
9.  Hereditary Thrombophilia in Korean Patients with Idiopathic Pulmonary Embolism 
Yonsei Medical Journal  2012;53(3):571-577.
Purpose
Hereditary thrombophilia (HT) is a major risk factor for idiopathic pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The prevalence and clinical characteristics of HT in Korean patients with iPE were investigated.
Materials and Methods
Patients with PE on computed tomography (CT) scan were recruited, and those with malignancy were excluded. Patients were divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE group was assessed by DNA sequencing of the corresponding gene in patients who had low levels of natural anticoagulants. The clinical characteristics of iPE with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE.
Results
Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among 54 patients in the iPE group whose coagulation profiles were tested, 28 patients were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups, the iPE/HT+ group showed the highest proportion of male patients (71.4%; p<0.001); the youngest mean age (44±14 years; p<0.001); and the highest frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%, p<0.001). Protein C deficiency was the most common HT. On molecular genetic tests, causative mutation was identified in 13 patients.
Conclusion
In this study of Korean patients, about half of the patients with iPE had HT. Patients with iPE and HT were mostly young males with deep venous thrombosis (DVT), previous venous thromboembolism (VTE), and frequent adverse clinical outcomes. Therefore, Korean patients with iPE should be tested for HT.
doi:10.3349/ymj.2012.53.3.571
PMCID: PMC3343445  PMID: 22477002
Pulmonary embolism; hereditary thrombophilia; protein C deficiency; Korea
10.  Angiopoietin-1 Gene Therapy Attenuates Hypertension and Target Organ Damage in Nitric Oxide Synthase Inhibited Spontaneously Hypertensive Rats 
Korean Circulation Journal  2011;41(10):590-595.
Background and Objectives
In our previous study, we found that the gene transfer of a potent derivative of cartilage oligomeric matrix protein Angiopoietin-1 (COMP-Ang-1) substantially prevented hypertension, microvascular rarefaction, and target organ damage in spontaneously hypertensive rats (SHRs). The purpose of the present study was to examine the role of nitric oxide (NO) in the therapeutic effects observed after COMP-Ang-1 gene transfer.
Materials and Methods
To exclude the NO-mediated effects in COMP-Ang-1 gene therapy, the SHRs were treated with an NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) before the electrophoretic gene transfer.
Results
The pretreatment with L-NAME induced a severe and sustained increase in systolic blood pressure (BP) in a LacZ plasmid transferred control SHR. However, the electrophoretic transfer of a COMP-Ang-1 plasmid instead of LacZ plasmid in L-NAME-pretreated SHRs substantially blocked the development of hypertension without any significant difference in comparison with L-NAME-untreated COMP-Ang-1 plasmid transferred groups. In addition, the COMP-Ang-1 plasmid transfer substantially attenuated microvascular rarefaction and arteriole remodeling in the heart and kidney, which might account for the mild histological alterations observed in the COMP-Ang-1 plasmid transferred group, in contrast to the severe fibrosis and necrosis seen in the LacZ plasmid controls.
Conclusion
These therapeutic outcomes of COMP-Ang-1 gene transfer even in NOS inhibited SHRs suggested that the antihypertensive effect of COMP-Ang-1 was not merely secondary to NO-mediated vasorelaxation, but it may be associated with its ability to protect the vascular endothelium probably via an NO-independent mechanism which serves to attenuate microvascular rarefaction and target organ damage, and also to prevent hypertension by reducing peripheral vascular resistance.
doi:10.4070/kcj.2011.41.10.590
PMCID: PMC3221901  PMID: 22125558
Angiopoietin-1; Endothelium; Hypertension; Nitric oxide
11.  Analysis of expert consultation referrals for anesthesia-related issues (December 2008-July 2010): KSA legislation committee report 
Korean Journal of Anesthesiology  2011;60(4):260-265.
Background
Since 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts.
Methods
This study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010.
Results
During the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation. Because six cases were excluded due to insufficient data, 40 cases were included in the final analysis. Of 40 cases, 29 (72.5%) resulted in death. Respiratory events were most common in both surviving/disabled and dead patients (36.4 vs. 51.7%, respectively; P > 0.05). Overall, respiratory depression due to the drugs used for monitored anesthesia care (MAC) was the most common specific mechanism (25%), in which all but one case (profound brain damage) resulted in death. In all of these cases, surgeons or physicians provided MAC without the help of anesthesiologists.
Conclusions
Overall, the most common damaging mechanism was related to respiratory depression due to sedatives or anesthetics used for MAC. Almost all MAC injury cases are believed to be preventable with the use of additional or better monitoring and an effective response to initial physiological derangement. Thus, it is essential to establish practical MAC guidelines and adhere to these guidelines strictly to reduce the occurrence of severe anesthesia-related adverse outcomes.
doi:10.4097/kjae.2011.60.4.260
PMCID: PMC3092961  PMID: 21602976
Complications; Malpractice; Medical legislation; Outcome assessment
12.  Genetic Analysis of Three Korean Patients with Clinical Features of Ehlers-Danlos Syndrome Type IV 
Journal of Korean Medical Science  2007;22(4):698-705.
Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotid-cavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor β receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea.
doi:10.3346/jkms.2007.22.4.698
PMCID: PMC2693823  PMID: 17728513
Ehlers-Danlos Syndrome Type IV; COL3A1; Mutation; Dissection; Carotid-cavernous Sinus Fistula
13.  Cardiac Dysrhythmias, Cardiomyopathy and Muscular Dystrophy in Patients with Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 1B 
Journal of Korean Medical Science  2005;20(2):283-290.
Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contractures of both elbows and ankles. Sinus arrest with junctional escape beats was noted. He was diagnosed as X-linked recessive EDMD (MIM 310300). A 28-yr-old female showed severe wasting and weakness of humeroperoneal muscles. Marked limitation of cervical flexion and contractures of both elbows and ankles were noted. Varying degrees of AV block were noted. She was diagnosed as autosomal dominant EDMD2 (MIM 181350). A 41-yr-old female had contractures of both ankles and limb-girdle type muscular dystrophy. ECG revealed atrial tachycardia with high grade AV block. She was diagnosed as autosomal dominant LGMD1B (MIM 159001). Cardiac dysrhythmias in EDMD and LGMD1B include AV block, bradycardia, atrial tachycardia, atrial fibrillation, and atrial standstill, causing sudden death necessitating pacemaker implantation. Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults.
doi:10.3346/jkms.2005.20.2.283
PMCID: PMC2808607  PMID: 15832002
Muscular Dystrophies; Cardiomyopathies; emerin; Lamins; Heart Conduction System
14.  Aldosterone Upregulates Connective Tissue Growth Factor Gene Expression via p38 MAPK Pathway and Mineralocorticoid Receptor in Ventricular Myocytes 
Journal of Korean Medical Science  2004;19(6):805-811.
The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pattern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each pathway revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways.
doi:10.3346/jkms.2004.19.6.805
PMCID: PMC2816296  PMID: 15608389
Connective Tissue Growth Factor; Aldosterone; Mitogen-activated Protein Kinase p38; Spironolactone; Receptor, Mineralocorticoid
15.  Transcriptional Profiles of Host-Pathogen Responses to Necrotic Enteritis and Differential Regulation of Immune Genes in Two Inbreed Chicken Lines Showing Disparate Disease Susceptibility 
PLoS ONE  2014;9(12):e114960.
Necrotic enteritis (NE) is an important intestinal infectious disease of commercial poultry flocks caused by Clostridium perfringens. Using an experimental model of NE involving co-infection with C. perfringens and Eimeria maxima, transcriptome profiling and functional genomics approaches were applied to identify the genetic mechanisms that might regulate the host response to this disease. Microarray hybridization identified 1,049 transcripts whose levels were altered (601 increased, 448 decreased) in intestinal lymphocytes from C. perfringens/E. maxima co-infected Ross chickens compared with uninfected controls. Five biological functions, all related to host immunity and inflammation, and 11 pathways were identified from this dataset. To further elucidate the role of host genetics in NE susceptibility, two inbred chicken lines, ADOL line 6 and line 7 which share an identical B2 major histocompatibility complex haplotype but differ in their susceptibility to virus infection, were compared for clinical symptoms and the expression levels of a panel of immune-related genes during experimental NE. Line 6 chickens were more susceptible to development of experimental NE compared with line 7, as revealed by decreased body weight gain and increased E. maxima oocyst shedding. Of 21 immune-related genes examined, 15 were increased in C. perfringens/E. maxima co-infected line 6 vs. line 7 chickens. These results suggest that immune pathways are activated in response to experimental NE infection and that genetic determinants outside of the chicken B complex influence resistance to this disease.
doi:10.1371/journal.pone.0114960
PMCID: PMC4263703  PMID: 25504150
16.  Genetic Traceability of Black Pig Meats Using Microsatellite Markers 
Pork from Jeju black pig (population J) and Berkshire (population B) has a unique market share in Korea because of their high meat quality. Due to the high demand of this pork, traceability of the pork to its origin is becoming an important part of the consumer demand. To examine the feasibility of such a system, we aim to provide basic genetic information of the two black pig populations and assess the possibility of genetically distinguishing between the two breeds. Muscle samples were collected from slaughter houses in Jeju Island and Namwon, Chonbuk province, Korea, for populations J and B, respectively. In total 800 Jeju black pigs and 351 Berkshires were genotyped at thirteen microsatellite (MS) markers. Analyses on the genetic diversity of the two populations were carried out in the programs MS toolkit and FSTAT. The population structure of the two breeds was determined by a Bayesian clustering method implemented in structure and by a phylogenetic analysis in Phylip. Population J exhibited higher mean number of alleles, expected heterozygosity and observed heterozygosity value, and polymorphism information content, compared to population B. The FIS values of population J and population B were 0.03 and −0.005, respectively, indicating that little or no inbreeding has occurred. In addition, genetic structure analysis revealed the possibility of gene flow from population B to population J. The expected probability of identify value of the 13 MS markers was 9.87×10−14 in population J, 3.17×10−9 in population B, and 1.03×10−12 in the two populations. The results of this study are useful in distinguishing between the two black pig breeds and can be used as a foundation for further development of DNA markers.
doi:10.5713/ajas.2013.13829
PMCID: PMC4093566  PMID: 25050032
Black Pig Populations; Genetic Traceability; Heterozygosity; Microsatellite Markers; Probability of Identity
17.  Comparative measurement of aortic root by transthoracic echocardiography in normal Korean population based on two different guidelines 
Background
Aortic root size is an important parameter in vascular diseases and can be easily assessed by transthoracic echocardiography. However, measurements values may vary according to cardiac cycle and the definition used for edge. This study aimed to define normal values according to the measurement method specified by two different guidelines to determine the influence of the different methods on echocardiographic measurements.
Methods
Healthy Korean adults were enrolled. The aortic root diameters were measured twice at four levels (aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta) by the 2005 American Society of Echocardiography (ASE) guidelines (measured from leading edge to leading edge during diastole) and the 2010 ASE pediatric guidelines (measured from inner edge to inner edge during systole).
Results
One hundred twelve subjects aged 20–69 years were enrolled. The aortic diameters (cm) determine by the aforementioned two guidelines showed significant difference. Measurements were larger in 2005 ASE guideline at aortic annuls, sinuses of Valsalva, and sinotubular junction level, but smaller at ascending aortic level with 2-3mm of differences. Intraobserver variability was similarly good, but interobserver variability was slightly higher than intraobserver variability in both measurement methods. BSA and age was most important determinant for aortic root size.
Conclusions
The measurement method of aortic root can affect the echocardiographic result. The measurement method should be noted when assessing clinical significance of aortic root measurement.
doi:10.1186/1476-7120-11-28
PMCID: PMC3751523  PMID: 23941562
Aortic root measurement; Normal reference; Transthoracic echocardiography
18.  Evaluation of Montanide™ ISA 71 VG Adjuvant during Profilin Vaccination against Experimental Coccidiosis 
PLoS ONE  2013;8(4):e59786.
Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus Montanide™ ISA 70 VG (ISA 70) or Montanide™ ISA 71 VG (ISA 71) water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin/ISA 70 vs. profilin alone and by profilin/ISA 71 vs. profilin alone. While immunization with profilin/ISA 70 vs. profilin alone altered the levels of more total transcripts compared with profilin/ISA 71 vs. profilin alone (509 vs. 296), the latter was associated with a greater number of unique biological functions, and a larger number of genes within these functions, compared with the former. Further, canonical pathway analysis identified 10 pathways that were associated with genes encoding the altered transcripts in animals immunized with profilin/ISA 71 vs. profilin alone, compared with only 2 pathways in profilin/ISA 70 vs. profilin alone. Therefore, ISA 71 was selected as a candidate adjuvant in conjunction with profilin vaccination for in vivo disease protection studies. Vaccination with profilin/ISA 71 was associated with greater body weight gain following E. acervulina infection, and decreased parasite fecal shedding after E. maxima infection, compared with profilin alone. Anti-profilin antibody levels were higher in sera of E. maxima- and E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. Finally, the levels of transcripts encoding interferon-γ, interleukin (IL)-2, IL-10, and IL-17A were increased in intestinal lymphocytes from E. acervulina-, E. maxima-, and/or E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. None of these effects were seen in chickens injected with ISA 71 alone indicating that the adjuvant was not conferring non-specific immune stimulation. These results suggest that profilin plus ISA 71 augments protective immunity against selective Eimeria species in chickens.
doi:10.1371/journal.pone.0059786
PMCID: PMC3620231  PMID: 23593150
19.  Peripheral Artery Disease in Korean Patients Undergoing Percutaneous Coronary Intervention: Prevalence and Association with Coronary Artery Disease Severity 
Peripheral artery disease (PAD) is an important marker for the risk stratification of patients with coronary artery disease (CAD). We investigated the prevalence of PAD in patients undergoing percutaneous coronary intervention (PCI) with CAD and the relationship between ankle-brachial pressure index (ABPI) and CAD severity. A total of 711 patients undergoing PCI for CAD from August 2009 to August 2011 were enrolled. PAD diagnosis was made using the ABPI. The prevalence of PAD was 12.8%. In PAD patients, mean values of right and left ABPI were 0.71 ± 0.15 and 0.73 ± 0.15. Patients with PAD had a higher prevalence of left main coronary disease (14.3% vs 5.8%, P = 0.003), more frequently had multivessel lesions (74.9% vs 52.1%, P < 0.001) and had higher SYNTAX score (18.2 ± 12.3 vs 13.1 ± 8.26, P = 0.002). Using multivariate analysis, we determined that left main CAD (OR, 2.954; 95% CI, 1.418-6.152, P = 0.004) and multivessel CAD (OR, 2.321; 95% CI, 1.363-3.953, P = 0.002) were both independently associated with PAD. We recommend that ABPI-based PAD screening should be implemented in all patients undergoing PCI with CAD, especially in severe cases.
doi:10.3346/jkms.2013.28.1.87
PMCID: PMC3546110  PMID: 23341717
Peripheral Artery Disease; Coronary Artery Disease; Atherosclerosis
20.  Successful Management of Pulmonary and Inferior Vena Cava Tumor Embolism from Renal Cell Carcinoma 
Pulmonary tumor embolism can be a cause of respiratory failure in patients with cancer even though it occurs rarely. We describe a 56-year-old man who underwent a pulmonary tumor embolectomy using cardiopulmonary bypass on beating heart combined with inferior vena cava embolectomy and right radical nephrectomy. Aggressive surgical treatment in this severe case is necessary not only to reduce the fatal outcome of pulmonary embolism in the short run, but also to improve the oncological prognosis in the long term.
doi:10.5090/kjtcs.2012.45.5.323
PMCID: PMC3487017  PMID: 23130307
Pulmonary embolism; Cancer; Great vessels; Embolectomy
21.  Plasma N-Terminal Pro-B-Type Natriuretic Peptide Is Predictive of Perioperative Cardiac Events in Patients Undergoing Vascular Surgery 
Background/Aims
Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery.
Methods
Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (≥ 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI.
Results
A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NT-proBNP level of > 302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p < 0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI.
Conclusions
Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.
doi:10.3904/kjim.2012.27.3.301
PMCID: PMC3443723  PMID: 23019395
Pro-B-type natriuretic peptide; Vascular surgical procedures; Postoperative complications
22.  Clinical Characteristics of Acute Aortic Syndrome in Korean Patients: From the Korean Multi-Center Registry of Acute Aortic Syndrome 
Korean Circulation Journal  2012;42(8):528-537.
Background and Objectives
Acute aortic syndrome (AAS) is a heterogeneous group of disorders that often present with severe chest or back pain. It includes acute aortic dissection (AD), intramural hematoma (IMH), dissecting aneurysm, and penetrating aortic ulcer (PAU). The clinical picture of AAS and its prognosis have not been studied in a large number of Korean patients. Therefore, we organized a multi-center registry to identify the clinical characteristics and treatment patterns, as well as long-term outcomes in Korean patients with AAS.
Subjects and Methods
Five-hundred twenty-eight patients, who had been diagnosed with AAS, were enrolled into this registry from 10 centers. On a retrospective basis, we collected demographic, laboratory, imaging data, as well as follow-up clinical outcomes by reviewing medical records from individual centers. All the data were collected in core lab and analyzed in detail.
Results
The mean patient age was 60.1±14.5 years; the male-to-female ratio was M : F=297 : 231. The prevalent risk factors for AAS included hypertension (361, 68.4%) and diabetes (52, 11.1%). The components of AAS that are included in this study are acute AD (446, 84.5%), IMH (57, 10.7%), and PAU (11, 2.1%). By type of AAS, patients diagnosed with Stanford A were 45.6% of enrolled patients, whereas those with Stanford B were 54.4% of enrolled patients. Among nearly half of the patients were treated with medicine (55.7%) alone, whereas 40.0% underwent surgery and 4.3% underwent endovascular treatment. Overall, the in-hospital event rate was 21.2% and the in-hospital death rate was 8.1%. The mean follow-up duration was 42.8 months and there showed 22.9% of total event and 10.1% of death during this period.
Conclusion
By organizing a multi-center registry of AAS, we could identify the characteristics of AAS in real-world Korean patients. Further, prospective study is warranted with a larger number of patients.
doi:10.4070/kcj.2012.42.8.528
PMCID: PMC3438262  PMID: 22977448
Aortic diseases; Dissection; Hematoma; Population characteristics
23.  Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells 
Journal of Korean Medical Science  2012;27(7):803-810.
The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-κB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-κB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-κB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.
doi:10.3346/jkms.2012.27.7.803
PMCID: PMC3390732  PMID: 22787379
Lysophosphatidylcholines; NF-kappa B; Oxidative Stress; Plasminogen Activator Inhibitor 1; Protein-Tyrosine Kinase; Muscle, Smooth, Vascular
24.  Ischemic Stroke in Takayasu's Arteritis: Lesion Patterns and Possible Mechanisms 
Background and Purpose
The purpose of the present study was to use brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to identify the mechanism of stroke in patients with Takayasu's arteritis (TA).
Methods
Among a retrospective cohort of 190 TA patients, 21 (3 males and 18 females) with a mean age of 39.9 years (range 15-68 years) who had acute cerebral infarctions were included in lesion pattern analyses. The patients' characteristics were reviewed, and infarction patterns and the degree of cerebral artery stenosis were evaluated. Ischemic lesions were categorized into five subgroups: cortical border-zone, internal border-zone, large lobar, large deep, and small subcortical infarctions.
Results
In total, 21 ischemic stroke events with relevant ischemic lesions on MRI were observed. The frequencies of the lesion types were as follows: large lobar (n=7, 33.3%), cortical border zone (n=6, 28.6%), internal border zone (n=1, 4.8%), small cortical (n=0, 0%), and large deep (n=7, 33.3%). MRA revealed that 11 patients had intracranial artery stenosis.
Conclusions
Hemodynamic compromise in large-artery stenosis and thromboembolic mechanisms play significant roles in ischemic stroke associated with TA.
doi:10.3988/jcn.2012.8.2.109
PMCID: PMC3391615  PMID: 22787494
vasculitis; thromboembolism; intracranial artery stenosis
25.  Risk factors for delayed recanalization of calf vein thrombosis 
Purpose
To determine the risk factors of delayed recanalization of isolated calf vein thrombosis (CVT).
Methods
One hundred fifty limbs of 110 patients with CVT between September 2007 and April 2010 were enrolled. We used ultrasonography for the diagnosis and follow-up examinations of CVT. We calculated recanalization rates at 1 and 3 months after initial diagnosis and analyzed the risk factors associated with delayed recanalization of CVT.
Results
CVTs were located in the muscular calf vein in 110 (73.3%), in the deep calf vein in 18 (12%), and in both in 22 cases (14.7%). Among all CVTs, 94 limbs (63%) were symptomatic. Major risk factors for CVT were orthopedic surgery (87.3%), malignancy (21.3%), and immobilization (15.3%). Sixty-seven patients (60.9%) were treated with oral anticoagulation therapy, while 43 patients by low molecular weight heparin (n = 19) or by conservative methods including elastic compression stockings and ambulation (n = 21). The cumulative recanalization rate at 1 and 3 months was 23% and 82% and it was significantly higher in patients who underwent oral anticoagulation therapy compared with patients without oral anticoagulation therapy (84% vs. 65%, P = 0.008 by log-rank test). Malignancy (odds ratio [OR], 2.789; P = 0.043) and immobilization (OR, 4.191; P = 0.029) were independent risk factors for delayed recanalization of CVT and oral anticoagulation (OR, 0.300; P = 0.020) was an independent factor in promoting recanalization in multivariate analysis.
Conclusion
For patients with isolated CVT, no oral anticoagulation resulted in higher rates of delayed recanalization compared to oral anticoagulation treatment. Immobilization and having malignancy were independent risk factors for delayed recanalization.
doi:10.4174/jkss.2012.82.5.306
PMCID: PMC3341480  PMID: 22563538
Thrombosis; Venous thrombosis; Deep vein thrombosis

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