Sang Hyung Kim

Evaluation of Subchronic Inhalation Toxicity of Dimethyl Disulfide in Rats

This study was carried out to investigate the potential subchronic inhalation toxicity of dimethyl disulfide (DMDS) via whole-body exposure in F344 rats. Groups of 10 rats of each sex were exposed to DMDS vapor by whole-body exposure at concentrations of 0, 5, 25, or 125 ppm for 6 h/day, 5 days/wk for 13 wk. All the rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. At 25 ppm, a decrease in the body weight gain, food intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) was observed in the males, but not in the females. However, at 125 ppm, a decrease in the body weight gain, food intake, and thymus weight and an increase in the weights of adrenal glands were observed in both genders. Serum biochemical investigations revealed a decrease in the AST, ALT, BUN, creatine phosphokinase (CPK), and triglyceride levels and an increase in the glucose level. In contrast, no treatment-related effects were observed in the 5 ppm group. The toxic potency of DMDS was slightly higher in males than that in females. In these experimental conditions, the target organ was not determined in rats. The no-observed-adverse-effect concentration (NOAEC) was found to be 5 ppm, 6 h/day for male rats and 25 ppm, 6 h/day for female rats.

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case-control study

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case-control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CIu2003=u20030.85-1.41) and that of the Pro/Pro genotype was 1.47 (95% CIu2003=u20031.02-2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CIu2003=u20030.92-1.67) and that of the Pro/Pro genotype was 1.77 (95% CIu2003=u20031.15-2.74) for EC overall. In never-smokers and ever-smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37-0.95) and 1.39 (95% CI = 1.00-1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case-control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.

Long-term Predictive Factors of Major Adverse Cardiac Events in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock

Background Cardiogenic shock (CS) after acute myocardial infarction (AMI) develops in 5~10% of patients and it is associated with high mortality. The aim of this study is to assess the predictive factors of mortality for patients with AMI and CS. Methods Two hundred fifty five AMI patients with CS (the mean age was 66.0±11.0 years, M:F=156:99) out of 1,268 AMI patients who admitted at Chonnam National University Hospital between July 2000 and June 2002 were analyzed according to the clinical characteristics, coronary angiographic findings and MACE during admission and for the 1-year clinical follow-up. Results Among the enrolled patients, 129 patients survived without MACE (Group I, mean age 64.2±10.6 years, M:F=76:53), and 126 patients had MACE (Group II, mean age 68.1±10.0 years, M:F=80:46) during admission or during the 1-year follow-up period. There were significant differences in age between the Groups I and II (64.2±10.6 vs. 68.1±11.0 years, respectively, p=0.004) and the previous MI history (0 vs. 17.4%, respectively, p<0.001). The left ventricular ejection fraction (EF) was lower in Group II (Group I vs. II: 49.1±13.0 vs. 39.1±12.9%, p<0.001). The levels of troponin (Tn) I and C-reactive protein (CRP) were higher in Group II (Group I vs. II: 29.2±7.72 vs. 50.8±5.17 ng/dL, p=0.017, 3.8±0.48 vs. 9.9±1.21 mg/dL, p<0.001 respectively). Left main stem lesion (LMSL) was more common in Group II than in Group I (0.7% vs. 22.0%, respectively, p=0.004). In-hospital death was associated with low Thrombolysis In Myocardial Infarction (TIMI) flow after coronary revascularization. Conclusion Old age, a previous MI history, high Tn and CRP, low EF and LMSL are associated with higher MACE for patients with AMI and CS. Coronary revascularization with TIMI 3 flow lowers the in-hospital mortality.

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.

Retrospective Analysis of Thoracoscopic Surgery for Esophageal Submucosal Tumors

Background Surgical enucleation is the treatment of choice for esophageal submucosal tumors (SMTs) with symptomatic, larger, or ill-defined lesions. The enucleation of SMTs has traditionally been performed via thoracotomy. However, minimally invasive approaches have recently been introduced and successfully applied. In this study, we present our experiences with the thoracotomic and thoracoscopic approaches to treating SMTs. Methods We retrospectively reviewed 53 patients with SMTs who underwent surgical enucleation between August 1996 and July 2013. Demographic and clinical features, tumor-related factors, the surgical approach, and outcomes were analyzed. Results There were 36 males (67.9%) and 17 females (32.1%); the mean age was 49.2±11.8 years (range, 16 to 79 years). Histology revealed leiomyoma in 51 patients, a gastrointestinal stromal tumor in one patient, and schwannoma in one patient. Eighteen patients (34.0%) were symptomatic. Fourteen patients underwent a planned thoracotomic enucleation. Of the 39 patients for whom a thoracoscopic approach was planned, six patients required conversion to thoracotomy because of overly small tumors or poor visualization in five patients and accidental mucosal injury in one patient. No mortality or major postoperative complications occurred. Compared to thoracotomy, the thoracoscopic approach had a slightly shorter operation time, but this difference was not statistically significant (120.0±45.6 minutes vs. 161.5±71.1 minutes, p=0.08). A significant difference was found in the length of the hospital stay (9.0±3.2 days vs. 16.5±5.4 days, p<0.001). Conclusion The thoracoscopic enucleation of submucosal esophageal tumors is safe and is associated with a shorter length of hospital stay compared to thoracotomic approaches.

Current Status of Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Artery Disease

Primary percutaneous coronary intervention (PCI) is a standard interventional treatment modality for ST-segment elevation myocardial infarction (STEMI). Diagnostic coronary angiogram during PCI reveals multivessel coronary artery disease in about half of patients with STEMI, and it is difficult to make decision on the extent of intervention in these patients. Although revascularization for the infarct-related artery only is still effective for STEMI patients, several studies have reported the efficacy of multivessel revascularization during primary PCI, as well as in a staged PCI procedure. Clinicians should consider clinical aspects such as initial cardiogenic shock and myocardial viability when performing primary multivessel intervention, including the risks and benefits of multivessel revascularization in patients undergoing primary PCI. This review describes the current status of performing multivessel PCI in patients with STEMI and proposes an optimal revascularization strategy based on the previous literature.

Clinical impact of early intervention in octogenarians with non-ST-elevation myocardial infarction

myocardial infarction☆ Zhe Hao Piao , Myung Ho Jeong ⁎, Li Jin , Da Wei Qian , Soo Young Jang , Jae Yeong Cho , Hae Chang Jeong , Ki Hong Lee , Keun-Ho Park , Doo Sun Sim , Kye Hun Kim , Young Joon Hong , Hyung Wook Park , Ju Han Kim , Youngkeun Ahn , Jeong Gwan Cho , Sang Hyung Kim , Jong Chun Park , Young Jo Kim , Myeong Chan Cho , Chong Jin Kim , Hyo Soo Kim f and Other Korea Acute Myocardial Infarction Registry (KAMIR) Investigator a Chonnam National University Hospital, Gwangju, Republic of Korea b Jilin Central Hospital, Jilin, China c Yeungnam University Hospital, Daegu, Republic of Korea d Chungbuk National University Hospital, Cheongju, Republic of Korea e Kyung Hee University Hospital, Seoul, Republic of Korea f Seoul National University Hospital, Seoul, Republic of Korea

Comparison of Resolute zotarolimus-eluting stents versus everolimus-eluting stents in patients with metabolic syndrome and acute myocardial infarction: Propensity score-matched analysis

BACKGROUNDnDespite common use of second-generation drug-eluting stents in treating patients with coronary artery disease, there is lack of data comparing these stents exclusively in patients with acute myocardial infarction (AMI), especially with metabolic syndrome (MetS), which is highly prevalent in AMI and potential to worsen clinical outcomes. The aim of this study was to compare clinical outcomes of everolimus-eluting stent (EES) and Resolute-zotarolimus-eluting stent (R-ZES) in AMI patients with MetS, in terms of stent-related and patient-related outcomes.nnnMETHODSnA total of 3942 AMI patients in the KAMIR (Korea Acute Myocardial Infarction Registry) were grouped according to the presence of MetS and stent type: EES (N=1582) and R-ZES (N=255) in MetS (1837). Target lesion failure (TLF) and patient-oriented composite events (POCE) at 1 year were evaluated.nnnRESULTSnIn MetS patients, TLF (3.7% vs. 2.7%, p=0.592) and POCE (7.9% vs. 6.7%, p=0.764) were similar between EES and R-ZES. Also in Non-MetS patients, TLF (3.9% vs. 3.1%, p=0.307) and POCE (6.4% vs. 7.3%, p=0.866) were similar between 2 groups. TLF was similar between MetS and Non-MetS patients (3.6% vs. 3.8%), while POCEs (7.7% vs. 6.6%) were higher in MetS. Propensity-score matching analysis showed similar results between stent groups in MetS and Non-MetS. In multivariate analysis, left ventricular ejection fraction and symptom-to-door time were independent predictors of TLF and POCE in MetS patients with AMI.nnnCONCLUSIONSnIn MetS patients with AMI, EES and R-ZES showed excellent performance and safety. However, patient-oriented composite events were relatively high, suggesting more efforts to improve them.

Influence of Thromboxane A2 on the Regulation of Adenosine Triphosphate-Sensitive Potassium Channels in Mouse Ventricular Myocytes

Background and Objectives Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. Subjects and Methods Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. Results In the excised inside-out patches, the thromboxane A2 analog, U46619, decreased the KATP channel activity in a dose-dependent manner; however, the thromboxane A2 receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced KATP channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced KATP channel activity. Conclusion Thromboxane A2 may inhibit KATP channel activity, and may have a harmful effect on ischemic myocardium.

Clinical outcome of statin plus ezetimibe versus high-intensity statin therapy in patients with acute myocardial infarction propensity-score matching analysis

BACKGROUNDnIt is unclear whether simvastatin-ezetimibe could be an alternative therapy to high-intensity statin therapy in high-risk patients. The aim of this study was to compare the clinical outcomes of simvastatin-ezetimibe and high-intensity statin therapy in patients with acute myocardial infarction (AMI), and especially in those with high-risk factor.nnnMETHODSnA total of 3520 AMI patients in the KAMIR (Korea Acute Myocardial Infarction Registry) were classified into simvastatin-ezetimibe group (n=1249) and high-intensity statin group (n=2271). Multivariate analysis and propensity-score matching analysis were performed. The primary endpoint was major adverse cardiac events (MACE) at 12-months follow-up.nnnRESULTSnIn overall AMI patients, MACE occurred in 116 patients (9.3%) in simvastatin-ezetimibe group and 116 patients (5.1%) in high-intensity statin group. The difference in MACE between groups was driven by repeat revascularization (5.9% vs. 2.2%). After propensity matching analysis, simvastatin-ezetimibe was associated with a higher incidence of MACE than high-intensity statin therapy (adjusted hazard ratio: 3.090, 95% confidence interval: 1.715 to 5.566, p<0.001). However, in patients with high-risk factors, such as diabetes, old age, or heart failure, simvastatin-ezetimibe had similar incidence of MACE compared with high-intensity statin therapy in further adjusted analysis.nnnCONCLUSIONSnIn overall AMI patients, high-intensity statin therapy had better clinical outcomes than simvastatin-ezetimibe. However, in patients with high-risk factor, simvastatin-ezetimibe had comparable clinical outcomes to high-intensity statin therapy. Therefore, simvastatin-ezetimibe could be used as an alternative to high-intensity statin therapy in such patients.