SCI 발표논문

2011년 177편

1172011

제1저자 최인실,이혜승 · 교신저자 이근욱

, , , , , , , ,
Biomarker analysis in patients with advanced gastric cancer treated with S-1 plus cisplatin chemotherapy: orotate phosphoribosyltransferase expression is associated with treatment outcomes.
Med Oncol. 2011;28(4):991-8.

Abstract
This study was performed to analyze the impact of protein expression related to fluoropyrimidine and cisplatin metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, orotate phosphoribosyltransferase [OPRT], excision repair cross-complementation 1, Fanconi anemia complementation group D2, glutathione S-transferase P1, and X-ray repair cross-complementing group 1) on treatment outcomes in patients with metastatic or relapsed gastric cancer (MRGC) receiving S-1/cisplatin chemotherapy. Protein expression was measured by immunohistochemistry (IHC). Of the 43 patients who had received S-1 (80 mg/m2/day; days 1-14) and cisplatin (60 mg/m2; day 1) every 3 weeks and had available tissue blocks, IHC was successfully performed in 41 patients. Patients with high OPRT levels in tumor tissues (IHC score≥6) had superior progression-free survival (PFS) (23.3 vs. 14.1 weeks [median]) and overall survival (OS) (72.4 vs. 55.4 weeks [median]) to those with low OPRT levels (IHC score≤5; P-values<.05). Expression levels of other proteins were not predictive of treatment outcomes. In multivariate analysis, both a good performance status and a high OPRT level were independently associated with prolonged PFS and OS. The OPRT expression level may be a good predictive marker in S-1/cisplatin-treated patients with MRGC.
PubMed IF 4.7 혈액종양내과
1162011

제1저자 박경우 · 교신저자 김효수

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Clinical outcomes of high on-treatment platelet reactivity in Koreans receiving elective percutaneous coronary intervention (from results of the CROSS VERIFY study).
Am J Cardiol. 2011;108(11):1556-63.

Abstract
Platelet reactivity after clopidogrel therapy varies among patients. Whether clopidogrel response variability can predict clinical outcomes has not been verified in Asians. A prospective cohort was analyzed to evaluate clinical impact of clopidogrel response variability in patients who underwent elective percutaneous coronary intervention (PCI). A total of 809 consecutive patients receiving clopidogrel after elective PCI were followed for 1 year. On-treatment platelet reactivity (OPR) after clopidogrel therapy was measured with a point-of-care test, the VerifyNow P2Y12 assay. The primary end point was the composite of cardiac death and nonfatal myocardial infarction (MI) at 1 year. In this exclusively Korean cohort, the median OPR was 236 P2Y12 reactivity units. Using the definition of OPR ≥235 P2Y12 reactivity units as high OPR (HOPR), 50.3% of the cohort showed HOPR. The group with HOPR had significantly higher rates of cardiac death and spontaneous MI (2.5% vs 0.5%, p = 0.022) than the group without HOPR. Multivariate-adjusted analysis showed that HOPR was an independent predictor of the composite of cardiac death and nonfatal MI. The difference in major adverse cardiac events between the groups with and without HOPR was more profound in those without major cardiovascular disease, such as hypertension, diabetes mellitus, or dyslipidemia. In conclusion, HOPR to clopidogrel was significantly associated with cardiac death and spontaneous MI after elective PCI, suggesting that clopidogrel response variability may be a significant risk factor of hard end points in Koreans.
PubMed IF 2.5 순환기내과
1152011

제1저자 방영주 · 교신저자 방영주

, , , , , , , , , , , , , , ,
Phase II study of sunitinib as second-line treatment for advanced gastric cancer.
Invest New Drugs. 2011;29(6):1449-58.

Abstract
PURPOSE This phase II, open-label, multicenter study assessed the oral, multitargeted, tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy.
EXPERIMENTAL DESIGN Patients received sunitinib 50 mg/day on Schedule 4/2 (4 weeks on treatment, followed by 2 weeks off treatment). The primary endpoint was objective response rate; secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, safety and tolerability, and quality of life.
RESULTS Of 78 patients enrolled, most had gastric adenocarcinoma (93.6%) and metastatic disease (93.6%). All were evaluable for safety and efficacy. Two patients (2.6%) had partial responses and 25 patients (32.1%) had a best response of stable disease for ≥6 weeks. Median PFS was 2.3 months (95% confidence interval [CI], 1.6-2.6 months) and median OS was 6.8 months (95% CI, 4.4-9.6 months). Grade ≥ 3 thrombocytopenia and neutropenia were reported in 34.6% and 29.4% of patients, respectively, and the most common non-hematologic adverse events were fatigue, anorexia, nausea, diarrhea, and stomatitis. Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports. There were no marked associations between baseline soluble protein levels, or changes from baseline, and measures of clinical outcome.
CONCLUSIONS The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer, its role in combination with chemotherapy merits further study.
PubMed IF 3.4 혈액종양내과
1142011

제1저자 최세연 · 교신저자 이근욱

, , , , , , , , , , , ,
Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients.
Thromb Haemost. 2011;106(6):1084-94.

Abstract
This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.
PubMed IF 5.2 혈액종양내과
1132011

제1저자 임우현 · 교신저자 김효수

, , , , , , , , , , ,
Stent coated with antibody against vascular endothelial-cadherin captures endothelial progenitor cells, accelerates re-endothelialization, and reduces neointimal formation.
Arterioscler Thromb Vasc Biol. 2011;31(12):2798-805.

Abstract
OBJECTIVE In contrast to CD34, vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC) whereas not on the early or myeloid EPC. Thus, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation through the ability of capturing EPC.
METHODS AND RESULTS The stainless steel stents were coated with rabbit polyclonal anti-human VE-cadherin antibodies and exposed to EPC for 30 minutes in vitro. The number of EPC that adhered to the surface of VE-cad stents was significantly higher than bare metal stents (BMS) in vitro, which was obliterated by pretreatment of VE-cad stent with soluble VE-cadherin proteins. We deployed VE-cad stents and BMS in the rabbit right and left iliac arteries, respectively. At 48 hours after stent deployment in vivo, CD-31-positive endothelial cells adhered to VE-cad stent significantly more than to BMS. At 3 days, scanning electron microscopy showed that over 90% surface of VE-cad stents was covered with endothelial cells, which was significantly different from BMS. At 42 days, neointimal area that was filled with smooth muscle cells positive for actin or calponin was significantly smaller in VE-cad stents than in BMS by histological analysis (0.95±0.22 versus 1.34±0.43 mm(2), respectively, P=0.02). Immuno-histochemical analysis revealed that infiltration of inflammatory cells was not significantly different between 2 stents.
CONCLUSIONS VE-cad stents captured EPC successfully in vitro, accelerated endothelial recovery on stent, and eventually reduced neointimal formation in vivo.
PubMed IF 8.8 순환기내과
1122011

제1저자 김재환/이우진 · 교신저자 이상협

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Clinical features of 20 patients with curatively resected biliary neuroendocrine tumours.
Dig Liver Dis. 2011;43(12):965-70.

Abstract
BACKGROUND Neuroendocrine tumours very rarely occur in the biliary tract; information about them is limited.
AIMS To present the clinical characteristics and prognosis of curatively resected biliary neuroendocrine tumours.
METHODS Review of medical records dated between 2000 and 2010 of 20 patients from three medical centres with biliary neuroendocrine tumour based on curative resection.
RESULTS Based on the World Health Organization 2010 classification, five and one patients had neuroendocrine tumour grades 1 and 2, seven had neuroendocrine carcinoma, and seven were diagnosed with mixed adenoneuroendocrine carcinoma. The locations were the following: seven in the gallbladder, four in the extrahepatic bile duct, and nine in the ampulla of Vater. Lymph node and hepatic metastases were noted in 11 and 4 patients, respectively. Fourteen patients experienced recurrence; most had recurrence in the liver. Patients with neuroendocrine tumour grade 1 had a lower rate of recurrence compared to others (p=0.001). The median disease-free and overall survival times were 5.8 (0.4-53.6) and 13.7 (1.9-102.1) months for all four subtypes. However, the median disease free and overall survival rates of neuroendocrine tumours were significantly longer than those of neuroendocrine carcinomas or mixed adenoneuroendocrine carcinoma.
CONCLUSIONS Patients with biliary neuroendocrine tumour showed extremely different clinical outcomes according to histopathologic subtypes by World Health Organization 2010 classification.
PubMed IF 4.9 소화기내과
1112011

제1저자 문기원 · 교신저자 이은봉

, , , , , ,
Risk factors for acute kidney injury by non-steroidal anti-inflammatory drugs in patients with hyperuricaemia.
Rheumatology (Oxford). 2011;50(12):2278-82.

Abstract
OBJECTIVE NSAIDs are commonly prescribed to control gout attacks in patients with hyperuricaemia. We investigated risk factors for NSAID-induced acute kidney injury (AKI) in patients with hyperuricaemia.
METHODS We identified 328 patients with hyperuricaemia treated with NSAIDs at Seoul National University Hospital between December 1998 and January 2008 to investigate risk factors for NSAID-induced AKI. The risk factors evaluated included age, sex, BMI, comorbidity, NSAID COX-2 selectivity, baseline glomerular filtration rate (GFR), serum uric acid, serum albumin, haemoglobin level, ratio of blood urea nitrogen and serum creatinine and the use of allopurinol. After extracting possible risk factors through univariate analysis, multivariate logistic regression analysis was performed with backward selection to derive a risk model for NSAID-induced AKI in patients with hyperuricaemia.
RESULTS Thirty (9.1%) NSAID users developed AKI. Univariate analysis revealed that old age (P = 0.008), low GFR (P = 0.001), low serum albumin (P < 0.001) and low haemoglobin levels (P < 0.001) were possible risk factors. Multivariate logistic regression analysis showed that low baseline GFR [odds ratio (OR) 4.86, 95% CI 1.27, 18.55, P = 0.021, for GFR 15-29 vs ≥60 ml/min/1.73 m(2)] and low serum albumin (OR 4.43, 95% CI 1.82, 10.80, P = 0.001, for albumin ≤4 vs >4 g/dl) are risk factors for NSAID-induced AKI in patients with hyperuricaemia.
CONCLUSION Low GFR and low serum albumin are risk factors for AKI in hyperuricaemic patients treated with NSAIDs. Our results suggest that NSAIDs should be used with caution in patients with low serum albumin.
PubMed IF 4.7 류마티스내과
1102011

제1저자 박영주, 이윤광 · 교신저자 이윤광, David D. Moore

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Dissociation of diabetes and obesity in mice lacking orphan nuclear receptor small heterodimer partner.
J Lipid Res. 2011;52(12):2234-2244.

Abstract
Mixed background SHP(-/-) mice are resistant to diet-induced obesity due to increased energy expenditure caused by enhanced PGC-1α expression in brown adipocytes. However, congenic SHP(-/-) mice on the C57BL/6 background showed normal expression of PGC-1α and other genes involved in brown adipose tissue thermogenesis. Thus, we reinvestigated the impact of small heterodimer partner (SHP) deletion on diet-induced obesity and insulin resistance using congenic SHP(-/-) mice. Compared with their C57BL/6 wild-type counterparts, SHP(-/-) mice subjected to a 6 month challenge with a Western diet (WestD) were leaner but more glucose intolerant, showed hepatic insulin resistance despite decreased triglyceride accumulation and increased β-oxidation, exhibited alterations in peripheral tissue uptake of dietary lipids, maintained a higher respiratory quotient, which did not decrease even after WestD feeding, and displayed islet dysfunction. Hepatic mRNA expression analysis revealed that many genes expressed higher in SHP(-/-) mice fed WestD were direct peroxisome proliferator-activated receptor alpha (PPARα) targets. Indeed, transient transfection and chromatin immunoprecipitation verified that SHP strongly repressed PPARα-mediated transactivation. SHP is a pivotal metabolic sensor controlling lipid homeostasis in response to an energy-laden diet through regulating PPARα-mediated transactivation. The resultant hepatic fatty acid oxidation enhancement and dietary fat redistribution protect the mice from diet-induced obesity and hepatic steatosis but accelerate development of type 2 diabetes.
PubMed IF 4.9 내분비대사내과
1092011

제1저자 박준범 · 교신저자 김효수

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Peroxisome proliferator-activated receptor-gamma agonists suppress tissue factor overexpression in rat balloon injury model with paclitaxel infusion.
PLoS One. 2011;6(11):e28327.

Abstract
The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, on myocardial infarction are poorly understood. We investigated the effects of this PPAR-γ agonist on the expression of tissue factor (TF), a primary molecule for thrombosis, and elucidated its underlying mechanisms. The PPAR-γ agonist inhibited TF expression in response to TNF-α in human umbilical vein endothelial cells, human monocytic leukemia cell line, and human umbilical arterial smooth muscle cells. The overexpression of TF was mediated by increased phosphorylation of mitogen-activated protein kinase (MAPK), which was blocked by the PPAR-γ agonist. The effective MAPK differed depending on each cell type. Luciferase and ChIP assays showed that transcription factor, activator protein-1 (AP-1), was a pivotal target of the PPAR-γ agonist to lower TF transcription. Intriguingly, two main drugs for drug-eluting stent, paclitaxel or rapamycin, significantly exaggerated thrombin-induced TF expression, which was also effectively blocked by the PPAR-γ agonist in all cell types. This PPAR-γ agonist did not impair TF pathway inhibitor (TFPI) in three cell types. In rat balloon injury model (Sprague-Dawley rats, n = 10/group) with continuous paclitaxel infusion, the PPAR-γ agonist attenuated TF expression by 70±5% (n = 4; P<0.0001) in injured vasculature. Taken together, rosiglitazone reduced TF expression in three critical cell types involved in vascular thrombus formation via MAPK and AP-1 inhibitions. Also, this PPAR-γ agonist reversed the paclitaxel-induced aggravation of TF expression, which suggests a possibility that the benefits might outweigh its risks in a group of patients with paclitaxel-eluting stent implanted.
PubMed IF 2.8 순환기내과
1082011

제1저자 김기환 · 교신저자 허대석

, , , , , , , , ,
Clinical significance of tumor-infiltrating FOXP3+ T cells in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.
Cancer Sci. 2011;102(11):1972-6.

Abstract
We evaluated the association between tumor-infiltrating FOXP3+ T cells and clinical outcomes in patients with ocular adnexal lymphoma of mucosa-associated lymphoid tissue type (OAML). Pretreatment formalin-fixed paraffin-embedded tissues from 42 patients with OAML were stained with 236A/E7 anti-FOXP3 murine monoclonal antibody as well as CD3, CD4 and CD8 antibodies. The amount of FOXP3+ T cells was numerically quantified using an image analysis program. Front-line treatments were as follows: combination chemotherapy (n = 25); radiotherapy (n = 9); doxycycline (n = 6); and wait and see (n = 2). Complete response (CR) was observed in 20 (50%) of 40 evaluable patients. Median progression-free survival (PFS) was 50 months. A high number of FOXP3+ T cells (n = 21, ≥ 180/0.58 mm(2)) showed a higher CR rate (33%vs 71%, P = 0.013) and tendency towards prolonged PFS (48 vs 67 months, P = 0.110). In the combination chemotherapy group, a high number of FOXP3+ T cells was significantly associated with a higher CR rate (29%vs 82%, P = 0.008) and prolonged PFS (17 vs 79 months, P = 0.003). A high number of tumor-infiltrating FOXP3+ T cells correlates with a favorable clinical outcome in OAML patients.
PubMed IF 4.9 혈액종양내과
1072011

제1저자 김미나 · 교신저자 김주성

, , , , , , , ,
Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection.
J Gastroenterol Hepatol. 2011;26(11):1619-25.

Abstract
BACKGROUND AND AIMS The incidence of early colorectal cancer (ECC) has been increasing. The aim of this study was to evaluate the clinical outcome and prognosis of ECC treated by endoscopic mucosal resection (EMR).
METHODS A total of 129 ECC patients who were initially treated by EMR between April 2005 and August 2007 were enrolled. Clinicopathological characteristics and prognoses were evaluated retrospectively.
RESULTS En bloc resection was performed in 85% of ECC patients, and piecemeal resection was performed in 15% of patients. Clear lateral and deep margins were achieved in 86% of cases. Of the 129 patients, 64 were found to have intramucosal cancer and 65 had submucosal cancer. Clinical characteristics were not different between patients with intramucosal cancer and submucosal cancer; however, poor differentiation and the absence of background adenoma showed significant association with submucosal cancer. Seven patients with submucosal cancer underwent subsequent surgical resection; five had lymphovascular invasion or a positive resection margin, one had perforation, and one patient requested surgical resection. Of these seven patients, one had residual cancer and two had lymph node metastasis. All patients with intramucosal cancer had no recurrence during the follow-up period. Seven patients with submucosal cancer showed adverse outcomes within 3 years, such as residual/recurrence of primary cancer or lymph node metastasis; five showed lymphovascular invasion or a positive deep margin, and two had no histological risk factors.
CONCLUSIONS Our results suggest that intramucosal cancer shows good prognosis, and a cure could be expected after EMR; however, adverse outcomes can occur in submucosal cancer. Therefore, meticulous endoscopic follow up is needed in patients with submucosal cancer for at least 3 years after EMR.
PubMed IF 3.5 소화기내과
1062011

제1저자 정재우 · 교신저자 강혜련

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HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency.
Nephrol Dial Transplant. 2011;26(11):3567-72.

Abstract
BACKGROUND Although allopurinol is a very effective urate-lowering drug for complicated hyperuricemia, in some patients, it can induce severe cutaneous adverse reactions (SCARs). Recent investigations suggest that HLA-B*5801 is a very strong marker for allopurinol-induced SCARs, especially in the population with a high frequency of HLA-B*5801. Korea is one of the countries with a high frequency of HLA-B*5801 which is the only subtype of HLA-B58 in the Korean population. Objective. This study was conducted to find out the incidence of allopurinol-induced hypersensitivity on patients with chronic renal insufficiency (CRI) according to HLA-B58 and the clinical implications of HLA-B58 as a risk marker for the development of allopurinol-induced hypersensitivity.
METHODS We retrospectively reviewed the medical records of patients with CRI who took allopurinol and carried out serologic human leukocyte antigen (HLA) typing for kidney transplantation between January 2003 and May 2010.
RESULTS Among a total of 448 patients with CRI, 16 (3.6%) patients experienced allopurinol hypersensitivity. Nine of these patients (2.0%) were diagnosed with SCARs (two Stevens-Johnson syndrome and seven allopurinol hypersensitivity syndrome) and seven patients (1.6%) had simple maculopapular rashes. The HLA-B58 allele was present in all patients with allopurinol-induced SCARs, while the frequency of HLA-B58 was only 9.5% in allopurinol-tolerant patients (P < 0.05). The incidence of allopurinol-induced SCARs in CRI shows a wide disparity according to HLA-B58 [18% in HLA-B58 (+) versus 0% in HLA-B58 (-)]. Among patients without HLA-B58, most (98.2%) of the CRI patients were tolerant to allopurinol and only 1.8% experienced simple rashes after taking allopurinol.
CONCLUSIONS In this study, the incidence of allopurinol-induced SCARs was considerably high in CRI patients with HLA-B58. This finding indicates that the presence of HLA-B58 may increase the risk of allopurinol-induced SCARs. Screening tests for HLA-B58 in CRI patients will be clinically helpful in preventing severe allopurinol hypersensitivity reactions.
PubMed IF 8.3 알레르기내과
1052011

제1저자 김고은 · 교신저자 김원

, , , , , , , , ,
Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus-related hepatocellular carcinoma after ablation therapy.
J Gastroenterol Hepatol. 2011;26(11):1638-45.

Abstract
BACKGROUND AND AIM Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV-related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation.
METHODS Patients with HBV-related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan-Meier method and Cox regression model to identify risk factors for intrahepatic recurrence.
RESULTS A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥2000 IU/mL. The median follow-up duration was 28.9 months (range, 12.0-57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P=0.026) and late (≥1 year) recurrence (HR, 0.288; P=0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P=0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence.
CONCLUSIONS These findings show that HBeAg-negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg-negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV-related HCC.
PubMed IF 3.5 소화기내과
1042011

제1저자 정성수 · 교신저자 박경수

, , , , , ,
Mechanism for antioxidative effects of thiazolidinediones in pancreatic β-cells.
Am J Physiol Endocrinol Metab. 2011;301(5):E912-21.

Abstract
Thiazolidinediones (TZDs) are synthetic ligands of peroxisome proliferator-activated receptor-γ (PPARγ), a member of the nuclear receptor superfamily. TZDs are known to increase insulin sensitivity and also to have an antioxidative effect. In this study, we tested whether TZDs protect pancreatic β-cells from oxidative stress, and we investigated the mechanism involved in this process. To generate oxidative stress in pancreatic β-cells (INS-1 and βTC3) or isolated islets, glucose oxidase was added to the media. The extracellular and intracellular reactive oxygen species (ROS) were measured to directly determine the antioxidant effect of TZDs. The phosphorylation of JNK/MAPK after oxidative stress was detected by Western blot analysis, and glucose-stimulated insulin secretion and cell viability were also measured. TZDs significantly reduced the ROS levels that were increased by glucose oxidase, and they effectively prevented β-cell dysfunction. The antioxidative effect of TZDs was abolished in the presence of a PPARγ antagonist, GW9662. Real-time PCR was used to investigate the expression levels of antioxidant genes. The expression of catalase, an antioxidant enzyme, was increased by TZDs in pancreatic β-cells, and the knockdown of catalase significantly inhibited the antioxidant effect of TZDs. These results suggest that TZDs effectively protect pancreatic β-cells from oxidative stress, and this effect is dependent largely on PPARγ. In addition, the expression of catalase is increased by TZDs, and catalase, at least in part, mediates the antioxidant effect of TZDs in pancreatic β-cells.
PubMed IF 4.2 내분비대사내과
1032011

제1저자 강정묵 · 교신저자 김나영

, , , , , , , , , , , , ,
Risk factors for peptic ulcer bleeding in terms of Helicobacter pylori, NSAIDs, and antiplatelet agents.
Scand J Gastroenterol. 2011;46(11):1295-301.

Abstract
OBJECTIVES The role of the Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and antiplatelet agents in the risk of peptic ulcer bleeding has not yet been established. This study was performed to identify the risk factors for peptic ulcer bleeding compared with non-bleeding peptic ulcer disease (PUD).
MATERIAL AND METHODS A total of 475 patients, 265 with bleeding PUD and 210 with non-bleeding PUD were consecutively recruited. H. pylori status was determined by histology, rapid urease test, and culture. Exposure to NSAIDs, aspirin, and antiplatelet agents (clopidogrel and ticlopidine) within 4 weeks was obtained.
RESULTS Compared with non-bleeding PUD, bleeding PUD had a higher proportion of male gender and current smoking, alcohol drinking, history of aspirin/antiplatelet use, and history of PUD. Whereas the proportion of H. pylori infection and history of H. pylori eradication in bleeding PUD were significantly lower than that in non-bleeding PUD. In multivariate analysis, male gender (OR 1.78, 95% CI 1.10-2.89), drinking alcohol (OR 2.08, 95% CI 1.29-3.14), aspirin/antiplatelet use (OR 2.35, 95% CI 1.45-3.82), and history of PUD (OR 2.46, 95% CI 1.36-4.46) remained independent risk factors for bleeding PUD. When H. pylori status and aspirin/antiplatelet agent use were combined, highest risk of bleeding peptic ulcers was found among H. pylori-negative patients with a history of aspirin/antiplatelet agent use (OR 3.03 95% CI 1.48-6.18) compared with H. pylori-positive patients with no history of aspirin/antiplatelet agent use.
CONCLUSIONS Patients with H. pylori-negative peptic ulcers who continuously took aspirin or antiplatelet agents had the highest peptic ulcer bleeding risk.
PubMed IF 1.8 소화기내과
1022011

제1저자 정수진 · 교신저자 김주성

, , , , , , , ,
Five-year risk for advanced colorectal neoplasia after initial colonoscopy according to the baseline risk stratification: a prospective study in 2452 asymptomatic Koreans.
Gut. 2011;60(11):1537-43.

Abstract
OBJECTIVE Postpolypectomy surveillance guidelines for colorectal cancer introduced the concept of 'risk stratification'; however, few studies have been conducted for validation of its usefulness. The aim of this study was to assess the 5-year incidence of advanced neoplasia recurrence based on the risk stratification scheme of the guidelines and to identify its risk factors.
METHODS A prospective study of surveillance colonoscopy after screening colonoscopy was carried out at the Seoul National University Hospital Healthcare System Gangnam Center. 3803 asymptomatic Koreans aged 50-69 were enrolled prospectively and 5-year cumulative adenoma rates were analysed according to three risk groups: normal (no baseline adenoma), low-risk (1-2 adenomas <10 mm) and high-risk (an advanced adenoma or ≥ 3 adenomas) groups. The RR was computed by HR using Cox proportional regression after multivariate adjustments. The primary outcome was the 5-year cumulative rate of recurrent advanced adenoma in each risk category and the secondary outcome was its predictive factors.
RESULTS Among 3803 subjects enrolled between 2003 and 2005, 2452 were followed-up within 5 years: 1242, 671 and 539 in the normal, low-risk and high-risk groups, respectively. Compared with the normal group, the low-risk group had a sufficiently low 5-year incidence and did not show an increased risk for subsequent advanced adenoma (2.4% vs 2.0%, HR=1.14, 95% CI 0.61 to 2.17). Conversely, a significantly higher 5-year rate (12.2%) and early recurrence (4.6, 7.4 and 9.6% at 1, 2 and 3 years) of advanced adenoma were revealed in the high-risk group. Among various patients and adenoma characteristics, only high-risk adenoma (HR=5.95, 95% CI 3.66 to 9.68) along with a number of ≥ 3 (HR=3.06, 95% CI 1.51 to 6.57) and size ≥ 10 mm (HR=3.02, 95% CI 1.80 to 5.06) were independent predictors.
CONCLUSIONS The surveillance interval for low-risk patients could be extended beyond 5 years. Colonoscopic surveillance should be targeted to high-risk patients, and 3-year follow-up after initial polypectomy may be appropriate.
PubMed IF 24.6 소화기내과
1012011

제1저자 최성희 · 교신저자 김민선

, , , , , , ,
Plasma vaspin concentrations are elevated in metabolic syndrome in men and are correlated with coronary atherosclerosis in women.
Clin Endocrinol (Oxf). 2011;75(5):628-35.

Abstract
OBJECTIVE Vaspin is visceral adipose-tissue-derived adipokine, which has an insulin-sensitizing effect in obese type 2 diabetic rodent models. As adipokines may serve as a link between visceral adiposity and atherosclerosis, we investigated whether plasma vaspin concentrations were associated with the metabolic syndrome and coronary atherosclerosis.
DESIGN AND METHODS We measured fasting plasma vaspin levels in 81 subjects with the metabolic syndrome and 241 age- and sex-matched control subjects without the metabolic syndrome using the enzyme-linked immunosorbent assay. Multi-detector row cardiac computed tomography was performed to evaluate coronary atherosclerosis. We analysed sex-specific plasma vaspin concentrations according to the presence of the metabolic syndrome and the severity of coronary atherosclerosis.
RESULTS Plasma vaspin concentrations were significantly higher in men with the metabolic syndrome compared with those without the metabolic syndrome [median 0·60 (inter-quartile range 0·40-0·99) ng/ml vs 0·40 (0·26-0·66) ng/ml, P = 0·002]. There was a positive correlation between plasma vaspin concentrations and body mass index, waist circumference, and per cent body fat in men. However, these relationships were not found in women. Plasma vaspin concentrations were associated with the presence and severity of coronary artery stenosis such as higher Agatstone calcium score, number of diseased vessels and characteristics of coronary artery plaque only in women.
CONCLUSIONS Higher plasma vaspin concentrations are significantly associated with metabolic syndrome in men. In women, vaspin concentrations are associated with coronary atherosclerosis. Further studies regarding the role of vaspin in the pathogenesis of obesity and atherosclerosis are required.
PubMed IF 2.8 내분비대사내과
1002011

제1저자 신동호 · 교신저자 구본권

, , , , , , , , ,
Discrepancy in the assessment of jailed side branch lesions by visual estimation and quantitative coronary angiographic analysis: comparison with fractional flow reserve.
Catheter Cardiovasc Interv. 2011;78(5):720-6.

Abstract
OBJECTIVE We sought to evaluate the variability in the assessment of jailed side branch (SB) lesions by visual estimation and quantitative coronary angiography (QCA) and to compare those results with fractional flow reserve (FFR).
METHODS Twenty jailed SB lesions with available FFR (median 0.76; range, 0.39-0.94) were selected from the PRESSURE trial. Lesions were assessed by three independent QCA core laboratories with different QCA systems and by three different cardiologist groups (five European bifurcation club members, five Korean experts, and five trainees). Agreements of the continuous measurements were expressed as the intraclass correlation coefficient (ICC) and average coefficient of variance (CV), and those of the categorical values as kappa.
RESULTS Mean minimum lumen diameter (MLD) and % diameter stenosis differed among the three QCA systems up to 0.30 mm and 9.65%, respectively (P < 0.001). Three QCA systems showed fair agreement for the measurements of reference diameter, % diameter stenosis, MLD, and lesion length (ICC 0.346-0.686, CV 8.7-29.5%), and a poor agreement on stenosis of 75% or more (Fleiss κ 0.14 and mean κ 0.18). Agreements of visual estimation among the three groups were poor to fair (Fleiss κ 0.167-0.367). Sensitivity and specificity for predicting ischemia-inducible lesion (FFR < 0.75) were 64.7% and 48.0% for visual estimation and 56.6% and 56.6% by QCA, respectively. Visual estimation overestimated the % diameter stenosis and functional significance of the lesions compared with QCA (P < 0.001) and FFR (P = 0.036).
CONCLUSIONS Angiographic assessment of jailed SB lesions by both QCA and visual estimation showed variability. Visual estimation tended to overestimate the severity of jailed SB lesions compared to FFR and QCA.
PubMed IF 1.9 순환기내과
992011

제1저자 김세훈 · 교신저자 장윤석

, , , , , , , , ,
Outcomes of premedication for non-ionic radio-contrast media hypersensitivity reactions in Korea.
Eur J Radiol. 2011;80(2):363-7.

Abstract
BACKGROUND Radio-contrast media (CM)-related adverse reactions are important clinical problems that may cause fatal anaphylaxis. Accordingly, it has been common practice to premedicate patients who have had previous reactions to CM with corticosteroids, antihistamines, and H2 blockers to prevent hypersensitive reactions. However, the effectiveness of premedication has not been properly demonstrated, especially in cases related to non-ionic CM. In this study, we evaluated the effectiveness of premedication at preventing of non-ionic CM immediate-type hypersensitivity reactions.
METHODS A total of 30 patients who had been pretreated with corticosteroid and H1 antihistamines and/or H2 blockers in a 3-year period were enrolled. The results of premedication were evaluated in terms of clinical characteristics and the features of breakthrough reactions.
RESULTS Hypersensitivity reactions were not prevented in 5 of the 30 patients who had experienced prior CM reactions (overall recurrence rate after premedication 16.7%; 4/17 patients with mild previous reactions, and 1/13 patients with severe previous reactions). The recurrence rate after premedication was significantly higher in patients with mild previous reactions than in those with severe reactions (23.5% vs. 7.7%; p<0.001). The breakthrough reactions were similar to the prior reactions in terms of severity and clinical manifestations.
CONCLUSION Premedication with corticosteroid and H1 antihistamines and/or H2 blockers effectively prevent non-ionic CM-related adverse events in most patients who have had severe previous reactions to CM. However, physicians should be aware of the possibility of premedication failing and of breakthrough reactions, even in cases in which the previous reactions were mild.
PubMed IF 3.9 알레르기내과
982011

제1저자 Pasaje · 교신저자 김윤준

, , , , , , , , , , ,
Lack of association of RAD51 genetic variations with hepatitis B virus clearance and occurrence of hepatocellular carcinoma in a Korean population.
J Med Virol. 2011;83(11):1892-9.

Abstract
The RecA homolog, E. coli (S. cerevisiae) (RAD51) may modulate hepatitis B virus (HBV) infection by maintaining genome integrity and mediating homologous DNA repairs. In this study, 16 sequence variations were detected by resequencing all exons, the exon-intron boundary, and promoter regions of the human RAD51 gene in DNA samples of 24 unrelated individuals. To investigate the association of common variations in the RAD51 locus with HBV infection and hepatocellular carcinoma (HCC) occurrence, six common polymorphisms were genotyped in a total of 1,103 Korean HBV cohort, composed of 433 spontaneously recovered patients as controls and 670 chronic carriers of HBV, who were stratified further into 327 cirrhosis/chronic hepatitis patients and 343 patients with HCC infected with HBV. Logistic analyses revealed no significant association of RAD51 polymorphisms and haplotypes with HBV clearance and HCC occurrence (P > 0.05). Furthermore, with age of infection as an important factor in disease progression to HCC, results from the Cox proportional hazards analysis showed no significant associations between any of the tested RAD51 variants and the age of onset of HCC (P > 0.05), suggesting that genetic polymorphisms of RAD51 may not play an important role in clearance of HBV and disease progression to HCC. Although studies in other populations are needed to confirm these findings, this preliminary data may contribute to the current knowledge on the pathogenesis of hepatitis.
PubMed IF 3.7 소화기내과
972011

제1저자 박상원 · 교신저자 문치숙

, , , , , , , ,
Severity predictors in eschar-positive scrub typhus and role of serum osteopontin.
Am J Trop Med Hyg. 2011;85(5):924-30.

Abstract
We prospectively evaluated severity predictors in terms of host, microorganism, and treatment factors in 153 eschar-positive scrub typhus patients. Severity was assessed with the Acute Physiology and Chronic Health Evaluation (APACHE) II score (< 10 versus ≥ 10) and predefined criteria of severe complications. Genotypes of Orientia tsutsugamushi were determined. Independent risk factors for severity (APACHE II score ≥ 10) were old age, diabetes mellitus, serum osteopontin > 100 ng/mL, and a group of underlying diseases (congestive heart failure, cerebrovascular disease, chronic liver disease, bronchial asthma, and chronic obstructive lung diseases). Anemia (≤ 10 g/dL) and C-reactive protein > 10 mg/dL were indicators of current severity. Neither the delay in antibiotics administration nor strain types (Boryong, Taguchi, or Kanda/Kawasaki) contributed to the severity. The risk factors for severe complications were similar. Serum osteopontin > 100 ng/mL had a negative predictive value of 96% for severe complications. This marker can be used to rule out severe disease status.
PubMed IF 1.9 감염내과
962011

제1저자 김세훈 · 교신저자 장윤석

, , , , , , , , , , , ,
Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans.
Epilepsy Res. 2011;97(1-2):190-7.

Abstract
BACKGROUND Although the US FDA recommends screening for HLA-B*1502 allele in most of Asian ancestry before initiating carbamazepine therapy, the HLA associations with carbamazepine hypersensitivity in non-Chinese Asian populations remain unclear. This study investigated the association between the HLA class I genotype and carbamazepine-induced severe cutaneous adverse reaction (SCAR) in Koreans.
METHODS Twenty-four patients who had developed carbamazepine-induced SCAR (7 Stevens-Johnson syndrome (SJS), 17 drug hypersensitivity syndrome (HSS)), 50 carbamazepine-tolerant controls from the Korean Pharmacogenetic Adverse Drug Reaction Research Network and data of 485 Korean general population from a previously published study were recruited. HLA-A, -B, and -C genotyping was performed by direct DNA sequence analysis.
RESULTS Only one of the seven SJS patients was positive for the B*1502 allele, but the frequency of B*1511 was much higher in the patients with CBZ-SJS than in the CBZ-tolerant control patients (P=0.011, P(c)=not significant; OR=18.0(2.3-141.2)). The frequencies of A*3101 in carbamazepine-induced HSS and SCAR were significantly higher than those in carbamazepine-tolerant controls (P(c)=0.011, OR=8.8(2.5-30.7) and P(c)=0.013, OR=7.3(2.3-22.5), respectively). The frequencies of B*1511 in carbamazepine-SJS and A*3101 in carbamazepine-HSS/SCAR were significantly higher than those in the general population.
CONCLUSIONS HLA-B*1502 does not seem to be an effective predictive marker for carbamazepine-induced SCAR, while HLA-B*1511 and A*3101 was associated with carbamazepine-induced SJS and HSS/SCAR respectively in the Korean population.
PubMed IF 2.3 알레르기내과
952011

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , , , , , , , , , , ,
Everolimus-eluting versus sirolimus-eluting stents in patients undergoing percutaneous coronary intervention: the EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) randomized trial.
J Am Coll Cardiol. 2011;58(18):1844-54.

Abstract
OBJECTIVES The goal of this study was to compare the angiographic outcomes of everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in a head-to-head manner.
BACKGROUND EES have been shown to be superior to paclitaxel-eluting stents in inhibiting late loss (LL) and clinical outcome. Whether EES may provide similar angiographic and clinical outcomes compared with SES is undetermined.
METHODS This was a prospective, randomized, open-label, multicenter trial to demonstrate the noninferiority of EES compared with SES in preventing LL at 9 months. A total of 1,443 patients undergoing percutaneous coronary intervention were randomized 3:1 to receive EES or SES. Routine follow-up angiography was recommended at 9 months. The primary endpoint was in-segment LL at 9 months, and major secondary endpoints included in-stent LL at 9 months, target lesion failure, cardiac death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis at 12 months. Data were managed by an independent management center, and clinical events were adjudicated by an independent adjudication committee.
RESULTS Clinical follow-up was available in 1,428 patients and angiographic follow-up in 924 patients (1,215 lesions). The primary endpoint of the study (in-segment LL at 9 months) was 0.11 ± 0.38 mm and 0.06 ± 0.36 mm for EES and SES, respectively (p for noninferiority = 0.0382). The in-stent LL was also noninferior (EES 0.19 ± 0.35 mm; SES 0.15 ± 0.34 mm; p for noninferiority = 0.0121). The incidence of clinical endpoints was not statistically different between the 2 groups, including target lesion failure (3.75% vs. 3.05%; p = 0.53) and stent thrombosis (0.37% vs. 0.83%; p = 0.38).
CONCLUSIONS EES were noninferior to SES in inhibition of LL after stenting, which was corroborated by similar rates of clinical outcomes. (Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting [EXCELLENT]; NCT00698607).
PubMed IF 22.3 순환기내과
942011

제1저자 김범석 · 교신저자 임석아

, , , , , , , , , , , , , ,
Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy.
BMC Cancer. 2011;11:452.

Abstract
BACKGROUND This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy.
METHODS Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response.
RESULTS The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008).
CONCLUSIONS The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype.
PubMed IF 4.1 혈액종양내과
932011

제1저자 송우정 · 교신저자 장윤석

, , , , , , ,
Histamine and allergen skin reactivity in the elderly population: results from the Korean Longitudinal Study on Health and Aging.
Ann Allergy Asthma Immunol. 2011;107(4):344-52.

Abstract
BACKGROUND The allergen skin prick test is the most representative diagnostic test for atopy, but its use has been limited because of the belief that skin reactivity decreases with aging.
OBJECTIVE To investigate skin reactivity and influencing factors in the elderly population.
METHODS This cross-sectional analysis included 854 subjects (aged ≥65 years) who participated in the Korean Longitudinal Study on Health and Aging cohort (September 2005 to August 2006) and underwent allergen skin prick tests. Skin prick tests were performed with 1 mg/mL of histamine and a panel of 12 aeroallergens that are common in Korea. The wheal diameters were measured and compared to identify the factors associated with skin reactivity.
RESULTS Older age and female sex were associated with reduced histamine skin reactivity in elderly subjects. This age-related decrease was apparent only among women, the reasons for which were not identified. In contrast to histamine, wheal response size induced by 2 major allergens, Dermatophagoides pteronyssinus and Dermatophagoides farinae, did not show sex differences and did not decrease with age among the subjects showing allergen-induced wheal size greater than 0 mm.
CONCLUSIONS This analysis demonstrates that age and sex can independently influence histamine skin reactivity among the elderly population. The allergen-induced wheal sizes did not decrease with age. The discrepancy between histamine and allergen skin reactivity may warrant further evaluation to redefine the cutoff value for the determination of a positive skin test result in elderly subjects.
PubMed IF 7.1 알레르기내과
922011

제1저자 김상현 · 교신저자 김효수

, , , , , ,
Efficacy and tolerability of a new extended-release formulation of nicotinic acid in Korean adults with mixed dyslipidemia: an 8-week, multicenter, prospective, randomized, double-blind, and placebo-controlled trial.
Clin Ther. 2011;33(10):1357-64.

Abstract
BACKGROUND Nicotinic acid is an effective treatment for dyslipidemia. Patients are more tolerant of the extended-release form of nicotinic acid because it has a lower incidence of side effects, such as facial flushing, than the immediate-release formulation.
OBJECTIVE This study was designed to evaluate the efficacy and tolerability of an experimental extended-release formulation of nicotinic acid in Korean adults with mixed dyslipidemia as a regulatory requirement to allow marketing of this product in Korea.
METHODS This study was a multicenter, prospective, randomized, double-blind, and placebo-controlled trial. Patients with low high-density lipoprotein cholesterol (HDL-C) levels, high low-density lipoprotein cholesterol (LDL-C) levels, or high triglyceride levels were enrolled. Patients in the treatment group received 500 mg of extended-release niacin for 4 weeks and 1000 mg of extended-release niacin for the next 4 weeks.
RESULTS Twenty-five patients (24% males; mean [SD] age, 57.4 [6.9] years) comprised the treatment group, and 22 patients (5% males; mean [SD] age 61.8 [8.3] years) comprised the placebo group. After 8 weeks of treatment, HDL-C levels were increased significantly in the treatment group (17.6% vs -1.7%, respectively, from 35 [7] mg/dL to 42 [11] mg/dL in the treatment group and from 38 [6] mg/dL to 36 [7] mg/dL in the placebo group; P < 0.001). LDL-C levels were decreased significantly in the treatment group (-11.4% vs 3.6%, respectively, from 147 [33] mg/dL to 126 [22] mg/dL in the treatment group and from 146 [31] mg/dL to 148 [26] mg/dL in the placebo group; P = 0.003). The incidence of drug-related adverse events, including facial flushing in the treatment group, was not significantly different from that in the placebo group.
CONCLUSIONS The tested extended-release formulation of nicotinic acid increased HDL-C levels significantly but decreased LDL-C levels with a low incidence of facial flushing in this small, select group of Korean adults with mixed dyslipidemia.
PubMed IF 3.7 순환기내과
912011

제1저자 김세훈 · 교신저자 조상헌

, , , , , ,
The effects of PG102, a water-soluble extract from Actinidia arguta, on serum total IgE levels: a double-blind, randomized, placebo-controlled exploratory clinical study.
Eur J Nutr. 2011;50(7):523-9.

Abstract
BACKGROUND Recent studies have reported that blocking IgE has a potentially beneficial role in the treatment of various allergic diseases. Previously, we found that PG102, a water-soluble extract prepared from the edible fruits of Actinidia arguta, can effectively reduce IgE levels using murine models.
AIMS To evaluate the efficacy of PG102 at lowering levels of total IgE in asymptomatic subjects with atopy.
METHODS A total of 90 asymptomatic subjects with atopy were randomized equally to a PG102 group or a placebo control group and treated for 8 weeks in a double-blind manner. Total serum IgE, eosinophilic cation protein (ECP), eotaxin, thymus, and activation-regulated chemokine (TARC), IL-4, IL-5, and IL-13 levels were measured. Eosinophil counts were determined before and after treatment, and results were compared. In addition, possible adverse reactions were thoroughly checked in this first human trial.
RESULTS Levels of total IgE significantly increased in the control group but showed no change in the PG102 group, and change differences between the control and PG102 groups were significant (+12.9%, vs.-5.7%, p = 0.015). Levels of ECP and eotaxin and eosinophil counts produced similar results. However, the other variables showed no significant changes after treatment.
CONCLUSION In this exploratory clinical trial, it was found that 8 weeks of treatment with PG102 effectively reduced the levels of total IgE in apparently asymptomatic subjects with atopy.
PubMed IF 4.5 알레르기내과
902011

제1저자 박진주 · 교신저자 이은봉

, , , , , , , ,
Copy number variation of β-defensin genes in Behçet's disease.
Clin Exp Rheumatol. 2011;29(4 Suppl 67):S20-3.

Abstract
OBJECTIVES Behçet's disease (BD) may be triggered by infectious agents in genetically susceptible persons. Human β-defensin 2 is an inducible antimicrobial peptide, the level of which can be influenced by copy number (CN) of the DEFB4. We investigated the relationship between copy number variation (CNV) of DEFB4 and BD.
METHODS One hundred and ninety-seven patients with BD and 197 healthy controls were enrolled. After measuring CN of DEFB4 with a paralogue ratio test, the CNV was compared between patients and controls. CNV was also analysed in comparison with the clinical manifestations of BD.
RESULTS The CN of DEFB4 was unimodally distributed among the study subjects with mean CN of 4.57 and standard deviation of 1.28. BD samples had numerically lower CN than controls, but the difference was not statistically significant (4.49 ± 1.21 vs. 4.65 ± 1.36, p=0.245). Regarding the relationship between CN of DEFB4 and clinical manifestations, there was no difference of CNV depending on the clinical manifestations.
CONCLUSIONS We found no significant difference in CNV of DEFB4 between patients with BD and controls. Our results suggest that CNV of DEFB4 may not contribute to the pathogenesis of BD.
PubMed IF 3.2 류마티스내과
892011

제1저자 최성희 · 교신저자 Henry N Ginsberg

,
Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance.
Trends Endocrinol Metab. 2011;22(9):353-63.

Abstract
Insulin resistance (IR) affects not only the regulation of carbohydrate metabolism but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of VLDL and increased plasma triglycerides, as well as with hepatic steatosis, despite the increased VLDL secretion. Here we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) size, is proatherogenic. Hepatic steatosis is a risk factor for steatohepatitis and cirrhosis. Understanding the complex inter-relationships between IR and these abnormalities of liver lipid homeostasis will provide insights relevant to new therapies for these increasing clinical problems.
PubMed IF 20.1 내분비대사내과
882011

제1저자 이승표 · 교신저자 김용진

, , , , , , , , ,
Deterioration of myocardial function in paradoxical low-flow severe aortic stenosis: two-dimensional strain analysis.
J Am Soc Echocardiogr. 2011;24(9):976-83.

Abstract
BACKGROUND The diagnosis and management of paradoxical low-flow (PLF) aortic stenosis (AS) is challenging in clinical practice. In addition, its pathophysiology has not been fully understood. The aim of this study was to test the hypothesis that left ventricular (LV) myocardial function is deteriorated in PLF AS and that it is closely related to global LV afterload.
METHODS Echocardiographic data from 103 patients with severe AS (aortic valve area < 1.0 cm(2)) with normal LV ejection fractions were prospectively collected. Global longitudinal and circumferential myocardial strain was analyzed using two-dimensional speckle-tracking imaging. PLF AS was defined as a stroke volume index < 35 mL/m(2).
RESULTS Sixteen patients were classified as having PLF AS. Compared with those with normal-flow AS, patients with PLF AS were more likely to have worse functional status (mean New York Heart Association functional class, 2.38 ± 0.70 vs 1.96 ± 0.62; P = .02), worse global longitudinal strain (GLS) (-12.6 ± 4.4% vs -16.4 ± 4.0%, P < .01), lower aortic valve area (0.53 ± 0.15 vs 0.78 ± 0.19 cm(2), P < .01), and higher valvuloarterial impedance (5.62 ± 1.33 vs 3.65 ± 0.83 mm Hg · m(2)/mL, P < .01). GLS showed a significant negative linear relationship with stroke volume index (r = -0.324, P = .001) and a positive relationship with E/E' ratio (r = 0.367, P < .001). Multivariate analysis showed that age (β = 0.08, P = .07) and valvuloarterial impedance (β = 1.54, P < .01) were significant predictors of GLS.
CONCLUSIONS GLS is depressed in patients with PLF AS. This implies that subclinical myocardial dysfunction may be more prominent in PLF AS compared with normal-flow AS and suggests the possible diagnostic and prognostic value of two-dimensional global strain in identifying PLF AS. In addition, global LV afterload is an important determinant of myocardial dysfunction in patients with severe AS.
PubMed IF 8.3 순환기내과

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