SCI 발표논문

전체 4,588편

10782012

제1저자 김지연 · 교신저자 김나영

, , , , , , , , , , , ,
Prevalence and clinicopathologic characteristics of gastric cardia cancer in South Korea.
Helicobacter. 2012;17(5):358-68.

Abstract
BACKGROUND AND AIM Western reports have suggested that the prevalence of gastric cardia cancer (GCC) has been increasing, and indicated some differences between GCC and gastric noncardia cancer (GNCC). However, few studies have been conducted in Asia. The aims of this study were to estimate the prevalence of GCC and to evaluate differences of clinicopathologic characteristics between GCC and GNCC in South Korea.
METHODS This study was single-center case-control study. A total of 829 patients with gastric cancer and 270 controls were enrolled between 2003 and 2011. Baseline characteristics, Helicobacter pylori (H. pylori) infection status, and histologic characteristics were compared among three groups (GCC, GNCC, and control).
RESULTS Sixty cases (7.2%) of gastric cancer were located in cardia. Multivariate analysis showed that male odds ratio (OR, 5.72; 95% CI, 1.72-19.07; p = .005) and cigarette smoking (OR, 5.38; 95% CI, 1.39-20.90; p = .015) were risk factors of GCC in comparison with control group, but H. pylori infection rate was not significant. In the case of GNCC, cigarette smoking (OR, 3.87; 95% CI, 1.81-8.29; p < .001), past alcohol intake (OR, 2.82; 95% CI, 1.28-6.20; p = .010), intestinal metaplasia (OR, 3.22; 95% CI, 2.00-5.17; p < .001), and H. pylori infection (OR, 3.06; 95% CI, 1.90-4.93; p < .001) were risk factors of GNCC. Gastroesophageal reflux disease symptoms were higher in the GNCC (21.2%) than control group (13.5%) (p = .008). However, in the case of GCC, they were similar between the GCC (12.7%) and control group (p = .872). According to multivariate analysis, history of H. pylori eradication (OR, 0.34; 95% CI, 0.19-0.61; p < .001) was associated with a protective effect on GNCC. GCC showed higher depth of invasion (p = .038) and frequent distant metastasis (p = .012) than GNCC.
CONCLUSION In this referral center based study, the prevalence of GCC was 7.2% in South Korea. Risk factors and clinicopathologic characteristics for GCC and GNCC were different, supporting that the pathophysiology is different in the development of GCC and GNCC.
PubMed IF 4.6 소화기내과
10772012

제1저자 김세중 · 교신저자 주권욱

, , , , , , , , ,
Hemodynamic and biochemical benefits of the objective measurement of fluid status in hemodialysis patients.
Tohoku J Exp Med. 2012;228(2):125-33.

Abstract
Subtle fluid imbalance can cause poor clinical outcomes among hemodialysis patients. However, the traditional subjective assessment of fluid status may be inadequate. We evaluated whether the objective measurement and optimization of fluid status could be beneficial for hemodynamic and biochemical parameters in hemodialysis patients. We enrolled 120 hemodialysis patients, who were clinically euvolemic for at least 3 months. Based on the results of a body composition monitor, we divided the patients into the following two groups: the hyperhydrated group (post hemodialysis fluid overload ≥ 1.1 L) and the dehydrated group (post hemodialysis fluid overload < -1.1 L). We reduced the patient's body weight in the hyperhydrated group and raised the body weight in the dehydrated group towards normohydration (-1.1 L ≤ fluid overload < 1.1 L) for 16 weeks. Forty-four of 120 patients were in the hyperhydrated group, and 18 of 120 patients in the dehydrated group. After 16 weeks, systolic blood pressure and pulse pressure decreased in the hyperhydrated group, while there was no increase in blood pressure in the dehydrated group after the intervention. Serum levels of monocyte chemotactic protein-1, an inflammatory marker, gradually decreased in the hyperhydrated group, and serum adiponectin levels, an anti-atherogenic biomarker, increased in the two groups. We found that hyperhydrated patients contributed over 1/3 of the participants despite enrolling clinically euvolemic patients and that body composition monitor-guided optimization of body fluid status may lead to improvement of inflammatory markers and anti-atherogenic adipokines as well as hemodynamic parameters in hemodialysis patients.
PubMed IF 1.5 신장내과
10762012

제1저자 김세중 · 교신저자 한진석

, , , , , , , , ,
Increased plasma osmolar gap is predictive of contrast-induced acute kidney injury.
Tohoku J Exp Med. 2012;228(2):109-17.

Abstract
Contrast-induced acute kidney injury (CIAKI) is a common complication after percutaneous coronary artery intervention (PCI). It is urgent to find a novel, easily measurable and accurate predictor for the early detection of CIAKI. Hyperosmolarity and large amounts of contrast media are risk factors for CIAKI. However, there is no study on plasma osmolar gap as a predictor of CIAKI. We enrolled 89 patients undergoing elective PCI and tested changes of serum sodium, osmolar gap, and renal function at 0, 6, 12 and 24 hours. Plasma osmolar gap was calculated using the following formula: measured plasma osmolarity - [2(Na) + serum urea nitrogen/2.8 + glucose/18]. CIAKI was defined as follows: increase in serum creatinine of ≥ 50%, increase in serum creatinine of ≥ 0.3 mg/dL, or decrease in estimated glomerular filtration rate of ≥ 25% within 24 hours after PCI. The incidence of CIAKI was 13.5% (12/89 patients). The CIAKI group had higher plasma osmolar gaps 6 hours after PCI. The adjusted hazard ratio of the plasma osmolar gap from hour 6 (1-mOsm/L increments) to the development of CIAKI was 1.12 (95% confidence interval [CI], 1.01-1.26; P = 0.041). Sensitivity and specificity of 7 mOsm/L or higher plasma osmolar gap at hour 6 were 70.0% and 76.6%, respectively (area under the ROC curve = 0.77 [95% CI, 0.65-0.89]). Increased plasma osmolar gap may precede the development of CIAKI in patients undergoing PCI. In conclusion, plasma osmolar gap may be a useful predictor for the development of CIAKI.
PubMed IF 1.5 신장내과
10752012

제1저자 안동원/서정균 · 교신저자 이상협

, , , , , , ,
Enhanced antitumor effect of combination therapy with gemcitabine and guggulsterone in pancreatic cancer.
Pancreas. 2012;41(7):1048-57.

Abstract
OBJECTIVES Guggulsterone is a dietary plant sterone possessing therapeutic potential against cancers. However, the antitumor effect of this natural compound on pancreatic cancer has not been determined yet. This study was designed to investigate the therapeutic efficacy of guggulsterone in pancreatic cancer.
METHODS In this study, we examined the effect of guggulsterone on cell proliferation and apoptosis in pancreatic cancer cell lines, and then, we investigated the mechanisms responsible for the effect of guggulsterone. Finally, we investigated whether the combination of guggulsterone and gemcitabine had an additional therapeutic effect compared to gemcitabine single regimen in pancreatic cancer cell lines (in vitro) and in a xenograft model using nude mice (in vivo).
RESULTS In vitro, the combination treatment resulted in more growth inhibition and apoptosis through the down-regulation of nuclear factor κB activity with suppression of Akt and BcL-2 and through the activation of c-Jun NH(2)-terminal kinase and Bax in pancreatic cancer cell lines. In vivo, the combination therapy augmented tumor growth inhibition through the same mechanisms in tumor tissue.
CONCLUSIONS The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor κB activity and by modulating apoptosis-related protein expression in pancreatic cancer.
PubMed IF 2.2 소화기내과
10742012

제1저자 배준설 · 교신저자 김윤준

, , , , , , , ,
Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver diseases.
Dig Liver Dis. 2012;44(10):849-54.

Abstract
BACKGROUND AND AIMS MicroRNAs have been recently identified as important regulators that influence human carcinogenesis, cancer progression, and the interaction between the host and virus. This study investigates an association between microRNAs (miR-101-1, miR-101-2, and miR-338) and the risk of liver diseases through clearance of hepatitis B virus infection, development of liver cirrhosis, and hepatocellular carcinoma occurrence.
METHODS Genetic variations were genotyped using the TaqMan assay in 1439 Korean hepatitis B virus patients. To investigate the relationship between four polymorphisms in three microRNAs and the disease phenotypes, differences in frequency distribution of variations were analysed using logistic and multiple regression analyses after adjusting for age and gender as covariates.
RESULTS We find that the rs7536540 polymorphism in miR-101-1 is significantly associated with development of liver cirrhosis and hepatocellular carcinoma occurrence. In addition, rs12375841 and its unique haplotype (ht2) in miR-101-2 show significant association with clearance of hepatitis B virus infection.
CONCLUSIONS To our knowledge, this is the first study to examine a relationship between the three microRNA genes and the risk of hepatitis B-related liver diseases. We expect that the findings in this study will be helpful to further genetic studies in the pathophysiology of hepatitis B virus-related liver diseases.
PubMed IF 4.9 소화기내과
10732012

제1저자 김학령 · 교신저자 구본권

, , , , , , , , , , , , , , , ,
Clinical and physiological outcomes of fractional flow reserve-guided percutaneous coronary intervention in patients with serial stenoses within one coronary artery.
JACC Cardiovasc Interv. 2012;5(10):1013-8.

Abstract
OBJECTIVES This study was performed to evaluate the physiological and clinical outcomes of fractional flow reserve (FFR)-guided revascularization strategy with drug-eluting stents in serial stenoses within the same coronary artery.
BACKGROUND Identifying a functionally significant stenosis is difficult when several stenoses exist within 1 coronary artery.
METHODS A total of 131 patients (141 vessels and 298 lesions) with multiple intermediate stenoses within the same coronary artery were assessed by FFR with pullback pressure tracings. In vessels with an FFR <0.8, the stenosis that caused the largest pressure step-up was stented first. Major adverse cardiac events were assessed during follow-up.
RESULTS FFR was measured 239 times and there were no procedure-related complications. There was a weak negative correlation between FFR and angiographic percent diameter stenosis (r = -0.282, p < 0.001). In total, 116 stents were implanted and revascularization was deferred in 61.1% (182 of 298) of lesions. When the vessels with an initial FFR <0.8 were divided into 2 groups according to FFR after first stenting (FFR ≥0.8 vs. FFR <0.8), there were no differences in baseline angiographic and physiological parameters between the 2 groups. During the mean follow-up of 501 ± 311 days, there was only 1 target vessel revascularization due to in-stent restenosis. There were no events related to deferred lesions.
CONCLUSIONS FFR-guided revascularization strategy using pullback pressure tracing in serial stenoses was safe and effective. This strategy can reduce unnecessary intervention and maximize the benefit of percutaneous coronary intervention with drug-eluting stents in patients with multiple stenoses within 1 coronary artery.
PubMed IF 12.7 순환기내과
10722012

제1저자 박완범 · 교신저자 유경상

, , , , , , , , , , ,
The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial.
Clin Infect Dis. 2012;55(8):1080-7.

Abstract
BACKGROUND Blood levels of voriconazole, a first line therapy for invasive aspergillosis, may correlate with adverse events and treatment response. However, no randomized controlled studies have been conducted to evaluate the clinical utility of routine therapeutic drug monitoring (TDM) of voriconazole. This study aimed to determine whether routine TDM of voriconazole reduces drug adverse events or improves treatment response in invasive fungal infections.
METHODS This was a randomized, assessor-blinded, controlled, single center trial. One hundred ten adult patients were randomly assigned to TDM or non-TDM groups. In the TDM group, voriconazole dosage was adjusted (target range, 1.0-5.5 mg/L) according to the serum trough level measured on the fourth day after initiation of voriconazole. The non-TDM group received a fixed, standard dosage. Voriconazole-related adverse events were monitored, and treatment response was assessed three months after the initiation of therapy.
RESULTS Baseline characteristics including the CYP2C19 genotype were comparable between the two groups. While the incidence of adverse events was not different between the TDM group and the non-TDM group (both 42%; P = .97), the proportion of voriconazole discontinuation due to adverse events was significantly lower in the TDM group than in the non-TDM group (4% vs 17%; P = .02). A complete or partial response was observed in 81% (30 of 37) of patients in the TDM group compared to 57% (20 of 34) in the non-TDM group (P = .04).
CONCLUSIONS Routine TDM of voriconazole may reduce drug discontinuation due to adverse events and improve the treatment response in invasive fungal infections.
CLINICAL TRIAL REGISTRATION NCT00890708.
PubMed IF 8.3 감염내과
10712012

제1저자 조유리 · 교신저자 이동호

, , , , , , , , , , , , , , ,
Higher prevalence of obesity in gastric cardia adenocarcinoma compared to gastric non-cardia adenocarcinoma.
Dig Dis Sci. 2012;57(10):2687-92.

Abstract
BACKGROUND AND AIMS Obesity is one of the main risk factors for gastric cardia adenocarcinoma (GCA) in the West. Also, recent studies have suggested that GCA is distinct from distal stomach tumor, with differing risk factors, tumor characteristics, and biological behavior. The objective of our research was to evaluate the relationship between obesity and GCA compared to non-cardia adenocarcinoma.
MATERIALS AND METHODS A total of 298 patients who were diagnosed with gastric adenocarcinoma and underwent surgery at Seoul National University Bundang Hospital were evaluated. Ninety-one cases were GCA, and 207 cases were non-cardiac adenocarcinoma. Obesity was estimated by body mass index (BMI, kg/m(2)). The degree of obesity was determined by using BMI <18.5, 18.5-23.9, 24-27.9, and ≥ 28 (kg/m(2)) as the cut-off points for underweight, normal weight, overweight, and obese, respectively. Association with obesity was estimated by odds ratio (OR) and 95% confidence interval (CI).
RESULTS Obesity was more prevalent in patients with GCA at the time of diagnosis for gastric cancer. Among obese persons with a BMI of 28 kg/m(2) or higher, the OR was 3.937 (95% CI, 1.492-10.389; p = 0.006) for GCA compared to non-cardia adenocarcinoma. For overweight individuals, the OR was 2.194 (95% CI, 1.118-4.305; p = 0.022). Multivariate analysis of age, Helicobacter pylori infection, smoking, stage, and BMI with logistic regression was performed. BMI was an independent risk factor for GCA (OR, 1.123; 95% CI, 1.037-1.217; p = 0.004).
CONCLUSION Obesity was more prevalent in patients with GCA compared to that in patients with gastric non-cardia adenocarcinoma. Also, BMI was an independent risk factor for GCA.
PubMed IF 2.8 소화기내과
10702012

제1저자 김광일 · 교신저자 김광일

, ,
Impaired health-related quality of life in elderly women is associated with multimorbidity: results from the Korean National Health and Nutrition Examination Survey.
Gend Med. 2012;9(5):309-18.

Abstract
BACKGROUND Multimorbidity is a common problem in elderly populations and is significantly associated with functional decline, disability, and mortality. However, the sex-specific characteristics of multimorbidity and its effect on patients' quality of life (QOL) have not been clearly established.
METHODS We analyzed the Korean National Health and Nutrition Examination Survey database. EuroQol 5D (a standardized health outcomes measurement instrument that includes 2 dimensions, the EuroQol 5 Dimension [EQ-5D] index score and the EuroQol visual analogue scale [EQ-VAS]) was used to evaluate QOL. Multimorbidity was evaluated using data on blood pressure measurements, blood chemistry examinations, and anthropometric assessments, as well as a survey that assessed health status.
RESULTS A total of 1419 patients aged ≥65 years were included in the analysis (age = 72.40 [0.19] years; 39.3% men). Multimorbidity was significantly associated with being a woman; however, it was not associated with age. The EQ-5D index score and EQ-VAS score were significantly lower in patients with multimorbidity, especially among the elderly women. The inverse association between QOL and the number of chronic diseases was maintained without a floor effect. Hypertension was the most common disease; however, QOL was significantly associated with musculoskeletal disease, stroke, and depression, all of which were more common in female patients. There was no significant difference in QOL between men and women with similar levels of comorbidity.
CONCLUSION Both the amount and pattern of chronic diseases have been associated with QOL in elderly populations. Elderly women have low levels of QOL due to multimorbidity and a higher prevalence of chronic disease, which is related to impaired QOL.
PubMed IF 2.101 순환기내과
10692012

제1저자 김세중, 오국환 · 교신저자 김성균

, , , , , , , , , ,
Biocompatible peritoneal dialysis solution preserves residual renal function.
Am J Nephrol. 2012;36(4):305-16.

Abstract
BACKGROUND/AIMS The long-term effects of biocompatible peritoneal dialysis (PD) solution on residual renal function (RRF), inflammation, adipokines and metabolic acidosis are controversial. We evaluated the effects of biocompatible PD solution in continuous ambulatory PD (CAPD) patients for an additional 12-month period.
METHOD Among 91 incident patients who started CAPD with either biocompatible PD solution (Balance®, Fresenius; LS, n = 48) or conventional PD solution (CAPD/DPCA®, Fresenius; CS, n = 43), 63 patients, who were followed for 12 months, were enrolled and followed for an additional 12 months.
RESULTS After 24 months of treatment, the glomerular filtration rate (GFR) of the LS group was twofold higher compared to the CS group (33.5 ± 30.7 vs. 16.3 ± 17.9 l/week/1.73 m(2), respectively, p = 0.021). In a subgroup of patients with an initial GFR >2 ml/min/1.73 m(2), the GFR of the LS group was significantly higher than the rate of the CS group after 24 months (43.7 ± 30.5 vs. 18.6 ± 19.0 l/week/1.73 m(2), respectively, p = 0.042). Over a 24-month period, effluent cancer antigen-125 levels were significantly increased in the LS group compared to the CS group, while effluent interleukin-6 levels did not differ between the two groups. The serum tCO(2) levels were consistently higher in the LS group compared to the CS group.
CONCLUSIONS We found that the effect of LS on preserving RRF may be maintained over a 24-month treatment period in CAPD patients, and LS use may have other benefits, such as the correction of metabolic acidosis.
PubMed IF 3.8 신장내과
10682013

제1저자 이주명 · 교신저자 조영석

, , , , , , , , , , , , , ,
Left ventricular thrombus and subsequent thromboembolism, comparison of anticoagulation, surgical removal, and antiplatelet agents.
J Atheroscler Thromb. 2013;20(1):73-93.

Abstract
UNLABELLED Left ventricular (LV) thrombus is one of the risk factors for systemic thromboembolism. The aims of this study were to compare the long-term clinical outcomes of LV thrombus using current therapeutics, anticoagulation, operative treatment, and antiplatelet agents and to identify independent predictors of systemic thromboembolism.
METHODS We screened 86,374 patients for intracardiac thrombus in the electronic medical records and imaging databases. Records of 62 patients with LV thrombus, diagnosed between May 2003 to November 2011, were comprehensively reviewed regarding baseline characteristics, imaging data and thrombus outcomes, thromboembolic events and treatment complications by treatment group.
RESULTS The majority (80.6%) had ischemic etiology. Systemic thromboembolism developed in 18 patients; 8 (45%) were post-treatment thromboembolisms while 10 events occurred before treatment began. No post-treatment thromboembolism occurred in the operative treatment group; in contrast, 7 post-treatment thromboembolisms occurred in anticoagulation group (17%) (Log rank p= 0.175). Independent predictors of post-treatment thromboembolism were dilated cardiomyopathy (HR 61.30, p= 0.001), previous cerebrovascular events (HR 7.06, p= 0.042), female gender (HR 7.11, p= 0.031), and echocardiographic left ventricular end-diastolic diameter (HR 1.15, p= 0.047).
CONCLUSIONS In this study, the rate of post-treatment thromboembolism was not significantly different among the treatment groups; however, operative treatment tended towards less post-treatment thromboembolism than other treatment groups.
PubMed IF 3.4 순환기내과
10672012

제1저자 조영민 · 교신저자 Timothy J. Kieffer

, ,
Targeting the glucagon receptor family for diabetes and obesity therapy.
Pharmacol Ther. 2012;135(3):247-78.

Abstract
Diabetes is a debilitating disease characterized by chronic hyperglycemia and is often associated with obesity. With diabetes and obesity incidence on the rise, it is imperative to develop novel therapeutics that will not only lower blood glucose levels, but also combat the associated obesity. The G protein-coupled receptors (GPCRs) for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon are emerging as targets to treat both hyperglycemia and obesity. GIP is rapidly released from intestinal K-cells following food intake and stimulates glucose-dependent insulin secretion from β-cells and the storage of fat in adipocytes. Both GIP receptor agonists and antagonists have been demonstrated to display therapeutic potential to treat diabetes and obesity. Similar to GIP, GLP-1 is released from intestinal L-cells following food intake and potentiates glucose-dependent insulin secretion from β-cells. In addition, GLP-1 reduces glucagon levels, suppresses gastric emptying and reduces food intake. As such, GLP-1 receptor agonists effectively lower blood glucose levels and reduce weight. Finally, glucagon is released from α-cells and raises blood glucose levels during the fasting state by stimulating gluconeogenesis and glycogenolysis in the liver. Thus, molecules that antagonize the glucagon receptor may be used to treat hyperglycemia. Given the structural similarity of these peptides and their receptors, molecules capable of agonizing or antagonizing combinations of these receptors have recently been suggested as even better therapeutics. Here we review the biology of GIP, GLP-1 and glucagon and examine the various therapeutic strategies to activate and antagonize the receptors of these peptides.
PubMed IF 13.5 내분비대사내과
10662012

제1저자 홍은실 · 교신저자 임수

, , , , , , , , ,
Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study.
Diabetes Obes Metab. 2012;14(9):795-802.

Abstract
AIM Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy.
METHODS We conducted a 24-week, randomized, active-competitor, parallel-group study in subjects with uncontrolled type 2 diabetes [haemoglobin A1c (HbA1c) = 7.5-11%] currently using insulin therapy. Subjects were randomly assigned to either the sitagliptin adding (100 mg daily, n = 70) or an insulin-increasing arm (≥ 10% at week 12 and ≥ 10% at week 24, n = 70) while continuing other medications.
RESULTS Average baseline HbA1c was 9.2% in both groups. HbA1c decreased more at 24 weeks in the sitagliptin adding than the insulin-increasing arm (-0.6 ± 0.1% vs. -0.2 ± 0.1%, p < 0.01). Insulin was increased by 25% at 24 weeks in the insulin-increasing group. Hypoglycaemic events were less common and less severe in sitagliptin adding arm than insulin-increasing arm (7.0 vs. 14.3 events per patient-year, p < 0.05). Weight was stable in the sitagliptin adding subjects (68.6 ± 11.6 vs. 68.1 ± 11.4 kg) but increased in the insulin-increasing subjects (66.2 ± 10.6 vs. 67.4 ± 9.7 kg, p < 0.05). Other adverse events occurred at similar rates in both arms.
CONCLUSIONS Compared to a 25% increase in insulin dose, adding sitagliptin to an insulin-based regimen was more effective at lowering HbA1c and associated with less hypoglycaemia and weight gain over 24 weeks.
CLINICAL TRIAL NUMBER NCT01100125.
PubMed IF 6.1 내분비대사내과
10652012

제1저자 조현재 · 교신저자 김효수

, , , , , , , , , , , , , , ,
Secondary sphere formation enhances the functionality of cardiac progenitor cells.
Mol Ther. 2012;20(9):1750-1766.

Abstract
Loss of cardiomyocytes impairs cardiac function after myocardial infarction (MI). Recent studies suggest that cardiac stem/progenitor cells could repair the damaged heart. However, cardiac progenitor cells are difficult to maintain in terms of purity and multipotency when propagated in two-dimensional culture systems. Here, we investigated a new strategy that enhances potency and enriches progenitor cells. We applied the repeated sphere formation strategy (cardiac explant → primary cardiosphere (CS) formation → sphere-derived cells (SDCs) in adherent culture condition → secondary CS formation by three-dimensional culture). Cells in secondary CS showed higher differentiation potentials than SDCs. When transplanted into the infarcted myocardium, secondary CSs engrafted robustly, improved left ventricular (LV) dysfunction, and reduced infarct sizes more than SDCs did. In addition to the cardiovascular differentiation of transplanted secondary CSs, robust vascular endothelial growth factor (VEGF) synthesis and secretion enhanced neovascularization in the infarcted myocardium. Microarray pathway analysis and blocking experiments using E-selectin knock-out hearts, specific chemicals, and small interfering RNAs (siRNAs) for each pathway revealed that E-selectin was indispensable to sphere initiation and ERK/Sp1/VEGF autoparacrine loop was responsible for sphere maturation. These results provide a simple strategy for enhancing cellular potency for cardiac repair. Furthermore, this strategy may be implemented to other types of stem/progenitor cell-based therapy.
PubMed IF 11.4 순환기내과
10642012

제1저자 이예나 · 교신저자 임수

, , , , , , , , , ,
Comparison of regional body composition and its relation with cardiometabolic risk between BMI-matched young and old subjects.
Atherosclerosis. 2012;224(1):258-65.

Abstract
OBJECTIVE Difference in regional body composition between young and old people may be related with differential cardiometabolic risks. We investigated regional body composition in BMI-matched young and old subjects to compare its relation with cardiometabolic risk.
METHODS We recruited 1:3 gender- and BMI-matched 86 young subjects (mean age 27.3 ± 2.9 years) and 258 older subjects (75.6 ± 8.2 years) from a community. Abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) and muscle area at mid-thigh level were evaluated by computed tomography. Fat depots in the gynoid area and lower extremity were measured by dual energy X-ray absorptiometry. Adiponectin, retinol binding protein-4 (RBP-4), and C-reactive protein (CRP) concentrations, pulse wave velocity (PWV) and ankle-brachial index (ABI) were measured for cardiometabolic risk.
RESULTS VAT was greater in older subjects while SAT was almost the same, resulting in twice higher VAT/SAT ratio in older men and women (1.03 ± 0.37 and 0.57 ± 0.18) than younger counterparts (0.55 ± 0.24 and 0.23 ± 0.23) (both P < 0.01). Fat mass in the gynoid area and lower extremity was smaller in older subjects than younger subjects. The VAT correlated with adiponectin level negatively and RBP-4 level positively while gynoid fat correlated with them in opposite direction. The CRP levels negatively correlated with mid-thigh muscle in older subjects. Older subjects had higher PWV and lower ABI compared to BMI-matched younger counterparts.
CONCLUSION In conclusion, older adults in this cohort had increased visceral fat and decreased gynoid and lower extremity fat, along with less muscle mass. These findings may help explain the worse cardiometabolic profiles in the elderly who have the same BMI as the young.
PubMed IF 7.1 내분비대사내과
10632012

제1저자 김보현, 이연재 · 교신저자 김원

, , , , , , ,
Efficacy of thymosin α-1 plus peginterferon α-2a combination therapy compared with peginterferon α-2a monotherapy in HBeAg-positive chronic hepatitis B: a prospective, multicenter, randomized, open-label study.
Scand J Gastroenterol. 2012;47(8-9):1048-55.

Abstract
OBJECTIVE Thymosin α-1 plus interferon α-2a offers superior efficacy over interferon α-2a alone in patients with chronic hepatitis B. The aim was to compare the antiviral efficacy of thymosin α-1 plus peginterferon α-2a and peginterferon α-2a alone in HBeAg-positive chronic hepatitis B patients.
MATERIALS AND METHODS HBeAg-positive CHB patients were enrolled in this prospective, randomized, open-label study. Fifty-one patients were assigned to either combination (26 patients; 180 μg of peginterferon α-2a weekly for 48 weeks and 1.6 mg of thymosin α-1 twice a week for the first 12 weeks) or monotherapy (25 patients; 180 μg of peginterferon α-2a weekly for 48 weeks) groups.
RESULTS The rates of the combined response, defined as HBeAg seroconversion, HBV DNA suppression, and normalization of serum ALT, were 4/26 (15.4%) and 3/25 (12.0%) for the combination group and the monotherapy group at the end of treatment (p = 0.725), and 6/26 (23.1%) and 5/25 (20.0%) at the end of follow-up (p = 0.789), respectively. Based on multiple logistic regression analysis, a >2 log₁₀ IU/mL reduction of HBV DNA at week 12 was identified as an independent predictor for combined response (OR, 9.72; 95% CI, 1.33-71.06; p = 0.025) at the end of follow-up. A lower pretreatment HBV DNA level (≤ 7 log(10) IU/mL) was another predictor for combined response (OR, 9.64; 95% CI, 1.23-75.32; p = 0.031). No significant differences in adverse events were observed.
CONCLUSIONS The short-term addition of thymosin α-1 was not superior to peginterferon α-2a alone in HBeAg-positive CHB patients on the basis of antiviral efficacy.
PubMed IF 1.8 소화기내과
10622012

제1저자 박경우 · 교신저자 김효수

, , , , , , , , ,
Amlodipine, clopidogrel and CYP3A5 genetic variability: effects on platelet reactivity and clinical outcomes after percutaneous coronary intervention.
Heart. 2012;98(18):1366-72.

Abstract
OBJECTIVE To test the effect of a loss-of-function variation of the cytochrome P450 (CYP) 3A5 on drug-drug interaction between amlodipine and clopidogrel. Amlodipine is a well-known inhibitor of CYP 3A4, an isoenzyme of CYP3A that activates clopidogrel. However, controversy exists regarding whether amlodipine adversely affects clopidogrel response and clinical outcome after percutaneous coronary intervention (PCI). In the presence of CYP3A4 inhibitors such as amlodipine, the genetic variation of CYP3A5, the isoenzyme responsible for the backup CYP3A activity, may play an important role in clopidogrel activation.
DESIGN Post hoc analysis of a prospectively enrolled cohort.
PATIENTS Patients enrolled in the CROSS-VERIFY cohort from June 2006 to June 2010, with successful genotyping of CYP3A5.
MAIN OUTCOME MEASURES The pharmacodynamic analysis end point was clopidogrel on-treatment platelet reactivity (OPR) and the clinical analysis end point was the composite of cardiac death, non-fatal myocardial infarction, ischaemic stroke and stent thrombosis at 12 months post-PCI.
RESULTS 1258 patients had successful genotyping and were categorised as CYP3A5 non-expressers (749 patients) and expressers (509 patients) according to the CYP3A5 genotype. Amlodipine users showed higher OPR versus non-users only in CYP3A5 non-expressers (249 ± 83 vs 228 ± 84 P2Y12 reaction units, p=0.013). These findings was corroborated by clinical outcomes, in which amlodipine users had a higher incidence of events compared with non-users only in CYP3A5 non-expressers (4.6% vs 0.6%, HR 7.731, CI 2.042 to 29.264, p=0.004).
CONCLUSIONS Treatment with amlodipine is associated with increased clopidogrel OPR and increased risk of thrombotic events after PCI, which is dependent on the CYP3A5 genetic status.
PubMed IF 4.4 순환기내과
10612012

제1저자 박영주, 이은경 · 교신저자 David D. Moore

, , , , ,
Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice.
Toxicol Appl Pharmacol. 2012;263(2):131-7.

Abstract
Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR-/- mice, but not in hypothyroid PXR-/- mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR-/- hypothyroid mice, and this induction was abolished in CAR-/- mice and in and CAR-/- PXR-/- double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR-/- mice and lowest in WT and PXR-/- mice. Hypothyroid WT or PXR-/- mice survived chronic CBZ treatment, but all hypothyroid CAR-/- and CAR-/- PXR-/- mice died, with CAR-/-PXR-/- mice surviving longer than CAR-/- mice (12.3±3.3 days vs. 6.3±2.1 days, p=0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge.
PubMed IF 3.6 내분비대사내과
10602012

제1저자 이세원 · 교신저자 김효수

, , , , , , , , , , , , ,
Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF.
EMBO Mol Med. 2012;4(9):924-38.

Abstract
Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and promoted mouse embryonic stem cells (mESCs) to differentiate into vascular-lineage. During spontaneous differentiation of embryoid bodies (EBs), hypoxic region was observed inside EB spheroids even under normoxic conditions. Indeed, hypoxia-primed EBs more efficiently differentiated into cells of vascular-lineage, than normoxic EBs did. We found that hypoxia suppressed Oct4 expression via direct binding of HIF-1 to reverse hypoxia-responsive elements (rHREs) in the Oct4 promoter. Furthermore, vascular endothelial growth factor (VEGF) was highly upregulated in hypoxia-primed EBs, which differentiated towards endothelial cells in the absence of exogenous VEGF. Interestingly, this differentiation was abolished by the HIF-1 or VEGF blocking. In vivo transplantation of hypoxia-primed EBs into mice ischemic limb elicited enhanced vessel differentiation. Collectively, our findings identify that hypoxia enhanced ESC differentiation by HIF-1-mediated inverse regulation of Oct4 and VEGF, which is a novel pathway to promote vascular-lineage differentiation.
PubMed IF 7.9 순환기내과
10592012

제1저자 방영주 · 교신저자 방영주

Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer.
J Clin Gastroenterol. 2012;46(8):637-48.

Abstract
In the past, patients with advanced or metastatic gastric or gastroesophageal junction cancer have had few treatment options and generally poor survival rates. The human epidermal growth factor receptor 2 (HER2) has been identified as a potential therapeutic target because of its overexpression or gene amplification in 6% to 35% of gastric or gastroesophageal junction cancers, although the methods of assessment and prognostic value of HER2 have been subject to debate. The phase III Trastuzumab for Gastric Cancer (ToGA) trial showed that adding the HER2-targeted humanized monoclonal antibody trastuzumab to chemotherapy significantly improves survival without negatively impacting quality of life in patients with advanced gastric or gastroesophageal junction cancer. As a result, trastuzumab is now the sole HER2-targeted therapy approved in several countries for this indication. The ToGA trial also demonstrated that patients who expressed higher levels of HER2 (determined by immunohistochemical screening) received the greatest benefit from trastuzumab therapy. This finding underlines the importance of accurate HER2 testing. Because of the unique characteristics of gastric cancer, a new gastric cancer-specific scoring system for HER2 expression was proposed during the ToGA trial. The aim of this review is to inform the gastroenterologist of the potential role of HER2-targeted therapy, to discuss the importance of accurate and reliable HER2 testing, and to discuss ongoing studies with HER2-targeted therapies that may have an impact on the future treatment of HER2-positive gastric cancer.
PubMed IF 2.7 혈액종양내과
10582012

제1저자 배현미 · 교신저자 이세훈

, , , , , , ,
Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis.
Lung Cancer. 2012;77(3):572-7.

Abstract
INTRODUCTION The skeletal system is one of the most common distant sites of metastatic non-small cell lung cancer (NSCLC) which may lead to skeletal-related event (SRE). The purpose of this study was to assess the frequency of SRE and the prognostic factors of overall survival (OS) in patients presenting bone metastasis in NSCLC.
METHODS Two hundred and twenty NSCLC patients with skeletal metastases at the time of diagnosis between January 2000 and August 2007 were investigated retrospectively.
RESULTS Forty-seven of 110 patients (43%) without a SRE at the time of diagnosis experienced their first SRE during the follow-up. Patients with squamous cell carcinoma had a 1.8-times higher risk of short OS [95% confidence interval (CI) 1.11-2.84, p=0.016], compared with patients with non-squamous cell carcinoma, and patients treated with EGFR TKIs achieved a 50% protective effect in OS compared with patients not treated with them (95% CI 0.32-0.80, p=0.004). Patients with ECOG performance status 0-1 and single bone metastasis had a 1.8-times (95% CI 1.13-2.60, p=0.003) and 2.4-times (95% CI 1.26-4.46, p=0.008) longer OS than patients with performance status≥2 and two or more bone metastases, respectively.
CONCLUSION Our study demonstrated that the frequency of SRE was common and single bone metastasis, good performance status (ECOG 0, 1), EGFR TKI treatment had good prognosis and histology of squamous cell carcinoma had bad prognosis.
PubMed IF 5.3 혈액종양내과
10572012

제1저자 김재성 · 교신저자 방영주

, , , , , , , , ,
Phase II clinical trial of induction chemotherapy with fixed dose rate gemcitabine and cisplatin followed by concurrent chemoradiotherapy with capecitabine for locally advanced pancreatic cancer.
Cancer Chemother Pharmacol. 2012;70(3):381-9.

Abstract
PURPOSE 5-FU-based concurrent chemoradiotherapy (CRT) has been the mainstay of treatment for locally advanced pancreatic cancer (LAPC) for the past decades, but the prognosis remains dismal.
METHODS Patients with pathologically confirmed LAPC of the pancreas, an ECOG PS of 0-2 and no prior chemo- or radiotherapy were eligible. The treatment consisted of induction (IND) chemotherapy with a fixed dose rate gemcitabine 1,000 mg/m(2) on days 1 and 8 and CDDP 60 mg/m(2) on day 1 every 3 weeks for 3 cycles. Subsequently, the patients without progression received CRT of 55.8 Gy/31 fractions with capecitabine 650 mg/m(2) twice daily. Gemcitabine was given for 3 cycles after CRT. The primary endpoint was time to progression.
RESULTS Thirty-seven patients with LAPC were enrolled. Median age was 55 years, there were 20 males and 17 females, and ECOG PS was 0 in 6 and 1 in 31. Three patients (9.7 %) achieved partial responses after IND chemotherapy. Twenty-five patients received CRT with a mean radiation dose of 54.0 Gy, with one additional patient achieving a partial response. The median time to progression was 7.2 months (95 % CI, 4.4-10), and the median overall survival was 16.8 months (95 % CI, 12.9-20.7). The grade 3/4 toxicities included neutropenia (29 %/6.5 %), thrombocytopenia (3.2 %/0 %) and anemia (9.7 %/0 %) during the IND phase and grade 3 neutropenia and diarrhea occurring in one and two patients during CRT phase.
CONCLUSIONS IND chemotherapy with gemcitabine and cisplatin followed by CRT with capecitabine and maintenance gemcitabine was well tolerated and exhibited promising efficacy for the treatment of LAPC.
PubMed IF 2.5 혈액종양내과
10562012

제1저자 오세원 · 교신저자 진호준

, , , , , ,
Clinical implications of pathologic diagnosis and classification for diabetic nephropathy.
Diabetes Res Clin Pract. 2012;97(3):418-24.

Abstract
AIM The usefulness of renal pathologic diagnosis in type II DM (diabetes mellitus) remains debate.
METHODS We grouped the pathologic diagnoses as pure DN (diabetic nephropathy), NDRD (non-diabetic renal disease), and NDRD mixed with DN (Mixed). We classified pure DN as the criteria suggested by Tervaert. We compared the accuracy of clinical parameters to predict DN and usefulness of pathology to predict renal prognosis.
RESULTS Among 126 enrolled patients, there were 50 pure DN, 65 NDRN, and 11 Mixed. The sensitivity and specificity for predicting DN with the presence of retinopathy were 77.8-73.6% and, with a cut-off value of 7.5 years of diabetic duration, the sensitivity and specificity were 64.5-67.2%. ESRD (end stage renal disease) occurred in 44.0% of DN, 18.2% of Mixed, and 12.3% of NDRD (p<0.001). Among pure DN, Class IV showed the lowest estimated glomerular filtration rate (eGFR). We estimated the 5-year renal survival rate as 100.0% in Classes I and IIa, 75.0% in Class IIb, 66.7% in Class III, and 38.1% in Class IV (p=0.002).
CONCLUSIONS Nephropathy of type II DM was diverse and could not be completely predicted by clinical parameters. The renal pathologic diagnosis was a good predictor for renal prognosis in type II DM.
PubMed IF 4.6 신장내과
10552012

제1저자 윤영광 · 교신저자 임석아/방영주

, , , , , , , , , , ,
Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancer.
Cancer Lett. 2012;321(2):128-36.

Abstract
We evaluated the effects of sunitinib monotherapy and in combination with cisplatin in human gastric cancer cell lines. Sunitinib showed antiproliferative effect in gastric cancer cells line with high PDGFRA expression. Knockdown of PDGFRA showed that sunitinib sensitivity was correlated with the basal expression of PDGFRA. Synergistic growth inhibitory activity in combination with cisplatin was identified. We further explored how sunitinib potentiated the activity of cisplatin. We found that sunitinib treatment resulted in the down-regulation of ERCC1 expression via the modulation of PDGFRA expression in gastric cancer cells. The effect was verified via SNU484 xenograft model. Our data support the rationale of clinical trial using sunitinib in combination of cisplatin in gastric cancer.
PubMed IF 11.8 혈액종양내과
10542012

제1저자 김정연, 이은영 · 교신저자 송영욱

, , , , , ,
Atorvastatin inhibits osteoclastogenesis by decreasing the expression of RANKL in the synoviocytes of rheumatoid arthritis.
Arthritis Res Ther. 2012;14(4):R187.

Abstract
INTRODUCTION Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have antiinflammatory and/or immunomodulatory effects and prophylactic and therapeutic effects in collagen-induced arthritis, an experimental model of rheumatoid arthritis (RA). The authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibits osteoclastogenesis.
METHODS FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of tumor necrosis factor-α (TNF-α) with or without atorvastatin. RANKL expressions were assayed with Western blotting and enzyme-linked immunosorbent assay. RANKL, RANK, and OPG expression were assayed with reverse transcription-polymerase chain reaction (RT-PCR). Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs.
RESULTS Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose-dependent manner, and the suppression of RANKL was prevented by mevalonate. However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14⁺ cells. Conversely, atorvastatin suppressed TNF-α-induced p38 phosphorylation in RA FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs.
CONCLUSION These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.
PubMed IF 5.4 류마티스내과
10532012

제1저자 김지원 · 교신저자 임석아

, , , , , , , , , , , , ,
ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy.
Oncology. 2012;83(4):218-27.

Abstract
OBJECTIVE The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy.
METHODS Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F) and then correlated them with the response rate, progression-free survival (PFS), overall survival (OS), and adverse events of patients.
RESULTS A total of 57 women were analyzed. The median age was 46 years (range 27-72). ABCB1 2677T carriers had a longer PFS (p = 0.037) along with a tendency toward a longer OS (p = 0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p = 0.039) along with a tendency toward a shorter OS (p = 0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p = 0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with response rate, PFS, and OS.
CONCLUSIONS Our data support that ABCB1 polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms could not predict treatment outcomes.
PubMed IF 1.9 혈액종양내과
10522012

제1저자 김미정 · 교신저자 이근욱

, , , , , , , , , , , ,
Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer.
BMC Cancer. 2012;12:347.

Abstract
BACKGROUND We evaluated the association between a KRAS mutational status and various clinicopathologic features including the metastatic pattern in patients with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed.
METHODS The KRAS mutational status in codons 12, 13, and 61 from formalin-fixed sections of both primary tumors and related metastases was determined by sequencing analysis. One hundred forty-three Korean patients with MRCRC with available tissues (resection or biopsy) from both primary tumors and related metastatic sites were consecutively enrolled.
RESULTS The KRAS mutation rate was 52.4% (75/143) when considering both the primary and metastatic sites. When the relationship between the KRAS status and initial metastatic sites at the time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the initial metastatic site in patients with the KRAS mutation than in patients without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs. 70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025) were less frequent as the initial metastatic organ in patients with the KRAS mutation than in patients without the KRAS mutation. The discordance rate of KRAS mutational status between primary and paired metastatic sites other than the lung was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate was significantly higher in matched lung metastases [32.4% (12/37)] than in other matched metastatic organs (P = 0.005).
CONCLUSIONS Organs initially involved by distant metastasis were different according to the KRAS mutational status in MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at metastatic sites other than the lung was generally high compared with primary tumor sites; however, lung metastasis had a high rate of KRAS discordance (32.4%).
PubMed IF 4.1 혈액종양내과
10512012

제1저자 이준구 · 교신저자 김태민

, , , , , , , , , , ,
Differential sensitivities to tyrosine kinase inhibitors in NSCLC harboring EGFR mutation and ALK translocation.
Lung Cancer. 2012;77(2):460-3.

Abstract
Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer (NSCLC) are mutually exclusive. However, several exceptional cases harboring both genetic alterations have been reported. In this study, a total of 444 patients with lung adenocarcinoma were examined for their EGFR and ALK status at Seoul National University Hospital between July 2008 and September 2011. EGFR mutations and ALK translocations were detected in 228 (51.4%) and 34 (7.7%) patients, respectively. Four patients (0.9%) had both genetic alterations and three underwent curative surgery. One patient who received both EGFR tyrosine kinase and ALK inhibitors, separately showed an objective response to the ALK inhibitor alone. Considering our and previous studies, patients harboring both EGFR mutation and ALK translocation showed differential sensitivities to both targeted therapies, suggesting a variable dependence on EGFR and ALK oncogenes.
PubMed IF 5.3 혈액종양내과
10502012

제1저자 윤순호 · 교신저자 임재준

, ,
Impact of sputum gross appearance and volume on smear positivity of pulmonary tuberculosis: a prospective cohort study.
BMC Infect Dis. 2012;12:172.

Abstract
BACKGROUND Although checking specimen quality upon sputum collection for acid-fast smear of suspected tuberculosis (TB) cases is recommended, this procedure is based on expert opinion. The purpose of this study was to elucidate the impact of sputum gross appearance and volume on smear positivity among patients with suspected pulmonary TB, according to sex.
METHODS From November 2010 through June 2011, we enrolled consecutive patients suspected to have active pulmonary TB. The association of sputum gross appearance and volume with smear positivity, along with other variables possibly affecting smear positivity such as symptoms, disease extent, and cavity on chest radiograph, were investigated.
RESULTS Among 2,439 patients undergoing TB examination, 170 (113 men, 57 women) with active pulmonary TB were enrolled. They submitted 492 sputa. There were 73 smear-positive patients (42.9%) and 164 smear-positive sputa (33.3%). While gross appearance was associated with smear positivity in both sexes (purulent or blood-tinged sputum (rather than mucoid sputum or saliva); odds ratio (OR), 2.05, 95% confidence interval (CI), 1.21-3.47 in men; OR, 2.78, 95% CI, 1.23-6.26 in women), the amount of sputum specimens was associated with smear positivity in only female patients (≥4 ml versus <4 ml; OR, 4.96, 95% CI, 1.98-12.37).
CONCLUSIONS Sputum gross appearance and volume were associated with smear positivity. A volume of 4 ml seems to be the the minimum sputum volume acceptable for smear microscopy in females suspected of TB. Those suspected of TB should be encouraged to expectorate grossly qualified sputum specimens.
PubMed IF 3.2 호흡기내과
10492012

제1저자 김광일 · 교신저자 진호준

, , , , , , , , ,
CRP level and HDL cholesterol concentration jointly predict mortality in a Korean population.
Am J Med. 2012;125(8):787-95.e4.

Abstract
BACKGROUND C-reactive protein (CRP) and high-density lipoprotein (HDL) cholesterol are well-known cardiovascular predictors. However, the joint effect of these parameters on long-term mortality has not been established.
METHODS We studied a total of 92,500 subjects older than 20 years who underwent routine health examination at the three health care centers affiliated with Seoul National University. High-sensitivity CRP and the lipid profile were obtained at baseline. Subjects were followed for a median of 45.5 months. Mortality data were obtained from the National Statistics Office of Korea.
RESULTS There were 649 deaths (0.7%) during the follow-up. The leading cause of death was cancer. The subjects who died were significantly older, had a male predominance, and had increased levels of inflammatory markers. A significant mortality difference was identified according to the CRP and HDL cholesterol levels. Considering both parameters jointly, subjects with a CRP ≥1.4 mg/L (highest quartile) and HDL cholesterol <45 mg/dL (lowest quartile) were at the highest risk for all-cause mortality, even after adjusting for covariates (hazard ratio 2.29, 95% confidence interval, 1.83~2.87). After matching on the propensity score, 6304 subjects with a high CRP and low HDL cholesterol were at high risk of death (hazard ratio 2.52, 95% confidence interval, 1.59~4.01). Interestingly, the joint effect of CRP and HDL cholesterol was observed for cardiovascular as well as cancer-related mortality prediction.
CONCLUSIONS Elevated CRP and low HDL cholesterol jointly contribute to the prediction of all-cause, cancer, and cardiovascular mortality in Koreans. The interactive relationship between them in mediating inflammatory processes might explain these results.
PubMed IF 6 순환기내과

서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.