SCI 발표논문

2012년 229편

1992012

제1저자 구본권 · 교신저자 김효수

, , , , , , , , , , , , , , ,
Assessment of clinical, electrocardiographic, and physiological relevance of diagonal branch in left anterior descending coronary artery bifurcation lesions.
JACC Cardiovasc Interv. 2012;5(11):1126-32.

Abstract
OBJECTIVES This study sought to investigate the clinical, electrocardiographic, and physiological relevance of main and side branches in coronary bifurcation lesions.
BACKGROUND Discrepancy exists between stenosis severity and clinical outcomes in bifurcation lesions. However, its mechanism has not been fully evaluated yet.
METHODS Sixty-five patients with left anterior descending coronary artery (LAD) bifurcation lesions were prospectively enrolled. Chest pain and 12-lead electrocardiogram were assessed after 1-min occlusion of coronary flow and coronary wedge pressure (Pw) was measured using a pressure wire.
RESULTS ST-segment elevation was more frequent during LAD occlusion (92%) than during diagonal branch occlusion (37%) (p < 0.001). Pain score was also higher with the occlusion of LAD than with the diagonal branch (p < 0.001). However, both Pw and Pw/aortic pressure (Pa) were lower in the LAD than in diagonal branches (Pw: 21.0 ± 6.5 vs. 26.7 ± 9.4, p < 0.0001; Pw/Pa: 0.22 ± 0.07 vs. 0.27 ± 0.08, p = 0.001). The corrected QT interval was prolonged with LAD occlusion (435.0 ± 39.6 ms to 454.0 ± 45.4 ms, p < 0.0001) but not with diagonal branch occlusion. There was no difference in vessel size between the diagonal branches with and without ST-segment elevation during occlusion. Positive and negative predictive values of vessel size (≥2.5 mm) to determine the presence of ST-segment elevation were 48% and 72%, respectively.
CONCLUSIONS Diagonal branch occlusion caused fewer anginas, less electrocardiogram change, less arrhythmogenic potential, and higher Pw than did a LAD occlusion. These differences seem to be the main mechanism explaining why aggressive treatment for side branches has not translated into clinical benefit in coronary bifurcation lesions. (Comparison Between Main Branch and Side Branch Vessels; NCT01046409).
PubMed IF 12.7 순환기내과
1982012

제1저자 윤연이 · 교신저자 구본권

, , , , , , , , , , , , , ,
Noninvasive diagnosis of ischemia-causing coronary stenosis using CT angiography: diagnostic value of transluminal attenuation gradient and fractional flow reserve computed from coronary CT angiography compared to invasively measured fractional flow reserve.
JACC Cardiovasc Imaging. 2012;5(11):1088-96.

Abstract
OBJECTIVES The aim of this study was to compare the diagnostic performance of coronary computed tomography angiography (CCTA)-derived computed fractional flow reserve (FFR(CT)) and transluminal attenuation gradient (TAG) for the diagnosis of lesion-specific ischemia.
BACKGROUND Although CCTA is commonly used to detect coronary artery disease (CAD), it cannot reliably assess the functional significance of CAD. Novel technologies based on CCTA were developed to integrate anatomical and functional assessment of CAD; however, the diagnostic performance of these methods has never been compared.
METHODS Fifty-three consecutive patients who underwent CCTA and coronary angiography with FFR measurement were included. Independent core laboratories determined CAD severity by CCTA, TAG, and FFR(CT). The TAG was defined as the linear regression coefficient between intraluminal radiological attenuation and length from the ostium; FFR(CT) was computed from CCTA data using computational fluid dynamics technology.
RESULTS Among 82 vessels, 32 lesions (39%) had ischemia by invasive FFR (FFR ≤0.80). Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of TAG (≤ -0.654 HU/mm) for detection of ischemia were 38%, 88%, 67%, 69%, 3.13, and 0.71, respectively; and those of FFR(CT) were 81%, 94%, 90%, 89%, 13.54, and 0.20, respectively. Receiver-operating characteristic curve analysis showed a significantly larger area under the curve (AUC) for FFR(CT) (0.94) compared to that for TAG (0.63, p < 0.001) and CCTA stenosis (0.73, p < 0.001). In vessels with noncalcified plaque or partially calcified plaque, FFR(CT) showed a larger AUC (0.94) compared to that of TAG (0.63, p < 0.001) or CCTA stenosis (0.70, p < 0.001). In vessels with calcified plaque, AUC of FFR(CT) (0.92) was not statistically larger than that of TAG (0.75, p = 0.168) or CCTA stenosis (0.80, p = 0.195).
CONCLUSIONS Noninvasive FFR computed from CCTA provides better diagnostic performance for the diagnosis of lesion-specific ischemia compared to CCTA stenosis and TAG.
PubMed IF 19 순환기내과
1972012

제1저자 김인경, 김병관 · 교신저자 김원

, , , , , ,
Clinical prediction of failure of Lamivudine prophylaxis for hepatitis B virus-infected patients undergoing cytotoxic chemotherapy for malignancy.
Antimicrob Agents Chemother. 2012;56(11):5511-9.

Abstract
Although lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray's model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94; P = 0.0063) and the use of rituximab (HR, 3.19; P = 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90; P = 0.007), liver cirrhosis (HR, 10.4; P = 0.002), and distant metastasis (HR, 5.14; P = 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance.
PubMed IF 4.2 소화기내과
1962012

제1저자 박효은 · 교신저자 최수연

, , ,
Cardio-ankle vascular index reflects coronary atherosclerosis in patients with abnormal glucose metabolism: assessment with 256 slice multi-detector computed tomography.
J Cardiol. 2012;60(5):372-6.

Abstract
OBJECTIVE The association between arterial stiffness, as measured by the cardio-ankle vascular index (CAVI), and coronary atherosclerosis, using coronary artery computed tomography (CT), was investigated in the asymptomatic general population, with special interest in subjects with abnormal glucose metabolism.
PATIENTS AND METHODS A total of 158 normoglycemic subjects and 373 subjects with abnormal glucose metabolism were evaluated. CAVI was assessed in relation with coronary artery calcium score (CACS) and degree of stenosis detected by CT.
RESULTS The association of CAVI with other clinical parameters was evaluated in patients with abnormal glucose metabolism. CAVI was higher, and CACS and the degree of coronary artery stenosis were both greater compared to the normal group. CAVI showed a significant correlation with CACS and the degree of stenosis (r=0.167, p=0.001; r=0.182, p<0.001, respectively). The cut-off level of CAVI from receiver operating characteristic (ROC) curve was ≥ 8.0 for predicting ≥ 50% coronary artery stenosis (area under the curve 0.713, sensitivity 69%, and specificity 61%). CAVI ≥ 8.0 was independently associated with significant coronary artery stenosis, even after adjusting for age, sex, and presence of hypertension and hypercholesterolemia (odds ratio 3.143, 95% confidence interval 1.004-9.842, p=0.049).
CONCLUSION CAVI is an independent parameter which reflects coronary atherosclerosis in patients with abnormal glucose metabolism. CAVI can be a useful tool not only to assess arterial stiffness, but also to evaluate the risk for subclinical coronary atherosclerosis in asymptomatic patients.
PubMed IF 3.5 순환기내과
1952012

제1저자 강현재 · 교신저자 김효수

, , , , , , , , , , , , , , , , ,
Effects of celecoxib on restenosis after coronary intervention and evolution of atherosclerosis (Mini-COREA) trial: celecoxib, a double-edged sword for patients with angina.
Eur Heart J. 2012;33(21):2653-61.

Abstract
AIMS In the previous COREA-TAXUS trial, a 6-month adjunctive use of celecoxib reduced target-lesion revascularization (TLR) without increased thrombotic risk. We aimed to confirm the effects of 3-month celecoxib in patients receiving drug-eluting stent (DES) implantation in the larger prospective, randomized trial.
METHODS AND RESULTS Patients (n = 909) treated for native coronary lesions were randomized into four groups: the control or the celecoxib group with stratification by stents: paclitaxel-eluting stent (PES) or zotarolimus-eluting stent (ZES). In the celecoxib group, 200 mg of celecoxib was given twice daily for 3 months after the procedure. The primary endpoint was in-stent late loss (LL) at 6 months. In-stent LL was significantly lower in the celecoxib group than the control group (0.64 ± 0.54 vs. 0.55 ± 0.47 mm, P = 0.02). The trend of LL reduction in the celecoxib group was maintained in the ZES and PES subgroups, although it did not reach statistical significance. There was a trend towards the reduced clinically driven TLR in the celecoxib group (5.7 vs. 3.2%, log-rank P = 0.09), but adverse cardiac events rate did not differ between the two groups (composite of cardiac death, non-fatal myocardial infarction, and TLR; 8.6 vs. 7.7%, log-rank P = 0.84). Non-fatal myocardial infarction and cardiac death occurred in 1.6% of the patients in the celecoxib group when compared with 0.2% in the control group (log-rank P = 0.03).
CONCLUSION Three-month adjunctive celecoxib would be useful to reduce LL of DES. However, this study may raise the concern about increased thrombotic risk with celecoxib even in patients receiving dual anti-platelet therapy.
PubMed IF 45.3 순환기내과
1942012

제1저자 장은선 · 교신저자 정숙향

, , , , , , , , , , ,
Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study.
BMC Gastroenterol. 2012;12:145.

Abstract
BACKGROUND Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees.
METHODS We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits.
RESULTS Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking.
CONCLUSIONS Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.
PubMed IF 3.2 소화기내과
1932012

제1저자 이반석/황진혁 · 교신저자 이상협

, , , , , , , , ,
Older adults with biliary tract cancer: treatment and prognosis.
J Am Geriatr Soc. 2012;60(10):1862-71.

Abstract
OBJECTIVES To compare survival in older (≥65) and younger (<65) individuals with biliary tract cancer (BTC) and to determine whether treatment efficacy varies according to age.
DESIGN Retrospective cohort study and nested case-control study.
SETTING Tertiary referral center in Korea.
PARTICIPANTS Five hundred thirty-one individuals diagnosed with BTC from 2003 to 2011.
MEASUREMENTS Demographic and clinical characteristics of 326 older (≥65) and 205 younger (<65) individuals with BTC were compared. Differences in survival were also assessed after matching according to propensity score.
RESULTS There were no significant differences in sex, symptoms and signs, tumor histology, stage, or surgery between the two groups, but older participants had more comorbidities and poorer performance status and underwent less chemotherapy and radiotherapy (P < .05). Survival of the two groups was compared. After adjustment for baseline characteristics using the propensity score method, survival was still comparable (P = .72). When survival of older participants in the treatment group (TG, those who underwent surgery, chemotherapy, or radiotherapy) was compared with that of those in the supportive care group (SCG, those who received only supportive care), those in the TG had a longer survival time than those in the SCG (P < .001). This result was confirmed in the propensity analysis (including individuals undergoing surgery, P < .001; excluding individuals undergoing surgery, P < .001). In the multivariable Cox analysis, surgical resection and chemotherapy were significantly associated with longer survival, and advanced tumor stage, lower baseline serum albumin level, and greater comorbidity were found to significantly predict poor survival. Age was not associated with survival in individuals with BTC (P = .33).
CONCLUSION Older age was not associated with poor survival in BTC, and treated individuals had longer survival in the older BTC population. Therefore, treatment should not be restricted on the basis of age.
PubMed IF 4.6 소화기내과
1922012

제1저자 정영희 · 교신저자 송경호

, , , , , , , , , , , , , , ,
Differences in characteristics between healthcare-associated and community-acquired infection in community-onset Klebsiella pneumoniae bloodstream infection in Korea.
BMC Infect Dis. 2012;12:239.

Abstract
BACKGROUND Healthcare-associated (HCA) infection has emerged as a new epidemiological category. The aim of this study was to evaluate the impact of HCA infection on mortality in community-onset Klebsiella pneumoniae bloodstream infection (KpBSI).
METHODS We conducted a retrospective study in two tertiary-care hospitals over a 6-year period. All adult patients with KpBSI within 48 hours of admission were enrolled. We compared the clinical characteristics of HCA and community-acquired (CA) infection, and analyzed risk factors for mortality in patients with community-onset KpBSI.
RESULTS Of 553 patients with community-onset KpBSI, 313 (57%) were classified as HCA- KpBSI and 240 (43%) as CA-KpBSI. In patients with HCA-KpBSI, the severity of the underlying diseases was higher than in patients with CA-KpBSI. Overall the most common site of infection was the pancreatobiliary tract. Liver abscess was more common in CA-KpBSI, whereas peritonitis and primary bacteremia were more common in HCA-KpBSI. Isolates not susceptible to extended-spectrum cephalosporin were more common in HCA- KpBSI than in CA-KpBSI (9% [29/313] vs. 3% [8/240]; p = 0.006). Overall 30-day mortality rate was significantly higher in HCA-KpBSI than in CA-KpBSI (22% [70/313] vs. 11% [27/240]; p = 0.001). In multivariate analysis, high Charlson's weighted index of co-morbidity, high Pitt bacteremia score, neutropenia, polymicrobial infection and inappropriate empirical antimicrobial therapy were significant risk factors for 30-day mortality.
CONCLUSIONS HCA-KpBSI in community-onset KpBSI has distinctive characteristics and has a poorer prognosis than CA-KpBSI, but HCA infection was not an independent risk factor for 30-day mortality.
PubMed IF 3.2 감염내과
1912012

제1저자 강해연 · 교신저자 김상균

, , , , ,
Effect of Helicobacter pylori eradication according to the IL-8-251 polymorphism in Koreans.
J Korean Med Sci. 2012;27(10):1202-7.

Abstract
Previous studies suggested that polymorphisms of proinflammatory cytokine genes are important host genetic factors in Helicobacter pylori infection. The present study evaluated whether IL-8-251 polymorphism affected H. pylori eradication rate and to investigate the effect of H. pylori eradication on angiogenesis and the inflammatory process according to the IL-8-251 polymorphism. A total of 250 H. pylori-positive patients treated by endoscopic resection of the gastric neoplasm were classified into 3 groups (134 H. pylori-eradicated group, 19 H. pylori-eradication failure group, and 97 H. pylori-infected group). H. pylori status, histology, and angiogenic factor levels were evaluated at baseline, 6 months, and 18 months. H. pylori eradication rate was 92.9% in AA genotype, 85.7% in AT genotype and 88.4% in TT genotype (P value = 0.731). Elevated IL-8 and matrix metalloproteinase-9 concentrations in H. pylori-infected gastric mucosa were reversible by successful eradication of H. pylori, independent of the IL-8-251 polymorphism. It is suggested that elevated IL-8 and MMP-9 concentrations in H. pylori-infected gastric mucosa are altered significantly after successful eradication and these conditions continue for 18 months. However, IL-8-251 polymorphism does not affect H. pylori eradication rate and the sequential changes of related angiogenic factors after H. pylori eradication in Koreans.
PubMed IF 3.2 소화기내과
1902012

제1저자 장제현 · 교신저자 김세중

, , , , , , , ,
Early start of dialysis has no survival benefit in end-stage renal disease patients.
J Korean Med Sci. 2012;27(10):1177-81.

Abstract
The timing for dialysis initiationis still debated. The aim of this study was to compare mortality rates, using a propensity-score approach, in dialysis patients with early or late starts. From January 2000 to June 2009, incident adult patients (n = 836) starting dialysis for end-stage renal disease (ESRD) were enrolled. The patients were assigned to either an early- or late-start group depending on the initiation time of the dialysis. After propensity-score-basedmatching, 450 patients remained. At the initiation of dialysis, the mean estimated glomerular filtration rate (eGFR) was 11.1 mL/min/1.73 m(2) in the early-start group compared with 6.1 mL/min/1.73 m(2) in the late-start group. There were no significant differences in survival between the patients in the early- and late-start groups (Log rank tests P = 0.172). A higher overall mortality risk was observed in the early-start group than in the late-start group for the patients aged ≥ 70 yr (hazard ratio [HR]: 3.29; P = 0.048) and/or who had albumin levels ≥ 3.5 g/dL (HR: 2.53; P = 0.046). The survival of the ESRD patients was comparable between the patients in the early and late-start groups. The time to initiate dialysis should be determined based on clinical findings as well as the eGFR.
PubMed IF 3.2 신장내과
1892012

제1저자 김상완 · 교신저자 Henry M Kronenberg

, , , , , , , ,
Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts.
J Bone Miner Res. 2012;27(10):2075-84.

Abstract
Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing the number of osteoblasts. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 3, 5, 7, 14, and 21. The animals were euthanized on postnatal day 23, 33, or 43 (2, 12, or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1-34, 80 µg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of the calvaria and the tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal-associated chromogen particles in thin cells prior to PTH administration and in cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo.
PubMed IF 6.5 내분비대사내과
1882012

제1저자 송우정 · 교신저자 장윤석

, , , , , , , , , , ,
Association between obesity and asthma in the elderly population: potential roles of abdominal subcutaneous adiposity and sarcopenia.
Ann Allergy Asthma Immunol. 2012;109(4):243-8.

Abstract
BACKGROUND Obesity is a significant risk factor for asthma; however, the association of asthma with obesity has rarely been studied in the elderly population. The role of central obesity has been suggested as a link between the 2 entities but has not been comprehensively studied in elderly populations.
OBJECTIVE To investigate the mechanisms of association between obesity and asthma in the elderly population.
METHODS This cross-sectional analysis included 994 participants (aged ≥65 years) in the Korean Longitudinal Study on Health and Aging. Asthma was defined by using questionnaires. Spirometry and chest radiography were performed to exclude asthma-mimicking conditions. Measurements of abdominal subcutaneous and visceral fat were calculated by computed tomography of the abdomen, and regional body compositions were measured by dual energy X-ray absorptiometry. Biochemical parameters were also measured.
RESULTS The prevalence of asthma was 5.4%. The study population had a mean body mass index (BMI) of 24.0. Multivariate logistic regression tests revealed that the risk of asthma increased in proportion to an increase in BMI or abdominal subcutaneous adiposity. However, no association was found with visceral adiposity, serum adiponectin levels, or serum vitamin D levels. The dual energy X-ray absorptiometry-measured appendicular fat-free mass index was inversely related to asthma among patients with a BMI of 25.0 or greater.
CONCLUSION Our findings suggest that the relationships between obesity and asthma in the elderly population may be mediated by factors such as abdominal subcutaneous adiposity and sarcopenia. These associations warrant further investigations to identify their potential roles.
PubMed IF 7.1 알레르기내과
1872012

제1저자 정우영, 강지훈 · 교신저자 조영석

, , , , , , , , , , , , ,
A randomized, prospective, two-center comparison of sirolimus-eluting stent and zotarolimus-eluting stent in acute ST-elevation myocardial infarction: the SEZE trial.
Chin Med J (Engl). 2012;125(19):3373-81.

Abstract
BACKGROUND The zotarolimus-eluting stent has shown larger in-stent late lumen loss compared to sirolimus-eluting stents in previous studies. However, this has not been thoroughly evaluated in ST elevation myocardial infarction.
METHODS This was a prospective, randomized, controlled trial evaluating angiographic outcomes in patients presenting with ST elevation myocardial infarction, treated with zotarolimus-eluting stents or sirolimus-eluting stents. From March 2007 to February 2009, 122 patients were randomized to zotarolimus-eluting stents or sirolimus-eluting stents in a 1:1 fashion. The primary endpoint was 9-month in-stent late lumen loss confirmed by coronary angiography, and secondary endpoints were percent diameter stenosis, binary restenosis rate, major adverse cardiac events (a composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization), and late-acquired incomplete stent apposition.
RESULTS Angiographic in-stent late lumen loss was significantly higher in the zotarolimus-eluting stent group compared to the sirolimus-eluting stent group ((0.49 ± 0.65) mm vs. (0.10 ± 0.46) mm, P = 0.001). Percent diameter stenosis at 9-month follow-up was also larger in the zotarolimus-eluting stent group ((30.0 ± 17.9)% vs. (17.6 ± 14.0)%, P < 0.001). In-segment analysis showed similar findings. There were no significant differences in binary restenosis rate, major adverse cardiac events, and late-acquired incomplete stent apposition.
CONCLUSIONS Compared to sirolimus-eluting stents, the zotarolimus-eluting stent is associated with significantly higher in-stent late lumen loss at 9-month angiographic follow-up in the treatment of ST elevation myocardial infarction. Although there was no significant difference in 1-year clinical outcomes, the clinical implication of increased late lumen loss should be further studied.
PubMed IF 9.1 순환기내과
1862012

제1저자 이은주 · 교신저자 김효수

, , , , , , , ,
Regeneration of peripheral nerves by transplanted sphere of human mesenchymal stem cells derived from embryonic stem cells.
Biomaterials. 2012;33(29):7039-46.

Abstract
In cell therapy, the most important factor for therapeutic efficacy is the stable supply of cells with best engraftment efficiency. To meet this requirement, we have developed a culture strategy such as three-dimensional sphere of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in serum-free medium. To investigate the in vivo therapeutic efficacy of hESC-MSC spheres in nerve injury model, we transected the sciatic nerve in athymic nude mice and created a 2-mm gap. Transplantation of hESC-MSC as sphere repaired the injured nerve significantly better than transplantation of hESC-MSC as suspended single cells in regard to 1) nerve conduction (sphere; 28.81 ± 3.55 vs. single cells; 18.04 ± 2.10, p < 0.05) and 2) susceptibility of nerve stimulation at low voltage (sphere; 0.38 ± 0.08 vs. single cells; 0.66 ± 0.11, p < 0.05) at 8 weeks. Recovery after sphere transplantation was near-complete when compared with the data of normal control (sphere 28.81 ± 3.55 vs normal 32.62 ± 2.85 in nerve conduction : sphere 0.38 ± 0.08 vs normal 0.36 ± 0.67 in susceptibility of nerve stimulation, no significant difference, respectively). Recovery in function of the injured nerve was well corroborated by the histologic evidence of regenerated nerve. In the mechanistic analysis, the supernatant of sphere-forming hESC-MSC contains hepatocyte growth factor and insulin-like growth factor-binding protein-1 significantly more than the supernatant of the single cells of hESC-MSC has, which might be the key factors for the improved engraftment efficiency and greater regeneration of injured peripheral nerve.
PubMed IF 13.6 순환기내과
1852012

제1저자 방영주 · 교신저자 방영주

Treatment of ALK-positive non-small cell lung cancer.
Arch Pathol Lab Med. 2012;136(10):1201-4.

Abstract
Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC). This approval came within just 4 years of the discovery of rearrangements in the ALK gene in a subset of patients with NSCLC. Oral crizotinib 250 mg twice daily showed excellent efficacy in patients with advanced ALK-positive NSCLC, with objective response rates of 61% and 51% in ongoing phase I and II studies, respectively. Objective response rates of current standard, single-agent, second-line therapies are less than 10%. Median progression-free survival was 10 months (95% confidence interval, 8.2-14.7) in the phase I study expanded cohort and has yet to be reached in the phase II study; progression-free survival with current therapies is less than 3 months. Crizotinib was well tolerated; grade 1/2 gastrointestinal toxicity and visual disturbances were the most common adverse events. Patients in the phase II study reported improvements in fatigue, dyspnea, and cough, based on quality of life assessments. Phase III studies investigating crizotinib for the first- and second-line treatment of advanced ALK-positive NSCLC, versus current standards of care, are ongoing. Crizotinib represents a new standard of care for patients with ALK-positive NSCLC and highlights the importance of the role of the pathologist, as molecular profiling becomes a part of initial workups for newly diagnosed patients with NSCLC. This approach will ensure effective individualized treatment for patients with NSCLC.
PubMed IF 3.3 혈액종양내과
1842012

제1저자 윤호일 · 교신저자 Don D. Sin

, , , , , , , , ,
The complex relationship of serum adiponectin to COPD outcomes COPD and adiponectin.
Chest. 2012;142(4):893-899.

Abstract
BACKGROUND COPD is a chronic inflammatory disorder with high risk of cardiovascular morbidity and mortality. Adiponectin is a hormone that has anti inflammatory, antidiabetic, and anti atherogenic activities. We investigated the relationship of serum adiponectin to health outcomes in COPD.
METHODS We measured adiponectin levels in serum samples from participants of the Lung Health Study, who were smokers with mild to moderate airflow limitation. We determined the relationship of serum adiponectin to hospitalization and mortality using a Cox proportional hazards model and to baseline lung function measurements and bronchial reactivity using multiple regression methods.
RESULTS Serum adiponectin concentrations were inversely related to hospitalizations and mortality from coronary heart disease (hazard ratio [HR], 0.73; 95% CI, 0.62-0.86) and to cardiovascular disease (HR, 0.83; 95% CI, 0.73-0.94) and positively related to deaths from respiratory causes (HR, 2.09; 95% CI, 1.41-3.11). However, serum adiponectin concentrations were not significantly related to total mortality (HR, 1.10; 95% CI, 0.93-1.29) or cancer-related mortality(HR, 1.11; 95% CI, 0.92-1.34). Serum adiponectin concentrations were significantly related to increased bronchial reactivity and an accelerated decline in lung function (both P , .0001). Smoking status had no material influence on serum adiponectin concentrations.
CONCLUSIONS Adiponectin is a complex serum biomarker in COPD that is associated with decreased risk of cardiovascular events but increased risk of respiratory mortality. Because serum adiponectin is not significantly influenced by smoking status, it is a very promising biomarker of cardiovascular outcomes in COPD.
PubMed IF 9.8 호흡기내과
1832012

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
1822012

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
1812012

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
1802012

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
1792012

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
1782012

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
1772012

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
1762012

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
1752012

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
1742012

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
1732012

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
1722012

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
1712012

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
1702012

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

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.