SCI 발표논문

2008년 130편

702008

제1저자 박수철 · 교신저자 정숙향

, , , , , , , , , , , , ,
High prevalence of hepatitis B virus infection in patients with B-cell non-Hodgkin's lymphoma in Korea.
J Med Virol. 2008;80(6):960-6.

Abstract
This study assessed the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with non-Hodgkin's lymphoma in a highly HBV-endemic area. The prevalence of either HBV or HCV infection in 235 patients with non-Hodgkin's lymphoma was compared with that of an age- and sex-matched hospital control group of 235 patients. The prevalence of HBV infection was higher in B-cell non-Hodgkin's lymphoma (15.5%) than control (8.1%), but the prevalence of HCV infection in the non-Hodgkin's lymphoma patients (2.1%) and control group (3%) was similar. HBV prevalence increased significantly with age in the B-cell non-Hodgkin's lymphoma patients. The presence of HBV proteins and DNA in lymphoma tissues and peripheral blood mononuclear cells (PBMCs) from HBV-infected non-Hodgkin's lymphoma patients was also investigated using immunohistochemistry and PCR. HBV DNA was frequently detected in PBMCs from HBV-infected non-Hodgkin's lymphoma patients, but HBV antigens were not. Therefore, HBV infection, but not HCV infection, was associated with B-cell non-Hodgkin's lymphoma in Korea, suggesting a possible role for HBV in the development of non-Hodgkin's lymphoma.
PubMed IF 3.7 소화기내과
692008

제1저자 오지영 · 교신저자 박경수

, , , , , , , , , , , , , , ,
A report on the diagnosis of intermediate hyperglycemia in Korea: A pooled analysis of four community-based cohort studies.
Diabetes Res Clin Pract. 2008;80(3):463-8.

Abstract
Many studies show poor agreement between fasting plasma glucose (FPG)-based and 2-h postchallenge glucose (2-h PG)-based criteria to assess glucose metabolism. We examined the rate of agreement between FPG- and 2-h PG-based criteria in the diagnosis of intermediate hyperglycemia in four representative cohort studies in South Korea and compared the clinical characteristics and biochemical parameters in subjects with impaired fasting glucose (IFG) according to their FPG values. Of 6234 subjects from four population-based studies performed from 1993 to 2000, 4610 individuals with data from a 75g oral glucose tolerance test (OGTT) and no previous history of diabetes were selected. We examined the concordance rate between the FPG and 2-h PG-based criteria. We also investigated the differences in the clinical characteristics and biochemical parameters between individuals with IFG according to their FPG values. The fasting and 2-h PG criteria had large discordance rates in the diagnosis of diabetes and impaired glucose tolerance (IGT) in Korean adults. When individuals with IFG were classified into stage 1 [5.6-6.1mmol/L (100-109mg/dL)] and stage 2 [6.1-7.0mmol/L (110-125mg/dL)] IFG, individuals with stage 2 IFG are more obese and had higher blood pressure and total cholesterol and triglycerides concentrations compared with those with stage 1 IFG. In addition, more individuals with stage 2 IFG were with diabetes as determined by a 2-h PG>or=11.1mmol/L (14.1% vs. 1.9%) (P<0.05). Considering the poorer metabolic profile and higher percentage of people with diabetes by OGTT, these data indicate that, in the Korean population, individuals with stage 2 IFG should be treated differently from those with stage 1 IFG. To detect more cases of diabetes, the OGTT is recommended for all individuals with stage 2 IFG and cases with stage 1 IFG with some additional risk factors for diabetes.
PubMed IF 4.6 내분비대사내과
682008

제1저자 최성희 · 교신저자 장학철

, , , , , , , , , ,
Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance.
J Clin Endocrinol Metab. 2008;93(6):2313-8.

Abstract
CONTEXT Elevated levels of retinol binding protein-4 (RBP4) are positively correlated with insulin resistance, obesity, diabetes mellitus, and cardiovascular disease (CVD). Subclinical hypothyroidism (SCH) has also been associated with CVD; however, the factors linking SCH to CVD are not clear.
OBJECTIVE The objective of the study was to evaluate risk factors for CVD in elderly patients grouped according to thyroid function.
DESIGN 217 subjects (> or =65 yr old) were randomly selected from a population and allocated to a euthyroid group (n = 177) and an SCH group (n = 40) on the basis of plasma concentrations of TSH and free T(4). We included subjects with normal glucose tolerance by a 75-g oral glucose tolerance test and subjects with impaired fasting glucose. We measured anthropometric parameters, levels of fasting glucose and insulin, hemoglobin A(1c), adiponectin, RBP4, lipid profiles, total body fat content, and the area of sc and visceral fat.
RESULTS The SCH group had higher RBP4 levels than the euthyroid group, irrespective of body mass index and fat content. Subcutaneous and visceral fat areas and total body fat percentage did not differ between groups and were not correlated with RBP4 level. Other CVD risk factors did not differ between groups. RBP4 level was positively correlated with TSH level (r = 0.241, P = 0.001) after adjustment for age, sex, and body mass index.
CONCLUSIONS Plasma RBP4 levels were associated with SCH independent of obesity in elderly subjects with normal glucose tolerance, indicating that RBP4 level could be used as an index of CVD risk in SCH.
PubMed IF 5.4 내분비대사내과
672008

제1저자 임수 · 교신저자 장학철

, , , , , , , ,
Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women.
J Clin Endocrinol Metab. 2008;93(6):2263-8.

Abstract
CONTEXT Exercise training enhances insulin sensitivity. Changes in retinol-binding protein-4 (RBP4) and adiponectin levels are linked to insulin resistance.
OBJECTIVE We tested whether the insulin-sensitizing effect of exercise is associated with age-related changes in circulating RBP4 and adiponectin levels in women.
DESIGN, SUBJECTS, AND INTERVENTION We studied 36 healthy young (22.4 +/- 2.8 yr) and 38 middle-aged (59.8 +/- 5.9 yr) women. All subjects performed 60 min of aerobic exercise three times per week for 10 wk at about 70% maximal exercise capacity.
RESULTS After a 10-wk training program, maximal exercise capacity was significantly increased in both young and middle-aged women, suggesting increased oxidative capacity. Insulin sensitivity was also improved, as indicated by decreases in plasma insulin levels and homeostasis model assessment for insulin resistance index. Serum adiponectin and RBP4 concentrations were increased and decreased more in older than younger women, respectively (P < 0.01). Concurrently, circulating transthyretin levels were also decreased in older subjects in response to exercise training. The older women showed higher correlations between changes in adiponectin or RBP4 levels and obesity indices or metabolic parameters than the younger group. When subjects showing increasing adiponectin or decreasing RBP4 levels were classified as responders, there were higher correlations between these changes in responders than in nonresponders.
CONCLUSIONS We conclude that the mechanism for the insulin-sensitizing effects of exercise could involve increased adiponectin and reduced RBP4 levels in exercise-trained women. These data suggest that alterations in circulating RBP4 and adiponectin levels could play an important role in regulating insulin sensitivity.
PubMed IF 5.4 내분비대사내과
662008

제1저자 김민정 · 교신저자 허대석

, , , , , , ,
Association of CD47 with natural killer cell-mediated cytotoxicity of head-and-neck squamous cell carcinoma lines.
Tumour Biol. 2008;29(1):28-34.

Abstract
OBJECTIVE Integrin-associated protein (CD47) binds specifically to the inhibitory receptor signal-regulatory protein. This study was designed to evaluate the role of CD47 in natural killer (NK) cell-mediated cytotoxicity against cancer cells.
METHODS Head-and-neck squamous cell carcinoma (HNSCC) cell lines were analyzed for the expression of CD47 and susceptibility to NK cell-mediated killing. Cytolytic activity was assessed by (51)Cr-specific release assays and by measuring cytokine production.
RESULTS HNSCC cell lines that had high CD47 expression showed lower levels of NK cytotoxicity than those with low CD47 expression. After pre-treating cells with neutralizing major histocompatibility complex (MHC) class I or anti-CD47 antibodies, NK cell-mediated cytotoxicity against HNSCC cell lines increased. In addition, when CD47 cDNA was transfected into Caco-2 cells, NK cell-mediated cytotoxicity decreased.
CONCLUSION These findings suggest that CD47 may play an inhibitory role in NK cell-mediated cytotoxicity against cancer cells, implying a possible mechanism of immune escape in human cancer.
PubMed IF 2.407 혈액종양내과
652008

제1저자 김성학 · 교신저자 김태유

, , , , , , , , ,
DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription.
Int J Biochem Cell Biol. 2008;40(11):2462-71.

Abstract
DNA methyltransferase 3B has been demonstrated to mediate gene silencing. The mechanisms how DNA methyltransferase 3B is targeted to specific regions and represses gene transcription, however, are not well understood. Here we show that by using yeast two-hybrid screening, DNA methyltransferase 3B interacts with the human polycomb protein, hPc2. This interaction was verified via co-immunoprecipitation and GST pull-down assay. Sequential deletion analysis showed that the region of DNA methyltransferase 3B responsible for interaction is mapped to the N-terminal regulatory domain. By performing a cDNA microarray analysis in HCT 116 cells, we identified that the expression of fibroblast growth factor receptor 3 is significantly increased upon the small interference RNA-mediated knockdown of hPc2, suggesting fibroblast growth factor receptor 3 as a potential target of hPc2. We further found that DNA methyltransferase 3B enhances hPc2-mediated transcriptional repression of fibroblast growth factor receptor 3, which does not require its de novo methyltransferase activity. Taken together, these results suggest that DNA methyltransferase 3B functions as a co-repressor of polycomb protein in inducing transcriptional repression independent of DNA methylation.
PubMed IF 3.5 혈액종양내과
642008

제1저자 김혜련 · 교신저자 임재준

, , , , , , , , , , , ,
Solid-organ malignancy as a risk factor for tuberculosis.
Respirology. 2008;13(3):413-9.

Abstract
BACKGROUND AND OBJECTIVE The effective control of tuberculosis (TB) requires that people at high risk for the reactivation of TB are identified. Haematological malignancy has been shown to be a risk factor for the development of TB, either through immune suppression by the tumour or through the effects of chemotherapy. This study assessed the hypothesis that solid-organ malignancy is a risk factor for the development of TB.
METHODS A retrospective cohort study was performed to determine the incidence of TB in patients with solid-organ malignancy and in control subjects without malignancy. Risk factors for the development of TB among patients with cancer were also assessed.
RESULTS The study recruited 1809 cases with cancer and 1809 control subjects and followed them for 3 years. The incidence of active TB per 1000 person-years was 3.07 in patients with cancer and 0.77 in controls (P = 0.009). Compared with the control group, patients with cancer had an increased risk of developing TB (incidence rate ratio (IRR) 4.69, 95% CI: 1.52-14.46). Proportional hazards regression analysis showed that the risk factors for development of TB were chronic renal failure (IRR 9.91, 95% CI: 1.17-83.60), old healed TB on CXR (IRR 45.05, 95% CI: 5.74-353.88), and anticancer chemotherapy (IRR 4.32, 95% CI: 1.10-16.89). An interaction between old healed TB and anticancer chemotherapy was observed.
CONCLUSION These findings indicate that immune suppression by cancer or by anticancer chemotherapy increases vulnerability to reactivation of TB, especially in cancer patients with old healed TB.
PubMed IF 7.2 호흡기내과
632008

제1저자 김형관 · 교신저자 김용진

, , , , , , ,
Hemodynamic and prognostic implications of net atrioventricular compliance in patients with mitral stenosis.
J Am Soc Echocardiogr. 2008;21(5):482-6.

Abstract
BACKGROUND On the basis of the close association of left atrial compliance with pulmonary hypertension in patients with mitral stenosis, we hypothesized that: (1) Doppler-derived net atrioventricular compliance (C(n)) can be used for predicting the occurrence of mitral valve (MV) replacement or percutaneous mitral commissurotomy (PMC); and (2) determinants of exercise capacity are variable depending on C(n).
METHODS We consecutively enrolled 26 patients (22 women; mean age, 47.0 +/- 6.1 years; range, 35-59 years) with pure moderate or severe mitral stenosis, in whom comprehensive echocardiography was performed at rest. C(n) was derived from the equation that has been previously validated (ie, C(n) = 1270 x [MV area by 2-dimensional planimetry/mitral E-wave downslope]. Measurements of stroke volume and systolic pulmonary artery pressure were repeated immediately after symptom-limited treadmill exercise test within 60 seconds.
RESULTS On the basis of earlier reports, C(n) less than 4 mL/mm Hg was selected to define abnormally small C(n). During a mean duration of 24-month follow-up, C(n) of less than 4 mL/mm Hg could reliably predict the occurrence of either MV replacement or PMC, which was confirmed by multivariate logistic regression analysis. In patients with C(n) less than 4 mL/mm Hg, exercise duration was found to be closely correlated primarily with resting systolic pulmonary artery pressure (r = -0.73, P = .03), whereas in patients with C(n) greater than or equal to 4 mL/mm Hg, postexercise stroke volume was the only determinant of exercise capacity (r = 0.49, P = .04). When combining C(n) less than 4 mL/mm Hg with MV area less than 1.0 cm(2) as a cut-off value for predicting MV replacement or PMC, the sensitivity improved from 63.6% to 81.8% (P = .05).
CONCLUSIONS Left atrial compliance estimated by C(n) with Doppler echocardiography allows us to effectively predict the future occurrence of MV replacement or PMC, with a special usefulness in patients with moderate mitral stenosis. In addition, determinants of exercise capacity were variable depending on the degree of C(n).
PubMed IF 8.3 순환기내과
622008

제1저자 김범석 · 교신저자 허대석

, , , , , , , ,
Aggressiveness of cancer-care near the end-of-life in Korea.
Jpn J Clin Oncol. 2008;38(5):381-6.

Abstract
OBJECTIVE The aim of this study was to examine the appropriateness of chemotherapy and care in Korean cancer patients near the end-of-life.
METHODS We designed a retrospective cohort composed of patients diagnosed as having metastatic cancer and who received palliative chemotherapy at Seoul National University Hospital in 2002. Two hundred and ninety-eight patients who died of cancer were evaluated in terms of the appropriateness of the cancer-care they received, including chemotherapy.
RESULTS Median duration of chemotherapy was 6.02 months compared with 8.67 months for median overall survival. The median period between last chemotherapy and death was 2.02 months. Of the 298 patients, 50.3% received chemotherapy during the last 2 months of life. Furthermore, 17 patients (5.7%) died within 2 weeks after receiving chemotherapy. The proportion who visited an emergency room (ER) more than once during the last months of life was 33.6%, and the average number of ER visits after a diagnosis of cancer was 1.72. Only 9.1% of patients were referred to a hospice consultation service and only 11.7% of patients agreed with written DNR.
CONCLUSIONS Among patients who died of cancer, significant proportions were found to have received chemotherapy up to the end-of-life and to have visited ERs. Hospice referrals and discussions about DNR were not conducted well during the end-of-life period in Korea.
PubMed IF 2.5 혈액종양내과
612008

제1저자 박영주 · 교신저자 이윤광

, , , , , , ,
Loss of orphan receptor small heterodimer partner sensitizes mice to liver injury from obstructive cholestasis.
Hepatology. 2008;47(5):1578-86.

Abstract
UNLABELLED The orphan nuclear hormone receptor small heterodimer partner (SHP) regulates the expression of several genes involved in bile acid homeostasis in the liver. Because bile acid toxicity is a major source of liver injury in cholestatic disease, we explored the role of SHP in liver damage induced by common bile duct ligation (BDL). Shp(-/-) mice show increased sensitivity in this model of acute obstructive cholestasis, with greater numbers of bile infarcts and higher mortality than wild-type C57BL/6 mice. This increased sensitivity could not be accounted for by differences in expression of bile acid homeostatic genes 2 or 5 days after BDL. Instead, higher basal expression of such genes, including the key biosynthetic enzyme cholesterol 7alpha hydroxylase (Cyp7A1) and the bile salt export pump, is associated with both an increase in bile flow prior to BDL and an increase in acute liver damage at only 1.5 hours after BDL in Shp(-/-) mice, as shown by bile infarcts. At 3 hours, Cyp7A1 expression still remained elevated in Shp(-/-) with respect to wild-type mice, and the hepatic and serum bile acid levels and total hepatobiliary bile acid pool were significantly increased. The increased sensitivity of mice lacking SHP contrasts with the decreased sensitivity of mice lacking the farnesoid X receptor (FXR; nuclear receptor subfamily 1, group H, member 4) to BDL, which has been associated with decreased intraductal pressure and fewer bile infarcts.
CONCLUSION We propose that differences in acute responses to BDL, particularly the early formation of bile infarcts, are a primary determinant of the differences in longer term sensitivity of the Fxr(-/-) and Shp(-/-) mice to acute obstructive cholestasis.
PubMed IF 18 내분비대사내과
602008

제1저자 곽한복 · 교신저자 송영욱

, , , , , , , , , ,
Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone-erosive experimental arthritis.
Arthritis Rheum. 2008;58(5):1332-42.

Abstract
OBJECTIVE Interferon-gamma-inducible protein 10 (IP-10; also called CXCL10), a chemokine important in the migration and proliferation of T cells, is induced in a wide variety of cell types. However, the role of IP-10 in rheumatoid arthritis (RA) remains largely unknown. The purpose of this study was to examine the potential role of IP-10 in bone resorption and RA through examination of a mouse model of collagen-induced arthritis (CIA).
METHODS The effects of IP-10 on mouse T cells during osteoclast differentiation were examined in migration assays. The bone-erosive activity of IP-10 was determined in vivo in a mouse model of CIA by histologic and immunostaining analyses. Cytokine levels in serum and culture medium were measured with sandwich enzyme-linked immunosorbent assays.
RESULTS Serum concentrations of IP-10 were significantly higher in mice with CIA than in control mice. RANKL greatly induced IP-10 expression in osteoclast precursors, but not in mature osteoclasts. IP-10 stimulated the expression of RANKL and tumor necrosis factor alpha (TNFalpha) in CD4+ T cells and induced osteoclastogenesis in cocultures of CD4+ T cells and osteoclast precursors. However, IP-10 did not induce RANKL or TNFalpha in CD8+ T cells. Treatment with neutralizing antibody to IP-10 significantly inhibited the infiltration of CD4+ T cells and F4/80+ macrophages into the synovium and attenuated bone destruction in mice with CIA. Furthermore, levels of RANKL and TNFalpha were inhibited by antibody to IP-10. Bone erosion was observed in mice infected with an IP-10 retrovirus.
CONCLUSION Our findings suggest that IP-10 plays a critical role in the infiltration of CD4+ T cells and F4/80+ macrophages into inflamed joints and causes bone destruction. Our results provide the first evidence that IP-10 contributes to the recruitment of inflammatory cells and is involved in bone erosion in inflamed joints.
PubMed IF 7.751 류마티스내과
592008

제1저자 강현재 · 교신저자 김효수,박영배

, , , , , , , ,
Effects of stem cell therapy with G-CSF on coronary artery after drug-eluting stent implantation in patients with acute myocardial infarction.
Heart. 2008;94(5):604-9.

Abstract
OBJECTIVE The effects of stem cell therapy on the coronary vasculature were investigated in patients with acute myocardial infarction who underwent peripheral blood stem cell (PBSC) therapy in the MAGIC Cell-3-DES study.
METHODS Among 50 patients with acute myocardial infarction who underwent either sirolimus-eluting stent or paclitaxel-eluting stent implantation for the culprit lesion, intravascular ultrasound was analysed in 36 patients (cell infusion: n = 19 and control: n = 17). In the cell infusion group, PBSCs mobilised by granulocyte-colony stimulating factor were delivered via intracoronary infusion into infarcted myocardium. Proximal and distal reference segments, and stented segments, were evaluated with intravascular ultrasound at immediate post-intervention and 6-month follow-up, respectively.
RESULTS In the proximal and distal reference segments, the serial changes of lumen area, vessel area, and plaque plus media area were not significantly different between the cell infusion and the control groups. Within stented segments, mean neointimal area was similar in the two groups (cell infusion: 0.2 (SD 0.5) mm(2) vs control: 0.3 (SD 0.4) mm(2), p>0.05). However, there was a significant increase in mean peri-stent area of stented segment in the cell infusion group compared with the control group (0.7 (SD 1.4) mm(2) vs -0.1 (SD 1.2) mm(2), p<0.05). This difference mainly came from paclitaxel-eluting stent-implanted patients.
CONCLUSION Intracoronary infusion of PBSCs mobilised with G-CSF does not aggravate de novo atherosclerotic lesion and neointimal hyperplasia with DES implantation. However, it may induce peri-stent tissue growth at the stented segment, especially in patients receiving PES. Its clinical significance needs to be evaluated with long-term follow-up.
PubMed IF 4.4 순환기내과
582008

제1저자 이동헌 · 교신저자 정숙향

, , , , , , , ,
Hepatitis a in Korea: epidemiological shift and call for vaccine strategy.
Intervirology. 2008;51(2):70-4.

Abstract
OBJECTIVE The number of adult hepatitis A cases has progressively been increasing during the last several years in Korea. The aim of the present study was to describe the recent clinical features of hepatitis A and the seroprevalence of hepatitis A virus (HAV), and to discuss HAV vaccine strategy in Korea.
METHODS Retrospective analysis of clinical characteristics of hepatitis A from 109 patients consecutively enrolled at a community hospital between 2003 and 2006 as well as cross-sectional study of seroprevalence of HAV from 307 patients of hospital population group during the same period were performed.
RESULTS Most hepatitis A cases were young adults in their twenties or thirties, and the severity of the disease was related to the age of patients. The seroprevalence of HAV was 62%, which was dependent on the age of patients. HAV seroepidemiology in Korea is rapidly changing and a growing number of young adults are susceptible to HAV infection.
CONCLUSIONS The clinical features and the epidemiological shift of HAV urge Korea, as well as other countries which are experiencing similar issues, to promote childhood vaccination and consider catch-up vaccination for adolescents and young adults.
PubMed IF 1.8 소화기내과
572008

제1저자 박정현 · 교신저자 김태유

, , , , , , ,
Class II histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors.
Biochem Biophys Res Commun. 2008;368(2):318-22.

Abstract
Vascular endothelial growth factor receptors (VEGFRs) perform pivotal roles in both tumor growth and angiogenesis. In this study, we report that histone deacetylase inhibitors (HDIs) induce a reduction in VEGFR1 and VEGFR2 protein expression via the inhibition of class II histone deacetylases (HDACs) in human cancer cell lines. After HDI treatment, VEGFR1 and VEGFR2 were shown to be downregulated in a proteasome-dependent manner. HDI treatment induced a reduction in the binding of heat shock protein (Hsp) 90 to VEGFR1 or VEGFR2, followed by an increase of the binding of Hsp70 to VEGFR1 or VEGFR2. However, we noted no remarkable changes in the binding of Hsp90/Hsp70 to VEGFR3. HDI treatment effectively inhibited the activities of HDAC6 and HDAC10. Furthermore, the knock-down of HDAC6 or HDAC10, which was accomplished via the siRNA transfection, induced depletion of VEGFR1 or VEGFR2 proteins. Overall, these results indicate that HDAC6 and HDAC10 play important roles in Hsp-mediated VEGFR regulation.
PubMed IF 2.5 혈액종양내과
562008

제1저자 강정묵 · 교신저자 김나영

, , , , , , , , , ,
The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea.
Helicobacter. 2008;13(2):146-56.

Abstract
BACKGROUND AND AIM This study was performed to determine whether serum pepsinogen (PG) and gastrin testing can be used to detect gastric cancer in Korea.
METHODS Serum levels of PG I (sPGI) and sPGII, PG I/II ratios, and gastrin levels were measured in 1006 patients with gastroduodenal diseases including cancer. Follow-up tests were performed 1 year after Helicobacter pylori eradication.
RESULTS sPGI and sPGII levels increased and PG I/II ratios decreased in line with the severity of activity, chronic inflammation, and the presence of H. pylori (p < .01). In contrast, sPGI levels and PG I/II ratios decreased in proportion with the severity of atrophic gastritis (AG)/intestinal metaplasia (p < .01). Gastrin levels were found to be correlated with chronic inflammation negatively in the antrum but positively in the corpus. H. pylori eradication reduced sPGI, sPGII, and gastrin levels, and increased PG I/II ratios to the levels of H. pylori-negative patients, and was found to be correlated with reductions in activity and chronic inflammation of gastritis. The sensitivity and specificity of a PG I/II ratio of < or = 3.0 for the detection of dysplasia or cancer were 55.8-62.3% and 61%, respectively. In addition, sPGI and sPGII levels of intestinal-type cancer were significantly lower than those of the diffuse type, respectively (p = .008 and p = .05, respectively). Gastric cancer risk was highest in the H. pylori-positive, low PGI/II ratio (< or = 3.0) group with an odds ratio of 5.52 (confidence interval: 2.83-10.77).
CONCLUSION PG I/II ratio (< or = 3.0) was found to be a reliable marker for the detection of dysplasia or gastric cancer, especially of the intestinal type. This detection power of PG I/II ratio (< or = 3.0) significantly increased in the presence of H. pylori, and thus, provides a means of selecting those at high risk of developing gastric cancer in Korea.
PubMed IF 4.6 소화기내과
552008

제1저자 우현구 · 교신저자 김윤준

, , , , , , , , , , , , , , , , , , ,
Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma.
Clin Cancer Res. 2008;14(7):2056-64.

Abstract
PURPOSE The poor prognosis of hepatocellular carcinoma (HCC) is, in part, due to the high rate of recurrence even after "curative resection" of tumors. Therefore, it is axiomatic that the development of an effective prognostic prediction model for HCC recurrence after surgery would, at minimum, help to identify in advance those who would most benefit from the treatment, and at best, provide new therapeutic strategies for patients with a high risk of early recurrence.
EXPERIMENTAL DESIGN For the prediction of the recurrence time in patients with HCC, gene expression profiles were generated in 65 HCC patients with hepatitis B infections.
RESULT Recurrence-associated gene expression signatures successfully discriminated between patients at high-risk and low-risk of early recurrence (P=1.9 x 10(-6), log-rank test). To test the consistency and robustness of the recurrence signature, we validated its prognostic power in an independent HCC microarray data set. CD24 was identified as a putative biomarker for the prediction of early recurrence. Genetic network analysis suggested that SP1 and peroxisome proliferator-activated receptor-alpha might have regulatory roles for the early recurrence of HCC.
CONCLUSION We have identified a gene expression signature that effectively predicted early recurrence of HCC independent of microarray platforms and cohorts, and provided novel biological insights into the mechanisms of tumor recurrence.
PubMed IF 10.9 소화기내과
542008

제1저자 곽재진 · 교신저자 김용진

, , , , , , , , , ,
Development of tricuspid regurgitation late after left-sided valve surgery: a single-center experience with long-term echocardiographic examinations.
Am Heart J. 2008;155(4):732-7.

Abstract
OBJECTIVES This study sought to investigate the incidence and identify the predictors of significant tricuspid regurgitation (TR) development long after left-sided valve surgery.
METHODS Of 615 patients who underwent surgery for left-sided valve disease between 1992 and 1995, 335 patients without significant TR who completed at least 5 years of clinical and echocardiographic follow-up were enrolled. Late significant TR development was assessed by echocardiography with a mean follow-up duration of 11.6 +/- 2.1 years.
RESULTS Significant late TR was found in 90 patients (26.9%). Patients with late TR showed an advanced age (47.6 +/- 13.4 vs 44.3 +/- 13.2 years, P = .04), a higher prevalence of preoperative atrial fibrillation (83.3 vs 46.5%, P < .001), a greater left atrial dimension (56.9 +/- 13.2 vs 52.4 +/- 11.5 mm, P = .006), and a higher prevalence of prior valve surgery (40.0 vs 25.3%, P = .01). In addition, late TR occurred more frequently in patients who had undergone mitral valve surgery than in those who did not (93.3 vs 72.2%, P < .001). However, multivariate analysis showed that the presence of preoperative atrial fibrillation (odds ratio 5.37; 95% CI 2.71-10.65; P < .001) was the only independent factor of late TR development. Patients who developed late TR had a lower event-free survival rate than those who did not (P = .03).
CONCLUSIONS The development of significant TR long after left-sided valve surgery is not uncommon with an estimated incidence of 27% and is closely associated with a poor prognosis. The presence of preoperative atrial fibrillation was identified as the only independent predictor of the development of late TR.
PubMed IF 3.4 순환기내과
532008

제1저자 김나영 · 교신저자 송인성

, , , , , ,
Gene expression of AGS cells stimulated with released proteins by Helicobacter pylori.
J Gastroenterol Hepatol. 2008;23(4):643-51.

Abstract
BACKGROUND AND AIM Interactions between released proteins by Helicobacter pylori (H. pylori) and the cells of gastric epithelium to which it adheres may contribute to gastric inflammation and epithelial damage. The present study was performed to evaluate the gene expression of AGS gastric cancer cells stimulated with released proteins by H. pylori.
METHODS Gene expression of AGS cells to the stimulation by H. pylori-released proteins (G27 strain) were monitored using oligonucleotide microarrays.
RESULTS Eighty-eight genes (0.88%) and eight genes (0.08%) were up- or downregulated, respectively, by treating AGS cells with H. pylori-released proteins but not by H. pylori adhesion after 12 h of coculture. Out of the selected 40 up- and five downregulated genes, 29 upregulated genes classified as general RNA polymerase II transcription factor activity (GTF2B, PPARGC1A), SH3/SH2 adaptor activity (CRKL), transferase activity (ACLY, CRKL, PIGC, PLK4), and oxidoreductase activity (IDH1) were confirmed to be upregulated by released proteins and not by H. pylori adhesion by real-time reverse transcription-polymerase chain reaction. When the concentrated H. pylori-cultured supernatant prepared by our protocol was treated by boiling, the upregulations of 26 of these 29 genes (89.7%) except for CD160, ZNF268, and PSAT1 disappeared. This confirmed that most of these upregulations were caused by released proteins.
CONCLUSION Host genes involving transcription, signaling and stress are significantly modulated by the proteins released by H. pylori. This might strengthen the gastroduodenal pathogenesis induced by H. pylori.
PubMed IF 3.5 소화기내과
522008

제1저자 김경묵 · 교신저자 김유영

, , , , , , , , , , ,
Korean ginseng-induced occupational asthma and determination of IgE binding components.
J Korean Med Sci. 2008;23(2):232-5.

Abstract
A number of case reports on occupational asthma caused by herbal medicines have been issued, for example, on Sanyak, Chunkung, Banha, and Brazilian ginseng. Recently, cases of occupational asthma induced by Sanyak and Korean ginseng have been reported, but the pathogenic mechanisms involved are unknown. This study was carried out to evaluate the immunologic mechanism underlying Korean ginseng-induced occupational asthma. A patient engaged in Korean ginseng wholesale was referred for recurrent dyspnea, wheezing, and nasal symptoms, which were aggravated at work. Allergen bronchial provocation testing to Korean ginseng extract showed a typical immediate response, and skin prick testing to Korean ginseng extract also showed a strong positive response. Moreover, serum-specific IgE levels to Korean ginseng extract were significantly higher than in controls. Enzyme-linked immunosorbent assay (ELISA) inhibition tests showed a dose-dependent inhibition by Korean ginseng, but not by Dermatophagoides farinae, wheat flour, or Chinese balloon flower. Sodium dodecylsulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblotting revealed four specific Immunoglobulin E (IgE) binding components at 26, 30, 47, and 60 kDa, which were not bound by control sera. These results strongly suggest that occupation asthma induced by Korean ginseng is induced via an IgE-mediated mechanism.
PubMed IF 3.2 알레르기내과
512008

제1저자 최효진 · 교신저자 송영욱

, , , , , , , ,
The clinical significance of serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients.
Clin Rheumatol. 2008;27(4):437-42.

Abstract
We evaluated the clinical significance of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in systemic sclerosis (SSc). We studied 45 SSc patients (30 with limited and 15 with diffuse cutaneous SSc) of mean age +/- SD 47.1 +/- 12.9 years, mean duration of disease 10.2 +/- 6.0 years, and 45 age- and sex-matched healthy controls. Pulmonary artery pressure was measured by echocardiography. Lung involvement was evaluated by pulmonary function testing and by using high-resolution computed tomography scores. Serum NT-proBNP levels were measured using a sandwich electrochemiluminescent immunoassay. Serum NT-proBNP levels were significantly higher in patients with SSc compared to healthy controls. When the patients were divided into clinical subsets, serum NT-proBNP was higher in diffuse SSc than in limited SSc. Serum NT-proBNP levels were found to be positively correlated with age, skin thickness score, and systolic pulmonary artery pressure and negatively correlated with percentage of carbon monoxide diffusion capacity (DLco). Multivariate analysis showed that serum NT-proBNP levels were positively correlated with age (p = 0.010), skin thickness score (p = 0.000), and blood pressure (p = 0.021) and negatively correlated with %DLco (p = 0.016). Fifty-seven percent of the variation in log (proBNP) can be explained by the multivariate model (R (2) = 0.57). Serum NT-proBNP levels were higher in SSc patients (particularly the diffuse subset) than in healthy controls and were found to be correlated with skin thickness and %DLco. We conclude that serum NT-proBNP may be a biologic marker of skin fibrosis and pulmonary vascular involvement in SSc.
PubMed IF 2.7 류마티스내과
502008

제1저자 임수 · 교신저자 조성일

, , , , , ,
Changes in metabolic syndrome of Korean children and adolescents in the period 1998 to 2001.
J Endocrinol Invest. 2008;31(4):327-33.

Abstract
The aim of this study was to compare the prevalence and pattern of metabolic syndrome in children and adolescents in the interval between the Korean National Health and Nutrition Examination Surveys (KNHANES) in 1998 and 2001. Two nationwide surveys (KNHANES) were conducted in Korea in 1998 and 2001. A stratified multistage probability sampling design was used to ensure representation of the entire Korean population. The National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III)-derived definition was used for the definition of metabolic syndrome. A total of 1763 (mean age+/-SD of 14.6+/-2.8 yr) and 1245 (14.1+/-2.8 yr) Korean children and adolescents in the age range 10-19 yr participated in the studies of 1998 and 2001, respectively. The prevalence of metabolic syndrome in male children and adolescents increased significantly from 5.7% in 1998 to 9.0% in 2001. However, there was no increase in females (5.1% in 1998 and 4.9% in 2001). Of the 5 components of metabolic syndrome, low HDL-cholesterolemia showed the highest increase in males and females during the 3 yr. Hypertriglyceridemia increased next in both genders. In contrast, the proportion of female subjects meeting the fasting glucose criterion decreased over the same period. As dyslipidemia was the principal contributor to the increase in metabolic syndrome in Korean male children and adolescents during the 3 yr, a strategy of dietary pattern change and the encouragement of physical activity should be introduced to these groups at a national level.
PubMed IF 4 내분비대사내과
492008

제1저자 이준규 · 교신저자 류지곤

, , , , , , ,
Effects of nafamostat mesilate on the prevention of cerulein-induced acute pancreatitis.
Pancreas. 2008;36(3):255-60.

Abstract
OBJECTIVES Protease inhibitors showed protective effects on animal models of acute pancreatitis when administered before induction of pancreatitis, and results when administered after induction are uncertain. We assessed the effects of nafamostat mesilate in a mouse model of cerulein-induced pancreatitis comparing results of before and after induction.
METHODS Cerulein was injected to mice intraperitoneally to induce pancreatitis, and they received intravenous nafamostat mesilate before and after induction. Serum concentrations of amylase and lipase, histological changes, and tissue expression of myeloperoxidase were measured. In addition, tissue activation of p38 mitogen-activated protein kinase (MAPK) and interleukin-6 was evaluated.
RESULTS Development of pancreatitis was prevented by pretreatment with nafamostat mesilate. However, such effect was not shown when given after induction, although it partially suppressed myeloperoxidase expression and infiltration of inflammatory cells. Tissue expression of phospho-p38 MAPK was prominent in mice with pancreatitis and suppressed by pretreatment with nafamostat mesilate. Interleukin-6 expression was not influenced by either cerulein or nafamostat mesilate.
CONCLUSIONS The development of pancreatitis was prevented by treating mice with nafamostat mesilate before induction, however, this finding was not observed if administered after injection of cerulein. Pretreatment with nafamostat mesilate suppressed activation of p38 MAPK.
PubMed IF 2.2 소화기내과
482008

제1저자 박경수 · 교신저자 이홍규

, , , , , , , , , , , , , , , , , ,
A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians.
Diabetologia. 2008;51(4):602-8.

Abstract
AIMS/HYPOTHESIS This multinational study was conducted to investigate the association between a mitochondrial DNA (mtDNA) T16189C polymorphism and type 2 diabetes in Asians. The mtDNA 16189C variant has been reported to be associated with insulin resistance and type 2 diabetes. However, a recent meta-analysis concluded that it is negatively associated with type 2 diabetes in Europids. Since the phenotype of an mtDNA mutant may be influenced by environmental factors and ethnic differences in the nuclear and mitochondrial genomes, we investigated the association between the 16189C variant and type 2 diabetes in Asians.
METHODS The presence of the mtDNA 16189C variant was determined in 2,469 patients with type 2 diabetes and 1,205 non-diabetic individuals from Korea, Japan, Taiwan, Hong Kong and China. An additional meta-analysis including previously published Asian studies was performed. Since mtDNA nucleotide position 16189 is very close to the mtDNA origin of replication, we performed DNA-linked affinity chromatography and reverse-phase liquid chromatography/tandem mass spectrometry and chromatin immunoprecipitation to identify protein bound to the 16189 region.
RESULTS Analysis of participants from five Asian countries confirmed the association between the 16189C variant and type 2 diabetes [odds ratio (OR) 1.256, 95% CI 1.08-1.46, p=0.003]. Inclusion of data from three previously published Asian studies (type 2 diabetes n=3,283, controls n=2,176) in a meta-analysis showed similar results (OR 1.335, 95% CI 1.18-1.51, p=0.000003). Mitochondrial single-stranded DNA-binding protein (mtSSB) was identified as a candidate protein bound to the 16189 region. Chromatin immunoprecipitation in cybrid cells showed that mtSSB has a lower binding affinity for the 16189C variant than the wild-type sequence.
CONCLUSIONS/INTERPRETATION The mtDNA 16189C variant is associated with an increased risk of type 2 diabetes in Asians.
PubMed IF 10.4 내분비대사내과
472008

제1저자 임종필 · 교신저자 김상균

, , , , ,
Clinical outcomes and patency of self-expanding metal stents in patients with malignant upper gastrointestinal obstruction.
Dig Dis Sci. 2008;53(4):938-45.

Abstract
This study was performed to evaluate clinical outcomes and factors associated with patency of self-expanding metal stents (SEMS) in patients with malignant upper gastrointestinal (UGI) obstruction. In 83 patients with malignant UGI obstruction, 118 SEMS placements were performed. Obstruction sites were esophagus/gastro-esophageal junction (GEJ) and gastric outlet (GO) in 41 and 42 patients, respectively. Technical success was achieved in 99.2% and clinical success in 90.5%, with no procedure-related complications. Re-obstruction and migration occurred in 38.1% during a mean follow-up of 137 days; both occurred significantly more often with GO than esophageal/GEJ obstruction (49.2% vs 23.9%). Patency rates of esophageal/GEJ obstruction were 93.5, 78.1 and 67.0% at 30, 90 and 180 days, respectively, and were significantly higher than those of GO obstruction-71.7, 51.8 and 32.5%. Palliative chemotherapy or radiation therapy was not associated with stent patency. Endoscopic SEMS placement is a safe and effective palliative treatment for malignant UGI obstruction, and complications or stent patency differed according to obstruction site.
PubMed IF 2.8 소화기내과
462008

제1저자 박영주 · 교신저자 박도준

, , , , , , ,
Ghrelin enhances the proliferating effect of thyroid stimulating hormone in FRTL-5 thyroid cells.
Mol Cell Endocrinol. 2008;285(1-2):19-25.

Abstract
Ghrelin regulates cell proliferation through the growth hormone secretagogue receptor (GHS-R). We confirmed the expression of GHS-R in FRTL-5 thyroid cells and investigated the effects of ghrelin in thyrocytes using FRTL-5 cells. Ghrelin increased intracellular calcium levels but not intracellular cyclic AMP levels. Ghrelin activated Erk within 2min, then activated Akt and STAT3. Erk phosphorylation was inhibited by the calcium inhibitor cyclopiazonic acid (CPA). Ghrelin alone did not stimulate FRTL-5 cell proliferation but enhanced the effects of thyroid stimulating hormone (TSH). Pretreatment with TSH potentiates the growth effects of ghrelin in thyroid cells, and p66Shc, a growth factor receptor adaptor protein, might mediate these synergistic effects. Ghrelin phosphorylated TSH-induced p66Shc, which was inhibited by CPA. Ghrelin did not affect the proliferation of ARO cells, which showed no increased expression of p66Shc after TSH treatment. Thus, ghrelin-induced intracellular calcium signaling enhanced the TSH-induced proliferation of thyrocytes, possibly mediated by the p66Shc pathway.
PubMed IF 3.4 내분비대사내과
452008

제1저자 김동완 · 교신저자 허대석

, , , , , , , , , , , , , ,
High tumour islet macrophage infiltration correlates with improved patient survival but not with EGFR mutations, gene copy number or protein expression in resected non-small cell lung cancer.
Br J Cancer. 2008;98(6):1118-24.

Abstract
The purpose of this study was to investigate the prognostic value of tumour-associated macrophages with a focus on micro-anatomical localisation and determine whether molecular changes of the epidermal growth factor receptor (EGFR) are related to macrophage infiltration in resected non-small cell lung cancer (NSCLC). One hundred and forty-four patients were included in this study. Immunohistochemistry was used to identify CD68+ macrophages in the tumour islet and surrounding stroma. Epidermal growth factor receptor mutations were studied by direct sequencing. The EGFR gene copy number and protein expression were analysed by fluorescence in situ hybridisation and immunohistochemistry. Patients with a high tumour islet macrophage density survived longer than did the patient with a low tumour islet macrophage density (5-year overall survival rate was 63.9 vs 38.9%, P=0.0002). A multivariate Cox proportional hazard analysis revealed that the tumour islet macrophage count was an independent prognostic factor for survival (hazard ratio 0.471, 95% confidence interval 0.300-0.740). However, EGFR mutations, gene copy number, and protein expression were not related to the macrophage infiltration. In conclusion, tumour islet macrophage infiltration was identified as a strong favourable independent prognostic marker for survival but not correlated with the molecular changes of the EGFR in patients with resected NSCLC.
PubMed IF 7.8 혈액종양내과
442008

제1저자 이근욱 · 교신저자 방영주

, , , , , , , , , , ,
Enzastaurin, a protein kinase C beta inhibitor, suppresses signaling through the ribosomal S6 kinase and bad pathways and induces apoptosis in human gastric cancer cells.
Cancer Res. 2008;68(6):1916-26.

Abstract
Activation of protein kinase C (PKC) has been implicated in gastric carcinogenesis. Enzastaurin is an oral ATP-competitive inhibitor of the PKC beta isozyme. Although enzastaurin was initially advanced to the clinic based on its antiangiogenic activity, it is also known to have a direct effect on a variety of human cancer cells, inducing apoptosis by inhibiting the Akt signal pathway. However, data on enzastaurin for gastric cancer are limited. Therefore, this study was performed to assess the antitumor activity of enzastaurin on gastric cancer cells and to investigate the underlying antitumor mechanisms. Enzastaurin suppressed the proliferation of cultured gastric cancer cells and the growth of gastric carcinoma xenografts. Enzastaurin did not have an effect on gastric cancer cell cycle progression; however, it had a direct apoptosis-inducing effect through the caspase-mediated mitochondrial pathway. Glycogen synthase kinase 3beta phosphorylation, a reliable pharmacodynamic marker of enzastaurin activity, and Akt phosphorylation were both decreased after treatment with enzastaurin. Although the p90 ribosomal S6 kinase (Rsk) was also dephosphorylated, Erk phosphorylation was not affected in the enzastaurin-treated gastric cancer cells. Enzastaurin activated Bad, one of the Bcl-2 proapoptotic proteins, through dephosphorylation at Ser(112), and depletion of Bad activity resulted in resistance to enzastaurin-induced apoptosis and cytotoxicity in gastric cancer cells. These data suggest that enzastaurin induces apoptosis through Rsk-mediated and Bad-mediated pathways, besides inhibiting the Akt signal cascade. Furthermore, enzastaurin had synergistic or additive effects when combined with 5-fluorouracil, cisplatin, paclitaxel, or irinotecan. These results warrant further clinical investigation of enzastaurin for gastric cancer treatment.
PubMed IF 22.6 혈액종양내과
432008

제1저자 한주용, 조현주 · 교신저자 김효수, 강현재

, , , , , , , , ,
Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction.
J Am Coll Cardiol. 2008;51(9):933-43.

Abstract
OBJECTIVES The goal of this study was to investigate the effect of pre-treatment of mesenchymal stem cells (MSCs) with growth factors (GFs) on cardiomyogenic differentiation, cytoprotective action on cardiomyocytes (CMCs), and their therapeutic efficacy in myocardial infarction.
BACKGROUND Mechanisms of myocardial repair with MSC transplantation have not been fully elucidated, and therapeutic efficacy needs to be enhanced.
METHODS The MSCs obtained from the bone marrow of Fisher344 rats were treated with fibroblast growth factor-2, insulin-like growth factor-1, and bone morphogenetic protein-2. The expression of cardiac specific markers and the cytoprotective effect of MSCs with its mechanism were evaluated. Efficacy of MSCs transplantation was studied in rat myocardial infarction model.
RESULTS Treatment of MSCs with cocktails of GFs enhanced expression of cardiac transcription factors and survival. Induction of cardiac specific markers by coculture with CMCs and gap junctional communication with CMCs was more active in GF-treated MSCs than untreated MSCs. The GF-treated MSCs reduced apoptosis of neighboring CMCs in a hypoxic condition and enhanced the phosphorylated Akt and phosphorylated c-AMP response element binding protein expression of CMCs, which was markedly reduced by gap junction blockade. In a rat myocardial infarction model, transplantation of GF-treated MSCs resulted in smaller infarct size and better cardiac function than transplantation of untreated MSCs. Additionally, GF treatment enhanced gap junction formation of transplanted MSCs, which did not aggravate arrhythmia.
CONCLUSIONS Pre-treatment of MSCs with GFs enhanced cytoprotective effects on neighboring CMCs through gap junction and improved the therapeutic efficacy of MSC transplantation for myocardial repair. "Priming of MSCs with GFs" before transplantation might improve the therapeutic efficacy of cell therapy.
PubMed IF 22.3 순환기내과
422008

제1저자 이상협 · 교신저자 류지곤

, , , , , , , , , ,
Optimal interventional treatment and long-term outcomes for biliary stricture after liver transplantation.
Clin Transplant. 2008;22(4):484-93.

Abstract
We undertook an evaluation of the clinical outcomes of endoscopic cholangioplasty (ECP) and percutaneous cholangioplasty (PCP) for biliary strictures after liver transplantation. We compared success rates of intervention, patency after successful intervention and procedure-related morbidities in 79 patients with anastomotic stricture (n = 54) or non-anastomotic stricture (n = 25). Twenty-five ECP and 61 PCP procedures were performed; seven PCP procedures were consecutively performed after failure of ECP. Fifty-one (64.6%) patients were successfully treated by cholangioplasty. Successful intervention rates (60.0% in ECP vs. 59.3% in PCP, p = 1.00) and patencies after successful intervention (44.8 +/- 7.4 months in ECP vs. 41.9 +/- 3.4 months in PCP, p = 0.47) were no different for the two techniques. However, the number of intervention sessions for PCP (7.2 +/- 0.6) was higher than for ECP (2.9 +/- 0.6) (p < 0.01). Multivariate analysis showed that only an anastomotic stricture was found to be related with a longer patency with an estimated odds ratio of 5.74 (p = 0.04) and had a tendency to be associated with successful intervention with an estimated odds ratio of 3.12 (p = 0.07) irrespective of techniques. Endoscopic access should be the preferred first approach in patients with biliary stricture after liver transplantation irrespective of the type of stricture, in view of its less invasive nature and patient convenience.
PubMed IF 1.8 소화기내과
412008

제1저자 조상호 · 교신저자 김효수

, , , , , , , , , , , , , ,
Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study.
Am Heart J. 2008;155(3):499.e1-8.

Abstract
BACKGROUND Contrast media cause oxidative stress, which has been suggested as one possible mechanism responsible for contrast-induced nephropathy. Statins appear to have pleiotropic effects, including antioxidant properties. We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography.
METHODS We conducted a prospective, randomized, double-blind, placebo-controlled, 2-center trial, involving 247 consecutive patients with chronic renal insufficiency (calculated creatinine clearance < or = 60 mL/min and/or serum creatinine > or = 1.1 mg/dL) undergoing coronary angiography. Patients were randomized to simvastatin (n = 124; 160 mg total, 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure) or placebo (n = 123). All patients received pre - and postprocedure hydration. The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients.
RESULTS There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography, the primary study end point (0.002 +/- 0.164 vs 0.017 +/- 0.230 mg/mL respectively, P = .559). The incidence of contrast-induced nephropathy, a secondary end point defined as increase of either > or = 25% or > or = 0.5 mg/dL in serum creatinine, was 2.5% in simvastatin-treated patients (3/118) and 3.4% in placebo-treated patients (4/118), a nonsignificant difference (P = 1.00). There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes.
CONCLUSIONS Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography.
PubMed IF 3.4 순환기내과

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