SCI 발표논문
2007년 129편
- 392007
제1저자 오병희 · 교신저자 Deborah L. Keefe
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Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension.J Am Coll Cardiol. 2007;49(11):1157-63.
PubMed IF 22.3 순환기내과Abstract
OBJECTIVES This dose-ranging study evaluated the antihypertensive efficacy and tolerability of aliskiren in patients with mild-to-moderate hypertension.
BACKGROUND Low blood pressure (BP) control rates among patients with hypertension indicate a need for improved treatment options. This study investigates aliskiren, the first in a new antihypertensive class called renin inhibitors.
METHODS Patients with mean sitting diastolic BP 95 to 109 mm Hg were randomized to aliskiren 150, 300, or 600 mg or placebo once daily for 8 weeks. Patients completing this treatment phase entered a 2-week treatment-free withdrawal period. Office BP was recorded at baseline, weeks 2, 4, 6, and 8 of treatment, and 4 days and 2 weeks after cessation of treatment. A subgroup of patients underwent ambulatory BP monitoring.
RESULTS In total, 672 patients were randomized to treatment. After 8 weeks, aliskiren 150, 300, and 600 mg significantly reduced mean sitting BP (systolic/diastolic) by 13.0/10.3, 14.7/11.1, and 15.8/12.5 mm Hg, respectively, versus 3.8/4.9 mm Hg with placebo (all p < 0.0001 for systolic and diastolic BP). The BP-lowering effect of aliskiren persisted for up to 2 weeks after treatment withdrawal. Aliskiren significantly reduced mean 24-h ambulatory BP (p < 0.0001 vs. placebo with all doses) exhibiting smooth, sustained effects and high trough-to-peak ratios. Aliskiren was well tolerated; overall adverse event rates were 40.1%, 46.7%, and 52.4% with aliskiren 150, 300, and 600 mg, respectively, and 43.0% with placebo. Few patients discontinued treatment due to adverse events.
CONCLUSIONS Aliskiren provides significant antihypertensive efficacy in patients with hypertension, with no rebound effects on blood pressure after treatment withdrawal.
- 382007
제1저자 이희석 · 교신저자 임재준
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Bronchial washing yield before and after forceps biopsy in patients with endoscopically visible lung cancers.Respirology. 2007;12(2):277-82.
PubMed IF 7.2 호흡기내과Abstract
BACKGROUND AND OBJECTIVE The need for routine use of bronchial washing in addition to forceps biopsy has been debated in the diagnosis of endoscopically visible lung tumours. Moreover, the optimal sequence for obtaining bronchial washing and forceps biopsy specimens from endoscopically visible tumours through a flexible bronchoscope has not been well established.
METHODS A multicentre 13-month prospective randomized study was performed. Two hundred and thirty consecutive patients with endoscopically visible tumours were randomly assigned into a bronchial washing before forceps biopsy (pre-biopsy) group and a bronchial washing after forceps biopsy (post-biopsy) group. Bronchial washing and forceps biopsy were performed according to the assigned sequence.
RESULTS Two hundred and seven patients with a definite cytological or histological diagnosis of lung cancer were included in the analyses. One hundred and three were in the pre-biopsy group and 104 were in the post-biopsy group. The diagnostic yield of bronchial washing was 57.3% (59/103) in the pre-biopsy group and 55.8% (58/104) in the post-biopsy group (P = 0.88). In addition, bronchial washing provided the diagnosis in six patients without definite diagnosis from forceps biopsy, and its addition to forceps biopsy significantly increased the overall diagnostic yield of bronchoscopy from 93.7% to 96.6% (P = 0.03).
CONCLUSION The sequence for performing bronchial washing before or after forceps biopsy did not affect the diagnostic yield of bronchial washing in patients with endoscopically visible lung cancers. However, bronchial washing led to a significant increase in the overall diagnostic yield of bronchoscopy in patients with lung cancers.
- 372007
제1저자 박주경 · 교신저자 김윤준
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Evaluation of hernia repair operation in Child-Turcotte-Pugh class C cirrhosis and refractory ascites.J Gastroenterol Hepatol. 2007;22(3):377-82.
PubMed IF 3.5 소화기내과Abstract
BACKGROUND AND AIM Abdominal wall hernia is a common feature of decompensated liver cirrhosis and frequently causes life-threatening complications or severe pain. However, there have been no data reported on postoperative mortality, hepatic functional deterioration and recurrence rate according to Child-Turcotte-Pugh (CTP) class and to the presence of refractory ascites.
METHODS The study population comprised 53 liver cirrhosis patients who underwent hernia repair operation. Comparisons were made of 30-day mortality among the different CTP classes, and between those with or without refractory ascites. Liver function was also analyzed just before the operation, in the immediate postoperative period, and in the remote postoperative period.
RESULTS Seventeen patients were in CTP class A, 27 patients in class B, and 9 patients in class C. The median follow-up duration was 24 months. There was single 30-day postoperative mortality in class C, and no CTP class deterioration after 30 days of operation. There was no mortality or recurrences in 17 patients with medically refractory ascites. The difference in 30-day mortality according to CTP class and the presence of refractory ascites did not show statistical significance (P = 0.17 and 0.97, respectively).
CONCLUSION Hernia operation could be done safely in CTP class A and B with low rate of recurrences, and there was no definitive increase in the operative risk in class C. In addition, refractory ascites did not increase operative risk and recurrence rate. Therefore, surgical repair might be recommended even in patients with refractory ascites and poor hepatic function to prevent life-threatening complications or severe pain.
- 362007
제1저자 김세형 · 교신저자 김윤준
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Esophageal varices in patients with cirrhosis: multidetector CT esophagography--comparison with endoscopy.Radiology. 2007;242(3):759-68.
PubMed IF 17.6 소화기내과Abstract
PURPOSE To evaluate the use of multidetector computed tomographic (CT) esophagography to grade esophageal varices and differentiate between varices at low risk and those at high risk for bleeding, with endoscopy as the reference standard.
MATERIALS AND METHODS This study was approved by the institutional review board; all subjects gave informed consent. Ninety patients with cirrhosis (65 men, 25 women; mean age, 54.8 years; range, 21-77 years) were prospectively enrolled and underwent endoscopy and CT esophagography. Esophageal varices were graded independently at endoscopy by two endoscopists. CT esophagograms were interpreted retrospectively with a four-point scale by two radiologists blinded to other findings. Interobserver agreement between each radiologist and endoscopist was determined; endoscopic and CT esophagographic grades of esophageal varices were correlated. Radiologist performance for differentiation between low- and high-risk varices for bleeding on the basis of morphology at endoscopy was evaluated with receiver operating characteristic analysis. Patients were interviewed to determine acceptance at both examinations.
RESULTS Thirty-seven of 90 patients had grade 0, 23 had grade 1, 18 had grade 2, and 12 had grade 3 esophageal varices. Thus, 60 patients were determined to be in a low-risk group and 30 in a high-risk group for variceal bleeding at endoscopy. There was almost perfect agreement in grading esophageal varices between endoscopists. There was close correlation (P < .001) and substantial agreement between endoscopic and CT esophagographic grades. Radiologist performance for differentiating between low- and high-risk varices was 0.931-0.958 (area under receiver operating characteristic curve). Patient interview results revealed that CT esophagography had better acceptance than did endoscopy (P < .001).
CONCLUSION Use of CT esophagography allows grading of esophageal varices and differentiation between low- and high-risk varices and shows better patient acceptance than does endoscopy.
- 352007
제1저자 이윤진 · 교신저자 이춘택
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Adenovirus expressing shRNA to IGF-1R enhances the chemosensitivity of lung cancer cell lines by blocking IGF-1 pathway.Lung Cancer. 2007;55(3):279-86.
PubMed IF 5.3 호흡기내과Abstract
RNA interference is a phenomenon whereby small double-stranded RNA knocks down the expression of a sequence-specific gene. Double-stranded siRNA transfection, as currently used, is considered to have transient and low transfection efficiency. We constructed an adenoviral vector-based short hair-pin(sh)RNA system to overcome the limitations of the genetic blockade of IGF-1R, one of most important cancer therapy targets. We constructed three different IGF-1R specific shRNAs (612, 801, and 3425) and generated three ad-shIGF-1Rs using BD Adeno-X expression system. We assessed the effect of ad-shIGF-1R on signal transduction, induction of apoptosis, and in vitro tumorigenicity of lung cancer cell lines. Western blot and FACS assays demonstrated that endogenous IGF-1R expression was efficiently suppressed after transduction of lung cancer cell lines with the three different ad-shIGF-1Rs. IGF-1R blockade by ad-shIGF-1R inhibited ligand induced phosphorylation of pAkt and pErk, and ad-shIGF-1R effectively blocked the in vitro tumorigenicity of lung cancer cell lines. Moreover, the transduction of a human lung cancer cell line with ad-IGF-1R(3425) enhanced chemosensitivity to anticancer drugs. We conclude that the adenoviral vector-based approach to the RNA interference of IGF-1R induced effective IGF-1R silencing in lung cancer cell lines as manifested by effective blocking of the downstream pathway of IGF-1R and by an antitumor effect. We believe that this system can be usefully applied to other cancer targets.
- 342007
제1저자 박흥우 · 교신저자 조상헌
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Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction.Thorax. 2007;62(3):265-9.
PubMed IF 9.1 알레르기내과Abstract
BACKGROUND Atopy is considered to be a complex genetic trait and does not follow a simple mendelian pattern of inheritance. It is now well recognised that gene-gene interactions are important in complex genetic disease.
AIM To analyse the influence of gene-gene interactions in the development of atopy.
METHODS A total of 2055 ethnically identical participants aged 10-18 years living in rural areas on Jeju Island, Korea, were randomly recruited. Atopy was defined as a positive skin prick test response to one or more common inhalant allergens. Gene-gene interactions among 12 polymorphic loci were analysed in the seven candidate genes of atopy using the multidimensionality-reduction method.
RESULTS A significant interaction was found between V297I in the gene coding vascular endothelial growth factor receptor 2 (KDR) and -308G-->A in the gene coding tumour necrosis factor (TNF)alpha on the risk of atopy, with a cross-validation consistency of 10 out of 10 and a prediction error of 35.9% (p = 0.001). Conventional logistic regression also revealed significant interactions between KDR and TNF for atopy. Individuals with the variant allele of -308G-->A in TNF (GA or AA) and V297I in KDR (VI or II) had a significantly higher risk of atopy (OR 2.23; 95% CI 1.48 to 3.57).
CONCLUSION KDR and TNF may synergistically influence the development of atopy through gene-gene interaction in Korean children and adolescents.
- 332007
제1저자 박경수 · 교신저자 Masashi Tannka
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Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians.Am J Hum Genet. 2007;80(3):407-15.
PubMed IF 7.7 내분비대사내과Abstract
Because mitochondria play pivotal roles in both insulin secretion from the pancreatic beta cells and insulin resistance of skeletal muscles, we performed a large-scale association study to identify mitochondrial haplogroups that may confer resistance against or susceptibility to type 2 diabetes mellitus (T2DM). The study population comprised 2,906 unrelated Japanese individuals, including 1,289 patients with T2DM and 1,617 controls, and 1,365 unrelated Korean individuals, including 732 patients with T2DM and 633 controls. The genotypes for 25 polymorphisms in the coding region of the mitochondrial genome were determined, and the haplotypes were classified into 10 major haplogroups (i.e., F, B, A, N9a, M7a, M7b, G, D4a, D4b, and D5). Multivariate logistic-regression analysis with adjustment for age and sex revealed that the mitochondrial haplogroup N9a was significantly associated with resistance against T2DM (P=.0002) with an odds ratio of 0.55 (95% confidence interval 0.40-0.75). Even in the modern environment, which is often characterized by satiety and physical inactivity, this haplogroup might confer resistance against T2DM.
- 322007
제1저자 정수진 · 교신저자 김주성
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Transforming growth factor-[beta]1 -509T reduces risk of colorectal cancer, but not adenoma in Koreans.Cancer Sci. 2007;98(3):401-4.
PubMed IF 4.9 소화기내과Abstract
The proliferation of colorectal epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes can modify the colorectal cancer risk. TGF-[beta]1 can act as both a tumor suppressor and a stimulator of tumor progression. TGF-[beta]1 C-509T polymorphism in the promoter sequence has been associated with increased levels of plasma TGF-[beta]1 in individuals with T allele. To evaluate the potential influences of this polymorphism on colorectal adenoma and cancer risk, a case-control study was conducted in Korea. A total of 646 subjects were prospectively enrolled in Seoul National University Hospital. Risk of colorectal neoplasms was evaluated separately for 244 patients with colorectal adenoma, 152 patients with colorectal cancer relative to 250 healthy controls. Genotypes were determined by the PCR-RFLP method. ORs and 95% CIs were calculated by a multivariate logistic regression analysis. The TGF-[beta]1 -509T allele containing genotypes posed a reduced risk of colorectal cancer (adjusted OR = 0.59, 95% CI = 0.28-0.92). But there was no association between this polymorphism and colorectal adenoma. Our results suggest that the TGF-[beta]1 -509T allele may have a protective role in the development of colorectal cancer, possibly consistent with its role as an inhibitor of epithelial malignant transformation.
- 312007
제1저자 명선정 · 교신저자 윤정환
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Bile acid-mediated thrombospondin-1 induction in hepatocytes leads to transforming growth factor-beta-dependent hepatic stellate cell activation.Biochem Biophys Res Commun. 2007;353(4):1091-6.
PubMed IF 2.5 소화기내과Abstract
In cholestasis, bile acids induce hepatocyte apoptosis, while activation of hepatic stellate cells (HSCs) results in fibrosis. Since transforming growth factor-beta (TGF-beta) is a critical mediator in this process, we hypothesized that bile acids may participate in TGF-beta-mediated HSC activation in cholestasis. Bile acid treatment increased TGF-beta transcription in hepatocytes, while the total TGF-beta concentration in culture media rapidly decreased following bile acid treatment. Bile acid treatment promptly induced thrombospondin-1 expression in hepatocytes, which is a potent activator of latent TGF-beta, whereas this induction was not observed in bile acid-treated HSCs. HSCs co-cultured with hepatocytes showed a significantly higher level of Smad2 phosphorylation and collagen alpha1 synthesis following bile acid treatment than cells cultured without hepatocytes. Moreover, this enhanced collagen synthesis was significantly inhibited in the presence of TGF-beta receptor inhibitor. These observations imply that bile acids induce thrombospondin-1 expression in hepatocytes, which activates latent TGF-beta leading to HSC activation.
- 302007
제1저자 이해영 · 교신저자 김효수
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Forkhead transcription factor FOXO3a is a negative regulator of angiogenic immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell proliferation and neointimal hyperplasia.Circ Res. 2007;100(3):372-80.
PubMed IF 18 순환기내과Abstract
Cysteine-rich angiogenic protein 61 (CYR61, CCN1) is an immediate early gene expressed in vascular smooth muscle cells (VSMCs) on growth factor stimulation, and its expression has been suggested to be associated with postangioplasty restenosis. The forkhead transcription factors are reported to play various roles in cellular proliferation, apoptosis, and even adaptation to cellular stress. We hypothesized that the forkhead transcription factor FOXO3a may regulate CYR61 expression in VSMCs and investigated the CYR61-modulating effect of FOXO3a in the process of vascular response to vasoactive signals and vascular injury. To evaluate the effect of FOXO3a on CYR61 expression, rat VSMCs were infected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Constitutively active FOXO3a gene transduction suppressed CYR61 expression. Luciferase assay with the deletion constructs of the forkhead factor binding motif in CYR61 promoter region, which resulted in a significant decrease in luciferase expression compared with the intact construct, and chromatin immunoprecipitation analysis confirmed transcriptional regulation of CYR61 by FOXO3a. Serum and angiotensin II rapidly induced CYR61 expression, which was significantly reduced by Ad-TM-FOXO3a. Reduction of VSMC proliferation and migration associated with FOXO3a activation was significantly reversed by cotransfection of adenoviral vector expressing CYR61, whereas apoptosis induction by FOXO3a was not influenced. In a rat balloon carotid arterial injury model, CYR61 was rapidly induced in VSMCs in the early stage of injury and remained elevated until 14 days, which was suppressed by Ad-TM-FOXO3a transfection. After 14 days, there was a significant reduction in neointima by FOXO3a transduction compared with the control group (0.06+/-0.02 versus 0.20+/-0.07 mm(2), P<0.01). Such reduction of neointimal hyperplasia by Ad-TM-FOXO3a was reversed by CYR61 replenishment. These data suggest that FOXO3a is a negative transcription factor of CYR61 and that suppression of CYR61 is among several mechanisms by which FOXO3a inhibits VSMC proliferation and neointimal hyperplasia.
- 292007
제1저자 최창민 · 교신저자 임재준
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Role of the C-reactive protein for the diagnosis of TB among military personnel in South Korea.Int J Tuberc Lung Dis. 2007;11(2):233-6.
PubMed IF 3.6 호흡기내과Abstract
Clinicians are frequently faced with the task of differentiating between pulmonary tuberculosis (PTB) and pneumonia. We evaluated the role of the C-reactive protein test (CRP) for differentiating between TB and pneumonia among military personnel in South Korea. Only immunocompetent males were eligible. Forty-six patients with PTB and 67 with pneumonia were enrolled prospectively. Median CRP concentration was lower in patients with TB than in patients with non-tuberculous pneumonia (3.2 mg/dl [range 0.1-15.7 mg/dl] vs. 8.3 mg/dl [range 0.2-33.7 mg/dl], P < 0.001). The sensitivity and specificity for TB of a low CRP concentration (< 11.2 mg/dl) in serum was 93.3% and 40.9%, respectively. CRP concentration measurement might be useful for eliminating the diagnosis of TB.
- 282007
제1저자 이희석 · 교신저자 임재준
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Determinants of diagnostic bronchial washing in peripheral lung cancers.Int J Tuberc Lung Dis. 2007;11(2):227-32.
PubMed IF 3.6 호흡기내과Abstract
OBJECTIVE To establish clinical determinants affecting the diagnostic yield of bronchial washing.
SETTING We performed bronchial washing in 241 consecutive patients with bronchoscopically invisible lung tumours. Of these, 150 patients known to have lung cancer were enrolled for the final analysis.
DESIGN A multi-centre study.
RESULTS Bronchial washing provided a diagnosis of lung cancer in 30 of the 150 patients (20%). Tumour size > or = 3 cm (P = 0.005), the location of the tumour within 8 cm of the carina (P = 0.003), and exposed type bronchus sign of tumour (P < 0.001) were factors affecting diagnostic bronchial washing for bronchoscopically invisible lung cancers. However, multivariate logistic regression revealed that exposed type bronchus sign was the sole determinant (OR 19.22, 95% CI 4.23-87.46, P < 0.001).
CONCLUSION Bronchial washing is a useful procedure for the diagnosis of bronchoscopically invisible lung cancers. As the tumour-bronchus relationship is the most important determinant of a diagnostic yield, the routine use of bronchial washing should be considered for tumours with exposed type bronchus sign.
- 272007
제1저자 김병관,이동호 · 교신저자 이상우,정현채
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Comparison of 7-day and 14-day proton pump inhibitor-containing triple therapy for Helicobacter pylori eradication: neither treatment duration provides acceptable eradication rate in Korea.Helicobacter. 2007;12(1):31-5.
PubMed IF 4.6 소화기내과Abstract
BACKGROUND AND AIMS Although triple combination therapy containing a proton pump inhibitor (PPI) and two antibiotics is considered as a standard regimen for the first-line anti-Helicobacter pylori treatment, there are still debates on the ideal duration of treatment. The aim of this study was to compare the efficacies of 7-day and 14-day PPI-containing triple therapy.
MATERIALS AND METHODS This study was performed in a randomized, multicenter, prospective manner. After upper gastrointestinal endoscopy, H. pylori-infected patients with a gastric ulcer and/or a duodenal ulcer were randomly assigned to a PAC7 group (omeprazole 20 mg or equivalent dose of other PPIs, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily for 7 days) or to a PAC14 group (the same regimen as the PAC7 group but for 14 days). H. pylori status was evaluated by (13)C urea breath test 5 weeks after anti-ulcer treatment completion.
RESULTS A total of 598 patients were enrolled; 337 were randomized to the PAC7 group and 261 to the PAC14 group. The two groups were comparable in terms of baseline characteristics. The eradication rates of the PAC7 group were not inferior to those of the PAC14 group in both intention-to-treat analysis (71.2% vs. 75.5%) and per-protocol analysis (83.6% vs. 86.6%). Incidences of adverse events were comparable.
CONCLUSIONS Although the 7-day PPI-containing triple anti-H. pylori therapy is not inferior to the 14-day therapy, neither treatment duration provides acceptable eradication rate reaching 90% in per-protocol analysis. New combination regimen with higher efficacy should be developed as a first-line eradication therapy for H. pylori in Korea.
- 262007
제1저자 임영석 · 교신저자 이효석
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Switch of cadherin expression from E- to N-type during the activation of rat hepatic stellate cells.Histochem Cell Biol. 2007;127(2):149-60.
PubMed IF 2.9 소화기내과Abstract
The activation of hepatic stellate cell (HSC) is a common pathway leading to hepatic fibrosis. However, the molecular mechanisms underlying HSC activation remain obscure. To elucidate the nature of the HSC activation, we investigated the expression of E-cadherin and its switch to N-cadherin during rat HSC activation, in vivo and in vitro. Immunohistochemical and immunocytochemical staining were performed to identify the expressions of E-cadherin, N-cadherin, and beta-catenin in rat HSCs, in vivo and in vitro. Serial changes in the expressions of these adhesion molecules during the spontaneous activation of cultured rat HSCs were also demonstrated by RT-PCR and by immunoblotting. E-cadherin and beta-catenin were expressed on opposing cell membranes of GFAP-positive rat HSCs and adjacent hepatocytes in vivo, and between desmin-positive rat HSCs in vitro. With the progression of rat HSC activation in tissue and in culture, E-cadherin disappeared gradually, whereas N-cadherin appeared at the cell periphery. The results of RT-PCR and immunoblotting were concordant with immunocytochemistry findings. In conclusion, resting rat HSCs express E-cadherin and beta-catenin both in vivo and in vitro, and E-cadherin switches to N-cadherin during HSC activation. These results suggest that HSC activation represents transdifferentiation from an epithelial to a mesenchymal phenotype.
- 252007
제1저자 진성지,박형규 · 교신저자 이홍규
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S-adenosyl-L-methionine increases skeletal muscle mitochondrial DNA density and whole body insulin sensitivity in OLETF rats.J Nutr. 2007;137(2):339-44.
PubMed IF 4.2 내분비대사내과Abstract
Both mitochondrial dysfunction and alterations in mitochondrial DNA (mtDNA) are implicated in type 2 diabetes mellitus and insulin resistance. Evidence also suggests that metabolism of S-adenosyl-L-methionine (SAM), the universal methyl donor for biological methylation, is associated with mitochondrial dysfunction and insulin resistance. We investigated the effect of SAM on mtDNA density and insulin sensitivity using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes mellitus and insulin resistance. To determine the short-term effect on mtDNA density, SAM (15 mg.kg-1.d-1) was administered intraperitoneally for 7 d to 6 male, 57-wk-old OLETF rats and 6 Long-Evans Tokushima Otsuka (LETO) rats of the same age as a nondiabetic control. To determine the long-term effect, the same dose of SAM was administered daily to 5 male, 6-wk-old OLETF rats until the age of 25 wk; 7 control OLETF rats received vehicle and 7 LETO rats were untreated. Skeletal muscle mtDNA density was measured by either competitive or multiplex PCR and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. SAM treatment for 1 wk increased skeletal muscle mtDNA density of both OLETF and LETO rats. The long-term SAM treatment significantly reduced body weight gain as well as increased skeletal muscle mtDNA density and whole body insulin sensitivity in OLETF rats compared with their vehicle-treated controls. Furthermore, in all 3 groups, skeletal muscle mtDNA density correlated with insulin sensitivity (r=0.752, P<0.001). In conclusion, SAM treatment increased mtDNA density in the skeletal muscle, improved whole body insulin sensitivity, and prevented body weight gain in OLETF rats.
- 242007
제1저자 강현재 · 교신저자 김효수
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Intracoronary infusion of the mobilized peripheral blood stem cell by G-CSF is better than mobilization alone by G-CSF for improvement of cardiac function and remodeling: 2-year follow-up results of the Myocardial Regeneration and Angiogenesis in Myocardial Infarction with G-CSF and Intra-Coronary Stem Cell Infusion (MAGIC Cell) 1 trial.Am Heart J. 2007;153(2):237.e1-8.
PubMed IF 3.4 순환기내과Abstract
BACKGROUND The results of stem cell therapy trials in myocardial infarction using granulocyte colony-stimulating factor (G-CSF) are inconsistent among trials, and the long-term outcome of G-CSF-based stem cell therapy remains unknown. We reported 2 years of follow-up results of 2 different strategies of G-CSF-based stem cell therapy.
METHODS AND RESULTS We compared outcomes of intracoronary infusion of the mobilized peripheral blood stem cells (PBSCs) with G-CSF, mobilization alone with G-CSF, and the control PCI alone in patients with myocardial infarction. At 2 years of follow-up evaluation, cell infusion improved left ventricular systolic function and remodeling compared to baseline, but G-CSF alone did not. Cell infusion group showed better improvements of left ventricular ejection fraction (+6.2% +/- 3.6% vs -4.3% +/- 10.1%, P = .004) and end-systolic volume (-15.7 +/- 13.0 vs +0.3 +/- 16.7 mL, P = .075) compared to G-CSF alone at 6 months of follow-up, and these trends were maintained till 2 years of follow-up (P = .094 and .046, respectively). Improvements in cell infusion group are not significantly better than that of control group because of small sample size. Patients who received G-CSF administration showed a tendency of modest increase of binary restenosis (50% vs 30%, P > .05) and a greater late loss of minimal luminal diameter (P > .05) at 6 months of follow-up, compared to the control group.
CONCLUSIONS Till 2 years follow-up, intracoronary cell infusion with mobilized PBSCs by G-CSF is better than G-CSF alone but not significantly better than control. Efficacy and safety of intracoronary infusion of mobilized PBSCs by G-CSF should be evaluated in a large randomized controlled trial.
- 232007
제1저자 손대원 · 교신저자 손대원
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Hemodynamic effects of tachycardia in patients with relaxation abnormality: abnormal stroke volume response as an overlooked mechanism of dyspnea associated with tachycardia in diastolic heart failure.J Am Soc Echocardiogr. 2007;20(2):171-6.
PubMed IF 8.3 순환기내과Abstract
BACKGROUND Prevention of tachycardia is an important therapeutic strategy in patients with relaxation abnormality.
METHODS Eleven patients with stable relaxation abnormality (group 1) and 8 healthy individuals (group 2) were enrolled. Left ventricular (LV) mean diastolic pressure, LV dimensions, stroke volume (SV), and LV ejection, filling, and isovolumic times between right atrial pacing rates of 80 and 120/min were compared.
RESULTS Both groups 1 and 2 showed significant decreases in LV mean diastolic pressure when heart rate (HR) increased. At a HR of 80/min, no significant difference was noted between groups 1 and 2 in SV (51.4 +/- 13.0 vs 45.2 +/- 9.0 mL, P = .35). However, a decrement in SV between a HR of 80 and 120/min was significantly greater for group 1. Therefore, group 1 showed a significantly lower SV (30.2 +/- 7.1 vs 40.1 +/- 6.9 mL, P < .05) at a HR of 120/min. In terms of time intervals between HRs of 80 and 120/min, group 1 showed a significantly greater reduction in LV ejection time (84.5 +/- 20.1 vs 30.0 +/- 34.6 milliseconds, P < .005) and a smaller reduction in LV filling time (106.4 +/- 38.5 vs 166.3 +/- 30.7 milliseconds, P < .005) than group 2.
CONCLUSIONS Results of our study suggest that an inadequate SV response to tachycardia may play an important role in the production of dyspnea associated with tachycardia in these patients.
- 222007
제1저자 조준성 · 교신저자 임재준
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The interval between initiation of anti-tuberculosis treatment in patients with culture-positive pulmonary tuberculosis and receipt of drug-susceptibility test results.J Korean Med Sci. 2007;22(1):26-9.
PubMed IF 3.2 호흡기내과Abstract
Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media.
- 212007
제1저자 구보경 · 교신저자 박경수
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Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population.Diabet Med. 2007;24(2):178-86.
PubMed IF 3.3 내분비대사내과Abstract
AIMS Kir6.2 is found in the pancreatic B-cell, cardiac and skeletal muscle and non-vascular smooth muscle. KCNJ11, encoding Kir6.2, has been shown to be associated with both Type 2 diabetes mellitus and cardiovascular disease in several populations. In this study, we investigated whether polymorphisms in KCNJ11 are associated with Type 2 diabetes and other metabolic phenotypes in the Korean population.
METHODS We sequenced KCNJ11 to identify common polymorphisms using 24 Korean DNA samples. Of the 14 polymorphisms found in KCNJ11, six common ones [genomic sequence (g.)-1709A>T, g.-1525T>C, g.67G>A (E23K), g.570C>T (A190A), g.1009A>G (I337V), and g.1388C>T] were genotyped in 761 Type 2 diabetic patients and in 630 non-diabetic subjects.
RESULTS All the polymorphic loci in KCNJ11 are in strong linkage disequilibrium in the Korean population and act as one haplotype block. g.67G>A and g.1009A>G were associated with an increased risk of Type 2 diabetes [age, sex, and body mass index (BMI)-adjusted odds ratios (OR) = 1.376 (1.085-1.745), P = 0.008 and 1.411 (1.111-1.791), P = 0.005, respectively], as was one haplotype (A-T-A-C-G-C in the order of polymorphisms as shown above) containing g.67A and g.1009G [OR = 1.359 (1.080-1.709), P = 0.009]. The haplotype (A-T-A-C-G-C) was also strongly associated with hypertension [OR = 1.655 (1.288-2.126), P < 0.001].
CONCLUSIONS Polymorphisms in KCNJ11 are associated with Type 2 diabetes and also with hypertension in the Korean population.
- 202007
제1저자 임수 · 교신저자 장학철
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Visceral fatness and insulin sensitivity in women with a previous history of gestational diabetes mellitus.Diabetes Care. 2007;30(2):348-53.
PubMed IF 22.6 내분비대사내과Abstract
OBJECTIVE The purpose of this study was to investigate the insulin sensitivity and visceral fatness in women with previous gestational diabetes mellitus (GDM), who are prone to develop type 2 diabetes.
RESEARCH DESIGN AND METHODS A 75-g oral glucose tolerance test (OGTT) performed 1 year postpartum identified 21 GAD(-) women with previous GDM and impaired glucose tolerance (GDM-IGT). Sixty age- and BMI-matched women with normal glucose tolerance (GDM-NGT) were selected by 1:3 matching to the GDM-IGT group. Another 18 women with normal glucose metabolism during a previous pregnancy and no family history of diabetes were recruited as the normal control group. Age and BMI matching was performed using a range of +/-1.0 years and +/-1.0 kg/m(2), respectively. Total body fat was measured by tetrapolar bioelectrical impedance, and visceral fat was determined using a single cut of a computed tomography scan. Insulin sensitivity was determined by the minimal model technique using the frequently sampled intravenous glucose tolerance test.
RESULTS One year postpartum, visceral fat was greater in the GDM-IGT group than in the age- and BMI-matched GDM-NGT or normal control groups. The insulin sensitivity index was lower in the GDM-IGT group than in the GDM-NGT or normal control groups. beta-Cell function, as measured by the acute insulin response to glucose, was also lower in GDM-IGT.
CONCLUSIONS High body fat content, especially visceral fat content, and a low insulin response to glucose seem to contribute simultaneously to the development of impaired glucose metabolism in Korean women with previous GDM.
- 192007
제1저자 박흥우 · 교신저자 조상헌
, , , , , , , ,
Outcomes in occupational asthma caused by reactive dye after long-term avoidance.Clin Exp Allergy. 2007;37(2):225-30.
PubMed IF 5 알레르기내과Abstract
BACKGROUND Reactive dye (RD) is known to be a causative agent of occupational asthma (OA). However, to date, no report has been issued concerning the long-term outcomes of RD-induced OA.
OBJECTIVES We sought to evaluate the long-term outcomes in cases of OA caused by RD.
METHODS A total of 11 OA patients confirmed by RD bronchial challenge were enrolled in this study. First and second follow-up examinations were conducted at 4.3+/-2.3 and 13.7+/-2.3 years (means+/-SD) after the initial examinations, respectively. Skin prick test with RD and 11 common inhalant allergens, pulmonary function test, methacholine bronchial provocation testing, symptom and medication scores were determined at each visit. In addition, inflammatory cells in induced sputum were measured at the second follow-up examinations.
RESULTS Reduced lung function at initial examinations did not recover at the first and second examinations despite cessation of exposure and proper pharmacological treatment. In addition, asthma severity (as determined by symptom and medication scores) and non-specific airway hyper-responsiveness to methacholine also did not improve. However, skin reactivity to RD almost disappeared at the second examinations. Interestingly, four of the six patients who showed negative skin responses to all 11 common inhalant allergens at initial examinations were found to be atopic at the second examinations. Moreover, in terms of airway inflammation, seven of the 11 patients showed eosinophilia in induced sputum (> or =3%) at the second examinations despite having been on high-dose inhaled corticosteroid medication.
CONCLUSION The present study demonstrates that reduced lung function and asthmatic symptoms persist in RD-induced OA even after long-term exposure avoidance.
- 182007
제1저자 임춘수 · 교신저자 임춘수
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Association between the clara cell secretory protein (CC16) G38A polymorphism and the progression of IgA nephropathy.Clin Nephrol. 2007;67(2):73-80.
PubMed IF 0.8 신장내과Abstract
AIMS Clara cell secretory protein (CC16) is a protein with anti-inflammatory and immunomodulatory properties. Moreover, both CC16 gene knockout and antisense-transgenic mouse models developed glomerulonephritis resembling IgA nephropathy (IgAN). In the present study, we evaluated the influence of the G38A polymorphism in the CC16 gene exon 1 on the development and progression of IgAN.
METHODS Korean patients with biopsy-proven IgAN (n=267) with a minimal follow-up of 4 years (mean +/- SD 103.8 +/- 52.6 months) were recruited. Healthy normal subjects (n=315) were included as controls. The G38A polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method.
RESULTS GG, GA and AA genotype frequencies were 36.3, 50.2 and 13.5% in IgAN patients, respectively, and 34.3, 50.2 and 15.5% in controls (chi2 = 0.596, p = 0.742). The G allele frequency was 0.614 in IgAN patients and 0.594 in controls (chi2 = 0.429, p = 0.512). Moreover, the GG genotype frequencies were 40.4% in patients showing stable disease course and 26.6% in those with progressive disease (chi2 = 4.029, p = 0.045). Patients with the GG genotype showed a better outcome by Kaplan-Meier analysis in terms of renal survival (p = 0.043). The CC16 polymorphism remained an independent risk factor for progression after multivariate analysis (Cox regression model, HR for CC16 AA genotype: 2.34, 95% CI 1.19-4.64, p = 0.014).
CONCLUSION Our results suggest that CC 16 gene G38A polymorphism is not associated with the development of IgAN, but that it is an important marker of progression in IgAN.
- 172007
제1저자 이은봉 · 교신저자 송영욱
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Haplotype association of IL-8 gene with Behcet's disease.Tissue Antigens. 2007;69(2):128-32.
PubMed IF 2.75 류마티스내과Abstract
Interleukin-8 (IL-8), a CXC chemokine that recruits and activates inflammatory cells, plays a critical role in the pathogenesis of Behcet's disease (BD). To investigate the association of the genetic polymorphism of IL-8 and BD, we genotyped IL-8 -845 T/C, -738 T/A, -353 A/T, -251 A/T, +293 G/T, +678 T/C and receptors CXCR-1 +2607 G/C and CXCR-2 +785 C/T polymorphisms in 119 Korean patients with BD and 119 age- and sex-matched healthy blood donors. Then, single nucleotide polymorphisms (SNPs) and haplotypes were analyzed between patients and controls. There were no SNPs associated with BD. However, the frequency of haplotype TAT inferred from SNPs, IL-8 -353 A/T, -251 A/T and +678 T/C, was significantly higher in patients with BD than controls (5.9 vs 0.0%, P = 0.0001), as was haplotype ATC (6.7 vs 0.0%, P < 0.0001). The haplotype difference was still valid in human leukocyte antigen-B51-negative subjects. In conclusion, we found a significant difference in the distribution of IL-8 gene haplotypes between patients with BD and healthy controls. These results suggest that the genetic polymorphisms of proinflammatory chemokine IL-8 can contribute to the pathogenesis of BD.
- 162007
제1저자 이종열 · 교신저자 김주성
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Simvastatin inhibits NF-kappaB signaling in intestinal epithelial cells and ameliorates acute murine colitis.Int Immunopharmacol. 2007;7(2):241-8.
PubMed IF 5.6 소화기내과Abstract
Statins, HMG-CoA reductase inhibitors exert pleiotropic anti-inflammatory properties in vitro and in vivo, and are associated with the risk reduction of colorectal cancer. It remains unknown, however, whether statin is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of simvastatin on intestinal epithelial cells (IEC) and on an experimental murine colitis model, and elucidated its molecular mechanisms. Simvastatin (50 micro M) significantly inhibited TNF-alpha-induced IL-8 gene expression in COLO 205 cells. Simvastatin (50 micro M) blocked TNF-alpha-induced NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation and DNA binding activity of NF-kappaB. Administration of simvastatin significantly reduced the severity of dextran sulfate sodium (DSS)-induced murine colitis as assessed by body weight, colon length, DAI, and histology in a dose-dependent manner. These results suggest that simvastatin inhibits proinflammatory gene expression by blocking NF-kappaB signaling in IEC, and attenuates DSS-induced acute murine colitis. Simvastatin could be a potential agent for the treatment of IBD.
- 152007
제1저자 김희정 · 교신저자 임재준
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Lack of association between the microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene and bronchiectasis among Koreans.Respirology. 2007;12(1):49-53.
PubMed IF 7.2 호흡기내과Abstract
BACKGROUND AND OBJECTIVE The genetic factors for the development of bronchiectasis are not well understood in most patients. The aim of this study was to elucidate the possible association between bronchiectasis and guanine-thymine (GT) repeat polymorphism in intron 2 of the human Toll-like receptor 2 (TLR2), which has a crucial role in adaptive as well as innate immunity.
METHODS A total of 194 patients with bronchiectasis and the same number of age- and gender-matched healthy blood donors were prospectively enrolled. The numbers of GT repeats were determined by PCR and gene scans. For further analysis, the alleles were classified into three subclasses: 12-16 GT repeats, short alleles (S allele); 17-22 repeats, medium-length alleles (M allele); and 23-27 repeats, long alleles (L allele).
RESULTS The overall distribution of alleles was not different between patient and control groups (P = 0.71). In addition, the frequencies of genotypes including short alleles were not different between patient and control groups (P = 0.92). Extent of bronchiectasis (P = 0.92) and bacterial colonization (P = 0.48) were not associated with any subclass genotype.
CONCLUSIONS Alleles and genotype including the shorter GT repeats in intron 2 of the TLR2, were not associated with the development, extent and bacterial colonization of bronchiectasis in Koreans.
- 142007
제1저자 김성한 · 교신저자 오명돈
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The persistence of humoral and cellular immunities more than three decades after smallpox vaccination.Clin Microbiol Infect. 2007;13(1):91-3.
PubMed IF 8.7 감염내과Abstract
This study assessed the persistence of humoral (neutralising antibody titre to vaccinia virus) and cellular (immediate vaccinia-specific interferon (IFN)-gamma-producing T-cell) immunities to smallpox in a Korean population. Individuals who were vaccinated 25-60 years previously had higher neutralising antibody titres (geometric mean titre (GMT) 13.7; 95% CI 11.0-17.2) than vaccinia-naive individuals (GMT 6.7; 95% CI 5.5-8.0; p <0.001). However, there was no significant difference in cellular immunity between individuals vaccinated previously and vaccinia-naive individuals, and only 15% of the individuals vaccinated previously displayed an immediate IFN-gamma-producing effector-memory response in ELISPOT assays.
- 132007
제1저자 김재현 · 교신저자 박경수
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Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs.Xenotransplantation. 2007;14(1):60-6.
PubMed IF 3.8 내분비대사내과Abstract
BACKGROUND Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse.
METHODS Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation.
RESULTS The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs.
CONCLUSIONS We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.
- 122007
제1저자 김형관 · 교신저자 손대원
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Assessment of left ventricular rotation and torsion with two-dimensional speckle tracking echocardiography.J Am Soc Echocardiogr. 2007;20(1):45-53.
PubMed IF 8.3 순환기내과Abstract
BACKGROUND Speckle tracking echocardiography (STE) has a unique feature of angle independence and, thus, may provide a powerful means of assessing left ventricular (LV) torsion (LVtor). The aims of this study were to assess: (1) the feasibility of 2-dimensional STE in the measurement of LVtor; and (2) the relationship of LVtor with age and conventional echocardiographic parameters.
METHODS We consecutively recruited 160 healthy volunteers. After obtaining conventional echocardiographic parameters, apical and basal short-axis rotations were assessed with STE. LVtor was defined as the net difference between rotation angles in the two short-axis planes normalized for LV longitudinal length.
RESULTS Reliable LVtor measurement was possible only in 56 volunteers (35%). This low feasibility was largely a result of the failure to obtain reliable basal rotation values. In 56 volunteers who were finally enrolled in this study, a significant correlation was found between LV ejection fraction and LVtor (r = 0.56, P < .001) and this correlation was attributed to apical (r = 0.47, P < .001) but not basal (P = .14) rotation. There was no significant change in LVtor with aging. However, initial counterclockwise motion (r = -0.51, P = .001) and its interval (r = -0.44, P = .001) in the basal rotation gradually decreased with aging, and correlated with early transmitral inflow velocity (r = 0.44 and 0.49, respectively) and its deceleration time (r = -0.43 and -0.48, respectively) (all P < .001). In contrast, such correlations were not found for initial clockwise motion and its interval in the apical rotation.
CONCLUSIONS Currently, STE has limited feasibility in the measurement of LVtor. There was no significant age-related change in LVtor. In LV rotations, basal rotation was affected by the age-related changes in the LV early diastolic filling, whereas apical rotation was mainly related to LV systolic performance.
- 112007
제1저자 조요한 · 교신저자 윤성수
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Pharmacokinetics and tolerability of intravenous busulfan in hematopoietic stem cell transplantation.Clin Transplant. 2007;21(3):417-22.
PubMed IF 1.8 혈액종양내과Abstract
Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean stem cell transplantation (SCT) patients. IV busulfan was administered at 0.8 mg/kg every six h for a total of 16 doses (days -7 to -4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 h for two d (days -3 and -2). The median AUC(inf) values (at the first dose) and AUC(ss) (at the steady state) were 1060.4 microM.min (range: 511.1-1812.7) and 1092.5 microM.min (range: 539.7-1560.8) respectively. All patients had an AUC(inf) of <1500 microM.min at the first dose, and 13 of the 16 (81.3%) maintained AUC(ss) levels between 800 and 1500 microM.min. Thirteen of 16 patients showed successful engraftments but four patients (25%) developed hepatic VOD (two of which were fatal), three of whom had advanced disease at the time of SCT. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable with those observed in other study. However, hepatic VOD was a major morbidity in patients with advanced disease.
- 102007
제1저자 윤탁 · 교신저자 윤성수
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Non-myeloablative allogeneic stem cell transplantation for metastatic renal cell carcinoma.Clin Transplant. 2007;21(3):337-43.
PubMed IF 1.8 혈액종양내과Abstract
Between 1999 and 2004, 11 patients with metastatic renal cell carcinoma (RCC) underwent non-myeloablative stem cell transplantation (NST) with conditioning using fludarabine-based regimens in two institutions of Korea. Among 11 patients, only one patient showed partial response (response rate: 9%), three showed stable disease, and six progressive disease. Three patients developed acute graft-versus-host disease (GVHD), and among them, one developed grade III acute GVHD which caused early death at day 60 after transplantation, and this patient showed partial response at day 30. Six patients developed chronic GVHD, three limited, and three extensive GVHD, respectively. Survival after one yr was 18% in transplanted patients. Median overall survival for entire cohort was 4.3 months. Eight patients died from progressive disease and three (27%) from treatment-related mortality. Only one patient survived 51.2 months after NST with slowly progressive disease. This patient received donor lymphocyte infusion three times after NST and achieved complete donor chimerism. NST does not lead to durable response and prolonged overall survival in the majority of patients with RCC in our series.
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