SCI 발표논문
전체 4,588편
- 2382007
제1저자 구본권 · 교신저자 김효수
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Effect of celecoxib on restenosis after coronary angioplasty with a Taxus stent (COREA-TAXUS trial): an open-label randomised controlled study.Lancet. 2007;370(9587):567-74.
PubMed IF 109 순환기내과Abstract
BACKGROUND In-vitro and animal experiments have shown that the cyclo-oxygenase 2 inhibitor celecoxib can reduce formation of neointima within stents. We aimed to test whether celecoxib has similar effects in a clinical setting.
METHODS In a randomised two-centre trial, we enrolled 274 patients who had angina pectoris or a positive stress test and who had native coronary artery lesions for which implantation of paclitaxel-eluting stents was feasible. All patients were given aspirin (100 mg daily) and clopidogrel (75 mg daily). 136 patients were randomly assigned to receive celecoxib (400 mg before the intervention, and 200 mg twice daily for 6 months after the procedure). The primary endpoint was late luminal loss on quantitative coronary angiography at 6 months after the intervention. Secondary endpoints were cardiac death, non-fatal myocardial infarction, and revascularisation of the target lesion. Analysis was done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00292721.
FINDINGS At 6 months, mean in-stent late luminal loss was lower in the celecoxib group (0.49 mm, SD 0.47) than in the control group (0.75 mm, 0.60) (absolute difference 0.26 mm; 95% CI 0.12-0.40). Frequency of secondary outcomes at 6 months was also lower in the celecoxib group, mainly because of a reduced need for revascularisation of the target lesion.
INTERPRETATION These data suggest that the adjunctive use of celecoxib for 6 months after stent implantation in patients with coronary artery disease is safe and can reduce the need for revascularisation of the target lesion.
- 2372007
제1저자 김성한 · 교신저자 오명돈
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Detailed kinetics of immune responses to a new cell culture-derived smallpox vaccine in vaccinia-naïve adults.Vaccine. 2007;25(33):6287-91.
PubMed IF 3.4 감염내과Abstract
The aim of the present study was to investigate the kinetics of humoral and cell-mediated immune responses to a new cell culture-derived smallpox vaccine (CJ-50300, CJ Corporation, South Korea) in 18 vaccinia-naïve volunteers. All subjects achieved positive humoral immune responses (plaque reduction neutralizing antibody assay) 28 days after vaccination, and cell-mediated immune responses (ELISPOT assay) 14 days after vaccination. Humoral immune responses increased up to 28 days after vaccination and were maintained up to 56 days after vaccination. In contrast, cell-mediated immune responses increased up to 14 days after vaccination and steadily decreased to 56 days after vaccination [Clinical Trial No. NCT 00336635].
- 2362007
제1저자 임정윤 · 교신저자 김나영
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Seroprevalence of Helicobacter pylori in South Korea.Helicobacter. 2007;12(4):333-40.
PubMed IF 4.6 소화기내과Abstract
BACKGROUND Helicobacter pylori-associated gastrointestinal diseases have been widely recognized. The aims of this study were to investigate the interval change of seropositivity of H. pylori between 1998 and 2005 in Korean adult population and to find the factors related to H. pylori infection.
METHODS Between January and December of 2005, a total of 15,916 health check-up subjects (aged > or = 16 years) from all parts of South Korea responded to the questionnaire, and the prevalence of H. pylori was investigated by measuring anti-H pylori IgG antibodies. The seropositivity in asymptomatic subjects (aged > or = 16 years) was compared with that of 1998, which was surveyed by the Korean H. pylori Study Group.
RESULTS The overall seropositivity rate (aged > or = 16 years) was 56.0%, and 13.9% of seropositive subjects were found to have a history of H. pylori eradication therapy. With the exclusion of subjects who had a history of H. pylori eradication and current gastrointestinal symptoms, the seropositivity rate of H. pylori became 59.6% in 8020 subjects. Seroprevalence of H. pylori was significantly higher in subjects aged 50-59 years, males, low income group, and subjects from provinces. The seroprevalence in 2005 (59.6%) significantly decreased compared with that of 1998 (66.9%), and the decrease was significant in subjects aged < 70 years, Seoul and Gyeonggi province (which is close to Seoul).
CONCLUSIONS The seroprevalence of H. pylori in asymptomatic health check-up adult subjects in 2005 decreased to 59.6% from 66.9% in 1998, probably as a result of the improvement of socioeconomic status and hygiene.
- 2352007
제1저자 이지원 · 교신저자 임재준
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Lack of association between matrix metalloproteinase 8 promoter polymorphism and bronchiectasis in Koreans.J Korean Med Sci. 2007;22(4):667-71.
PubMed IF 3.2 호흡기내과Abstract
The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/ T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex-matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans.
- 2342007
제1저자 박영주 · 교신저자 박소연
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Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules.J Korean Med Sci. 2007;22(4):621-8.
PubMed IF 3.2 내분비대사내과Abstract
The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC). The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.
- 2332007
제1저자 조수정 · 교신저자 이효석
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Do young hepatocellular carcinoma patients with relatively good liver function have poorer outcomes than elderly patients?J Gastroenterol Hepatol. 2007;22(8):1226-31.
PubMed IF 3.5 소화기내과Abstract
BACKGROUND AND AIM The risk of hepatocellular carcinoma (HCC) is known to be age dependent; the influence of age on prognosis is, however, controversial. The aim of this study was to compare the tumor characteristics and survival rates of young and old HCC patients, with respect to tumor stage.
METHODS We reviewed the clinical data and survival times of 71 young HCC patients from 1987 to 2003 and compared these with those of their older counterparts (n = 239). Patients were categorized into three age groups: group A, age <30 years (n = 71); group B, age >/=30 to <61 years (n = 168); and group C, age >/=61 years (n = 81). Kaplan-Meier methods and Cox proportional hazards regression were used to analyze survival.
RESULTS The overall survival time of group A was shorter than groups B or C (P = 0.0071). Survival was not different in the three groups in subgroup analysis according to several tumor staging systems (e.g. Japan Integrated Staging score, Cancer of the Liver Italian Program scoring system and Barcelona Clinic Liver Cancer staging classification). The multivariate hazard ratio of group B was 0.840 (95% confidence interval [CI] 0.490-1.440) and that of group C was 0.770 (95% CI 0.410-1.446) in reference to group A.
CONCLUSIONS Young HCC patients showed a poorer prognosis than older HCC patients because they have a more advanced tumor stage at diagnosis. However, age was not an independent prognostic factor when stages were matched. Therefore, we suggest that periodic surveillance in young chronic hepatitis B virus carriers would improve outcomes.
- 2322007
제1저자 주권욱 · 교신저자 안규리
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MCP-1 and RANTES polymorphisms in Korean diabetic end-stage renal disease.J Korean Med Sci. 2007;22(4):611-5.
PubMed IF 3.2 신장내과Abstract
Macrophage infiltration has been observed in the renal biopsy specimens of diabetic nephropathy (DN), and hyperglycemic state stimulates the renal expression of RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP- 1 (monocyte chemoattractant protein-1). Upregulation of RANTES and MCP-1 with infiltrating macrophages may play a crucial role in the development and progression of DN. Genetic polymorphisms of RANTES and its receptors were reported to be independent risk factors for DN. We genotyped single nucleotide polymorphism (SNPs) in the MCP-1 G-2518A, CCR2 G46295A, RANTES C-28G and G-403A in 177 diabetic end-stage renal disease (ESRD) patients and 184 patients without renal involvement (controls) in order to investigate the effects of these SNPs on DN in Korean patients with type 2 DM. There were no differences in the frequencies of SNPs and the distribution of haplotypes of RANTES promoter SNPs between two groups. In conclusion, there were no associations of MCP-1, CCR2 and RANTES promoter SNPs with diabetic ESRD in Korean population. Prospective studies with clearly-defined, homogenous cohorts are needed to confirm the effect of these genetic polymorphisms on DN.
- 2312007
제1저자 이상협 · 교신저자 류지곤
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How to predict the outcome of endoscopic mechanical lithotripsy in patients with difficult bile duct stones?Scand J Gastroenterol. 2007;42(8):1006-10.
PubMed IF 1.8 소화기내과Abstract
OBJECTIVE Endoscopic mechanical lithotripsy is frequently used to overcome the difficulties of removing large bile duct stones endoscopically. The aim of this study was to identify predictors of endoscopic mechanical lithotripsy failure.
MATERIAL AND METHODS One hundred and thirty-four patients who underwent mechanical lithotripsy for difficult choledocholithiasis were evaluated retrospectively. Predictive factors of outcome and procedure-related complications were analyzed. The clinical outcomes of subsequent management were also evaluated in cases of unsuccessful endoscopic mechanical lithotripsy.
RESULTS Endoscopic mechanical lithotripsy was successful in 102 patients (76.1%). Stone impaction, size (>or=30 mm), and the stone size to bile duct diameter ratio (>1.0) were significant predictors of endoscopic mechanical lithotripsy failure, with estimated odds ratios of 17.83, 4.32 and 5.47, respectively. There was no difference in complication rates between the successful and failed mechanical lithotripsy groups. When mechanical lithotripsy failed, all patients were successfully treated using various modalities, including surgery, without mortality.
CONCLUSIONS An impacted stone, stone size (>or=30 mm) and stone size to bile duct diameter ratio (>1.0) were predictors of failure of endoscopic mechanical lithotripsy for a difficult bile duct stone. Alternative approaches should be considered in patients with predictors of unsuccessful endoscopic mechanical lithotripsy in order to avoid wasting time and resources.
- 2302007
제1저자 최윤식 · 교신저자 오세일
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Typical atrioventricular nodal reentrant tachycardia in a patient with fasciculoventricular pathway.J Electrocardiol. 2007;40(6):535-8.
PubMed IF 1.5 순환기내과Abstract
We report a 34-year-old female patient with preexcitation electrocardiogram and recurrent paroxysmal palpitations. Standard 12-lead electrocardiogram showed minimal preexcitation with normal PR interval and normal frontal QRS axis. The electrophysiologic study showed normal AH intervals, short HV intervals, and no change in the degree of preexcitation by rapid atrial pacing. These findings were compatible with the fasciculoventricular pathway. Typical atrioventricular nodal reentrant tachycardia with narrow QRS complex and normal HV interval was induced reproducibly by programmed electrical stimulation. Slow pathway was ablated successfully with radiofrequency catheter ablation, and then the patient remained asymptomatic during a follow-up of 12 months. Although the fasciculoventricular pathway is rare and supraventricular tachycardia in a patient with fasciculoventricular pathway may mimic Wolff-Parkinson-White syndrome, possibility of typical atrioventricular nodal reentrant tachycardia with fasciculoventricular pathway should be considered as a mechanism of supraventricular tachycardia in a patient showing preexcitation electrocardiogram.
- 2292007
제1저자 김진욱 · 교신저자 Jian Wu
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Short hairpin RNA causes the methylation of transforming growth factor-beta receptor II promoter and silencing of the target gene in rat hepatic stellate cells.Biochem Biophys Res Commun. 2007;359(2):292-7.
PubMed IF 2.5 소화기내과Abstract
Small interfering RNA (siRNA) induces transcriptional gene silencing (TGS) in plant and animal cells. RNA dependent DNA methylation (RdDM) accounts for TGS in plants, but it is unclear whether siRNA induces RdDM in mammalian cells. To determine whether stable expression of short hairpin siRNA (shRNA) induces DNA methylation in mammalian cells, we transduced rat hepatic stellate SBC10 cells with lentiviral vectors which encode an U6 promoter-driven shRNA expression cassette homologous to the transforming growth factor-beta receptor (TGFbetaRII) promoter region. Sequencing analysis of bisulfite-modified genomic DNA showed the methylation of cytosine residues both in CpG dinucleotides and non-CpG sites around the target region of the TGFbetaRII promoter in SBC10 cells transduced with the promoter-targeting lentiviral vector. In these cells, real-time RT-PCR showed a decrease in TGFbetaRII mRNA levels which were reversed by treatment with 5-aza-2-deoxycytidine. Our results demonstrate that recombinant lentivirus-mediated shRNA delivery resulted in the methylation of the homologous promoter area in mammalian cells, and this approach may be used as a tool for transcriptional gene silencing by epigenetic modification of mammalian cell promoters.
- 2282007
제1저자 이관식 · 교신저자 이효석
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Clevudine therapy for 24 weeks further reduced serum hepatitis B virus DNA levels and increased ALT normalization rates without emergence of viral breakthrough than 12 weeks of clevudine therapy.Intervirology. 2007;50(4):296-302.
PubMed IF 1.8 소화기내과Abstract
OBJECTIVES The objectives of the study were to evaluate the safety and antiviral activity of 24-week treatment with clevudine 30 mg in HBeAg(+) chronic hepatitis B patients. Biochemical and serological responses were also assessed.
METHOD Twenty-one patients received clevudine 30 mg for 24 weeks and were followed up for another 24 weeks off therapy.
RESULTS Median decreases from baseline in HBV DNA were 4.65 and 1.96 log(10) copies/ml at week 24 (end of treatment) and week 48 (24 weeks off therapy), respectively. Analysis of individual data showed that HBV DNA levels were below the lower limit of detection (300 copies/ml) by Amplicor PCR assay in 19, 57, 19 and 0% at week 12, 24, 34 and 48, respectively. The proportion of patients with normal ALT were 67, 81 and 75% at week 24 (end of treatment), 34 and 48 (24 weeks off therapy), respectively. The rates of HBeAg loss were 24 and 20% at week 24 and 48, respectively. No viral breakthrough during treatment was observed.
CONCLUSION Clevudine 30 mg treatment for 24 weeks was well tolerated and exhibited more potent antiviral activity and a higher ALT normalization rate than 12-week treatment with durable efficacy at week 24 off therapy.
- 2272007
제1저자 이재호 · 교신저자 이춘택
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Haemoptysis due to chronic tuberculosis vs. bronchiectasis: comparison of long-term outcome of arterial embolisation.Int J Tuberc Lung Dis. 2007;11(7):781-7.
PubMed IF 3.6 호흡기내과Abstract
OBJECTIVE To evaluate the factors that influence the outcome of bronchial arterial embolisation (BAE) in chronic tuberculosis (TB). In cases of chronic TB, non-bronchial systemic arteries (NBSA) provide a significant source of massive or recurrent haemoptysis.
DESIGN Medical records and radiological findings of 30 consecutive TB patients who underwent BAE were retrospectively analysed and compared with those of 19 bronchiectasis patients.
RESULTS Chronic TB patients had higher numbers of total feeding vessels (4.40 + or - 3.85 vs. 1.79 + or - 1.51, P = 0.007) and NBSA (1.57 + or - 1.63 vs. 0.42 + or - 0.61, P = 0.005) than the bronchiectasis patients. The number of embolisations required for obliterating feeding vessels (3.87 + or - 2.48 vs. 1.95 + or - 1.47, P = 0.004), and the incidence of incomplete embolisation (30% vs. 5.3%, P = 0.033) were also higher in the TB patients. Moreover, recurrence after BAE was more frequent in the TB patients (17/30, 56.7% vs. 5/19, 26.3%, P = 0.037). Male sex, past history of haemoptysis and incomplete embolisation during BAE were associated with higher recurrence of haemoptysis in chronic TB patients. The existence of a fungus ball or significant pleural thickening (> or =10 mm) was not found to influence the recurrence rate of haemoptysis.
CONCLUSION The haemoptysis recurrence rate was higher in chronic TB than in bronchiectasis; this was found to be related to incomplete feeding vessel embolisation.
- 2262007
제1저자 김병수 · 교신저자 윤성수
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Combination of SK-7041, one of novel histone deacetylase inhibitors, and STI571-induced synergistic apoptosis in chronic myeloid leukemia.Anticancer Drugs. 2007;18(6):641-7.
PubMed IF 2 혈액종양내과Abstract
Although STI571 still plays a key role in the treatment of chronic myeloid leukemia, emergence of resistance to STI571 is a major obstacle to successful outcome. Therefore, new agents that increase the sensitivity of chronic myeloid leukemia cells to STI571 are urgently required. SK-7041 is a novel hybrid synthetic histone deacetylase inhibitor derived from the hydroxamic acid of trichostatin A and pyridyl ring of MS-275. Its cytotoxic effects were examined both as a single agent and in combination with STI571 in acute and chronic myeloid leukemia. SK-7041 exhibited growth inhibition of leukemia cells by downregulation of CDK4, cyclin E and cyclin B1 expression, and by upregulation of p21 expression with subsequent activation of the mitochondria-mediated caspase pathway. SK-7041 showed synergism on growth inhibition, cell cycle arrest and induction of apoptosis in chronic myeloid leukemia (K562) when combined with STI571. The synergistic effect was mediated through the same mechanism as in SK-7041 alone, involving reduction of cyclin D1 and induction of p21. Taken together, our findings suggest that SK-7041 is active against leukemia and offers new prospects for overcoming STI571 resistance in chronic myeloid leukemia.
- 2252007
제1저자 최성희 · 교신저자 차봉수
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The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats.Diabetes Metab Res Rev. 2007;23(5):411-8.
PubMed IF 8.3 내분비대사내과Abstract
OBJECTIVE To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model.
METHODS OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content.
RESULTS Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 +/- 0.04 vs 0.88 +/- 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 +/- 0.4 vs 20.6 +/- 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 +/- 1.2 vs 18.8 +/- 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement.
CONCLUSION The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats.
- 2242007
제1저자 허진,윤창환 · 교신저자 김효수
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Akt is a key modulator of endothelial progenitor cell trafficking in ischemic muscle.Stem Cells. 2007;25(7):1769-78.
PubMed IF 4.8 순환기내과Abstract
Trafficking of transplanted endothelial progenitor cells (EPCs) to ischemic tissue is enhanced by stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF). However, it has not been studied how these cytokines modulate the local milieu to entrap EPCs. This study was performed to elucidate a molecular pathway of trafficking EPCs through Akt and to test its application as an adjuvant modality to increase EPC homing. In a mouse hind limb ischemia model, systemically administered 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled mouse EPCs showed three stages of homing to ischemic limb: adhesion to endothelial cells (ECs), incorporation to capillary, and transendothelial migration into extravascular space. As an underlying mechanism to control adhesion of EPCs to ECs, we found that Akt was activated in ECs of ischemic muscle by ischemia-induced VEGF and SDF-1. In vitro and in vivo experiments using adenoviral vector for constitutively active or dominant-negative Akt genes showed that activated Akt enhanced intercellular adhesion molecule 1 (ICAM-1) expression on ECs. Akt activation in ECs also enhanced EPC incorporation to ECs and transendothelial migration in vitro experiments. Activated Akt was sufficient for induction of EPC homing even in normal hind limb, where VEGF or SDF-1 was not increased. Finally, local Akt gene transfer to ischemic limb significantly enhanced homing of systemically administered EPCs, new vessel formation, blood flow recovery, and tissue healing. Akt plays a key role in EPC homing to ischemic limb by controlling ICAM-1 and transendothelial migration. Modulation of Akt in the target tissue may be an adjunctive measure to enhance homing of systemically administered stem cells, suggesting a possibility of cell-and-gene hybrid therapy. Disclosure of potential conflicts of interest is found at the end of this article.
- 2232007
제1저자 김나영,조수정 · 교신저자 송인성
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The anti-cancer effect of COX-2 inhibitors on gastric cancer cells.Dig Dis Sci. 2007;52(7):1713-21.
PubMed IF 2.8 소화기내과Abstract
Epidemiologic studies have shown that nonsteroidal anti-inflammatory drugs could reduce the risk of cancer development including gastric cancer. This study was performed to identify the antineoplastic mechanism in gastric cancer cells affected by celecoxib, a selective COX-2 inhibitor. MTT assay, ELISA for prostaglandin E(2) (PGE(2)), cell-cycle analyses, immunofluorescent staining, and flow cytometry were performed after treating human gastric cancer cell lines (AGS and MKN-45) with celecoxib or indomethacin. The viabilities of celecoxib-treated cells decreased in a dose- and time-dependent manner compared with indomethacin. Drop of PGE(2) levels was more prominent in the presence of indomethacin than in that of celecoxib. Celecoxib arrested the cell cycle in the G(0)-G(1) phase, which reduced cell numbers in the S phase. Moreover, celecoxib increased the apoptotic cell proportions, a 4-fold increase over control cells. The anticancer effects of celecoxib on gastric cancer cells appear to be mediated by cell-cycle arrest and apoptosis, and not by COX-2 or PGE(2) suppression alone.
- 2222007
제1저자 이은봉 · 교신저자 송영욱
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Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis.Arthritis Rheum. 2007;56(7):2443-8.
PubMed IF 7.38 류마티스내과Abstract
OBJECTIVE To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).
METHODS To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age- and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism or sequence-specific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chi-square tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.
RESULTS There was significant evidence of gene-gene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.
CONCLUSION Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.
- 2212007
제1저자 명선정 · 교신저자 윤정환
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Wnt signaling enhances the activation and survival of human hepatic stellate cells.FEBS Lett. 2007;581(16):2954-8.
PubMed IF 3.1 소화기내과Abstract
Wnt signaling was implicated in pulmonary and renal fibrosis. Since Wnt activity is enhanced in liver cirrhosis, Wnt signaling may also participate in hepatic fibrogenesis. Thus, we determined if Wnt signaling modulates hepatic stellate cell (HSC) activation and survival. Wnt3A treatment significantly activated human HSCs, while this was inhibited in secreted frizzled-related protein 1 (sFRP1) overexpressing cells. Wnt3A treatment significantly suppressed TRAIL-induced apoptosis in control HSCs versus sFRP1 over-expressing cells. Particularly, caspase 3 was more activated in sFRP1 over-expressing cells following TRAIL and Wnt3A treatment. These observations imply that Wnt signaling promotes hepatic fibrosis by enhancing HSC activation and survival.
- 2202007
제1저자 오도연 · 교신저자 오도연
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Artificial nutrition and hydration in terminal cancer patients: the real and the ideal.Support Care Cancer. 2007;15(6):631-636.
PubMed IF 3.4 혈액종양내과Abstract
INTRODUCTION To better understand current practice relating to artificial nutrition/hydration in terminal cancer patients, we enrolled terminal cancer patients who were admitted at Seoul National University Boramae Hospital for supportive care only and who died with a duration of hospital stay to death of more than 1 week between 2003 and 2004. We detailed oral intake and intravenous nutrition/hydration status on admission, 1 week after admission, and 2 days before death. Administered calories and changes in these according to time and "DNR" (do-not-resuscitate) status were noted.
RESULTS Of the total 165 patients, oral intake was possible in 84 patients (50.9%) on admission, in 79 patients (47.8%) on 1 week after admission, and in 29 patients (17.5%) 2 days before death (p < 0.01). Intravenous nutrition/hydration was administered to 133 patients (80.6%) on admission, to 125 patients (75.7%) at 1 week, and to 137 patients (83.0%) 2 days before death (p = 0.7). The calories administered to the patient by oral intake were 393 kcal on admission, 353 kcal 1 week after admission, and 89 kcal 2 days before death. In addition, the calories delivered by intravenous fluid were 369, 386 and 465 kcal, respectively. Near to death, calories by oral intake continuously reduced (p < 0.01) and intravenous calories continuously increased (p = 0.04), but total administered calories reduced (p = 0.03). Intravenous nutrition/hydration stopped after the attainment of the advance directive of DNR in 9% of patients.
CONCLUSION This study showed the high prevalence of artificial nutrition/hydration, especially intravenous infusion, in Korean terminal cancer patients compared with situation in other countries. More studies are needed to verify the efficacy of artificial nutrition/hydration in terminal cancer patients.
- 2192007
제1저자 박완범 · 교신저자 최강원
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Early modification of initial HAART regimen associated with poor clinical outcome in HIV patients.AIDS Res Hum Retroviruses. 2007;23(6):794-800.
PubMed IF 1 감염내과Abstract
Although the importance of the initial regimen in highly active antiretroviral therapy (HAART) has been emphasized, the effect on clinical outcome of early modification of the initial HAART regimen has not been well-defined. The analysis included antiretroviral-naive HIV patients who started HAART between 1999 and 2005 at a university hospital. Early modification was defined as any drug change within 2 months of starting HAART. The effect of early regimen modification on the occurrence of new AIDS-defining illness or death was assessed using Kaplan-Meier survival estimates, and hazard ratios were estimated using Cox's proportional hazards regression model. Of 398 patients beginning HAART, 21% experienced early modification of their regimen, the most common reason being gastrointestinal toxicity (49%). After adjusting for risk factors for occurrence of a new AIDS event or death, identified by univariate analysis, the hazards ratio contrasting early modification with maintenance of initial HAART regimen was 3.06 (95% confidence interval, 1.36-6.90; p = 0.007). There were significant differences between the AIDS event-free survival curves of patients in clinical categories B or C with or without early modification of initial HAART regimen (p = 0.0002), but no significant difference in patients in clinical category A (p = 0.706). A considerable proportion of patients who started HAART changed treatment regimen mainly due to intolerance early after start of HAART. Early modification of an initial HAART regimen was associated with poor clinical outcome in HIV patients in the advanced clinical categories.
- 2182007
제1저자 나기영 · 교신저자 한진석
, , , , , , , , ,
Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney.Am J Physiol Renal Physiol. 2007;292(6):F1701-9.
PubMed IF 3.6 신장내과Abstract
Furosemide administration stimulates distal acidification. This has been attributed to the increased lumen-negative voltage in the distal nephron, but the aspect of regulatory mechanisms of H(+)-ATPase has not been clear. The purpose of this study is to investigate whether chronic administration of diuretics alters the expression of H(+)-ATPase and whether electrogenic Na(+) reabsorption is involved in this process. A 7-day infusion of furosemide or hydrochlorothiazide (HCTZ) lowered urine pH significantly. However, this effect of furosemide-induced distal acidification was not changed with amiloride-blocking electrogenic Na(+) reabsorption. On immunoblotting, a polyclonal antibody against the H(+)-ATPase B1 subunit recognized a specific approximately 56-kDa band in membrane fractions from the kidney. The protein abundance of H(+)-ATPase was significantly increased by furosemide and HCTZ infusion in both the cortex and outer medulla. Furosemide plus amiloride administration also increased the H(+)-ATPase protein abundance significantly. However, no definite subcellular redistribution of H(+)-ATPase was observed by furosemide +/- amiloride infusion with immunohistochemistry. Chronic furosemide +/- amiloride administration induced a translocation of pendrin to the apical membrane, while total protein abundance was not increased. The mRNA expression of H(+)-ATPase was not altered by furosemide +/- amiloride infusion. We conclude that chronic administration of diuretics enhances distal acidification by increasing the abundance of H(+)-ATPase irrespective of electrogenic Na(+) reabsorption. This upregulation of H(+)-ATPase in the intercalated cells may be the result of tubular hypertrophy by diuretics.
- 2172007
제1저자 정수진 · 교신저자 이동호
, , , , , , , , ,
Eradication rates of helicobacter pylori infection with second-line treatment: non-ulcer dyspepsia compared to peptic ulcer disease.Hepatogastroenterology. 2007;54(76):1293-6.
PubMed IF 0.7 소화기내과Abstract
BACKGROUND/AIMS Initial proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) infection is less effective in patients with nonulcer dyspepsia (NUD) than those with peptic ulcer disease (PUD). To date, there have been no studies on the difference in eradication rates in NUD compared to PUD with regard to second-line therapy. Therefore, we retrospectively analyzed the difference in eradication rates of a second-line quadruple therapy for NUD and PUD patients.
METHODOLOGY Between June 2003 and December 2005, patients who failed to respond to initial PPI-based triple therapy, received 7 days of quadruple therapy (PPI b.i.d., bismuth 300mg q.i.d., metronidazole 500mg t.i.d., tetracycline 500mg q.i.d.) as a second-line treatment regimen. Four weeks after the completion of the course of medication, a 13C-urea breath test was performed for detection of H. pylori.
RESULTS A total of 87 patients received second-line quadruple therapy. Of these, 43 patients had NUD and 44 patients had PUD (19 gastric ulcers, 23 duodenal ulcers, 2 both ulcers). The eradication rates were 76.7% (33/43) in the NUD group and 90.9% (40/44) in the PUD group by per-protocol analysis. Therefore, the eradication rates in the NUD group were significantly lower than those in the PUD group (p = 0.034).
CONCLUSIONS A 7-day bismuth-based second-line quadruple therapy for H. pylori infection was less effective in patients with NUD than those with PUD. Therefore, a more potent second-line treatment regimen or extension of treatment duration of quadruple therapy should be considered for the eradication of H. pylori in patients with NUD.
- 2162007
제1저자 정우영 · 교신저자 조영석
, , , , , , , , , , ,
Effects of the early administration of heparin in patients with ST-elevation myocardial infarction treated by primary angioplasty.Circ J. 2007;71(6):862-7.
PubMed IF 5.8 순환기내과Abstract
BACKGROUND The effect of adjunctive heparin for primary angioplasty in patients with ST-elevation myocardial infarction (STEMI) is not well established, so the authors investigated the effect of early heparin administration in the emergency room (ER) on initial patency of the infarct-related artery (IRA) and on the clinical outcome in STEMI patients.
METHODS AND RESULTS One hundred and twenty consecutive patients who presented with STEMI less than 12 h from pain onset and who were eligible for primary percutaneous coronary intervention were allocated to an early heparin group (heparin administered in ER) or a late heparin group (heparin administered after angiography). In the early heparin group, unfractionated heparin (60 U/kg bolus IV, then 14 U . kg(-1) . h(-1) IV infusion) or enoxaparin (1 mg/kg bolus SC) were administered 144+/-95 min before angioplasty. No significant differences in baseline characteristics were observed between the early heparin group (n=56) and the late heparin group (n=64). However, initial Thrombolysis In Myocardial Infarction (TIMI) flow grade in the IRA was significantly different between the 2 groups (frequency of TIMI 0/1/2/3; 48/4/7/41% vs 70/8/11/11%, early vs late respectively, p=0.002). TIMI 2 or 3 flow was significantly more frequent in the early heparin group than in the late heparin group (48% vs 22%, p=0.002). However, no significant differences were noted between the 2 groups in terms of in-hospital major adverse cardiac events (7% vs 11%, p=0.472) and TIMI major bleeding (2% vs 3%, p=0.639).
CONCLUSIONS In STEMI patients, early heparin therapy administered in the ER improves coronary patency, despite not reaching clinical benefit.
- 2152007
제1저자 박흥우 · 교신저자 조상헌
, , , , , ,
Complementary roles of capsaicin cough sensitivity test and induced sputum test to methacholine bronchial provocation test in predicting response to inhaled corticosteroids in patients with chronic nonproductive cough.Ann Allergy Asthma Immunol. 2007;98(6):533-9.
PubMed IF 7.1 알레르기내과Abstract
BACKGROUND The capsaicin cough sensitivity test (CCST), methacholine bronchial provocation test (MBPT), and induced sputum test (IST) are widely used in the clinical evaluation of chronic nonproductive cough. However, little is known about their roles in predicting response to inhaled corticosteroids (ICSs) in patients with chronic nonproductive cough.
OBJECTIVE To test the hypothesis that the CCST and IST play complementary roles to the MBPT for predicting the response to ICS treatment in patients with chronic nonproductive cough.
METHODS A total of 43 patients with chronic nonproductive cough who showed isolated capsaicin cough hypersensitivity (CCST group) and 55 patients with chronic nonproductive cough who had methacholine airway hyperresponsiveness (MBPT group) were enrolled. These patients underwent the IST followed by treatment with ICSs for 4 weeks. Measurement of symptom improvement was recorded by the visual analog scale.
RESULTS The response rates to ICS treatment in the CCST and MBPT groups were similar (74.5% vs 86.0%; P = .21). Only the neutrophil count in the IST group was significantly different in responders and nonresponders after the ICS treatments (P = .005 for the CCST group and P = .006 for the MBPT group). Interestingly, the absence of sputum neutrophilia used as a criterion for subgroup analysis increased response rates in the patients with either methacholine airway hyperresponsiveness or capsaicin cough hypersensitivity.
CONCLUSIONS In the present study, we demonstrate that CCST and IST play complementary roles to MBPT. By combining the results of these tests, we are able to identify more patients with chronic nonproductive cough and treat patients more successfully with ICSs by improving the response rate to ICS treatment.
- 2142007
제1저자 양재석 · 교신저자 안규리
, , , , , ,
Molecular characterization of cDNA encoding porcine IP-10 and induction of porcine endothelial IP-10 in response to human TNF-alpha.Vet Immunol Immunopathol. 2007;117(1-2):124-8.
PubMed IF 1.8 신장내과Abstract
Donor-derived chemokines may play an important role in xenograft rejection, as well as allograft rejection. We have cloned the cDNA encoding porcine IP-10 (interferon-gamma-inducible protein 10), and evaluated its induction in miniature porcine endothelial cells in response to various human cytokines. The cloned sequence is 764 nucleotides long, and the open reading frame consists of 312 nucleotides. The deduced protein sequence includes a predicted mature protein of approximately 83 residues. The comparison of porcine IP-10, and its human, mouse, rat, goat, and sheep counterparts exhibited high similarity among different mammalian species. The sequences of important regulatory elements such as the interferon-stimulated response element (ISRE), and two NF-kappaB binding elements are conserved in the proximal promoter region of porcine IP-10, like other mammalian IP-10s. Human TNF-alpha induced the expression of IP-10 mRNA in porcine endothelial cells, while both human IFN-gamma and human IL-1beta failed. Together, the data of this study suggest that porcine IP-10 may interact with human leukocytes across the species barrier.
- 2132007
제1저자 김주성 · 교신저자 송인성
, , , , , , ,
Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease.Br J Cancer. 2007;96(9):1324-8.
PubMed IF 7.8 소화기내과Abstract
A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2-3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11-125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10-22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication.
- 2122007
제1저자 조영재 · 교신저자 임재준
, , , , , ,
Clinical characteristics of tuberculosis in patients with liver cirrhosis.Respirology. 2007;12(3):401-5.
PubMed IF 7.2 호흡기내과Abstract
BACKGROUND AND OBJECTIVES Patients with liver cirrhosis are likely to be susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of this study was to elucidate the clinical characteristics and treatment responses in TB patients with cirrhosis.
METHODS Cases were patients with TB detected during their follow up for liver cirrhosis over a 4-year period. Controls were randomly selected patients with TB but no liver disease, matched to cases by age and gender in a 3:1 ratio.
RESULTS Thirty-six cases and 108 controls were enrolled. Extrapulmonary TB was more common in cases than controls (31% vs 12%, P = 0.02). Clinical and radiographic manifestations and response to treatment did not differ between the two groups. The frequency of hepatotoxicity was higher in the cases than in the controls who were treated with a regimen containing rifampicin and isoniazid, although the difference was not statistically significant (27% vs 10%, P = 0.079).
CONCLUSIONS TB patients with liver cirrhosis show extrapulmonary involvement more frequently. Patients with pulmonary TB and cirrhosis usually respond well to anti-TB treatment although appear to present more frequently with treatment-related hepatotoxicity.
- 2112007
제1저자 한세원 · 교신저자 김태유
, , , , , , , , , , , ,
Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth factor receptor and gefitinib responsiveness in non-small-cell lung cancer.Pharmacogenet Genomics. 2007;17(5):313-9.
PubMed IF 1.6 혈액종양내과Abstract
OBJECTIVE Limited availability of tumoral tissue in non-small-cell lung cancer and presence of epidermal growth factor receptor mutation-independent responses call for investigation of other molecular predictive marker of gefitinib responsiveness. Therefore, CA repeat polymorphism in intron 1 was analyzed for its association with gefitinib responsiveness together with epidermal growth factor receptor mutation in Korean patients.
PATIENTS AND METHODS For 86 advanced non-small-cell lung cancer patients treated with gefitinib, epidermal growth factor receptor mutation was analyzed by direct sequencing (exons 18-21) from tumor tissue and CA repeat polymorphism was assessed by fragment length analysis from tumor and/or normal tissue.
RESULTS CA repeat status was identical in 33 patients with matched tumor and normal tissue. CA repeat was low (sum of both alleles < or =37) in 40 (46.5%) and high (sum > or =38) in 46 (53.5%) patients. Although epidermal growth factor receptor mutation was more frequent in high CA repeat patients [17.5% (7/40) in low vs. 28.3% (13/46) in high, P=0.18], response rate was higher in low CA repeat patients [25.0% (10/40) in low vs. 13.0% (6/46) in high, P=0.16]. In multivariate analysis, low CA repeat was associated with better objective response (odds ratio 7.1, 95% confidence interval 1.2-40.8; P=0.029) and time-to-progression (hazard ratio 0.54, 95% confidence interval 0.34-0.88; P=0.014), independent of the epidermal growth factor receptor mutational status. CA repeat status was not associated with epidermal growth factor receptor expression.
CONCLUSION Low number of CA repeats in intron 1 of epidermal growth factor receptor is associated with gefitinib responsiveness in non-small-cell lung cancer patients independent of epidermal growth factor receptor mutation.
- 2102007
제1저자 송영욱 · 교신저자 송영욱
, , , , , , , , , , ,
Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial.Clin Ther. 2007;29(5):862-873.
PubMed IF 3.7 류마티스내과Abstract
BACKGROUND SKI306X, which consists of biologically active ingredients from Clematis mandsburica, Tricbosantbes kirilowii, and Prunella vulgaris, was developed and tested in preclinical trials in Korea. Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect, and that it can delay the destruction of cartilage in rheumatoid arthritis (RA).
OBJECTIVE The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA.
METHODS This study was a 6-week, multicenter, randomized, double-blind, double-dummy, Phase III, noninferiority clinical trial. Eligible patients were aged 18 to 80 years, had a history of RA with a disease duration of > or =3 months, and were functional American College of Rheumatology (ACR) class I, II, or III before entry. After a washout period of 2 weeks, patients were randomized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks. The primary end point was a change in patient assessment of pain intensity using a visual analog scale (VAS). The secondary end points were a 20% improvement in response rate as defined by the ACR (ACR20) and the frequency of rescue medication use. Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator.
RESULTS Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and randomized to 1 of 2 treatment groups. Ninety-one patients (10 male, 81 female; mean [SD] age, 52.13 [12.64] years; mean [SD] duration of RA, 9.08 [10.23] years; no. [%] of ACR class I, II, and III, 13 [14.29], 44 [48.35] and 34 [37.36] patients, respectively) received SKI306X 200 mg TID and 92 patients (10 male, 82 female; mean [SD] age, 51.78 [10.94] years; mean [SD] duration of RA, 8.78 [7.78] years; no. [%] of ACR class I, II, and III, 14 [15.22], 44 [47.83], and 34 [36.96] patients, respectively) received celecoxib 200 mg BID. An analysis of the change in reported pain intensity as determined by VAS (mm) score between baseline and week 3 (mean [SD], 13.64 [16.62] vs 14.45 [15.89]), and between baseline and week 6 (18.4 [20.8] vs 17.9 [19.1], respectively) suggested that SKI306X was not inferior to celecoxib. The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 (16/87 [18.4%] vs 24/87 [27.6%], respectively) and at week 6 (29/87 [33.3%] vs 29/87 [33.3%]). The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 (54/87 [62.1%] vs 47/87 [54.0%], respectively) or week 6 (57/87 [65.5%] vs 49/87 [56.3%]). Drug-related AEs were reported by 27 (29.7%) patients in the SKI306X group and 22 (23.9%) patients in the celecoxib group. The most frequent drug-related AEs were epigastric pain (9/91 [9.9%]) in the SKI306X group and glutamyltranferase elevation (4/92 [4.3%]) in the celecoxib group. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs.
CONCLUSION The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA.
- 2092007
제1저자 이준규 · 교신저자 김용태
, , , , , , ,
The efficacy of nonsurgical treatment of infected pancreatic necrosis.Pancreas. 2007;34(4):399-404.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES We conducted this study to evaluate the efficacy of nonsurgical treatment for patients with infected pancreatic necrosis (IPN).
METHODS Among 224 patients with acute pancreatitis from 2000 to 2004, there were 31 patients diagnosed as having IPN complication. The diagnostic criteria for IPN were either a positive culture or free gas in the pancreas of patients with acute pancreatic necrosis. Nonsurgical management including percutaneous drainage or endoscopic drainage (ED) followed by vigorous irrigation was initially attempted in all patients. Surgery was planned only when there was no clinical improvement after the initial nonsurgical treatment.
RESULTS Percutaneous drainage or ED was performed in 18 and 5 patients, respectively. Eight patients received antibiotics only. Four patients (12.9%) (3 from percutaneous drainage group and 1 from ED group) required surgery. Sepsis or fistula developed in 32% and 6% of patients, respectively, and was managed successfully. One patient (3.2%) died as a result of rapidly progressing multiorgan failure. The mean duration of hospitalization was 37 days. During the follow-up period, 7 patients were readmitted because of fever; they were managed by reposition of the drainage tube.
CONCLUSIONS Intensive nonsurgical treatment is very effective and safe and should be considered as an initial treatment modality for patients with IPN.
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