Biomedical subjects

Yong Han Paik

Publications and source records attributed to Yong Han Paik.

14 recordsLinked to original sources

PubMed2006

Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ((166)Ho)/chitosan complex injection (PHI) therapy for small hepatocellular carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor. EXPERIMENTAL DESIGN: Forty patients with single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI. RESULTS: Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site. The 1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients. CONCLUSIONS: PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.

Administration, Cutaneous↗

PubMed2006

Association of genetic variations in CCR5 and its ligand, RANTES with clearance of hepatitis B virus in Korea.

Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. The aim of current study was to investigate the association of clearance of hepatitis B virus (HBV) with promoter polymorphisms within the CC chemokine receptor 5 (CCR5) and its major ligand, regulated upon activation, normal T cells expressed and secreted (RANTES) genes. Five chemokine system polymorphisms (CCR5 Delta32, CCR5 promoter 59029G/A, 59353C/T, RANTES -403G/A, and -28C/G) were studied in a total of 698 subjects. The carriage of each genetic variant was compared among "spontaneously recovered" group (n = 243), "chronic carrier" group (n = 349), and "unexposed" group (n = 106). CCR5 59029G promoter variant was associated with clearance of HBV infection in an acute phase (OR = 1.71, P = 0.006, dominant model; OR = 2.17, P < 0.001, recessive model) and amelioration of hepatic inflammation (P = 0.003) with the control of HBV replication (P = 0.04) in chronic carriers. Interestingly, CCR5 59029 was linked completely to CCR5 59353, and CCR5 Delta32 homozygosity or heterozygosity was not found in any Korean patient. No association was seen with RANTES polymorphisms at position -403 and -28. The CCR5 59029G/CCR5 59353T polymorphism may play a role in the clearance of HBV infection.

Adult↗

PubMed2006

[Protein expression profiles in a rat cirrhotic model induced by thioacetamide].

BACKGROUND/AIMS: The reactive oxygen species from thioacetamide (TAA) induces rat liver cirrhosis that resembles the human disease, and it can serve as a suitable animal model for studying human liver cirrhosis. The aim of this study was to identify the molecular protein signatures via a proteomics approach with using a rat model with TAA-induced liver cirrhosis. METHODS: Male Wistar rats were treated with 0.3 g/L TAA in their drinking water. The animals were then sacrificed at 9 and 30 weeks after TAA administration. The development of liver cirrhosis was observed with histological study. The livers were processed for proteins extraction and the proteins were analyzed by 2-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionizing time-of-flight mass spectrometry and this was validated by immunohistochemical staining. RESULTS: On the proteomics analysis of the liver tissues, a total of 88 proteins showed significant change in their expression between the controls and the cirrhotic rats. When the proteins were categorized by their function, they included ECM/cellular skeleton, cell proliferation/death signal, metabolism, DNA damage/stress and immune response related proteins. The level of expression gradually increased up to 30 weeks for interleukin-6 (IL-6) precursor, transforming growth factor-beta (TGF-beta) induced protein, TIMP-1 and MMP-9. Cytochrome P450 2B, which is required for the metabolic activation of TAA, also showed the same increasing pattern. In contrast, the expression level of the proteins did not show a significant change at 9 weeks, but this increased to 3-fold at 30 weeks for carbonic anhydrase VII, ras related protein Rab 6, Annexin A2, neurofibromatosis type 2 and aldehyde dehydrogenase. CONCLUSIONS: This study showed that there is a repertoire of proteins during the development of liver cirrhosis via TAA. In this model, IL-6, TGF-beta, MMP-9 and TIMP-1 were reconfirmed as the molecular signatures during the development of TAA-induced liver cirrhosis.

Animals↗

PubMed2006

[Natural history of HBeAg negative chronic hepatitis B virus infection: a cohort study].

BACKGROUND/AIMS: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. METHODS: A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4 x 10(5)) genomes/mL, Digene Diagnostics, Silver Spring, USA). RESULTS: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. CONCLUSIONS: We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant.

Adult↗

PubMed2005

Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma.

BACKGROUND: Biliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first-line therapy in patients with advanced and/or metastatic biliary carcinoma. METHODS: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m(2) on Days 1 and 8) plus oral capecitabine (650 mg/m(2) twice daily on Days 1-14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined. RESULTS: A total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8-8.1) and 14 (range, 11.4-16.6) months, respectively. The 1-year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand-foot syndrome were the most common adverse events. CONCLUSIONS: CapGem is an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home-based therapy.

Adult↗

PubMed2005

Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study.

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p = 0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0 --> 4.2, p = 0.000); lactulose group (11.3 --> 5.0, p = 0.000)). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.

Female↗

PubMed2005

Usefulness of urine strip test in the rapid diagnosis of spontaneous bacterial peritonitis.

PURPOSE: Rapid and accurate diagnosis of spontaneous bacterial peritonitis (SBP) is mandatory for timely treatment in cirrhotic patients. The purpose of this study was to assess the usefulness of two different reagent strips, the UriSCAN and the Multistix10SG, for the rapid bedside diagnosis of SBP. METHODS: A total of 75 paracenteses in 53 cirrhotic patients with ascites were performed. All ascitic fluid was analyzed with the two reagent strips, and compared with the manual cell count with differential and ascitic fluid culture. SBP was defined as an ascitic polymorphonuclear cell count > or =250/mm3. RESULTS: SBP was diagnosed in 18 of the 75 samples. If we considered the positive UriSCAN result of 2 or more, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. When we considered the positive UriSCAN result of 3, the sensitivity, specificity, PPV, and NPV were 67%, 100%, 100%, and 89%, respectively. When we considered the positive Multistix10SG result of 3, the sensitivity, specificity, PPV, and NPV were 50%, 100%, 100%, and 87%, respectively. CONCLUSION: Urine reagent strip might be useful for rapid and accurate diagnosis of SBP in cirrhotic patients with ascites.

Ascitic Fluid↗

PubMed2004

Hepatitis B virus infection after renal transplantation in the presence of antibody to hepatitis B surface antigen immunity.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection has been known to be hampered by immunity against hepatitis B surface antigen (HBsAg). However, HBV with mutations within the common antigenic epitope of HBsAg, the "a" determinant region, can escape from humoral immunity. Moreover, HBV infection by "a" determinant mutants in chronic HBV patients has been reported after renal transplantation. In the present study, the authors investigated HBV infection after renal transplantation despite passive immunization or resolved HBV infection. METHODS: A total of 1682 patients who underwent a renal transplant between 1979 and 1998 at the Severance Hospital, Yonsei University College of Medicine, Korea, were enrolled. The sequence of the HBV genome was analyzed from two patients with antibody to HBsAg (anti-HBs) immunity. RESULTS: Of 1682 patients who were HBsAg negative before transplantation, 21 patients were found to be HBsAg positive, with elevated aspartate aminotransferase and alanine aminotransferase levels after transplantation. Interestingly, six of 21 (28.6%) patients were anti-HBs positive before the transplantation. Sequence analysis of the cloned HBV from two of six patients with anti-HBs immunity showed no evidence of significant mutations within the "a" determinant region, suggesting a wild-type of HBV. Their donors were not exposed to HBV before transplantation (all HBV markers were negative). Seven deaths of 21 patients were ascribed to HBV-related complications. CONCLUSIONS: Regardless of anti-HBs immunity, HBV infection occurred in immunosuppressed patients in a high endemic area. The molecular mechanism and clinical impact of HBV infection after renal transplantation in patients with anti-HBs immunity should be further reappraised.

Adult↗

PubMed2004

[Type of electric currents used for standard endoscopic sphincterotomy does not determine the type of complications].

BACKGROUND/AIMS: The blended current is usually used for endoscopic sphincterotomy (EST) to minimize bleeding. The pure cutting current may induce less edema of the ampulla and therefore result in less injury to the pancreas theoretically. The aim of this study was to evaluate effects of electric currents used on the development of serum pancreatic enzyme evaluation, clinical pancreatitis or bleeding after EST. METHODS: One hundred and eighteen consecutive patients who underwent EST with standard papillotome alone for the treatment of choledocholithiasis were reviewed. All EST had been performed by two endoscopists whose experience on EST was similar: one uses 'blended current' (BC group, n=74), while the other uses 'pure cutting current' (PC group, n=44). RESULTS: Baseline clinical, laboratory, and procedural parameters were similar in both groups. The incidences of hyperamylasemia and hyperlipasemia were similar between two groups. There was no significant difference in the incidence of clinical pancreatitis between two groups (BC 6.8% vs PC 0.0%, p=0.1557). All episodes of pancreatitis were mild. No episodes of significant bleeding occurred after EST. The incidences of sepsis, cholangitis and perforation were also not different between two groups. CONCLUSIONS: Development of complications after standard EST such as hyperamylasemia, clinical pancreatitis, and bleeding may not depend on the electric current used.

Aged↗

PubMed2004

[Changes of ascites nitric oxide according to the treatment course in cirrhotic patients with spontaneous bacterial peritonitis].

BACKGROUND/AIMS: Nitric oxide (NO) is a molecule involved in vascular dilatation and pathogen suppression. It also has immunologic and regulatory functions. Liver cirrhosis is characterized by an increased risk for bacterial infections, including spontaneous bacterial peritonitis (SBP). The role of NO in SBP which develops in cirrhosis has not been clearly established. The aim of this study was to investigate the role of NO in the pathogenesis of SBP and its clinical usefulness for prediction of disease prognosis. METHODS: This study was designed to investigate the changes of ascites NO in the course of treatment. Nitric oxide metabolite (nitrites+nitrates [NOx]) was measured by chemiluminescence in 84 ascites samples obtained from 84 cirrhotic patients. Among them, the 38 patients with SBP were treated with cefotaxime 2.0 g, q 12hr for 7 days. In 24 of SBP patients, ascites was obtained consecutively before treatment (day 0), during treatment (day 2), and after treatment (day 7). RESULTS: Ascites NO levels in the patients with SBP (n=38; 82.3 +/- 14.4 microM) were not different from those in patients with sterile ascites (n=46; 54.6 +/- 13.0 microM). There was no significant change of NO levels in sequential ascites samples during antibiotic treatment. Ascites NO level before treatment was significantly higher in SBP patients who responded to antibiotics (n=26; 101.86 microM/L) than that in SBP patients who did not respond to antibiotics (n=12; 40.03 microM/L, P=0.044). A significant direct correlation was found between ascites and serum NO levels before treatment (Pearson correlation, r2=0.86, P=0.001). Among the SBP patients, treatment response rate to antibiotics were significantly higher in those patients with pretreatment NO level > or = 80 microM/L in multivariate analysis. CONCLUSIONS: Ascites NO level was not different between ascites from SBP patients and ascites from cirrhotic patients with sterile ascites. There were no changes of ascites NO in SBP patients during treatment. Therefore ascites NO was not useful to predict the progress of SBP. Ascites NO levels reflect serum NO levels, and the patients with higher NO level may have better response to antibiotics.

Adult↗

PubMed2004

[Clinical features and prognostic factors of fulminant hepatic failure in Koreans].

BACKGROUND/AIMS: There have been scant reports on the prognostic factors of fulminant hepatic failure for selecting the patients who need liver transplantation. We investigated the clinical features and prognostic factors throughout the clinical course of the disease in Korean patients with fulminant hepatic failure. METHODS: Between 1992 and 2003, a total of 60 patients with fulminant hepatic failure were divided into the survival group and the non-survival group, and these groups were compared according to gender, age, etiology, values of the laboratory tests, grade of the encephalopathy that was obtained at the time of admission and the worst clinical status (hepatic encephalopathy). RESULTS: The mean age of the total patients was 40.9 years (M:F=31:29) and the survival rate was 28.3% (n=17). Drugs (n=25, 12 herbal medicines) and viral infection (n=24, 18 HBV infection) were most common causes. On univariate analysis, the WBC, AST, ALT, total bilirubin and HE IV stage at the time of admission were the significant factors for a poor prognosis. Total bilirubin, albumin and HE IV stage also remained as significant factors at the time of the worst clinical status. On multivariate analysis, total bilirubin (P=0.033) and ALT (P=0.042) at admission were the prognostic factors, and the progression to HE IV stage (P=0.019) or hypoalbuminemia (P=0.028) during hospitalization represented the significant factors for a poor prognosis. CONCLUSIONS: In contrast to Western countries, HBV infection and herbal medicines were major causes of fulminant hepatic failure in Korea. The total serum bilirubin level and progressive hyperbilirubinemia with HE (stage IV) during hospitalization seemed to be the most important prognostic factors, and liver transplantation should be considered before the patient reaches this status.

Adult↗

PubMed2003

Screening test data analysis for liver disease prediction model using growth curve.

This study was done based on screening test data accumulated from 1994 to 2001 for studying of risk factor related with liver disease and prediction model of liver disease. In the existing study related with liver, the main current is studying on liver cancer, not on liver disease, previous step into liver cancer. As a result of estimating prediction model through the risk factors of liver disease and the growth curve on the basis of data, it is shown that most of the risk factors about liver disease are also those about known well as liver cancer. In addition, to investigate liver disease prevalence from the viewpoint of the future, this study presumed risk factor through the various growth curve analysis and examined logistic regression, decision tree and neural network from those estimators. In the case of neural network using growth curve estimator of Xi(5)=alphai+betaiT+epsiloniT, accuracy of liver disease was 72.55% and sensitivity was 78.62%. On the other hand, in the case of liver disease prediction model using recent screening test data estimator, accuracy was 72.09% and sensitivity was 71.72%. Those are lower than liver disease prediction model of growth curve analysis. In the various liver disease prediction models assumed by growth curve and many distinction models, when growth curve estimator was used, sensitivity value was improved.

Humans↗

PubMed2003

Colorectal flat neoplasia.

BACKGROUND AND AIMS: An attempt has been made to evaluate the clinicopathological characteristics of flat colorectal neoplastic lesions, and analyse the factors associated with the malignancy. PATIENTS AND METHODS: A total of 115 flat neoplastic lesions, > or = 5 mm in size, diagnosed in 87 patients by colonoscopy, were investigated. RESULTS: The rectum was the most common location. Almost half (49.6%) of the flat neoplasms were small (5-10 mm), 27.8% were 11-20 mm and the remainder (22.6%) larger than 20 mm. The surface was smooth in 55.7%, granular in 20.0% and nodular in 24.3%. Histologically, the flat lesions were tubular, tubulovillous and villous adenomas in 69.6%, 20.9% and 5.2%, respectively. Five lesions (4.3%) were composed of carcinomas without adenoma. High-grade dysplasia, intramucosal carcinoma and invasive carcinoma were diagnosed in 9.6%, 7.8% and 6.1% of all flat neoplasms, respectively. Univariate analysis demonstrated that the location, size, surface pattern and histologic type of the flat lesions were factors associated with malignancy. However, in multivariate analysis, the size of the flat lesions was the only significant risk factor for malignant transformation. CONCLUSIONS: Flat neoplastic lesions of the colorectum have a relatively high rate of malignancy, and size is the most important factor associated with malignancy.

Adenocarcinoma↗

PubMed2003

NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis.

Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated the role of NADPH oxidase in Ang II-induced effects in hepatic stellate cells (HSCs), a fibrogenic cell type. Human HSCs express mRNAs of key components of nonphagocytic NADPH oxidase. Ang II phosphorylated p47phox, a regulatory subunit of NADPH oxidase, and induced reactive oxygen species formation via NADPH oxidase activity. Ang II phosphorylated AKT and MAPKs and increased AP-1 DNA binding in a redox-sensitive manner. Ang II stimulated DNA synthesis, cell migration, procollagen alpha1(I) mRNA expression, and secretion of TGF-beta1 and inflammatory cytokines. These effects were attenuated by N-acetylcysteine and diphenylene iodonium, an NADPH oxidase inhibitor. Moreover, Ang II induced upregulation of genes potentially involved in hepatic wound-healing response in a redox-sensitive manner, as assessed by microarray analysis. HSCs isolated from p47phox-/- mice displayed a blunted response to Ang II compared with WT cells. We also assessed the role of NADPH oxidase in experimental liver fibrosis. After bile duct ligation, p47phox-/- mice showed attenuated liver injury and fibrosis compared with WT counterparts. Moreover, expression of smooth muscle alpha-actin and expression of TGF-beta1 were reduced in p47phox-/- mice. Thus, NADPH oxidase mediates the actions of Ang II on HSCs and plays a critical role in liver fibrogenesis.

Angiotensin II↗