BACKGROUND: Quinidine appeared to increase serum digoxin levels when given with quinidine. Therefore elevated serum digoxin concentrations and clinical toxicity have been reported in patient receiving quinidine. Currently, Bayesian method which estimates the most probable parameters of the drug for each patient from population parameters data is useful approach for adjusting digoxin dosage. To increase the accuracy of Bayesian method, it is desirable to use population parameters of Korean. Therefore we evaluated the effect of quinidine on digoxin clearance in Korea. METHOD: Patient's records from 19 adult cardiac disease without CHF having normal renal and liver function from Seoul National University of Hospital respectively wre evaluated. Digoxin pharmacokinetic parameters, CL and Vd, were obtained from serum concentration of digoxin of single and combined therapy at each steady-state by using bayesian method. RESULTS: This study show that quinidine reduced the total body clearance of digoxin from 2.39+/-0.17 to 1.51+/-0.08ml/min/kg(p<0.05) and reduced the digoxin volume of distribution from 8.57+/-0.29 to 4.98+/-0.19L/kg(p<0.05). This results show that digoxin dosage reduced to 40-50% in Korean, if quinidine therapy is initiated.
Adult ; Bayes Theorem ; Digoxin* ; Drug Interactions ; Heart Diseases ; Humans ; Korea ; Liver ; Pharmacokinetics ; Quinidine* ; Seoul

The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1alpha protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1alpha was increased by 1.69+/-0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1alpha expression by bilirubin. HIF-1alpha expression decreased by 10 microM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1alpha concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1alpha mRNA expression. In coonclusion, bilirubin enhances HIF-1alpha transcription as well as the up-regulation of HIF-1alpha protein translation through the attenuation of ROS and subunits of NADPH oxidase.
Bilirubin/*pharmacology ; Cell Line ; Epithelial Cells/cytology/metabolism ; Humans ; Hydrogen Peroxide/toxicity ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Kidney Tubules, Proximal/cytology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; NADPH Oxidase/antagonists & inhibitors/genetics/metabolism ; Oxygen/*pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism ; Transcriptional Activation/*drug effects ; Up-Regulation/drug effects

Despite the availability of effective antiviral drugs, human cytomegalovirus (CMV) infection is still a serious life-threatening complication in recipients of allogeneic hematopoietic stem cell transplantation. Ganciclovir (GCV) preemptive therapy is currently the usual treatment for CMV disease and antigenemia. However, prolonged GCV therapy results in the emergence of drug-resistant virus. Most GCV-resistant clinical CMV isolates contain a mutation in the UL97 phosphotransferase gene. We report a case that GCV-resistant CMV antigenemia by UL97 phosphotransferase mutant strain at codon 460 and 605 which was improved by reduction of immunosuppressants for posttransplant lymphoproliferative disease after unrelated cord blood transplantation.
Antiviral Agents ; Codon ; Cytomegalovirus ; Fetal Blood* ; Ganciclovir ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents

BACKGROUND: We evaluated the outcomes of serum galactomannan (GM) assay for the screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients while on primary antifungal prophylaxis (PAP). METHODS: This study included patients with hematologic disorders who underwent alloHSCT from January 2013 to November 2015. Patients received routine PAP with fluconazole before 2014 and micafungin after 2014; serum GM tests were performed and retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum GM tests for detection of probable/proven IPA were evaluated. The serial change of serum GM levels was illustrated on a time series plot. RESULTS: A total of 136 alloHSCT recipients at Seoul National University Hospital were included in the study. Fluconazole was administered in 72 patients for PAP, while micafungin was administered in the remaining 64 patients. The overall sensitivity, specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI] 78.9–99.9%), 93.8% (95% CI 91.7–95.5%), and 99.8% (95% CI 99.1–100.0%), respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI 23.9–48.2%). The serial change in serum GM levels differed according to the antifungal agents used. With effective PAP using micafungin, serial serum GM levels showed zero order kinetics during the neutropenic period. CONCLUSION: Although the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.
Antifungal Agents ; Fluconazole ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Invasive Pulmonary Aspergillosis* ; Kinetics ; Mass Screening* ; Retrospective Studies* ; Sensitivity and Specificity ; Seoul ; Stem Cell Transplantation* ; Stem Cells*

BACKGROUND: Genistein and daidzein are two major soybean isoflavones. They have received increasing attention because of their possible roles for cancer prevention. However, their mechanisms of action and molecular targets on the human colon cancer cells are not fully understood. METHODS: Human colon cancer HCT-116 cells were treated with genistein and daidzein to investigate their effects on the cell growth and this was analyzed with MTT assay. TUNEL assay and Hoechst33342 stain were carried out to identify apotosis. RESULTS: Daidzein was able to inhibit cell proliferation and induce apoptosis of the HCT-116 cells, but genistein didn't affect the cell growth. The ER antagonist ICI182780 didn't attenuate the antiproliferative and proapoptotic effects of daidzein: this means the effect of daidzein on the HCT-116 cells may not be dependent on the ER pathway. The other soybean isoflavone, genistein, attenuated the effects of daidzein on the HCT-116 cells and its mechanism should be elucidated. CONCLUSIONS: These data suggest that daidzein may act as a preventive agent on human colon cancer, and its mechanism of action doesn't involve the ER-dependent pathway.
Apoptosis ; Cell Proliferation ; Colon* ; Colonic Neoplasms* ; Genistein* ; HCT116 Cells* ; Humans* ; In Situ Nick-End Labeling ; Isoflavones ; Soybeans

PURPOSE: Current clinical data support a safe warm ischemia time (WIT) limit of 30 minutes during laparoscopic partial nephrectomy (LPN) or robot-assisted partial nephrectomy (RPN). We evaluated independent factors predicting prolonged WIT (more than 30 minutes) after LPN or RPN. MATERIALS AND METHODS: A retrospective data review was performed for 317 consecutive patients who underwent LPN or RPN performed by the same surgeon from October 2007 to May 2013. Patients were divided into two groups: group A was defined as prolonged WIT (> or =30 minutes) and group B as short WIT (<30 minutes). We compared clinical factors between the two groups to evaluate predictors of prolonged WIT. RESULTS: Among 317 consecutive patients, 80 were in the prolonged WIT group. Baseline characteristics were not significantly different between the groups. In the univariable analysis, PADUA (preoperative aspects and dimensions used for an anatomical) score (p=0.001), approach method (transperitoneal or retroperitoneal approach; p<0.001), and surgeon experience (p<0.001) were significantly associated with prolonged WIT. In the multivariable analysis, PADUA score (p=0.032), tumor size (> or =25 mm; odds ratio, 2.98; 95% confidence interval, 1.48-5.96; p=0.002), and surgeon experience (p<0.001) were independent predictors of prolonged WIT. CONCLUSIONS: Surgeon experience, tumor size, and PADUA score predicted prolonged WIT after RPN or LPN. Among these factors, increasing surgical experience with LPN or RPN is the most important factor for preventing prolonged WIT.
Adult ; Aged ; Carcinoma, Renal Cell/pathology/*surgery ; Clinical Competence ; Female ; Humans ; Intraoperative Period ; Kidney Neoplasms/pathology/*surgery ; Laparoscopy/methods ; Male ; Middle Aged ; Nephrectomy/*methods ; Pneumoperitoneum, Artificial/*methods ; Retrospective Studies ; Risk Factors ; Robotic Surgical Procedures/methods ; Warm Ischemia/*methods

Background/Aims: The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. Methods: This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. Results: For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-tohigh risk category. No such differences were noted in the low-risk category. Conclusions The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.
Cohort Studies ; Coronavirus ; Coronavirus Infections* ; Follow-Up Studies ; Humans ; Korea ; Middle East* ; Pneumonia* ; Prospective Studies ; Survivors

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.
Aged ; Biopsy, Needle/methods ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Precancerous Conditions/*pathology/surgery ; Predictive Value of Tests ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies