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

No abstract available.
Atrioventricular Block

BACKGROUND/AIMS: Several lines of evidences suggest that the distribution of colorectal adenomatous polyps are different according to age and gender. Therefore, the efficacy of screening sigmoidoscopy for colorectal cancer not considering age and gender necessitates reappraisal. We aimed to evaluate the distributions of colorectal adenomatous polyps according to age and gender. METHODS: Total of 1,886 patients (1,322 men, 564 women) who underwent colonoscopy at Severance hospital, Seoul, Korea between July 1995 and September 2002, were included. The proximal colon was defined as the colon proximal to the sigmoid-descending junction. The advanced polyp was defined as the adenomatous polyp with one or more of the following features: (1) 1 cm or larger in diameter, (2) villous histology, (3) high grade dysplasia or adenocarcimoma. RESULTS: The risk of adenomatous polyps in the proximal colon was higher in men than women (OR, 1.63; 95% CI, 1.33~1.99, p < 0.05), and increased with age (p < 0.05). The risk of advanced polyps in the proximal colon tended to be higher in men than women, and to increase with age, but did not reach statistical significance. Among 1,886 patients with colorectal adenomatous polyps, 587 patients (31.1%) had polyps only in the proximal colon. Among 814 patients with advanced colorectal adenomatous polyps, 217 patients (26.7%) had advanced polyps only in the proximal colon. The risks of adenomatous polyps or advanced polyps found only in the proximal colon were not different according to sex, but tended to increase with age. CONCLUSIONS: The risk of adenomatous polyps in the proximal colon was higher in men compared to women and increased with age. About one third of the patients with colorectal adenomatous polyps had polyps only in the proximal colon. Colonoscopy is a better strategy for endoscopic screening for colorectal cancer compared with sigmoidoscopy, especially, in elderly male.
Adenomatous Polyps* ; Aged ; Colon* ; Colonoscopy ; Colorectal Neoplasms ; Female ; Humans ; Korea ; Male ; Mass Screening ; Polyps ; Seoul ; Sigmoidoscopy

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

PURPOSE: To provide the insight into the role of LXR alpha on the progression of diabetic nephropathy, we measured the production of extracellular matrix in the cultured mesangial cells treated with the LXR agonist. METHODS: With the mesangial cells extracted from C57BL6 mice, we cultured them in the presence of 25 mM glucose with or without TO901317, an agonist of LXRalpha We transfected siRNAs of SREBP1 and LXR alpha into the mesangial cell to suppress the activity of the two genes. RESULTS: TO901317 increased expressions of LXR alpha, SREBP-1, TGF beta-1, and collagen IV and triglyceride amount in mesangial cells cultured in 25mM glucose. These effects of TO901317 were attenuated by inhibiting transcription of LXR alpha or SREBP-1 with transfection of siRNAs. In mesangial cells transfected with siRNA of SREBP-1, changes by TO901317 were attenuated regardless of increased expression of LXR alpha. That suggested the activation of SREBP-1, an downstream gene of LXR alpha, would be more important to induce changes in mesangial cells by TO901317. CONCLUSION: The TO901317, an agonist of LXR alpha, increases extracellular matrix, collagen IV, and TGF beta-1 production in cultured mesangial cells. The SREBP-1 as well as dyslipidemia in mesangial cells enhanced by LXR agonist would be the important mechanism to induce those changes.
Animals ; Collagen ; Diabetic Nephropathies ; Dyslipidemias ; Extracellular Matrix ; Glucose ; Hypertriglyceridemia ; Liver ; Mesangial Cells ; Mice ; Orphan Nuclear Receptors ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 1 ; Transfection

The incidence of abdominal trauma has increased in recent decades as the frequency of traffic accidents increased. Early symptoms and signs of blunt abdominal trauma may be absent and associated injuries frequently detract physicians from early diagnosis of abdominal trauma. Delayed diagnosis has been shown to be associated with higher morbidity and mortality. Gastrointestinal tract is the third most commonly injured organ from blunt abdominal trauma. Gastric ruptures after blunt abdominal trauma were reported occasionally, but reports of upper gastrointestinal bleeding by gastric mucosal tear were very rare. Four cases of upper gastrointestinal bleeding due to gastric mucosal tear after blunt abdominal trauma are herein reported with a review of related literatures.
Accidents, Traffic ; Delayed Diagnosis ; Early Diagnosis ; Gastrointestinal Tract ; Hemorrhage ; Incidence ; Mortality ; Stomach Rupture

BACKGROUND/AIMS: Benzodiazepine is generally used when sedation is required for endoscopy, while propofol, a phenol-derived intravenous anesthetic agent, appears to have a more suitable phamacokinetic profile. The aim of this study was to evaluate the effectiveness and safety of propofol as premedication for upper gastrointestinal endoscopy. METHODS: Between July 1998 and October 1998, 44 male patients and 70 female patients were involved in this study. The relative ease of upper gastrointestinal endoscopy, patient's tolerance, and amnestic effects on 64 patients with propofol was compared with 50 patients with non-sedation. Pulse rate and arterial oxygen saturation was monitored. The endoscopist and patients replied to a questionnaire. RESULTS: Patients receiving propofol tolerated endoscopy much more than patients with non-sedation (p<0.01). The change in pulse rate was less variable but arterial oxygen saturation showed a statistically significant decrease in patients receiving propofol (p<0.01). Propofol induced complete amnesia in 93.7% of the patients and partial anesthesia in 4.7%. Most of the patients receiving propofol accepted the same sedative methods in their next endoscopy (p<0.01). CONCLUSIONS: Propofol is highly effective, with a short recovery time and satisfaction of the patients, but careful monitoring is recommended because of its untoward effect of hypoxia. It is recommended that propofol be used as a premedication especially in patients who are apprehensive about a repeated endoscopy.
Amnesia ; Anesthesia ; Anoxia ; Benzodiazepines ; Endoscopy ; Endoscopy, Gastrointestinal* ; Female ; Heart Rate ; Humans ; Male ; Oxygen ; Premedication* ; Propofol* ; Surveys and Questionnaires

Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.
Coronavirus ; Coronavirus Infections* ; Dyspnea ; Enzyme-Linked Immunosorbent Assay ; Fever ; Humans ; Interleukin-6 ; Korea ; Middle East Respiratory Syndrome Coronavirus* ; Middle East* ; Neutrophils ; Oxygen ; Prospective Studies ; Thorax

We report a case of a mediastinal pseudocyst with a pleural effusion that developed in a patient suffering from alcohol-related chronic pancreatitis. A 53-year-old man was admitted to another institution complaining of pleuritic chest pain and coughing. A chest X-ray revealed a pleural effusion with a collapse of the right middle and lower lobes. Pleural fluid taken by thoracentesis was exudative, and the patient was transferred to our institution. A CT scan showed a loculated cystic lesion in the mediastinum and pancreatic changes that were consistent with chronic pancreatitis. The endoscopic retrograde cholangiopancreatography (ERCP) findings were compatible with chronic pancreatitis showing severe pancreatic ductal stricture at the head with an upstream dilation and distal bile duct stricture. After a one week of treatment with fasting and octreotide without improvement, both pancreatic and biliary stents were placed endoscopically. After stenting, the pleural effusion and pseudocyst rapidly resolved. The stents were changed 3 months later, at which time a repeated CT demonstrated a complete resolution of the pseudocyst. Since the initial stenting, he has been followed up for 7 months and is doing well with no recurrence of the symptoms, but he will need to undergo regular stent changes. Overall, endoscopic pancreatic stenting appears to be a good option for managing selected cases of mediastinal pancreatic pseudocysts.
*Endoscopy ; Human ; Male ; Mediastinal Neoplasms/*complications/radiography/therapy ; Middle Aged ; *Pancreatic Ducts ; Pancreatic Pseudocyst/*complications/radiography/therapy ; Pleural Effusion/*complications/therapy ; Radiography, Thoracic ; *Stents ; Tomography, X-Ray Computed ; Treatment Outcome

PURPOSE: High Gleason score (8 to 10) is a poor prognostic factor regardless of treatment. Pathological downgrading sometimes occurs in high grade prostate cancer. The aim of this study is to evaluate treatment outcomes in patients with high grade prostate cancer on biopsy who were pathological downgrading after radical prostatectomy (RP). The impact on outcomes according to changes in the Gleason score after RP was evaluated. MATERIALS AND METHODS: Of 3,236 men who underwent RP between September 1995 and December 2014, 541 patients with biopsy Gleason score 8 to 10 were retrospectively reviewed. We analyzed incidence and biochemical recurrence (BCR) free probability in this downgraded group according to the Gleason grade of cancer in the RP specimen. RESULTS: Of 541 patients had a prostate biopsy Gleason score of 8 to 10. Two hundred ten patients showed pathological downgrading after RP (38.8%). Five-year BCR-free probability of patients who had Gleason score of 7 or less after RP was 46.8%. However, 5-year BCR-free probability of patients who remained Gleason scores 8 to 10 after RP was 28.5%. There was a significantly higher BCR-free probability in pathological downgrading group (p<0.001). On multivariate analysis, biopsy Gleason 8, lower PSA, clinical T2 stage was a significant predictor of downgrading. CONCLUSIONS: In this study, 38.8% of patients with high grade prostate cancer had a Gleason score of 7 or less in the RP specimen. Downgraded prostate cancer had more favorable treatment outcome. Serum PSA, clinical stage and biopsy Gleason score were the predictive factors for pathological downgrading.
Biopsy* ; Humans ; Incidence* ; Male ; Multivariate Analysis ; Neoplasm Grading* ; Prostate* ; Prostatectomy* ; Prostatic Neoplasms* ; Recurrence ; Retrospective Studies ; Treatment Outcome*