BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. METHODS: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. RESULTS: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). CONCLUSIONS: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.
Antiviral Agents ; DNA ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Lamivudine* ; Multivariate Analysis ; Tenofovir ; Treatment Outcome

In Korea, scrub typhus usually occurs in October and November. Hemophagocytic lymphohistiocytosis (HLH) is a distinct clinical entity characterized by a high fever, pancytopenia, hepatosplenomegaly, histiocyte proliferation, and hemophagocytosis. We encountered a summertime case of severe scrub typhus presenting as HLH. A 49-year-old female complained of abdominal pain and fever 3 days in duration. On hospital day 3 she was transferred to the intensive care unit because of clinical deterioration accompanied by severe sepsis. As an eschar was evident on the right shoulder, we commenced doxycycline. Her condition improved dramatically and she was discharged on day 14. Although the indirect immunofluorescence antibody test (IFA) for Orientia tsutsugamushi was negative on admission, a repeat IFA test was positive; the antibody titer was 1:5,120 on hospital day 10. Scrub typhus should be considered during differential diagnosis in a patient with severe sepsis in any season except the fall.
Abdominal Pain ; Diagnosis, Differential ; Doxycycline ; Female ; Fever ; Fluorescent Antibody Technique, Indirect ; Histiocytes ; Humans ; Intensive Care Units ; Korea ; Lymphohistiocytosis, Hemophagocytic* ; Middle Aged ; Orientia tsutsugamushi ; Pancytopenia ; Scrub Typhus* ; Seasons ; Sepsis ; Shoulder

PURPOSE: Metastatic cancers spread from the primary site of origin to other parts of the body. Matrix metalloproteinase-9 (MMP-9) is essential in metastatic cancers owing to its major role in cancer cell invasion. Crotonis fructus (CF), the mature fruits of Croton tiglium L., have been used for the treatment of gastrointestinal disturbance in Asia. In this study, the effect of the ethanol extract of CF (CFE) on MMP-9 activity and the invasion of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells was examined. METHODS: The cell viability was evaluated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The expression of MMP-9 was examined by Western blotting, zymography, and real-time polymerase chain reaction. An electrophoretic mobility gel shift assay was performed to detect activator protein-1 (AP-1) DNA binding activity and cell invasiveness was measured by an in vitro Matrigel invasion assay. RESULTS: CFE significantly suppressed MMP-9 expression and activation in a dose-dependent manner. Furthermore, CFE attenuated the TPA-induced activation of AP-1. CONCLUSION: The results indicated that the inhibitory effects of CFE against TPA-induced MMP-9 expression and MCF-7 cell invasion were dependent on the protein kinase C δ/p38/c-Jun N-terminal kinase/AP-1 pathway. Therefore, CFE could restrict breast cancer invasiveness owing to its ability to inhibit MMP-9 activity.
Asia ; Blotting, Western ; Breast Neoplasms ; Cell Survival ; Croton ; DNA ; Ethanol ; Fruit ; In Vitro Techniques ; Matrix Metalloproteinase 9* ; MCF-7 Cells* ; Neoplasm Invasiveness ; Protein Kinase C ; Real-Time Polymerase Chain Reaction ; Transcription Factor AP-1*

OBJECTIVE: The purpose of this study was to investigate the clinical features and outcomes of pediatric cavernous malformation (CM) in the central nervous system. METHODS: Twenty-nine pediatric patients with supratentorial CM underwent microsurgical excision. In selected cases, transparent tubular retractor system (TTRS) was used to reduce retraction injury and intraoperative neuromonitoring (IONM) was held to preserve functioning cortex. Patients' demographics and symptoms were reviewed and surgical outcomes were discussed. RESULTS: The main initial clinical manifestations included the following : seizures (n=13, 45%), headache (n=7, 24%), focal neurological deficits (n=3, 10%), and an incidental finding (n=6, 21%). Overt hemorrhage was detected in 7 patients (24%). There were 19 children (66%) with a single CM and 10 (34%) children with multiple CMs. In 7 cases with deep-seated CM, we used a TTRS to minimize retraction. In 9 cases which location of CM was at eloquent area, IONM was taken during surgery. There was no major morbidity or mortality after surgery. In the 29 operated children, the overall long-term results were satisfactory : 25 (86%) patients had no signs or symptoms associated with CMs, 3 had controllable seizures, and 1 had mild weakness. CONCLUSION: With the assistance of neuronavigation systems, intraoperative neuromonitoring, and TTRS, CMs could be targeted more accurately and excised more safely. Based on the satisfactory seizure outcome achieved, complete microsurgical excision in children is recommended for CMs presenting with seizures but removal of hemosiderin-stained areas seems to be unnecessary.
Central Nervous System ; Child ; Demography ; Headache ; Hemangioma, Cavernous, Central Nervous System* ; Hemorrhage ; Humans ; Incidental Findings ; Mortality ; Neuronavigation ; Seizures

As the duration of diabetes mellitus (DM) increases, the risk of complications increases and the prevalence of depression becomes higher. Most studies on depression in Korean patients with DM have focused on a point 5-10 years after diagnosis, and there has not been much data reported regarding the early stages of DM, including newly developed DM. In this study, we examined whether blood glucose levels could be associated with emotional symptoms such as depression (DS) and anxiety (AS) in patients newly diagnosed with DM. Serum glucose and HbA1c were measured in 89 patients with DM. The Impact of Event Scale (IES) was used to investigate the extent of the psychological impact of a diagnosis of DM. The IES comprises four elements: hyperarousal, intrusiveness, avoidance, and sleep problems. DS and AS were investigated using the Hospital Anxiety and Depression Scales. DS was observed in 32 patients (36%) and AS was observed in 21 patients (23.6%), indicating a higher prevalence of DS and AS than in the general population. There was an inverse correlation between HbA1c and DS (Pearson's correlation coefficient: R = -0.227; P = 0.035), but no correlation was found for AS. The four elements of the IES had significant correlations with DS and AS. Logistic regression analysis showed that sleep problems (OR = 1.437) and HbA1c (OR = 0.51) were associated with DS, but only intrusiveness (OR = 0.629) showed a correlation with AS. In patients newly diagnosed with DM, DS is associated with sleep problems and low HbA1c levels. Emotional symptoms should be considered as part of glucose control, and efforts to mitigate psychological stress during the initial period of diabetes management should be made.
Anxiety ; Blood Glucose ; Depression ; Diabetes Mellitus ; Glucose ; Humans ; Logistic Models ; Prevalence ; Stress, Psychological ; Weights and Measures

PURPOSE: The prediction of breast cancer recurrence is a crucial factor for successful treatment and follow-up planning. The principal objective of this study was to construct a novel prognostic model based on support vector machine (SVM) for the prediction of breast cancer recurrence within 5 years after breast cancer surgery in the Korean population, and to compare the predictive performance of the model with the previously established models. METHODS: Data on 679 patients, who underwent breast cancer surgery between 1994 and 2002, were collected retrospectively from a Korean tertiary teaching hospital. The following variables were selected as independent variables for the prognostic model, by using the established medical knowledge and univariate analysis: histological grade, tumor size, number of metastatic lymph node, estrogen receptor, lymphovascular invasion, local invasion of tumor, and number of tumors. Three prediction algorithms, with each using SVM, artificial neural network and Cox-proportional hazard regression model, were constructed and compared with one another. The resultant and most effective model based on SVM was compared with previously established prognostic models, which included Adjuvant! Online, Nottingham prognostic index (NPI), and St. Gallen guidelines. RESULTS: The SVM-based prediction model, named 'breast cancer recurrence prediction based on SVM (BCRSVM),' proposed herein outperformed other prognostic models (area under the curve=0.85, 0.71, 0.70, respectively for the BCRSVM, Adjuvant! Online, and NPI). The BCRSVM evidenced substantially high sensitivity (0.89), specificity (0.73), positive predictive values (0.75), and negative predictive values (0.89). CONCLUSION: As the selected prognostic factors can be easily obtained in clinical practice, the proposed model might prove useful in the prediction of breast cancer recurrence. The prediction model is freely available in the website (http://ami.ajou.ac.kr/bcr/).
Artificial Intelligence ; Breast ; Breast Neoplasms ; Estrogens ; Follow-Up Studies ; Hospitals, Teaching ; Humans ; Lymph Nodes ; Recurrence ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; Support Vector Machine

PURPOSE: Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis. METHODS: The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry. RESULTS: A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells. CONCLUSION: Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.
Apoptosis ; Blotting, Western ; Breast ; Breast Neoplasms ; Cell Death ; Cell Survival ; Humans ; MCF-7 Cells ; Milk Thistle ; Prostate ; Silymarin ; Skin

A 59-year-old woman presented to our hospital with fever, petechiae, pyuria, gross hematuria, and rapidly progressive glomerulonephritis (GN). She had a history of urinary tract infection. A renal biopsy specimen revealed crescentic GN and an echocardiogram showed a vegetation 3.15x1.73 cm in size on the mitral valve and severe mitral valve regurgitation. Blood cultures grew Enterococcus faecalis. Treatment with antibiotics alone resulted in clinical improvement of the renal function and resolution of the fever. Three months after hospitalization, the echocardiogram showed mild mitral valve regurgitation. This case suggests that crescentic glomerulonephritis associated with even a huge vegetation of infectious endocarditis can be treated with antibiotics alone and result in stable renal function.
Anti-Bacterial Agents ; Biopsy ; Endocarditis ; Endocarditis, Bacterial ; Enterococcus faecalis ; Female ; Fever ; Glomerulonephritis ; Hematuria ; Hospitalization ; Humans ; Middle Aged ; Mitral Valve ; Mitral Valve Insufficiency ; Purpura ; Pyuria ; Urinary Tract Infections

PURPOSE: To compare the variable inflammatory parameters of acute pyelonephritis patients treated with inpatient therapy at 13 hospitals, according to the age and gender distributions. MATERIALS AND MATHODS: A total of 3,544 medical records of patients with confirmed acute pyelonephritis, and admitted to hospital between January 2000 and December 2005, were retrospectively analyzed. RESULTS: The mean age of the patients was 43.2+/-16.2 years old, with a male:female ratio of 1 : 5.1. The average duration of hospital admission was 7.9+/-5.3 days. Underlying diseases were found in 23.0% (749/3,252 patient), largely due to diabetes (35.1%). Radiological abnormal findings were found in 13.7%. The leukocyte count, ratio of segmented form, erythrocyte sedimentation rate (ESR), c-reactive protein, pyuria, positive blood culture, positive urine culture were 11,014+/-5,778/mm(3), 74.8+/-14.5%, 44.0+/-32.0 mm/hr, 12.4+/-9.3mg/dl, 83.9%, 10.5% and 46.7%, respectively. E. coli grow in 79% of the urine culture positive patients. In a comparison of 3 age groups (<40 years, 40-60 years, >61 years), the elderly patients had a greater number of underlying diseases and more pathogens in cultured blood. When divided into males and females, the elderly male patients had more pathogen in cultured urine, but contrary to the male patients, the elderly female patients had elevated leukocyte count and erythrocyte sedimentation rate. Also, the old patient group had more resistance to ampicillin when they had E. coli as the uropathogen (p=0.021). Patients with higher ESR required longer hospital admission periods. CONCLUSIONS: It was found that variable clinical parameters of acute pyelonephritis patients treated with inpatient therapy differed according to both gender and age group in Korea. Therefore, these factors should be taken into account in the treatment plan.
Aged ; Ampicillin ; Blood Sedimentation ; C-Reactive Protein ; Female ; Humans ; Inpatients ; Korea ; Leukocyte Count ; Male ; Medical Records ; Pyelonephritis* ; Pyuria ; Retrospective Studies

PURPOSE: Chlormadinone acetate (CMA) therapy for benign prostatic hyperplasia (BPH) may lower the serum prostate specific antigen (PSA) level. However, little is known about the effect of CMA on the total or free serum PSA levels of PSA. Such information would be important since PSA testing is useful for prostate cancer screening. Thus, we prospectively studied the effect of CMA therapy on the total and free serum PSA levels. MATERIALS AND METHODS: The patients with lower urinary tract symptoms (LUTS) and BPH who were aged over 50 years were treated with 50mg CMA for 6 months. Men with a PSA level greater than 10ng/ml were excluded to reduce the likelihood of including cases of occult prostate cancer. Those with suspicious findings on the digital rectal examination and serum PSA testing were biopsied to rule out prostate cancer. alpha- blocking agents were permitted to treat the men with LUTS. Serum levels of the total and free PSA were measured at the study baseline and after approximately 3 and 6 months. The prostate volume (PV) was assessed by transrectal ultrasonography. RESULTS: The analysis included 170 patients with a mean age of 67.9 years, a baseline PV of 47.3ml and a baseline total PSA of 4.1ng/ml. The total PSA levels declined from 4.1ng/ml at baseline to 2.0ng/ml after 6 months of treatment (50.7% decrease, p<0.01). The mean percent free PSA (21% to 22% at baseline) was not significantly altered by CMA treatment. The PSA levels and PV at baseline did not affect the rate of decline of PSA. CONCLUSIONS: The total PSA serum levels decreased by an average of 50% during CMA therapy, but the percent free PSA did not change significantly. This information is potentially useful in the interpretation of the PSA data that's used for early detection of prostate cancer in the men receiving CMA.
Chlormadinone Acetate* ; Digital Rectal Examination ; Humans ; Lower Urinary Tract Symptoms ; Male ; Mass Screening ; Prospective Studies ; Prostate* ; Prostate-Specific Antigen* ; Prostatic Hyperplasia* ; Prostatic Neoplasms ; Ultrasonography