PURPOSE: To evaluate the efficacy of focal verteporfin photodynamic therapy (PDT) in patients diagnosed with chronic central serous chorioretinopathy (CSC).METHODS: This study enrolled 52 eyes of 52 patients with chronic CSC who had received verteporfin PDT. The laser spot size of 26 eyes covering only the localized hyperfluorescent area in indocyanine green angiography was classified as focal PDT. The PDT spot size of the other 26 eyes covered the total area of retinal pigment epithelial detachment including the leaking point and was defined as conventional PDT. The central subfield thickness and subfoveal choroidal thickness were measured using Heidelberg Spectralis optical coherence tomography before PDT and at months 1, 3, 6, and 12 after PDT.RESULTS: The mean spot size of the PDT was 1,995 µm in the focal group and 2,995 µm in the conventional group. Central subfield thickness steadily decreased in both groups. The mean baseline subfoveal choroidal thickness for the two groups was 334.95 and 348.35 µm, respectively, with no significant difference (p = 0.602). Subfoveal choroidal thickness decreased significantly to 304.20 µm at 1 month, 284.85 µm at 3 months, 271.60 µm at 6 months, and 265.95 µm at 12 months in the focal group (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively, compared with baseline). In the conventional group, subfoveal choroidal thickness decreased significantly to 318.75, 300, 284, and 272 µm at 1, 3, 6, and 12 months, respectively (p < 0.001, p < 0.001, p < 0.001 and p < 0.001 compared with baseline). There were no significant differences between the two groups in subfoveal choroidal thickness based on PDT spot size at 1, 3, 6, and 12 months (p = 0.633, p = 0.625, p = 0.676, and p =0.755, respectively).CONCLUSIONS: Focal verteporfin PDT for CSC significantly decreased the subretinal fluid and sufoveal choroidal thickness to the same extent as conventional PDT.
Angiography ; Central Serous Chorioretinopathy ; Choroid ; Humans ; Indocyanine Green ; Photochemotherapy ; Retinal Detachment ; Subretinal Fluid ; Tomography, Optical Coherence

PURPOSE: This study aimed to evaluate the clinical course and prognostic factors of acquired third, fourth, and sixth cranial nerve (CN) palsy grouped according to etiology. METHODS: This study involved a retrospective review of the medical records of 153 patients who were diagnosed with acquired paralytic strabismus from January 2004 to July 2015. Outcomes, recovery rates, and time to recovery were investigated according to the affected CN: CN3, CN4, and CN6 palsies. The patients were classified into four groups based on etiology: idiopathic, traumatic, neoplastic, and vascular. RESULTS: The mean age of the patients was 59.8 ± 14.5 years and the mean follow-up period was 10.8 months. Out of the 153 patients, 63 (41.2%) had CN3 palsy, 35 (22.9%) had CN4 palsy, and 55 (35.9%) had CN6 palsy. The most common causes were vascular related (54.9%), followed by idiopathic (28.1%), trauma (8.5%), and neoplasm (5.88%). About 50% of the patients recovered within six months. Among the four etiologic groups, the idiopathic group showed the best prognosis because about 50% of the patients in this group recovered within three months. This was followed by the vascular, traumatic, and neoplastic groups. Cox proportional hazard analysis revealed a significant association between the baseline prism diopter and recovery rate. CONCLUSIONS: The prognosis and natural history of paralytic strabismus vary depending on its cause. The vascular group had the best recovery rate and shortest recovery time, whereas the neoplastic group required the longest time to recover.
Abducens Nerve Diseases* ; Abducens Nerve* ; Cranial Nerve Diseases ; Follow-Up Studies ; Humans ; Medical Records ; Natural History ; Paralysis ; Prognosis ; Retrospective Studies ; Strabismus

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

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

Pancreatic neoplasm is complicated and can be preceded by extra-pancreatic manifestations, such as cutaneous and musculoskeletal symptoms. Awareness of these associations is important for timely diagnosis and appropriate treatment. We report a case of pancreatic neuroendocrine tumor (NET) presenting with arthritis and panniculitis. The patient had a two month history of right knee pain and subcutaneous nodules in both legs. Synovial fluid analysis from the right knee joint revealed a mildly increased white blood cell count without crystallization. A skin biopsy of a subcutaneous nodule revealed lobular panniculitis. The initial treatment with empirical antibiotics did not alleviate the symptoms; however, the right knee arthritis and skin nodules improved with steroid treatment. On the eighth day of hospitalization, the patient complained of abdominal discomfort. Abdominopelvic computed tomography scanning revealed a 14-cm sized pancreatic mass with peritoneal metastasis. Percutaneous needle biopsy confirmed the diagnosis of pancreatic NET.
Anti-Bacterial Agents ; Arthritis* ; Biopsy ; Biopsy, Needle ; Crystallization ; Diagnosis ; Hospitalization ; Humans ; Knee ; Knee Joint ; Leg ; Leukocyte Count ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreatic Neoplasms ; Panniculitis* ; Skin ; Synovial Fluid

OBJECTIVE: To evaluate the colonic motility and nutrients intake in adults with cerebral palsy (CP) and to compare the results with those of normal adults. METHOD: Thirty-nine adults with CP were participated. They took the radioopaque markers for 3 successive days. Then, abdominal X-ray was taken on the fourth day. The total and segmental colon transits were estimated by the simplified assessment of a single-film technique by Metcalf et al. The amounts of nutrients intake for 3 days were recorded and nutritional factors were analyzed by ESHA(r) Food Processor. Then, daily intakes of the nutrients were compared with Recommended Dietary Allowance of Korean Nutrition Society. RESULT: Colon transit time were more than 2 times delayed in adults with CP as compared with those of normal controls. Colon transit time was significantly prolonged in non- functional ambulators (p<0.05). Colon transit time tended to be delayed in subjects with spastic type, but not related with the degree of cognitive function. On the evaluation of daily nutrients intake, several nutritional factors were inadequate in adults with CP. CONCLUSION: Adults with CP had the problems in colonic motility and nutritional intake. Also, delayed colon transit time was significantly related with poor mobility, and possibly related with spasticity.
Adult* ; Cerebral Palsy* ; Colon* ; Humans ; Muscle Spasticity ; Recommended Dietary Allowances

Cordycepin (3'-deoxyadenosine) has been shown to exhibit many pharmacological activities, including anti-cancer, anti-inflammatory, and anti-infection activities. However, the anti-skin photoaging effects of cordycepin have not yet been reported. In the present study, we investigated the inhibitory effects of cordycepin on matrix metalloproteinase-1 (MMP-1) and -3 expressions of the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed cordycepin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated NF-kappa B activity, which was determined by I kappa B alpha degradation, nuclear localization of p50 and p65 subunit, and NF-kappa B binding activity. However, UVB-induced NF-kappa B activation and MMP expression were completely blocked by cordycepin pretreatment. These findings suggest that cordycepin could prevent UVB-induced MMPs expressions through inhibition of NF-kappa B activation. In conclusion, cordycepin might be used as a potential agent for the prevention and treatment of skin photoaging.
Aging/physiology ; Cells, Cultured ; Deoxyadenosines/*pharmacology ; *Dermis/cytology/drug effects/physiology/radiation effects ; Dose-Response Relationship, Drug ; Enzyme Induction/drug effects ; Fibroblasts/drug effects/metabolism/radiation effects ; Gene Expression Regulation, Enzymologic ; Humans ; Infant, Newborn ; Male ; *Matrix Metalloproteinase 1/antagonists & inhibitors/biosynthesis/genetics/radiation effects ; Matrix Metalloproteinase 3/antagonists & inhibitors/*biosynthesis/genetics/radiation effects ; NF-kappa B/*antagonists & inhibitors/genetics/metabolism ; Skin/physiopathology/radiation effects ; *Ultraviolet Rays

TNF-alpha plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-alpha has been known to downregulate PTEN via NF-kappaB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF-kappaB in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappaB with p65 anisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappaB pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha-treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappaB activation in human leukemic cells.
Up-Regulation/*drug effects ; Tumor Necrosis Factor-alpha/*pharmacology ; Signal Transduction/*drug effects ; PTEN Phosphohydrolase/genetics/*metabolism ; NF-kappa B/genetics/*metabolism ; Leukemia/genetics/*metabolism ; Humans ; Gene Expression ; Cell Line, Tumor