BACKGROUND: AND PURPOSE: The aim of this study was to determine the diagnostic performance and safety of a new ¹⁸F-labeled amyloid tracer, ¹⁸F-FC119S. METHODS: This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹⁸F-FC119S PET, ¹⁸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹⁸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹⁸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored. RESULTS: Visual assessments of the ¹⁸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹⁸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹⁸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods. CONCLUSIONS ¹⁸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.

BackgroundGlehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice.

MethodsA total of 39 male ICR mice (12 weeks old) were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups (n = 13 in each group). Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects of G. littoralis extract, we performed immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU, an indicator for cell proliferation) and doublecortin (DCX, an immature neuronal marker) and double immunofluorescence staining for BrdU and neuronal nuclear antigen (NeuN, a mature neuronal marker). In addition, we examined expressional changes of brain-derived neurotrophic factor (BDNF) and its major receptor tropomyosin-related kinase B (TrkB) using Western blotting analysis.

ResultsTreatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive () and DCX cells (48.0 ± 3.1 and 72.0 ± 3.8 cells/section, respectively) in the subgranular zone (SGZ) of the dentate gyrus (DG) and BrdU/NeuN cells (17.0 ± 1.5 cells/section) in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and TrkB (about 232% and 244% of the vehicle-treated group, respectively) were significantly increased in the DG of the mice treated with 200 mg/kg of G. littoralis extract.

ConclusionG. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases of BDNF and TrkB proteins by G. littoralis extract treatment.

Animals ; Apiaceae ; chemistry ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Dentate Gyrus ; cytology ; drug effects ; Hippocampus ; cytology ; drug effects ; Immunohistochemistry ; Male ; Mice ; Microtubule-Associated Proteins ; metabolism ; Neurogenesis ; drug effects ; Neuropeptides ; metabolism ; Plant Extracts ; pharmacology ; Receptor, trkB ; metabolism

The genus Populus (poplar) belonging to the Salicaceae family has been used in traditional medicine, and its several species show various pharmacological properties including antioxidant and anti-inflammatory effects. No study regarding protective effects of Populus species against cerebral ischemia has been reported. Therefore, in the present study, we examined neuroprotective effects of ethanol extract from Populus tomentiglandulosa (Korea poplar) in the hippocampal cornu ammonis (CA1) area of gerbils subjected to 5 minutes of transient global cerebral ischemia. Pretreatment with 200 mg/kg of P. tomentiglandulosa extract effectively protected CA1 pyramidal neurons from transient global cerebral ischemia. In addition, glial fibrillary acidic protein immunoreactive astrocytes and ionized calcium binding adapter molecule 1 immunoreactive microglia were significantly diminished in the ischemic CA1 area by pretreatment with 200 mg/kg of P. tomentiglandulosa extract. Briefly, our results indicate that pretreatment with P. tomentiglandulosa extract protects neurons from transient cerebral ischemic injury and diminish cerebral ischemia-induced reactive gliosis in ischemic CA1 area. Based on these results, we suggest that P. tomentiglandulosa can be used as a potential candidate for prevention of ischemic injury.
Astrocytes ; Brain Ischemia* ; Calcium ; Ethanol ; Gerbillinae* ; Glial Fibrillary Acidic Protein ; Gliosis* ; Hippocampus ; Humans ; Medicine, Traditional ; Microglia ; Neurons* ; Neuroprotective Agents ; Populus* ; Pyramidal Cells ; Salicaceae

PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography. CONCLUSION: Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.
Acetylcholine ; Aged ; Angina Pectoris/diagnosis ; Calcium Channel Blockers/therapeutic use ; Cardiovascular Agents/*therapeutic use ; Coronary Angiography/adverse effects ; Coronary Artery Disease/prevention & control ; Coronary Vasospasm/diagnosis/*drug therapy ; Diltiazem/*therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Myocardial Infarction/prevention & control ; Nitrates/*therapeutic use ; Propensity Score ; Time Factors ; Vasodilator Agents/therapeutic use

BACKGROUNDGlehnia littoralis, as a traditional herbal medicine to heal various health ailments in East Asia, displays various therapeutic properties including antioxidant effects. However, neuroprotective effects of G. littoralis against cerebral ischemic insults have not yet been addressed. Therefore, in this study, we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia (TGCI).

METHODSGerbils were subjected to TGCI for 5 min. G. littoralis extract (GLE; 100 and 200 mg/kg) was administrated orally once daily for 7 days before ischemic surgery. Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. Gliosis was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1. For neuroprotective mechanisms, immunohistochemistry for superoxide dismutase (SOD) 1 and brain-derived neurotrophic factor (BDNF) was done.

RESULTSPretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 (CA1) area from ischemic insult area (F = 29.770, P < 0.05) and significantly inhibited activations of astrocytes (F = 22.959, P < 0.05) and microglia (F = 44.135, P < 0.05) in the ischemic CA1 area. In addition, pretreatment with GLE significantly increased expressions of SOD1 (F = 28.561, P < 0.05) and BDNF (F = 55.298, P < 0.05) in CA1 pyramidal neurons of the sham- and ischemia-operated groups.

CONCLUSIONSOur findings indicate that pretreatment with GLE can protect neurons from ischemic insults, and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD1 and BDNF expressions as well as attenuation of glial activation.

PURPOSE: To evaluate the clinical outcomes of visual acuity and foveal thickness after vitrectomy for an idiopathic epiretinal membrane (ERM). METHODS: We retrospectively reviewed the records of 62 patients (62 eyes) with ERM who had been treated with vitrectomy between 2004 and 2009. Visual acuity and central macular thickness from optical coherence tomography imaging were obtained preoperatively and at every postoperative follow-up visit. RESULTS: Mean preoperative visual acuity and central macular thickness were 0.495 +/- 0.292 log MAR and 414.645 +/- 95.528 microm, respectively. Mean visual acuity and central macular thickness 1 month after surgery were 0.389 +/- 0.373 log MAR and 341.484 +/- 73.676 microm, respectively. Visual acuity improved within 9 months and central macular thickness significantly decreased 12 months after surgery. Most of the changes in visual acuity and central macular thickness took place during the first 3 months. The only parameter which was significantly correlated with final visual acuity was preoperative visual acuity (0.635) (p < 0.001). CONCLUSIONS: Visual acuity and central macular thickness improved 12 months months after vitrectomy in patients with idiopathic ERM. Preoperative visual acuity had a significant correlation with final visual acuity.
Epiretinal Membrane ; Follow-Up Studies ; Humans ; Hypogonadism ; Mitochondrial Diseases ; Ophthalmoplegia ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity ; Vitrectomy

Sarcoidosis is multi-systemic disorder of an unknown etiology, and this is histologically characterized by noncaseating granulomatous inflammation. Sarcoidosis may affect the lung, skin, lymph nodes and eyes, but it rarely affects the subcutaneous tissue. There has been no report of diffuse subcutaneous sarcoidosis in Korea. We experienced a 57-year-old female with diffuse subcutaneous sarcoidosis that presented as thickened extremities. The patient complained of edema and skin thickening on both upper extremities. Magnetic resonance imaging revealed the reticular form of sarcoidosis on the forearm and the biopsy showed noncaseating granuloma. She was finally diagnosed as diffuse subcutaneous sarcoidosis and she improved after treatment with corticosteroid. We report here on this unusual case along with a review of the relevant literature.
Biopsy ; Edema ; Extremities ; Eye ; Female ; Forearm ; Granuloma ; Humans ; Inflammation ; Korea ; Lung ; Lymph Nodes ; Magnetic Resonance Imaging ; Middle Aged ; Sarcoidosis ; Skin ; Subcutaneous Tissue ; Upper Extremity

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m2) and cisplatin (60 mg/m2) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.
Adenocarcinoma/*drug therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse ; Cisplatin/administration & dosage/adverse effects ; Female ; Fluorouracil/administration & dosage/adverse effects ; Humans ; Leucovorin/administration & dosage/adverse effects ; Male ; Middle Aged ; Organoplatinum Compounds/administration & dosage/adverse effects ; Paclitaxel/administration & dosage/adverse effects ; Stomach Neoplasms/*drug therapy/mortality ; Survival Rate ; Treatment Failure

BACKGROUND: Acute myelogenous leukemia (AML) is frequently encountered in elderly patients whereas intensive chemotherapy yield lower rate of complete remission (CR) and survival than young patients. This study was aimed to review the clinical features and treatment outcomes of elderly patients (>or=60) with AML. METHODS: We respectively reviewed the clinical features, laboratory findings and outcomes of treatment from the medical records of 115 patients with the elderly AML (>or=60), admitted in Seoul National University Hospital, between Jan.1995 and Dec.2004. RESULTS: Their median age was 66 (60~86) years with male predominance (M:F=68:47). Complete response rate in patients with conventional chemotherapy was 66.7% (42 of 63 patients; 95% CI 50.2~78.4). Median overall survival (OS) was 5.2 months with clinical benefit in the conventional chemotherapy group, compared to supportive or palliative group (11.5 vs 0.9months; p<0.0001). In between two age groups, the sixties (n=69) showed higher CR rate (69.0 vs 61.9%; p=0.9) and longer median overall survival (7.0 vs 4.4months; p=0.8) than patients group of the seventies (n=38) but without statistical significance. CONCLUSIONS: Conventional induction chemotherapy improved survival rate than palliative or supportive treatment.
Aged* ; Drug Therapy ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute* ; Male ; Medical Records ; Prognosis ; Retrospective Studies* ; Seoul ; Survival Rate

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.
Aged ; Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Boronic Acids/administration & dosage/adverse effects/*therapeutic use ; Dexamethasone/administration & dosage/adverse effects ; Disease Progression ; Drug Resistance, Neoplasm ; Female ; Humans ; Korea ; Male ; Middle Aged ; Multiple Myeloma/*drug therapy ; Neoplasm Recurrence, Local ; Pilot Projects ; Pyrazines/administration & dosage/adverse effects/*therapeutic use ; Research Support, Non-U.S. Gov't ; Survival Analysis ; Thrombocytopenia/chemically induced ; Time Factors