Purpose: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. Materials and Methods: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. Results: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. Conclusion Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Background and Objectives: This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). Methods: A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). Results: During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. Conclusion Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

BACKGROUND/AIMS: Because of the limited geographic distribution, there have been insufficient data regarding hepatitis C virus (HCV) genotype 6 in Korea. This study aimed to investigate the clinical characteristics and available treatment outcomes of patients with genotype 6 HCV in Korea. METHODS: From 2004 to 2014, data were collected from Korean patients infected with genotype 6 HCV in eight hospitals. RESULTS: Thirty-two patients had genotype 6 HCV. The median age was 44 years, and 6c was the most common subtype. The baseline median alanine transaminase level was 88 (21 to 1,019) IU/mL, and the HCV RNA level was 1,405,000 (96,500 to 28,844,529) IU/mL. Twenty-five patients were treated with peginterferon (PEG-IFN) and ribavirin. Three follow-up losses occurred. Additionally, 13 patients attained a sustained virologic response (SVR), seven patients relapsed, and two patients exhibited a null response. The SVR rates were 40% and 75% for the 24- and more than 48-week treatments, respectively, and five of the six patients who achieved a rapid virologic response (RVR) attained a SVR. CONCLUSIONS: Korean patients infected with genotype 6 HCV are relatively young, and 6c is the most common subtype. When treated with PEG-IFN and ribavirin, the SVR rate was 52%. Similar to other genotypes, a longer duration of treatment and attainment of RVR are important for SVR.
Alanine Transaminase ; Follow-Up Studies ; Genotype* ; Hepacivirus* ; Hepatitis C* ; Hepatitis C, Chronic ; Hepatitis* ; Humans ; Korea* ; Ribavirin* ; RNA ; Treatment Outcome*

This study examined the mechanism of action of a local anesthetic, lidocaine.HCl. Energy transfer between the surface fluorescent probe, 1-anilinonaphthalene-8-sulfonic acid, and the hydrophobic fluorescent probe, 1,3-di(1-pyrenyl) propane, was used to determine the effect of lidocaine.HCl on the thickness (D) of the synaptosomal plasma membrane vesicles (SPMV) isolated from the bovine cerebral cortex, and liposomes of the total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. The thickness (D) of the intact SPMV, SPMVTL and SPMVPL were 1.044+/-0.008, 0.914+/-0.005 and 0.890+/-0.003 (arbitrary units, n=5) at 37degrees C (pH 7.4), respectively. Lidocaine.HCl decreased the thickness of the neuronal and model membrane lipid bilayers in a dose-dependent manner with a significant decrease in the thickness, even at 0.1 mM. The decreasing effect of lidocaine.HCl on the membrane thickness might be responsible for some, but not all of its anesthetic action.
Anilino Naphthalenesulfonates ; Cell Membrane ; Cerebral Cortex ; Energy Transfer ; Lipid Bilayers ; Liposomes ; Membranes ; Neurons ; Phospholipids ; Propane

BACKGROUND/AIMS: To date, an effective salvage chemotherapy regimen for the treatment of refractory or relapsing non-Hodgkin's lymphoma (NHL) has not been discovered. This study was conducted to evaluate the efficacy and safety of gemcitabine, etoposide, cisplatin, and dexamethasone in relapsed or refractory NHL patients. METHODS: All patients had histologically proven relapsed or refractory NHL. Treatments consisted of gemcitabine 700 mg/m2 by continuous i.v. on days 1 and 8; etoposide 40 mg/m2 by i.v. on days 1-4; cisplatin 60 mg/m2 by i.v. on day 1; or dexamethasone 40 mg by i.v. on days 1-4 (GEPD) every 21 days. The primary end point was the patient response rate following two cycles of treatment. After two cycles, stem cells were harvested using mobilizing regimens (ESHAP or GEPD plus filgrastim), and this was followed by autologous stem cell transplantation or four additional cycles of GEPD. RESULTS: Between January 2005 and January 2006, 20 patients (13 males and 7 females) were enrolled in the study. The median age was 53 (range 16-75) years. The most common histology was diffuse large B-cell lymphoma (n=10). The median follow-up duration was 5.2 (range 1.0-16.0) months. After two cycles, the overall response rate was 50.0% (10/20), including two complete responses and eight partial responses. The doselimiting toxicity was myelosuppression. Grade IV neutropenia and thrombocytopenia occurred in 13 (65.0%) and 6 patients (30.0%), respectively. The median number of CD34-positive cells collected was 6.0 (range, 2.8-11.6)x10(6)/kg. Of the 17 patients < 66 years of age, 4 (23.5%) proceeded to autologous stem cell transplantation. CONCLUSIONS: GEPD chemotherapy in patients with refractory or relapsed NHL was effective as a salvage therapy and helpful for stem cell harvest followed by autologous transplantation.
Adolescent ; Adult ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biopsy ; Cisplatin/administration & dosage ; Deoxycytidine/administration & dosage/analogs & derivatives ; Dexamethasone/administration & dosage ; Etoposide/administration & dosage ; Female ; Follow-Up Studies ; Glucocorticoids/administration & dosage ; Humans ; Immunosuppressive Agents/administration & dosage ; Lymphoma, Large B-Cell, Diffuse/*drug therapy/pathology/surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/pathology/surgery ; Prospective Studies ; Stem Cell Transplantation/methods ; Treatment Outcome ; Young Adult

Substernal goiter is defined as a thyroid mass of which more than half is located below the thoracic inlet. As substernal goiter enlarges within the bony thoracic cavity, and vascular and visceral structures may slowly become compressed and compromised. Airway obstruction can occur due to the compression or the displacement of the trachea. Tracheal compression may rarely lead to severe respiratory compromise. Recently, we experienced a case of huge substernal goiter causing acute respiratory failure in a 63-year old female. We present this case with a review of the literature.
Airway Obstruction ; Bays ; Displacement (Psychology) ; Female ; Goiter, Substernal ; Humans ; Respiratory Insufficiency ; Thoracic Cavity ; Thyroid Gland ; Trachea

OBJECTIVES: Bioterrorism (BT) preparedness and response plans are particularly important among healthcare workers who will be among the first involved in the outbreak situations. This study was conducted to evaluate the current status of education for BT preparedness and response in healthcare-related colleges/junior colleges and to develop learning objectives for use in their regular curricula. METHODS: We surveyed all medical colleges/schools, colleges/junior colleges that train nurses, emergency medical technicians or clinical pathologists, and 10% (randomly selected) of them that train general hygienists in Korea. The survey was conducted via mail from March to July of 2007. We surveyed 35 experts to determine if there was a consensus of learning objectives among healthcare workers. RESULTS: Only 31.3% of medical colleges/schools and 13.3% of nursing colleges/junior colleges had education programs that included BT preparedness and responses in their curricula. The most common reason given for the lack of BT educational programs was 'There is not much need for education regarding BT preparedness and response in Korea'. None of the colleges/junior colleges that train clinical pathologists, or general hygienists had an education program for BT response. After evaluating the expert opinions, we developed individual learning objectives designed specifically for educational institutions. CONCLUSIONS: There were only a few colleges/junior colleges that enforce the requirement to provide education for BT preparedness and response in curricula. It is necessary to raise the perception of BT preparedness and response to induce the schools to provide such programs.
*Bioterrorism ; Curriculum ; Disaster Planning/*organization & administration ; Humans ; Korea ; Schools, Health Occupations/*organization & administration

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor. Although it is well known to have various physiological roles in cancer, its inhibitory effect on inflammation remains poorly understood. In the present study, a human PTEN gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-PTEN fusion protein. The expressed and purified PEP-1-PTEN fusion protein were transduced efficiently into macrophage Raw 264.7 cells in a time- and dose- dependent manner when added exogenously in culture media. Once inside the cells, the transduced PEP-1-PTEN protein was stable for 24 h. Transduced PEP-1-PTEN fusion protein inhibited the LPS-induced cyclooxygenase 2 (COX-2) and iNOS expression levels in a dose-dependent manner. Furthermore, transduced PEP-1-PTEN fusion protein inhibited the activation of NF-kappa B induced by LPS. These results suggest that the PEP-1-PTEN fusion protein can be used in protein therapy for inflammatory disorders.
Animals ; Cell Line ; Cyclooxygenase 2/*metabolism ; Cysteamine/*analogs & derivatives ; Enzyme Activation ; Humans ; Lipopolysaccharides/*pharmacology ; Macrophages/*metabolism ; Mice ; NF-kappa B/metabolism ; Nitric Oxide/*biosynthesis ; Nitric Oxide Synthase Type II/metabolism ; PTEN Phosphohydrolase/*genetics ; Peptides/*genetics ; Recombinant Fusion Proteins/*biosynthesis/genetics ; Signal Transduction

BACKGROUND: The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC). METHODS: Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists. RESULTS: There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3. CONCLUSIONS: The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.
Adenocarcinoma

BACKGROUND: Iron is essential for life, but iron overload state cause potentially fatal health risk. There is growing evidence that only mildly increased amounts of hepatic iron can be damaging, particulary if combined with other hepatotoxic factors such as alcoholic or chronic viral hepatits B,C. The aim of this study was to assess the serum iron status of patients with various forms of hepatitis and cirrhosis of liver and to determine the correlation between the degree of hepatocyte damage (expressed as ALT activity) and status of serum iron parameters. METHODS: Our research involved 107 patients (69 male ranging in age from 27-67 and 38 female ranging in age from 32-62) diagnosed with chronic viral hepatitis B or type C, alcoholic hepatitis or cirrhosis of the liver. Serum iron parameters such as serum iron, ferritin, TIBC, and aminotransferase measured as necroinflammatory activity in Chronic hepatitis. RESULTS: There was no difference s-iron level between chronic hepatitis and cirrhosis but, significantly higher in alcoholic hepatitis and cirrhosis than viral hepatitis and cirrhosis respectively. s-Ferritin level was significantly higher in cirrhosis than hepatits group, and more higher in alcoholic hepatitis and cirrhosis than viral hepatitis and cirrhosis respectively. In chronic hepatitis groups, there are significant correlation between ALT and s-ferritin level regardness of etiology. CONCLUSION: Serum iron overload state was prominent in alcoholic hepatitis and cirrhosis than viral hepatitis and cirrhosis. High serum ferritin level can predict hepatocyte damage in chronic hepatitis.
Alcoholics ; Female ; Ferritins ; Fibrosis ; Hepatitis ; Hepatitis B ; Hepatitis, Alcoholic ; Hepatitis, Chronic ; Hepatocytes ; Humans ; Iron Overload ; Iron* ; Liver Diseases* ; Liver* ; Male