Objective: To evaluate the long-term safety and efficacy of intranasal esketamine in patients with treatment-resistant depression from the Asian subgroup of the SUSTAIN-2 study. Methods: SUSTAIN-2 was a phase 3, open-label, single-arm, multicenter study comprising a 4-week screening, 4-week induction, 48-week optimization/maintenance, and 4-week follow-up (upon esketamine discontinuation) phase. Patients with treatment-resistant depression received esketamine plus an oral antidepressant during the treatment period. Results: The incidence of ≥ 1 serious treatment-emergent adverse event (TEAE) among the 78 subjects from the Asian subgroup (Taiwan: 33, Korea: 26, Malaysia: 19) was 11.5% (n = 9); with no fatal TEAE. 13 Asian patients (16.7%) discontinued esketamine due to TEAEs. The most common TEAEs were dizziness (37.2%), nausea (29.5%), dissociation (28.2%), and headache (21.8%). Most TEAEs were mild to moderate in severity, transient and resolved on the same day. Upon discontinuation of esketamine, no trend in withdrawal symptoms was observed to associate long-term use of esketamine with withdrawal syndrome. There were no reports of drug seeking, abuse, or overdose. Improvements in symptoms, functioning and quality of life, occurred during in the induction phase and were generally maintained through the optimization/maintenance phases of the study. Conclusion The safety and efficacy of esketamine in the Asian subgroup was generally consistent with the total SUSTAIN-2 population. There was no new safety signal and no indication of a high potential for abuse with the long-term (up to one year) use of esketamine in the Asian subgroup. Most of the benefits of esketamine occurred early during the induction phase.

PURPOSE: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. MATERIALS AND METHODS: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. RESULTS: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. CONCLUSIONS: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.
Adenosine ; Adenosine Triphosphate ; Antibodies ; Cell Death ; Cisplatin ; Doxorubicin ; Drug Screening Assays, Antitumor ; Drug Therapy ; Epirubicin ; Etoposide ; Fluorouracil ; Gastrectomy ; Granzymes ; Humans ; Lymphocytes, Tumor-Infiltrating* ; Methotrexate ; Mitomycin ; Paclitaxel ; Pilot Projects* ; Stomach Neoplasms*

BACKGROUND: The treatment success rates in patients with tuberculosis are known to be lower in the private sector compared to the public sector. To improve treatment outcomes in the private sector we developed a public-private collaboration model for strengthening health education and case holding activities with public health nursing in the private sector. METHODS: We performed a prospective cohort study in new smear positive pulmonary tuberculosis patients treated at private hospitals, selected by non-randomization, with an intervention consisting of health education and case holding activities by specially trained public health nurses (intervention group) results were compared with cases treated without the intervention (conventional group). Physicians were asked to treat both groups routinely. The treatment outcomes of patients under treatment by the National Tuberculosis Programme were also analyzed for comparison. RESULTS: There were 172 cases each in the intervention and conventional groups. The mean age was 48.9+/-19.0 and 48.2+/-19.7 in the respective groups (p=0.66). The PHN interacted with the cases in the intervention group by initial face to face interview and telephone calls an average of 7.1+/-9.2 times during the initial six months. The intervention group showed a significantly higher treatment success rate, 91.6%, (Rate Ratio [RR]; 1.23, 95% Confidence Interval [CI]; 1.12~1.36), lower default, 3.6%, (RR; 0.31, 95% CI; 0.13~0.75) and transfer-out rate, 3.0%, (RR; 0.32, 95% CI; 0.12~0.86) than the conventional group where they were: 75.0%, 11.6%, 9.3%, respectively. The success rate was even higher than the rate (80.5%) of 1,027 cases treated in health centers (RR; 1.11, 95% CI; 1.05~1.17). Of the completed cases in the intervention group, 82.2% regarded the role of the public health nurse as very helpful. CONCLUSION: The treatment success rate, of tuberculosis patients in the private sector, was significantly improved by an intervention using a public-private collaboration model.
Cohort Studies ; Cooperative Behavior ; Health Education ; Hospitals, Private ; Humans ; Private Sector ; Prospective Studies ; Public Health Nursing ; Public Sector ; Telephone ; Tuberculosis ; Tuberculosis, Pulmonary

The aims of this study were to find an optimal basal infusion dose of fentanyl for parent-controlled analgesia (PrCA) in children undergoing cleft palate repair and the degree of parents' satisfaction with PrCA. Thirty consecutive children between 6 months and 2 yr of age were enrolled. At the end of surgery, a PrCA device with a basal infusion rate of 2 mL/hr and bolus of 0.5 mL with lockout time of 15 min was applied. Parents were educated in patient-controlled analgesia (PCA) devices, the Wong Baker face pain scoring system, and monitoring of adverse effects of fentanyl. Fentanyl was infused 0.3 microgram/kg/hr at first, and we obtained a predetermined fentanyl regimen by the response of the previous patient to a larger or smaller dose of fentanyl (0.1 microgram/kg/hr as the step size), using an up-and-down method. ED50 and ED95 by probit analysis were 0.63 microgram/kg/hr (95% confidence limits, 0.55-0.73 microgram/kg/hr) and 0.83 microgram/kg/hr (95% confidence limits, 0.73-1.47 microgram/kg/hr), respectively. Eighty seven percent of the parents were satisfied with participating in the PrCA modality. PrCA using fentanyl with a basal infusion rate of 0.63 microgram/kg/hr can be applied effectively for postoperative pain management in children undergoing cleft palate repair with a high level of parents' satisfaction.
*Analgesia, Patient-Controlled ; Child, Preschool ; Cleft Palate/*surgery ; Female ; Fentanyl/therapeutic use ; Humans ; Infant ; Male ; *Parents

PURPOSE: Although many studies have demonstrated improvements in short-and long-term outcomes of gastric cancer surgery, changes in long-term survival over time are not well-established. This study was conducted to evaluate changes in host, tumor, and treatment factors in patients treated at a single institution over a period of 45-yr. PATIENTS AND METHODS: We retrospectively evaluated 9282 patients with gastric cancer from 1955 to 1999, and divided the 45-yr into 4 time frames based on published articles: 1955 to 1962 (n=228), 1963 to 1972 (n=891), 1973 to 1988 (n=2789), and 1989 to 1999 (n=5374). RESULTS: Remarkable changes were noted in host, tumor, treatment factors, and prognosis. Among host factors, patients of more advanced age were identified in the 4th period and mean age shifted from 49 to 55 yrs. Among tumor factors, early gastric cancers and upper body tumors increased up to 32% and from 7% to 13%, respectively. An increase in the annual number of patients (from 29 to 649), gastrectomies (from 14 to 600), rate of resection (from 50% to 90%), rate of curative resection (up to 92%), and proportion of total gastrectomy (from 8% to 29%) was noted. Operative mortality was reduced from 6.1% to 0.7%. The overall 5-yr survival rate significantly increased from 22% to 65%. CONCLUSION: Treatment results of gastric cancer surgery have improved remarkably over the 45-year period. Increase of early stage gastric cancer with early diagnosis considerably influenced the improved survival of patients with gastric cancer.
Age Distribution ; Aged ; Aged, 80 and over ; Female ; Gastrectomy/adverse effects/*methods/statistics & numerical data ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Sex Distribution ; Stomach Neoplasms/mortality/pathology/*surgery ; Survival Analysis ; Survival Rate ; Treatment Outcome

BACKGROUND: Surveillance of TB drug resistance (DR) is essential for providing information on the magnitude and trends in resistance, for developing treatment guidelines and for monitoring the effect of interventions. Up to now national surveys of drug resistance of M. tuberculosis have been conducted four times since 1994 among patients registered at health centers. The purpose of this study is to estimate the prevalence of primary drug resistance among new cases identified in private sector, and to compare it with the previous national drug resistance surveys. METHODS: The study collected results of drug susceptibility testing (DST) performed at the Korean Institute of Tuberculosis by the request of private sector from January 2003 to December 2005, and then finally selected new cases for the analysis from the database of Korean TB Surveillance (KTBS) by matching patients' name and social identification numbers. RESULTS: Of the 5,132 new patients included in the study, 689 (13.4%) patients were found to have drug resistance at least one drug, 530 patients (10.3%) were isoniazid resistant, 195 patients (3.8%) were multi-drug resistant (MDR), and 21 patients (0.4%) were extensively drug resistant (XDR). The rate of drug resistance tended to decrease annually but it was not statistically significant. When compared with previous national DR surveys in 2003 and in 2004 respectively, they were not significantly different. CONCLUSION: The prevalence of DR among new cases managed in the private sector did not show significant difference from that of new patients registered in the public sector in the same year.
Drug Resistance ; Humans ; Isoniazid ; Prevalence ; Private Sector ; Public Sector ; Social Identification ; Tuberculosis ; Tuberculosis, Pulmonary

PURPOSE: Laparoscopic wedge resection (LWR) is replacing open wedge resection (OWR) as the standard surgical treatment for gastric submucosal tumors. However, few scientific comparisons exist as to whether LWR or OWR is better in terms of postoperative outcomes. This study was performed to compare these two treatment modalities for the treatment of gastric submucosal tumors by evaluating the postoperative outcomes. METHODS: Between 1993 and 2004, 112 patients with a gastric submucosal tumor had undergone either LWR (n=42) or OWR (n=70). Their medical records were retrospectively reviewed with regard to tumor size, operative time, time to first flatus, postoperative hospital stay and analgesics use. RESULTS: The demographics and tumor characteristics of the patients were similar in both groups. Four (9 %) cases in the LWR group were converted to an open procedure. The mean operation time was longer in the LWR than the OWR group (100.6 vs. 84.3 min)(P = 0.015). The time to first flatus (1.8 +/- 0.1 vs. 3.3 +/- 0.1 days, respectively, P < 0.0001) and soft diet intake (3.5 +/- 0.3 vs. 6.0 +/- 0.2 days, respectively, P < 0.0001) were shorter in the LWR compared to the OWR group. The postoperative hospital stay was significantly shorter in the LWR than in the OWR group (5.3 +/- 0.6 vs. 8.5 +/- 0.2 days) (P < 0.0001). The number of analgesics uses (2.7 +/- 0.4 times) in the LWR was less than that in the OWR group (2.7 +/- 0.4 vs. 4.1 +/- 0.5 times)(P=0.0056). CONCLUSION: Laparoscopic wedge resection of a gastric submucosal tumor was superior to open wedge resection in terms of the postoperative outcomes. Laparoscopic wedge resection could be considered the first-line treatment for gastric submucosal tumors.
Analgesics ; Demography ; Diet ; Flatulence ; Humans ; Length of Stay ; Medical Records ; Operative Time ; Retrospective Studies ; Stomach*

OBJECTIVE: Papaverine has been used in treating vasospasm following subarachnoid hemorrhage(SAH). However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. RESULTS: Papaverine of 100 microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by BKCa(large conductance calcium dependent potassium channels)blocker, IBX(iberiotoxin), and calcium chealator, BAPTA(1, 2-bis(o-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid), in whole cell mode. CONCLUSION: These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.
Animals ; Basilar Artery ; Baths ; Calcium ; Calcium Channels ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Papaverine* ; Patch-Clamp Techniques ; Potassium ; Potassium Channels ; Rats* ; Relaxation

BACKGROUND: Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance METHODS: The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results. RESULTS: Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests. CONCLUSION: EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself.
Codon ; DNA ; Drug Resistance ; Ethambutol ; Humans ; Isoniazid ; Korea ; Mycobacterium tuberculosis* ; Mycobacterium* ; Point Mutation ; Polymerase Chain Reaction ; Tuberculosis

BACKGROUND: Rifabutin (ansamycin) is a spiro-piperidyl rifamycin, which is highly active against Mycobacterium tuberculosis. It has been found that some clinical isolates of tubercle bacilli that are resistant to rifampicin are susceptible to rifabutin, with some patients with multi-drug resistant pulmonary tuberculosis having shown favorable clinical and bacteriological responses to the rifabutin. This study was conducted to find the proportion of rifabutin- susceptible strains among rifampicin-resistant isolates from Korean MDR-TB patients, and investigate the presence of specific rpoB mutations, which may confer resistance to rifampicin, but not to rifabutin. METHODS: 201 rifampicin-resistant and 50 pan-susceptible M. tuberculosis isolates were randomly selected for this study. The isolates were retested at rifampicin and rifabutin concentrations of 0, 20, 40 and 80 microgram/ml, respectively. The isolates that grew at and/or over a rifabutin concentration of 20 microgram/ml were judged rifabutin-resistant. The rpoB gene was extracted from the isolates, and then amplified for direct sequencing to investigate specific rpoB mutations that conferred rifabutin- susceptibility but rifampicin-resistance. RESULTS: Out of the 201 rifampicin-resistant M. tuberculosis, 41 strains (20.4%) were susceptible to rifabutin using the absolute concentration method on Lowenstein-Jensen media. The rpoB mutation types that showed susceptibility to rifabutin were Leu511Pro, Ser512Arg, Gln513Glu, Asp516Ala, Asp516Gly, Asp516Val, Asp516Tyr, Ser522Leu, His526Asn, His526Leu, His526Cys, Arg529Pro and Leu533Pro. A reverse hybridization technique was able to detect 92.5% of the rifabutin-susceptible isolates, with a specificity of 96.1% among 195 M. tuberculosis isolates with the rpoB mutation. CONCLUSIONS: Around 20% of the rifampicin-resistant isolates in Korea showed susceptibility to rifabutin, which was associated with some specific mutations of rpoB. Rifabutin could be used for the treatment of MDR-TB patients, especially when drug susceptibility testing reveals susceptibility to rifabutin.
Humans ; Korea ; Mycobacterium tuberculosis ; Rifabutin ; Rifampin ; Tuberculosis ; Tuberculosis, Pulmonary