BACKGROUND: The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). METHODS: This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. RESULTS: After 6 weeks, the polmacoxib-placebo treatment difference was −2.5 (95% confidence interval [CI], −4.4 to −0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, −0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were “much improved” at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. CONCLUSIONS: Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.
Arm ; Celecoxib* ; Electrocardiography ; Hip ; Humans ; Knee ; Ontario ; Osteoarthritis* ; Outcome Assessment (Health Care) ; Physical Examination ; Vital Signs

This research aimed to investigate the changes in ethical issues in everyday clinical practice recognized by critical care nurses during two observation periods. We conducted a retrospective analysis of data obtained by prospective questionnaire surveys of nurses in the intensive care units (ICU) of a tertiary university-affiliated hospital in Seoul, Korea. Data were collected prospectively during two different periods, February 2002-January 2003 (Period 1) and August 2011-July 2012 (Period 2). Significantly fewer cases with ethical issues were reported in Period 2 than in Period 1 (89 cases [2.1%] of 4,291 ICU admissions vs. 51 [0.5%] of 9,302 ICU admissions, respectively; P < 0.001). The highest incidence of cases with identified ethical issues in both Periods occurred in MICU. The major source of ethical issues in Periods 1 and 2 was behavior-related. Among behavior-related issues, inappropriate healthcare professional behavior was predominant in both periods and mainly involved resident physicians. Ethical issue numbers regarding end-of-life (EOL) care significantly decreased in the proportion with respect to ethical issues during Period 2 (P = 0.044). In conclusion, the decreased incidence of cases with identified ethical issues in Period 2 might be associated with ethical enhancement related with EOL and improvements in the ICU care environment of the studied hospital. However, behavior-related issues involving resident physicians represent a considerable proportion of ethical issues encountered by critical care nurses. A systemic approach to solve behavior-related issues of resident physicians seems to be required to enhance an ethical environment in the studied ICU.
Critical Care Nursing/*ethics ; Humans ; *Intensive Care Units ; Nurses ; Retrospective Studies ; Terminal Care ; Tertiary Care Centers

alpha-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of alpha-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of alpha-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. alpha-Asarone significantly reduced TNF-alpha and IL-1beta mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of alpha-asarone treatment. alpha-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. alpha-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of alpha-asarone treatment. In the Morris water maze test, alpha-asarone significantly prolonged the swimming time spent in the target and peri-target zones. alpha-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by alpha-asarone may be one of the mechanisms for the alpha-asarone-mediated ameliorating effect on memory deficits.
Animals ; Cell Size ; Cytokines* ; Head ; Hippocampus ; Immunohistochemistry ; Learning ; Maze Learning ; Memory ; Memory Disorders* ; Mice* ; Microglia ; Neurons ; RNA, Messenger ; Swimming ; Tumor Necrosis Factor-alpha ; Up-Regulation

alpha-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of alpha-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of alpha-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. alpha-Asarone significantly reduced TNF-alpha and IL-1beta mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of alpha-asarone treatment. alpha-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. alpha-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of alpha-asarone treatment. In the Morris water maze test, alpha-asarone significantly prolonged the swimming time spent in the target and peri-target zones. alpha-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by alpha-asarone may be one of the mechanisms for the alpha-asarone-mediated ameliorating effect on memory deficits.
Animals ; Cell Size ; Cytokines* ; Head ; Hippocampus ; Immunohistochemistry ; Learning ; Maze Learning ; Memory ; Memory Disorders* ; Mice* ; Microglia ; Neurons ; RNA, Messenger ; Swimming ; Tumor Necrosis Factor-alpha ; Up-Regulation

Hemifacial spasm is defined as unilateral, involuntary, irregular twitching of all or parts of the muscles innervated by facial nerves. Here, we present a case of recurrent hemifacial spasm after microvascular decompression (MVD) treated with pulsed radiofrequency (PRF) treatment with good results. A 35-year-old woman suffered from recurrent hemifacial spasm after MVD that was refractory to medical treatment and botulinum toxin injections. We attempted a left facial nerve block twice. Then, we applied PRF at a maximum temperature of 42degrees C for 120 sec. Some response was observed, so we applied PRF two additional times. The frequency of twitch decreased from 3-4 Hz to < 0.5 Hz, and subjective severity on a visual analogue scale also decreased from 10/10 to 2-3/10. PRF treatment might be an effective medical treatment for refractory hemifacial spasm and has fewer complications and is less invasive compared with those of surgery.
Botulinum Toxins ; Facial Nerve ; Female ; Hemifacial Spasm ; Humans ; Microvascular Decompression Surgery ; Muscles ; Pulsed Radiofrequency Treatment

A 60-year-old man presented with pain on the left cheek and lateral nose. The patient had been diagnosed with facial herpes zoster in the left V2 area 6 months previously. Medical treatment was prescribed for 6 months but it had little effect. We blocked the left infraorbital nerve under ultrasound guidance, but pain relief was short term. Therefore, we performed pulsed radiofrequency treatment on the left infraorbital nerve under ultrasound guidance. Six months after the procedure, the reduction of pain was still maintained, and there was no need for further management.
Cheek ; Herpes Zoster ; Humans ; Nose ; Pulsed Radiofrequency Treatment

PURPOSE: N-acetylcysteine (NAC) is a potent antioxidant, and a free radical scavenger. We investigated the possible effects of NAC after ischemia/reperfusion (I/R) of rat bladder. MATERIALS AND METHODS: I/R injury was induced by abdominal aorta clamping and ischemia for 60minutes, followed by 120minutes reperfusion. Twenty rats were divided into four groups: sham operation + saline group (S+S), sham operation + NAC group (S+NAC), I/R + saline group (I/R+S), I/R + NAC group (I/R+NAC). Blood levels of reactive oxygen species (ROS) were determined using the free oxygen radical tests (FORT). Superoxide generation was measured based on lucigenin-enhanced chemiluminescence. The level of malondialdehyde (MDA) was analyzed in order to measure lipid peroxidation. RESULTS: In I/R+S group, the isometric contractile responses to carbachol were significant lower than other groups and were reversed by the pretreatment with NAC. The level of FORT and MDA showed a marked increase in I/R+S group compared with S+S group. NADPH-stimulated superoxide production was also significantly increased. I/R+NAC decreased these parameters compared with I/R+S group. CONCLUSION: Our results suggest that treatment with NAC reversed the low contractile responses of rat bladder and prevented oxidative stress following I/R.
Acetylcysteine ; Animals ; Aorta, Abdominal ; Carbachol ; Constriction ; Ischemia ; Lipid Peroxidation ; Luminescence ; Malondialdehyde ; Oxidative Stress ; Oxygen ; Panax* ; Rats* ; Reactive Oxygen Species ; Reperfusion ; Superoxides ; Urinary Bladder*

BACKGROUND: This study was designed to evaluate the effects of continuous infusion of ondansetron on postoperative nausea and vomiting (PONV) in patients receiving intravenous patient controlled analgesia (IV-PCA) following laparoscopic gynecological surgery. METHODS: Sixty ASA class I and II patients scheduled for gynecological laparoscopic surgery were randomly divided into the following 3 groups that received the specified dosages of ondansetron mixed with IV-PCA: placebo (group 1), ondansetron 8 mg (group 2), ondansetron 16 mg (group 3). The incidences of nausea, vomiting, visual analogue scale (VAS), and side effects were then recorded in the recovery room, 24 h, 48 h and 72 h postoperatively. RESULTS: There were no significant differences in the occurrence of nausea between group 1 and 2. However, the incidence of nausea in group 3 was significantly lower than in group 1 at 24 h and 48 h after surgery. In addition, significant differences in the occurrence of vomiting were observed among the three groups. However, with the exception of pruritus, no side effects were observed in any of the groups. CONCLUSIONS: IV-PCA mixed with 16 mg of ondansetron effectively prevented nausea at 24 h and 48 h after gynecologic laparoscopic surgery.
Alfentanil ; Analgesia ; Analgesia, Patient-Controlled ; Female ; Gynecologic Surgical Procedures ; Humans ; Incidence ; Laparoscopy ; Nausea ; Ondansetron ; Postoperative Nausea and Vomiting ; Pruritus ; Recovery Room ; Vomiting

PURPOSE: Dual reporter gene imaging has several advantages for more sophisticated molecular imaging studies such as gene therapy monitoring. Herein, we have constructed hepatoma cell line expressing dual reporter genes of sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP), and the functionalities of the genes were evaluated in vivo by nuclear and optical imaging. MATERIALS AND METHODS: A pRetro-PN vector was constructed after separating NIS gene from pcDNA-NIS. RSV-EGFP-WPRE fragment separated from pLNRGW was cloned into pRetro-PN vector. The final vector expressing dual reporter genes was named pRetro-PNRGW. A human hepatoma (HepG2) cells were transfected by the retrovirus containing NIS and EGFP gene (HepG2-NE). Expression of NIS gene was confirmed by RT-PCR, radioiodine uptake and efflux studies. Expression of EGFP was confirmed by RT-PCR and fluorescence microscope. The HepG2 and HepG2-NE cells were implanted in shoulder and hindlimb of nude mice, then fluorescence image, gamma camera image and I-124 microPET image were undertaken. RESULTS: The HepG2-NE cell was successfully constructed. RT-PCR showed NIS and EGFP mRNA expression. About 50% of cells showed fluorescence. The iodine uptake of NIS-expressed cells was about 9 times higher than control. In efflux study, T(1/2) of HepG2-NE cells was 9 min. HepG2-NE xenograft showed high signal-to-background fluorescent spots and higher iodine-uptake compared to those of HepG2 xenograft. CONCLUSION: A hepatoma cell line expressing NIS and EGFP dual reporter genes was successfully constructed and could be used as a potential either by therapeutic gene or imaging reporter gene.
Animals ; Carcinoma, Hepatocellular* ; Cell Line* ; Clone Cells ; Fluorescence* ; Gamma Cameras ; Genes, Reporter* ; Genetic Therapy ; Hep G2 Cells ; Heterografts ; Hindlimb ; Humans ; Iodine ; Ion Transport* ; Mice ; Mice, Nude ; Molecular Imaging ; Optical Imaging ; Retroviridae ; RNA, Messenger ; Shoulder ; Sodium Iodide* ; Sodium*

PURPOSE: To evaluate the pathological prognostic factors related to local recurrence after radical surgery and adjuvant radiation therapy in advanced rectal cancer. MATERIALS AND METHODS: Fifty-four patients with advanced rectal cancer who were treated with radical surgery followed by adjuvant radiotherapy and chemotherapy between February 1993 and December 2001 were enrolled in this study. Among these patients, 14 patients experienced local recurrence. Tissue specimens of the patients were obtained to determine pathologic parameters such as histological grade, depth of invasion, venous invasion, lymphatic invasion, neural invasion and immunohistopathological analysis for expression of p53, Ki-67, c-erb, ezrin, c-met, phosphorylated S6 kinase, S100A4, and HIF-1 alpha. The correlation of these parameters with the tumor response to radiotherapy was statistically analyzed using the chi-square test, multivariate analysis, and the hierarchical clustering method. RESULTS: In univariate analysis, the histological tumor grade, venous invasion, invasion depth of the tumor and the over expression of c-met and HIF-1 alpha were accompanied with radioresistance that was found to be statistically significant. In multivariate analysis, venous invasion, invasion depth of tumor and over expression of c-met were also accompanied with radioresistance that was found to be statistically significant. By analysis with hierarchical clustering, the invasion depth of the tumor, and the over expression of c-met and HIF-1 alpha were factors found to be related to local recurrence. Whereas 71.4% of patients with local recurrence had 2 or more these factors, only 27.5% of patients without local recurrence had 2 or more of these factors. CONCLUSION: In advanced rectal cancer patients treated by radical surgery and adjuvant chemo-radiation therapy, the poor prognostic factors found to be related to local recurrence were HIF-1 alpha positive, c-met positive, and an invasion depth more than 5.5 mm. A prospective study is necessary to confirm whether these factors would be useful clinical parameters to measure and predict a radio-resistance group of patients.
Chemoradiotherapy* ; Drug Therapy ; Humans ; Multivariate Analysis ; Prospective Studies ; Radiotherapy ; Radiotherapy, Adjuvant ; Rectal Neoplasms* ; Recurrence* ; Ribosomal Protein S6 Kinases