Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Platelet Disorders/chemically induced ; Child ; Child, Preschool ; Contrast Media/*adverse effects/diagnostic use ; Databases, Factual ; Female ; Humans ; Infant ; Infant, Newborn ; Iodine Radioisotopes/chemistry ; Male ; Middle Aged ; Neoplasms/radionuclide imaging ; Radiopharmaceuticals/*adverse effects/diagnostic use ; Urologic Diseases/chemically induced ; Young Adult

Fetal alcohol syndrome (FAS) is a developmental neuropathology resulting from in utero exposure to ethanol; many of ethanol's effects are likely to be mediated by the neurotransmitter gamma-aminobutyric acid (GABA). We studied modulation of the neurotransmitter receptor GABABR and its capacity for intracellular signal transduction under conditions of ethanol treatment (ET) and RNA interference to investigate a potential role for GABA signaling in FAS. ET increased GABAB1R protein levels, but decreased protein kinase A-alpha (PKA-alpha), calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of cAMP-response element binding protein (p-CREB), in cultured hippocampal neurons harvested at gestation day 17.5. To elucidate GABAB1R response to ethanol, we observed the effects of a GABABR agonist and antagonist in pharmacotherapy for ethanol abuse. Baclofen increased GABABR, CaMKII and p-CREB levels, whereas phaclofen decreased GABABR, CaMKII and p-CREB levels except PKA-alpha. Furthermore, when GABAB1R was knocked down by siRNA treatment, CaMKII and p-CREB levels were reduced upon ET. We speculate that stimulation of GABAB1R activity by ET can modulate CaMKII and p-CREB signaling to detrimental effect on fetal brain development.
Animals ; Baclofen ; Brain ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Carrier Proteins ; Ethanol ; Fetal Alcohol Syndrome ; gamma-Aminobutyric Acid ; Hippocampus ; Neurons ; Neurotransmitter Agents ; Phosphorylation ; Pregnancy ; Protein Kinases ; Rats ; Receptors, Neurotransmitter ; RNA Interference ; RNA, Small Interfering ; Signal Transduction

OBJECTIVES: The early detection of ectopic tubal pregnancy in unruptured state is increased as the transvaginal sonography and sensitive serum hCG test are available. For this unruptured tubal pregnancy, the medical treatment using methotrexate via various routes and dosage is being tried. Our study was to evaluate the efficacy of single systemic injection of methotrexate in the treatment of unruptured tubal pregnancies. Material and METHODS: From the January 1997 to July 1999, of 152 ectopic pregnancy patients, 22 patients who were diagnosed as unruptured tubal pregnancies were treated with single-dose systemic methotrexate injection (50 mg/m2/IM). Exclusion criteria were unstable vital signs with hemoperitoneum, adnexal mass > 5-6 cm. Serum hCG titers were checked before injection and 4, 7 day after injection. If serum hCG titer declined more than 15% on 7 day after injection compared with titer on 4 day, the weekly hCG titer was followed until it was <10 mIU/ml .If the hCG titer did not decline more than 15 %, a second dose was given. If hCG titer was not decreased or vital signs became unstable after 1-2 injections, the treatment was considered failure and surgery was done. RESULTS: 18 cases (82%) of 22 were successfully treated with single-dose methotrexate. The mean size of ectopic mass and initial serum hCG titers were 2.7+/-1.3 cm (range, 1.5-5.4 cm) and 3,298+/-1,007 mIU/ml (range, 132-12,239), respectively. Of 22, 6 cases (28%) needed second dose of methotrexate. The mean time to resolution of serum beta-hCG titer was 27.5+/-13.6 days (range, 8-53 days). Elevation of liver enzyme did not occurred in all cases during treatment. Initial hCG titer was more important prognostic factor than ectopic mass size for successful medical treatment. CONCLUSION: Single-dose methotrexate appears to be an effective medical treatment for the unruptured tubal pregnancy. However, patients selection using strict criteria is needed to increase its success rate.
Female ; Hemoperitoneum ; Humans ; Liver ; Methotrexate* ; Pregnancy ; Pregnancy, Ectopic ; Pregnancy, Tubal* ; Vital Signs

A 26-year-old man with intermittent lower, abdominal, cramping pain, nausea, vomiting, and diarrhea was found to have intussusception by computed tomography. Whole emergency laparotomy was performed, intus-susception reduced spontaneously. Postoperately, familial adenomatous polyposis (FAP) was diagnosed by colonoscopy and barium enema. Innumerous polyps were found in the entire colon and one of these was presumed to have caused sigmoid invagination. If is believed that FAP is quite a rare cause of colonic intus-susception. This case of a 26-year-old man with an intussusception of the colon due to FAP is herein reported. It is important that surgeons and internists are aware of this rare cause of intussusception due to FAP because of the therapeutic implications.
Adenomatous Polyposis Coli* ; Adult ; Barium ; Colon* ; Colon, Sigmoid ; Colonoscopy ; Diarrhea ; Emergencies ; Enema ; Humans ; Intussusception* ; Laparotomy ; Muscle Cramp ; Nausea ; Polyps ; Vomiting

PURPOSE: To gain insight on transcriptional repression of Topo II a in HL-60 cells arrested to G2/M and M phase, the levels of Topo IIa mRNA and the binding activity of ATF have been investigated with Northern blot hybridization and DNA mobility shift assay, respectively. MATERIALS AND METHODS: HL-60 cells were grown in RPMI 1640 medium supplemented with 10% heat-mactivated fetal bovine serum and antibiotics in a humidified 5% CO2 at 37C degree. Total RNA was prepared by a modification of the method of Karlinsey et al. Northern blot hybridization was performed by the method of Virca et al. A Xho I-Mlu I fragment of phTOP2 was used as probe for Northern blot analysis of Topo II a mRNA. DNA mobility shift assay was performed by the method of Lim et al. End labeled DNA oligomer (upper strand, 5-TCTCCGCTATGACGCCGAGTGGTG-3) for ATF binding activity was mixed with nuclear extracts in a 20 pl reaction volume containing 60 mM KC1, 12 mM HEPES, pH 7.9, 5 mM MgCl2, 0.2 mM EDTA, 0.2 mM DTT, 12% glycerol, and 2 ug of poly [dI-dC]. RESULTS: HL-60 cells were arrested at G2/M phase and M phase after taxol or nocodazole treatment. The levels of Topo II a mRNA were reduced at 24 hours after exposure with nocodazole or taxol but the unknotting activities were not changed. DNA mobility shift assay using oligonucleotide containing the ATF binding site showed that ATF binding activity was reduced after pretreatment of nododazole or taxol. CONCLUSIONS: These results suggest that the reduction of ATF binding activity may be important to transcriptional repression of Topo II a gene by nocodazole and taxol in HL- 60 cells.
Anti-Bacterial Agents ; Binding Sites ; Blotting, Northern ; Cell Division* ; DNA Topoisomerases, Type I* ; DNA Topoisomerases, Type II* ; DNA* ; Edetic Acid ; Electrophoretic Mobility Shift Assay ; Genes, vif ; Glycerol ; HEPES ; HL-60 Cells ; Humans ; Hydrogen-Ion Concentration ; Magnesium Chloride ; Nocodazole ; Paclitaxel ; Repression, Psychology ; RNA ; RNA, Messenger

BACKGROUND: Many ophthalmic procedures can be performed using a retrobulbar regional anesthetic technique. However, retrobulbar block is painful and most of patients express anxiety about the procedure. In addition, several life-threatening complications may occur. We compared the effects of midazolam and midazolam-ketamine as a sedative during retrobulbar block in cataract surgery. METHODS: Thirty patients undergoing cataract surgery were randomly allocated into two groups, group I (n=15) was received midazolam and group II (n=15), midazolam-ketamine. Mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO2) were compared before administration of drugs and 1, 2, 3, 4, 5, 10, 20, and 30 min after administration of drugs. Patients' movement requiring restraint were also checked. In the recovery room, postoperative nausea and vomiting, recall, delirium and/or hallucinations, and ocular complications were recorded. RESULTS: There were no significant differences in MAP and SpO2 between groups but heart rates were significantly increased at 1, 2, 3, 4, and 5 min than baseline in group II. Movement score was significantly lower in Group II than in Group I during the block (p<0.05). Recall during performance of the nerve block occured more often in Group I than in Group II (p<0.05). CONCLUSION: Low-dose midazolam-ketamine sedation sequence was superior to a midazolam technique regarding patients' movement and recall.
Anxiety ; Arterial Pressure ; Cataract* ; Delirium ; Hallucinations ; Heart Rate ; Humans ; Midazolam* ; Nerve Block ; Oxygen ; Postoperative Nausea and Vomiting ; Recovery Room

In order to investigate the clinical results of clear lens extraction for high myopia, the effects of 5.5mm sutureless corneoscleral procedure with low power IOL insertion on 21 patients (31 eyes) who were followed up averagely for 9.43 months were analyzed retrospectively. Prophylactic retinal treatment with argon laser was performed in 23 eyes to prevent retinal detachment. Eighty-seven percent (25/31 eyes) of eyes were within +/-1D of targeted refractive error and all eyes were within +/-2D of targeted refractive error. The postoperative corrected visual acuities were increased in 96.8% (30/31 eyes) and 80.7% (25/31 eyes) among them gained two or more lines. the corrected visual acuity of 20/40 or better were increased from 35.5%(11/31 eyes) preoperatively to 93.6% (29/31 eyes) postoperatively. Posterior capsular opacification was developed in two eyes and YAG laser posterior capsulotomy was performed at 2 and 7 months postoperatively. No retinal break, no cystoid macular edema were developed during the follow up period. In conclusion, the clear lens extraction was effective method for correction of severe high myopia but longer follow-up is needed to evaluate it`s complications.
Argon ; Follow-Up Studies ; Humans ; Lasers, Solid-State ; Macular Edema ; Myopia* ; Posterior Capsulotomy ; Refractive Errors ; Retinal Detachment ; Retinal Perforations ; Retinaldehyde ; Retrospective Studies ; Visual Acuity

OBJECTIVES: The poor survival rates among patients receiving surgery alone for stages II and III non-small cell lung cancer prompted several trials of adjuvant therapy after resection. We performed a prospective phase II study in patients with stage II-IIIA non-small cell lung cancer after resection to evaluate the feasibility, activity and toxicity of the postoperative sequential MVP chemotherapy and radiotherapy. METHODS: Between February 1991 and May 1995, 60 patients with resected stage II, IIIA non-small cell lung cancer received 2 cycles of MVP combination chemotherapy (Mitomycin-C 6 mg/m2, Vinblastine 6 mg/m2, Cisplatin 60 mg/m2) within 3 weeks after surgery, followed by thoracic irradiation (5,040 cGy after complete resection and 900 cGy booster to microscopically positive resection margin at 1.8 Gy per fraction) within 3-4 weeks after chemotherapy. RESULTS: Forty nine men and 11 women with a median age of 60.5 years (range 33-81 years) were included. During the median follow-up period of 828 days (61-2,015 days), 25 patients had developed recurrence. Among the 25 failures, 3 were local relapse only and 20 were distant metastasis only and 2 had both local and distant sites of recurrence. Three-year overall survival and event-free survival were 43% and 37%, respectively. Neutropenia of grade I-II was observed only in 13 patients. Eleven patient showed grade I-II radiation pneumonitis and 32 had grade I-II radiation esophagitis. CONCLUSION: Postoperative sequential MVP chemotherapy and radiotherapy in resected stage II-IIIA non-small cell lung cancer is well-tolerated and shows interesting activity.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Disease-Free Survival ; Drug Therapy* ; Drug Therapy, Combination ; Esophagitis ; Female ; Follow-Up Studies ; Humans ; Male ; Mitomycin* ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies ; Radiation Pneumonitis ; Radiotherapy* ; Recurrence ; Survival Rate ; Vinblastine*

Computerized tomography(CT) have been available for diagnosis and localization of intracerebral hematoma. CT-guided stereotactic evacuation of spontaneous intracerebral hematoma was performed in 34 cases; 25 basal ganglionic hematomas with or without ventricular perforation, 4 subcortical, 3 thalamic, 1 cerebellar and 1 pontine. The biplane CT image were taken to determine the coordinates of the target point, which was the center of the hematoma. The liquefied or solid portion of the hematoma was aspirated through a burr-hole under local anesthesia. And a silastic tube(3.3mm in outer diameter and 2.0mm in inner diameter) was then inserted into the center of the hematoma. Immediately after the first trial of hematoma aspiration, urokinase(6000IU/5ml saline) was administered through the tube. Subsequently, aspiration and infusion of urokinase were repeated every 6 or 12 hours until the hematoma was almost completely evacuated. The follow-up results indicate that this procedure was more superior over the conventional craniotomy. This CT-guided stereotactic operation has the following advantages; 1) the procedure is simple and safe; 2) the procedure can be performed under local anesthesia; and 3) the hematoma can be completely drained with the aid of urokinase. This procedure can be used as a standard treatment for intracerebral hematoma. We have draw the following conclusions; As a result of the above study 1) Stereotactic surgery is more effective in the patients with neurologic grade 3 than conservative one (p<0.05). 2) To use urokinase or perform the early surgery within 24 hours did not seem to be the cause of rebleeding. 3) In the case of pons or cerebellar hemorrhage, stereotactic surgery had definite benefit in the recovery of consciousness even if recovery of motor function was dismal. 4) In patients with spontaneuous ICH, the favorable prognostic indicatiors were as follows: the size of hematoma less thas 50ml, no signs of transtentorial herniation and patient's age under 60.
Anesthesia, Local ; Consciousness ; Craniotomy ; Diagnosis ; Follow-Up Studies ; Ganglion Cysts ; Hematoma* ; Hemorrhage ; Humans ; Pons ; Urokinase-Type Plasminogen Activator