Background and Objectives: Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. Methods: and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. Conclusions Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.

BACKGROUND/AIMS: We investigated the time taken for patients with metastatic non-small cell lung cancer (NSCLC) to develop brain metastases (BM), as well as their subsequent overall median survival following diagnosis, considering the epidermal growth factor receptor (EGFR) mutational status. METHODS: We retrospectively investigated the medical records of 259 patients diagnosed with advanced NSCLC from January 2010 to August 2013, who were tested for EGFR mutations. The time from the diagnosis of advanced NSCLC to the development of BM and the overall median survival after BM development (BM-OS) were evaluated and compared by EGFR mutational status. RESULTS: Sixty-seven patients (25.9%) developed BM. Synchronous BM occurred more often in patients with EGFR mutation type (MT) (n = 20, 27.4%) compared with EGFR wild type (WT) (n = 27, 14.5%, p < 0.009). The median BM-OS was significantly longer in patients with EGFR MT than in those with EGFR WT (25.7 months vs. 3.8 months, p < 0.001), and a similar trend was noticed for patients with synchronous BM (25.7 months for EGFR MT vs. 6.8 months for EGFR WT, p < 0.001). However, in patients with metachronous BM development, the difference in BM-OS between patients with EGFR MT (14.6 months) and EGFR WT (2.5 months) did not reach statistical significance (p = 0.230). CONCLUSIONS Synchronous BM was more common in NSCLC patients with EGFR MT than in those with EGFR WT. However, EGFR mutations were associated with significantly longer median BM-OS, especially when the brain was the first metastatic site.

Nontuberculous mycobacteria (NTM) have been increasingly recognized as an important cause of chronic pulmonary infections. The Mycobacterium avium complex (MAC), which is composed of two species, Mycobacterium avium and Mycobacterium intracelluare, is the most commonly encountered pathogen associated with NTM lung disease. MAC pulmonary infection typically presents in a fibrocavitary form or a nodular bronchiectatic form. However, there have been atypical presentations of MAC pulmonary infections, including solitary pulmonary nodules (SPN). There have been several previous reports of SPN due to MAC infection in the United States, Japan, and Korea. In 2009, Sekine and colleagues reported a case of MAC pulmonary infection presenting with multiple nodules. To date, however, there have been no cases of NTM lung infection with multiple cavitary pulmonary nodules, and neither a fibrotic change nor nodular bronchiectasis. The present case showed a multiple cavitating nodular lung infection due to MAC, which is very rare and different from the typical presentation of MAC pulmonary infections. We also showed that percutaneous transthoracic needle aspiration can be a useful diagnostic tool to evaluate a case of multiple cavitary nodules.
Bronchiectasis ; Japan ; Korea ; Lung ; Lung Diseases ; Mycobacterium avium ; Mycobacterium avium Complex* ; Mycobacterium* ; Needles ; Nontuberculous Mycobacteria ; Solitary Pulmonary Nodule ; United States

BACKGROUND: The adverse effects of the phosphodiesterase-4 inhibitor roflumilast, appear to be more frequent in clinical practice than what was observed in chronic obstructive pulmonary disease (COPD) clinical trials. Thus, we designed this study to determine whether adverse effects could be reduced by starting roflumilast at half the dose, and then increasing a few weeks later to 500 microg daily. METHODS: We retrospectively investigated 85 patients with COPD who had taken either 500 microg roflumilast, or a starting dose of 250 microg and then increased to 500 microg. We analyzed all adverse events and assessed differences between patients who continued taking the drug after dose escalation and those who had stopped. RESULTS: Adverse events were reported by 22 of the 85 patients (25.9%). The most common adverse event was diarrhea (10.6%). Of the 52 patients who had increased from a starting dose of 250 microg roflumilast to 500 microg, 43 (82.7%) successfully maintained the 500 microg roflumilast dose. No difference in factors likely to affect the risk of adverse effects, was detected between the dose-escalated and the discontinued groups. Of the 26 patients who started with the 500 microg roflumilast regimen, seven (26.9%) discontinued because of adverse effects. There was no statistically significant difference in discontinuation rate between the dose-escalated and the control groups (p=0.22). CONCLUSION: Escalating the roflumilast dose may reduce treatment-related adverse effects and improve tolerance to the full dose. This study suggests that the dose-escalated regimen reduced the rate of discontinuation. However, longer-term and larger-scale studies are needed to support the full benefit of a dose escalation strategy.
Clinical Protocols ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Diarrhea ; Humans ; Phosphodiesterase 4 Inhibitors ; Pulmonary Disease, Chronic Obstructive* ; Retrospective Studies

A twenty-year-old male was diagnosed with common variable immunodecifiency (CVID) according to decreased blood level of immunoglobulins along with a history of recurrent sinopulmonary infection since early childhood, no response to prior vaccination, and the absence of all other defined immunodeficiency. Eleven months after the initiation of intravenous immunoglobulin replacement, he presented with petechiae on both lower legs for three weeks. Bone marrow exam was conducted as pancytopenia was not resolved over a month and severe aplastic anemia was diagnosed. Allogenic stem cell transplantation (Allo-SCT) with reduced intensity conditioning (RIC) enabled both a clinical resolution from propensity to infection with an appropriate production of immunoglobulins and a successful rescue of hematopoiesis. This report suggests that Allo-SCT using RIC is a potentially curable option in patients with CVID complicated by SAA if adequate efforts to minimize Allo-SCT-related complications are accompanied.
Anemia, Aplastic* ; Bone Marrow ; Common Variable Immunodeficiency* ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulins ; Leg ; Male ; Pancytopenia ; Purpura ; Stem Cell Transplantation* ; Stem Cells* ; Vaccination

Background: DNA prevalence and type distribution of human papillomavirus (HPV) varies geographically. We investigated HPV prevalence and type distribution in Korean women using the MyHPV DNA chip testing. Methods: A total of 2,368 women from five regions of the country underwent Pap smear examination and MyHPV chip testing. Results: Overall HPV positivity was 15.8% and 78.4% in women with normal and abnormal cytology, respectively. High-risk HPV infection was strongly correlated with cytological atypia. In women with abnormal cytology, the five most common HPV types were 16, 58, 18, 52, and 56/53, and HPV16 was significantly the most common type in most geographical regions. After HPV16, HPV58, and 52 were the next most frequently detected types. Women with normal cytology, in contrast, showed heterogeneity in HPV type distribution. High-grade intraepithelial lesions infected with HPV16, 18, 31 or 45 are more likely to progress to carcinoma. Conclusions: The HPV chip test can provide useful data regarding HPV positivity and type. The most common HPV type in Korean women with abnormal cytology is HPV16, with HPV58 and 52 being frequently present. Our data may have important implications for vaccination programs and the development of cervical screening.
Cervix Uteri ; DNA ; Female ; Genotype ; Humans ; Mass Screening ; Oligonucleotide Array Sequence Analysis ; Population Characteristics ; Prevalence ; Republic of Korea ; Vaccination ; Vaginal Smears

OBJECTIVE: To evaluate pathological complete remission rate (pCR), survival rate, recurrence rate, 91 patients who had clinical complete remission with epithelial ovarian cancer were studied. METHODS: From 1983 to 2002, 91 consecutive patients with epithelial ovarian cancer underwent surgical cytoreduction followed by platinum-based chemotherapy at the Department of Obstetrics and Gynecology, Hanyang University Hospital. At the conclusion of chemotherapy, all patients who were clinically disease free and whose CA 125 was < 35 were offered a second-look operation that obtained over 20 specimens. Of 91 patients who qualified for second-look, 57 underwent the procedure and 34 did not undergo the laparotomy. RESULTS: Among 57 patients who had been performed second-look laparotomy, 40 patients (70%) had negative pathology, 9 (16%) were microscopically positive, and 8 (14%) had gross disease. Patients with positive findings received individualized salvage therapy (14/17). FIGO stage (p<0.01), initial CA 125 level (p=0.07) and residual tumor at primary surgery (p=0.01) correlated with second-look results. Eight (20%: 8/40) of the patients with negative pathology have recurred. Five year survival rate was 95% in patients refusing second look (n=34) was similar to 77% in patients who had been performed second-look operation (n=57). Five-year and ten-year survival rates were 77% and 68% in patients who had performed second-look laparotomy. And 5-year and 10-year survival rates were 84%, 84% in 40 patients with negative pathology, however, 53%, 34% of 17 patients with positive result. Stepwise logistic regression selected two covariates significantly affecting survival: the stage and residual tumor. CONCLUSION: Using the protocol described in a population of optimally resected patients with advanced stage ovarian cancer, second-look laparotomy can impact positively on survival. Patients with residual tumor > 2 cm with advanced stage at primary surgery and negative second-look findings should be the focus of future protocols for consolidation chemotherapy.
Consolidation Chemotherapy ; Drug Therapy ; Gynecology ; Humans ; Laparotomy* ; Logistic Models ; Neoplasm, Residual ; Obstetrics ; Ovarian Neoplasms* ; Pathology ; Recurrence ; Salvage Therapy ; Survival Rate

Primary adenosquamous carcinoma of the liver is a very rare type of cholangiocarcinoma and is defined as a cancer containing both squamous and adenomatous components in the same lesion. Recently, we experienced a primary adenosquamous carcinoma of the liver presented as liver abscess. A 63-year-old man was presented with a 4-day history of fever and chill. The radiologic study showed a 4 cm-sized, central hypoattenuated mass with peripheral rim enhancement in the left lobe of the liver. Ultrasonography-guided aspiration and biopsy suggested an adenocarcinoma with abscess in the liver. At laparotomy, the tumor occupied the left lobe of the liver and invaded the right diaphragm. An extended left lobectomy and a partial excision of the involved diaphragm were done. Grossly, the tumor was 6x5x5 cm in size and had an eccentric necrosis. Microscopically, the tumor was composed of adenocarcinoma and squamous cell carcinoma with a transitional area.
Carcinoma, Adenosquamous/*complications/pathology/surgery ; Case Report ; Human ; Liver Abscess/*etiology ; Liver Neoplasms/*complications/pathology/surgery ; Male ; Middle Age

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of mortality and morbidity, but its management is still challenging. The limitations of diagnostic methods to identify etiologic agents rapidly make it necessary to use empiric antibiotics in almost all patients, and furthermore the discovery of new respiratory pathogens and the emergence of antibiotic-resistant organisms pose difficulties to the selection of an empiric antibiotic regimen. To clarify the factors necessary for the optimal choice of empirical antibiotics, such as the frequency of etiologic agents, the attributable rates to death and antimicrobial resistance rates in the community, six university hospitals in Seoul and one university hospital in Cheonan were participating in this study. METHODS: Medical records of adults (> 15 years of age) hospitalized for CAP or pulmonary tuberculosis between March 1995 and February 1996, were reviewed. Patients who satisfied all of the following criteria were included in the study: (1) fever or hypothermia; (2) respiratory symptoms; and (3) pulmonary infiltrates on chest roentgenogram. To exclude cases of pulmonary tuberculosis whose roentgenographic features were so typical that it could be easily differentiated from conventional pneumonia, two additional criteria were required for inclusion: antibiotic treatment during the first week of hospital admission and initiation of anti-tuberculosis medications thereafter. Organisms isolated from sterile body sites, acid-fast bacilli or Mycobacterium tuberculosis isolated from sputum, pathogens diagnosed by a 4-fold rising titer to "atypical" pathogens, or pathogens revealed by histopathology were defined as definitive cause of pneumonia; isolates from sputum with compatible Gram stain, pathogens diagnosed by a single diagnostic titer plus use of a specific antimicrobial agent, or tuberculosis diagnosed by clinical response to anti-tuberculosis medications were considered probable cause of pneumonia. The records of the clinical microbiology were reviewed for isolates of S. pneumoniae, H. influenzae, M. catarrhalis, Mycobacterium or acid-fast bacilli, and mycoplasma. Then the frequency of these agents, antimicrobial resistance rates of respiratory pathogens from all body sites, and their clinical significance were evaluated. RESULTS: After excluding 365 patients (230 with pulmonary tuberculosis and 135 with CAP) who were screened for inclusion but did not meet the inclusion criteria, 246 persons were enrolled in this study. Their mean age was 58.2 years old with slight male predominance (58.2%), and 171 (71%) patients had underlying illnesses. Blood cultures were performed on 191 (77.6%) patients and serologic tests on 44 (18.3%) patients. The etiologic agents were identified in 31.3%, and the list of individual agents, in decreasing order, was pulmonary tuberculosis (17 definite and 3 probable: data of six hospitals), S. pneumoniae (8 definite and 10 probable), non-pneumococcal streptococci (3 definite), aerobic gram-negative bacilli (7 definite and 4 probable), Haemophilus spp. (11 probable), mycoplasma (1 definite and 4 probable), polymicrobial infections (2 definite and 2 probable : E. coli and S. agalactiae, M. tuberculosis and S. aureus, S. pneumoniae and H. influenzae, and A. baumannii and K. pneumoniae), S. aureus (2 definite and 2 probable), and mucormycosis (1 definite). Among gram-negative bacilli, K. pneumoniae was the most common agent (8 isolates). The rates of admission to the intensive care unit and of using assisted ventilation were 18% and 9.3% respectively. The mortality was 13.8% and logistic regression analysis showed that hypothermia and tachypnea were associated with death. Hospital stay averaged 19 days. Susceptible rates of S. pneumoniae isolated from all body sites to penicillin ranged from 8% to 28% but all seven isolates from blood of patients with pneumonia were susceptible to penicillin. Also all 8 isolates of K. pneumoniae from patients with pneumonia were susceptible to cefotaxime and gentamicin. CONCLUSION: In Korea, in addition to S. pneumoniae, M. tuberculosis is an important agent causing community-acquired pneumonia. The low incidence of etiologic diagnosis is probably related to infrequent requesting of test to "atypical" pathogens and does not represent the true incidence of infections by "atypical" pathogens, which will be answered by a prospective study. The antimicrobial resistance rates of major respiratory pathogens from sterile body sites are low, however, because of a small number of the isolates this result needs confirmation by a nationwide surveillance of antimicrobial resistance.
Adult ; Anti-Bacterial Agents ; Anti-Infective Agents ; Cefotaxime ; Chungcheongnam-do ; Coinfection ; Diagnosis ; Fever ; Gentamicins ; Haemophilus ; Hospitals, University* ; Humans ; Hypothermia ; Incidence ; Influenza, Human ; Intensive Care Units ; Korea ; Length of Stay ; Logistic Models ; Male ; Medical Records ; Mortality ; Mucormycosis ; Mycobacterium ; Mycobacterium tuberculosis ; Mycoplasma ; Penicillins ; Pneumonia* ; Prospective Studies ; Seoul ; Serologic Tests ; Sputum ; Streptococcus pneumoniae ; Tachypnea ; Thorax ; Tuberculosis ; Tuberculosis, Pulmonary ; Ventilation

No abstract available.
Cervix Uteri* ; Female