Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

BACKGROUND: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. METHODS: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. RESULTS: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. CONCLUSION: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.
Base Sequence ; Codon ; Drug Resistance, Multiple ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Korea* ; Mycobacterium tuberculosis* ; Mycobacterium* ; Rifampin ; Tuberculosis ; Tuberculosis, Multidrug-Resistant

OBJECTIVES: The purpose of this study was to assess the associations between oral health, activity of daily living, and cognitive impairment among elderly people who live at home in a rural area. METHODS: A total of 183 participants older than 70 years of age were recruited from a public health center in a rural Korean city. Trained examiners conducted questionnaire surveys and at-home oral exams to assess oral health, geriatric function, and cognitive impairment. Oral health was assessed by counting remaining teeth and examining salivary flow. Geriatric function and cognitive impairment were assessed using the Mini-Nutritional Assessment (MNA), the Mini-Mental State Examination for Dementia Screening (MMSE-DS), and an activity of daily living (ADL) questionnaire. RESULTS: Mean age (SD) of the participants was 83.77 (5.99) years and 68.9% of them were women. The participants who had a lower number of remaining teeth were significantly older, had severe cognitive impairment, and poor ADL and MNA results. The participants with severe cognitive impairment were significantly older and had fewer remaining teeth and low salivary flow. Simple linear regression analysis showed an association between remaining teeth and cognitive impairment with a P-value of 0.000, which disappeared after adjusting for sex and age or sex, age, denture use, and salivary flow, respectively. CONCLUSIONS: Possible associations between remaining teeth and salivary flow, activity of daily living, and cognitive impairment were discovered among some elderly people living in a rural area.
Activities of Daily Living ; Aged* ; Dementia ; Dentures ; Female ; Humans ; Linear Models ; Mass Screening ; Oral Health ; Pilot Projects* ; Public Health ; Tooth*

BACKGROUND: Pyrazinamide (PZA) is an effective antitubercular drug that becomes toxic to Mycobacterium tuberculosis when converted to pyrazinoic acid by pyrazinamidase (PZase), encoded by mycobacterial pncA. A strong association was noted between the loss of PZase activity and PZA resistance. The causative organisms in extrapulmonary tuberculosis are rarely cultured and isolated. To detect pncA mutations in specimens from extrapulmonary tuberculosis as confirmative diagnosis of mycobacterial infection and alternative susceptibility test to PZA. METHODS: Specimens were collected from clinically proven extrapulmonary tuberculosis. pncA was sequenced and compared with wild-type pncA. RESULTS: pncA from 30 specimens from 23 donors were successfully amplified (56.6% in specimens, 59% in donors). Six mutations in pncA were detected (20.0% in amplified specimens, 26.1% in specimen donors) at nucleotide positions of 169, 248 and 419. The mutation at position 169 results in substitution of aspartic acid for histidine, a possible allelic variation of M. bovis that have intrinsic PZA resistance. The mutation at position 248 changes proline into arginine and that at position 419, arginine into histidine. CONCLUSION: DNA-based diagnosis using pncA may be simultaneously useful for the early diagnosis of mycobacterial infection and the rapid susceptibility to PZA in extrapulmonary tuberculosis. A potential implication of pncA allelic variation at 169 might be suggested as a rapid diagnostic test for M. bovis infection or Bacille Calmette-Guerin (BCG) reactivation.
Amidohydrolases ; Antitubercular Agents ; Arginine ; Aspartic Acid ; Diagnostic Tests, Routine ; Early Diagnosis ; Histidine ; Humans ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Proline ; Pyrazinamide ; Tissue Donors ; Tuberculosis

OBJECTIVE: To investigate the effect of regular exercise program on cognitive function in chronic cerebral hypoperfused rat. METHOD: Forty-eight male Sprague-Dawley rats were used. Chronic cerebral hypoperfusion was induced by bilateral common carotid arteries occlusion (BCCAO). All rats were randomly divided into 4 groups: normal rats (group A); normal rats with regular exercise program (group B); BCCAO rats (group C); BCCAO rats with regular exercise program (group D). Regular exercise program was composed of daily 30-minute treadmill exercise for 4 weeks. Cognitive function was evaluated by Morris water maze (MWM) test. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were checked. The neurons were microscopically analyzed on Hematoxylin-Eosin and Cresyl violet stains. RESULTS: After regular exercise program, there was significant difference in the escape latency among 4 groups in hidden platform trial of MWM test (p<0.05). There was significant difference in the number of crossings among 4 groups in probe trial of MWM test (p<0.05). The activities of SOD of group A and group D were significantly higher than those of group C, respectively (p<0.05). Histopathological study displayed the formation of apoptotic cell bodies and pyknotic cells in group C and group D. There were more normal neurons in group D than group C. CONCLUSION: Regular treadmill exercise was helpful in improving cognitive function in chronic cerebral hypoperfused rat. Therefore, regular exercise program would be one of the useful strategies for treating chronic neurodegenerative diseases.
Animals ; Benzoxazines ; Carotid Artery, Common ; Cognition ; Dementia ; Humans ; Male ; Malondialdehyde ; Maze Learning ; Neurodegenerative Diseases ; Neurons ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; United Nations ; Viola

BACKGROUND: Acute myelogenous leukemia (AML) is frequently encountered in elderly patients whereas intensive chemotherapy yield lower rate of complete remission (CR) and survival than young patients. This study was aimed to review the clinical features and treatment outcomes of elderly patients (>or=60) with AML. METHODS: We respectively reviewed the clinical features, laboratory findings and outcomes of treatment from the medical records of 115 patients with the elderly AML (>or=60), admitted in Seoul National University Hospital, between Jan.1995 and Dec.2004. RESULTS: Their median age was 66 (60~86) years with male predominance (M:F=68:47). Complete response rate in patients with conventional chemotherapy was 66.7% (42 of 63 patients; 95% CI 50.2~78.4). Median overall survival (OS) was 5.2 months with clinical benefit in the conventional chemotherapy group, compared to supportive or palliative group (11.5 vs 0.9months; p<0.0001). In between two age groups, the sixties (n=69) showed higher CR rate (69.0 vs 61.9%; p=0.9) and longer median overall survival (7.0 vs 4.4months; p=0.8) than patients group of the seventies (n=38) but without statistical significance. CONCLUSIONS: Conventional induction chemotherapy improved survival rate than palliative or supportive treatment.
Aged* ; Drug Therapy ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute* ; Male ; Medical Records ; Prognosis ; Retrospective Studies* ; Seoul ; Survival Rate

BACKGROUND: The use of non-myeloablative stem cell transplantation (NST) has recently been increasing for treating the patients who cannot tolerate ablative hematopoietic stem cell transplantation (HSCT). Although graft-versus-host disease (GVHD) is one of the greatest problems in HSCT, the clinical effect of GVHD following NST is not clear. We undertook this study to evaluate the clinical manifestations of GVHD and the outcomes after NST. METHODS: From October 2000 to October 2004, 61 patients underwent NST with a fludarabine-based conditioning regimen. The cumulative incidence of GVHD and the survival rates were obtained from the Kaplan-Meier curves. RESULTS: With a median follow-up of 195 days, the estimate for overall three-year survival was 32%. The cumulative incidences of grades II~IV acute GVHD and chronic GVHD were 33% (18/53) and 78% (29/37), respectively. The response rates for acute and chronic GVHD were 33% and 89%, respectively. The survival rates of patients with acute and chronic GVHD were 27% and 89%, respectively. The median survival time was 6.5 months CONCLUSION: The incidence of GVHD after NST did not differ from that after ablative HSCT. This study suggests that the aggressive treatment of acute GVHD should be considered to improve the overall survival after NST.
Follow-Up Studies ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; Stem Cell Transplantation ; Survival Rate

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.
Aged ; Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Boronic Acids/administration & dosage/adverse effects/*therapeutic use ; Dexamethasone/administration & dosage/adverse effects ; Disease Progression ; Drug Resistance, Neoplasm ; Female ; Humans ; Korea ; Male ; Middle Aged ; Multiple Myeloma/*drug therapy ; Neoplasm Recurrence, Local ; Pilot Projects ; Pyrazines/administration & dosage/adverse effects/*therapeutic use ; Research Support, Non-U.S. Gov't ; Survival Analysis ; Thrombocytopenia/chemically induced ; Time Factors

OBJECTIVE: Although advances in neuroradiologic imagings have enabled us to diagnose intrauterine central nervous system(CNS) anomalies, it's management remains difficult because the natural history and postnatal outcome were not well understood. This study is undertaken to clarify the natural history and postnatal outcome of prenatally diagnosed CNS anomaly. METHODS: Between January 1999 and October 2002 there were 18 cases of a fetus with a CNS anomaly prenatally diagnosed by ultrasonography. In six cases, intrauterine magnetic resonance(MR) image was undertaken to confirm the findings when ultrasonography was inconclusive. In this prospective follow-up study the authors have applied the "perspective classification of congenital hydrocephalus(PCCH)" proposed by Oi et al. RESULTS: Hydrocephalus was diagnosed in three cases at PCCH stage I, in six cases at stage II, in 9 cases at stage III. In 8 cases, termination of pregnancy were performed due to severe CNS anomalies. Among these cases, hydrocep halus was diagnosed in 3 cases(100%) at stage I, in 3 cases(50%) at stage II, in 2 cases(22.2%) at stage III. Out of these 8 cases, 5 cases underwent autopsy following parental consent. Of the 10 cases who were delivered, 4(40%) patients were treated. In these 4 cases, hydrocephalus was diagnosed at PCCH stage III(3 fetuses survived, 1 fetus died at 6 months after birth). CONCLUSION: The postnatal outcome is significantly poor in the fetuses with CNS anomaly diagnosed in the early gestation. So it is important to diagnose the fetal CNS anomalies in the early stage of gestation and follow up periodically.
Autopsy ; Central Nervous System* ; Classification ; Fetus ; Follow-Up Studies* ; Humans ; Hydrocephalus ; Natural History ; Parental Consent ; Pregnancy ; Prospective Studies* ; Ultrasonography

OBJECTIVE: In this study, we investigated the cell growth inhibition, regulation of cell cycle and induction of apoptosis through recombinant p53 adenoviral vector delivery into cervical cancer cell line SiHa, to explore the possibility of p53 gene therapy. METHODS: We infected SiHa with AdCMVp53 at 50 MOI. After 48 hours, the regulation of cell cycle and apoptosis were investigated with FACS. The gene expression profiling associated with cell cycle was also investigated with cell cycle DNA membrane chip. RESULTS: SiHa cells were arrested in the G1 phase by AdCMVp53 and showed cell growth inhibition via apoptosis. The gene expression profiles involved in cell cycle including cyclin-dependent kinase inhibitor 1C (p57, Kip2), RAD9 (S.pombe) homolog, and MAD2 (mitoticarrest deficient, yeast, homolog)-like 2 were up-regulated by more than three-fold, as compared to control group. In contrast, 6 genes such as retinoblastoma-like 2 (p130), and cyclin H were down-regulated by more than three-fold. Several genes known as being differentially up- or down-regulated compared to control were confirmed by RT-PCR and Western blotting assays. CONCLUSION: The adenoviral p53 gene delivery into cervical cancer cell line, suggesting the possibility of p53 gene therapy in cervical neoplasia make the cell growth inhibition and changes of cell cycle-associated gene expression.
Apoptosis ; Blotting, Western ; Cell Cycle Proteins* ; Cell Cycle* ; Cell Line* ; Cyclin H ; Cyclin-Dependent Kinase Inhibitor p57 ; DNA ; G1 Phase ; Gene Expression ; Gene Expression Profiling ; Genes, p53 ; Membranes ; Transcriptome ; Uterine Cervical Neoplasms* ; Yeasts