• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.528-534
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• 2004

Background : Microscopic examination of sputum smears for acid-fast bacilli (AFB) is the most important and rapid diagnostic test for pulmonary tuberculosis. However, the AFB observed on the smear may represent either M. tuberculosis or nontuberculous mycobacteria (NTM). This study examined the clinical usefulness of a polymerase chain reaction test for M. tuberculosis (TB-PCR) for the differentiation of pulmonary tuberculosis and NTM lung disease in patients with smear-positive sputums in a tertiary hospital in Korea. Material and Methods : From January, 2003 to December, 2003, 826 AFB smear-positive and culture-positive sputum specimens were collected from 299 patients. Results : NTM were recovered from 26.6% (220/826) of the smear-positive sputum specimens and 23.4% (70/299) of the patients with smear-positive sputum. All the patients with isolated NTM had clinically significant NTM lung disease; 38 patients (54.3%) had M. avium and 26 patients (37.1%). had M. abscessus. In the patients with pulmonary tuberculosis, 78.7% of the patients (74/94) showed TB-PCR positivity, and all the patients with NTM lung disease showed negative results on the TB-PCR test (p<0.001). A positive result of the TB-PCR test on the sputum or bronchial washing fluid specimens was able to predict pulmonary tuberculosis with 88.4% sensitivity, 100% specificity, a 100% positive predictive value and a 79.7% negative predictive value for the patients with smear-positive sputum. Conclusion : The TB-PCR test for sputum specimens or bronchial washing fluid specimens could be useful for differentiating pulmonary tuberculosis and NTM lung disease for the patients with smear-positive sputum in Korea.

• Tuberculosis and Respiratory Diseases
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• v.62 no.3
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• pp.184-191
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• 2007

Background: For the diagnosis of pleural tuberculosis, polymerase chain reaction (PCR) of pleural effusion specimens has shown very low sensitivity, which might be due to the small number of bacilli in the samples. The purpose of this investigation is to determine whether the sensitivity of PCR testing can be improved when increasing the amount of pleural effusion specimens. Methods: We prospectively analyzed pleural effusion specimens obtained from 53 patients for whom the exclusion of the possibility of tuberculous pleural effusion was necessary. We performed Mycobacterium tuberculosis PCR testing using the Cobas Amplicor MTB test (Roche Diagnostic Systems) with three different amounts (10ml, 25ml, and 50ml) of pleural effusion specimen in each patient. Pleural tuberculosis was defined as having one of the following: culture-positive pleural fluid sample, histopathologic finding consistent with tuberculosis on pleural biopsy, culture-positive sputum specimen, and/or positive response to anti-tuberculous medication without other possible causes of pleural effusion. Results: Of the 53 patients, 26 received the diagnosis of pleural tuberculosis. The sensitivities of AFB smearing, Mycobacterium tuberculosis culture of pleural effusion specimen, pleural biopsy, and measurement of ADA were 3.8%, 15.4%, 84.6%, and 88.5%, respectively. The results of PCR testing were positive for 3 (11.5%), 4 (15.4%), and 3 (11.5%) of the 26 patients when using 10ml, 25ml, and 50ml of pleural effusion specimens, respectively. These results did not show a statistically significant difference in the sensitivity of PCR testing when increasing the amount of pleural effusion samples (p>0.05, symmetry exact test). Conclusion: For specimens such as pleural effusion, in which the bacillary load is very low, the clinical utility of PCR testing seems highly limited with the kits designed for the diagnosis of pulmonary tuberculosis. An increased amount of pleural effusion sample does not improve the sensitivity of PCR testing.

• Tuberculosis and Respiratory Diseases
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• v.53 no.1
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• pp.17-26
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• 2002

Background : The detection and early elimination of the causes for acute respiratory distress syndrome(ARDS) at the initial stage can result in a more favorable prognosis. Miliary tuberculosis as a cause of the ARDS is quite rare. A diagnosis of miliary tuberculosis is difficult due to the diversity of radiological patterns and non-specific clinical finfings, and low sensitivity of sputum examinations for acid-fast bacilli(AFBs). An analysis of the clinical data is the first step in diagnosing these unusual, rare cases. Materials and Methods : In this study the clinical features, laboratory data, radiological findings and diagnostic methods were analyzed in 9 cases with an initial presentation of ARDS due to miliary tuberculosis. The ARDS was defined by the definition of the American-Europian consensus conference 1992. Results : The mean age of the patients was $67{\pm}18$ years (F:M=7:2). The chief complaints were dyspnea(5/9), coughing (3/9) and fever(5/9). On a physical examination, fine or coarse crackles were noted(6/9). The ARDS developed on average 6.7 days after the initial respiratory symptoms. The mean $PaO_2/FiO_2$ of the patients was $133.5{\pm}53.4$, the number of cases with a WBC<5000/$mm^3$ was 4 out of 9 cases. A platelet count<70,000/$mm^3$ was observed in 2 out of 9 cases, and the serum albumin level was $2.6{\pm}0.6$ g/dL. The initial simple chest PA showed ground glass appearances and consolidation in all cases, However, the miliary nodular densities were observed in only 4 out of the 9 cases. HRCT revealed alveolar densities and a consolidation in 5 out of 6 cases, and miliary nodules in 5 out of 6 cases, The diagnosis of tuberculosis was made by a liver biopsy (4/4, 100% sensitivity), a bone marrow biopsy (1/2, 50% sensitivity), and an open lung biopsy (1/1), the sputum AFB was positive in only 2 out of 9 cases. The patient was treated with INH, RFP, EMB, PZA, and steroids. The survival rate was 55.5%. Conclusion : Miliary tuberculosis should be considered as one of the causes for ARDS in areas where there is a high prevalence of tuberculosis. The chief complaints of the patients on admission are dyspnea, fever and coughing without any specific riskfactors. A liver biopsy is particularly useful in ARDS patients with mechanical ventilation to determine the causes of the ARDS if miliary tuberculosis is suspected as being the underlying disease.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.277-284
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• 2006

Background : Delayed treatment of pulmonary tuberculosis is an important problem because it results in greater mortality and the nosocomial transmission of tuberculosis. This study was conducted to analyze the factors that contribute to the delayed treatment of pulmonary tuberculosis in a university hospital and we wanted to provide basic data for instituting an effective management program for tuberculosis. Methods : we retrospectively reviewed the medical records of 155 patients with smear-positive or culture-positive pulmonary tuberculosis and who were treated between May 1999 and October 1999. A case-control study was performed to analyze the factors. We then tried to follow up the patients in delayed treatment group via telephone for the purpose of assessing the therapeutic interventions. Results : Among 150 patients, 55 (37%) were included in the delayed treatment group. The factors associated with delayed treatment on the univariate analysis included age (61 vs 40 years old; p <0.001), a smear-negative sputum test for acid-fast bacilli (AFB) (85% vs 55%; p <0.001) and no visits to a private clinic before the patient presented to the university hospital (56% vs 36%; p = 0.014). Multivariate analysis revealed that old age (p = 0.001), a smear-negative sputum for AFB (p = 0.001), and lower lobe infiltrate on chest X-ray (p = 0.041) were the independent predictors of delayed treatment. Of the 22 patients who did not receive any treatment, 20 of them 91%) consented to our suggestion of revisiting the hospital. Conclusion : Delayed treatment of patients with pulmonary tuberculosis is not uncommon in a university hospital. Old age, smear-negative for AFB, and lower lobe infiltrate on chest X-ray are the risk factors for delayed treatment. A more systematic management system is required for achieving better control of tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.169-178
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• 2000

Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.248-260
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• 2004

Background : As an effective regimen for isoniazid (INH)-resistant pulmonary tuberculosis, several treatment regimens have been recommended by many experts. In Korea, a standard regimen has not been established for INH-resistant tuberculosis, and the treatment by individual physicians has been performed on an empirical bases. The purpose of the present study was to retrospectively describe the treatment characteristics and evaluate the treatment outcomes of patients with INH-resistant tuberculosis. Materials and Methods : Sixty of 69 patients reported to have INH-resistant tuberculosis from 1994 to 2001 were retrospectively analyzed. Exclusion criteria included: death from other causes, with the exceptions of tuberculosis and incomplete treatment, including a patient's transfer-out. Results : A previous tuberculosis history was found in 28 (46.7%) patients. The sputum smear for acid-fast bacilli was positive in 44 (73.3%) patients, and 30 (50.0%) had cavitary disease. Streptomycin resistance coexisted in 25.0% of isolates. INH was to be prescribed continuously, even after INH resistance was reported, in 86.0% of patients. The treatment regimens were diverse between the patients according to drug regimen composition and treatment duration. The most frequent prescribed regimen included rifampin, ethambutol and pyrazinamide, with and without INH, for the full 12-month term of treatment. Treatment failure occurred in 13 (21.7%) patients. Cavitary disease (p=0.005) and a treatment regimen with second-line drugs, excluding rifampin (p=0.015), were associated with treatment failure. One patient experienced a relapse. Conclusions : Standardized treatment guidelines will be needed in Korea to improve the treatment efficacy for INH-resistant tuberculosis.

• Biomedical Science Letters
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• v.18 no.3
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• pp.201-209
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• 2012

Apoptosis is a physiological programmed cell death process. Tubercle bacilli inhibit apoptosis of alveolar macrophages and phagolysosome fusion. We investigated whether the Bcl-2 family anti-apoptotic member, Bfl-1/A1, plays an important role in the anti-apoptotic process during mycobacterial infection. PMA-treated human monocytoid THP-1 cells were infected with mycobacteria (H37Rv, BCG, and K-strain) at a multiplicity of infection (MOI) of 10 for 0, 1.5, 3, 6, 9, 12, 18, 24, 48, or 72 h. In addition, PMA-treated THP-1 cells were pretreated with specific inhibitors for 45 min before stimulation with mycobacteria at an MOI of 10 for 4 h. After the indicated time, the cells were subject to reverse transcription-polymerase chain reaction (RT-PCR) analysis, and a Bfl-1/A1-specific Western blot was performed. In PMA-differentiated THP-1 cells, the expression level of Bfl-1/A1 mRNA was increased by Mycobacterium tuberculosis (MTB) H37Rv infection. The mRNA level of Bfl-1/A1 peaked 3 h after MTB infection, then declined gradually until 9 h. However, Bfl-1/A1 mRNA induction gradually re-increased from 24 h to 72 h after MTB infection. No difference in Bfl-1/A1 expression was detected following infection with MTB H37Rv, K-strain, or M. bovis BCG. These results were not dependent on mycobacterial virulence. Moreover, mRNA levels of other anti-apoptotic molecules (Mcl-1, Bcl-2, and Bcl-xL) were not increased after MTB H37Rv or K-strain infection. These results suggest that mycobacteria induce the innate immune host defense mechanisms that utilize Bfl-1/A1 molecules at early time points, regardless of virulence.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.15-26
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• 2019

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

• Biomedical Science Letters
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• v.26 no.3
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• pp.170-178
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• 2020

Mycobacterium tuberculosis (MTB) continues to be one of the main causative agents of tuberculosis (TB); moreover, the incidence of nontuberculous mycobacteria (NTM) infections has been rising gradually in both immunocompromised and immunocompetent patients. Precise and rapid detection and identification of MTB and NTM in respiratory specimens are thus important for MTB infection control. Molecular diagnostic methods based on the nucleic acid amplification test (NAAT) are known to be rapid, sensitive, and specific compared to the conventional acid-fast bacilli (AFB) smear and mycobacterial culture methods. In the present study, the clinical performances of three commercial molecular diagnostic assays, namely TB/NTM PCR (Biocore), MolecuTech Real MTB-ID^® (YD Diagnostics), and REBA Myco-ID^® (YD Diagnostics), were evaluated with a total of 92 respiratory specimens (22 AFB smear positives and 67 AFB smear negatives). The sensitivity and specificity of TB/NTM PCR were 100% and 75.81%, respectively. The corresponding values of MolecuTech Real MTB-ID^® and REBA Myco-ID^® were 56.52% and 90.32%, and 56.52% and 82.26%, respectively. TB/NTM PCR showed the highest sensitivity; however, the concordant rate was 10% compared with sequence analysis. Although MolecuTech Real MTB-ID^® showed lower sensitivity, its specificity was the highest among the three methods. REBA Myco-ID^® allowed accurate classification of NTM species; therefore, it was the most specific diagnostic method. Of the three PCR-based methods, MolecuTech Real MTB-ID^® showed the best performance. This method is expected to enable rapid and accurate identification of MTB and NTM.

• Korean Journal of Microbiology
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• v.45 no.3
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• pp.281-285
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• 2009

In this study, we compared the BacT/Alert liquid culture system with Ogawa and $L\ddot{o}wenstein$-Jensen (L-J) media for sputum culture and drug susceptibility test (DST) of Mycobacterium tuberculosis. Rapid liquid culture systems have been widely employed both for primary cultures of M. tuberculosis from clinical specimens and for drug susceptibility test because of its greater sensitivity and faster turn-around time than the conventional egg-based culture methods (Ogawa, $L\ddot{o}wenstein$-Jensen media). Sputum specimens were decontaminated with N-acetyl-L-cysteine (NALC)-4% NaOH and inoculated into the BacT/Alert culture bottles and Ogawa media. 95 from among 135 sputa were smear-positive, 97 (71.9%) were culture-positive by the BacT/Alert culture system, while 89 (65.9%) were positive by Ogawa media. The mean time to culture-positive by the BacT/Alert process system was about 11.3 days, which was significantly shorter than that by Ogawa media (22.4 days). Of 32 M. tuberculosis cultures examined for drug sensitivity, the concordant rate between the two methods (BacT/ Alert liquid culture system, $L\ddot{o}wenstein$-Jensen media) ranged from 87.5% for isoniazid and 90.6% for rifampicin.