• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.344-352
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• 2003

Background : The prevalence of multidrug resistant tuberculosis (MDR-TB), resistant to isoniazid (INH) and rifampin (RFP), was 5.3% worldwide in 1995 and its increment has raised important public health problems. Resistance to RFP, one of the key drugs in the treatment of tuberculosis, results in grim clinical outcome. Recently rapid detection of RFP-resistant mutations in rpoB gene based on PCR method has become available. This study evaluated the prevalence of RFP resistance in first diagnosed, treatment failure, and recurred patients using INNO-LiPA test, and compared the results of INNO-LiPA with those of conventional mycobacterial drug susceptibility test. Methods : Forty-six patients, who were diagnosed of pulmonary tuberculosis and had revealed positive sputum AFB smear, were enrolled in this study from 1998 to 2002. The cases were classified as one three groups; first diagnosed, treatment failure, or recurred. RFP resistance was studied using an INNO-LiPA Rif. TB kit and compared with that obtained from drug susceptibility based on M. tuberculosis culture study. Results : Twenty-one out of 46 patients were enrolled under first diagnosis of pulmonary tuberculosis, 17 under treatment failure with first line drugs, and 8 under recurrence. The positive and negative predictive values of INNO-LiPA test in diagnosis in RFP resistant tuberculosis compared with conventional mycobacterial drug susceptibility test were 85.7% and 76.0%, respectively. INNO-LiPA result revealed rpoB gene mutation in 20 (80.0%) out of 25 patients who were diagnosed as treatment failure or recurrence, but in only 4 (19.0%) out of 21 patients who were first diagnosed as pulmonary tuberculosis. Conclusion : This study showed that RFP resistance could be diagnosed rapidly and accurately using INNO-LiPA test and that this test might be helpful for choosing second line anti-mycobacterial drugs. It might be of great help in clinical diagnosis and decision when used in complimentarily with drug susceptibility test based on M. tuberculosis culture.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.114-123
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• 1997

Background : To assess the diagnostic role of bronchoscopic lavage for the evaluation of pneumonia in intensive care unit(ICU), the results were compared to blind endobronchial specimen. Method : From September 1993 to August 1996, twenty-eight ICU patients suspected pneumonia on the basis of clinical evidence and performed bronchoscopy under the diagnostic or therapeutic purpose were studied retrospectively for the clinical findings including culture of bronchoscopic and blind endobronchial specimen. Bronchoscopic specimen was got through small amount of bronchoalveolar lavage with 20-40ml saline, one or two times on the suspected site. Results : l. Main reasons of ICU admission were respiratory and impending respiratory failure Nosocomial pneumonia was most common with 16 cases; each for community acquired and immunocompromised type with 6 cases. Diagnostic purpose of bronchoscopy was performed in 20 cases as 71 percent in total, whereas therapeutic removal of secretion in 8 cases. The complication during bronchoscopic evaluation was trivial. 2. The agreement between blind endobronchial and bronchoscopic specimen on microbial culture was only 39.3 percent. However, 2 cases each for aspergillosis and tuberculosis were diagnosed under bronchoscopic evaluation. 3 The application of mechanical ventilation occured significantly frequently in multidrug resistant pneumonia compared with other pneumonia in terms of bronchoscopic specimen. 4. The application of mechanical ventilation was significantly common in nosocomial pneurmonia compared with other types of pneumonia. Conclusion : The selective bronchoalveolar lavage and therapeutic removal of bronchial secretion with bronchoscopy in ICU patient accompanying pneumonia is a very useful tool with safety. The multidrug resistant pneumonia or nosocomial pneumonia could be closely associated with the use of mechanical ventilation.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.282-288
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• 2016

Background: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. Methods: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on $L{\ddot{o}wenstein$-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. Results: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). Conclusion: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1245-1255
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• 1997

Background : Rifampicin(RFP) is a key component of the antituberculous short-course chemotherapy and the RFP resistance is a marker of multi-drug resistant(MDR) tuberculosis. RPoB gene encodes the $\beta$-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. And rpoB gene mutations are the cause of RFP resistance of M. tuberculosis. Although several reports showed that PCR-SSCP would be a rapid diagnostic method for identifying the RFP resistance, there were few reports Performed using direct, clinical specimens. So we Performed PCR-SSCP analysis of rpoB gene of M. tuberculosis in direct, clinical specimens. Methods : 75 clinical specimens were collected from patients at Asan Medical Center from June to August 1996. After PCR of IS 6110 fragments, 43 both AFB smear-positive and IS6110 fragment PCR-positive specimens were evaluated. The RFP susceptibility test was referred to the referral laboratory of the Korean Tuberculosis Institute. DNA was extracted by bead beater method. And heminested PCR was done using 0.1ul(1uCi) [$\alpha-^{32}P$]-dCTP. SSCP analysis was done using non-denaturating MDE gel electrophoresis. Results : The results of PCR of IS6110 fragments of M. tuberculosis were positive in 55(73%) cases of 75 AFB smear-positive clinical specimens. Of the 55 specimens, RFP susceptibility was confirmed in only 43 specimens. Of the 43 AFB smear-positive and IS6110 fragment-positive specimens, 29 were RFP susceptible and 14 were RFP resistant. All the RFP susceptible 29 strains showed the same mobility compared with that of RFP sensitive H37Rv in SSCP analysis of ropB gene. And all the other RFP resistant 13 strains showed the different mobility. In other words they showed 100% identical results between PCR-SSCP analysis and traditional susceptibility test. Conclusion : The PCR-sseP analysis of rpoB gene in direct clinical specimens could be used as a rapid diagnostic method for detecting RFP resistant M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.368-371
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• 2007

Pulmonary cavities are caused by bacterial pneumonia, fungal diseases, lung cancer, and tuberculosis (TB). However, in Korea, patients with cavitary lung lesions are generally considered to have pulmonary TB, where the incidence of TB is approximately 70/100,000 per year. We report a case of chronic necrotizing pulmonary aspergillosis that was obscured by multidrug-resistant pulmonary TB.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.546-557
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• 2000

Background : Oligonucleotide chip technology has proven to be a very useful tool in the rapid diagnosis of infectious disease. Rifampin resistance is considered as a useful marker of multidrug-resistance in tuberculosis. Mutations in the rpoB gene coding $\beta$ subunit of RNA polymerase represent the main mechanism of rifampin resistance. The purpose of this study was to develop a diagnosis kit using oligonucleotide chip for the rapid and accurate detection of rifampin-resistance in Mycobacterium tuberculosis. Method : The sequence specific probes for mutations in the rpoB gene were designed and spotted onto the glass slide, oligonucleotide chip. 38 clinical isolates of Mycobacterium were tested. A part of rpoB was amplified, labelled, and hybridized on the oligonucleotide chip with probes. Results were analyzed with a laser scanner. Direct sequencing was done to verify the results. Result : The low-density oligonucleotide chip design어 to determine the specific mutations in the rpoB gene of M. tuberculosis accurately detected rifampin resistance associated with mutations in 28 clinical isolates. Mutations at codons 531, 526, and 513 were confirmed by direct sequencing analysis. Conclusion : Mutant detection using oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of multidrug-resistance in M. tuberculosis.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.287-293
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• 1999

Background: Medical treatment of multiple drug resistant(MDR) pulmonary tuberculosis has been quite unsuccessful. We analyzed our experience to identify the benefits and complications of the pulmonary resection in MDR pulmonary tuberculosis. Material and Method: A retrospective review was performed in 27 patients who unerwent pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Mean age was 40 years and the average history of diagnosis prior to surgery was 3.1 years. All had resistance to an average of 4.4 drugs, and received second line drugs selected according to the drug sensitivity test. Most patients (93%) had cavitary lesions as the main focus. Bilateral lesions were identified in 19 patients (70%), however, the main focus was recognized in one side of the lung. Eleven patients (41%) were converted to negative sputum smear and/or culture before surgery. Result: Pneumonectomy was performed in 9 patients, lobectomy in 16 and segmentectomy in 2. There was no operative mortality. Morbidity had occurred in 7 patients (26%), prolonged air leak in 3 patients, reoperation due to bleeding in 2, bronchopleural fistula in 1, and reversible neurologic defect in 1. Median follow up period was 15 months (3-45 months). Sputum negative conversion was initially achieved in 22 patients (82%), and with continuous postopertive chemotherapy negative conversion was achieved in other 4 patients (14%). Only one pneumonectized patient (4%) failed due to considerable contralateral cavity. Conclusion: For patients with localized MDR pulmonary tuberculosis and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

• Journal of Chest Surgery
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• v.34 no.1
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• pp.72-79
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• 2001

배경: 일반적으로 다제내성 폐결핵의 경우 화학요법만으로는 치료성적이 만족스럽지 못하였다. 이에 수술적 치료와 항결핵 화학요법의 병합사용이 높은 균음전율과 장기 생존율을 보여주고 있으므로 이러한 치료전략이 다제내성 폐결핵환자의 일반적인 치료방법으로 정립되리라는 전망을 갖게 하고 있다. 대상 및 방법: 1995년 1월부터 1999년 12월까지 국립마산결핵병원에서 폐결핵에 대한 수술을 시행받은 130례 중 다제내성 폐결핵으로 폐절제수술을 받은 49례를 대상으로 의무기록 및 검사기록 등을 근거로 후향적 조사를 실시하였다. 결과: 대상환자들의 평균연령은 35세였고, 내성약제의 수는 평균 4.5였다. 43례(87.8%)의 환자에서 공동성 병소를 보였으며 31례(63.3%)의 환자에서 술전 객담내 균양성 소견을 보였다. 수술술식은 12례에서 전폐적출술을, 28례에서 폐엽절제술을, 7례에서는 폐엽절제술과 구역절제술 혹은 설상절제술 등을, 그리고 설상절제술과 공동성형술을 각각 1례에서 시행하였다. 술후 지속적인 내과적 약물치료를 병합하여 장기적인 균음전율은 93.5%였고 술후 사망환자는 없었다. 술후 합병증으로는 1주일 이상 지속되는 공기유출 6례와 술후 출혈, 창상분열이 각각 1례씩 있었다. 결론: 다제내성 폐결핵환자에서 폐절제 수술에 대해서는 적절한 적응증, 수술후 처방, 그리고 술후 치료기간 등에 대한 이견이 있지만 적극적으로 고려되어야 하며 술후 내과적 치료와 병행함으로 좋은 치료효과를 얻을 수 있었다.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.41-58
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• 2003

Background : The resurgence of tuberculosis and the widespread emergence of multidrug-resistant M. tuberculosis have emphasized the importance of rapid and accurate diagnostic procedures. Recently, the oligonucleotide chip has proven to be a useful tool in the rapid diagnosis of infectious diseases. The purpose of this study was to rapidly and accurately detect specific mutations in the rpoB, katG and rpsL genes associated with rifampin, isoniazid and streptomycin resistance in M. tuberculosis, respectively, using a single oligonucleotide chip. Method : For detection of drug-resistance, 7 wild-type and 13 mutant-type probes for rifampin, 2 wild-type and 3 mutant-type probes for isoniazid, and 2 wild-type and 2 mutant-type probes for streptomycin were designed and spotted onto glass slides. Fifty-five cultured samples of M. tuberculosis were amplified by PCR, and then underwent hybridization and scanning. Direct sequencing was done to verify the results from the oligonucleotide chip and to analyze the types of mutations. Result : Thirty-five cases out of 40 rifampin-resistant strains(~88%) had mutations in the rpoB gene. One case had a new mutation(D516F, GAC R TTC) and another known mutation together. Twenty cases out of 42 isoniazid-resistant strains(~50%) had mutations in the katG gene, while 7 cases out of 9 streptomycin-resistant strains(~78%) had mutations in the rpsL gene. From these results, the oligonucleotide chip was confirmed to be able to detect the most frequent mutations from the genes associated with rifampin, isoniazid and streptomycin resistance. The results proved that the drug-resistance detection probes were specific. When the results from the oligonucleotide chip and DNA sequencing were compared, the types of mutations were exactly matched. Conclusion : The diagnostic oligonucleotide chip with mutation specific probes for drug resistance is a very reliable and useful tool for the rapid and accurate diagnosis of drug resistance against rifampin, isoniazid and streptomycin in M. tuberculosis infections.

• The Journal of the Korea Contents Association
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• v.21 no.4
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• pp.487-497
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• 2021

The purpose of this study is to identify factors affecting length of stay(LOS) and death in tuberculosis(TB) patients by disease type, patient characteristic, admission and disease characteristic, and hospital characteristic from 2008 to 2017. Survey data was using Korean national hospital discharge in-depth survey data produced by Korea Disease Control and Prevention Agency. Study subjects were 10,634 inpatients with TB(A15, A16, A17, A18, A19, U88.0, U88.1, U84.30, U84.31) and analyzed frequency, chi-square test, Fisher's exact test, and logistic regression by using STATA 13.0. As a study result, the type of TB(extrapulmonary TB, multidrug-resistant TB, extensively drug-resistant TB), sex(woman), age(35-49, 50-64, 65-74, 75 years old or older), admission type(outpatient department), CCI(1-2 point, 3 point over), hospital location(metropolitan city) and bed size(300-499, 500-999, over 1000) were significantly influence LOS. Also, the type of TB(extrapulmonary TB, extensively drug-resistant TB), sex(woman), age(50-64, 65-74, 75 years old or older), residence(small town/rural), admission type(outpatient department), CCI(1-2 point, 3 point over), hospital location(provincial) were significantly influence death. In conclusion, the existing tuberculosis management has been patient management with rapid diagnosis and treatment following early detection. But other studies should be carried out for the system that identifies and supports high-risk groups of the long-term length of stay in hospital or high mortality rates as a result of treatment.