• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.179-185
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• 2005

Background : To evaluate the clinical efficacy of pulmonary resection combined with first-line antituberculous drug therapy in patients with well-localized, cavities-containing pulmonary multidrug-resistant tuberculosis (MDR-TB). Method : From February 1998, seventeen patients with well-localized, cavities-containing pulmonary MDR-TB were enrolled and followed prospectively up to December 2004. After radical pulmonary resection, the patients were treated with antituberculous drugs comprising of isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) (3HERZS/3HERS/6HER). Results : All recovered isolates of M. tuberculosis were resistant to both isoniazid and rifampin, and to a mean of 4.8 antituberculous drugs (range, 2 to 7 drugs). Surgical procedures included lobectomy (13 patients), lobectomy plus segmentectomy (3 patients), and pneumonectomy (1 patient). The median time for postoperative sputum smear and culture conversion was 2 days (range, 1 to 23 days). Fifteen (94%) patients had durable cures (mean follow-up period, 39.0 months). One patient failed to convert her sputum and was successfully switched to second-line therapy; one patient developed active disease again almost 7 years later, likely due to re-infection with a new M. tuberculosis strain. Conclusion : Radical resection combined with administration of first-line antituberculous agents was effective in patients with well-localized, cavities-containing pulmonary MDR-TB.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.613-618
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• 2005

Background : Recently, medical treatment of multi-drug resistant pulmonary tuberculosis has been unsuccessful. Through analyzing the cases with surgical treatment, we hope to provide some help in treating multi-drug resistant pulmonary tuberculosis in the future. Material and Method : A retrospective review was performed with 138cases of surgical treatment of multi-drug resistant tuberculosis during 10years from January 1994 to December 2003 at National Masan Hospital. Results : The ratio of men to women, 5.1:1 indicates that there were more incidences in men. The number of the resistant drugs was 5.3 with a mean age of 42.6 years. Cavitary lesions on the plain chest X-rays were seen in 94cases (68.1%). 128cases had positive sputum culture preoperatively. Types of operations were 24 pnemonectomies, 83 lobectomies, 10 bilobectomies, 19 lobectomies with segmentectomies or wedge resections, 1 wedge resection, and 1 carvenoplasty. There was no death after operation. There were 6cases of air leakage over a week, 6cases of postoperative bleeding, 8cases of bronchopleural fistula and empyema, 16cases of dead space, 1case of atelectasis, 1case of wound infection, 1case of cyst as postoperative complication. Postoperative complication showed higher long-term negative conversion rate of 92.8%. Conclusion : There has been many discussions about operative indications, postoperative drug regimens, length of postoperative chemotherapy. In our study, we showed higher long-term success rate of postoperative chemotherapy with pulmonary resection on multi-drug resistant pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.226-233
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• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.367-377
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• 2003

Background : It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). Methods : HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. Results : Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. Conclusion : HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.11
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• pp.5012-5018
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• 2011

According to the nationwide survey of tuberculosis from 1965 to 1995, the incidence and drug resistance rate of tuberculosis have been decreased in Korea, but the prevalence of multidrug resistance of Mycobacterium tuberculosis is still a serious problem. The purpose of this study is to investigate the drug resistance rate and pattern of tuberculosis in Daejeon from 2001 to 2008. Of the total 581cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 104 cases(17.9%) of these, 68(11.7%) were resistant to at least INH and 41(7.1%) were resistant to at least RFP. Single-drug resistance was found for isolates from 37(6.4%) ; 18(3.1%) of these were resistant to INH and 5(0.9%) to RFP. Multidrug resistance, where TB was resistant to at least isoniazid and refampin, was found in 35 cases(6.0%). and Factors associated with MDR-TB included age under 40-60.The drug-resistance rate of pulmonary TB, especially MDR-TB, is higher in the initial treated patients at a private referral hospital than in those in the pubulic sector. Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment. The need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance. Multidrug resistance rate is still problem in korea. Efforts to decrease multidrug resistance rate either independently or in cooperation with the pubulic sector will be needed.

• Tuberculosis and Respiratory Diseases
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• v.64 no.2
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• pp.95-101
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• 2008

Background: Drug resistant tuberculosis (TB) in patients who have not received previous TB treatment (initial drug resistance) is a serious problem for the control of TB. However, prevalence of initial drug resistance among pulmonary TB patients has not been well characterized in Korea, especially in the private sector. We assessed the prevalence of initial drug resistance and evaluated the risk factors for drug resistance in pulmonary TB patients, at a regional tertiary hospital in Cheonan. Methods: We performed a drug susceptibility test for both first and second line anti-TB drugs in all culture-confirmed pulmonary TB patients who had not received a previous TB treatment at Dankook University Hospital from September 2005 to September 2007. In addition, we evaluated the initial drug resistance pattern and clinical characteristics of patients to evaluate the risk factors for initial drug resistance. We also assessed the influence of the drug susceptibility test results on the treatment regimen. Results: Of the total 156 cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 21 cases (15.6%) and multidrug resistance, where TB was resistant to at least isoniazid and rifampin, was found in one case (0.6%). Multivariate logistic regression showed no clinical characteristics were independently associated with initial drug resistance. Of the total 156 patients who underwent the drug susceptibility test, the treatment regimen was changed for 15 patients (9.6%) according to the results of the drug susceptibility test. Conclusion: Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment.

• Tuberculosis and Respiratory Diseases
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• v.62 no.6
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• pp.492-498
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• 2007

Background: Several lines of evidence suggest that a host's genetic factors influence the outcome of exposure to Mycobacterium tuberculosis. The aim of this study was to determine whether polymorphism in NRAMP1 (natural resistance associated macrophage protein 1) gene is associated with the susceptibility or resistance to tuberculosis infection for patients with drug-sensitive pulmonary tuberculosis (DS-TB) and multi-drug resistant pulmonary tuberculosis (MDR-TB). Methods: Eight genetic polymorphisms of the NRAMP1 gene were investigated in patients suffering with DS-TB (n=100) or MDR-TB (n=102), and in healthy normal controls (NC, n=96). The genetic polymorphisms of NRAMP1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of D543N A/G heterogygotes was significantly higher in the DS-TB subjects than the NCs (OR=2.10, 95% CI: 1.00 to 4.41, p=0.049). The frequency of 823C/T T/C heterozygotes was significantly higher in the DS-TB subjects (OR=2.79, 95% CI: 1.11 to 7.04, p=0.029) and the MDR-TB subject (OR=3.30, 95% CI 1.33 to 8.18, p=0.010) than in the NCs. However, the frequency of these genotypes was not different between the DS-TB and MDR-TB subjects. Conclusion: A significant association was found between NRAMP1 823 C/T polymorphism and pulmonary tuberculosis. This result suggests that NRAMP1 polymorphism may be involved in the development of pulmonary tuberculosis in Koreans.

• 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.60 no.3
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• pp.353-356
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• 2006

Acute transverse myelitis (TM) is a neurological syndrome caused by inflammation of the spinal cord. TM is rare but is frequently caused by viral or bacterial infections. TM caused by tuberculosis (TB) is extremely rare and there are no reports of TM caused by multidrug-resistant TB (MDR-TB). We report a case of acute TM due to MDR-TB in a 40-year-old man. The patient had been diagnosed with pulmonary TB and was started on the first-line anti-TB treatment. However, the chest radiographic findings were aggravated and neurological symptoms such as weakness in both lower extremities, sensory changes, and voiding difficulty were newly developed. The T2-weighted magnetic resonance image of the spine showed diffusely increased signal intensity in the spinal cord, particularly at the lower cervical and upper thoracic levels, without any definite evidence of myeloradicular compression, which is consistent with a diagnosis of TM. A drug susceptibility test revealed MDR and second-line anti-TB drugs were prescribed. The chest radiographic findings showed improvement after treatment, the mycobacterial culture converted to negative, the MRI findings improved, and there was partial improvement in the low extremity weakness. The patient has been prescribing second-line anti-TB medications for 14 months.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.194-204
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• 2006

Background : Even though tuberculosis (TB) is still a major public concern in Korea, there is little data on the management of TB patients and its outcomes in the private sector. This study evaluated the status of TB treatment in the private sector. Methods : Sixteen-hundred-sixty-six TB patients who were notified in a private university hospital from 2001 to 2002 were enrolled in this study. The patients were divided into pulmonary ($TB_P$), extrapulmonary ($TB_E$), and combined ($TB_{P+E}$) groups, and were also divided into initial and retreatment groups. The clinical characteristics, diagnostic methods, treatment regimens, and outcomes were analyzed and compared. Results : The mean age of the 1,666 patients was 48.9 years and the male-to-female ratio was 1.3:1. The number of patients in the initial and retreatment groups of $TB_P$, and those of ($TB_E+TB_{P+E}$) were 809, 276, 480, 101, respectively. A bacteriological study was performed in 92.0% of cases, and a positive culture was confirmed in 58.1% and 31.7% of patients with TBP and ($TB_E+TB_{P+E}$), respectively (p<0.05). The AFB smear was positive in 45.4 % of the $TB_P$ patients. PCR was carried out in 60.4% of the ($TB_E+TB_{P+E}$) group. The MDR was detected in 14.0% of isolates. Overall, the treatment completion, default, and death rates were 70.2%, 13.5% and 1.9%, respectively. Conclusion : Even though the management of TB patients in a private hospital was satisfactory in terms of the national guidelines, the high default rate was is still a problem. Efforts to decrease the default rate either independently or in cooperation with the public sector will be needed.