• Tuberculosis and Respiratory Diseases
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• v.58 no.3
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• pp.285-290
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• 2005

Background : Some malignancies including lymphoma, head and neck cancer, and lung cancer are believed to be associated with the reactivation of tuberculosis (TB) because cyclic anti-cancer chemotherapy can induce the leukopenia or immunological deterioration. This report describes the clinical characteristics and treatment response of TB that developed during cyclic anti-cancer chemotherapy in patients with a solid tumor. Materials and Methods : From January 1 2000 to July 31 2004, patients with TB diagnosed microbiologically, pathologically, or clinically during anti-cancer chemotherapy in a tertiary hospital were enrolled, and their medical records were reviewed. Patients with the known risk factors for the reactivation of TB were excluded. Results : Twenty-two patients were enrolled and their mean age was 56.5 years (range 21-78). The male to female ratio was 3.4:1 and pulmonary TB was the main variant (20 patients, 90.9%). Gastric cancer (10 patients, 45.4%) and lymphoma (4 patients, 18.2%) were the leading underlying malignancies. The other malignancies included lung cancer, head and neck cancer, breast cancer, cervix cancer, and ovary cancer. Fifteen patients (68.2%) had a healed scar on a simple chest radiograph suggesting a previous TB infection. Among these patients, new TB lesions involved the same lobe or the ipsilateral pleura in 13 patients (87.6%). An isoniazid and rifampicin based regimen were started in all the subjects except for one patient with a hepatic dysfunction. The mean duration of medication was $9.9{\pm}2.4$ months and no adverse events resulting in a regimen change were observed. With the exception of 5 patients who died of the progression of the underlying malignancy, 70.6% (12/17) completed the anti-TB treatment. Conclusion : The clinical characteristics and response to anti-TB treatment for TB that developed during anticancer chemotherapy for a solid tumor were not different from those of patients who developed TB in the general population.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.618-627
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• 1999

Background : Rifampicin (RFP) is a key component of the antituberculous short-course chemotherapy. Usually the RFP resistant M.tuberculosis is also resistant to isoniazid (INH), so the RFP resistance is the marker of multi-drug resistant (MDR) tuberculosis. But unusual cases of mono-RFP-resistant tuberculosis have been recently reported with increasing frequency, especially associated with HIV infection in western countries. Therefore, we conducted a retrospective study to investigate the frequency, causes, and the clinical characteristics of mono-RFP-resistant tuberculosis in Korea. Methods : Of the bacteriologically confirmed and susceptibility-proven 699 pulmonary tuberculosis patients (921 isolates) who visited Asan Medical Center from January 1990 to August 1997, eighteen patients with INH-susceptible and RFP-resistant tuberculosis were evaluated. Previous history of tuberculosis, antituberculous drug compliances, associated systemic illness, drug susceptibility patterns, and clinical outcomes were analysed. And rpoB gene sequencing was done in 6 clinical isolates of M. tuberculosis. Results : The mean age of 18 patients was $43{\pm}14$ years, and the sex ratio is 12:6 (M : F). Sixteen (89%) patients had previous history of tuberculosis. None had diagnosed gastrointestinal disorders, and 2 HIV tests that were performed came out negative. Susceptibility tests were done repeatedly in eleven patients, and six (55%) were mono-RFP resistant repeatedly while five (45%) evolved to MDR tuberculosis. Eight (44%) patients were cured, six (33%) failed, three (17%) were lost to follow-up, and the other one is now on treatment. rpoB gene sequencing showed 5 mutations, codon 531 TCG to TIG mutation in 4 isolates and 526 CAC to TAC in 1 isolate. Conclusion : The clinical characteristics of mono-RFP resistant tuberculosis were similar to that of MDR tuberculosis in Korea where the HIV infection rate is lower than western countries. But some patients with mono-RFP-resistant tuberculous could be cured by primary drug regimens including RFP, suggesting that mono-RFP-resistant tuberculous is a different entity from MDR 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.60 no.3
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• pp.285-289
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• 2006

Background : North Korea's economic and public health problems began in the early 1990s as a result of the gradual loss of economic support from its communist allies, combined with an inordinate number of natural disasters. The decline in public health has increased the incidence of tuberculosis in North Koreans and refugees. This study investigated tuberculosis situation in North Korean refugees in order to prepare for the future impact of tuberculosis control in Korea. Material and Methods : From 2001 to 2005, tuberculosis patients among North Korean refugees who were diagnosed before or after arriving in South Korea, based on the official records of OO hospital, were enrolled in this study. The demographic and clinical data of the cases were evaluated retrospectively. Results : A total of 42 TB cases were reviewed during the study period. Of these, 37 (88.1%) cases were pulmonary TB. based on the cases identified among the number of North Korean refugees' arriving each year, the annual incidence of pulmonary TB were 900 per 100,000 in 2004, 700 in 2003, The number of smear-positive patients was 20 (47.6%) and the number of culture-positive patients was 18 (42.9%). Of the M. tuberculosis isolates, 2 cases were found to be susceptible to all anti-TB drugs available, 4 were resistant to isoniazid, and 3 were multi-drug resistant. Conclusion : The prevalence of pulmonary TB in North Korean Refugees is high. In addition, North Korean refugees suffer from more severe tuberculosis in bacteriological and radiological aspects.

• Tuberculosis and Respiratory Diseases
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• v.62 no.4
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• pp.270-275
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• 2007

The QuantiFERON-TB Gold assay and tuberculin skin test (TST) have been useful test for diagnosing latent tuberculosis infections (LTBI). However, there are few reports on the efficacy of the QuantiFERON-TB Gold assay and TST in evaluating the response after the treatment of LTBI. This study examined the changes in the TST and QuantiFERON-TB Gold assay before and after a treatment for latent tuberculosis in health care workers (HCWs) at a local tertiary hospital. Methods: A cohort of volunteers working as nurses and doctors who underwent a TST and QuantiFERON-TB Gold assay was established. The volunteers positive for the QuantiFERON-TB Gold assay had been treated with 3 months of isoniazid (INH) and rifampin (RFP). After completing treatment, the TST and QuantiFERON-TB Gold assay were repeated. Results: Of the 48 participants (14 doctors, 34 nurses, M: F=11:37, mean $age=29.9{\pm}5.5$ years, mean employment $period=74.9{\pm}64.3$ months), 19 (39.6%) tested positive to the TST (mean induration=$19.1{\pm}9.7mm$) and 8 (16.7%) were QuantiFERON-TB Gold assay. Among them, one had active pulmonary tuberculosis. Seven volunteers were consistently positive to both the TST and QuantiFERON-TB Gold assay after being medicated with INH and RFP for 3 months. Conclusion: TST and QuantiFERON-TB Gold assay are unsuitable for evaluating the treatment response of LTBI because they were consistently positive both before and after the anti-tuberculosis medication.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.409-418
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• 1997

Objective : Appropriate antituberculosis chemotherapy may not prevent occurrence or progression of tracheobronchial stenosis and obstruction in the patients with endobronchial tuberculosis. The effect of corticosteroid treatment combined with antituberculosis chemotherapy was inconclusive. We evaluated prospectively the effect of corticosteroid treatment. Methods : We diagnosed endobronchial tuberculosis by bronchoscopic examination and bronchial biopsy in the patients of tuberculosis within one month of antituberculosis chemotherapy. After randomization, we prescribed isoniazid, rifampin, ethambutol, and pyrazinamide with or without prednisolone 40 mg for 4 weeks. We carried out bronchoscopy in second month and ninth month of treatment. Results : Edematous endobronchial tuberculosis showed significant improvement of bronchial stenosis after corticosteroid treatment(p < 0.05). Corticosteroid treatment did not have advantage of improvement of bronchial stenosis in the patients with infiltrative endobronchial tuberculosis. Conclusion : Corticosteroid is effective in the treatment of bronchial stenosis when endobronchial tuberculosis is edematous type, in the early period of antituberculosis chemotherapy.

• 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.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.95-102
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• 1985

This report offers descriptive data about the drugs utilized in out patient department (OPD) of Yeungnam University Hospital (YUH) in the period of march to august in 1985. The data in this report were produced by the computerized totalization of the number of mentions of individual drugs included in the prescriptions. The 100 drug entries that were most frequently recorded are listed in rank order. The listing is arbiturarily restricted to the drugs that were prescribed as single preparations, the drugs of basis of compound preparations and the drugs of adjuvent or corrective of compound preparations that have significant therapeutic effects either by generic names. And in addition, the listing also involves the compound preparations used in relatively large frequency, and the individual components of which have the unique pharmacological actions each other by proprietary names. And all routes of administrations were allowed. The 10 drugs most frequently named are diazepam, aluminum compounds, acetaminophen, isoniazid, metoclopramide, $polaramine^{(R)}$, carboxymethylcystem, ephedrine, codeine and caroverine in order. The 521,855 drug mentions listed as above are described by the chief therapeutic usage that each is intended to apply generally. The drugs which account the largest proportion of total mentions were those acting on the central nervous system (20.57%), including tranquilhzers and sedative hypnotics (11.71%), analgesic antipyretics (5.55%), antidepressants (2.15%) etc. Gastrointestinal drugs and smooth muscle preparations (18.64%) included antacids and anti-ulcer drugs (9.24%), antiemetics (3.57%), spasmolytics (3.14%) and others. Respiratory drugs (16.11%) included expectorants and cough preparations (10.99%) and bronchodilators (5.12%). Chemotherapeutic agents (15.12%) included the antiTbc drugs (7.09%) most frequently, and the penicillins (3.33%) accounted the largest proportion among the antibiotics. Cardiovascular drugs (5.64%) included cardiac drugs and coronary vasodilator (4.12%) and antihypertensives and vasodilators (1.06%). And anti-inflammatory drugs (4.33%), vitamins of single preparations (3.76%), hormones and their antagonists (3.29%), common cold preparations (3.12%), diuretics (2.81%), drugs supporting liver function (2.02%), drugs affecting autonomic nervous system(1.89%) including anti-glaucomas, atropine and cerebral vasodilators, antihistamine drugs (1.02%) and disinfectants (0.74%) were following in order. The data in this report were compared to those reported by H. Koch, et al. in United States (US), 1981 as "Drugs Most Frequently Used in Office Practice:National Ambulatory Medical Case Survey, 1981." Cardiovascular drugs prescribed in YUH were much less in proportion than in US (10.56%), but gastrointestinal drugs accounted the larger proportion than in US (3.72%). Expectorants and cough preparations in YUH also accounted the larger proportion than in US (2.74%). In conclusion, in the period of march to august, 1985, OPD of YUH prescribed the CNS drugs including diazepam most frequently, and gastrointestinal, repiratory and chemotherapeutic drugs in next orders. It is supposed that the eating habits of Koreans and a unique atmospheric condition in Taegu as a basin were some important factors that affected the proportions of drugs acting on gastrointestinal and respiratory tracts.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.676-683
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• 2000

Background : Surgery may have a role when medical treatment alone is not successful in patients with multidrug resistant (MDR) pulmonary tuberculosis (PTB). To document the role of resection in MDR PTB, we analyzed 4 years of our experience. Methods : A retrospective review was performed on thirteen patients that underwent pulmonary resection for MDR PTB between May 1996 and February 2000. All patients had organisms resistant to many of the first-line drugs including isoniazid (INH) and rifampicin (RFP). Results : The thirteen patients were $37.5{\pm}12.4$ years old (mean${\pm}$S.D.)(M : F=5:8), and their sputum was culture positive even with adequate medication for prolonged periods ($109.7{\pm}132.0$ months), resistant to 2-8 drugs including isoniazid and rifampin. All patients had localized lesion(s) and most (92.3%) had cavities. At least 3 sensitive anti-TB medications were started before surgery in all patients according to the drug sensitivity test. The preoperative $FEV_1$ was $2.37{\pm}0.83$ L. Lobectomy was performed in 11 patients and pleuropneumonectomy in two. Postoperative mortality did not occur, but pneumonia occurred as a complication in one (7.7%). After $41.5{\pm}58.9$ days (range 1~150 days) follow up, negative conversion of sputum culture was achieved in all patients within 5 months. Only one patient (7.7%) recurred 32 months after lung resection. Conclusion : When medical treatment alone is not successful, surgical resection can be a good treatment option in patients with localized MDR PTB.

• Journal of Microbiology and Biotechnology
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• v.26 no.1
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• pp.180-189
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• 2016

The widespread occurrence of drug-resistant Mycobacterium tuberculosis places importance on the detection of TB (tuberculosis) drug susceptibility. Conventional drug susceptibility testing (DST) is a lengthy process. We developed a rapid enzymatic color-reaction-based biochip assay. The process included asymmetric multiplex PCR/templex PCR, biochip hybridization, and an enzymatic color reaction, with specific software for data operating. Templex PCR (tem-PCR) was applied to avoid interference between different primers in conventional multiplex-PCR. We applied this assay to 276 clinical specimens (including 27 sputum, 4 alveolar lavage fluid, 2 pleural effusion, and 243 culture isolate specimens; 40 of the 276 were non-tuberculosis mycobacteria specimens and 236 were M. tuberculosis specimens). The testing process took 4.5 h. A sensitivity of 50 copies per PCR was achieved, while the sensitivity was 500 copies per PCR when tem-PCR was used. Allele sequences could be detected in mixed samples at a proportion of 10%. Detection results showed a concordance rate of 97.46% (230/236) in rifampicin resistance detection (sensitivity 95.40%, specificity 98.66%) and 96.19% (227/236) in isoniazid (sensitivity 93.59%, specificity 97.47%) detection with those of DST assay. Concordance rates of testing results for sputum, alveolar lavage fluid, and pleural effusion specimens were 100%. The assay provides a potential choice for TB diagnosis and treatment.