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Clinical Effects of Prothinoamide, Cycloserine, Para-Aminosalicylic Acid, Ofloxasine in Retreatment of Pulmonary Tuberculosis (폐결핵 재치료 환자에서 Prothionamide, Cycloserine, Paraminosalicylic acid, Ofloxasine을 이용한 경구 4제 요법의 임상 효과)

  • Hong, Jae-Rak;Yoo, Min-Kyu;Jeong, Jae-Man;Kim, Young-Jun;Son, Mal-Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.5
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    • pp.693-700
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    • 1996
  • Background : Antituberculous therapy is set a short-term therpy used isoniazid(INH), rifampin(RFP), ethambutol(EMB), pyrazinamide(PZA) from 1970s' and treatment rate has been very improved. But drug interruption or irregular medication due to side effects and resistance of drug are serious problem to retreatment cases, specially. Ofloxasine(OFX), developed from Quinolone at 1980's is effective not only other respiratory infectious disease but also pulmonary tube rculosis. And this is useful drug instead of injection agents for retreatment patients who have side effects to other drugs, lived far distance from medical clinics. So, we will evaluate theffectiveness as four oral drugs involving OFX. Method : A retrospective study was made through the regular follow up of smear positive cases,who treated by four drug, namely, prothionamide (PTA) cycloserine(CS), OFX, paraminosalicylic acid(pAS). Results: 1) Out of 66case with positive sputum AFB smear, 42(64%)cases achieved the negative conversion. 2) Considering the negative conversion in all group, 34 case (52%) of sputum conversion occured within first 6 months, on the extent of diease was minimal, moderate, far advanced pulmonary tuberculosis, sputum AFB smear negative response to treatment was 100%, 78%, 46% respectively. 3) The roentgenological improvement occured in 38(58%), extent of diease was minimal, moderately, far advanced pulmonary tuberculosis, Roentgenological improvement to retreatment was 75%, 64%, 46%. 4) When the drnation of patients illness was less than 1 year, 1 to 3 years, 3 10 5 years and more than 5 years, sputum AFB smear negative response to retreatment was 100%, 88%, 80%, 52 %. 5) On side effects, major problems are gastrointestinal troubles, mild liver function abnormality, psychotic problemes, and skin problem(urticaria, itching sensation). Conclusion : The duration & extents of patients illness was shorter & minimal, sputum AFB smear negative response rate was better. Radiologic response is better as shorter duration and minimal extent of diease. But, as diease is longer duration & far advanced, sputum negative conversion & Roentgenological improvement is poor and limited. The adverse reaction was mainly observed gastrointestinal troubles(indigestion, abdominal pain, nausea, vomiting, diarrhea) and are well controled by symptomatic management in most patients, as regard to tolerance to the secondary drugs.

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The Prevalence and Risk Factors of Drug Resistant Pulmonary Tuberculosis Investigated at One University Hospital in Seoul (서울지역 한 대학병원에서 조사된 폐결핵 약제 내성률 및 위험인자)

  • Kim, Do Kyun;Kim, Mi Ok;Kim, Tae-Hyung;Sohn, Jang Won;Yoon, Ho Joo;Shin, Dong Ho;Park, Sung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.3
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    • pp.243-247
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    • 2005
  • Background : The prevalence of tuberculosis is slowly decreasing in Korea. However, the drug-resistance of pulmonary tuberculosis is a major risk factor of treatment failure. Moreover, the National Surveillance System has recently been discontinued. Therefore, a continuous survey is necessary for the exact detection of the rate of drug resistance. We studied the recent 4-year drug resistance rate of tuberculosis at a single University hospital in Seoul. Materials and Methods : The study included 239 pulmonary tuberculosis patients performed with a tuberculosis culture and a drug-sensitivity test at Hanyang University Medical Center from March 1999 to March 2003. Results : Of the 239 patients included in the study during the 4-year period, 52 patients showed resistance to one or more anti-tuberculosis drug (21.8%). The rate of multi-drug resistance was 12.6%. The resistance rates to isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide were 18.4%, 13.8%, 11.7%, 6.7% and 8.4%, respectively. Ninety patients had a history of previous anti-tuberculosis treatment, and the rates of the overall drug resistance and multi-drug resistance of these patients were 36.7% and 25.6%, respectively. The patients with drug-resistance showed a higher rate of a previous tuberculosis treatment history (63.5%) than the drug-sensitive group patients (30.5%). Conclusion : The rate of drug resistant tuberculosis is 21.8%, and multi-drug resistant tuberculosis is 12.6%. The rate of drug resistance is higher in those previously treated for tuberculosis.

A Color-Reaction-Based Biochip Detection Assay for RIF and INH Resistance of Clinical Mycobacterial Specimens

  • Xue, Wenfei;Peng, Jingfu;Yu, Xiaoli;Zhang, Shulin;Zhou, Boping;Jiang, Danqing;Chen, Jianbo;Ding, Bingbing;Zhu, Bin;Li, Yao
    • 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.

Study on function evaluation tools for stroke patients (뇌졸중(腦卒中) 환자(患者)의 기능평가방법(機能評價方法)에 대(對)한 연구(硏究))

  • Ko, Seong-Gyu;Ko, Chang-Nam;Chox, Ki-Ho;Kim, Young-Suk;Bae, Hyung-Sup;Lee, Kyung-Sup
    • The Journal of Korean Medicine
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    • v.17 no.1 s.31
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    • pp.48-83
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    • 1996
  • Our conclusions for function evaluation tools of Stroke patients are as follows. 1. Evaluating tools of Activities of Daily Living, Katz Index, Barthel Index, Modified Barthel Index have high validity and reliability because of ease of measuring, high accuracy, consistency, sensitivity and sufficient stastistics, but they mainly measure motor function except sense, mentation, language, and social conception. Therefore cerebrovascular disease and brain injury in trauma patients with lacked acknowledgement and sensation, we are not able to apply these tools. 2. PULSES Profile is a useful scale for measuring the patient's over-all status, upper and lower limb functions, sensory components, excretary functions, and intellectual and emotional adaptabilities. It is recognized as a good, useful tool to evaluate patient's whole function. 3. Motor Assessment Scale was designed to measure the progress of stroke patients. The scale was supplemented with upper arm function items. We believe that the Motor Assessment Scale could be a useful evaluation tool with inter-rater reliability ,test-retest reliability. 4. The existing evaluation tools, Katz Index, Barthel Index, Modified Barthel Index, PULSES Profile, Motor Assessment Scale, mainly measured the rehabilitational motor function of sequela of cerebrovascular patients. On the other hand CNS & INH stroke scale can measure cerebrovascular disease patient's neurologic deficits and over-all stautus, which are recognition ability, speech status, motor function, sensory function, activities of daily living. Those scales have been recognized as useful tools to measure function of cerebrovascular disease patients and have increased in use. 5. Every function evaluation tool was recognized to have some validity and inter-rater, test-retest reliability in items of each evaluation tool and total scores of each evaluation tools, but it is thought that none of these scales have been fully validated and proved reliable. Therefore afterward, the development of a highly reliable rating system may best be accomplished by a careful comparison of several tools, using the same patients and the same observers in order to choose the most reliable items from each. 6. Ideal evaluation tools must have the following conditions; (1) It should show the objective functional statues at the same time. (2) It should be repeated consecutively to know changed function status. (3) It should be easy to observe the treatment program. (4) It should have the same result with another rater to help rater exchange information with treatment team members. (5) It should be practical and simple. (6) The patient should not suffer from the observer.

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A Clinical Effect of Retreatment by Prothionamide, Cycloserine, Para-Aminosalicylic Acid, Streptomycin (Kanamycin or Tuberactinomycin) on Pulmonary Tuberculosis (폐결핵 재치료의 Prothionamide, Cycloserine, Para-Aminosalicylic Acid, Streptomycin (Kanamycin or Tuberactinomycin) 4제 요법 임상 효과)

  • Shin, Cheol-Shick;Im, Young-Jae;Kim, Young-Jun;Koh, Seok-Shin;Kim, Moon-Shik
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.2
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    • pp.167-171
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    • 1992
  • Background:In the management of patients whose primary chemotherapy has failed, very careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Kongju Tuberculosis Hospital. Method: A retrospective study was made through the regular follow-up of 112 smear positive cases, who were treated by four-drug regimen between July 1985 and June 1990. Four drugs were, namely prothionamide, cycloserine, para-aminosalicylic acid, and streptomycin (kanamycin or tuber-actinomycin). The duration of follow-up was over one year. Results: 1) Out of 112 cases with positive sputum AFB smear, 72 (64%) achieved the negative conversion. 2) Among the 72 patients, 85% achieved negative conversion within 3 months after treatment. 3) When the duration of patient's illness was less than 2 years, 2 to 4 years and more than 5 years, the favourable response to retreatment was 86%, 62% and 54%, respectively. 4) When the number of sensitive drugs was 4,3,2 and 1, the favourable response rate was 74%, 68%, 39% and 0%, respectively. Conclusion: The shorter the duration of patient's illness was, the larger the number of sensitive drugs was. And the larger the number of sensitive drugs was, the better the result of treatment was. Thus it is very crucial to successfully treat newly discovered patients with adequate regimens and proper case-holding.

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Outcome of Chemotherapy with Pulmonary Tuberculosis Resistant to Isoniazid and Rifampin (다제내성 폐결핵의 화학치료)

  • Park, Seung-Kyu;Kwon, Eun-Soo;Ha, Hyun-Cheol;Hwang, Su-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.1
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    • pp.25-35
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    • 1999
  • Background : The treatment for multi-drug resistant tuberculosis(MDRTB) is encountered to be important clinically, but there are still a few reports about it all over the world. So, we evaluated the outcomes of only chemotherapy for the pulmonary MDRTB retrospectively. Method: We reviewed the clinical courses of 63 patients with pulmonary disease due to M.tuberculosis resistant to rifampin and isoniazid who were under follow-up between March 1996 and June 1996 after hospitalization at our hospital between January 1993 and January 1996. We performed cohort retrospective study for all these patient's records. Their regimens were selected individually and preferably included four medications that they had not been given previously and to which the strain was fully susceptible. Results: The 63 patients(mean age, 43.2 years) had previously received a median 5.1drugs. Fifty two(82.5%) patients responded to chemotherapy(as indicated by negative sputum cultures for at least three consecutive months) ; eleven patients(17.5 %) had no response, as shown by continually positive cultures. In a univariate analysis, an unfavorable response was significantly associated with greater number of resistant drugs before the current courses of therapy(relative risk 21.5 ; 95 percent confidence interval, 1.2-3.0; p<0.05). The mean period of follow-up was seventeen months. There was no relapse suooequently among the patients with responses. There was no death related to tuberculosis. Conclusion: In this report from National Masan Tuberculosis Hospital in Korea, multi-drug resistant pulmonary tuberculosis responded relatively well to carefully selected regimens.

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Pulmonary Resection Combined with Isoniazid-and Rifampin-based Drug Therapy for Patients with Multidrug-resistant Tuberculosis (다제내성 폐결핵 환자에서 폐절제술 후 일차 항결핵제 치료)

  • Park, Seung-Kyu;Kim, Jin-Hee;Kim, Jun-Ho
    • 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.

A Case Report of Three Patients with Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium kansasii (Mycobacterium kansasii에 의한 비결핵성 마이코박테리아 폐질환 3례)

  • Koh, Won Jung;Kwon, O Jung;Suh, Gee Young;Chung, Man Pyo;Kim, Hojoong;Lee, Nam Yong;Kim, Tae Sung;Lee, Kyung Soo;Park, Eun Mi;Park, Young Kil;Bai, Gill Han
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.459-466
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    • 2003
  • Mycobacterium kansasii is the second most common cause of nontuberculous mycobacterial pulmonary disease in Western countries and Japan. The clinical and radiological features of pulmonary disease caused by M. kansasii usually resemble those of pulmonary tuberculosis including cavitary infiltrates with an upper lobe predilection. It is also now apparent that patients with M. kansasii pulmonary disease can present with noncavitary nodular bronchiectatic infiltrates similar to lung diseases of M. avium complex. With rifampin-containing regimens, treatment success rates are almost 100%. Timely diagnosis before the development of extensive disease and effective overall treatment strategies are very important to ensure that patients receive the appropriate medications for a sufficiently long period of time. To our knowledge, there has been no Korean case report of M. kansasii pulmonary disease in the immunocompetent patient until now. We report three cases of M. kansasii pulmonary disease in immunocompetent adult patients.

The Analysis of Risk Factors of Pulmonary Tuberculosis Patients Failed in Retreatment (재치료실패 폐결핵 환자의 위험인자 분석)

  • Kim, Hyoung-Soo;Lee, Won-Jin;Kong, Seok-Jun;Shon, Mal-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.684-690
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    • 2000
  • Background : The most common cause of treatment failure of pulmonary tuberculosis is early stoppage of treatment or irregular medication. The most important aspect of a retreatment is regular medication provided over a long period. Inadequate treatment may cause drug resistance and prolong the duration of chemotherapy. This study analyzed the risk factors of pulmonary tuberculosis patients, who failed in retreatment, and to use the results as basic data in the management of intractable tuberculosis patients with improving the rate of retreatment success. Methods : We performed a retroactive study of 62 pulmonary tuberculosis patients in retreatment at National Mokpo Tuberculosis Hospital from Jan. 1994 to Dec. 1995. The patients were separated into two groups: group I was retreatment failure and group II was retreatrnent success. For the analysis of risk factors in retreatment failure, we compared the difference between the two groups and tested the confidence limit about results of the results by independent t-test, ${\chi}^2$ test and Fisher's exact test. Results : The treatment failure rate of retreatment patients was 13(21%), and treatment success 49(79%). No significant difference (p>0.05)in age, sex, number of treatment, irregular rate of treatment, extent of the disease & cavitary lesion on the chest X-ray, number of resistance drugs, number of used drugs to medication, number of sensitive bactericidal drugs to medication, rate of sensitive drugs to medication and resisiance to INH & RFP had not significant difference. was found. However, the number of treatment was $2.4{\pm}0.8$ in group I and $1.6{\pm}0.9$ in group II, and had showing a significant difference(p<0.05) between the two groups. Conclusion : The risk factor of retreatment failure was more irregular previous treatment the irregularity of the previous treatment. For reducing the retreatment failure of pulmonary tuberculosis, greater efforts are needed more need to be done to prevent failure of first treatment.

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Analysis of rpoB Gene in Rifampin-Resistant M. Tuberculosis by Direct Sequencing and Line Probe Assay (염기서열결정과 Line Probe 분석법에 의한 Rifampin내성 결핵균의 rpoB 유전자 분석)

  • Lee, Min-Ki;Kim, Yun-Seong;Lee, Hyo-Jin;Cheon, Du-Su;Yun, Sang-Myung;Park, Sam-Seok;Kim, Cheol-Min;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.251-263
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    • 1997
  • Background : The emergence of multidrug-resistant strains of Mycobacterium tuberculosis presents a significant challange to the treatment and control of tuberculosis, and there is an urgent need to understand the mechanisms by which strains acquire multidrug resistance. Recent advances in molecular methods for the detection of M. tuberculosis genetic targets have approached the sensitivity of culture. Furthermore the prospect of determining resistance in mycobacteria at the nucleic acid level particulary to first-line drugs like rifampin, isoniazid has provided a glimps of the next generation of sensitivity test for M. tuberculosis. Previous studies in RMP resistant M. tuberculosis have shown that mutation in $\beta$subunit of RNA polymerase is main mechanism of resistance. Method : In this study, rpoB gene for the $\beta$subunit of RNA polymerase from M. tuberculosis of 42 cultured samples (32 were RMP resistant and 10 were sensitive cases) were isolated and characterised the mutations. Direct sequencing data were compared with the results of INNO-LiPA Line Probe Assay (LiPA, Innogenetics, Belgium), commercial RMP resistance detecting kit using reverse hybridization method. Results : All of the RMP resistant samples were revealed the presence of mutation by LiPA. In 22 samples (68.8%) out of 32 RMP resistant cases, the mutation types were confirmed by the positive signal at one of 4 mutation bands in the strip. The most frequent type was R5 (S531L) which were 17 cases (77.3%). Results of direct sequencing were identified the exact characteristics of 8 mutations which were not confirmed by LiPA. S522W type point mutation and 9 base pair deletion at codon 513~515 were new identified mutations for the first time. Conclusion : Mutations in rpoB gene is the main mechanism of RMP resistance in M. tuberculosis and LiPA is a very useful diagnostic tool for the early diagnosis of RMP resistance in M. tuberculosis.

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