• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.404-409
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• 1993

Background: There are many retreatment failure patients admitted in National Kongju Tuberculosis Hospital. But there is not satisfactory treatment method for them at present. We think that more attentions and active measures for them are needed. Method: We reviewed sex and age, duration of illness, previously used antituberculosis drugs, drug resistance, extent of disease, reasons for early stopping or irregular medication and schooling of 50 retreatment failure patients admitted in National Kongju Tuberculosis Hospital from April 1992 to February 1993. Results: 1) The male to female ratio was 3:2 and 62% of the patients were between 21 and 40 years of age. 2) Twenty eight cases (56%) had the duration of illness over 10 years. 3) All cases had used most of the antituberculosis drugs. 4) Drug sensitivity test showed resistance to RMP in 46 cases (96%), INH in 40 cases (83%) and other drugs in 3-32 cases (6-67%). 5) Forty eight cases (96%) had far advanced disease on chest P-A film. 6) Twenty eight cases (56%) in primary chemotherapy and twenty one cases (42%) in retreatment had the histories of premature stopping or irregular ingestion of the drug. The reasons for premature stopping or irregular ingestion of the drug were as follows; in primary chemotherapy, 29 cases (75%) were due to 'having no symptoms', while in retreatment, 6 cases (29%) were due to 'having no symtoms', 6 cases (29%) were 'too, busy' and 3 cases (14%) were for 'financial problem'. 7) Twenty seven cases (54%) had at least graduated from high school. Conclusion: Greater efforts are needed to prevent tratment failure. More supports and admission treatment for retreatment failure patients are needed to prevent infection and to treat properly.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.311-316
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• 1999

Background: The drug-resistant tuberculosis has recently decreased in Korea, but it is still one of the major obstacles in the treatment of pulmonary tuberculosis. Unfortunately there are no reliable ways to figure out the drug sensitivity pattern of the M. tuberculosis in the starting point of treatment. At least several months which is critical for the success of treatment have to be passed away before getting the report of drug-sensitivity test. The aim of this study was to find out the clinical and radiological parameters that make it possible to predict the drug-resistant pulmonary tuberculosis and to make a correct decision on the antituberculosis drug regimens. Method: We studied 253 pulmonary TB patients with sputum and/or bronchial washing fluid culture-positive diagnosed at the Chung-Ang University Young-San Hospital in the period of 1989-1994. The differences in the clinical and raiological variables between the drug-sensitive and the drug-resistant tuberculosis patients were evaluated. Results: In 66 out of 253 patients(26.1%), drug resistant tuberculosis to at least one antituberculosis drug were found. Patients with retreatment showed higher resistance rate than those with initial treatment(30/69, 43.5% vs 36/184, 19.5%, p<0.01). Patients with cavitary TB showed higher resistance rate than those with non-cavitary TB(24/54, 44.4% vs 42/199, 21.1%, p<0.05). Among patients with initial treatment, those with far-advanced TB showed a higher drug resistance rate than those with minimal lesion(9/23, 36.9% vs 10/82, 12.5%, p<0.05). Patients with culture positive only in the bronchial washing fluid showed lower resistance rate than those with sputum culture positive(7/63, 11.1 % vs 59/190, 31.1%, p<0.05). Conclusion: Prior treatment history for pulmonary tuberculosis, the presence of cavity & far advanced tuberculosis in the radiologic exam, sputum rather than solely bronchial washing culture positivity would be the related factors to the drug resistance. So in the patients with such characteristics, it is needed to try to find out the drug sensitivity pattern of the infecting tuberculosis organism as soon as possible.

• YAKHAK HOEJI
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• v.55 no.4
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• pp.352-360
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• 2011

Standard combination chemotherapy including isoniazid, rifampin, pyrazinamide, and ethambutol is very effective against tuberculosis. But, these medicines can cause hepatotoxicity which is the main reason for treatment interruption or change in drug regimen. In order to identify risk factors associated with hepatotoxcity in Koreans and assess elevated baseline LFTs' contributions to hepatotoxicity, a retrospective case control study was performed. The medical records of 277 patients who diagnosed with tuberculosis at a community hospital from January 1st, 2007 to June 30th, 2010 were reviewed. Patients were categorized into 3 groups (non toxic group, patients without increase in LFT levels; mild to moderate hepatotoxic group and severe hepatotoxic group). And the correlation between risk factors and hepatotoxicity was analyzed by using SPSS program. The overall incidence of hepatotoxicity was 18% and 8.7% of patients developed severe toxicity. Patients in the severe toxic group had the longest treatment period among the three groups. In 75% of severe toxic group, hepatotoxicity occurred within 18.3 days after starting medication. Hypoalbuminemia (serum albumin <3 g/dl) was a significant risk factor for development of severe toxicity. Elevated baseline transaminase (except ALT), total bilirubin, and preexisting hepatitis were also risk factors which were more than twice as likely to increase risk of severe hepatotoxicity (p>0.05). In conclusion, hypoalbuminemia (serum albumin level <3 g/dl) was a significant risk factor for anti-tuberculosis druginduced severe toxicity. Therefore, before starting antituberculosis chemotherapy, serum albumin level should be assessed at baseline. In high-risk patients (hypoalbuminemia, elevated LFTs) for hepatotoxicty, liver function should be closely monitored up to at least 21 days after taking medication.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.725-729
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• 1993

A case of cavitary pulmonary tuberculosis with persistent positive bacilli due to resistant strain was treated successfully with artificial pneumothorax with antituberculosis chemotherapy. Negative conversion of Tubercle bacilli was noticed by four months on sputum smears and by 11 months on sputum cultures after the starting of artificial pneumothorax. The cavitary lesion was collapsed by 13 months. Artificial pneumothorax is one of the collapse therapies of pulmonary tuberculosis which had been used widely in the early 20th century before the era of antituberculosis chemotherapy. Nowadays, this method is almost neglected due to its inferiority in efficacy as compared to chemotherapy and complications. But we recommend considering this method when no other measure is likely to be useful in open cavitary lesion.

• Tuberculosis and Respiratory Diseases
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• v.38 no.2
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• pp.93-98
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• 1991

A clinical trial was made on 76 patients with pulmonary tuberculosis to determine the effectiveness and acceptibility of 6 month 2SHRZ/4HR antituberculosis regimen. Out of 76 patients, 13 patients (17.1%) dropped out and 11 patients (14.5%) were excluded due to drug resistance. In 3 patients (3.9%), regimen was changed due to adverse effects. Treatment failure rate was 2.0% in 50 patients. One patient, who had far advanced lesion, was treated longer than 6 months due to failure of sputum conversion. The most common adverse effect was arthralgia, which was controlled by the administration of allopurinol and nonsteroidal anti-inflammatory drug. In conclusion, 2SHRZ/4HR for 6 months was effective regimen in treating the newly-diagnosed patients with tuberculosis, but change of the regimen and duration might be carefully considered by the severity of the lesion and adverse effect of the drug But further study will be needed to evaluate not only the efficacy and efficiency of 6 month chemotherapy but also relapse rates.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.261-268
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• 2004

Background : The resurgence of tuberculosis and outbreaks of multidrug resistant (MDR) tuberculosis have increased the emphasis for the development of new susceptibility testing of the Mycobacterium tuberculosis for the effective treatment and control of the disease. Conventional drug susceptibility testings, such as those using egg-based or agar-based media have some limits, such as the time required and difficulties in determining critical inhibitory concentrations, but these are still being used in many diagnostic laboratories because of no better lternatives, considering cost and accuracy. To overcome these limits, a rapid and simple method for new susceptibility testing, using live and dead assays, was applied for a bacterial cell viability assay to distinguish dead from live bacterial cells based on two-color fluorescence. Materials and Methods Strains : Forty strains were used in this study, 20 susceptible to all antituberculosis drugs and the other 20 resistant to the four first line antituberculosis drugs isoniazid, rifampicin, streptomycin and ethambutol. Antibiotics : The four antibiotics were dissolved in 7H9 broth to make the following solutions: $0.1{\mu}g\;isoniazid(INH)/m{\ell}$, $0.4{\mu}g\;rifampicin(RMP)/m{\ell}$, $4.0{\mu}g\;streptomycin(SM)/m{\ell}$ and $4.0{\mu}g\;ethambutol(EMB)/m{\ell}$. Results : Live and dead Mycobacterium tuberculosis cells fluoresced green and red with the acridin (Syto 9) and propidium treatments, respectively. These results are very well accorded with conventional drug susceptibility testing by proportional method on Lowensen-Jensen media (L-J) containing 4 drugs (INH, RMP, EMB and SM), showing a 93.7 % accordance rate in susceptible strains and 95% in resistant strains. Conclusion : The results of the drug susceptibility testing using the live and dead bacterial cell assay showed high accordance rates compared with the conventional proportion method on L-J. This finding suggests that the live and dead bacterial cell assay can be used as an alternative to conventional drug susceptibility testing for M. tuberculosis strains.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.182-185
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• 2005

We used the IS1096 transposon to construct Mycobacterium bovis BCG mutants resistant to an antituberculosis drug PA-824 and isolated several different mutants. We identified the locations of the insertions and found that the insertions were at various sites including the genes for the PPE proteins. HPLC analyses of the extracts of these five PPE mutant cells showed that three mutants produced only F0, and intermediate for the synthetic pathway of coenzyme $F^{420}$, and the remaining two neither F0 nor $F^{420}$. These data suggest that the products of these PPE genes are somehow involved in the biosynthesis of the coenzyme $F^{420}$.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.412-420
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• 2000

Background : There is increasing concern in many countries about the problem of drug-resistant tuberculosis. Prevalence of primary drug-resistant tuberculosis is the optimal epidemiological indicator for long term monitoring of national tuberculosis control program. Our purpose was The purpose of our study is to assess clinical characteristics and socioeconomic status of patients with drug-resistant tuberculosis. Method : We studied 68 cases with drug-resistant Mycobacterium tuberculosis infection diagnosed at the Ewha Womans University Mokdong Hospital from March, 1995 to February, 2000. Results : Patients with primary drug-resistant tuberculosis(PDR) were younger (39.6$\pm$16.3 years vs. 48.2$\pm$16.5 years ; p<0.05), had more population of less than more were under the age of 40 years aged -group(62.9% vs. 36.4% ; p<0.05) and were more highly educated than those with acquired drug-resistant tuberculosis(ADR)(38.9% vs. 11.1% ; p<0.05). In patients with ADR, the rates of familial history of tuberculosis and living in a rented house residence in a rented house were increased higher than compared with to those of patients with PDR. Patients with ADR had more involved lobes(2.0$\pm$0.8 vs. 1.4$\pm$0.7 ; p<0.01) and longer treatment duration than those with PDR(18.3$\pm$7.2 months vs. 10.6$\pm$6.3 months ; p<0.05). Patients with ADR showed larger numbers of resistant were resistant to more number of drugs, lower hospitalization rate and higher rate of self-interruption of medication than those with PDR. In patients with PDR, mono-drug resistance was increased, whereas poly- and multi-drug resistances were decreased compared with those with ADR. Resistance to isoniazid was the highest among antituberculosis drugs, and resistance to isoniazid in patients with ADR was higher than that in patients with PDR(90.9% vs. 71.4% ; p<0.05). Conclusions : Patients with ADR were more likely to include more population be of lower socioeconomic class, and patients with PDR seem seemed to be young and socially active population. For control of drug-resistant Mycobacterium tuberculosis infection, proper isolation and prevention of patient with drug-resistant tuberculosis are needed.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.29-41
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• 2001

Background : The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. Methods : In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. Results : Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. Conlcusion : An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drugsusceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.173-181
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• 1998

Rifampin is common drug to treat tuberculosis. Rifampin induced acute renal failure, hemolytic anemia and thrombocytopenia is rare and severe complication. We have experienced a case of rifampin induced acute renal failure, hemolytic anemia and thrombocytopenia. Forty-six years old male was suffered from reactivation of pulmonary tuberculosis, and had to medicate antituberculosis drugs including rifampin(600mg/day). Seven years ago, antituberdulosis medication were successfully administered to treat pulmonary tuberculosis without any side effects of drugs. But eight days after readministration of rifampin, fever, abdominal pain, vomiting, oliguria, elevated BUN and creatinine were developed. And thrombocytopenia was also identified after administration of rifampin. The patient was recovered slowly after discontinuation of rifampin & intensive medical care. The renal function was normalized at 55 days after cessation of rifampin. The renal pathologic findings were interstitial nephritis and acute tubular necrosis. And, the rifampin dependent antibodies were identified by indirect antiglobulin test in the presence of rifampin. So we report this case with a brief review of literature.