• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.367-372
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• 2001

Bacillus Calmette-Guerin(BCG) has been widely used for the prophylaxis of superficial bladder tumor recurrence and for the treatment of bladder carcinoma in situ. More than 95% of patients who receive BCG instillation tolerate the treatment well and side reactions have been reported in less than 5% of patients. Most side effects are minor and self-limiting. However, a rare occurrence of severe systemic reactions have been reported. Among the severe systemic reactions, hypersensitivity pneumonitis should be considered in patients with pneumonic complications after BCG instillation in cases where the culture for mycobacteria is negative in the sputwn, brochoalveolar lavage and blood specimen. In addition, a fiberoptic bronchoscopy with transbronchial lung biopsy demonstrates a fibrosis of the alveolar septums, where there is and an increased lymphocyte count with out tuberculous inflammatory changes, the and CD4 : CD8 ratio is increased and no symptomatic response to antituberculosis chemotherapy is observed. Here we report a 68 years old man with interstitial pneumonitis following intravesical BCG instillation.

• 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.

• 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 $F^{420}$.

• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.947-952
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• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• 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.

• Journal of Chest Surgery
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• v.35 no.11
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• pp.799-806
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• 2002

In spite of the establishment of chemotherapy and the gradual decrease in prevalence, pulmonary tuberculosis is still mainly treated with an operation. Through analyzing and examining some cases of surgical treatment, we hope to provide some help in treating of pulmonary tuberculosis in the future. Material and Method: By comparing four journals previously published in our department with 144 cases of lung surgery during ten years from January of 1991 to December of 2000 performed by the department of thoracic and cardiovascular surgery of the National Medical Center, we analyzed and reviewed the most recent trends and the results of the surgical treatment. Annual frequency of the operation, distribution of age, examination of sputum, adaptability and types of techniques, complications, and results of the postoperative follow-up were used as methods. Result: It was found that the annual frequency of operations had decreased. The ratio of men to women, 2:1 indicates that there are more incidences in men. Aging of patients could be speculated by the .results that the decrease in the incidence rate in the 20s age range and increase rate in the 50s age range. The range of preoperative lesions belonged mostly to far advanced and moderately advanced tuberculosis. By monitoring the period of use in preoperative antituberculosis drugs, cases for more than 3 years remarkably increased from 16.0 % to 55.6 %. The positive reactive rate for preoperative sputum examinations were drastically decreased from 91 % to 27 %. Total pulmonary destruction and partial destruction were the most common cases in terms of adaptability to the operations and there were significant increases in forming empyema accompanied by parenchymal lesions from 4.0 % to 20.1 %. Pneumonectomy and pulmonary lobectomy were the major type of operations. Especially, there were increases in the incident rate of empyema and recurrence of tuberculosis resulted. Post operative follow-up indicates that the rate of complete recovery was more than 70 % and the rate of gradual increase in treating with persistent antituberculosis drug was from 5.8 % to 18.0 %. Conclusion: In recent cases, there is an increasing number of patients showing tolerance to chemotherapy. Patients with pleural tuberculosis and severe lesions were typically increased. It is important to accurately analyze those complaints accurately that are mostly difficult to be treated medically. Surgical treatment is strongly recommended Before multiple drug resistance occurs.

• Tuberculosis and Respiratory Diseases
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• v.40 no.5
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• pp.509-518
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• 1993

Background: By amplifying small amount of DNA, polymerase chain reaction (PCR) can be used for the detection of very small amount of microbial agent, and may be especially useful in certain cases which are difficult to be diagnosed microbiologically or serologically. Tuberculous pleurisy is a disease that can be diagnosed in only 70% of cases by conventional diagnostic tools, and PCR would be a very rapid, easy, and sensitive diagnostic method. Method: The specificity and sensitivity of PCR to detect Mycobacterium tuberculosis DNA were evaluated using various strains of Mycobacteria. To evaluate the diagnostic usefulness of PCR in tuberculous pleurisy, we used PCR to detect Mycobacterium tuberculosis DNA in pleural fluid. The amplification target was 123 base pair DNA, a part of IS6110 fragment, 10~16 copies of which are known to exist per genome. The diagnostic yield of PCR was compared with conventional methods, including pleural fluid adenosine deaminase (ADA) activity. Also, the significance of PCR in undiagnosed pleural effusion was evaluated prospectively with antituberculosis treatment. Results: 1) Using cultured Mycobacterium tuberculosis and other strains, PCR could detect upto 1 fg DNA and specific for only Mycobacterium tuberculosis and Mycobacterium bovis. 2) Using pleural effusions of proven tuberculosis cases, the sensitivity of PCR was 80.0% (16/20), and the specificity 95.0% (19/20). 3) Among 13 undiagnosed, but suspected tuberculous effusion, the positive rate was 60% in 10 improved cases after antituberculosis medications, and 0% in 3 cases of proven malignancy later. 4) Adenosine deaminase level of proven and clinically diagnosed tuberculous pleurisy patients was significantly higher than that of excluded patients, and correlated well with PCR results. Conclusion: We can conclude that PCR detection of Mycobacterium tuberculosis in pleural effusion has acceptable sensitivity and specificity, and could be an additional diagnostic tool for the diagnosis of tuberculous pleurisy.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.323-330
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• 1996

Objective : Cavitary lesion in pulmonary tuberculosis sometimes makes problems in the course of treatment. Especially, retreatment cases tend to respond poorly to current antituberculosis agents. So, authors tried to render a guideline for clinical approach toward cavitary lesions in pulmonary tuberculosis. Methods : Retrospective analysis of 33 pulmonary tuberculosis patients with cavitary lesions was made. All the patients had got treatment at National Masan Tuberculosis Hospital from Jan. 1995 to Aug. 1995. Results: The ratio between male and female was 10:1. Age distribution was 69.7% in 3rd and 4th decades. The locations of cavitary lesion were 60.6% in right upper lung field and 36.4% in left upper lung field. In the extent of disease, there were 12 cases(36.4%) in moderate advanced and 21 cases in far advanced. Cavitary lesions were closed in 5 eases and remained in 28 eases. In the cases of closed cavity, it was happened within $10.6{\pm}4.72$ months after they took treatment, the size of cavity was $35.5{\pm}17.1$ in long diameter, $27.0{\pm}12.2$ in short diameter and $4.6{\pm}2.1\;mm$ in wall thickness. In the cases of remained cavity, the size of cavity was $31.9{\pm}12.3$ in long diameter, $21.0{\pm}9.8$ in short diameter and $5.04{\pm}2.0\;mm$ in wall thickness. In terms of negative conversion, it took $3.8{\pm}2.17$ months in the case of closed cavity but it was happened within 5 months for only 4 patients in the case of remained cavity. In the point of past medication history, there was none in closed cavities but there were none in 1 case, once in 3 cases, two times in 9 cases and more than three times in 13 cases among remained cavitary lesions. Conclusion : In the retreatment cases of pulmonary tuberculosis with cavitary lesions, they tend to respond poorly to current antituberculosis agents. So, if the lesions are localized, operative intervention may be a proper method as adjunctive treatment.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.852-861
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• 1996

Background : Many clinicians have experienced the difficulty of decision on termination of antituberculosis chemotherapy after the 6th month due to relapse of disease. There is still controversy in the effect of 2S(K)HRZ/4HRZ 6-month short course chemotherapy including pyrazinamide for 6 months in patiems with pulmonary tuberculosis. And there is no long term follow-up study of 6-month short course chemotherapy for pulmonary tuberculosis in korea. So we had performed the study to find the result of 6-month antituberculosis chemotherapy for 4 years. Method : We studied prospectively the effect of 2S(K)HRZ/4HRZ in one hundred-fifty patients with pulmonary tuberculosis and followed up fifty-nine patients for more than 1 year to 4 years after the completion of 6-month short course therapy. Results : 1) Out of one hundred-fifty patients, seventy-two patients(48%) completed the prescribed 6-month chemotherapy. Sixty-eight patients(45.3%) have experienced premature discontinuation and the most common cause of premature discontinuation was drop-out against advice(thirty-six patients, 24%). Ten patients(6.7%) were treated beyond the 6 months mainly due to irregular treatment. 2) Fifty-nine patients(81.9%) among seventy-two patients with completed treatment have been followed up for more than 1 year and 32 patients(44.4%) for more than 4 years. There was three relapse patients of whom two patients have experienced relapse of pulmonary tuberculosis within 1 year after the termination of chemotherapy. 3) Among one hundred-thirty-four patients who have been assessible for more than two months of chemotherapy, including the patients who experienced within 2 months, there were eighty-two patients(61.2%) who have experienced adverse reactions and the treatment regimen was changed only in thirteen patients(9.7%). The most frequent cause of adverse reactions was arthralgia and/or hyperuricemia, which had occurred in 33 patients(24.6%). Conclusion : In a university hospital in Korea, 6-month shot course chemotherapy of 2S(K)HRZ/4HRZ had unnegligible relapses and premature discontinuation. Therefore, change of the regimen might be carefully considered by drug susceptibility results. Close monitoring of patients, retrial of sputum exam and radiologic evaluation during treatment might be required in the endemic area of drug resistant strains like in Korea. Further study about the effect of 6-month short course chemotherapy including pyrazinamide for 6-month might be needed.