• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1245-1255
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• 1997

Background : Rifampicin(RFP) is a key component of the antituberculous short-course chemotherapy and the RFP resistance is a marker of multi-drug resistant(MDR) tuberculosis. RPoB gene encodes the $\beta$-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. And rpoB gene mutations are the cause of RFP resistance of M. tuberculosis. Although several reports showed that PCR-SSCP would be a rapid diagnostic method for identifying the RFP resistance, there were few reports Performed using direct, clinical specimens. So we Performed PCR-SSCP analysis of rpoB gene of M. tuberculosis in direct, clinical specimens. Methods : 75 clinical specimens were collected from patients at Asan Medical Center from June to August 1996. After PCR of IS 6110 fragments, 43 both AFB smear-positive and IS6110 fragment PCR-positive specimens were evaluated. The RFP susceptibility test was referred to the referral laboratory of the Korean Tuberculosis Institute. DNA was extracted by bead beater method. And heminested PCR was done using 0.1ul(1uCi) [$\alpha-^{32}P$]-dCTP. SSCP analysis was done using non-denaturating MDE gel electrophoresis. Results : The results of PCR of IS6110 fragments of M. tuberculosis were positive in 55(73%) cases of 75 AFB smear-positive clinical specimens. Of the 55 specimens, RFP susceptibility was confirmed in only 43 specimens. Of the 43 AFB smear-positive and IS6110 fragment-positive specimens, 29 were RFP susceptible and 14 were RFP resistant. All the RFP susceptible 29 strains showed the same mobility compared with that of RFP sensitive H37Rv in SSCP analysis of ropB gene. And all the other RFP resistant 13 strains showed the different mobility. In other words they showed 100% identical results between PCR-SSCP analysis and traditional susceptibility test. Conclusion : The PCR-sseP analysis of rpoB gene in direct clinical specimens could be used as a rapid diagnostic method for detecting RFP resistant M. tuberculosis.

• Investigative Magnetic Resonance Imaging
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• v.17 no.1
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• pp.1-7
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• 2013

Purpose : The purpose of this study is to correlate the imaging findings and the clinical findings in patients with transient splenial lesions (TSL). Materials and Methods: Total of 7 patients (M: F = 4: 3; age range 11 - 38 years, mean age 25.5 years) were studied between November 2006 and April 2011. The MRI findings and clinical findings in all patients were retrospectively reviewed. The location, MR signal intensity, restricted diffusion, enhancement pattern and reversibility from the follow up images were reviewed. Clinical features were reviewed with respect to the presented symptoms, signs, treatment and outcome. Results: The lesions were located in the splenium of corpus callosum in all patients. All lesions showed high signal intensity on diffusion weighted imaging (DWI), and six patients showed restricted diffusion on the apparent diffusion coefficient (ADC) map. ADC map was not available in one patient. All lesions (n = 7) showed high signal intensity on the T2 weighted image (T2WI). Five of the patients (71.4%) with follow up images (range 7 - 34 days) showed complete resolution of focal high signal intensity on DWI, with recovery of ADC values as well as T2WI. After contrast media administration, none of the lesions showed any enhancements. All lesions with various etiologies including TB medication were developed in younger age patients and showed reversibility after the acceptable period of minimum 7 days with conservative treatment. Conclusion: All TSL showed nonspecific imaging findings, including restricted diffusion on DWI and ADC map on the initial images. However, reversibility of the lesions and the young age preference can be a characteristic finding of TSL with acceptable period of minimum 7 days. In addition, to keep it in mind that various etiologies including TB medication may cause TSL, is important for radiologists as well as clinicians.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.144-151
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• 1994

Background: Miliary tuberculosis almost always results from the discharge of infected caseous material into the blood stream, usually from a well hidden lymph node in the presentation of this disease in the past four decades, and although it is seen less frequent1y today than previously, its presentation and manifestation may require greater suspicion and diligence by the physician. We investigated the clinical characteristics, predisposing factors and accompanying diseases of miliary tuberculosis and tried to acquire the early diagnosis and treatment of this disease. Methods: A retrospective clinical study was done on 40 cases of miliary tuberculosis admitted to Hanyang University Hospital from Mar. 1989 to Dec.1992. The study investigated age and sex distribution, seasonal distribution, duration of symptoms before admission, pre-disposing factors, clinical symptoms, biochemical findings, chest X-ray findings, extrapulmonary tuberculosis associated with miliary tuberculosis, prognosis and mortality rate. Results: 1) The patients were most common in the age group between 20 and 29(23%) and the ratio of male to female was 1.4:1(male 23 : female 17). 2) Sputum smears for tubercle bacilli were positive in 5 cases(13%). 3) The most common clinical symptoms were fever with chilling(47.5%), coughing(47.5%), second most common symptom was dyspnea(32.5%), and the physical findings on admission were tachycardia(30%), weight loss(27.5%), meningeal signs(17.5%) in order. 4) The predisposing factors were heavy alcohol drinking(6 cases), steroid use(3 cases), pregnancy(2 cases) etc. 5) The chest X-ray findings on admission were miliary shadow only(40%), in addition pneumonic infiltration, pleurisy, and calcification in order. 6) The extrapulmonary tuberculosis associated with miliary tuberculosis were tuberculous meningitis(30%), bone and joint tuberculosis(17.5%), intestinal tuberculosis(15%) in order. 7) Biochemical findings were increased SGOT/SGPT(32.5%), increased alkaline phosphatase(32.5%), hypoalbuminemia(15%), hyponatremia(15%) etc. 8) About 4-6 weeks later after treatment(INH, RFP, PZA, EMB), 26 cases(65%) were improved on clinical symptoms or chest X-ray, 12 cases(30%) were stationary or aggravated, and 2 cases(5%) were died. Conclusion: For the early diagnosis and treatment of miliary tuberculosis, we must see its presentation and manifestation with greater interest and suspicion and investigate its predisposing factors and accompanying diseases.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.870-878
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• 2000

Background : We have studied the $^{67}Ga$ SPECT to determine the activity of pulmonary tuberculosis, especially in patients with minimal extent of the disease on chest radiographs. Because active minimal pulmonary tuberculosis is sometimes difficult to diagnose by means of initial chest X-ray, sputum examination and $^{67}Ga$ planar imaging, we compared $^{67}Ga$ planar imaging with SPECT to evaluate minimal pulmonary tuberculosis activity. Methods : $^{67}Ga$ planar imagings and SPECTs of 69 patients suspected of minimal pulmonary tuberculosis by the initial chest X-ray were performed and compared to each other. Active pulmonary tuberculosis was defined by a positive AFB smear and/or culture in the sputum and changes shown on the serial chest X-ray findings. Results : 1) $^{67}Ga$ planar imaging imagings showed positive uptakes in 24 patients and no uptakes in 13 patients, patients, which confirms active pulmonary tuberculosis. But SPECT imagings showed positive uptakes in 25 patients and no uptakes in 12 patients. 2) Patients confirmed with inactive pulmonary tuberculosis showed no uptake on $^{67}Ga$ planar imaging. Only one of the 32 patients confirmed as having inactive pulmonary tuberculosis showed positive uptake on $^{67}Ga$ SPECT imaging. Conclusions : According to the results of our study, $^{67}Ga$ planar imaging and SPECT are both sensitive in detecting the activity of minimal pulmonary tuberculosis. The difference between the two methods is not statistically significant, and the negative predictive value of the $^{67}Ga$ SPECT is not higher than that of $^{67}Ga$ planar imaging.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.842-851
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• 1996

Background : Rifampicin(RFP) is a key component of the antituberculous shon-course chemotherapy and the RFP-resistance is a marker of multi-drug resistant(MDR) M. tuberculosis. rpoB gene encodes the ${\beta}$-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. Recent reports show that rpoB gene mutations are the cause of RFP resistance of M. tuberculosis and the main mechanism of rpoB gene mutation is point mutation. And PCR-SSCP is a rapid and easy method for detecting point mutations. So we performed PCR-SSCP of rpoB gene of M. tuberculosis and compared the result with traditional RFP sensitivity test. Method : The 27 RFP sensitive M. tuberculosis culture isolates and 25 RFP resistant isolates were evaluated. The RFP sensitivity test was done at the Korean Tuberculosis istitute. The DNA was extracted by bead beater method and was amplified with primers TR-8 and TR-9 in a 20ul PCR reaction containing 0.1ul(luCi) [${\alpha}-^{32}P$] - dCTP. After amplification, SSCP was done using non-denaturaring polyacrylamide gel electrophoresis. Then direct sequencing was done in cases of different eletrophoretic mobility compared with that of H37Rv. In 19 cases, we compared PCR-SSCP results with patient's clinical course and the results of traditional RFP sensitivity test. Results : 1) All 27 RFP sensitive M. tuberculosis isolates showed the same electrophoretic mobility compared with that of H37Rv. And all 25 RFP resistant M. tuberculosis isolates showed different electrophoretic mobility. 2) The mechanism of rpoB gene mutation of M. tuberculosis is mainly point mutation. 3) The PCR-SSCP results correlate well with traditional RFP sensitivity and patient's clinical response to antituberculous treatment. Conclusion: The PCR-SSCP of rpoB gene is a very sensitive and rapid mehod in detecting RFP- resistant M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.14-21
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• 1996

Objectives: Although outbreak of MDR Tb has been a recent problem in western countries, it has been a longstanding problem in Korea. The poor outcome of MDR Tb is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. Thus, to improve the outcome of MDR Tb, it is crucial to make individualized adequate prescription based on the knowledge of the patterns of resistance to each drugs in the community as well as the natural history. The purpose of present study is to evaluate the clinical features of Korean MDR Tb patients including patterns of drug resistance and success rate of treatment which was prescribed according to the sensitivity tests. Methods: Retroscpective analysis of 71 Korean patients with MDR Tb was made. All strains isolated from patients showed resistence to at least two first line drugs. Patients profile, previous treatment history, patterns of drug resistance, outcome of treatment was analysed. Initial treatment regimen was selected according to the previous treatment history and was modified according to the sensitivity reports. The regimen was composed to include at least 4 sensitive drugs when possible. Results: The patients showed resistance to 4.1 drugs on average. 90% of them were resistant to INH and RFP. Among 71 patients, 35 patients(49%) had cavitary lesions in CXR. Treatment outcome was analysed in 55 patients. 35 patients(67%) were improved after treatment and 18 patients(33%) showed treatment failure. 5 patients showed primary resistance. Treatment outcome could be evaluated in 4 of them and all showed improvement after treatment. 14 patients(20%) had to change their regimens due to drug side effects. The most frequent side effect was elevation of liver enzymes(6 patients). Others included dizziness, hyperuricemia, tinnitus, skin rash, GI troubles. More than 50% of side effects developed within 3 months. In repeated drug sensitivity test, the concordance rate of resistance to INH was 100% and RFP 98%. EMB, PZA showed 80% concordance rate. But in the other drugs, the concordances were less than 50%. Operation was done in 5 patient - 1 patients as a adjunctive means of chemotherapy -. In that case, negative conversion of sputum AFB was done. Conclusion: 2/3 patients of multidrug-resistant tuberculosis were improved by appropriate prescription and regular medication suggesting that more aggressive management and monitoring is indicated in multidrug-resistant tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.709-719
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• 2000

Background : The different features of high-resolution CT(HRCT) findings of active pulmonary tuberculosis(TB) were studied between acid fast bacilli(AFB) smear or culture positive and negative group. Methods : We prospectively evaluated 36 patients who had been confirmed for active pulmonary tuberculosis by the smear or culture of AFB in sputum(n=25), and changes on serial chest radiographs(n=11). The patients were divided into 3 groups by the results of sputum AFB stain and culture. Group 1(n= 11) is negative in both AFB stain and culture; group 2(n=13) is negative in AFB stain but positive in culture ; and group 3(n=12) is positive in both AFB stain and culture. We evaluated the findings of HRCT in each group randomly. Result : On the HRCT scans, acinar nodule(100%), macronodule(75%), and cavity(75%) in group 3 were more frequently found than group 1(63%. 18%, 9%) and group 2(46%, 15%, 23%)(p<0.05). The centrilobular nodule and branching structure were more frequently observed in group 3(92%) than in group 1(54%)(p<0.05), but were similarly observed in group 2(77%)(p>0.05). AFB positive group was statistically different than the negative group in the HRCT findings with to acinar nodule(100% vs 54%), macronodule(75% vs 17%), and cavity(75% vs 17%)(p<0.05). TB culture positive group was statistically different than the negative group in the HRCT findings with respect to acinar nodule(72% vs 45%) and cavity(48% vs 9%)(p<0.05). Conclusions : HRCT scans are helpful in determining disease acitivity in sputum AFB stain-negative pulmonary tuberculosis. When HRCT shows centrilobular nodule and branching structure, acinar nodule, macronodule, cavity, further studies as sputum induction and bronchoscopy can be performed to determine the presence of bacilli in patients of AFB stain-negative tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.61 no.3
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• pp.285-288
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• 2006

Interferon alpha is an immunomodulator that is used as an antiviral agent to treat chronic active viral hepatitis C. However, interferon can induce or exacerbate sarcoidosis. We report a case of 42-year-old man with an exacerbation of pulmonary sarcoidosis after the cessation of interferon and ribavirin therapy for chronic hepatitis C. The patient's sarcoidosis improved spontaneously and he continues to be monitored regularly without steroid therapy.

• 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.50 no.6
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• pp.686-692
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• 2001

Background : Outbreaks of multidrug-resistant tuberculosis(MDR-TB) are caused by the low rate of treatment response due to limitation in number of available drugs and high rates of adverse drug side-effects. This study analysed the risk factors for MDR-TB patients, who did not respond to treatment, with an aim to improve the rate of treatment response. Methods : Retrospective study of 111 MDR-TB patients at National Mokpo Tuberculosis Hospital from Jan. 1996 to Dec. 1998 was made. The patients were separated into two groups ; group I comprised of patients who were treated successfully and group II comprised of those were not treated successfully. In order to analyze the risk factors for treatment failure, differences between the two groups were compared and the confidence limit regarding the results were tested using an independent t-test. chi-square test and a Fisher's exact test. Results : The treatment failure rate of MDR-TB patients was 32% (36 patients), and treatment success rate 68%(75 patients). This study found no significant difference between two groups in terms of age, sex, family history, extent of the disease on the chest X-ray, the number of sensitive drugs in the treatment regimen, and the number of sensitive bactericidal drugs in the treatment regimen (p>0.05). However, a past history of pulmonary tuberculosis, cavitary lesions on the chest X-ray, the number of treatments, the number of resistant drugs and the number of drugs used showed a significant difference(p<0.05). Conclusion : The rate of treatment failure in MDR-TB was increased by a past history of pulmonary tuberculosis, cavitary lesions on the chest X-ray, the number of treatments, the number of resistant drugs and the number of drugs used. For improving the treatment response of MDR-TB, every effort should be made to reduce the drug resistance caused by failure of the first treatment.