• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.606-612
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• 2005

Background : It has been reported that nontuberculosis mycobacterium(NTM) isolates account for approximately 10% of patients with a positive Acid-Fast Bacilli(AFB) smear. Therefore, it is necessary to consider NTM pulmonary disease when such a positive test is encountered. The aim of this study was to evaluate the etiologies and clinical characteristics of patients with NTM pulmonary disease who had been treated at a national tuberculosis hospital. Methods : The NTM isolates were recovered from the sputum or bronchial washing specimens submitted to a clinical laboratory of National Masan TB Hospital from August 2002 to July 2003. All samples were identified using a polymerase chain reaction-restriction fragment length polymorphism analysis method, which amplifies the rpoB gene. The patients were diagnosed with NTM disease according to the American Thoracic Society diagnostic criteria. Results : One hundred NTM isolates were recovered from 57 patients. Of the 100 isolates, M. avium complex(MAC) was the most common species, which was found 55%(n=55) of patients, followed by M. abscessus(n=25), and M. fortuitum( n=9). 26(45.6%) patients had NTM disease. Twenty-six (45.6%) patients had NTM disease according to The American Thoracic Society classification. The main organisms involved in NTM disease were MAC(n=19, 73.1%) and M. abscessus(n=5, 19.2%). The pathogenic potential was 67.9% in M. intracellulare and 41.7% in M. abscessus. The predictive factors related to NTM disease were a positive sputum smear (OR 6.4, p=0.02) and the isolation of either MAC or M. abscessus(OR 6.9, p=0.007). Fifteen patients(57.7%) were cured. There were no significant factors associated with the treatment success. Conclusion : There was a relatively high proportion of NTM disease in NTM isolates and the common species were MAC and M. abscessus. The predictive factors for NTM disease were a positive sputum smear and the isolation of either MAC or M. abscessus.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.35-42
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• 1993

Background: In order to establish the etiology of the pleural effusion, routine analysis of the fluid, bacteriologic studies, cytologic tests and pleural biopsies are currently being employed. However, even with the above mentioned tests, the exact causes cannot be determined in approximately 10-20% of cases. The purpose of our study is to determine the diagnostic value of measuring ADA activity and CEA simultaneously in various pleural fluids which their etiologies have confirmed Methods: We have studied 61 cases of tuberculous pleural effusions, 17 cases of suspected tuberculous pleural effusions, 17 cases of malignant pleural effusions, 22 cases of suspected malignant pleural effusions, and 7 cases of parapneumonic pleural effusions. We have measured the ADA activity and CEA level simultaneously in pleural fluid samples in each cases. Results: 1) The ADA activity in tuberculous pleural effusion was significantly higher than that in malignant effusion. 2) The CEA level in malignant pleural effusion was significantly higher than that in tuberculous effusion. 3) With the cut-off values of the pleural fluid ADA activity more than 40 U/L and the CEA level less than 12 ng/mL, the sensitivity was 86.9%, and the specificity was 100% in the diagnosis of tuberculous effusion. With the cut-off values of the pleural fluid CEA level more than 12 g/mL and the ADA activity less than 40 U/L, the sensitivity was 76.5%, and the specificity was 100% in the diagnosis of malignant effusion. Conclusion: It is suggested that the combined assay of pleural fluid ADA activity and CEA level is very useful in the differential diagnosis of tuberculous and malignant pleural effusion.

• 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.59 no.4
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• pp.406-412
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• 2005

Background : Recently, two commercialized whole-blood assays, $QuantiFERON^{(R)}-TB$ Gold (QFT) and T $SPOT-TB^{(R)}$ (SPOT), which measure the $IFN-{\gamma}$ released in the whole blood after being incubation with mycobacterial antigens, were approved for the diagnosis of a latent tuberculosis infection (LTBI). However, there is data on whether or not the previously used PPD skin tests (TST) have any influence on the diagnostic ability of these ex-vivo $IFN-{\gamma}$ assays. Methods : Forty-six 15 year-old students who did not appear to be infected with Mycobacterium tuberculosis were enrolled in this study. The peripheral blood was collected and used for two $IFN-{\gamma}$ assays. The $IFN-{\gamma}$ assays and TST were performed at the baseline ($1^{st}$). The TST was repeated two months later ($2^{nd}$), and the $IFN-{\gamma}$ assays were repeated two ($2^{nd}$) and four months ($3^{rd}$) later only in those subjects who had negative results at the baseline in both the $IFN-{\gamma}$ assays and TST. An induration size > 10 mm was considered to be positive in the TST. Results : The mean TST value was $3.1{\pm}5.4mm$ (range: 0-20). Of the 46 subjects examined, 13 subjects (28.3%) showed positive results in the two-step TST. Nine (19.6%) were SPOT-positive and only one (2.2%) was QFT-positive. The $2^{nd}$ and $3^{rd}$ QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The $2^{nd}$ SPOT was performed in 23 subjects and only one (4.3%) showed a weak-positive result. Conclusion : Even though there were some discrepancies in the results of the two ex-vivo $IFN-{\gamma}$ assays, it appears that their results were not influenced by a previous TST carried out in two or four months earlier.

• Tuberculosis and Respiratory Diseases
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• v.65 no.3
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• pp.177-182
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• 2008

Background: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis (TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from the treatment regimen. Methods: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control), Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ, Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU) counts were determined. Results: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups (Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew in the spleen at some time points after completion of treatment. Conclusion: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are necessary to clarify the role of INH in the standard first-line regimen for treating TB.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.133-141
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• 2005

"소기도"라 일컬어지는 해부학적 부위는 말단부 막성 세기관지와 호흡성 세기관지로 구성된 직경 3 mm 이하의 기도부위이다. 방사선학적으로는 고해상 전산화단층촬영(CT)에서 흉막직하의 직경 약 1.0 cm으로 이루어진 2차 소엽내의 중심부에 위치하게 된다. 그러므로 이 부위의 질환때에는 중심소엽성 세기관지내의 가득찬 물질로 인해 나타나는 중심소엽성 결절들과 선상음영들이 보인다. 이외의 소견으로는 중심소엽성 폐기종, 모자이크 모양의 폐음영, 분절하 무기폐등이 있고, 호기시 CT 촬영에서 나타나는 공기포획이 있다. 최근에는 다검출기형식의 CT (multidetector CT)의 발전으로 인하여 이차원 재구성 (2 dimension reformat) 관상면, 시상면 CT 스캔을 매우 명확하고 빨리 얻을 수 있고, 기관지에 대한 삼차원 볼륨 영상 (3 dimentional volume rendering image) 등을 얻어서 가시적인 효과를 높이고 진단의 정확성에 보다 더 접근하게 되었다. 소기도를 침범하는 질환은 일차적인 것과 이차적인 것이 있는데, 병리조직학적으로는 원인별로 흡연으로 인한 소기도 질환, 세포성 세기관지염, 수축성 세기관지염, 증식성 세기관지염등으로 구분하며 여기에는 이와 같은 병리질환을 일으키는 다양한 원인들이 포함된다. 이외에도 드문 질환으로 미만성 범세기관지염, 광물질에 의한 소기도 질환등이 있다.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.227-233
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• 1998

Typhoid fever is an acute systemic febrile disease caused by Salmonella typhi. The classic picture of the disease consists of prolonged continuous or remitting fever, abdominal pain, diarrhea, rose spots and delirium. Salmonella infection can lead to diffuse organ involvement., including bone, lung, thyroid, kidney, liver, spleen, heart, pericardium, intestine and skin and cause a variety of complications. Pulmonary manifestations occur in only 1 percent of the patients. Mild cough with sticky sputum is the earliest symptom and bronchitis, pneumonia and lung abscess were presented. Recently we experienced a case of typhoid fever complicated by bronchitis, dysplasia in a 37-year-old male physician who was improved with ceftriaxone and ciprofloxacin We report this case with a review of the literature.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1414-1418
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• 1997

Typhoid fever is an acute systemic febrile disease caused by Salmonella typhi. The classic picture of the disease consists of prolonged continuous or remitting fever, abdominal pain, diarrhea, rose spots and delirium. Salmonella infection can lead to diffuse organ involvement, including bone, lung, thyroid, kidney, liver, spleen, heart, pericardium, intestine and skin and cause a variety of complications. Pulmonary manifestations occur in only 1 percent of the patients. Mild cough with sticky sputum is the earliest symptom and bronchitis, pneumonia and lung abscess were presented. Recently we experienced a case of typhoid fever complicated by bronchitis, dysplasia in a 37-year-old male physician who was improved with ceftriaxone and ciprofloxacin We report this case with a review of the literature.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.257-265
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• 2005

Background : Rifabutin (ansamycin) is a spiro-piperidyl rifamycin, which is highly active against Mycobacterium tuberculosis. It has been found that some clinical isolates of tubercle bacilli that are resistant to rifampicin are susceptible to rifabutin, with some patients with multi-drug resistant pulmonary tuberculosis having shown favorable clinical and bacteriological responses to the rifabutin. This study was conducted to find the proportion of rifabutin-susceptible strains among rifampicin-resistant isolates from Korean MDR-TB patients, and investigate the presence of specific rpoB mutations, which may confer resistance to rifampicin, but not to rifabutin. Methods : 201 rifampicin-resistant and 50 pan-susceptible M. tuberculosis isolates were randomly selected for this study. The isolates were retested at rifampicin and rifabutin concentrations of 0, 20, 40 and $80{\mu}g/ml$, respectively. The isolates that grew at and/or over a rifabutin concentration of $20{\mu}g/ml$ were judged rifabutin-resistant. The rpoB gene was extracted from the isolates, and then amplified for direct sequencing to investigate specific rpoB mutations that conferred rifabutin- susceptibility but rifampicin-resistance. Results : Out of the 201 rifampicin-resistant M. tuberculosis, 41 strains (20.4%) were susceptible to rifabutin using the absolute concentration method on Lowenstein-Jensen media. The rpoB mutation types that showed susceptibility to rifabutin were Leu511Pro, Ser512Arg, Gln513Glu, Asp516Ala, Asp516Gly, Asp516Val, Asp516Tyr, Ser522Leu, His526Asn, His526Leu, His526Cys, Arg529Pro and Leu533Pro. A reverse hybridization technique was able to detect 92.5% of the rifabutin-susceptible isolates, with a specificity of 96.1% among 195 M. tuberculosis isolates with the rpoB mutation. Conclusions : Around 20% of the rifampicin-resistant isolates in Korea showed susceptibility to rifabutin, which was associated with some specific mutations of rpoB. Rifabutin could be used for the treatment of MDR-TB patients, especially when drug susceptibility testing reveals susceptibility to rifabutin.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.479-492
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• 1997

Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.