• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.869-878
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• 1999

Intravesical instillation of the bacillus Calmentte-Gu$\acute{e}$rin(BCG), an attenuated strain of Mycobacterium bovis, is an approved method for the treatment of superficial bladder cancer. Because BCG is a living organism, the potential for infection exists. BCG is generally well tolerated, with complications in less than 5% of those treated with use of current practices. The most frequent symptoms of toxicity associated with intravesical BCG immunotherapy include bladder irritation, frequency, and dysuria. Systemic reactions are less common but more serious than local side effects, and include fever, chills, malaise, rash, hepatitis, pneumonitis, arthritis and sepsis. In rare cases, BCG treatment can result in a systemic infection that requires antituberculous therapy. The pulmonary toxicity that results from intravesical BCG treatment is generally characterized by one of two types : systemic allergic reaction with pulmonary reticulonodular opacities depicted on chest radiographs with cellular findings consisting of activated lymphocytes, and actual BCG mycobacteremia with a miliary pattern depicted on chest radiographs and granuloma formation which rarely results in positive acid-fast stain or culture results. Recently we experienced two types of pulmonary complications following intravesical BCG immunotherapy in patients with superficial bladder cancer. We report two cases with a review of literatures.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.497-503
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• 2003

Pulmonary aspergillosis usually results from the colonization of the existing lung lesions by chronic pulmonary diseases, such as tuberculosis. Most cases of pulmonary aspergilloma have been treated surgically for many years because it is a potentially life-threatening disease causing massive hemoptysis. Here we reviewed our results from the last 10 years. Material and Method: We reviewed 31 cases surgically treated from Aug. 1992 to Jul. 2002. retrospectively. This investigation is designed to illustrate the peak age incidence, sex ratio, chief complaints, preoperative study, anatomic location of operative site, postoperative pathologic finding and postoperative complications. Result: The peak age Incidence laid in the 3rd and 4th decade of 20 cases (64.5%). The most common complaint was hemoptysis in 27 cases (87.1%). The 31 cases had a history of treatment with anti-tuberculous drugs under impression of pulmonary tuberculosis. The 19 cases (61.3%) showed the so-called “Air-meniscus sign” on the preoperative chest X-ray. In the 31 cases (100%) on the chest computed tomography. as a preoperative diagnostic modality, positivity was shown in 37.9%, 83.3% was shown on the fungus culture of sputum for Aspergillus, serum immunodiffusion test for A. fumigatus, respectively. The anatomical location of aspergilloma was mainly in the upper lobe in 19 cases (61.3%) and the majority of cases were managed by lobectomy. The postoperative pathologic findings showed that 31 cases (100%) were combined with tuberculosis. The postoperative complications include empyema, prolonged air leakage, remained dead space, postoperative bleeding and these numbers of cases is 3 cases (9.7%), 2 cases (6.45%), 2 cases (6.45%), 1 case (3.23%), respectively. one case was died postoperatively due to massive beeding, and asphyxia. Conclusion: Compared with the previous study, there is no significant difference in results. Preoperative chest computed tomography and immunodiffusion test were more commonly available and showed high positivity. Operations often became technically difficult because of pleural space obliteration, indurated hilar structures, and poor expansion of the remaining lung, which were more prominent in the patients with complex aspergillosis. In such cases, medical treatments and interventional procedures like bronchial artery embolization are preferred. However, cavernostomy is also recommanded with few additional morbidity because of its relatively less invassiveness. Early surgical intervention is the recommended management for patients with simple aspergilloma considering the Row surgical mortality and morbidity in recent days.

• 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.

• Journal of Chest Surgery
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• v.36 no.11
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• pp.839-845
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• 2003

Background: Even today when chemotherapy has been established as a treatment for tuberculosis and the prevalence of tuberculosis is gradually decreasing, multi-drug resistance tuberculosis still results in poor treatment performance and lowered survival periods. This research sought to analyze the surgery of multi-drug resistance tuberculosis, and determine the usefulness and danger of surgery in connection with this disease. Material and Method: Starting from February 1990 to February 2002, retrospective surveys were conducted targeted at 21 cases involving 20 patients who underwent surgery due to multi-drug resistance tuberculosis. The survey included 14 males cases and 6 females cases with the age averaging 42.8$\pm$12.1 years. 10.3$\pm$7.6 years on average passed after patients were initially diagnosed with tuberculosis. 13 patients (65%) tested positive in the pre-operative sputum AFB test, and all showed resistance against an average of 3.5 anti-tuberculosis agents including INH and RFP. Pre-operative radiologic examinations revealed cavitary lesions in 15 patients (75%), and three patients had lesions in the both lung fields, with the major lesions existing in the unilateral area. 13 patients (75%) failed negative conversion with medical treatment, while two patients (10%) with recurrent hemoptysis and five patients (25%) with lesions involving high recurrence-rate received the operation. Operations included nine cases (40%) of pneumonectomy, nine cases (45%) of lobectomy, and three cases of lobectomy with segmentectomy. The average follow-up period of patients stood at 23 months. Result: There was no post-operative death, and found were a total of eleven cases involving complications were found: three cases of long-term air leakage, three cases of bleeding requiring re-operation, two cases of empyemas due to broncho-pleural fistula, and one case of atelectasis, wound infection and chest wall fistula each. Eleven cases (85%) of negative conversion were completed immediately after the operation, and two cases failed negative conversion. Eleven months after the operation, the disease recurred in one case of negative conversion patients, and the patient was cured by completion pneumonectomy. Conclusion: If patients' lung function was sufficient and appropriate resection was possible, multi-drug resistance tuberculosis could achieve high-rate negative conversion and cure using combination of surgical and medical treatment, and also there were not many serious complications.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.669-676
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• 1995

Background: The cell-mediated immunity is needed for eradicating the tubercle bacilli. Prostaglandin(PG), especially PG $E_2$, is involved in cellular immunosuppression. It is known that the PG $E_2$ is suppressed by indomethacin. For using indomethacin as a immunomodulator of intractable pulmonary tuberculosis(Tbc) patients, we measured the tuberculin skin test(TST) and the plasma PG $E_2$ levels. Method: The forty-eight inpatients with sputum positive acid-fast stain bacilli were classified into 6 groups according to antiTbc chemotherapy history(new and intractable cases), plain chest roetgenogram(minimal and far advanced cases), and TST reaction(nagative and positive cases). Except for one group(n=2; new, minimal, and negative cases of TST reaction) of the 6 groups, all subjects(n=46) were measured for the plasma PG $E_2$, levels with radioimmunoassay. Results: 1) There was no significant difference in the plasma PG $E_2$ levels among A group(far advanced and positive TST reaction cases, n=10, $11.22{\pm}2.86\;pg/ml$), B group(minimal and negative TST reaction cases, n=9, $11.35{\pm}2.20$) and C group(far advanced and positive TST reaction cases, n=7, $11.11{\pm}2.30$) in the new cases(p>0.05). 2) There was no significant difference in the plasma PG $E_2$ levels between positive(n=10, $9.25{\pm}2.21$) and negative(n=10, $8.25{\pm}1.13$) groups by TST in the intractable cases(p>0.05). 3) Comparing the plasma PG $E_2$ levels between new(n=26, $11.35{\pm}2.41$) and intractable(n=20, $8.75{\pm}1.78$) groups, the intractable group had significi- andy lower plasma PG $E_2$ levels(p<0.05). 4) There was no significant difference in the plasma PG $E_2$ levels between negative(n=19, $9.88{\pm}2.43$) and positive(n=27, $10.46{\pm}2.56$) groups by TST(p>0.05). 5) There was no significant difference in the plasma PG $E_2$ levels between male(n=32, $10.07{\pm}2.44$) and female(n=14, $10.56{\pm}2.70$)(p>0.05). 6) There was no significant difference in the plasma PG $E_2$ levels among 2nd(n=5, $10.21{\pm}2.86$), 3rd(n=9, $9.97{\pm}2.47$), 4th(n=13, $11.35{\pm}2.33$) and 5th(n=19, $9.57{\pm}2.48$) decades(p>0.05). 7) There was no significant correlation between the induration sizes of the TST and the plasma PG $E_2$ levels(r=0.054, p>0.05). Conclusion: From the above results, the plasma PG $E_2$ levels of intractable group are not higher as the authors had expected. There was no significant difference in the plasma PG $E_2$ levels by the lesion sizes of plain chest roentgenogram and the induration sizes of TST, so more study will be needed to use the indomethacin as a immunomodulator for intractable pulmonary tuberculosis patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1143-1153
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• 1998

Background : Recent outbreaks of pulmonary disease due to drug-resistant strains of Mycobacterium Tuberculosis have resulted in significant morbidity and mortality in patients worldwide. We reviewed our experience to evaluate the effects of pulmonary resection on the management of multidrug-resistant tuberculosis. Method : A retrospective review was performed of 41 patients undergoing pulmonary resection for multidrug-resistant tuberculosis between January 1993 and December 1997. We divided these into 3 groups according to the radiologic findings : (1) patients who have reasonably localized lesion (Localized Lesion Group ; LLG) (2) patients who have cavitary lesions after pulmonary resection on chest roentgenogram (Remained Cavity Group : RCG) (3) patients who have Remained infiltrative lesions postoperatively (Remained infiltrative group : RIG). We evaluated the negative conversion rate after resection and overall response rate of the groups. Then they were compared with the results of the chemotherapy on the multi drug-resistant tuberculosis which has been outcome by Goble et al. Goble et al reported that negative conversion rate was 65% and overall response rate, 56% over a mean period of 5.1 months. Results : Seventy five point six percent were men and 24.4% women with a median age of 31 years (range, 16 to 60 years). Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 22 of 41 were still sputum culture positive at the time of surgery. 20 of 22 patients(90.9%, p<0.01) responded which is defined as negative sputum cultures within 2 months postoperative. Of 26 patients with the sufficient follow up data, 19 have Remained sputum culture negative for a mean duration of 25.7 months (73.1%, p<0.05). The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 15, consisted of 8 in RIG and 7 in RCG, of 41. 12 of 12 patients (100%, p<0.01) who were sputum positive at the time of surgery in LLG converted successfully. 14 of 15 patients (93.3%, p<0.05) with the follow up have completed treatment and not relapsed for a mean period of 25. 7 months. The mean length of postoperative drug therapy of LLG was 12.2 months. In RIG, postoperative negative conversion rate was 83.3% which was not significant statistically. There was a statistical significance in overall response rate (100%, p<0.05) of RIG for a mean period of 24.4 months with a mean length of postoperative chemotherapy, 11.8 months. In RCG a statistically lower overall response rate (14.3%, p<0.01) has been revealed for a mean duration of follow up, 24.2 months. A negative conversion rate of RCG was 75% which was not significant statistically. Conclusion : Surgery plays an important role in the management of patients with multidrug-resistant Mycobacterium tuberculosis infection. Aggressive pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection to avoid treatment failure or relapse. Especially all cavitary lesions on preoperative chest roentgenogram should be resected completely. If all of them could not be resected perfectly, you should not open the thorax.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.33-42
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• 2007

Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.37-41
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• 2009

Hot tub lung has been described as a pulmonary illness associated with exposure to nontuberculous mycobacteria,mainly hot bathtub water contaminated with Mycobacterium avium complex (MAC) and hence the name. Although not entirely clear, its etiology has been thought to involve either an infection or a hypersensitivity pneumonitis secondary to MAC. Herein, we describe 2 female patients (60 and 53 years old) admitted to our hospital with hot tub lung, and both of whom worked in a public bath. Both women were initially admitted following several months of exertional dyspnea and cough. The patients had been working as body-scrubbers in a public bath for several years. Their chest CT scans showed bilateral diffuse ground-glass opacities with multifocal air-trappings and poorly defined centrilobular nodules in both lungs. Pathological findings from lung specimens revealed small non-necrotizing granuloma in the lung parenchyme with relatively normal-looking adjacent alveoli. Discontinuation of working in the public bath led to an improvement in symptoms and radiographic abnormalities, without antimycobacterial therapy.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.774-779
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• 2000

Pseudomembranous colitis, although uncommon, is an important complication of antibiotics that is related to a variety of deleterious effects on the gastrointestinal tract. Rifampicin is one of the 1st line agents in the treatment of tuberculosis and a large number of patients are exposed to its potential adverse effects. We report upon a patient that had diarrhea due to pseudomembranous colitis after receiving antitubeculous medication, and which was probably caused by rifampicin. A 77-year-old man was admitted with diarrhea of three weeks duration. One month previously, he suffered from left pleuritic chest pain and left pleural effusion was noticed at chest X-ray. One week prior to the onset of diarrhea, he was started on empirically isoniazid, rifampicin, ethambutol and pyrazynamide as antituberculous medication. On admission, he complained of diarrhea, left pleuritic chest pain, dyspnea and sputum. On physical examination, breathing sound was decreased in the left lower lung field and bowel sound increased. Pleural biopsy revealed chronic granulomatous inflammation, which was compatible with tuberculosis, Sigmoidoscopy showed whitish to yellowish pseudomembrane with intervening normal mucosa, and his stool was positive for C.difficle toxin. He was diagnosed as pseudomembranous colitis and treated with oral metronidazole and vancomycin. The diarrhea did not recur after reinstitution of the anti-tuberculous medication without rifampicin inpatients with severe diarrhea receiving anti-tuberculous medication, rifampicin induced pseudomembranous colitis should be excluded.