• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1214-1222
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• 1998

Background : The intrapleural hypofibrinolysis is caused by mainly excessive concentration of pleural plasminogen activator inhibitor-1 antigen(PAI-1 Ag), which binds tissue type plasminogen activator. In pleural inflammation induced by sclerosing agents for pleurodesis, levels of pleural PAI-1 antigen increase in relation to decreasing D-dimer levels. It has been known that the pleural mesothelial cells have the capability of secreting PAI-1 Ag in response to inflammation in vivo. Therefore, we estimated whether pleural inflammation changes the balance between fibrinolytic and coagulative properties in exudative pleural effusions. Method : The thirty cases was included in our study. We determined the pleural levels of glucose, lactic dehydrogenase(LDH), pH and the counts of white blood cell(WBC), polymorpho leukocyte(PMN), lymphocyte as the parameters of pleural inflammation and cellular components of pleural fluid. The plasma level of fibrinogen in fluid and the neutrophil count in blood were determined. The levels of D-dimer, PAI-1 Ag and thrombinantithrombin III complex(TAT) were determined by ELISA(Behring, Marburg, Germany). Result : The causes of pleural effusion were as following : tuberculous in 14 cases, malignant in 10 cases and parapneumonic in 6 cases. The levels of pleural D-dimer, PAI-1 Ag and TAT was significantly higher than that of plasma(p<0..001). The severity of pleural inflammation did not correlated with pleural D-dimer, PAI-1 Ag, TAT and their plasma levels. But the level of pleural TAT correlated with pleural WBC and lymphocyte count. Conclusion : We found that the severity of pleural inflammations did not correlated with pleural D-dimer, PAI-1 Ag, TAT and the possibility of local production of PAI-1 antigen is present.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.329-337
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• 1997

Background : Since endotracheal tube is the most important factor involved in the imposed work of breathing during mechanical ventilation, extubation of endotracheal tube is supposed to reduce respiratory work of patient. However, some patients show labored breathing after extubation despite acceptable blood gases. We investigated the changes of work of breathing before and after extubation and the factors involved in the change of WOB after extubation. Methods : The subjects were 34 patients(M : F = 20 : 14, mean age = $61{\pm}17yre$) who recovered from respiratory failure after ventilatory support and were considered to be ready for extubation. The patients with clinical or radiologic evidences of upper airway obstruction before endotracheal intubation for mechanical ventilation were excluded. Vital sign, physical examination, chest X-ray, work of breathing and other respiratory mechanic indices were measured prior to, immediately, 6, 24 and 48 hours after extubation serially. Definition of weaning failure after extubation was resumption of ventilatory support or reintubation of endotracheal tube within 48 hour after extubation because of respiratory failure. The patients were classified into group 1(decreased work of breathing), group 2(unchanged work of breathing) and group 3(increased work of breathing) depending on the statistical difference in the change of work of breathing before and after extubation. Results : Work of breathing decreased in 33%(11/34, group 1), unchanged in 41%(14/34, group 2) and increased in 26%(9/34, group 3) of patients after extubation compared with before extubation. Weaning failure occurred 9%(1/11) of group, 1, 28.6%(4/14) of group 2 and 44%(4/9) of group 3 after extubation(p = 0.07). The change of work of breathing after extubation was positively correlated with change of mean airway resistance(mRaw). (r = 0.794, p > 0.01). In three cases of group 3 whose respiratory indices could be measured until 48 hr after extubation, the change in work of breathing paralleled with the sequential change of mRaw. The work of breathing was peaked at 6 hr after extubation, which showed a tendency to decrease thereafter. Conclusions : Reversible increase of work of breathing after extubation may occur in the patients who underwent extubation, and the increase in mRaw could be responsible for the increase in work of breathing. In addition, the risk of weaning failure after extubation may increase in the patients who have increased WOB immediately after extubation.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.546-557
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• 2000

Background : Oligonucleotide chip technology has proven to be a very useful tool in the rapid diagnosis of infectious disease. Rifampin resistance is considered as a useful marker of multidrug-resistance in tuberculosis. Mutations in the rpoB gene coding $\beta$ subunit of RNA polymerase represent the main mechanism of rifampin resistance. The purpose of this study was to develop a diagnosis kit using oligonucleotide chip for the rapid and accurate detection of rifampin-resistance in Mycobacterium tuberculosis. Method : The sequence specific probes for mutations in the rpoB gene were designed and spotted onto the glass slide, oligonucleotide chip. 38 clinical isolates of Mycobacterium were tested. A part of rpoB was amplified, labelled, and hybridized on the oligonucleotide chip with probes. Results were analyzed with a laser scanner. Direct sequencing was done to verify the results. Result : The low-density oligonucleotide chip design어 to determine the specific mutations in the rpoB gene of M. tuberculosis accurately detected rifampin resistance associated with mutations in 28 clinical isolates. Mutations at codons 531, 526, and 513 were confirmed by direct sequencing analysis. Conclusion : Mutant detection using oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of multidrug-resistance in M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.887-897
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• 2000

Background : Since the exact pathogenesis of sepsis-induced ARDS has not been elucidated, the mechanisms of enhanced neutrophilic respiratory burst were probed in endotoxin primed neutrophils associated with the roles of phospholipase A2(PLA2), platelet activating factor(PAF) and apoptosis. Methods : In isolated fresh human neutrophils, effects of the inhibition of PLA2 and PAF on the apoptosis were examined by the method of Annexin-FITC/dual PIflow cytometry. The roles of PLA2 and PAF on the neutrophilic respiratory burst were also examined by measuring oxidant generation in cytochrome-c reduction assay. Activities of the PLA2 and lysoPAF acetyltransferase (lysoPAF AT) of the neutrophils were determined to understand the effect of endotoxin on these enzymatic activities which may be related to the neutrophilic respiratory burst and apoptosis. In addition, the role roles of PLA2 and PAF in neutrophilic adhesion to bovine endothelial cells were examined in vitro by neutrophil adhesion assay. To investigate the effect of oxidants on pulmonary surfactant, cytochemical ultrastructural microscopy was performed. To inhibit PLA2 and PAF, non-specific PLA2 inhibitor mepacrine (100 nM) and WEB 2086 (100 nM) or ketotifen fumarate (10 ${\mu}g$/ml) were used respectively in all in vitro experimental sets. WEB 2086 is PAF receptor antagonist, and ketotifen fumarate is a lyso PAF AT inhibitor. Results: The mapacrine treatment, provided and the endotoxin (ETX) treatment, resulted in increased apoptosis of neutrophils (p<0.001) while treatments of WEB 2086 and ketotifen did not. The inhibition of PLA2 and PAF decreased (p<0.001) production of oxidants from PMA-stimulated neutrophils. While endotoxin increased the PLA2 activity of neutrophils (p<0.01), mepacrine supressed (p<0.001) the activity, provided after treatment of ETX. The lyso PAF actyltransferase activity (lyso PAF AT) increased (p<0.01) after treatment of ETX. In contrast, mepacrine, WEB 2086 and ketotifen showed a tendency of decreasing the activity after treatment of ETX. The treatment of ETX incresed (p<0.001) neutrophil adhesion to endothelial cells, which was reversed by inhibition of PLA2 and PAF (p<0.01). The binding of oxidants to pu1monary surfactant was identified histologically. Conclusions : The enhanced neutrophilic respiratory burst by ETX plays a pivotal role in the pathogenesis of ARDS in terms of oxidayive oxidative stress. Increased production of oxidants from neutrophils is mediated by the activations of PLA2 and lyso PAF AT.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.460-470
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• 1999

Background : In 1993, American Thoracic Society (ATS) recommended a guideline for the initial management of adults with community-acquired pneumonia(CAP). However, etiologic organisms and medical system in Korea seem to be different from those in Western countries. Retrospective analysis was done to evaluate the efficacy of antibiotics chosen by ATS guideline in the treatment of Korean patients with CAP admitted to a tertiary university medical center. Methods : Hospitalized patients with CAP at Samsung Medical Center from April 1997 through March 1998 were retrospectively reviewed. Patients who fulfilled all of the following criteria were included in this study : (1) fever ${\geq}38^{\circ}C$ (2) purulent sputum (3) pulmonary infiltrates on chest X-ray. Patients were classified as : 1) ATS group ; patients whose initial antibiotics were chosen by ATS guideline 2) Non-ATS overuse group ; additional antibiotics administered more than those of ATS guideline, and 3) Non-ATS underuse group ; initial antibiotics were insufficient to ATS guideline. Response of empirical antibiotics and etiologic organisms of 3 groups were identified. Results : Sixty-four patients were enrolled. Thirty-six patients were classified into ATS group, 10 patients Non-ATS overuse group, and 18 patients Non-ATS underuse group. Thirty-three patients of 36 ATS group, 9 patients of 10 Non-ATS overuse group, and 14 patients of 18 Non-ATS underuse group showed improvement by initial empirical antibiotics. There was no statistical difference in antibiotic response between 3 groups (p>0.05). S. pneumoniae (12.5%), K. pneumoniae (9.4%), and P. aeruginosa (4.7%), Mycoplasma (3.1%) were the most commonly isolated organisms. In 18 patients with severe CAP, P. aeruginosa was isolated only in 1 patient and Legionella organism not isolated. Conclusion : Initial empirical antibiotics chosen by ATS guideline were effective in the management of Korean patients with CAP admitted to a tertiary hospital. However, well-designed large-scale prospective study is needed to identify etiologic organisms and choose an adequate initial empirical antibiotics in Korean adults patient with severe CAP.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.735-746
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• 1999

Background: As the prevalence of nontuberculous mycobacteriosis has been increasing rapidly, there has been recent advance in diagnostic methods and drug therapies for disease. Although the incidence of pulmonary disease caused by nontuberculous mycobacteria(NTM) has been increasing in Korea since 1990, detailed clinical description about the disease were very few. In this study we described the clinical manifestations, radiologic findings, and therapeutic outcomes of nontuberculous mycobacterial pulmonary disease. Methods: Medical records and radiologic findings were retrospectively reviewed in 27 patients who were fulfilled the diagnostic criteria of ATS guideline for NTM pulmonary disease between January of 1990 and August of 1998 in Seoul National University Hospital(SNUH). Results: Of the 27 patients, 15 were male. The mean age was 51.5 yr($\pm$11.9). Twenty patients(74.1%) had preexisting pulmonary diseases. Among them, 19 patients had previous pulmonary tuberculosis. Sixteen patients(59.2%) had cavitary lesions and the majority showed slow progression over 1 yr during follow up period on radiography. Susceptibility test to standard antituberculous drugs showed 100% resistance to INH, 72.2% to RMP, 81.5% to EMB, 92.6% to PZA. The average resistance rate to 2nd-line antituberculous drugs was 66.1%. Among twenty-one patients(77.8%) who received drug therapy over 6 months, 11 subjects were improved and 10 subjects were aggravated. Of six subjects(22.2%) without therapy, 5 patients were aggravated. Presence of cavity and less than 3 sensitive drugs in the regimen were indicators for adverse outcome. Conclusion : The nontuberculous mycobacterial pulmonary diseases in our hospital developed predominantly in older patients with preexistent pulmonary disease. The results of antituberculous drug therapy has been frustrating and disappointing. To improve treatment response, different susceptibility tests and drug regimens for different species of NTM should be performed. Also, diagnostic and therapeutic guidelines of Korea should be made in the recent future.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.540-549
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• 2001

Background : Usual interstitial pneumonia (UIP) is a progressive fibrous lung disease with occasional fatal outcomes. However, the extent and rate of progression varies markedly from one patient to another. As a result, it is difficult to determine the time of the initial treatment and assess the disease activity and course. Fibroblast foci (FF) is well known to synthesize collagen actively by their myofibroblasts component. However, the prognostic value of the FF have not been evaluated in patients with VIP. Therefore this study was undertaken to determine how the number of fibroblastic foci can reflect the disease activity and progression. Methods: Twenty patients with UIP(M : F=13 : 7), who were diagnosed by a surgical lung biopsy. The number of fibroblastic foci was analyzed in terms of its correlation with the clinical manifostations, pulmonary function test, arterial blood gas analysis, and a bronchoalveolar lavage(BAL). Results : The number of fibroblastic foci did not correlate with the various lung function tests and the other clinical parameters. Interestingly, the percentage of neutrophils in the bronchoalveolar lavage fluid did correlate with the quantity of the normalized Vv of FF(r=0.60, p<0.05). The patients were divided into 2 groups, group I and II, arbitrarily, according to the value of the normalized Vv. The clinical parameters and the PIT results were not different between the two groups. In particular, the survival rate between the two groups according to the Kaplan-Meier analysis were not different. Conclusion : A large number of FF does not imply a bad prognosis in patients with UIP.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.570-578
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• 2001

Background: With cases of chronic obstructive pulmonary disease(COPD), weight loss and low body weight have been found to correlate with increased mortality and poor prognosis. Therefore, nutritional aspects are an important part of the treatment in cases of COPD. In Korea, there is only limited data available for the changes of resting pulmonary function in relation to nutritional status. This study was carried out to investigate the differences of resting pulmonary function in relation to the nutritional status of patients with COPD. Method : 83 stable patients, with moderate to severe COPD, were clinically assessed for their nutritional status and resting pulmonary function. The patients' nutritional status was evaluated by body weight and fat-free mass (FFM), which was assessed by bioelectrical impedance analysis. According to their nutritional status, the 83 patients were divided into two groups, designated as the depleted, and non-depleted, groups. Result : Of the 83 patients, 31% were characterized by body weight loss and depletion of FFM, whereas 28% had either weight loss or depleted FFM. In the depleted group, significantly lower peak expiratory flow rate(p<0.05) and Kco(p<0.01), but significantly higher airway resistance(Raw, p<0.05) were noted. There was no difference for the non-depleted group in forced expiratory volume at one second, residual volume, inspiratory vital capacity, or total lung capacity. Maximal inspiratory pressure($P_{Imax}$) was also significantly lower in the depleted group(p<0.05). Conclusion : We conclude, from our clinical studies, that nutritional depletion is significantly associated with the change in resting pulmonary function for patients with moderate to severe COPD.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.488-497
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• 1999

Background : Identification of the histologic cell type of lung cancer is important because it is related to the treatment modality and prognosis. Currently, many diagnostic methods are used to determine the cell type. We have studied to evaluate the histologic accuracy of each diagnostic methods in lung cancer. Method : 168 cases were analysed retrospectively, who underwent curative thoracotomy for lung cancer in Seoul National University Hospital from January, 1994 to February, 1997. Sputum cytology, percutaneous needle aspiration(PCNA), percutaneous needle biopsy(PCNB), bronchial washing cytology and flexible bronchoscopic biopsy were evaluated respectively. The k coefficient was applied to evaluate the degree of concordance between the histologic diagnosis obtained by each methods and the one derived from thoracotomy. Results : The k value in sputum cytology was 0.86. In the 34 cases with squamous cell carcinoma(SQ), 32 cases were finally diagnosed as having such by thoracotomy. 7 of the 8 cases with adenocarcinoma(AD) turned out to have the same. The k value in PCNA was 0.51. In the 31 cases with SQ, only 14 cases were finally diagnosed as having such. All of the 3 cases with small cell carcinoma(SC) turned out to have the same. The k value in PCNB was 0.77. The diagnosis was correct in 13 of the 16 patients with SQ and in 30 of the 32 cases with AD. The k value in bronchial washing cytology was 1.0. In all of the 29 cases with SQ and all of the 7 cases with AD, the diagnosis was correct. The k value in flexible bronchoscopic biopsy was 0.77. The diagnosis was correct in 51 of the 52 cases with SQ and in 1 of the 2 cases with SC. Conclusion : The concordance rate with the final histologic diagnosis in sputum cytology, PCNB, bronchial washing cytology and flexible bronchoscopic biopsy were excellent ($k{\geq}0.75$), while that in PCNA was fair (k=0.53). Because PCNA showed lower concordance rate than other diagnostic methods, PCNA is recommended to perform with PCNB.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.169-178
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• 2000

Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.