• Tuberculosis and Respiratory Diseases
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• v.41 no.1
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• pp.1-10
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• 1994

Background: Patients with mitral stenosis(MS) have been demonstrated to have a variable degree of pulmonary dysfunction and exercise impairment. The hemodynamic changes of MS can be reversed after percutaneous mitral balloon valvuloplasty(PMV), but the extent and time course of the imporvement in pulmonary function and exercise capacity are not defined. Methods: In order to investigate the early(3 weeks or less)and late(3 months or more) effects of PMV on pulmonary function and determine if the pulmonary dysfunction is reversible even in patients with moderate to severe pulmonary hypertension, we performed the spirometry, measurements of diffusing capacity and lung volumes, and incremental exercise tests in patients with MS before and after PMV. Results: In 46 patients with MS(age: $40{\pm}12$years, male to female ratio: 1:2, mitral valve area: $0.8{\pm}0.2cm^2$) there was a significant increase in FVC(P<0.0025), $FEV_1$(P<0.001), $FEF_{25-75%}$(P<0.001, $FEF_{50%}$(P<0.001), PEF(P<0.0005), MVV(P<0.005), $\dot{V}O_2$max (P<0.0001), and AT(P<0.0001) after average 10 days of PMV. Also there was a significant decrease in DLco(P<0.0001) and DL/VA(P<0.0001). At later($5{\pm}2$months) follow-up in 11 patients, there was no further improvement in any parameters of pulmonary function and exercise test. Twenty nine patients with sinus rhythm were divided into 16 patients with pulmonary arterial pressure(PAP) more than 35mmHg and/or tricuspid regurgitation grade n or more(group A) and 13 patients with PAP less than 35mmHg(group B). Group A Patients had significantly lower FVC(P<0.001), $FEV_1$(P<0.001), DLco(P<0.05), $\dot{V}O_2$ max(P<0.025) and mitral valve area(P<0.025) than group B patients. Group A patients after PMV, showed significant increase in FVC(P<0.001), maximum $O_2$ pulse(P<0.00001) and $\dot{V}O_2$ max(P<0.00025). Both group showed an increase in AT(P<0.0001, P<0.005), but group A showed greater decrease in $\dot{V}E/\dot{V}O_2$ and $\dot{V}E/\dot{V}CO_2$ both at AT(P<0.001, P<0.001) and $\dot{V}O_2$ max(P<0.0001, P<0.0001) after PMV compared with group B. Conclusion: These data suggest that patients with MS can show increased pulmonary function and exercise performance within 1 month after PMV. Patients with moderate to severe pulmonary hypertension had a significant increase in exercise performance compared with those with mild to no pulmonary hypertension and it is thought to be related to a significat decrease of ventilation for a given oxygen consumption at maximum exercise.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.729-741
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• 1997

Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.

• 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.