Rifabutin susceptibility and rpoB gene mutations in multi-drug resistant mycobacterium tuberculosis / 결핵

BACKGROUND: Following several decades of decline, the incidence of tuberculosis has recently begun to increase in many countries and the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutaitions of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB. METHODS: Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients two visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the result were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB. RESULTS: Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526. CONCLUSION: The frequency and pattern of mutations of the rpoB gene of Korean MDR-Tb isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.

Exercise Capacity and Maximum Oxygen Consumption before and after Percutaneous Mitral Balloon Valvuloplasty

To evaluate exercise capacity, treadmill test and exercise pulmonary function test with cycle ergometer were preformed in 52 patients(pts) (M/F : 18/34, mean age : 43+/-11 yrs) with mitral stenosis before and 5~10 days after percutaneous mitral balloon valvuloplasty(PMV). Twenty four pts had atrial fibrillation. The results are as follow : 1) The mitral valve area increased from 0.9+/-0.2 to 1.8+/-0.3cm2(P<0.001). 2) The duration of exercise time on treadmill test(modified Bruce protocol) increased from 7.7+/-3.3min to 11.1+/-2.6min(P<0.001), but peak heart rate(HR) and maximum double product(MDP) did not change significantly. After exclusion of the patients with atrial fibrillation, peak HR and MDP increased from 157+/-24beats/min and 22350+/-8220mmHg beat to 165+/-19beats/min and 26290+/-5770mmHg beat respectively(P<0.05). 3) Diffusion capacity and diffusing capacity/alveolar volume at rest decreased from 95+/-25% and 112+/-24% to 87+/-22% and 100+/-18% respectively(p<0.001). 4) FVC, FEV1, FEV1/FVC, FEF25~75% and maximum voluntary ventilation increased from 77+/-12%, 79+/-16%, 104+/-10%, 69+/-25%, and 68+/-14%, to 80+/-11%, 84+/-14%. 106+/-9%, 78+/-25%, and 74+/-12%, respectively(P<0.05). But total lung capacity, residual volume and functional residual capacity did not change significantly. 5) Maximum oxygen consumption, anaerobic threshold, oxygen pulse and maximum work load during exercise increased form 53+/-14%, 34+/-8%, 6.2+/-2.1ml/min and 48+/-18 watts to 61+/-13%, 39+/-7%, 7.3+/-2.0ml/min and 58+/-20 watts respectively(P<0.0005). We conclude that oxygen transport and exercise capacity improve within 10days after PMV and the improvement results from not only hemodynamic improvement but also improvement of static pulmonary function.