Pulmonary arterial hypertension (PAH) is often difficult to diagnose and challenging to treat. Untreated, it is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. The past decade has seen remarkable improvements in therapy, driven largely by the conduct of randomized controlled trials. Still, the selection of most appropriate therapy is complex, and requires familiarity with the disease process, evidence from treatment trials, complicated drug delivery systems, dosing regimens, side effects, and complications. We tried to provide evidencebased treatment recommendations for physicians involved in the care of these complex patients. Due to the complexity of the diagnostic evaluation required, and the treatment options available, it is strongly recommended that consideration be given to referral of patients with PAH to a specialized center. (Tuberc Respir Dis 2006; 60: 142-150)
Background : Excision repair cross complementing gene 1 (ERCC1) not only has a protective role against carcinogens, but plays an important role in cisplatinresistance via the repair of cisplatinDNA adducts. This study investigated the association between the ERCC1 expression levels in sputum and survival after cisplatinbased chemotherapy in patients with inoperable nonsmall cell lung cancer (NSCLC).Methods : Using the sputum collected from 67 inoperable (stage
Background : The aberrant promoter hypermethylation of p16INK4a, as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of p16INK4a promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation.Methods : Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16INK4amethylation was determined using methylation-specific polymerase chain reaction.Results : p16INK4a methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum.Conclusions : There was a higher level of p16INK4a methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that p16INK4a promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.(Tuberc Respir Dis 2006; 60: 160-171)
Background : Despite the emerging danger of MDRTB to human beings, there have only been a limited number of drugs developed to treat MDRTB since 1970. This study investigated the crossresistance rate between rifampicin (RFP) and rifabutin (RBU) in order to determine the efficacy of rifabutin in treating MDRTB. In addition, the results of rifabutin were correlated with the rpoB mutations, which are believed to be markers for MDRTB and RFP resistance.Methods : The MICs of RBU were tested against 126 clinical isolates of MDRTB submitted to the clinical laboratory of National Masan TB Hospital in 2004. Five different concentrations (10160μg/ml) were used for the MICs. The detection of the rpoB mutations was performed using a RFP resistance detection kit with a line probe assay(LiPA), which contains the oligonucleotide probes for 5 wide type and 3 specific mutations (513CCA, 516GTC, and 531TTG) The rpoB mutation was determined by direct sequencing.Results : The rate of crossresistance between RFP and RBU was 70.5%(74/105) at 20μg/ml RBU(ed note: How much RFP?) Most mutations (86.3%) occurred in the 524~534 codons. The His526Gln, His526Leu, Leu533Pro, Gln513Glu, and Leu511Pro mutations(Ed note: Is this correct?) were associated with the susceptibilty to RBU.Conclusion : Based on the crossresistance rate between RFP and RBU, RBU may be used effectively in some MDRTB patients. Therefore, a conventional drug susceptibility test for RBU and a determination of the critical concentration are needed. However, rpoB gene mutation test may be have limited clinical applications in detecting RBU resistance.(Tuberc Respir Dis 2006; 60: 171-179)
Background : Para-aminosalicylic acid(PAS) is a 2nd-line drug that can cause severe adverse reactions leading to poor patient compliance. This study evaluated the relapse rate according to the discontinuance of PAS at a certain point after bacteriological conversion during the course of chemotherapy for multidrug-resistant tuberculosis(MDR-TB).Methods : 42 out of 452 MDR-TB patients were enrolled in this study. All subjects were receiving chemotherapy including PAS at National Masan TB Hospital between Jan. 1, 2000 and Dec. 31, 2001. The relapse rate was evaluated after the discontinuance of PAS from their initial regimen as a result of the severe adverse reactions at a certain point after the bacteriological conversion during the course of chemotherapy for MDR-TB.Results : The male to female ratio was 2.5:1, and the mean age was 47.2 years old. The average number of past histories, used drugs and resistant drugs was 1.2, 3.9 and 4.3. The mean number of sensitive drugs included in the inirial regimen was 3.9. The mean time for bacteriological conversion and discontinuance of the PAS was 2.3 months after initiating treatment and 6 months after bacteriological conversion, respectively. There was no relapse after discontinuing PAS during a mean follow up period of 31.6 months.Conclusion : PAS may be discontinued in the cases of serious gastrointestinal problems approximately 6 months after bacteriological conversion without concern about relapse.(Tuberc Respir Dis 2006; 60: 180-186)
Background : Normal cell proliferation and viability is strongly depends on the availability of metabolic energy and the maintenance of the appropriate adenylate-nucleotide pools. Hypothetically, changes in adenylate kinase (AK) expression could therefore be associated with adaptation to altered growth characteristics or inversely altered growth characteristics of proliferating cells could drive the changes in the metabolic profile. This study investigated whether the expression of either AK1 or a Mycobacterium tuberculosis adenylate kinase mutant which has the same catalytic activity of AK1 could affect the growth rate of slow-growing BCG. Method : Recombinant BCGs, which were cloned the human muscle-type adenylate kinase synthetic gene (AK1) and adenylate kinase mutation gene (AKmtDM) of Mycobacterium tuberculosis into the Mycobacterium/E.coli expression vectors, were constructed. Recombinant BCGs and wild-type BCG were cultured in 7H9 media and the optical density at 600nm was measured at intervals of 2-3 days.Result : There wasn't the growth rate change induced by AK1 or AKmtDM expression in recombinant BCGs. Conclusion : The expression of AK1 or Mycobacterium tuberculosis adenylate kinase mutant in BCG does not affect the growth rate of BCG.(Tuberc Respir Dis 2006; 60: 187-193)
Background : Even though tuberculosis (TB) is still a major public concern in Korea, there is little data on the management of TB patients and its outcomes in the private sector. This study evaluated the status of TB treatment in the private sector.Methods : Sixteen-hundred-sixty-six TB patients who were notified in a private university hospital from 2001 to 2002 were enrolled in this study. The patients were divided into pulmonary (TBP), extrapulmonary (TBE), and combined (TBP+E) groups, and were also divided into initial and retreatment groups. The clinical characteristics, diagnostic methods, treatment regimens, and outcomes were analyzed and compared.Results : The mean age of the 1,666 patients was 48.9 years and the male-to-female ratio was 1.3:1. The number of patients in the initial and retreatment groups of TBP, and those of (TBE + TBP+E) were 809, 276, 480, 101, respectively. A bacteriological study was performed in 92.0% of cases, and a positive culture was confirmed in 58.1% and 31.7% of patients with TBP and (TBE + TBP+E), respectively (p<0.05). The AFB smear was positive in 45.4 % of the TBP patients. PCR was carried out in 60.4% of the (TBE + TBP+E) group. The MDR was detected in 14.0% of isolates. Overall, the treatment completion, default, and death rates were 70.2%, 13.5% and 1.9%, respectively.Conclusion : Even though the management of TB patients in a private hospital was satisfactory in terms of the national guidelines, the high default rate was is still a problem. Efforts to decrease the default rate either independently or in cooperation with the public sector will be needed.(Tuberc Respir Dis 2006; 60: 194-204)
Background : Acute exacerbations form a major component of the socioeconomic burden of COPD. As yet, little information is available about the long-term outcome of patients who have been hospitalized with acute exacerbations, although high mortality rates have been reported. The aim of this study was to determine predictors of long-term mortality after hospitalization for acute exacerbation of COPD.Methods : We performed a retrospective cohort study of consecutive patients admitted to the hospital for COPD exacerbation between 2000 through 2004. Patients who had died in hospital or within 6-months after discharge, had tuberculosis scar, pleural thickening or bronchiectasis by chest radiography or had been diagnosed with malignancy during follow-up periods were excluded.Results : Mean age of patients was 69.5 years, mean follow-up duration was 49 months, and mean FEV1 was 1.00L (46% of predicted). Mortality was 35% (17/48). In the multivariate Cox regression analysis, heart rate of 100/min or more (p=0.003; relative risk [RR], 11.99; 95% confidence interval [CI], 2.34-61.44) and right ventricular systolic pressure (RVSP) of 35mmHg or more (p=0.019; RR, 6.85; 95% CI, 1.38-34.02) were independent predictors of mortality.Conclusion : Heart rate and RVSP in stable state may be useful in predicting long-term mortality for COPD patients admitted to hospital with acute exacerbation.(Tuberc Respir Dis 2006; 60: 205-214)
Background : Acinetobacter baumannii is an important pathogen associated with nosocomial infections in intensive care units, and is responsible for nosocomial pneumonia, UTI, bacteremia, etc. The main concern is that this pathogen is often resistant to many antimicrobial agents, particularly to carbapenem. This study compared the clinical those of ICU admitted patients with the carbapenem resistant A. baumannii isolated from the sputum with characteristics of patients with carbapenem sensitive A. baumannii.Methods : A total of 49 patients with A. baumannii from a sputum culture who were admitted to the ICU from January to December 2003 were enrolled in this study. This study evaluated the demographic variables, mortality, APACHE II score, comorbidity, antibiotics used, hospital and ICU stay, Clinical Pulmonary Infection Score, and mechanical ventilation. A retrospective analysis was made by a review of the patients' medical records.Results : Carbapenem sensitive and resistant A. baumannii was isolated from 23 patients and 26 patients respectively. Univariate analysis revealed renal disease, the use of carbapenem and aminoglycoside to be statistically significant factors for carbapenem resistance. Multivariate analysis revealed carbapenem use(p=0.024; OR, 8.17; CI 1.32 to 50.68) to be positively associated with carbapenem resistance, and aminoglycoside use(p=0.026; OR, 0.18; CI, 0.04 to 0.82) to be negatively associated with carbapenem resistance. There was no significant difference in mortality between the carbapenem sensitive and resistant group(30 vs 42%. P=0.39).Conclusion : The occurrence of carbapenem resistant A. baumannii is positively associated with carbapenem use and negatively associated with aminoglycoside use. Carbapenem resistance in the sputum culture did not affect the mortality rate. (Tuberc Respir Dis 2006; 60: 228-234)
Exogenous lipoid pneumonia (ELP) is an uncommon condition resulting from aspiration or inhalation of vegetable, animal or mineral oil. It results in foreign body type inflammatory reaction of the lung and can show various clinical presentations from asymptomatic incidental finding to severe pneumonia leading to acute respiratory failure. Although many cases have been reported, severe ELP requiring steroid or whole lung lavage for treatment is rare. We report a case of 51year old man with esophageal cancer who developed severe ELP following ingestion of large dose shark oil (Squalene) and successfully treated with prednisolone.(Tuberc Respir Dis 2006; 60: 235-238)