• Tuberculosis and Respiratory Diseases
• /
• v.50 no.1
• /
• pp.94-105
• /
• 2001

Background : Examining the biological susceptibility of Mycobacterium tuberculosis to pyrazinamide (PZA) in vitro is very difficult as PZA is inactive under normal culture conditions. The biological susceptibility test, an enzyme assay for Pzase activity, and a genetic test for pncA gene mutations, were performed in order to predict PZA resistance. Methods : 28 cultured clinical isolates of Mycobacterium tuberculosis were tested. The biological susceptibility was performed by the absolute concentration method using Lowenstein-Jensen media. The PZase activity was tested by means of Wayne's method. A 710-bp region includes the entire open reading frame of pncA was amplified and sequenced. Results : All six strains with positive PZase activity exhibited no pncA mutations with one strain showing a false resistance in the biological susceptibility test. Among the 22 strains with no PZase activity, 21 exhibited showed pncA mutations. In the biological susceptibility test, 20 strains were resistant, and one was susceptible, and the other flied to test. The mutation types varied with ten missense, one silent and one nonsense mutation 1 slipped-strand mispairing, and 6 frameshift mutations. Three strains had an adenine to guanine mutation at position -11 upstream of the start codon. Conclusion : The mutation at the pncA promotor region is frequent at -11 upstream position. Automatic sequencing of pncA is a useful tool for rapid and accurate detection of PZA resistant M. tuberculosis, and for demonstrating the epidemiological relatedness of the PZA resistant M. tuberculosis strains.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.1
• /
• pp.84-93
• /
• 2001

Backgrounds : In the absence of distant metastasis, small cell lung cancer (SCLC) patients presenting with supraclavicular lymph node (SCLN) involvement and pleural effusion can benefit from thoracic radiotherapy. But there are some debate as to the prognostic significance of both SCLN involvement and pleural effusion. The purpose of this study was to determine the prognostic significance of SCLN involvement and pleural effusion in SCLC. Methods : Two Hundred and fifteen patients with histologically confirmed small cell lung cancer, who were treated either at the Keimyung university Dongsan hospital and Kyungpook national university hospital from January 1994 to June 1998, were evaluated retrospectively. The patients were classified as having either limited or extensive stage using the Veterans Administration staging system. Results : SCLN was presented in 10.5% of patients(n=21). The median survival was 247 days for patients with SCLN(n=21) and 264 days for patients without(n=194) (p=0.52). After treatment, the median survival was 298 days for patients with SCLN(n=13) and 348 days for patients without(n=115) (p=0.52). SCLN involvement was not correlated with the presence of distant metastases. Median survival was 459 days for patients with a limited stage without SCLN(n=66), 650 days for those with a limited stage with SCLN (n=7) (p=0.96). Pleural effusion was presented in 24.7% of patients(n=52). The median survival was 198 days for patients with pleural effusion(n=52) and 275 days for patients without(n=163) (p<0.05). After treatment, the median survival was 294 days for patients with a pleural effusion(n=25) and 286 days for patients without(n=103) (p=0.39). The presence of pleural effusion was not correlated with that of distant metastases. The median survival was 395 days for patients with a limited stage without a pleural effusion(n=63), 451 days for those with a limited stage with pleural effusion(n=10) (p=0.92). Conclusionsa : In this study, SCLN involvement does not explain the poor survival rate and the relevance to extensive staged disease. Furthermore, the existence of a pleural effusion did not correlated with the presence of distant metastases. However, the presence of a pleural effusion appears to be a minor prognostic factor in our study. Therefore supraclavicular lymph node involvement and the presence of a pleural effusion in SCLC are not poor prognostic factors, which does not justify any amendment to the staging system currently used.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.2
• /
• pp.388-396
• /
• 1998

Background: Etiologic diagnosis of pleural effusion is usually made by clinical characteristics, pleural fluid analysis and pleural biopsy. But, despite careful diagnostic study, the cause of pleural effusion cannot be found in about 20 percent of patients, especially in loculated pleural effusions. Tuberculous pleurisy is one of the most common cause of pleural effusion in Korea. But, pleural fluid culture for Mycobacterium tuberculosis are positive in only 20 to 30 percent of patients and typical pleural biopsy finding in less than 50 percent of patients with this disease. In recent studies, adenosine deaminse(ADA) and its isoenzymes were proposed to be a useful diagnostic tool for differential diagnosis of pleural effusion. We investigated the pattern of ADA and its iscenzyme activities in various cause of pleural effusions to evaluate the diagnostic value of measuring ADA and its isoenzymes. Method: We measured total ADA and its isoenzyme activities in pleural fluid and serum from 54 patients with pleural effusion(25 tuberculous pleural effusion, 10 parapneumonic effusion, 14 malignant pleural effusion, 5 transudative pleural effusion), including 5 loculated tuberculous pleural effusions and 6 loculated parapneumonic effusions. Total ADA activity was measured by the spectrophotometric method and ADA2 isoenzyme activity was measured with same method using EHNA, potent inhibitor of ADA1 isoenzyme activity. Result: Total ADA activity of tuberculous pleural effusion was higher than malignant pleural effusion(p<0.01), but no significant difference was found between tuberculous pleural effusion and parapneumonic effusion(tuberculous pleural effusion: $148.9{\pm}89.9IU/L$, parapneumonic effusion: $129.0{\pm}119.4IU/L$, malignant pleural effusion: $48.7 {\pm}39.7IU/L$). Percentage of ADA2 activity to total ADA activity(ADA2%) of pleural effusion of tuberculous pleurisy was higher than parapneumonic effusion(p<0.05). but no significant difference was found between tuberculous pleural effusion and malignant pleural effusion(tuberculous pleural effusion: $57.2{\pm}10.7%$, parapneumonic effusion: $35.9{\pm}17.8%$, malignant pleural effusion: $60.7{\pm}4.1%$). In loculated pleural effusion, ADA2% of tuberculous pleural effusion was higher than parapneumonic effusion(tuberculous pleural effusion: $53.3{\pm}3.9%$, parapneumonic effusion: $27.8{\pm}7.9%$). Conclusion: Measurement of ADA isoenzyme activity is useful for differentiating tuberculous pleural effusion from parapneumonic effusion, especially in loculated pleural effusion.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.1
• /
• pp.54-66
• /
• 2000

Background: Pneumoconiosis, like other chronic respiratory diseases, is essentially incurable and, for many, progressive. While improved survival time is an important aim of treatment, there is growing recognition that for some people, improving the quality of life is more important than extending the length of life. Currently the measurement of the quality of life is used to assess the efficacy of therapeutic agents. Methods: Sixty-three pnemoconiotics who were admitted to St. Mary's Hospital between April and August 1999 were interviewed using COOP charts, Chronic Respiratory Questionnaire(CRQ) and Pneumoconiotic Respiratory Questionnaire(PRQ), a newly developed questionnaire concerning clinical and socioeconomic features of pneumoconiotics. Also, ILO classification of the chest film, pulmonary function test, and arterial blood gas analysis of the patients were evaluated. The scores between Industrial Accident Compensation Insurance(IACI) covered and uncovered patients and between clinically stable and unstable patients were compared. Results: Domains of CRQ and PRQ showed a high internal consistency reliability($\alpha$=0.86-0.89, 0.77-0.81) except the dyspnea domain($\alpha$=0.63) of CRQ. The scores on the CRQ and PRQ showed statistically significant correlations with the results of COOP charts, pulmonary function test and arterial blood gas analysis. The dyspnea domain and social activity domain of the PRQ showed significant difference between IACI covered and uncovered patients and between clinically stable and unstable patients. Conclusion : Korean translation of the Chronic Respiratory Questionnaire and the newly developed Pneumoconiotic Respiratory Questionnaire are reliable and valid methods and are likely to be useful in measuring the quality of life in patients with the chronic respiratory disease including pneumoconiosis.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.2
• /
• pp.280-289
• /
• 1998

Background: It is sometimes difficult to differentiate tuberculous pleural effusion from malignant pleural effusion by clinical symptoms, signs, by routine tests of pleural fluid, and by pathologic studies. And recently, it was discovered that cytokines such as IL-2, IFN-$\gamma$, TNF-$\alpha$ are elevated in tuberculous pleural fluid, and there have been several attempts to diagnose tuberculous pleural effusion by using these immunological mediators. There are several studies regarding the diagnostic value of IFN-$\gamma$, and there are two studies in Korea. But the diagnostic values of IFN-$\gamma$ in these studies were slightly lower than those in other countries. To compare the diagnostic value of IFN-$\gamma$ with those of CEA and ADA, and to determine the sensitivity and specificity of IFN-$\gamma$ in Korean, we mesured IFN-$\gamma$, CEA level and ADA activity in pleural effusions. Methods: ADA activity, IFN-$\gamma$ level and CEA level as well as cell count, differential count, and biochemical assays such as protein content and lactate dehydrogenase were measured in 40 cases of tuberculous pleuritis and 42 cases of malignant pleural effusion. Results: Tuberculous pleural fluid showed higher levels of IFN-$\gamma$ and ADA ($832.6{\pm}357.2$ pg/ml and $82.5{\pm}25.9$ U/L, respectively) than those of malignant pleural effusion ($2.6{\pm}8.0$ pg/ml and $19.2{\pm}10.9$ U/L, respectively) (p<0.01). Malignant pleural effusions showed higher median value (102.2 ng/ml) than tubercalous pleural effusions (1.8 ng/ml) (p<0.01). The sensitivities of IFN-$\gamma$, ADA, CEA were 0.97, 0.87, 0.67 and the specificities of IFN-$\gamma$, ADA, CEA were 1.0, 0.97, 1.0, respectively. There was no significant correlation between ADA activity and IFN-$\gamma$ level. Conclusion: This study showed that IFN-$\gamma$ test would be a very useful clinical test for differential diagnosis of tuberculous pleuritis and malignant pleural effusion because it is very sensitive and specific, although it is an expensive test.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.5
• /
• pp.942-952
• /
• 1998

The aim of this study was to evaluate spontaneous and LPS stimulated proinflammatory cytokines and chemokine release of alveolar macrophages in the patients with pulmonary tuberculosis and healthy individuals, as a control. Alveolar macrophages recovered from bronchoalveolar lavage fluids were cultured with or without LPS 0.1, 1, or 10 ${\mu}g/ml$ for 24 and 48 hours in 37C, 5% CO2. TNF-$\alpha$, IL-1$\beta$, IL-6 and IL-8 amount were evaluated using ELISA kit from the supernatants. There were a significant increase in the spontaneous 24 hours release of TNF-$\alpha$ and IL-6 from the involved segments of tuberculosis patients compared with uninvolved segments and normal control There were also increasing trends of release of them after LPS stimulation in involved segments, but not significant. IL-1$\beta$ and IL-8 were not evaluated from the involved segments of tubeculosis and there were not significant differences of them between uninvolved segments of tuberculosis and normal control. It is concluded that cytokine release of alveolar macrophages in the pulmonary tuberculosis was markedly increased, and it was localized to the alveolar macrophages from the involved segments.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.6
• /
• pp.703-714
• /
• 2000

Background : Surfactant protein A (SP-A) is important in the regulation of surfactant secretion, synthesis and recycling. SP-A has important roles in regulating surfactant metabolism as well as in determining surfactant's physical properties. Since systemic sepsis is one of the common causes of acute respiratory distress syndrome (ARDS) and abnormalities in surfactant function have been described in ARDS, the authors investigated the effects of endotoxemia on the accumulation of mRNA encoding SP-A and SP-A protein content. Methods : Adult rats were given various doses of intraperitoneal endotoxin from Salmonella enteritidis and sacrificed at different times. SP-A mRNA was measured by filter hybridization method. Lung SP-A protein content was determined by double sandwich ELISA assay using a polyclonal antiserum raised in rabbits against purified rat SP-A. Results : 1) The accumulation of SP-A mRNA in the endotoxin treated group 24 hours after 2mg/kg and 5mg/kg endotoxin treatments was significantly increased 50.9% and 27.3%, respectively, compared to the control group (P<0.001, P<0.025). 2) The accumulation of SP-A mRNA 24 hours in the 5mg/kg endotoxin treated group was significantly increased by 26.5% compared to the control group (P<0.01). 3) Total amount of lung SP-A was not altered at 24 hours by various doses of treatment. Total lung SP-A content 144 hours after endotoxin administration was significantly decreased by 51.4% compared to the control group (P<0.01). Conclusions : The specific regulation of SP-A by various time course in vivo is evident. The late decline in SP-A protein content was unexpected and suggests that SP-A may be differentially regulated during lung inflammation. The functional significance of these alterations remains to be clarified.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.6
• /
• pp.715-723
• /
• 2000

Background : Obstructive sleep apnea syndrome (OSAS) affects systemic blood pressure and cardiac function. The development of cardiovascular dysfunction including the changes of systemic blood pressure and cardiac rhythm, suggests that recurrent hypoxia and arousals from sleep may increase a sympathetic nervous system activity. Continuous positive airway pressure (CPAP) therapy has been found to be an effective treatment of OSAS. However, only a few studies have investigated the cardiovascular and sympathetic effects of CPAP therapy. We evaluated influences of nasal CPAP therapy on the cardiovascular system and the sympathetic activity in patients with OSAS. Methods : Thirteen patients with OSAS underwent CPAP therapy and were monitored using polysomnography, blood pressure, heart rate, presence of arrhythmia and the concentration of plasma catecholamines, before and with CPAP therapy. Results: The apnea-hypopnea index (AHI) was significant1y decreased (p<0.01) and the lowest arterial oxygen saturation level was elevated significantly after applying CPAP (p<0.01). Systolic blood pressure tended to decrease after CPAP but without statistical significance. Heart rates during sleep were not significantly different after CPAP. However, the frequency and number of types of arrhythmia decreased and sinus bradytachyarrhythmia disappeared after CPAP. Although there was no significant difference in the level of plasma epinephrine concentration, plasma norepinephrine concentration significantly decreased after CPAP (p<0.05). Conclusion : CPAP therapy decreased the apnea-hypopnea index, hypoxic episodes and plasma norepinephrine concentration. In addition, it decreased the incidence of arrhythmia and tended to decrease the systemic blood pressure. These results indicate that CPAP may play an important role in the prevention of cardiovascular complications in patients with OSAS.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.5
• /
• pp.1039-1046
• /
• 1998

Background: Sleep-related breathing disorders(SRBD) and periodic leg movements disorder(PLMD) are both common, and are considered as separate sleep disorders. However, both disorders show high comorbidity. SRBD and PLMD can result in excessive daytime sleepiness and insomnia due to frequent sleep fragmentation. So, it is very important to consider the presence of PLMD, when we are dealing with the diagnosis and management of SRBD. The objectives of this study were to determine the incidence of PLMD in patients with SRBD, and to describe any differences between patients with and without PLMD. Method: The authors reviewed the sleep recordings of 106 patients with a final diagnosis of SRBD(obstructive sleep apnea or upper airway resistance syndrome), who underwent full nocturnal polysomnography, including the monitoring of the anterior tibialis electromyogram. All sleep records were recorded and scored using the standard criteria. The data was analyzed by the student t-test. Result: 106 patients(M=76, F=30) were included in the analysis. Data revealed a mean age of $49.5{\pm}13.6$ years, a respiratory disturbance index(RDI) of $22.3{\pm}25.4$/hour sleep, a lowest oxygen saturation of $84.9{\pm}11.3%$, a maximal esophageal pressure of $-41.0{\pm}19.1cmH_2O$, and PLM index(PLMI) of $13.1{\pm}22.4$movements/hour sleep. Forty four percent(47 of 106 patients) had a PLMI of greater than 5 on this study. The mean age of the patients with PLMD was significantly higher than that of the patients without PLMD(p<0.005). Female patients with SRBD accompanied more PLMD(p<0.05). The apnea index of the patients with PLMD was significantly lower than that of the patients without PLMD(p<0.01). The percentage of stage 1 sleep in the patients with PLMD was significantly lower than that of the patients without PLMD(p<0.05). Conclusion: The prevalence of PLMD in the patients with SRBD was high at 44.3%. The patients with PLMD were older and had more high RDI in comparison to the patients without PLMD, which was consistent with previous findings. The authors recommend that more careful consideration of PLMD is required when diagnosing and treating SRBD.

• Tuberculosis and Respiratory Diseases
• /
• v.58 no.4
• /
• pp.352-358
• /
• 2005

Microsatellites are short tandem repeated nucleotide sequences that are present throughout the human genome. Variations in the repeat number or a loss of heterozygosity around the microsatellites have been termed a microsatellite alteration (MA). A MA reflects the genetic instability caused by an impairment in the DNA mismatch repair system and is suggested to be a novel tumorigenic mechanism. A number of studies have reported that MA in the DNA extracted from the plasma occurs at varying frequencies among patients with a non-small cell lung carcinoma (NSCLC). The genomic DNA from 9 subjects with a non-small cell lung cancer (squamous cell cancer 6, adenocarcinoma 2, non-small cell lung cancer1) and 9 age matched non-cancer control subjects (AMC: tuberculosis 3, other inflammatory lung disease 6) and 12 normal control subjects (NC) were extracted from the peripheral blood leukocytes and plasma. Three microsatellite loci were amplified with the primers targeting the Gene Bank sequence D21S1245, D3S1300, and D3S1234. MA in the form of an allelic loss or a band shift was examined with 6% polyacrylamide gel electrophoresis and silver staining. None (0/12) of the NC subjects less than 40 years of age showed a MA in any of the three markers, while 88.9%(8/9) of the AMC above 40 showed a MA in at least one of the three markers (p<0.05). Sixty percent(6/10) of the control subjects with a smoking history showed a MA in one of the three markers, while 9.1%(1/11) of the control subjects without smoking history showed a MA (p<0.05). However, not only did 66.7%(6/9) of lung cancer patients show a MA in at least one of the three markers but so did 88.9%(8/21) of the AMC patients (p>0.05). In conclusion, a MA in the D21S1245, D3S1300, and D3S1234 loci using DNA extracted from the plasma was detected in 66.7% of lung cancer while no MA was found in the young non-smoking control subjects. However, many of the non-cancer control subjects (aged smokers) also showed a MA, which compromised the specificity of the MA analysis as a screening test. Therefore, a further study with a larger sample size will be needed.