• Tuberculosis and Respiratory Diseases
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• v.40 no.5
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• pp.474-482
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• 1993

Background: As a physiologic plasminogen activator, tissue-type plasminogen activator (t-PA) could induce effective thrombolysis in massive pulmonary embolism, without the risk of systemic hemorrhage. However, therapeutic doses of t-PA has been associated with systemic lytic state, and fibrin selectivity may be influenced by the dosing regimen of t-PA. To investigate the effects of duration of t-PA infusion on blood coagulation system, we performed this study. Method: In a canine model of pulmonary embolism, which was induced by injection of autologous blood clots, we administered equal doses of t-PA (1 mg/kg) over 15 minutes in $t-PA_{15}$ group, over 180 minutes in $t-PA_{180}$ group, and only saline in control group. Then serial blood samplings were made to check complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrin, plasminogen, ${\alpha}_2$-antiplasmin, coagulation factor V and VIII, and fibrin(ogen) degradation products. Results: 1) In all 3 groups, complete blood count showed same changes. Hemoglobin, hematocrit and platelet count decreased, but WBC count increased. 2) Prothrombin time, activated partial thromboplastin time, and thrombin time were prolonged during 15-60 minutes after t-PA administration in $t-PA_{15}$ group, and from 30 minutes through 180 minutes after administration in $t-PA_{180}$ gorup. 3) Fibrin, ${\alpha}_2$-antiplasmin, and cogulation factor V and VIII decreased in both $t-PA_{15}$ and $t-PA_{180}$ group, but returned to basal levels earlier in $t-PA_{15}$ group. 4) Fibrin(ogen) degradation products increased after pulmonary embolism in all groups, and further increased in both $t-PA_{15}$ and $t-PA_{180}$ groups after t-PA infusion. But more pronounced increment was noted in $t-PA_{180}$ gorup. Conclusion: In pulmonary embolism, the shorter (15 minutes) infusion of t-PA would have less risk of systemic hemorrhage than the longer (180 minutes) infusion when the doses is equal. And, this suggests that manipulating the duration of t-PA infusion can reduce the risk of major bleeding.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.397-404
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• 1994

Background: To decide the optimal antibiotics and application of chest tube, examination of pleural fluid is fundamental in the management of empyema. Some criteria for drainage of pleural fluid have been recommended but some controversies have been suggested. Recently, newer radiologic methods including ultrasound and computed tomography scanning, have been applied to the diagnosis and management of pleural effusions. We undertook a retrospective analysis of 30 patients with pleural effusion who had CT scans of the chest in order to apply the criteria of Light et al retrospectively to patients with loculation and to correlate the radiologic appearance of pleural effusions with pleural fluid chemistry. Method: We analyzed the records of 30 out of 147 patients with pleural effusion undergoing chest CT scans. Results: 1) Six of the pleural fluid cultures yielded gram negative organisms and three anaerobic bacterias and one Staphylococcus aureus and one non-hemolytic Streptococci. No organism was cultured in ninteen cases(63.0%). 2) The reasons for taking chest CT scans were to rule out malignancy or parenchymal lung disease(46.7%), poor response to antibiotics(40.0%), hard to aspirate pleural fluid(10.0%) and to decide the site for chest tube insertion(3.3%). 3) There was no significant correlations between ATS stages and loculation but there was a tendency to loculate in stage III. 4) There was a significant inverse relationship between the level of pH and loculation(p<0.05) but there appeared to be no relationship between pleural fluid, LDH, glucose, protein, loculation and pleural thickening. 5) In 12 out of 30, therapeutic measures were changed according to the chest CT scan findings. Conclusion: We were unable to identify any correlations between the plerual fluid chemistry, ATS stages and loculations except pH, and we suggest that tube thoracotomy should be individualized according to the clinical judgement and serial observation. All patients with empyema do not need a chest CT scan but a CT scan can provide determination of loculation, guiding and assessing therapy which should decrease morbidity and hospital stay.

• Tuberculosis and Respiratory Diseases
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• v.40 no.5
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• pp.501-508
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• 1993

Background: Sleep apnea syndrome is a common disorder which is estimated to affect about 1~4% of adult male population. And if untreated, sleep apnea can cause significant sequelae, such as hypertension, nocturnal cardiac arrhythmia, daytime hypersomnolence, and cognitive impairment. Various kinds of treatment for obstructive sleep apnea (OSA) have been developed. Among them nasal CPAP, first introduced by Sullivan et al in 1981, has received widespread interest and acclaim as a treatment of OSA, and is currently recommended as first-line treatment for OSA. We evaluated the effect of nasal CPAP in OSA and the side effects of nasal CPAP hindering patients from using nasal CPAP. Methods: We performed sleep studies in 20 OSA patients at 2 consecutive nights; baseline night at first day and CPAP night at second day. We compared apnea index, lowest oxygen concentration during apnea, maximal apnea time, and total apnea duration per total sleep time before and after CPAP. We also evaluated the side effects of CPAP with inquiry to the patients. Results: 1) Apnea index was significantly decreased after CPAP in 17 out of 20 OSA patients (85%) and increased in 3 patients (15%). 2) Average apnea index was significantly decreased after CPAP ($34.1{\pm}18.9/h{\rightarrow}15.4{\pm}10.3/h$, p<0.01). 3) Total apnea duration per total sleep time was also significantly decreased after CPAP ($28.5{\pm}16.0%{\rightarrow}11.9{\pm}9.3%$, p<0.05). 4) The lowest oxygen satuation and maximal apnea time were not significantly changed after CPAP. 5) The most frequent side effect of nasal CPAP was mask discomfort (80%), and the next was drying of nasal passages (65%). Conclusion: Nasal CPAP is an effective treatment for OSA. Futher studies should be concentrated on long term follow up of nasal CPAP for its therapeutic effects and the study of methods to enhance patients' compliance.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.612-618
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• 2002

Background : Bronchoscopy is an important diagnostic and a therapeutic tool in chest medicine. However, most patients feel that a bronchoscopy is an unpleasant procedure, and it is important to sedate the patients appropriately, particularly where repetitive examinations are required. Midazolam is a sedative drug with amnestic qualities and a rapid 2 hour half-life. This study have attempted to determine the safety, appropriate dosage, and the effect of midazolam premedication in patients who underwent a bronchoscopy. Methods : One hundred and eighty consecutive patients undergoing bronchoscopy were enrolled in this study. The patients received a midzolam doses of 0.03 mg/kg, 0.06 mg/kg, or a placebo. An additional dose of lidocaine, the total number of coughs, and the duration of the procedures were recorded with monitoring the the blood pressure, heart rate, and oxygen saturation. The level of satisfaction was assessed by the patient, bronchoscopist, and the nurse. Results : The blood pressure, pulse rates, oxygen saturation, number of coughs, lidocaine dose, and procedure time in the 3 groups were similar. There was a trend for the midazolam 0.03 mg/kg group to satisfy bronchoscopists more than the other two groups. The nurses' acceptability was lower in the midazolam 0.06 mg/kg group than the other groups. The patients' acceptablity was greater in both the midazolam 0.03 mg/kg and 0.06 mg/kg groups than in the control group. Conclusion : Sedation with low doses of intravenous midazolam is a safe technique for fiberoptic bronchoscopy with a low morbidity and high acceptable to patients and bronchoscopists.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.441-452
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• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.178-186
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• 2004

Background : Photodynamic therapy (PDT) is a new therapeutic method aimed at the selective destruction of cancer cells. The outcome is death of cancer cells through apoptosis or necrosis. The aim of this study was to investigate the characterization of PDT induced cell death in A549 lung cancer cells. Materials and methods : A549 cells were used as the lung cancer cell. 5 aminolevulinic acid (ALA) was used as the photosensitizer and a 632nm diode laser (Biolitec, Germany) as the light source. Cells were incubated with various concentrations of ALA. The 632nm diode laser was then administered for various laser irradiation times. The treated cells were incubated with 24, 48 and 72 hours. The cell viabilities were measured using the crystal violet assay and light microscopy. To observe the cell death mechanism after PDT, cells were observed under fluorescence microscopy after double staining with Hoechst 33342 and propium iodide after PDT. Results : In the crystal violet assay at 24 hours after PDT with a $3.2J/cm^2$ laser irradiation power, the cell viabilities were $89.56{\pm}4.11$, $87.67{\pm}5.48$, and $69.37{\pm}8.84$ with ALA concentrations of 10, 100, and $1mg/m{\ell}$, respectively. In crystal violet assay at 24 hours after PDT with $1mg/m{\ell}$ of ALA, the cell viabilities were $74{\pm}19.85$, $55{\pm}6.1$, and $49.06{\pm}16.64%$ with 1.6, 3.2 and $6.4J/cm^2$ laser irradiation powers, respectively. However, increasing the interval time after PDT did not change the cell viabilities. In the apoptosis assay, photodynamic therapy was inducing the apoptotic cell death. Conclusions : This study shows the apoptotic anticancer effect of photodynamic therapy in A549 lung cancer cells. However, further evaluations with other cancer cells and photosensitizers are necessary.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.178-185
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• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.280-287
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• 2009

Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.272-277
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• 2008

Background: The efficacy of the use of the interventional bronchoscope for palliation of patients with central airway obstruction has been established. In the palliative setting to alleviate central airway obstruction, the use of laser resection, electrocautery, argon plasma coagulation, photodynamic therapy and cryotherapy can provide relief of an airway obstruction. Cryotherapy is the therapeutic application of extreme cold for the local destruction of living tissue. Recently, this technique has been used for endoscopic management of central airway obstructions in Korea. We report the role and complications of the use of cryotherapy for airway obstructions in patients with advanced lung cancer. Methods: We used a flexible cryoprobe for cryotherapy using nitrous oxide as a cryogen. The cryoprobe was applied through the working channel of a flexible fiberoptic bronchoscope. The temperature of the tip was approximately $-89^{\circ}C$, and the icing time was 5~20 seconds. Results: Four patients with a central airway obstruction from advanced lung cancer were treated with cryotherapy. Three of the four patients were treated successfully and the airway obstruction was improved after the cryotherapy procedure. Dyspnea, hypoxia and atelectais were improved in three cases. Two patients experienced complications- one patient experienced pneumomediastinum and the other patient experienced massive hemoptysis during the cryotherapy procedure. However, these complications resolved and did not influence mortality. Conclusion: This technique is effective and relatively safe for palliation of inoperable advanced lung cancer with a central airway obstruction.

• Progress in Medical Physics
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• v.9 no.4
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• pp.227-245
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• 1998

A most appropriate model of 3-D conformal radiotherapy has been induced by clinical evaluation and animal study, and therapeutic gains were evaluated by numerical equation of tumor control probability(TCP) and normal tissue complication probability (NTCP). The radiation dose to the tumor and the adjacent normal organs was accurately evaluated and compared using the dose volume histogram(DVH). The TCP and NTCP was derived from the distribution of given dosage and irradiated volume, and these numbers were used as the biological index for the assessment of the treatment effects. Ten patients with liver disease have been evaluated and 3 dogs were sacrificed for this study. Based on the 3-D images of the tumor and adjacent organs, the optimum radiation dose and the projection direction which could maximize the radiation effect while minimizing the effects to the adjacent organs could be decided. 3). The most effective collimation for the normal adjacent organs was made through the beams eye view with the use of multileaf collimator. When the dose was increased from 50Gy to 70Gy, the TCP for the conventional 2-port radiation and the 5-port multidimensional therapy was 0.982 and 0.995 respectively, while the NTCP was 0.725 and 0.142 respectively, suggesting that the 3-D conformal radiotherapy might be the appropriate therapy to apply sufficient radiation dose to the tumor while minimizing the damages to the normal areas of the liver. Positive correlation was observed between the NTCP and the actual complication of the normal liver in the animal study. The present study suggest that the use of 3-D conformal radiotherapy and the application of the mathematical models of TCP and NTCP may provide the improvements in the treatment of hepatoma with enhanced results.