• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.724-732
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• 2000

Background : In patients with severe chronic lung diseases even a small pneumothorax can result in life-threatening respiratory distress. It is important to treat the attack by chest tube drainage until the lung expands. Pneumothorax with a persistent air leak that does not resolve under prolonged tube thoracostomy suction is usually treated by open operation to excise or oversew a bulla or cluster of blebs to stop the air leak. Pleurodesis by the instillation of chemical agents is used for the patient who has persistent air leak and is not good candidate for surgical treatment. When the primary trial of pleurodesis with common agent fails, it is uncertain which agent should be used f or stopping the air leak by pleurodesis. It is well known that inappropriate drainage of hemothorax results in severe pleural adhesion and thickening. Based on this idea, some reports described a successful treatment with autologous blood instillation for pneumothorax patients with or without residual pleural space. We tried pleurodesis with autologous bood for pneumothorax with persistent air leak and then we evaluated the efficacy and safety. Methods : Fifteen patients who had persistent air leak in the pneumothorax complicated from the severe chronic lung disease were enrolled. They were not good candidates for surgical treatment and doxycycline pleurodesis failed to stop up their air leaks. We used a mixture of autologous blood and 50% dextrose for pleurodesis. Effect and complications were assessed by clinical out∞me, chest radiography and pulmonary function tests. Results : The mean duration of air leak was 18.4${\pm}$6.16 days before ABP (autologous blood and dextrose pleurodesis) and $5.2{\pm}1.68$ days after ABP. The mean severity of pain was $2.3{\pm}0.70$ for DP(doxycycline pleurodesis) and $1.7{\pm}0.59$ for ABDP (p<0.05). There was no other complication except mild fever. Pleural adhesion grade was a mean of $0.6{\pm}0.63$. The mean dyspnea scale was $1.7{\pm}0.46$ before pneumothrax and $2.0{\pm}0.59$ after ABDP (p>0.05). The mean $FEV_1$ was $1.47{\pm}1.01$ before pneumothorax and $1.44{\pm}1.00$ after ABDP (p>0.05). Except in 1 patient, 14 patients had no recurrent pneumothorax. Conclusion : Autologous blood pleurodesis (ABP) was successful for treatment of persistent air leak in the pneumothorax. It was easy and inexpensive and involved less pain than doxycycline pleurodesis. It did not cause complications and severe pleural adhesion. We report that ABP can be considered as a useful treatment for persistent air leak in the pneumothorax complicated from the severe chronic lung disease.

• Journal of the Korean Society of Radiology
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• v.4 no.4
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• pp.17-24
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• 2010

Hemoptysis which is comparatively common symptom in respiratory disease patients is a clinical symptom which has high risk of death in spite of many curative means. Bronchial tube embolization is a very useful medical procedure when hemoptysis does not stop for treatment of internal medicine or surgery and in addition to the purpose of instant hemostasis, for patients for whom surgical operation is impossible or for the purpose of gaining time to improve the state of the patient before surgical operation. In relation to this, this study is to know of the usefulness of bronchial tube artery embolization. The objects were 60 persons for whom bronchial tube artery embolizations are conducted because of large hemoptysis occurred from March 2007 to December 2009 in J hospital. They had large hemoptysis of 400ml or more per day and 200ml or more at a time or though the quantity of hemoptysis was less than 400ml they did not respond to the treatment of internal medicine for 10 days or longer. The average age was 60.5 years and cause diseases were tuberculosis, bronchiectasis, and pneumonia and lung cancer. Embolus parts were Rt bronchial artery 19 examples, Lt bronchial artery, both bronchial artery, Rt Intercostobronchial artery, and they were the case where embolization for many blood vessels were simultaneously carried out. As embolus materials, PVA (conteour) and microcoil were used. In 76.6% of 60 persons of patients hemorrhage stopped with the lapse of time after the procedure and in 4 examples (6.6) re-embolization was carried out due to re-bleeding after the procedure. Bronchial tube artery embolization has high early success rate and effectively controls hemoptysis in the treatment of hemoptysis and is an effective emergency remedy for hemorrhage due to large hemoptysis and will be a good medical procedure which reduces death rate. In addition, primarily if it is conducted together with the treatment of internal medicine it will be, as an effective curative means for hemorrhage due to large hemoptysis, a good mediate radial rays medical procedure which reduces death rate.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1114-1124
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• 1997

Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.728-735
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• 1996

Background : Recognition and ingestion of opsonized microorganisms by neutrophils induces the burst of oxidative metabolic activity. Products of the respiratory burst activity provide powerful oxygen dependent killing mechanism. Measurement of respiratory burst activity has been a major indicator of the functional capacity of neutrophils. We determined the respiratory burst activity of neutrophils in patients with pneumonia and observed the changes during the clinical course of pneumonia. Methods: The EDTA blood was drawn from 24 normal controls and same numbers of pneumonia patients. The respiratory burst activity(with the production of $H_2O_2$ which changes nonfluorescent DCF-DA to green fluorescent DCF) in the non-stimulated state and the stimulated state with fMLP and PMA of neutrophils was measured by flowcytometry at day 1, 3, 5, 7 and 9 of admission. Results: The respiratory burst activity of neutrophils was mildly increased by stimulation with fMLP. But there was no statistical significance between normal control and patients with pneumonia. The respiratory burst activity of neutrophils was markedly increased by stimulation with PMA in both groups. There was a significant difference in response to PMA between normal control and patients with pneumonia. The production of hydrogen peroxide from neutrophils was decreased during early course of pneumonia and it was recuperated gradually to normal level in 9 days. Conclusion : Hydrogen peroxide production from neutrophils was suppressed during early course of pneumonia and restored after treatment. It is suggested that the production of oxygen radical in response to PMA stimulation from each neutrophils is decreased rather than increased during the early course of pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.473-479
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• 2005

Background : A pulmonary embolism often presents with nonspecific symptoms and signs. However, a delayed diagnosis can result in catastrophic outcome. The majority of preventable deaths associated with a pulmonary embolism can be ascribed to a missed diagnosis rather than to the failure of existing treatments. Therefore, accurate and rapid diagnostic methods are essential for the management of a pulmonary embolism. The recent generation of multidetector-row spiral CT scanners appears to outperform other imaging modalities in detecting a central and peripheral pulmonary embolism. However, there are some variations in the interpretations of the findings between observers. This study examined the inter-observer differences of the diagnoses in patients with a pulmonary embolism. Method : 64 patients who were diagnosed with a pulmonary embolism either clinically or with spiral chest CT from 2002 to 2004, were included. Two thoracic radiologists interpreted the multidetector-row spiral CT in terms of the diagnosis of a pulmonary embolism and the location of the thrombus independently. Among 64 patients, 14 patients were excluded because there was no evidence of a pulmonary embolism or there was different interpretation of the pulmonary embolism between radiologists. A clinical diagnosis was based on "Rules for predicting the probability of embolism". Results : The mean score of the patients according to the Wells method was $3.91{\pm}0.30$ (0-9). The accordance of the radiologists was 95% in the main, 85% in the lobar, 91.2% in the segmental, and 96% in the sub-segmental pulmonary arteries. After excluding the negative interpretation from both radiologists, their agreement was 76.2%(${\kappa}.$ 0.83) in the main, 57.6%(${\kappa}.$ 0.63) in the lobar, 51.5%(${\kappa}.$ 0.63) in the segmental, and 34.6%(${\kappa}.$ 0.49) in the sub-segmental pulmonary arteries. Conclusion : Chest CT has been recently applied to patients suspected of having a pulmonary embolism. It was found that spiral CT is a rapid test for diagnosing a thrombus, and there was reliable accordance between the observers from the area of the large pulmonary arteries. However, there was a lack of agreement between the observers in diagnosing thrombi located distal to the sub-segmental arteries.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.