• Journal of Chest Surgery
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• v.31 no.12
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• pp.1134-1146
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• 1998

Background: The tumor suppressor gene p53 is one of the most frequently altered genes in human tumors, including those of the lung. There is now a compelling evidence that wild-type p53 can negatively influence cell growth by causing G1 arrest or by inducing apoptosis. The possibilities of using p53 for gene therapy are also gathering much interest. Material and Method: Our approach towards understanding p53 function would be to study the biological consequences of overexpression of wild-type p53 in normal and tumor cells by using adenovirus vectors capable of giving high levels of the p53 gene product in cells. We have used this vector containing wild-type p53 to infect tumor cells with different p53 status (null, mutant, or wild-type) to confirm that expression of p53 in null or mutant cell lines becomes possible by Adenovirus-p53 transduction, to examine the effects of high levels of p53 expression on the growth properties of tumor cells, to evaluate the role of apoptosis in p53-mediated biological effects, and to examine the effect of Adenovirus-p53 on the tumorigenicities of the lung cancer cell lines in vitro. Result: The results of our study showed that cells expressing endogenous mutant p53 and those devoid of p53 expression altogether were significantly more sensitive to Adenovirus-p53-mediated cytotoxicity compared to tumor cells expressing endogenous wild-type p53 and that overexpression of wild-type p53 induced programmed cell death. Also we knew that Adenovirus-p53 significantly reduced tumor colony formation of human non-small cell lung cancer cell lines, and decreased the growth of pre-formed colonies in vitro. Conclusion: These results suggest that adenovirus is an efficient vector for mediating transfer and expression of tumor suppressor genes in human non-small cell lung cancer cells and that the tumor cells null for p53 or expressing mutant p53 readily undergo apoptosis by Adenovirus-p53.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.495-503
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• 1999

Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.221-227
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• 2006

Background : Cough may be a consequence of bronchial hyperresponsiveness or inflammation. Empirical treatment is important in this context because it difficult to verify the obvious cause of cough using laboratory tests, Corticosteroid has a nonspecific anti-inflammatory effect, and can be used for cough management. However, its response rate has not yet been fully elucidated. This study investigated the short- term effects of inhaled corticosteroid on chronic cough Methods : Patients with chronic cough with a normal chest radiograph and a pulmonary function test were enrolled. Cases with a prior respiratory infection within 8 weeks, a history of bronchial asthma, objective wheezing on examination, subjective symptoms of gastroesophageal reflux or taking an ACE inhibitor were excluded. On the first visit, a methacholine bronchial provocation test, spontaneous sputum eosinophil count performed twice and a paranasal sinus radiograph were checked, and the patients were treated with budesonide turbuhaler $800{\mu}g/day$ for ten days. The primary outcome measure was a decrease in the cough score after treatment. Results : Sixty nine chronic coughers were finally analyzed. The final diagnoses by the routine tests were as follows: bronchial asthma 13.0%, eosinophilic bronchitis 18.8%, paranasal sinusitis 23.2% and non-diagnostic cases 53.6%. The following responses to the inhaled corticosteroid were observed: definite responders, 76.8%, possible responders, 2.9% and non-responders, 20.3%. The response rate was not affected by the final diagnosis even in the non-diagnostic cases. There were minimal adverse drug related effects during the empirical treatment. Conclusion : Routine objective tests such as methacholine provocation, sputum eosinophil count and simple radiographs were notare not suitable for diagnosing chronic cough Therefore, empirical treatment is important. Short term inhaled corticosteroid is effective and can guide a further treatment plan for chronic cough.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.274-282
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• 1993

Background: Pulmonary paragonimiasis is caused by consumption of raw or improperly cooked crabs infected by a laval stage (metacercaris) of the parasite. In our country it had been a highly prevalent endemic disease until th late 1960s, and after then it's prevalence has been markedly decreased. But because some people have continued to ingest undercooked crabs, this disease have yet occured sporadically. Methods: We reviewed the clinical and radiological findings retrospectively in seventy-four patients of pulmonary paragonimiasis including familial infestation in 7 familes (20 cases) who were confirmed by food history, clinical and radiological findings, and labaratory data. Results: The male: female ratio was 2.2:1 and most prevalent age was 40-49 years old. Twen6ty nine patients (39%) had ova-positive infection. The detection sites were sputum (48%), pleural fluid (17%), fine needle aspiration biopsy of nodular or cystic lesion (17%), pleural biopsy (7%), skin nodule biopsy (7%), and stool (3%). The patients had pulmonary symptoms in 63 cases (85%) but 9 cases did not have any symptoms. The 53 cases (72%) had abnormal radiological findings in lung parenchyme (75%) and pleura (63%). However 21 cases (28%) showed no specific findings in their chest X-ray. Serum titers (ELISA) of specific IgG for paragonimiasis in 13 cases were followed for average 9.8 months after treatment, which showed slow decreasement. In the evaluation of family member (7 family, 20 cases), all members having the common dietary history together with a proven patients were confirmed this disease by serological test, regardless of the presence or the abscence of clinical or radilogical symptoms. Conclusion: We evaluated the clinical and radiological findings in 74 cases of pulmonary paragonimiasis including 7 family members who had a history of ingestion of improperly cooked crabs together with patients. The paients of pulmonary paragonimiasis have various findings in clinical and radiological findings. Common diet exposure history and laboratory findings including specific IgG were important in earlier diagnosing and treating in family members of patients.

• Journal of Chest Surgery
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• v.39 no.9 s.266
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• pp.659-667
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• 2006

Background: Experimental studies of vascular remodeling in the pulmonary arteries have been performed actively. These models required a persistent vascular insult for intimal injury induced by chronic hypoxia, monocrotaline intoxication or chronic air embolism and characterized medial hypertrophy and neointimal formation by active synthesis of the extracellular matrix protein. The purpose of this study was to determine the pattern of pulmonary vascular remodeling after obstruction of the pulmonary vein. Material and Method: Obstruction of the right pulmonary vein with a metal clip was performed in Sprague-Dawley rats $(352{\pm}18g,\;n=10)$ to cause pulmonary vascular disease. Fifteen days later, experimental studies were done and finally the both lungs and hearts were extirpated for experimental measurement. Pulmonary arterial pressure, weight ratio of right ventricle (RV) to left ventricle (LV) and ventricular septum (S) (RV/LV +S weight ratio), and pulmonary artery morphology (percent wall thickness, %WT) were evaluated and compared with normal control groups. Result: Pulmonary hypertension $(38{\pm}12mmHg\;vs\;13{\pm}4mmHg;\;p<0.05)$ and right ventricular hypertrophy (right ventricular/left ventricular and septal weight ratio, $0.52{\pm}0.07\;vs\;0.35{\pm}0.04;\;p<0.05$) with hypertrophy of the muscular layer of the pulmonary arterial wall (percent wall thickness, $22.4{\pm}6.7%\;vs\;6.7{\pm}3.4%;\;p<0.05$) were developed by 15 days after obstruction of the pulmonary vein. Conclusion: Obstruction of the pulmonary vein developed elevation of pulmonary blood pressure and medial hypertrophy of the pulmonary artery. These results are a part of the characteristic vascular remodeling. Theses results demonstrate that obstruction of the pulmonary vein can develope not only high pulmoanry blood flow of contralateral lung but also intima injury inducing vascular remodeling.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.501-510
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• 2002

Background: The various pathogeneses of acute respiratory distress syndrome have been suggested but not established yet. In the present study, the role of group II phospholipase $A_2$($PLA_2$) in the pathogenesis of gut ischemia-reperfusion(I/R) induced acute lung injury (ALI), especially in the pulmonary oxidative stress with infiltration of neutrophils was investigated. Material and Method: To induce ALI, reperfusion of mesentery was done for 120 min after clamping of superior mesenteric artery for 60 min in Sprague-Dawley rats that weighed about 300g. To exmaine the role of group II $PLA_2$ in ALI, especially endothelial injury associated with the action of neutrophils, lung myeloperoxidase activity, lung leak index, bronchoalveolar lavage fluid protein were measured, and pulmonary $PLA_2$ activity changes in gut I/R were also measured. The role of group II $PLA_2$in the neutrophilic generation of free radicals was assessed by inhibiting group II $PLA_2$ with rutin, manoalide and scalaradial. Furthermore, to verify the oxidative stress in the lung, histologic and free radical detecting cytochemical electron microscopy were done. Result: After reperfusion, ALI was developed with accumulation of neutrophils in the lung, which was confirmed by the increase of myeloperoxidase activity, lung leak index and bronchoalveolar lavage protein (p<0.001). The pulmonary and intestinal group II $PLA_2$ activities significantly increased after gut I/R which were reversed by rutin(p<0.001). In vitro, cytochrome-c reduction assay denoted the inhibitory effects of rutin, scalaradial and manoalide on the production of free radicals from isolated human neutrophils. Histologically, neutrophilic accumulation and pericapillary edema in the lung after gut I/R was detected by light microscopy which was suppressed by rutin. In $CeCl_3$ cytochemical electron microscopy, the increased production of hydrogen peroxide in the lung after gut I/R was confirmed and also the production of hydrogen peroxide was decreased by rutin. Conclusion: On the basis of these experimental results, the inhibition of group II $PLA_2$ seemed to mitigate gut I/R-induced ALI by suppressing the production of free radicals from the infiltrated neutrophils. Collectively, group II $PLA_2$ seems to play a crucial role in gut I/R-induced ALI by neutrophilic oxidative stress.

• Journal of Chest Surgery
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• v.43 no.2
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• pp.144-149
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• 2010

Background: Many studies have demonstrated the various therapeutic options for treating hemoptysis caused by inflammatory lung disease. However, there is debate over the surgical management of the ongoing hemoptysis. Therefore, we evaluated the clinical results of pulmonary resection that was done due to hemoptysis in patients with concomitant inflammatory lung disease. Material and Method: We performed a retrospective analysis of 75 patients who received pulmonary resection for hemoptysis and concomitant inflammatory lung disease between 2001 and 2007. The mean age was $52.1{\pm}12.5$ years old, and the male; female ratio was 52：23. Result: The underlying disease was aspergilloma in 30 patients (40%), pulmonary tuberculosis in 20 patients, bronchiectasis in 18 patients and other causes in 7 patients. The surgical treatment included lobectomy in 55 patients, bilobectony in 2 patients, pneumonectomy in 17 patients and wedge resection in 1 patient. There were 3 early deaths, and the causes of death were pneumonia in 1 patient and BPF in 2 patients. The early mortality was statistically higher for such risk factors as a preoperative Hgb level <10 g/dL, COPD and an emergency operation. Conclusion: In conclusion, pulmonary resection for treating hemoptysis showed the acceptable range of mortality and it was an effective method for the management of hemoptysis in patients with inflammatory lung disease. However, relatively high rates of mortality and morbidity were noted for an emergency operation, and so meticulous care is needed in this situation.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.461-467
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• 2005

Pleura, diaphragm, pericardial fat pad, intercostal muscles and omentum can be used to protect and revascularize the bronchial suture line of tracheal transplantation, lung transplantation and pulmonary resection. The purpose of the present study is to compare the influence of the pleura, diaphragm and omentum in survival of isolated tracheal segments in the experimental animals. Material and Method: Sprague-Dawley rats weighing 250- 350g were used. The animals were divided in three groups; the pleura, omentum and diaphragm. Following intraperitoneal anesthesia, endotracheal intubation was performed. Then the trachea was exposed. A three-ring sec- tion of cervical trachea was excised. The resected trachea was implanted at each sites. After 2 weeks, rats were sacrificed. Histopathological examination of the tracheal segments was performed. For comparison of each groups, histopathological viability of resected tracheal segment was scored by three tissue layers; epithelium, submucosa, and cartilage. The results were presented as average score. Result: In histopathological examination, submucosa and cartilage using tracheal segment necrosis scoring system. The pleural group showed well preserved tissue. There was minimal necrosis and inflammation compared with other groups. In the pleural group, tracheal necrosis scores were $2.17\pm0.983$at epithelium, $1.67\pm0.516$ at submucosa and $2.17\pm0.753$ at cartilage. At the omental group, scores were $1.00\pm0.00,\;1.60\pm0.548\;and\;1.80\m0.447$. In the diaphragmatic group, scores were $1.40:\pm0.894,\;2.40\pm0.547\;and\;2.20\pm0.447$. Total necrosis score were $6.00\pm1.789$ in the pleural group, $4.40\pm0.894$ in the omental group and $6.00\pm1.414$ in the diaphragmatic group. Conclusion: There were no significant viability differences in terms of total necrosis score for the viability of resected tracheal segment. But the best result was achieved in the omental group. Therefore, omental wrapping on tracheal graft site will be beneficial for the prevention of graft necrosis.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.468-475
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• 2005

Transmyocardial revascularization (TMR) in end stage ischemic heart disease results in variable clinical responses. We investigated the acute effect of early reperfusion and the angiogenesis after formation of the transmyocardial channel in a transplanted rat heart model with acute myocardial infarction. Material and Method: In the 30 transplanted hearts we induced acute myocardial infarction by ligating the proximal left coronary artery and inserted a porous 22G intravenous cannula into the left ventricle. After ten minutes of reperfusion, we removed the cannula. At every stage, we recorded the heart rate, QRS size, and left coronary arterial blood flow using the electrocardiogram and Doppler. One week later the rats were sacrificed and evaluated for the patency of intramyocardial channels and the angiogenesis. Result: The heart rates after ligation and after cannula insertion were $239.1\pm61.7,\;235.8\pm58.0bpm$ respectively, and they were statistically significantly slower than that of before ligation, $277.6\pm40.3bpm\;(p=0.017,\;p=0.007\;respectively)$. QRS sizes before ligation, after ligation, and after cannula insertion were $3.6\pm3.3mm,\;2.8\pm3.3 mm,\;and\;2.4\pm2.2mm,$respectively, and there was no significant difference in the three groups. Doppler findings after ligation showed that average peak and mean values of coronary perfusion were significantly decreased from $2.11\pm0.17kHz,\;1.25\pm0.22kHz\;to\;0.83\pm0.15kHz,\;0.38\pm0.11kHz$(p<0.05 respectively). After insertion of the porous cannula, the average peak and mean values of coronary perfusion were $0.61\pm0.05kHz\;and\;0.33\pm0.05 kHz$ respectively, but there was no statistically significant change compared to values after ligation. In all cases except one, pathologic findings showed no patent channels in the acute stage, however, one case showed the angiogenesis. Conclusion: We confirmed that TMR in a rat heart transplant model did not show blood flow through the channel in the acute stage. However, reperfusion effect in some cases had a potential for angiogenesis.

• Journal of Chest Surgery
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• v.37 no.1
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• pp.11-18
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• 2004

Background: We tested the effect of indomethacine and total spinal anesthesia on the improvement of placental flow during cardiopulmonary bypass on fetal lamb. Material and Method: Twenty fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Ten served as a control group in which placenta was worked as an oxygenator during bypass (Control group). The remainder worked as an experimental group in which pretreatment with indomethacine and total spinal anesthesia was performed before bypass with the same extracorporeal circulation technique as control group (Experimental group). Observations were made every 10 minutes during a 30-minute bypass and 30-minute post bypass period. Result: Weights of the fetuses ranged from 2.2 to 5.2 kg. In Control group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of Pa$CO_2$ increased from 61.9 to 129.6 mmHg at each time points during bypass. Flow rate was suboptimal (74.3 to 97.0 $m\ell$/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. On the contrary, in Experimental group, means of arterial pressure reamined higher (45.8 to 30 mmHg) during bypass (p<0.05). Means of Pa$CO_2$ were less ranging from 59.8 to 79.4 mmHg during bypass (P<0.05). Flow rates were higher (78.8 to 120.2 $m\ell$/kg/min) during bypass (p<0.05). There were slower deterioration of cardiac function after cessation of bypass. Conclusion: In this study, we demonstrated that the placental flow was increased during fetal cardiopulmonary bypass in the group pretreated with indomethacine and total spinal anesthesia. However, further studies with modifications of the bypass including a creation of more concise bypass circuit, and a use of axial pump are mandatory for the clinical application.