• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.478-487
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• 2003

Background : There have been several studies showing that the angiotensin II and angiotensin converting enzyme(ACE) contributes to the apoptosis of alveolar epithelial cells in idiopathic interstitial pneumonia and the activation of fibroblasts during the process of pulmonary fibrosis. These results suggest that the pulmonary fibrosis can be inhibited by the angiotensin II receptor antagonist(AGIIRA). This study was performed to identify the therapeutic effect of AGIIRA in idiopathic pulmonary fibrosis(IPF). Method : Thirteen patients with IPF, who were diagnosed with an open lung biopsy(6 patients) and furfilling the ATS criteria(7 patients) between March 1999 and October 2001 at the Gachon medical center, were enrolled in this study. Of these patients, eight patients were treated with a regimen including AGIIRA(AT group), and five were treated without AGIIRA(NT group). The pulmonary function tests and dyspnea(ATS scale) were measured at diagnosis and 1 year after treatment. All the data was collected to analyze the therapeutic effect of AGIIRA on the patients with IPF. Results : The AT group contained 8 patients(M:F=4:4) and the NT group contained 5 patients(M:F=3:2). There was no significant difference in the serum angiotensin II level between the two groups($202.5{\pm}58.5$ vs $163.7{\pm}47.3pg/ml$, p>0.05). The AT group showed an upward trend in TLC(+3%), FVC(+4%), FEV1(+3%) and DLco(+2%) compared to the NT group(TLC(-14%), FVC(-3%), FEV1(-4%) except for DLco(+5%)). The dyspnea score in the AT group improved significantly but not in the NT group. Conclusion : These results suggest that the angiotensin II receptor antagonist may have an effect on stabilizing IPF.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.15-21
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• 2003

Background : There are many risk factors for osteoporosis in patients with chronic obstructive pulmonary disease(COPD). These include smoking, a low body mass index, insufficient exercise, and the use of glucocortcoids. However, there is lack of data on the incidence of osteoporosis according to the different glucocorticoid administration methods in patients with COPD. This study compared the incidence of osteoporosis according to the different administration methods of glucocorticoid. Methods : A matched case-controlled study (gender, age, cumulative steroid dose and pack-years of smoking) was conducted. Forty-five patients with documented COPD for at least a 3 year duration and a cumulative glucocorticoid dose above 1,000 mg were enrolled in study. The patients were classified into the following three groups. First, fifteen patients received continuous inhaled glucocorticoid with intermittent oral steroids but had no admission history due to an acute exacerbation(Group I). Secondly, fifteen patients received a multiple course of oral steroids with additional inhaled glucocorticoid but had no admission history due to their acute exacerbation(Group II). Lastly, fifteen patients received intermittent oral or inhaled glucocorticoids and had an admission history due to the acute exacerbation with intravenous steroid treatment for at least 2 weeks per year(Group III). The enrolled patients had apulmonary function test and bone densitometry performed at the lumbar spine and femoral neck. Results : The patients from Group III had significantly high incidence of osteoporosis in the lumbar and femoral neck compared to Group I and Group II (p<0.01). Conclusion : The incidence of osteoporosis in patients with COPD appears to be strongly affected by the method of steroid administration. This result suggests that intravenous steroid administration is strongly associated with the risk of osteoporosis.

• Tuberculosis and Respiratory Diseases
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• v.63 no.6
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• pp.497-506
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• 2007

Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase $A_2$ ($cPLA_2$) activation by plateletactivating factor (PAF). Methods: The possible formation of the positive feedback loop of the $cPLA_2$ activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung. Results: Five hours after intratracheal instillation of PAF ($5{\mu}g/rat$), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic $cPLA_2$ activity were increased following PAF exposure and exposure to hydrogen peroxide increased $cPLA_2$ activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by $CeCl_3$ cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment. Conclusion: PAF mediates acute oxidative lung injury by the activation of $cPLA_2$, which may provoke the generation of free radicals in neutrophils.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1366-1381
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• 1997

Background : Uvulopalatopharyngoplasty(UPPP) has become the most common surgical treatment for obstructive sleep apnea syndrome(OSAS). However, the results of this therapeutic modality have been quite variable with successful results by several authors and poor results by others. Until recently, in Korea, there is only a few reports about the clinical efficacy of UPPP. A prospective study was undertaken to evaluate the effectiveness and complications of UPPP. Method : Twenty-six OSAS patients who had undergone UPPP with preoperative and postoperative polysomnographic studies were included in this study. Two definitions of surgical success were used. The responder was defined, using a conventional criteria, as a 50% or more reduction in apnea index(AI) or apneahypopnea index(AHI) after UPPP, or a postoperative AI of <10 or AHI of <20. The initial cure was defined, using our own criteria, as a postoperative AI of <5 or AHI of <10. Complications were categorized in two groups : early(disorders during the first 10 postoperative days) and late. Results : Eighteen patients(69.2%) were responders, and ten patients(38.5%) were considered as initial cure. On the other hand, in five patients (19.2%), postoperative polysomnographic data demonstrated deterioration compared with preoperative data. Reduction rate of AI or AHI following UPPP was not significantly related to the preoperative body mass index, AI or AHI. There was no significant change of sleep architecture before and after UPPP in responder and initial cure groups. Early complications such as pain, dyspnea, bleeding, nasal reflux, dysphagia or wound disruption were observed in all patients. Late complications such as nasal reflux, voice change, dysphagia, loss of taste, pharyngeal dryness or foreign body sensation were discovered in 22 patients (84.6%). However, all early and late complications were of minor importance. Conclusion : The response to UPPP was favorable in approximately 70% of OSAS patient. However, the initial Cure rate of UPPP was relatively low. We suggest that selection of more appropriate surgical candidates and adequate surgical protocol is necessary to obtain a more successful result with UPPP.

• Journal of Chest Surgery
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• v.38 no.2 s.247
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• pp.101-109
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• 2005

Background: In sudden cardiac arrest, the effective maintenance of coronary artery blood flow is of paramount importance for myocardial preservation as well as cardiac recovery and patient survival. The purpose of this study was to directly compare the effects of pulsatile and non-pulsatile circulation to coronary artery flow and myocardial preservation in cardiac arrest condition. Material and Method: A cardiopulmonary bypass circuit was constructed in a ventricular fibrillation model using fourteen Yorkshire swine weighing $25\~35$ kg each. The animals were randomly assigned to group I (n=7, non-pulsatile centrifugal pump) or group II (n=7, pulsatile T-PLS pump). Extra-corporeal circulation was maintained for two hours at a pump flow of 2 L/min. The left anterior descending coronary artery flow was measured with an ultrasonic coronary artery flow measurement system at baseline (before bypass) and at every 20 minutes after bypass. Serologic parameters were collected simultaneously at baseline, 1 hour, and 2 hours after bypass in the coronary sinus venous blood. The Mann-Whitney U test of STATISTICA 6.0 was used to determine intergroup significances using a p value of < 0.05. Result: The resistance index of the coronary artery was lower in group II and the difference was significant at 40 min, 80 min, 100 min and 120 min (p < 0.05). The mean velocity of the coronary artery was higher in group II throughout the study, and the difference was significant from 20 min after starting the pump (p < 0.05). The coronary artery blood flow was higher in group II throughout the study, and the difference was significant from 40 min to 120 min (p < 0.05) except at 80 min. Serologic parameters showed no differences between the groups at 1 hour and 2 hours after bypass in the coronary sinus blood. Conclusion: In cardiac arrest condition, pulsatile extracorporeal circulation provides more blood flow, higher flow velocity and less resistance to coronary artery than non-pulsatile circulation.

• Journal of Chest Surgery
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• v.34 no.6
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• pp.454-464
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• 2001

Background: It has been recognized that systemic inflammatory reaction and oxygen free radical formed by activated leukocyte in the procedure of cardiopulmonary bypass(CPB) frequently produce postoperative cardiac and pulmonary dysfunction. The purpose of this study was to evaluate the efficacy of leukocyte-depleting filters in the cardiopulmonary bypass circuit for patients undergoing open heart surgery(OHS). Material and method: The study involved 15 patients who underwent OHS with a Leukoguard-6 leukocyte filter placed in the arterial limbs of the bypass circuit(filter group, n=15) and 15 patients who did not have the filter(control group, n=15). We analyzed the differences between the groups in intraoperative changes of peripheral blood leukocyte and platelet counts, pre- and postbypass changes of malondialdehyde(MDA), troponin-T(TnT), 5'-nucleotidase(5'-NT) in coronary sinus blood, spontaneous recovery rate of heart beat after CPB, pre-and postoperative cardiac index(Cl) and pulmonary vascular resistance(PVR), and the amounts of postoperative bleeding and sternal wound complication. Result: During CPB, total leukocyte count of the filter group(9,567$\pm$ 842/㎣) was significantly less than that of the control group(13,573+1,167/㎣) (p<0.01), but there was no significant difference in platelet count between the groups. Postoperative levels of MDA(3.78+0.32 $\mu$mol/L vs 5.86+0.65 $\mu$mo1/L, p<0.01), TnT(0.40$\pm$0.04 ng/mL vs 0.59$\pm$0.08 ng/mL, p<0.05) and 5'-NT(3.88$\pm$0.61 U/L vs 5.80$\pm$0.90 U/L, p<0.05) were all significantly lower in the filter group than the control group. Postoperative Cl was higher in the filter group than the control group(3.26$\pm$0.18 L/$m^2$min vs 2.75$\pm$0.17 L/$m^2$/min, p=0.05). PVR of the filter group was lower than that of the control group(65.87$\pm$7.59 dyne/sec/cm$^{5}$ vs 110.80+12.22 dyne/sec/cm$^{5}$ , p<0.01). Spontaneous recovery rate of heart beat in the filter group was higher than that in the control group(12 patients vs 8 patients, p<0.05). Postoperative wound infection occurred in one case in the filter group and 4 case in the control group(p<0.05). Postoperative 24 hour blood loss of the filter group was more than that of the control group (614$\pm$107 mL vs 380+71 mL, p=0.05).

• Journal of Chest Surgery
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• v.37 no.12
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• pp.967-977
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• 2004

Background: DNA methylation is one of the important gene expression mechanisms of the cell. When cytosine of CpG dinucleotide in promotor is hypomethylated, expression of some genes that is controlled by this promoter is altered. In this study, the author investigated the effect of DNA demethylating agent, 5-aza-2'-deoxycytidine (ADC), on the expressions of cancer antigen genes, MHC and B7 in 4 lung cancer cell lines, NCIH1703, NCIH522, MRC-5, and A549. Material and Method: After treatment of cell lines, NCIH1703, NCIH522, MRC-5 and A549 with ADC (1 uM) for 48 hours, RT-PCR was performed by using the primers of MAGE, GAGE, NY-ESO-1, PSMA, CEA, and SCC antigen gene. In order to find the optimal ADC treatment condition for induction of cancer antigen, we studied the effect of ADC treatment time and dose on the cancer antigen gene expression. To know the effect of ADC on the expression of MHC or B7 and cell growth, cells were treated with 1 uM of ADC for 72 hours for FACS analysis or cells were treated with 0.2, 1 or 5 uM of ADC for 96 hours for cell counting. Result: After treatment of ADC (1 uM) for 48 hours, the expressions of MAGE, GAGE, NY-ESO-1, and PSMA genes increased in some cell lines. Among 6 MAGE isotypes tested, and gene expression of MAGE-1, -2, -3, -4 and -6 could be induced by ADC treatment. However, CEA gene expression did not change and SCC gene expression was decreased by ADC treatment. Gene expression was generally induced 24 - 28 hours after ADC treatment and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC ADC teatment, and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC teatment in ADC-Free medium. Most gene expression could be induced at 0.2 uM of ADC, but gene expression increased dependently on ADC treatment dose. The expression of MHC and B7 was not increased by ADC treatment in all four cell lines, and the growth rate of 4 cell lines decreased significantly with the increase of ADC concentrations. Conclusion: Treatment of lung cancer cell lines with ADC increases the gene expression MAGE, GAGE and NY-ESO-1 that are capable of induction of cytotoxic T lymphocyte response. We suggest that treatment with 1 uM of ADC for 48 hours and then culturing in ADC-free medium is optimal condition for induction of cancer antigen. However, ADC has no effect on MHC and B7 induction, additional modification for increase of expression of MHC, B7 and cytokine will be needed for production of efficient cancer cell vaccine.

• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.359-365
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• 2006

Background: Arterial grafts have been used to achieve better long-term results for coronary revascularization. Bilateral internal thoracic artery (ITA) grafts have a better results, but it may be not used in some situations such as diabetes and chronic obstructive pulmonary disease (COPD). We evaluated the clinical and angiographic results of composite left internal thoracic artery-radial artery (LITA-RA) Y graft. Material and Method: Between April 2002 and September 2004, 119 patients were enrolled in composite Y graft for coronary bypass surgery. The mean age was $62.6{\pm}8.8$ years old and female was 34.5%. Preoperative cardiac risk factors were as follows: hypertension 43.7%, diabetes 33.6%, smoker 41.2%, and hyperlipidemia 22.7%, There were emergency operation (14), cardiogenic shock (6), left ventricle ejection fraction (LVEF) less than 40% (17), and 17 cases of left main disease. Coronary angiography was done in 35 patients before the hospital discharge. Result: The number of distal anastomoses was $3.1{\pm}0.91$ and three patients (2.52%) died during hospital stay. The off-pump coronary artery bypass (OPCAB) was applied to 79 patients (66.4%). The LITA was anastomosed to left anterior descending system except three cases which was to lateral wall. The radial Y grafts were anastomosed to diagonal branches (4), ramus intermedius (21), obtuse marginal branches (109), posterolateral branches (12), and posterior descending coronary artery (8). Postoperative coronary angiography in 35 patients showed excellent patency rates (LITA 100%, and RA 88.5%; 3 RA grafts which anastomosed to coronary arteries <70% stenosed showed string sign with competitive flow). Conclusion: The LITA-RA Y composite graft provided good early clinical and angiographic results in multivessel coronary revascularization. But it should be cautiously used in selected patients.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.824-835
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• 1999

Background: Sleep-related breathing disorders are commonly found in patients with chronic renal failure and particularly, sleep apnea may have an influence on the long-term mortality rates in these patients. Maintenance hemodialysis is the mainstay of medical measures for correcting the metabolic derangements of chronic renal failure but it is uncertain whether it may alleviate sleep disorders including sleep apnea. Methods: Forty seven patients on maintenance hemodialysis were surveyed with the sleep questionnaire about their clinical symptoms related to sleep disorders. Among them, 15 patients underwent the polysomnography and their blood levels of urea nitrogen, creatinine, electrolytes and the arterial blood gases in the nights before and following hemodialysis were measured. Results: Forty(85.1%) of the 47 patients complained of the symptoms associated with sleep-wake cycle disturbances, 55.3% experienced snoring and 27.7% reported witnessed apneas. The duration of REM sleep increased significantly in the nights after hemodialysis compared to the nights without hemodialysis(p<0.05) and the percentage of total sleep time comprising NREM sleep decreased significantly in the nights following hemodialysis compared to the nights before hemodialysis(p<0.05). The percentage of total sleep time consisting of the stage 1 and 2 NREM sleep showed the trend for a decrease in the nights after hemodialysis(p=0.051), while the percentage of total sleep time comprising the stage 3 and 4 NREM sleep did not change between nights. The obstructive sleep apnea was more predominant type than the central one in both nights and there were no differences in the apnea index and the apnea-hypopnea index between the nights. The decrease in the blood level of urea nitrogen, creatinine, potassium and phosphorus was observed after hemodialysis(p<0.05), but the differences of parameters measured during polysomnography between the nights did not correlate with the changes of biochemical factors obtained on the two nights. Arterial blood gas analysis showed that pH was significantly greater in the nights after hemodialysis than in the nights before hemodialysis(p<0.05), but there were no correlations between the parameters examined during polysomnography and the parameters of arterial blood gas analysis(p<0.05). Conclusion: These results suggest that chronic renal failure is an important systemic disorder which is strongly associated with sleep disorders. Maintenance hemodialysis, although it is a widely accepted measure to treat chronic renal failure, did not significantly modulate the sleep architecture and the severity of sleep apnea. Thus, taking the patients with chronic renal failure into account, it is advisable to try not only to find a substantial way for correcting metabolic derangements but also to consider the institution of more effective treatments for sleep disorders.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.813-822
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• 1998

Background: Extubation is recommended to be performed at minimum pressure support (PSmin) during the pressure support ventilation (PSV). In field, physicians sometimes perform additional 1 hr T-piece trial to the patient at PSmin to reduce re-intubation risk. Although it provides confirmation of patient's breathing reserve, weaning could be delayed due to increased airway resistance by endotracheal tube. Methods: To investigate the effect of additional 1 hr T-piece trial on weaning outcome, a prospective study was done in consecutive 44 patients who had received mechanical ventilation more than 3 days. Respiratory mechanics, hemodymic, and gas exchange measurements were done and the level of PSmin was calculated using the equation (PSmin=peak inspiratory flow rate $\times$ total ventilatory system resistance) at the 15cm $H_2O$ of pressure support. At PSmin, the patients were randomized into intervention (additional 1 hr T-piece trial) and control (extubation at PSmin). The measurements were repeated at PSmm, during weaning process (in cases of intervention), and after extubation. The weaning success was defined as spontaneous breathing more than 48hr after extubation. In intervention group, failure to continue weaning process was also considered as weaning failure. Results: Thirty-six patients with 42 times weaning trial were satisfied to the protocol. Mean PSmin level was 7.6 (${\pm}1.9$)cm $H_2O$. There were no differences in total ventilation times (TVT), APACHE III score, nutritional indices, and respiratory mechanics at PSmin between 2 groups. The weaning success rate and re-intubation rate were not different between intervention group (55% and 18% in each) and control group (70% and 20% in each) at first weaning trial. Work of breathing, pressure time product, and tidal volume were aggravated during 1 hr T-piece trial compared to those of PSmin in intervention group ($10.4{\pm}1.25$ and $1.66{\pm}1.08$ J/L in work of breathing) ($191{\pm}232$ and $287{\pm}217$cm $H_2O$ s/m in pressure time product) ($0.33{\pm}0.09$ and $0.29{\pm}0.09$ L in tidal volume) (P<0.05 in each). As in whole, TVT, and tidal volume at PSmin were significantly different between the patients with weaning success ($246{\pm}195$ hr, $0.43{\pm}0.11$ L) and the those with weaning failure ($407{\pm}248$ hr, $0.35{\pm}0.10$L) (P<0.05 in each). Conclusion : There were no advantage to weaning outcome by addition of 1 hr T-piece trial compared to prompt extubation to the patient at PS min.