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A Study on Legal and Institutional Improvement Measures for the Effective Implementation of SMS -Focusing on Aircraft Accident Investigation-

  • Yoo, Kyung-In
    • The Korean Journal of Air & Space Law and Policy
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    • v.32 no.2
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    • pp.101-127
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    • 2017
  • Even with the most advanced aviation technology benefits, aircraft accidents are constantly occurring while air passenger transportation volume is expected to double in the next 15 years. Since it is not possible to secure aviation safety only by the post aircraft accident safety action of accident investigations, it has been recognized and consensus has been formed that proactive and predictive prevention measures are necessary. In this sense, the aviation safety management system (SMS) was introduced in 2008 and has been carried out in earnest since 2011. SMS is a proactive and predictive aircraft accident preventive measure, which is a mechanism to eliminate the fundamental risk factors by approaching organizational factors beyond technological factors and human factors related to aviation safety. The methodology is to collect hazards in all the sites required for aircraft operations, to build a database, to analyze the risks, and through managing risks, to keep the risks acceptable or below. Therefore, the improper implementation of SMS indicates that the aircraft accident prevention is insufficient and it is to be directly connected with the aircraft accident. Reports of duty performance related hazards including their own errors are essential and most important in SMS. Under the policy of just culture for voluntary reporting, the guarantee of information providers' anonymity, non-punishment and non-blame should be basically secured, but to this end, under-reporting is stagnant due to lack of trust in their own organizations. It is necessary for the accountable executive(CEO) and senior management to take a leading role to foster the safety culture initiating from just culture with the safety consciousness, balancing between safety and profit for the organization. Though a Ministry of Land, Infrastructure and Transport's order, "Guidance on SMS Implementation" states the training required for the accountable executive(CEO) and senior management, it is not legally binding. Thus it is suggested that the SMS training completion certificates of accountable executive(CEO) and senior management be included in SMS approval application form that is legally required by "Korea Aviation Safety Program" in addition to other required documents such as a copy of SMS manual. Also, SMS related items are missing in the aircraft accident investigation, so that organizational factors in association with safety culture and risk management are not being investigated. This hinders from preventing future accidents, as the root cause cannot be identified. The Aircraft Accident Investigation Manuals issued by ICAO contain the SMS investigation wheres it is not included in the final report form of Annex 13 to the Convention on International Civil Aviation. In addition, the US National Transportation Safety Board(NTSB) that has been a substantial example of the aircraft accident investigation for the other accident investigation agencies worldwide does not appear to expand the scope of investigation activities further to SMS. For these reasons, it is believed that investigation agencies conducting their investigations under Annex 13 do not include SMS in the investigation items, and the aircraft accident investigators are hardly exposed to SMS investigation methods or techniques. In this respect, it is necessary to include the SMS investigation in the organization and management information of the final report format of Annex 13. In Korea as well, in the same manner, SMS item should be added to the final report format of the Operating Regulation of the Aircraft and Railway Accident Investigation Board. If such legal and institutional improvement methods are complemented, SMS will serve the purpose of aircraft accident prevention effectively and contribute to the improvement of aviation safety in the future.

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The Effect of Nasal BiPAP Ventilation in Acute Exacerbation of Chronic Obstructive Airway Disease (만성 기도폐쇄환자에서 급성 호흡 부전시 BiPAP 환기법의 치료 효과)

  • Cho, Young-Bok;Kim, Ki-Beom;Lee, Hak-Jun;Chung, Jin-Hong;Lee, Kwan-Ho;Lee, Hyun-Woo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.190-200
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    • 1996
  • Background : Mechanical ventilation constitutes the last therapeutic method for acute respiratory failure when oxygen therapy and medical treatment fail to improve the respiratory status of the patient. This invasive ventilation, classically administered by endotracheal intubation or by tracheostomy, is associated with significant mortality and morbidity. Consequently, any less invasive method able to avoid the use of endotracheal ventilation would appear to be useful in high risk patient. Over recent years, the efficacy of nasal mask ventilation has been demonstrated in the treatment of chronic restrictive respiratory failure, particularly in patients with neuromuscular diseases. More recently, this method has been successfully used in the treatment of acute respiratory failure due to parenchymal disease. Method : We assessed the efficacy of Bilevel positive airway pressure(BiPAP) in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD). This study prospectively evaluated the clinical effectiveness of a treatment schedule with positive pressure ventilation via nasal mask(Respironics BiPAP device) in 22 patients with acute exacerbations of COPD. Eleven patients with acute exacerbations of COPD were treated with nasal pressure support ventilation delivered via a nasal ventilatory support system plus standard treatment for 3 consecutive days. An additional 11 control patients were treated only with standard treatment. The standard treatment consisted of medical and oxygen therapy. The nasal BiPAP was delivered by a pressure support ventilator in spontaneous timed mode and at an inspiratory positive airway pressure $6-8cmH_2O$ and an expiratory positive airway pressure $3-4cmH_2O$. Patients were evaluated with physical examination(respiratory rate), modified Borg scale and arterial blood gas before and after the acute therapeutic intervention. Results : Pretreatment and after 3 days of treatment, mean $PaO_2$ was 56.3mmHg and 79.1mmHg (p<0.05) in BiPAP group and 56.9mmHg and 70.2mmHg (p<0.05) in conventional treatment (CT) group and $PaCO_2$ was 63.9mmHg and 56.9mmHg (p<0.05) in BiPAP group and 53mmHg and 52.8mmHg in CT group respectively. pH was 7.36 and 7.41 (p<0.05) in BiPAP group and 7.37 and 7.38 in cr group respectively. Pretreatment and after treatment, mean respiratory rate was 28 and 23 beats/min in BiPAP group and 25 and 20 beats/min in CT group respectively. Borg scale was 7.6 and 4.7 in BiPAP group and 6.4 and 3.8 in CT group respectively. There were significant differences between the two groups in changes of mean $PaO_2$, $PaCO_2$ and pH respectively. Conclusion: We conclude that short-term nasal pressure-support ventilation delivered via nasal BiPAP in the treatment of acute exacerbation of COPD, is an efficient mode of assisted ventilation for improving blood gas values and dyspnea sensation and may reduce the need for endotracheal intubation with mechanical ventilation.

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Clinical Indices Predicting Resorption of Pleural Effusion in Tuberculous Pleurisy (결핵성 늑막염에서 삼출액의 흡수에 영향을 미치는 임상적 지표)

  • Lee, Joe-Ho;Chung, Hee-Soon;Lee, Jeong-Sang;Cho, Sang-Rok;Yoon, Hae-Kyung;Song, Chee-Sung
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.660-668
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    • 1995
  • Background: It is said that tuberculous pleuritis responds well to anti-tuberculous drug in general, so no further aggressive therapeutic management is unnecesarry except in case of diagnostic thoracentesis. But in clinical practice, we often see some patients who need later decortication due to dyspnea caused by pleural loculation or thickening despite several months of anti-tuberculous drug therapy. Therefore, we want to know the clinical difference between a group who received decortication due to complication of tuberculous pleuritis despite of anti-tuberculous drug and a group who improved after 9 months of anti-tuberculous drug only. Methods: We reviewed 20 tuberculous pleuritis patients(group 1) who underwent decortication due to dyspnea caused by pleural loculation or severe pleural thickening despite of anti-tuberculous drug therapy for 9 or more months, and 20 other tuberculous pleuritis patients(group 2) who improved by anti-tuberculous drug only and had similar degrees of initial pleural effusion and similar age, sex distribution. Then we compared between the two groups the duration of symptoms before anti-tuberculous drug treatment and pleural fluid biochemistry like glucose, LDH, protein and pleural fluid cell count and WBC differential count, and we also wanted to know whether there was any difference in preoperative PFT value and postoperative PFT value in the patients who underwent decortication, and obtained following results. Results: 1) Group 1 patients had lower glucose level{$63.3{\pm}30.8$(mg/dl)} than that of the group 2{$98.5{\pm}34.2$(mg/dl), p<0.05}, and higher LDH level{$776.3{\pm}266.0$(IU/L)} than the group 2 patients{$376.3{\pm}123.1$(IU/L), p<0.05}, and also longer duration of symptom before treatment{$2.0{\pm}1.7$(month)} than the group 2{$1.1{\pm}1.2$(month), p<0.05}, respectively. 2) In group 1, FVC changed from preoperative $2.55{\pm}0.80$(L) to postoperative $2.99{\pm}0.78$(L)(p<0.05), and FEV1 changed from preoperative $2.19{\pm}0.70$(L/sec) to postoperative $2.50{\pm}0.69$(L/sec)(p<0.05). 3) There was no difference in pleural fluid protein level($5.05{\pm}1.01$(gm/dL) and $5.15{\pm}0.77$(gm/dl), p>0.05) and WBC differential count between group 1 and group 2. Conclusion: It is probable that in tuberculous pleuritis there is a risk of complication in the case of showing relatively low pleural fluid glucose or high LDH level, or in the case of having long duraton of symptom before treatment. We thought prospective study should be performed to confirm this.

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Tuberculin Skin Test and Plasma Prostaglandin $E_2$ In Patients of New and Intractable Pulmonary Tuberculosis (초치료 및 난치 폐결핵 환자의 투베르쿨린 피부검사와 혈장 Prostaglandin $E_2$)

  • Kim, Ji-Hong;Choi, In-Hwan;Kim, Mee-Ae;Shin, Chul-Shik;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.669-676
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    • 1995
  • Background: The cell-mediated immunity is needed for eradicating the tubercle bacilli. Prostaglandin(PG), especially PG $E_2$, is involved in cellular immunosuppression. It is known that the PG $E_2$ is suppressed by indomethacin. For using indomethacin as a immunomodulator of intractable pulmonary tuberculosis(Tbc) patients, we measured the tuberculin skin test(TST) and the plasma PG $E_2$ levels. Method: The forty-eight inpatients with sputum positive acid-fast stain bacilli were classified into 6 groups according to antiTbc chemotherapy history(new and intractable cases), plain chest roetgenogram(minimal and far advanced cases), and TST reaction(nagative and positive cases). Except for one group(n=2; new, minimal, and negative cases of TST reaction) of the 6 groups, all subjects(n=46) were measured for the plasma PG $E_2$, levels with radioimmunoassay. Results: 1) There was no significant difference in the plasma PG $E_2$ levels among A group(far advanced and positive TST reaction cases, n=10, $11.22{\pm}2.86\;pg/ml$), B group(minimal and negative TST reaction cases, n=9, $11.35{\pm}2.20$) and C group(far advanced and positive TST reaction cases, n=7, $11.11{\pm}2.30$) in the new cases(p>0.05). 2) There was no significant difference in the plasma PG $E_2$ levels between positive(n=10, $9.25{\pm}2.21$) and negative(n=10, $8.25{\pm}1.13$) groups by TST in the intractable cases(p>0.05). 3) Comparing the plasma PG $E_2$ levels between new(n=26, $11.35{\pm}2.41$) and intractable(n=20, $8.75{\pm}1.78$) groups, the intractable group had significi- andy lower plasma PG $E_2$ levels(p<0.05). 4) There was no significant difference in the plasma PG $E_2$ levels between negative(n=19, $9.88{\pm}2.43$) and positive(n=27, $10.46{\pm}2.56$) groups by TST(p>0.05). 5) There was no significant difference in the plasma PG $E_2$ levels between male(n=32, $10.07{\pm}2.44$) and female(n=14, $10.56{\pm}2.70$)(p>0.05). 6) There was no significant difference in the plasma PG $E_2$ levels among 2nd(n=5, $10.21{\pm}2.86$), 3rd(n=9, $9.97{\pm}2.47$), 4th(n=13, $11.35{\pm}2.33$) and 5th(n=19, $9.57{\pm}2.48$) decades(p>0.05). 7) There was no significant correlation between the induration sizes of the TST and the plasma PG $E_2$ levels(r=0.054, p>0.05). Conclusion: From the above results, the plasma PG $E_2$ levels of intractable group are not higher as the authors had expected. There was no significant difference in the plasma PG $E_2$ levels by the lesion sizes of plain chest roentgenogram and the induration sizes of TST, so more study will be needed to use the indomethacin as a immunomodulator for intractable pulmonary tuberculosis patients.

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The Usefulness of Pressure-regulated Volume Control(PRVC) Mode in Mechanically Ventilated Patients with Unstable Respiratory Mechanics (기계 호흡 중 불안정한 호흡역학을 보인 환자에서 압력조절용적조정양식(Pressure-regulated Volume Control Mode)의 효용)

  • Sohn, Jang-Won;Koh, Youn-Suck;Lim, Chae-Man;Shim, Tae-Sun;Lee, Jong-Deog;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.6
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    • pp.1318-1325
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    • 1997
  • Background : Since the late 1960s, mechanical ventilation has been accomplished primarily using volume controlled ventilation(VCV). While VCV allows a set tidal volume to be guaranteed, VCV could bring about excessive airway pressures that may be lead to barotrauma in the patients with acute lung injury. With the increment of knowledge related to ventilator-induced lung injury, pressure controlled ventilation(PCV) has been frequently applied to these patients. But, PCV has a disadvantage of variable tidal volume delivery as pulmonary impedance changes. Since the concept of combining the positive attributes of VCV and PCV(dual control ventilation, DCV) was described firstly in 1992, a few DCV modes were introduced. Pressure-regulated volume control(PRVC) mode, a kind of DCV, is pressure-limited, time-cycled ventilation that uses tidal volume as a feedback control for continuously adjusting the pressure limit However, no clinical studies were published on the efficacy of PRVC until now. 'This investigation studied the efficacy of PRVC in the patients with unstable respiratory mechanics. Methods : The subjects were 8 mechanically ventilated patients(M : F=6 : 2, $56{\pm}26$ years) who showed unstable respiratory mechanics, which was defined by the coefficients of variation of peak inspiratory pressure for 15 minutes greater than 10% under VCV, or the coefficients of variation of tidal volume greater than 10% under PCV. The study was consisited of 3 modes application with VCV, PCV and PRVC for 15 minutes by random order. To obtain same tidal volume, inspiratory pressure setting was adjusted in PCV. Respiratory parameters were measured by pulmonary monitor(CP-100 pulmonary monitor, Bicore, Irvine, CA, USA). Results : 1) Mean tidal volumes($V_T$) in each mode were not different(VCV, $431{\pm}102ml$ ; PCV, $417{\pm}99ml$ ; PRVC, $414{\pm}97ml$) 2) The coefficient of variation(CV) of $V_T$ were $5.2{\pm}3.9%$ in VCV, $15.2{\pm}7.5%$ in PCV and $19.3{\pm}10.0%$ in PRVC. The CV of $V_T$ in PCV and PRVC were significantly greater than that in VCV(p<0.01). 3) Mean peak inspiratory pressure(PIP) in VCV($31.0{\pm}6.9cm$ $H_2O$) was higher than PIP in PCV($26.0{\pm}6.5cm$ $H_2O$) or PRVC($27.0{\pm}6.4cm$ $H_2O$)(p<0.05). 4) The CV of PIP were $13.9{\pm}3.7%$ in VCV, $4.9{\pm}2.6%$ in PVC and $12.2{\pm}7.0%$ in PRVC. The CV of PIP in VCV and PRVC were greater than that in PCV(p<0.01). Conclusions : Because of wide fluctuations of VT and PIP, PRVC mode did not seem to have advantages compared to VCV or PCV in the patients with unstable respiratory mechanics.

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Clinical Efficacy of Erdosteine in Patients with Acute or Chronic Bronchitis -A Randomized, Double Blind, Comparative Study vs. Ambroxol- (급.만성 기관지염 환자에서 엘도스$^{(R)}$(Erdosteine)의 임상효과 -염산 암브록솔과의 무작위 이중맹검 비교시험-)

  • Kim, Seok-Chan;Lee, Sang-Hoak;Song, So-Hyang;Kim, Young-Kyoon;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.6
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    • pp.1296-1307
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    • 1997
  • Background : Erdosteine is a thiol derivative developed for the treatement of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis. Erdosteine has mucomodulating and antioxidant properties and especially exhibits excellent gastrointestinal tolerability. Methods : The study was conducted as a prospective evaluation, with 2 comparative groups orally treated with erdosteine 300mg (bid.) or ambroxol 30mg (b.i.d.) for 7 days and the design of trial was double-blind. The treatments have been assigned randomly to patients (n=80) with acute or chronic bronchitis. The primary end-point used to determine efficacy in this study was subjective symptoms including expectorating frequence, expectoration volume, expectorating difficulty, expectoration viscosity, cough intensity and dyspnea. The secondary end-points of efficacy was the result of arterial blood gas analysis and pulmonary function test. Safety was evaluated with adverse drug reactions and laboratory tests monitoring. 61 patients was included in the efficacy analysis, due to the fact that 19 patients drop-out for different reasons. The obtained values have been analyzed with paired Hest., ANOVA test., multivariate $t^2$-test, repeated measures analysis of covariance, two sample t-test, loglinear-logit model analysis, Fisher's exact test. Results : 1) There was no significant difference on demographic data and vital signs between erdosteine and ambroxol treated groups. 2) The comparison between erdosteine and ambroxol treated groups showed no significant difference in improvement of each symptom in spite of the more favorable efficacy obtained with erdosteine. No difference on the contrary was observed for arterial blood gas analysis and pulmonary function test. 3) As safety is concerned, no clinical significant changes in laboratory test and symptom were induced in erdosteine and ambroxol treated group and two patients in ambroxol treated group drop-out for adverse reactions in symptom. 4) In the evaluation of final clinical efficacy, erdosteine improved more effectively patient's overall symptoms {very good effect (11/31), good effect (12/31), moderate effect (6/31), no effect (2/31), aggravation (0/31)} than ambroxol {very good effect (6/30), good effect (14/30), moderate effect (5/30), no effect (4/30), aggravation (2/30)}. And the probability of symptomatic improvement by erdosteine compared to ambroxol was 2.5 times. (p<0.05). Conclusion : This study showed that erdosteine was clinically effective and safe drug for treatment of acute and chronic bronchitis.

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The Significance of IL-10, IL-12, IFN-$\gamma$ and ADA in Tuberculous Pleural Fluid (결핵성 흉수에서 IL-10, IL-12, IFN-$\gamma$, ADA 측정의 의의)

  • Jeon, Doo-Soo;Yun, Sang-Myung;Park, Sam-Seok;Lee, Hyo-Jin;Kim, Yun-Seong;Lee, Min-Ki;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.301-310
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    • 1998
  • Background: Cell mediated immune response mediated by interaction between CD4+ T lymphocytes and macrophagies is thought to play an important role in tuberculous pleurisy. This interaction is dependent on the interplay of various cytokines. The immunologic response of tuberculous pleurisy is thought to depend on the balance between helper T cell(Th1) cytokine Interleukin-12, Interferon gamma and Th2 cytokine IL-4, IL-10. To understand immunologic mechanism in tuberculous pleurisy and evaluate diagnostic value of these cytokines, the concentrations of Th1 cytokine IL-12, IFN -$\gamma$ and Th2 cytokine IL-10 were measured in tuberculous pleurisy and malignant pleural effusion group. Material and Methods: The concentrations of IL-10, IL-12 and IFN-$\gamma$ were measured by ELISA method in pleural fluids and serums of 20 patients with tuberculous pleurisy and 20 patients with malignant pleural effusion ADA activities were measured by spetrophotomery in pleural fluids of both groups. Results: In tuberculous pleurisy, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL and $420.4{\pm}285.9$ pg/mL. These were significantly higher than that of serum, $21.2{\pm}60.9$ pg/mL, 194.5 pg/mL, $30.1{\pm}18.3$ pg/mL respectively(p< 0.01). In malignant pleural effusion, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL and $30.5{\pm}54.8$ pg/mL respectively. Compared with that of serum ($43.4{\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL), only IL-10 was significantly higher (p<0.001), but IL-12, IFN-$\gamma$ were not significant. In tuberculous pleural effusion compared with malignant pleural effusion, the concentration of IL-12, IFN-$\gamma$, ADA were significantly higher (p=value 0.046, <0.001, <0.001), but IL-10 was not significant. For differential diagnosis of tuberculous pleurisy from malignant pleural effusion, using cut-off value of IL-12, IFN-$\gamma$, ADA as 300 pg/mL. 100 pg/mL, 45 U/L, the sensitivity/specificity were 60%/70%, 90%/87.5%, 85%/90% respectively. Conclusion: In tuberculous pleurisy, IL-10, IL-12 and IFN-$\gamma$ were selectively concentrated highly in pleural space than serum. Compared with malignant pleural effusion, IL-12 and IFN-$\gamma$ were significantly higher, but IL-10 were not in tuberculous pleural effusion. The results suggest that Th1 pathway contributes to immune resistant mechanism in tuberculous pleurisy. IFN-$\gamma$ and ADA revealed useful methods of differential diagnosis in tuberculous pleurisy from malignant pleural effusion.

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Prognostic Value of TNM Staging in Small Cell Lung Cancer (소세포폐암의 TNM 병기에 따른 예후)

  • Park, Jae-Yong;Kim, Kwan-Young;Chae, Sang-Cheol;Kim, Jeong-Seok;Kim, Kwon-Yeop;Park, Ki-Su;Cha, Seung-Ik;Kim, Chang-Ho;Kam, Sin;Jung, Tae-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.322-332
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    • 1998
  • Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

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Triptolide-induced Transrepression of IL-8 NF-${\kappa}B$ in Lung Epithelial Cells (폐상피세포에서 Triptolide에 의한 NF-${\kappa}B$ 의존성 IL-8 유전자 전사활성 억제기전)

  • Jee, Young-Koo;Kim, Yoon-Seup;Yun, Se-Young;Kim, Yong-Ho;Choi, Eun-Kyoung;Park, Jae-Seuk;Kim, Keu-Youl;Chea, Gi-Nam;Kwak, Sahng-June;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.52-66
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    • 2001
  • Background : NF-${\kappa}B$ is the most important transcriptional factor in IL-8 gene expression. Triptolide is a new compound that recently has been shown to inhibit NF-${\kappa}B$ activation. The purpose of this study is to investigate how triptolide inhibits NF-${\kappa}B$-dependent IL-8 gene transcription in lung epithelial cells and to pilot the potential for the clinical application of triptolide in inflammatory lung diseases. Methods : A549 cells were used and triptolide was provided from Pharmagenesis Company (Palo Alto, CA). In order to examine NF-${\kappa}B$-dependent IL-8 transcriptional activity, we established stable A549 IL-8-NF-${\kappa}B$-luc. cells and performed luciferase assays. IL-8 gene expression was measured by RT-PCR and ELISA. A Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation and an electromobility shift assay was done to analyze NF-${\kappa}B$ DNA binding. p65 specific transactivation was analyzed by a cotransfection study using a Gal4-p65 fusion protein expression system. To investigate the involvement of transcriptional coactivators, we perfomed a transfection study with CBP and SRC-1 expression vectors. Results : We observed that triptolide significantly suppresses NF-${\kappa}B$-dependent IL-8 transcriptional activity induced by IL-$1{\beta}$ and PMA. RT-PCR showed that triptolide represses both IL-$1{\beta}$ and PMA-induced IL-8 mRNA expression and ELISA confirmed this triptolide-mediated IL-8 suppression at the protein level. However, triptolide did not affect $I{\kappa}B{\alpha}$ degradation and NF-$_{\kappa}B$ DNA binding. In a p65-specific transactivation study, triptolide significantly suppressed Gal4-p65T Al and Gal4-p65T A2 activity suggesting that triptolide inhibits NF-${\kappa}B$ activation by inhibiting p65 transactivation. However, this triptolide-mediated inhibition of p65 transactivation was not rescued by the overexpression of CBP or SRC-1, thereby excluding the role of transcriptional coactivators. Conclusions : Triptolide is a new compound that inhibits NF-${\kappa}B$-dependent IL-8 transcriptional activation by inhibiting p65 transactivation, but not by an $I{\kappa}B{\alpha}$-dependent mechanism. This suggests that triptolide may have a therapeutic potential for inflammatory lung diseases.

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Clinical Study on Thoracic Actinomycosis (흉부 방선균종의 임상적 고찰)

  • Hong, Sang-Bum;Kim, Woo-Sung;Lee, Jae-Hwan;Bang, Sung-Jo;Shim, Tae-Son;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Lee, In-Chul;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.1058-1066
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    • 1998
  • Background: Actinomycotic infection is uncommon and primary actinomycosis of the lung and chest wall has been less frequently reported. This disease may present as chronic debilitating illness with radiologic manifestation simulating lung tumor, pulmonary infiltrating lesion, or chronic suppuration. Diagnosis of choice was not definded yet and role of bronchoscopy on diagnosis was not described yet. Methods: From 1989 to 1998, we experienced 17 cases of thoracic actinomycosis. We have reviewed the case notes of 17 patients with thoracic actinomycosis. The mean age at presentation was $53{\pm}13$ years, 11 were male. Results: Cough, hemoptysis, sputum production, chest pain and weight loss were the commonest symptoms. The mean delay between presentation and diagnosis was $6.6{\pm}7.8$ months. There were six patients who presented with a clinical picture of a suppurative lesion and eleven patients were suspected of having primary lung tumor initially. In no cases was made an accurate diagnosis at the time of hospital admission. Associated diseases were emphysema (1 case), bronchiectasis (2 cases) and tuberculosis (2 cases). Bronchoscopic findings were mucosal swelling and stenosis(n=4), mucosal swelling, stenosis and necrotic covering (n=2), mass (n=3), mass and necrotic covering (n=1) and normal(n=6). Radiologic findings were mass lesion(n=8), pneumonitis(n=3), atelectasis(n=3), pleural effusion(n=2), and normal(n=3). Final diagnosis was based on percutaneous needle aspiration and biopsy (n=3), bronchoscopic biopsy specimens (n=9), mediastinoscopic biopsy (n=1) and histologic examination of resected tissue in the remaining patients(n=4) who received surgical excision. Among 17 patients, 13 were treated medically and the other 4 received surgical intervention followed by antibiotic treatment. Regarding the surgically treated patients, suspected malignancy is the most common indication for operation. However. both medically and surgically treated patients achieved good clinical results. Conclusion: Thoracic actinomycosis is rare. but should still be considered in the differential diagnosis of a chrinic, localized pulmonary lesion. Thoracic actinomycosis may co-exist with pulmonary tuberculosis or lung cancer. If the lesion is located in the central of the lung. the bronchoscopy is recommanded for the diagnosis.

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