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Effects of FK224, a $NK_1$ and $NK_2$ Receptor Antagonist, on Plasma Extravasation of Neurogenic Inflammation in Rat Airways (미주 신경의 전기적 자극으로 유발된 백서의 기도내 혈장 유출에 대한 FK224의 효과)

  • Shim, Jae-Jeong;Lee, Sang-Yeub;Lee, Sang-Hwa;Park, Sang-Myun;Seo, Jeong-Kyung;Cho, Jae-Yun;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.744-751
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    • 1995
  • Background: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin receptors. Three types of neurokinin receptors, such as $NK_1$, $NK_2$, and $NK_3$, are currently recognized, at which substance p, neurokinin A, and neurokinin B may be the most relevant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the $NK_2$ receptors in airway smooth muscles. These receptors are used to evaluate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both $NK_1$ and $NK_2$ receptors. Purpose: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. Method: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(1mg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsulphoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg, dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide($37^{\circ}C$, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. Results: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, $14.1{\pm}1.6$ to $49.7{\pm}2.5$, $17.5{\pm}2.0$ to $38.7{\pm}2.8$, and $12.7{\pm}2.2$ to $19.1{\pm}1.6ng$ of dye per mg of tissue(mean ${\pm}$ SE), respectively(p<0.05). But there was not significantly changed in lung parenchyma(p>0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. Conclusion: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.

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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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Comparision of Chest Radiographs and Pulmonary Function in Coal Workers' Pneumoconiosis and Welders' Lung (탄광부 진폐증과 용접공 폐증에 있어 흉부-X선 소견과 폐기능의 비교)

  • Park, Dong-Youl;Hwang, Joo-Ho;Kang, Byung-Son;Chung, Chan-Su;Kim, Wha-Jo
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.713-722
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    • 1995
  • Background: Chest X-ray of coal workers' pneumoconiosis and shipyard welders' lung show similar and regular opacities mostly, it is very difficult that we distinguish the former from the latter by only chest X-ray. so we performed this study to understand the progression of the disease and to provide the disease by considering pulmonary function and other factors in proportion to the profusion of small regular opacities of chest X-ray in both groups. Method: 430 coal workers' pneumoconiosis were compared with 311 shipyard welders' lung by the number, the age, the duration of dust exposure, %vital capacity(%VC), %FEV1.0, the type of ventilatory impairment, the combined pulmonary disease according to the profusion of small regular opacities on the chest radiographs, which were classified into category 0/1, category 1, and category 2. Result: 1) the percent of category 2 in coal workers' pneumoconiosis was 54.4%. the percent of category 1, and category 2 in welders' lung were 60.0%, 7.4%. the progression to the category 2 was higher in coal workers' pneumoconiosis than in welders' lung 2) The mean age was higher in coal workers' pneumoconiosis than in welders' lung, significantly increased in proportion to the progresion of profusion of small regular opacities in both groups 3) There was no difference in the duration of dust exposure by category 1/0, but the duration of dust exposure by category 1, 2 in coal workers' pneumoconiosis more significantly increased than in welders' lung. the duration in the proportion of category 2 to category 0/1, 1 significantly increased in the proportion to small regular opacities in coal workers' pneumoconiosis. but there was no significant difference in the proportion to small regular opacities in duration of dust exposure in welders' lung. 4) There was no significant difference of mean values of %VC(%vital capacity)in both groups except for category 1. the mean values of %VC had no relationship between the progression of small regular opacities in both groups. 5) The mean values of %FEV1.0 decreased more significantly in coal workers' pneumoconiosis than in welders' lung except for category 0/1. and decreased significantly in proportion to the profusion of small regular opacities in coal workers' pneumoconiosis. there was significant difference of %FEV1.0 in the proportion of category 2 to category 011 in welders' lung. 6) there were no significant difference of %FEV1.0, %VC in smoker and nonsmoker in both groups. 7) With regard to the type of ventilation in both groups in coal workers' pneumoconiosis 21.4 percent of patients belonged to the restrictive type, 11.6 percent to the obstructive type, 5.6 percent to the combined type, but in welders' lung 21.8 percent to the restrictive type, 2.9 percent to the obstructive type, 1.9 percent to the combined type. 8. in the pulmonary disease, the incidence of the pulmonary tuberculosis was the most in both groups, was more in coal workers' pneumoconiosis than welders' lung Conclusion: If we compare coal workers' pneumoconiosis with electric arc welders'lung by considering pulmonary function and other factors in proportion to the profusion of chest X-ray, I think that we will have the better result in understanding the progression of the disease and provision of the disease in both groups.

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The Effect of External PEEP on Work of Breathing in Patients with Auto-PEEP (Auto-PEEP이 존재하는 환자에서 호흡 일에 대한 External PEEP의 효과)

  • Chin, Jae-Yong;Lim, Chae-Man;Koh, Youn-Suck;Park, Pyung-Whan;Choi, Jong-Moo;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.201-209
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    • 1996
  • Background : Auto-PEEP which develops when expiratory lung emptying is not finished until the beginning of next inspiration is frequently found in patients on mechanical ventilation. Its presence imposes increased risk of barotrauma and hypotension, as well as increased work of breathing (WOB) by adding inspiratory threshold load and/or adversely affecting to inspiratory trigger sensitivity. The aim of this study is to evaluate the relationship of auto-PEEP with WOB and to evaluate the effect of PEEP applied by ventilator (external PEEP) on WOB in patients with auto-PEEP. Method : 15 patients, who required mechanical ventilation for management of acute respiratory failure, were studied. First, the differences in WOB and other indices of respiratory mechanics were examined between 7 patients with auto-PEEP and 8 patients without auto-PEEP. Then, we applied the 3 cm $H_2O$ of external PEEP to patients with auto-PEEP and evaluated its effects on lung mechanics as well as WOB. Indices of respiratory mechanics including tidal volume ($V_T$), repiratory rate, minute ventilation ($V_E$), peak inspiratory flow rate (PIFR), peak expiratory flow rate (PEFR), peak inspiratory pressure (PIP), $T_I/T_{TOT}$, auto-PEEP, dynamic compliance of lung (Cdyn), expiratory airway resistance (RAWe), mean airway resistance (RAWm), $p_{0.1}$, work of breathing performed by patient (WOB), and pressure-time product (PTP) were obtained by CP-100 Pulmonary Monitor (Bicore, USA). The values were expressed as mean $\pm$ SEM (standard error of mean). Results : 1) Comparison of WOB and other indices of respiratory mechanics in patients with and without auto-PEEP : There was significant increase in WOB ($l.71{\pm}0.24$ vs $0.50{\pm}0.19\;J/L$, p=0.007), PTP ($317{\pm}70$ vs $98{\pm}36\;cm$ $H_2O{\cdot}sec/min$, p=0.023), RAWe ($35.6{\pm}5.7$ vs $18.2{\pm}2.3\;cm$ H2O/L/sec, p=0.023), RAWm ($28.8{\pm}2.5$ vs $11.9{\pm}2.0cm$ H2O/L/sec, p=0.001) and $P_{0.1}$ ($6.2{\pm}1.0$ vs 2.9+0.6 cm H2O, p=0.021) in patients with auto-PEEP compared to patients without auto-PEEP. The differences of other indices including $V_T$, PEFR, $V_E$ and $T_I/T_{TOT}$ showed no significance. 2) Effect of 3 cm $H_2O$ external PEEP on respiratory mechanics in patients with auto-PEEP : When 3 cm $H_2O$ of external PEEP was applied, there were significant decrease in WOB ($1.71{\pm}0.24$ vs $1.20{\pm}0.21\;J/L$, p=0.021) and PTP ($317{\pm}70$ vs $231{\pm}55\;cm$ $H_2O{\cdot}sec/min$, p=0.038). RAWm showed a tendency to decrease ($28.8{\pm}2.5$ vs $23.9{\pm}2.1\;cm$ $H_2O$, p=0.051). But PIP was increased with application of 3 cm $H_2O$ of external PEEP ($16{\pm}2$ vs $22{\pm}3\;cm$ $H_2O$, p=0.008). $V_T$, $V_E$, PEFR, $T_I/T_{TOT}$ and Cdyn did not change significantly. Conclusion : The presence of auto-PEEP in mechanically ventilated patients was accompanied with increased WOB performed by patient, and this WOB was decreased by 3 cm $H_2O$ of externally applied PEEP. But, with 3 cm $H_2O$ of external PEEP, increased PIP was noted, implying the importance of close monitoring of the airway pressure during application of external PEEP.

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Role of Oxygen Free Radical in the Expression of Interleukin-8 and Interleukin-$1{\beta}$ Gene in Mononuclear Phagocytic Cells (내독소에 의한 말초혈액 단핵구의 IL-8 및 IL-$1{\beta}$ 유전자 발현에서 산소기 역할에 관한 연구)

  • Kang, Min-Jong;Kim, Jae-Yeol;Park, Jae-Seok;Lee, Seung-Joon;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.862-870
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    • 1995
  • Background: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor $NF{\kappa}B$ from cytoplasm to nucleus by releasing an inhibitory protein subunit, $I{\kappa}B$. Activation of $NF{\kappa}B$ is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor $NF{\kappa}B$ might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of $NF{\kappa}B$. From above facts, we can assume the expression of IL-8 and IL-$1{\beta}$ gene by LPS stimulation may occur through the activation of $NF{\kappa}B$, which is mediated through the release of $I{\kappa}B$ by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. Method: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of $H_2O_2$-induced IL-8 and IL-$1{\beta}$ mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL-$1{\beta}$ mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL-$1{\beta}$ mRNA was performed. Results: In PBMC, dose and time dependent expression of IL-8 and IL-$1{\beta}$ mRNA by exogenous $H_2O_2$ was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL-$1{\beta}$ mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. Conclusion: Oxygen free radical may have some role in the expression of IL-8 and IL-$1{\beta}$ mRNA of PBMC but that radical might not be $H_2O_2$.

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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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The Effect of Heat Shock Response on the Tumor Necrosis Factor-$\alpha$-induced Acute Lung Injury in Rats (Tumor Necrosis Factor-$\alpha$로 유도되는 백서의 급성 폐손상에 열충격반응이 미치는 효과)

  • Koh, Youn-Suck;Lim, Chae-Man;Kim, Mi-Jung;Cho, Won-Kyung;Jeoung, Byung-O;Song, Kyu-Young;Shim, Tae-Sun;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.1343-1352
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    • 1997
  • Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

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The Influence of Aging on Pulmonary Function Tests in Elderly Korean Population (한국에서 노화에 따른 폐기능지표의 변화양상)

  • Lee, Jae-Myung;Kim, Eun-Jung;Kang, Min-Jong;Son, Jee-Woong;Lee, Seung-Joon;Kim, Dong-Gyu;Park, Myung-Jae;Lee, Myung-Goo;Hyun, In-Gyu;Jung, Ki-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.752-759
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    • 2000
  • Background : Many studies have shown that pulmonary function differs widely among race, age and geographical residency. By virtue of the improvement of nutrition and environment, the elderly population in Korea is markedly increasing and so are the ages of patients complaining respiratory symptoms. However, we do not have our own data on the pulmonary functional reserve of elderly persons in Korea. We evaluate the deterioration of pulmonary functional reserve and standardize the predictive values of pulmonary function in the elderly population. Method : Pulmonary function tests were conducted in 100 men and 100 women over the age of 65. We analyzed changes of FVC and $FEV_1$ according to age and height by linear regression. We compared our new multiple linear regression equation with other equations currently used in Korea. Results : In men, the mean age was $71.5{\pm}5.2$(mean${\pm}$SD) years and the mean height was $163.6{\pm}6.2$cm. The mean FVC was $3.42{\pm}0.49{\ell}$ and the mean $FEV_1, $2.72{\pm}v$. In women, the mean age was $72.0{\pm}5.1$ years and the mean height was $149.1{\pm}5.9$cm. The mean FVC was $2.22{\pm}0.42{\ell}$ and the mean $FEV_1$ $1.83{\pm}0.34{\ell}$. Multiple linear regression equation using age and height as an independent factors was as follows : FVC(${\ell}$)=1.857-0.0356$\times$age(year)+0.02517$\times$height(cm) (p<0.01, $R^2$=0.279), $FEV_1(${\ell}$)=1.340-0.02698$\times$age(year)+0.02021$\times$height(cm) (p<0.01, $R^2$=0.255) in men, FVC(${\ell}$) =-0.09765-0.03332$\times$age(year)+0.03164$\times$height(cm) (p<0.01, $R^2$=0.435), $FEV_1(${\ell}$)=-0.l69-0.02469$\times$age(year)+0.02539$\times$height(cm) (p<0.01, $R^2$=0.41) in women. Conclusion : We established prediction regressions for pulmonary functional tests in the elderly Korean population. We also confirmed that currently adopted equations do not exactly anticipate the expected pulmonary functional reserve in the aged person over 65 years old. We suggest that our new equations from this study should be applied to interpret the pulmonary function tests in the elderly population in Korea.

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Analysis of Specificity for Tumor Marker CYFRA 21-1 in Patients with Pulmonary Tuberculosis (폐결핵 환자에서 종양표지자 CYFRA 21-1의 특이도 분석)

  • Ha, Hyun-Cheol;Lee, Jae-Sung;Song, Sun-Dae;Kim, Cheol-Min;Lee, Min-Gi;Kim, In-Joo
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.290-300
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    • 1998
  • Background: CYFRA 21-1 is a tumor marker which measures a fragment of cytokeratin 19 expressed by epithelial cells in bronchus. It is known that cytokeratin 19 is abundant in squamous epithelial cell cancer of the lung. However, if the incidence of elevated serum CYFRA 21-1 level in patients with benign lung diseases or pulmonary tuberculosis with severe parenchymal damage is high the specificity of CYFRA 21-1 could be decreased. The purpose of this study is to investigate the changes of serum CYFRA 21-1 according to the degree of parenchymal damage and the usefulness of CYFRA 21-1 for diagnosing possibly combined lung cancer in patients with pulmonary tuberculosis. Method: We studied the changes of serum CYFRA 21-1 according to the sputum AFB stain, radiologic manifestation and history of treatment in 81 patients with pulmonary tuberculosis, and 20 healthy persons, 25 patients with lung cancer, as a control group. CYFRA 21-1 concentration in serum was quantified by the immunoradiometry assay(Centocor$^{(R)}$). Result: The results were as follow; Serum CYFRA 21-1 level was significantly lower in patients with pulmonary tuberculosis($1.54{\pm}1.19ng/mL$, p<0.01) as compared to patients with lung cancer($12.25{\pm}15.97ng/mL$), and was slightly higher than the level in heathy persons($0.90{\pm}0.49ng/mL$) but there was no significant difference. Serum CYFRA 21-1 level was below the cut-off value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis but it was above the cut-off value in 64 percent of patients with lung cancer. Serum CYFRA 21-1 level was significantly higher in the initial treatment group($1.91{\pm}1.55ng/mL$, p<0.05) as compared to the treatment. failure group ($0.92{\pm}0.30ng/mL$). According to the sputum AFB smear, serum CYFRA 21-1 level in patients with negative result was slightly higher than the level in patients with positive result but there was no significant difference. According to the radiologic manifestation, serum CYFRA 21-1 level was significantly higher in patients with infiltrative lesion ($2.15{\pm}1.63ng/mL$, p<0.01) as compared to patients with destructive lesion ($l.04{\pm}0.54ng/mL$). As the size of cavity or destructive lesion was larger, the level was significantly lower(p<0.05). Conclusion: As serum CYFRA 21-1 level was significantly higher in the initial treatment group and patients with infiltrative lesion, it suppose to be closely related with the degree of parenchymal damage of the lung of the pulmonary tuberculosis. However CYFRA 21-1 could be useful method for diagnosing lung cancer even in patients with pulmonary tuberculosis combined with lung cancer because of the fact that it was below the cutoff value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis.

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