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The Role of Tumor Necrosis Factor-$\alpha$ and Interleukin-$1{\beta}$ as Predictable Markers for Development of Adult Respiratory Distress Syndrome in Septic Syndrome (패혈증 증후군환자에서 성인성 호흡곤란 증후군 발생의 예측 지표서의 혈중 Tumor Necrosis Factor-$\alpha$와 Interleukin-$1{\beta}$에 관한 연구)

  • Koh, Youn-Suck;Jang, Yun-Hae;Kim, Woo-Sung;Lee, Jae-Dam;Oh, Soon-Hwan;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.452-461
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    • 1994
  • Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

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Effect of Posture on the Distribution of Pulmonary Ventilation in Patients with Increased Closing volume (폐쇄용적(Closing Volume)이 증가된 만성 폐질환 환자에서 체위에 따른 폐환기량의 변화)

  • Kim, Young-Tae;Kim, Mee-Kyung;Lim, Chae-Man;Koh, Youn-Suck;Kim, Woo-Sung;Ryu, Jin-Sook;Lee, Myung-Hae;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.6
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    • pp.631-637
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    • 1993
  • Background: In normal adults, ventilation is uneven and greater in the base than the apex of the lung in tidal volume breathing. However infants have fragile chest wall and reduced elastic recoil, resulting in easy closure of peripheral airways especially in the dependent portion of the lung. So ventilation in infants is greater in the apex than the base of the lung. We assumed that in adults whose closing volume is increased, dependent portion could be easily collapsed during tidal breathing and ventilation could be greater in the uppear than than the lower portion of the lung. Methods: We measured spirometry and closing volume(CV) in normal controls and in patients with chronic lung disease. Also we measured fractional distribution of ventilation at supine, left lateral and right lateral decubitus with $^{133}Xe$ ventilation scan in normal controls, patients with normal closing volume and patients with increased closing volume. Results: The subjects consisted of 7 normal controls(mean $age{\pm}SD$, $62.9{\pm}6.1$ years). 6 patients with normal CV($62.8{\pm}8.2$ years) and 7 patients with increased CV($63.0{\pm}15.3$ years). 1) Normal controls have mean(${\pm}SD$) FVC $104{\pm}11%$ of predicted value, $FEV_1\;120{\pm}16%,\;FEV_1/FVC\;112{\pm}5%$ and CV $86.9{\pm}12.5%$. Patients with normal CV have FVC $62{\pm}11%,\;FEV_1\;54{\pm}17%,\;FEV_1/FVC\;84{\pm}23%$ and CV $92.6{\pm}15.5%$. Patients with increased CV, have FVC $53{\pm}9%,\;FEV_1\;38{\pm}13,\;FEV_1/FVC\;69{\pm}16%$ and CV $176.1{\pm}36.6%$, CV was significantly different between two patient groups(p<0.02) 2). In normal controls mean fractional ventilation to left lung was $48.1{\pm}5.3%$ at supine, $54.1{\pm}9.8%$ at dependent and $40.9{\pm}6.5%$ at left uppermost position. In patients with normal CV mean fractional ventilation to left lung was $44.6{\pm}2.1%$ at supine, $59.7{\pm}5.6%$ at left dependent and $31.7{\pm}8.3%$ at left uppermost position. In patients with increased CV mean fractional ventilation to left lung was $48.7{\pm}4.5%$ at supine, $41.7{\pm}6.6%$ at left dependent and $60.9{\pm}15.7%$ at left uppermost position. In normal controls and patients with normal CV, ventilation to left lung at left dependent position tends to be higher than that at supine position but without statisitical significance and it was significantly lower at left uppermost than at left lung dependent position. In patients with increased CV, ventilation to left at left dependent position tends to be higher than that at supine position but without significance and it was significantly higher at left uppermost than that at left dependent position. Conclusion: These data suggest that in patients with increased CV ventilation to one side of lung could be higher at uppermost than at dependent position on lateral decubitus during tidal breathing and this fact should be taken into account in positioning of patients with unilateral lung disease.

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Experimental investigation of the photoneutron production out of the high-energy photon fields at linear accelerator (고에너지 방사선치료 시 치료변수에 따른 광중성자 선량 변화 연구)

  • Kim, Yeon Su;Yoon, In Ha;Bae, Sun Myeong;Kang, Tae Young;Baek, Geum Mun;Kim, Sung Hwan;Nam, Uk Won;Lee, Jae Jin;Park, Yeong Sik
    • The Journal of Korean Society for Radiation Therapy
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    • v.26 no.2
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    • pp.257-264
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    • 2014
  • Purpose : Photoneutron dose in high-energy photon radiotherapy at linear accelerator increase the risk for secondary cancer. The purpose of this investigation is to evaluate the dose variation of photoneutron with different treatment method, flattening filter, dose rate and gantry angle in radiation therapy with high-energy photon beam ($E{\geq}8MeV$). Materials and Methods : TrueBeam $ST{\time}TM$(Ver1.5, Varian, USA) and Korea Tissue Equivalent Proportional Counter (KTEPC) were used to detect the photoneutron dose out of the high-energy photon field. Complex Patient plans using Eclipse planning system (Version 10.0, Varian, USA) was used to experiment with different treatment technique(IMRT, VMAT), condition of flattening filter and three different dose rate. Scattered photoneutron dose was measured at eight different gantry angles with open field (Field size : $5{\time}5cm$). Results : The mean values of the detected photoneutron dose from IMRT and VMAT were $449.7{\mu}Sv$, $2940.7{\mu}Sv$. The mean values of the detected photoneutron dose with Flattening Filter(FF) and Flattening Filter Free(FFF) were measured as $2940.7{\mu}Sv$, $232.0{\mu}Sv$. The mean values of the photoneutron dose for each test plan (case 1, case 2 and case 3) with FFF at the three different dose rate (400, 1200, 2400 MU/min) were $3242.5{\mu}Sv$, $3189.4{\mu}Sv$, $3191.2{\mu}Sv$ with case 1, $3493.2{\mu}Sv$, $3482.6{\mu}Sv$, $3477.2{\mu}Sv$ with case 2 and $4592.2{\mu}Sv$, $4580.0{\mu}Sv$, $4542.3{\mu}Sv$ with case 3, respectively. The mean values of the photoneutron dose at eight different gantry angles ($0^{\circ}$, $45^{\circ}$, $90^{\circ}$, $135^{\circ}$, $180^{\circ}$, $225^{\circ}$, $270^{\circ}$, $315^{\circ}$) were measured as $3.2{\mu}Sv$, $4.3{\mu}Sv$, $5.3{\mu}Sv$, $11.3{\mu}Sv$, $14.7{\mu}Sv$, $11.2{\mu}Sv$, $3.7{\mu}Sv$, $3.0{\mu}Sv$ at 10MV and as $373.7{\mu}Sv$, $369.6{\mu}Sv$, $384.4{\mu}Sv$, $423.6{\mu}Sv$, $447.1{\mu}Sv$, $448.0{\mu}Sv$, $384.5{\mu}Sv$, $377.3{\mu}Sv$ at 15MV. Conclusion : As a result, it is possible to reduce photoneutron dose using FFF mode and VMAT method with TrueBeam $ST{\time}TM$. The risk for secondary cancer of the patients will be decreased with continuous evaluation of the photoneutron dose.

Efficacy of Pigtail Catheter Drainage in Patients with Thoracic Empyema or Complicated Parapneumonic Effusion (농흉 및 합병된 부폐렴성 흉막 삼출 환자에서 Pigtail 도관 배액의 유용성)

  • Park, Jeong Woo;You, Seung Min;Seol, Won Jong;Paik, Eun Ki;Lee, Kyu Hoon;Seo, Joon Beom;Jeong, Seong Hwan;An, Chang Hyeok;Lim, Youg Hee;Park, Jeong Woong
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.2
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    • pp.219-229
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    • 2003
  • Background : The management of thoracic empyema and complicated parapneumonic effusion requires adequate antibiotics use and prompt drainage of infected pleural space. Tube thoracostomy for loculated empyema has low success rate and is also an invasive procedure with potential morbidity. Complications include hemothorax, perforation of intra-abdominal or intra-thoracic organs, diaphragmatic laceration, empyema, pulmonary edema, and Horner's syndrome. Given the potential morbidity of traditional chest tube insertion, use of the image-guided pigtail catheter drainage(PCD) of empyema has been employed. We retrospectively analyzed the medical records of patients with empyema or complicated parapneumonic effusion to determine the efficacy of percutaneous pigtail catheter drainage. Materials and Methods : 45 patients with complicated parapneumonic effusions or empyema were treated at Gil medical center from January 1998 to June, 1999. All were initially given PCD procedure and the following data were collected: clinical symptoms at the time of diagnosis, alcohol and smoking history, the characteristics of pleural effusion, radiologic findings (at the time of catheter insertion, removal and 1 month after catheter removal), the amount of effusion drained for initial 24 hours, the time from catheter insertion to removal and the use of surgical approach. Results : Male gender was more frequent (42 men vs. 3 women), the mean age of the study population was 52(range: 21~74) years. Empyema was found in 23 patients, complicated parapneumonic effusion in 22 patients. Four patients(three, parapneumonic effusion and one, with empyema) with PCD only treated, were cast off. Among the available patients, 36(80%) patients were treated with PCD only or PCD with urokinase. Among the 23 patients with empyema, surgical approach was required in five patients(27.1%, one required decortication, four open thoracostomy), one patient, treated with surgical procedure, died of sepsis. There was no significant difference of the duration of catheter insertion, the duration of hospital admission after catheter insertion and the mean amount of effusion drained for initial 24 hours between the patients with only PCD treated and the patients treated with PCD and urokinase. The duration of catheter insertion($9.4{\pm}5.25days$ vs. $19.2{\pm}9.42days$, p<0.05) and the duration of hospital admission after catheter insertion($15.9{\pm}10.45days$ vs. $38.6{\pm}11.46days$, p<0.01) of the patients with only PCD treated were more longer than those of the patients treated with surgical procedure after PCD. They were same between the patients treated with urokinase after PCD and the patients treated with surgical procedure after PCD($11.1{\pm}7.35days$ vs. $19.2{\pm}9.42days$, p<0.05, $17.5{\pm}9.17days$ vs. $38.6{\pm}11.46days$, p<0.01). In 16 patients(44.4%) with only PCD treated or PCD and urokinase treated, the amount of effusion at the time of catheter removal was decreased more than 75% and in 17 patients(47.2%) effusion decreased 50~75%. .In one patient effusion decreased 25~50%, in two patients effusion decreased less than 25%. One month after catheter removal, in 35 patients(97.2%, four patients were cast off), the amount of pleural effusion was successfully decreased more than 50%. There were no complications related to pigtail catheter insertion. Conclusion : In this study, PCD seemed to be an early efficacious procedure in treating the patients with complicated parapneumonic effusion or empyema without any serious procedure related complication.

Effects of Dietary Germanium Biotite in Weaned, Growing and Finishing Pigs (이유자돈, 육성돈 및 비육돈에 있어 게르마늄흑운모의 급여 효과)

  • Kwon, O.S.;Kim, I.H.;Hong, J.W.;Lee, S.H.;Jung, Y.K.;Min, B.J.;Lee, W.B.;Shon, K.S.
    • Journal of Animal Science and Technology
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    • v.45 no.3
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    • pp.355-368
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    • 2003
  • In Exp. 1, this study was conducted to determine the effect of dietary germanium biotite on growth performance and nutrient digestibility in nursery pigs. A total of sixty crossbred pigs (initial body weight 15.09$\pm$0.18kg) were used in this experiment. This study was carried out for 28 days. The five treatments were control (CON; basal diet), GB0.1 (basal diet + germanium biotite 0.1%), GB0.3 (basal diet + germanium biotite 0.3%), GB0.6 (basal diet + germanium biotite 0.6%) and GB1.0 (basal diet + germanium biotite 1.0%). For overall period, ADG and Gain/feed were not significantly different among the treatments. In Exp. 2, a study was conducted to evaluate the effect of germanium biotite as a substitute for antibiotics in growing pigs. A total of fifty five crossbred pigs (initial body weight 32.47$\pm$0.9kg) were used in this experiment. The three treatments were negative control (NC: basal diet without antibiotic), positive control (PC: basal diet + 200ppm CTC) and GB0.3 (basal diet + germanium biotite 0.3%). Pigs fed PC (17%, 385 vs 451 g/d) and GB0.3 (14%, 385 vs 438 g/d) diets grew faster(P<0.05) than pigs fed NC diet. Pigs fed PC and GB0.3 diets resulted higher(P<0.05) ADFI than pigs fed CON diet. However, pigs fed GB0.3 diet had improved gain/feed compared to pigs fed NC diet(P<0.05). Apparent digestibility of DM and N by pigs fed PC and GB0.3 diets were greater(P<0.05) than those by pigs fed NC diet. In Exp. 3, a study was conducted to determine the effect of dietary germanium biotite on growth performance, plasma characteristics, backfat thickness and fecal ammonia gas concentration in finishing pigs. A total of seventy-two finishing pigs (initial body weight 78.56$\pm$1.32kg) were used in this experiment. The treatments included 1) Control (CON; basal diet) 2) GB1.0 (basal diet + germanium biotite 1.0%), 3) GB3.0 (basal diet + germanium biotite 3.0%). Pigs fed GB1.0 diet grew faster than pigs fed CON diet and GB0.3 diet (P<0.05). Also, pigs fed CON diet showed higher(p<0.05) ADFI than pigs fed GB3.0 diet. Pigs fed GB diets had improved gain/feed compared to pigs fed CON diet(P<0.05). Total?and VLDL concentrations in plasma of pigs fed GB diets treatments were significantly decreased compared to those in pig fed CON diet(P<0.05). However, HDL-cholesterol concentration in plasma of the pig was significantly increased compared to those in pigs fed CON diet (P<0.05). Pigs fed CON diet exerted higher(P<0.05) backfat thickness than pigs fed GB1.0 (5.4%, 27.19 vs 25.71mm) and GB3.0 (16.1%, 27.19 vs 22.81mm) diets. Feces from CON treatment were higher in fecal ammonia gas concentration than faces from pigs fed GB1.0 (64.1%, 17.00 vs 6.10mg/kg)and GB3.0 (61.8%, 17.00 vs 6.50mg/kg) treatments(P<0.05). In conclusion, the results suggest that the dietary addition of germanium biotite into diets for nursery pigs did not affect growth performance. The results also suggest the possibility of germanium biotite to replace antibiotic in diets for growing pigs. In finishing pigs, dietary supplementation of germanium biotite was an effective means for improving growth performance and for decreasing Total-and LDL+VLDL-plasma cholesterols, backfat and fecal ammonia gas concentration.

Lipopolysaccharide-induced Synthesis of IL-1beta, IL-6, TNF-alpha and TGF-beta by Peripheral Blood Mononuclear Cells (내독소에 의한 말초혈액 단핵구의 IL-1beta, IL-6, TNF-alpha와 TGF-beta 생성에 관한 연구)

  • Jung, Sung-Hwan;Park, Choon-Sik;Kim, Mi-Ho;Kim, Eun-Young;Chang, Hun-Soo;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yang-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.846-860
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    • 1998
  • Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

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Radioimmunoassay Reagent Survey and Evaluation (검사별 radioimmunoassay시약 조사 및 비교실험)

  • Kim, Ji-Na;An, Jae-seok;Jeon, Young-woo;Yoon, Sang-hyuk;Kim, Yoon-cheol
    • The Korean Journal of Nuclear Medicine Technology
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    • v.25 no.1
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    • pp.34-40
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    • 2021
  • Purpose If a new test is introduced or reagents are changed in the laboratory of a medical institution, the characteristics of the test should be analyzed according to the procedure and the assessment of reagents should be made. However, several necessary conditions must be met to perform all required comparative evaluations, first enough samples should be prepared for each test, and secondly, various reagents applicable to the comparative evaluations must be supplied. Even if enough comparative evaluations have been done, there is a limit to the fact that the data variation for the new reagent represents the overall patient data variation, The fact puts a burden on the laboratory to the change the reagent. Due to these various difficulties, reagent changes in the laboratory are limited. In order to introduce a competitive bid, the institute conducted a full investigation of Radioimmunoassay(RIA) reagents for each test and established the range of reagents available in the laboratory through comparative evaluations. We wanted to share this process. Materials and Methods There are 20 items of tests conducted in our laboratory except for consignment tests. For each test, RIA reagents that can be used were fully investigated with the reference to external quality control report. and the manuals for each reagent were obtained. Each reagent was checked for the manual to check the test method, Incubation time, sample volume needed for the test. After that, the primary selection was made according to whether it was available in this laboratory. The primary selected reagents were supplied with 2kits based on 100tests, and the data correlation test, sensitivity measurement, recovery rate measurement, and dilution test were conducted. The secondary selection was performed according to the results of the comparative evaluation. The reagents that passed the primary and secondary selections were submitted to the competitive bidding list. In the case of reagent is designated as a singular, we submitted a explanatory statement with the data obtained during the primary and secondary selection processes. Results Excluded from the primary selection was the case where TAT was expected to be delayed at the moment, and it was impossible to apply to our equipment due to the large volume of reagents used during the test. In the primary selection, there were five items which only one reagent was available.(squamous cell carcinoma Ag(SCC Ag), β-human chorionic gonadotropin(β-HCG), vitamin B12, folate, free testosterone), two reagents were available(CA19-9, CA125, CA72-4, ferritin, thyroglobulin antibody(TG Ab), microsomal antibody(Mic Ab), thyroid stimulating hormone-receptor-antibody(TSH-R-Ab), calcitonin), three reagents were available (triiodothyronine(T3), Tree T3, Free T4, TSH, intact parathyroid hormone(intact PTH)) and four reagents were available are carcinoembryonic antigen(CEA), TG. In the secondary selection, there were eight items which only one reagent was available.(ferritin, TG, CA19-9, SCC, β-HCG, vitaminB12, folate, free testosterone), two reagents were available(TG Ab, Mic Ab, TSH-R-Ab, CA125, CA72-4, intact PTH, calcitonin), three reagents were available(T3, Tree T3, Free T4, TSH, CEA). Reasons excluded from the secondary selection were the lack of reagent supply for comparative evaluations, the problems with data reproducibility, and the inability to accept data variations. The most problematic part of comparative evaluations was sample collection. It didn't matter if the number of samples requested was large and the capacity needed for the test was small. It was difficult to collect various concentration samples in the case of a small number of tests(100 cases per month or less), and it was difficult to conduct a recovery rate test in the case of a relatively large volume of samples required for a single test(more than 100 uL). In addition, the lack of dilution solution or standard zero material for sensitivity measurement or dilution tests was one of the problems. Conclusion Comparative evaluation for changing test reagents require appropriate preparation time to collect diverse and sufficient samples. In addition, setting the total sample volume and reagent volume range required for comparative evaluations, depending on the sample volume and reagent volume required for one test, will reduce the burden of sample collection and planning for each comparative evaluation.

Assessment of Bone Metastasis using Nuclear Medicine Imaging in Breast Cancer : Comparison between PET/CT and Bone Scan (유방암 환자에서 골전이에 대한 핵의학적 평가)

  • Cho, Dae-Hyoun;Ahn, Byeong-Cheol;Kang, Sung-Min;Seo, Ji-Hyoung;Bae, Jin-Ho;Lee, Sang-Woo;Jeong, Jin-Hyang;Yoo, Jeong-Soo;Park, Ho-Young;Lee, Jae-Tae
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.1
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    • pp.30-41
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    • 2007
  • Purpose: Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with $^{18}F-2-deoxyglucose$ (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. Materials and Methods: The study group comprised 157 women patients (range: $28{\sim}78$ years old, $mean{\pm}SD=49.5{\pm}8.5$) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Results: Six patients(4.4%) showed metastatic bone lesions. Four(66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients(100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion($4.79{\pm}3.32$ vs $1.45{\pm}0.44$, p=0.000, $3.08{\pm}2.85$ vs $0.30{\pm}0.43$, p=0.000). Among 108 osseous metastatic lesions, 76 lesions showed as abnormal uptake on bone scan, and 76 lesions also showed as increased FDG uptake on PET/CT scan. There was good agreement between FDG uptake and abnormal bone scan finding (Kendall tau-b : 0.689, p=0.000). Lesion showed increased bone tracer uptake had higher SUVmax and SUVrel compared to lesion showed no abnormal bone scan finding ($6.03{\pm}3.12$ vs $1.09{\pm}1.49$, p=0.000, $4.76{\pm}3.31$ vs $1.29{\pm}0.92$, p=0.000). The order of frequency of osseous metastatic site was vertebra, pelvis, rib, skull, sternum, scapula, femur, clavicle, and humerus. Metastatic lesion on skull had highest SUVmax and metastatic lesion on rib had highest SUVrel. Osteosclerotic metastatic lesion had lowest SUVmax and SUVrel. Conclusion: These results suggest that FDG-PET/CT is more sensitive to detect breast cancer patients with osseous metastasis. CT scan must be reviewed cautiously skeleton with bone window, because osteosclerotic metastatic lesion did not showed abnormal FDG accumulation frequently.

Matrix Metalloproteinase in Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증환자의 기관지폐포세척액 및 폐포대식세포 배양액의 Matrix metalloproteinase의 변화)

  • Park, Joo-Hun;Shim, Tae-Sun;Lim, Chae-Man;Koh, Youn-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.4
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    • pp.303-314
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    • 2001
  • Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

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Correlation of p53 Protein Overexpression, Gene Mutation with Prognosis in Resected Non-Small Cell Lung Cancer(NSCLC) Patients (비소세포폐암에서 p53유전자의 구조적 이상 및 단백질 발현이 예후에 미치는 영향)

  • Lee, Y.H.;Shin, D.H.;Kim, J.H.;Lim, H.Y.;Chung, K.Y.;Yang, W.I.;Kim, S.K.;Chang, J.;Roh, J.K.;Kim, S.K.;Lee, W.Y.;Kim, B.S.;Kim, B.S.
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.4
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    • pp.339-353
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    • 1994
  • Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

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