• Journal of Hospice and Palliative Care
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• 제1권1호
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• pp.47-55
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• 1998

Background : It is almost important therapy modality to control pain for the terminal cancer patients for the last 24 hours because those terminally illed patient deserved to have pain free and peaceful time before death. Physician who is deal with terminal cancer patients for their last 24 hours does not need to worry about drug addiction or other untoward side reactions of pain medications. The purpose of this study was to evaluate if terminally illed cancer patient was given pain medication properly and sufficiently and if there was any different behavior to control pain of terminal cancer patients between medical physicians and surgeons in terms of type, amount and administration route and frequency. Methods : A retrospective chart audit of analgesic type, amount and administration route was performed on the medical recorders of 160 hospitalized terminal cancer patients who had died in the Korea University Medical Center Anam Hospital during the period of July 1, 1994 to June 30, 1995. Patients were classified into 103 patients were cared for by medical physicians and 57 patients were cared for by surgeons. After then, we analysed the difference of pain control pattern between them. Different types and amount of analgesics were converted to a common standard, an oral morphine equivalents(OME) relative to 1mg of oral morphine. Results : 1) The total number of patients was 160, male 102 cases(63.8%), and the female was 58 cases(36.2%) respectively. 2) The mean age was 56.4(${\pm}14.62$) years old and mean admission period was 27.8 days(${\pm}34.85$). 3) The frequent cancer site was stomach 42 cases(26.315), lung and liver 29 cases(18.1%) each, pancreas 10 cases(6.2%) in order 4) 125 out of 160 subjects (78.13%) complained pain, and 66 out of 103(64.08%) and 31 out of 57(54.39%) were treated with analgesics to relieve pain. 50 out of 97(51.55%) were able to continue on oral medication. 5) 86 cases(53.75%) were well oriented 24 hours prior to death. 6) The frequent analgesics for regular basis were long acting form of oral morphine 34 cases(Medical phsicians 24, Surgeons 10), intravenous morphine 26 cases(Medical physicians 20, Surgeons 6) in order, and the most common p.r.n.(pro re nata) analgesics used was intravenous morphine. 7) The mean amount of analgesics on regular basis was 115.41 OME by medical physicians and 52.7 OME by surseons(P<0.05). The mean amount of p.r.n. analgesics was significantly larger in patients are for by surgeons(66.64 OME) than medical physicians 23.49 OME(P<0.01). 8) The mean frequency of administrated number of p.r.n. analgesics was 0.62 times/day on medical part and 1.88 times/day on surgical part (P<0.001). Conclusion : Of the 97 patients with advanced cancer, 51.55% were able to take oral medications in the last day of life. The parenteral analgesics were more frequently used in the patients cared for by surgeons than medical physicians. Over the half of terminal cancer patients were well oriented in the last day of life. Doctor's knowledge and attitude towards pain is very important to mange the pain, effectively.

• Tuberculosis and Respiratory Diseases
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• 제44권1호
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• pp.124-135
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• 1997

Background : Diffuse panbronchiolitis(DPB) is a disease characterized clinically by chronic cough, expectoration and dyspnea; and histologically by chronic inflammation localized mainly in the region of the respiratory bronchiole. It is prevalent in Japanese, but is known to be rare in Americans and Europians. Only a few cases in Chinese, Italians, North Americans and Koreans have been reported. It is diagnosed by characteristic clinical, radiological and pathologic features. High-resolution CT(HRCT) is known to be valuable in the study of the disease process and response to therapy in DPB. To our knowledge, there has been no correlation of its appearance on HRCT with the severity of the disease process, and radioaerosol scan(RAS) of the lung has not previously been used for the diagnosis of DPB. Method : During recent two years we have found 12 cases of DPB in Kangnam St. Mary's Hospital, Catholic University Medical College. We analysed the clinical characteristics, compared HRCT classifications with clinical stages of DPB, and determined characteristic RAS manifestations of DPB. Results : 1. The ages ranged from 31 to 83 years old(mean 54.5 years old), and male female ratio was 4:8. 75%(9/12) of patients had paranasal sinusitis, and only one patient was a smoker. 2. The patients were assigned to one of three clinical stages of DPB on the basis of clinical findings, sputum bacterology and arterial blood gas analysis. of 12 cases, 5 were in the first stage, 4 were in the second stage, and 3 were in the third stage. In most of the patients, pulmonary function tests showed marked obstructive and slight restrictive impairments. Sputum culture yielded P.aeruginosa in 3 cases of our 12 cases, K.pneumoniae in 2 cases, H.influenzae in 2 cases, and S.aureus in 2 cases. 3. Of 12 patients, none had stage I characteristics as classified on HRCT scans, 4 had slage II findings, 5 had stage III findings, and 3 had stage IV characteristics. 4. We peformed RAS in 7 of 12 patients With DPB. In 71.4% (5/7) of the patients, RAS showed mottled aerosol deposits characteristically in the transitional and intermediary airways with peripheral airspace defects, which contrasted sharply with central aerosol deposition of COPD. 5. There were significant correlations between HRCT stages and clinical stages(r= 0.614, P < 0.05), between HRCT types and Pa02(r= -0.614, P < 0.05), and between HRCT types and ESR(r= 0.618, P < 0.01). Conclusion : The HRCT classifications correspond well to the clinical stage. Therfore in the examination of patients with DPB, HRCT is useful in the evaluation of both the location and severity of the lesions. Also, RAS apears to be a convenient, noninvasive and useful diagnostic method of DPB.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.871-888
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• 1997

Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.1094-1104
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• 1997

Background : Spontaneous pneumothoraces(SP) are divided into primary spontaneous pneumothoraces (PSP) which develop in healthy individuals without underlying pulmonary disorders and secondary spontaneous pneumothoraces(SSP) which occur in those who have underlying disorders such as tuberculosis or chronic obstructive lung diseases. Yet there is no established standard therapeutic approach to this disorder, i.e., from the spectrum of noninvasive treatment such as clinical observation with or without oxygen therapy, to aggressively invasive thoracoscopic bullectomy or open thoracotomy. Although chest tube thoracostomy has been most widely used, the patients should overcome pain in the initiation of tube insertion or during indwelling it potential infection and subcutaneous emphysema. Thus smaller-caliber tube has been challenged for the treatment of pneumothorax. Previously, we studied the therapeutic efficacy of 8 French catheter for spontaneous pneumothorax. But there has been few data for effectiveness of small-caliber catheterization in comparison with that of chest tube. In this study, we intended to observe the long-term effectiveness of 8 French catheter for the treatment of spontaneous pneumothoraces in comparison with that of chest tube thoracostomy. Method : From January, 1990 to January, 1996, sixty two patients with spontaneous pneumothoraces treated at Chung-Ang University Hospital were reviewed retrospectively. The patients were sub-divided into a group treated with 8 French catheter(n=23) and the other one with chest tube insertion(n=39). The clinical data were reviewed(age, sex, underlying pulmonary disorders, past history of pneumothorax, size of pneumothorax, follow-up period). And therapeutic effect of two groups was compared by treatment duration(duration of indwelling catheter or tube), treatment-associated complications and recurrence rate. Results : The follow-up period(median) of 8 French catheter group and chest tube group was 28 and 22 months, which had no statistical significance. Ther was no statistically significant difference of clinical characteristics between two groups with SP, PSP, SSP. The indwelling time of 8 French catheter group was $6.2{\pm}3.8$ days, which was significantly shorter than that of chest tube group in SP, $9.1{\pm}7.5$ days(p=0.047). In comparison of treatment-related complication in PSP, 8 French catheter group as 6.25% of complication showed lower tendency than the other group as 23.8% (p=0.041 ; one-tailed, p=0.053; two-tailed). The recurrence rate in each group of SP was 17.4%, 10.3%, which did not show any statistically significant difference. Conclusion : Treatment with 8 French catheter resulted in shorter indwelling time in sponteous pneumothorax, and lower incidence of treatment-related complication in primary spontaneous pneumothorax. And the recurrence rate in each of treatment group showed no statistically significant difference. So, we can recommend the 8 French small-caliber catheter for the initial therapy for spontaneous pneumothorax for the replacement of conventional chest tube thoracostomy. But further prospective study with more subjects of spontaneous pneumothorax will be needed for the evaluation of effectiveness of 8 French cateter.

• Tuberculosis and Respiratory Diseases
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• 제43권4호
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• pp.558-570
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• 1996

Background : The detection of Collapsible airways has important therapeutic implications in chronic airway disease and bronchial asthma. The distinction of a purely collapsible airways disease from that of asthma is important because the treatment of the dormer may include the use of pursed lip breathing or nasal positive pressure ventilation whereas in the latter, pharmacologic approaches are used. One form of irreversible airflow limitation is collapsible airways, which has been shown to be a Component of asthma or to emphysema, it can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmography. Method : To investigate whether volume difference between slow and forced vital Capacity(SVC-FVC) by spirometry may be used as a surrogate index of airway collapse, we examined pulmonary function parameters before and after bronchodilator agent inhalation by spirometry and body plethysmography in 20 cases of patients with evidence of airflow limitation(chronic obstructive pulmonary disease 12 cases, stable bronchial asthma 7 cases, combined chronic obstructive pulmonary disease with asthma 1 case) and 20 cases of normal subjects without evidence of airflow limitation referred to the Pusan National University Hospital pulmonary function laboratory from January 1995 to July 1995 prospectively. Results : 1) Average and standard deviation of age, height, weight of patients with airflow limitation was $58.3{\pm}7.24$(yr), $166{\pm}8.0$(cm), $59.0{\pm}9.9$(kg) and those of normal subjects was $56.3{\pm}12.47$(yr), $165.9{\pm}6.9$(cm), $64.4{\pm}10.4$(kg), respectively. The differences of physical characteristics of both group were not significant statistically and male to female ratio was 14:6 in both groups. 2) The difference between slow vital capacity and forced vital capacity was $395{\pm}317ml$ in patients group and $154{\pm}176ml$ in normal group and there was statistically significance between two groups(p<0.05). Sensitivity and specificity were most higher when the cut-off value was 208ml. 3) After bronchodilator inhalation, reversible airway obstructions were shown in 16 cases of patients group, 7 cases of control group(p<0.05) by spirometry or body plethysmography d the differences of slow vital capacity and forced vital capacity in bronchodilator response group and nonresponse group were $300.4{\pm}306ml$, $144.7{\pm}180ml$ and this difference was statistically significant. 4) The difference between slow vital capacity and forced vital capacity before bronchodilator inhalation was correlated with airway resistance before bronchodilator(r=0.307 p=0.05), and the difference between slow vital capacity and forced vital capacity after bronchodilator was correlated with difference between slow vital capacity and forced vital capacity(r=0.559 p=0.0002), thoracic gas volume(r=0.488 p=0.002) before bronchodilator and airway resistance(r=0.583 p=0.0001), thoracic gas volume(r=0.375 p=0.0170) after bronchodilator, respectively. 5) The difference between slow vital capacity and forced vital capacity in smokers and nonsmokers was $257.5{\pm}303ml$, $277.5{\pm}276ml$, respectively and this difference did not reach statistical significance(p>0.05). Conclusion : The difference between slow vital capacity and forced vital capacity by spirometry may be useful for the detection of collapsible airway and may help decision making of therapeutic plans.

• Tuberculosis and Respiratory Diseases
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• 제61권4호
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• pp.330-338
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• 2006

Background: The main factors associated with weight loss in patients with COPD are not well known. Since chronic inflammation and oxidative stress play a major pathogenic role in COPD, these factors may be responsible for the patients' weight loss. Therefore, this study measured the body mass index (BMI) in COPD patients and evaluated the variables, such as systemic inflammatory marker, oxidative stress and lung function, that correlate with the BMI. Method: The stable COPD patients (M:F=49:4, mean age=$68.25{\pm}6.32$) were divided into the lower (<18.5), normal (18.5-25) and higher (>25) BMI group. The severity of the airway obstruction was evaluated by measuring the $FEV_1$. The serum IL-6 and TNF-$\alpha$ levels were measured to determine the degree of systemic inflammation, and the carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ level was measured to determine the level of oxidative stress. Each value in the COPD patients and normal control was compared with the BMI. Results: 1) Serum 8-iso-prostaglandin $F_2{\alpha}$ in COPD patients was significantly higher ($456.08{\pm}574.12pg/ml$) than that in normal control ($264.74{\pm}143.15pg/ml$) (p<0.05). However, there were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein between the COPD patients and normal controls. 2). In the COPD patients, the $FEV_1$ of the lower BMI group was significantly lower ($0.93{\pm}0.25L$) than that of the normal BMI ($1.34{\pm}0.52L$) and higher BMI groups ($1.72{\pm}0.41L$) (p<0.05). The lower $FEV_1$ was significantly associated with a lower BMI in COPD patients (p=0.002, r=0.42). The BMI of very severe COPD patients was significantly lower ($19.8{\pm}2.57$) than that of the patients with moderate COPD ($22.6{\pm}3.14$) (p<0.05). 3). There were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ according to the BMI in the COPD patients. Conclusion: The severity of the airway obstruction, not the systemic inflammatory markers and oxidative stress, might be associated with the BMI in stable COPD patients. Further study will be needed to determine the factors associated with the decrease in the BMI of COPD patients.

• The Korean Journal of Nuclear Medicine Technology
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• 제14권2호
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• pp.122-127
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• 2010

Purpose: The Xpress3.$cardiac^{TM}$ which is a kind of wide beam reconstruction (WBR) method developed by UltraSPECT (Haifa, Israel) enables the acquisition of at quarter time while maintaining image quality. The purpose of this study is to investigate the usefulness of WBR method for decreasing scan times and to compare to it with filtered back projection (FBP), which is the method routinely used. Materials and Methods: Phantom and clinical studies were performed. The anthropomorphic torso phantom was made on an equality with counts from patient's body. The Tl-201 concentrations in the compartments were 74 kBq (2 ${\mu}Ci$)/cc in myocardium, 11.1 kBq (0.3 ${\mu}Ci$)/cc in soft tissue, and 2.59 kBq (0.07 ${\mu}Ci$)/cc in lung. The non-gated Tl-201 myocardial perfusion SPECT data were acquired with the phantom. The former study was scanned for 50 seconds per frame with FBP method, and the latter study was acquired for 13 seconds per frame with WBR method. Using the Xeleris ver. 2.0551, full width at half maximum (FWHM) and average image contrast were compared. In clinical studies, we analyzed the 30 patients who were examined by Tl-201 gated myocardial perfusion SPECT in department of nuclear medicine at Asan Medical Center from January to April 2010. The patients were imaged at full time (50 second per frame) with FBP algorithm and again quarter-time (13 second per frame) with the WBR algorithm. Using the 4D MSPECT (4DM), Quantitative Perfusion SPECT (QPS), and Quantitative Gated SPECT (QGS) software, the summed stress score (SSS), summed rest score (SRS), summed difference score, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were analyzed for their correlations and statistical comparison by paired t-test. Results: As a result of the phantom study, the WBR method improved FWHM more than about 30% compared with FBP method (WBR data 5.47 mm, FBP data 7.07 mm). And the WBR method's average image contrast was also higher than FBP method's. However, in result of quantitative indices, SSS, SDS, SRS, EDV, ESV, EF, there were statistically significant differences from WBR and FBP(p<0.01). In the correlation of SSS, SDS, SRS, there were significant differences for WBR and FBP (0.18, 0.34, 0.08). But EDV, ESV, EF showed good correlation with WBR and FBP (0.88, 0.89, 0.71). Conclusion: From phantom study results, we confirmed that the WBR method reduces an acquisition time while improving an image quality compared with FBP method. However, we should consider significant differences in quantitative indices. And it needs to take an evaluation test to apply clinical study to find a cause of differences out between phantom and clinical results.

• Journal of Chest Surgery
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• 제32권5호
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• pp.448-455
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• 1999

Background: Recent developments in techniques of video-assisted thoracic surgery(VATS) and endoscopic equipment has expanded the application of video-assisted surgical procedures in the field of thoracic surgery. Especially, it will probably become the treatment of choice of spontaneous pneumothorax(SP). There is, however, a high recurrence rate, high cost, and paucity of long-term results. We report the results of postoperative follow-up and analyze perioperative parameters affected to recurrence, retrospectively. Material and Method: From march 1992 to march 1997, 276 patients with spontaneous pneumothorax underwent 292 VATS procedures. Conversion to open thoracotomy was necessitated in eight patients, and this patients excluded from the study. Result: The sex distribution was 249 males and 31 females. The mean age was 28.1 12.2 years(range, 15 to 69 years). Primary SP was 237cases(83.5%) and secondary SP was 47cases(16.5%). The major underlying lung diseases associated with secondary SP were tuberculosis 27cases(57.4%) and emphysema 8cases (38.3%). Operative indications included Ipsilateral recurrence 123(43.9%), persistent air-leak 53(18.9%), x-ray visible bleb 40(14.3%), tension 30(10.7%), contralateral recurrence 21(7.5%), uncomplicated first episode 8(2.9%), bilateral 3(1.1%), complicated episode 2(0.7%). Blebs were visualized in 247cases(87%) and 244cases(85.9%) performed stapled blebectomy. Early postoperative complications occurred in 33 cases(11.6%): 16 prolonged air-leak more than 5 days(four of them were required a second operation and found missed blebs); 5 bleeding; 5 empyema; 2 atelectasis; 1 wound infection. No deaths occured. The mean operative time was 52.8 23.1 minutes(range, 20 to 165 minutes). The mean d ration of chest tube drainage was 5.0 4.5 days(range, 2 to 37 days). The mean duration ofhospital stay was 8.2 5.5 days (range, 3 to 43days). At a mean follow-up 22.3 18.4 months(range, 1 to 65 months), 12 patients(4.2%) were lost to follow-up. There were 24 recurrences and seven patients underwent second operation and 6 patients(85.7%) were found the missed blebs. 12 perioperative parameters(age, sex, site, underlying disease, extent of collapse, operative indication, size of bleb, number of bleb, location of bleb, bleb management, pleural procedure, prolonged postoperative air-leak) were analyzed statistically to identify significant predictors of recurrence. The significant predictors of recurrence was the underlying disease[17.0%(8/47): 6.8%(16/237), p=0.038], prolonged postoperative air-leakage[37.5%(6/16): 6.7%(18/268), p=0.001], and pleural procedure [11.4%(19/167): 4.3%(5/117), p=0.034]. Blebectomy has less recurrence rate then non-blebectomy [8.2%(20/244) : 10.0%(4/40), p>0. 5]. However, this difference was not statistically significant(p=0.758). Conclusion: We conclude that it is important that we shoud careful finding of bleb during VATS due to reducing of recurrnece, and cases of no bleb identified and secondary spontaneous pneumothorax were indicated of pleurodectomy. VATS is a valid alternative to open procedure for the treatment of spontaneous pneumothorax with less pain, shorter hospital stay, more rapid return to work, high patient acceptance, less scar and exellent cosmetics. But, there is high recurrence rate and high cost, and than it is necessary to evaluate of long-term results for recurrence and to observate carefully during VATS.

• The Korean Journal of Nuclear Medicine
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• 제35권3호
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• The Korean Journal of Nuclear Medicine
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• 제37권6호
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.