• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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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.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.530-541
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• 2002

Background : Pleural fluid adenosine deaminase (ADA) activity can be helpful in a differntial diagnosis of an exudative pleural effusion because it is increased in a tuberculous pleural effusion. The ADA activity is determined mainly by the lymphocyte function. Age-associated immune decline is characterized by a decrease in T-lymphocyte function. For that reason, the pleural fluid ADA level would be lower in older patients with exudative pleural effusion. This study focused on the influence of age on the pleural fluid ADA activity in patients with exudative pleural effusion. Methods : A total of 81 patients with exudative pleural effusion were enrolled in this study. In all patients, the pleural fluid ADA activity was measured using an automated kinetic method. Results : The mean age of the patients was $52.7{\pm}21.2$ years. In all patients with exudative pleural effusion, the pleural fluid ADA activity revealed a significant difference between young patients (under 65 years of age) and old patients (p<0.05), and showed a negative correlation with age (r=-0.325, p<0.05). In the 60 patients with a tuberculous pleural effusion, the pleural fluid ADA activity revealed a significant difference between the young and older patients : $103.5{\pm}36.9$ IU/L in young patients Vs. $72.2{\pm}31.6$ IU/L in old patients (p<0.05), and showed a negative correlation with age (r=-0.384, p<0.05). In the 21 patients with non-tuberculous exudative pleural effusion, the pleural fluid ADA activity of the young patients and old patients was similar : $23.7{\pm}15.3$ IU/L in young patients Vs. $16.1{\pm}10.2$ IU/L in old patients (p>0.05), and did not show any correlation with age (r=-0.263, p>0.05). The diagnostic cutoff value of pleural fluid ADA activity for tuberculous pleural effusion was lower in the older patients (25.9 IU/L) than in the younger patients (49.1 IU/L) or all patients (38.4 IU/L) with exudative pleural effusion. Conclusion : Tuberculous pleural effusion is an important possibility to consider in older patients with a clinical suspicion of a tuberculous pleural effusion, although no marked increase in the pleural fluid ADA activity is usually detected. For a diagnosis of a tuberculous pleural effusion in old patients, the cutoff for the pleural fluid ADA activity should be set lower.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Journal of Chest Surgery
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• v.39 no.1 s.258
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• pp.1-11
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• 2006

Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.43-48
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• 2014

Purpose: In the PET/CT images, The SUV (standardized uptake value) enables the quantitative assessment according to the biological changes of organs as the index of distinction whether lesion is malignant or not. Therefore, It is too important to enter parameters correctly that affect to the SUV. The purpose of this study is to evaluate an allowable error range of SUV as measuring the difference of results according to input errors of Activity, Weight, uptake Time among the parameters. Materials and Methods: Three inserts, Hot, Teflon and Air, were situated in the 1994 NEMA Phantom. Phantom was filled with 27.3 MBq/mL of 18F-FDG. The ratio of hotspot area activity to background area activity was regulated as 4:1. After scanning, Image was re-reconstructed after incurring input errors in Activity, Weight, uptake Time parameters as ${\pm}5%$, 10%, 15%, 30%, 50% from original data. ROIs (region of interests) were set one in the each insert areas and four in the background areas. $SUV_{mean}$ and percentage differences were calculated and compared in each areas. Results: $SUV_{mean}$ of Hot. Teflon, Air and BKG (Background) areas of original images were 4.5, 0.02. 0.1 and 1.0. The min and max value of $SUV_{mean}$ according to change of Activity error were 3.0 and 9.0 in Hot, 0.01 and 0.04 in Teflon, 0.1 and 0.3 in Air, 0.6 and 2.0 in BKG areas. And percentage differences were equally from -33% to 100%. In case of Weight error showed $SUV_{mean}$ as 2.2 and 6.7 in Hot, 0.01 and 0.03 in Tefron, 0.09 and 0.28 in Air, 0.5 and 1.5 in BKG areas. And percentage differences were equally from -50% to 50% except Teflon area's percentage deference that was from -50% to 52%. In case of uptake Time error showed $SUV_{mean}$ as 3.8 and 5.3 in Hot, 0.01 and 0.02 in Teflon, 0.1 and 0.2 in Air, 0.8 and 1.2 in BKG areas. And percentage differences were equally from 17% to -14% in Hot and BKG areas. Teflon area's percentage difference was from -50% to 52% and Air area's one was from -12% to 20%. Conclusion: As shown in the results, It was applied within ${\pm}5%$ of Activity and Weight errors if the allowable error range was configured within 5%. So, The calibration of dose calibrator and weighing machine has to conduct within ${\pm}5%$ error range because they can affect to Activity and Weight rates. In case of Time error, it showed separate error ranges according to the type of inserts. It showed within 5% error when Hot and BKG areas error were within ${\pm}15%$. So we have to consider each time errors if we use more than two clocks included scanner's one during the examinations.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.232-240
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• 1997

Background : Postprimary pulmonary tuberculosis is located mainly in upper lobes. The tuberculous lesion involving the lower lobes usually arises from the upper lobe cavity through endobronchial spread. When tuberculosis is confined to the lower lung field, it often masquerades as pneumonia, lung cancer, bronchiectasis, or lung abscess. Thus the correct diagnosis may be sometimes delayed for a long time. Methods : We carried out, retrospectively, a clinical study on 50 patients confirmed with lower lung field tuberculosis who visited the Department of Pulmonary Medicine at Hanyang University Hospital from January 1992 to December 1994. The following results were obtained. Results : Lower lung field tuberculosis without concomitant upper lobe disease occurred in fifty patients representing 6.9% of the total admission with active pulmonary tuberculosis over a period of 3 years. It occurred most frequently in the third decade but age distribution was relatively even. The mean age was 43 years old. Female was more frequently affected than male (male to female ratio 1 : 1.9). The most common symptom was cough(68%), followed by sputum(52%), fever(38%), and chest discomfort(30%). On chest X-ray of the 50patients, consolidation was the most common finding in 52%, followed by solitary nodule(22%) collapse(16%), cavitary lesion(10%), in decreasing order. The disease confined to the right side in 25 cases, left side 20 cases, and both sides 5 cases. Endobronchial tuberculosis (1) Endobronchial involvement was proved by bronchoscopic examination in 20 of 50patients. (2) Mean age was 44years old and female was more affected than man (male to female ratio 1 : 3). Sputum AFB stain and Mycobacterium tuberculosis culture were positive only in 50% of cases unlikely upper lobe tuberculosis, additional diagnostic methods were needed. In our study, bronchoscopic examination and percutaneous fine needle aspiration biopsy increased diagnostic yield by 18% and 32%, respectively. The most common associated condition was diabetes mellitus(18%) and others were anemia, anorexia nervosa, stomach cancer, and systemic steroid usage. Conclusion : When we find a lower lung field lesion, we should suspect tuberculosis if the patient has diabetes mellitus, anemia, systemic steroid usage, malignancy or other immune suppressed states. Because diagnostic yield of sputum AFB smear & Mycobacterium tuberculosis culture was low, additional diagnostic methods such as bronchoscopy and fine needle aspiration biopsy were needed.

• Journal of Ginseng Research
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• v.26 no.3
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• pp.111-131
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• 2002

Korean ginseng (Panax ginseng C.A. Meyer) received a great deal of attention from the Orient and West as a tonic agent, health food and/or alternative herbal therapeutic agent. However, controversy with respect to scientific evidence on pharmacological effects especially, evaluation of clinical efficacy and the methodological approach still remains to be solved. Author reviewed those articles published since 1980 when pharmacodynamic studies on ginseng have intensively started. Special concern was paid on metabolic disorders including diabetes mellitus, circulatory disorders, malignant tumor, sexual dysfunction, and physical and mental performance to give clear information to those who are interested in pharmacological study of ginseng and to promote its clinical use. With respect to chronic diseases such as diabetes mellitus, atherosclerosis, high blood pressure, malignant disorders, and sexual disorders, it seems that ginseng plays preventive and restorative role rather than therapeutics. Particularly, ginseng plays a significant role in ameliorating subjective symptoms and preventing quality of life from deteriorating by long term exposure of chemical therapeutic agents. Also it seems that the potency of ginseng is mild, therefore it could be more effective when used concomitantly with conventional therapy. Clinical studies on the tonic effect of ginseng on work performance demonstrated that physical and mental dysfunction induced by various stresses are improved by increasing adaptability of physical condition. However, the results obtained from clinical studies cannot be mentioned in the indication, which are variable upon the scientist who performed those studies. In this respect, standardized ginseng product and providing planning of the systematic clinical research in double-blind randomized controlled trials are needed to assess the real efficacy for proposing ginseng indication. Pharmacological mode of action of ginseng has not yet been fully elucidated. Pharmacodynamic and pharmacokinetic researches reveal that the role of ginseng not seem to be confined to a given single organ. It has been known that ginseng plays a beneficial role in such general organs as central nervous, endocrine, metabolic, immune systems, which means ginseng improves general physical and mental conditons. Such multivalent effect of ginseng can be attributed to the main active component of ginseng,ginsenosides or non-saponin compounds which are also recently suggested to be another active ingredients. As is generally the similar case with other herbal medicines, effects of ginseng cannot be attributed as a given single compound or group of components. Diversified ingredients play synergistic or antagonistic role each other and act in harmonized manner. A few cases of adverse effect in clinical uses are reported, however, it is not observed when standardized ginseng products are used and recommended dose was administered. Unfavorable interaction with other drugs has also been suggested, which the information on the products and administered dosage are not available. However, efficacy, safety, interaction or contraindication with other medicines has to be more intensively investigated in order to promote clinical application of ginseng. For example, daily recommended doses per day are not agreement as 1-2g in the West and 3-6 g in the Orient. Duration of administration also seems variable according to the purpose. Two to three months are generally recommended to feel the benefit but time- and dose-dependent effects of ginseng still need to be solved from now on. Furthermore, the effect of ginsenosides transformed by the intestinal microflora, and differential effect associated with ginsenosides content and its composition also should be clinically evaluated in the future. In conclusion, the more wide-spread use of ginseng as a herbal medicine or nutraceutical supplement warrants the more rigorous investigations to assess its effacy and safety. In addition, a careful quality control of ginseng preparations should be done to ensure an acceptable standardization of commercial products.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1981.05a
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• pp.7-8
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• 1981

Authors observed clinically 34 cases of the corrosive esophagitis caused by various corrosive agents at Kyung Hee University Hospital from Aug. 1978 to Dec. 1980. The results obtained were as follows; 1. Among the 34 patients, male was 19 (55.9%) and female 15(44.1%). Most frequently found age was 3rd decade. 2. 18 cases(52.9%) came to the hospital within 24 hours after ingestion of the agents, and 13 cases(38.2%) within 2 to 7 days. 3. Seasonal distribution showed most frequently in spring(35.3%). 4. The moment of the accident was suicidal attempt in 27 cases(79.4%) and misdrinking in 7 cases(20.6%). 5. Acetic acid was a most commonly used agent, showing 23 cases(67.6%), lye and insecticides were next in order. 6. Common chief complaints were swallowing difficulty and sore throat. 7. The average hospital days was 14.8 days. 8. Esophagogram was performed between 3 to 7 days after ingestion in 13 cases(38.2 %), findings were constrictions on the 1st narrowing portion in 4 cases(30.8%) and within normal limits in 3 cases(23.1%). 9. Esophagoscopy was performed in 31 cases(91.2%) between 2 to 7 days after ingestion, which revealed edema and coating on entrance of the esophagus in 9 cases (29.0 %). Diffuse edema on entire length of the esophagus and within normal limits were next in order. 10. Laboratory results were as follows: Anemia was in 1 cases(2.9%), leukocytosis. in 21 cases (61.8%), increase ESR in 9 cases (26.5%), markedly increased BUN and creatinine in 3 cases (8.8%), and hypokalemia in 1 cases(2.9%). Proteinuria in 10 cases(29.4%) hematuria in 4 cases(l1.8%), and coca cola urine in 3 cases (8.8%). 11. Associated diseases were 3 cases(8.8%) of cancer, 1 cases (2.9%) of diabetes mellitus, and 1 cases(2.9%) of manic depressive illness. 12. Various treatment was given: Esophageal and gastric washing in 23 cases(67.6%) for the emergent treatment, antibiotics in 32 cases(94.1%), steroids in 30 cases(88.2%), bougienation in 5 cases(14.7%), hemodialysis in 1 case(2.9%), and partial esophagectomy with gastrostomy and gastroileal anastomosis in 1 cases(2.9%). 13. Serious complications were observed in 9 cases (26.5%), consisted of 6 cases(17.6%) of esophageal stricture, 1 cases(2.9%), of aute renal failure, 1 cases (2.9%) of pneu momediastinum with pneumonia, and 1 cases (2.9%) of pneumonia.

• The Korean Journal of Nuclear Medicine
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• v.38 no.6
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• pp.516-521
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• 2004

Background: Radioactive iodine (RAI) therapy and whole-body scanning are the fundamentals of treatment and follow-up of patients with differentiated thyroid cancer. It is generally accepted that a Thyroid-Stimulating Hormone (TSH) level of at least 30 ${\mu}U/ml$ is a prerequisite for the effective use of RAI, and that it requires 4-6 weeks of off-thyroxine to attain these levels. Because thyroxine withdrawal and the consequent hypothyroidism are often poorly tolerated, and occasionally might be hazardous, it is important to be certain that these assumptions are correct. We have measured serial changes in serum TSH after total thyroidectomy or withdrawl of thyroxine in patients with thyroid cancer. Subjects and Methods: Serum TSH levels were measured weekly after thyroidectomy in 10 patients (group A) and after the discontinuation of thyroxine in 12 patients (group B). Symptoms and signs of hypothyroidism were also evaluated weekly by modified Billewicz diagnostic index. Results: By the second week, 78% of group A patients and 17% of group B patients had serum TSH levels ${\geq}30{\mu}U/ml$. By the third week, 89% of group A patients and 90% of group B patients had serum TSH levels ${\geq}30{\mu}U/ml$. By the fourth week, all patients in two groups achieved target TSH levels and there were no overt hypothyroidism. Conclusion: in all patients, serum TSH elevated to the target concentration (${\geq}30{\mu}U/ml$) within 4 weeks without significant manifestation of hypothyroidism. The schedule of RAI administration could be adjusted to fit the needs and circumstances of individual patients with a shorter preparation period than the conventional.