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물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가
김정철,윤정한,범희승,제갈영종,송호천,민정준,정환정,김성민,허영준,이명호,박영규,정준기 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2
목적 : 분화갑상선암 환자에 대한 방사성옥소(I-131) 치료는 재발율과 사망률을 감소시키는 효과적인 치료법이지만, 치료용량을 증가시킴으로써 치료율을 향상시킬 수 있는지에 대해서는 아직 논란이 있다. 본 연구에서는 최대허용선량 치료법의 효용성을 검증하고자 하였다. 대상 및 방법 : 임상적 병기가 제3, 4병기이고, 6개월 이후에 I-131 전신스캔(이하 IWBS)과 혈중 thyroglobulin (이하 Tg), anti-thyroglobulin antibody (이하 ATA), 초음파검사 (이하 US) 및 F-18 FDG PET 등을 통해 치료여부를 확인할 수 있었던 58명(남:여=9:49, 평균연령 50±11세)의 유두상갑상선암 환자를 대상으로 하였다. 이중 11명은 제4병기, 47명은 제3병기였으며, 43명(남:여=4:39), 평균연령 50±11세)은 7.4 GBq 이하의 고식적인 저용량치료법으로 치료하였고, 9.25 GBq 이상의 고용량 치료를 받은 환자는 15명(남:여=5:10, 평균연령 50±12세)으로 고용량군에서 남자가 더 많았으나 연령의 차이는 없었다. 고용량군 환자 모두에서 추적용량의 방사성옥소(평균 77±3 MBq)를 경구 투여한 후 혈중 방사능소실곡선을 통해 최대허용선량(maximum permissible dose, 이하 MPD)을 계산하였으며, 7명에서는 말초혈액림프구의 중기염색체분석법에 의해 생물학적으로 MPD를 계산하였다. 14명에서는 치료용량의 방사성옥소를 투여한 후 혈중 방사능소실곡선을 통해 MPD를 계사하였다. 완전치유(complete response, 이하 CR)는 IWBS에서 병소가 없어지고, 혈중 Tg치가 1 ng/mL 이하로 감소한 경우로 정의하였으며, 부분치유(partial response, 이하 PR)는 IWBS에서 병소가 없어졌더라도 혈중 Tg, ATA치가 높거나, US 또는 PET 검사에서 병소가 남아있는 경우로 정의하였다. 치료후 IWBS에서 병소가 오히려 증가하거나 변함없는 경우는 없었다. 방사성옥소 치료에 의한 부작용은 입원기간 중 타액선이 현저하게 붓고 통증이 있거나, 구토를 심하게 하는 경우, 그리고 퇴원후 1개월째 백혈구수가 20% 이상 감소한 경우로 정의하였다. 결과 : 양 군간에 연속적인 수치변화를 비교하는 경우는 paired t-test를 이용하였으며, 대상군간 치료효과와 부작용의 비교는 chi-square test를 이용하였다. p값 0.05 미만을 통계적으로 유의한 차이로 인정하였다. 고용량군 환자 모두에서 추적용량과 치료용량의 방사성옥소 투여 후 혈액의 피폭선량은 각각 0.012±0.3 Gy, 1.66±25 Gy였으며, 방사성옥소 투여 후 혈액에 전달되는 피폭선량은 추적용량보다 치료용량에서 더 많았고 (1.21: 166 rad, p<0.001), 방사성옥소 1 mCi당 혈액에 전달되는 피폭선량은 차이가 없었다(0.58±0.1 vs. 0.56±0.1 rad/37 MBq, p=0.34). 추적용량 방사성옥소 투여 후 구한 MPD는 평균 13.3±1.9 GBq (9.7 ~ 16 GBq) 이였고, 치료용량 방사성옥소 투여 후 구한 MPD는 평균 13.8±2.1 GBq (10.4 ~ 16.3 GBq)로 유의한 차이가 없었으며 (p=0.20), 두 수치간에는 유의한 상관 관계가 있었다(r=0.8, p<0.0001). 7명의 환자에서 말초혈액림프구 중기염색체 분석법으로 MPD를 측정하였는데 혈액의 피폭선량은 1.78±0.03 G였으며, 같은 환자에서 혈중 방사능소실곡선으로부터 구한 피폭선량은 1.54±0.03 G로 유의하게 낮았으나 (p=0.01), 두 측정치 간에는 유의한 상관관계(r=0.86, p=0.01)가 있었다. 저용량 치료군 43명 중 22명(51.2%)에서 완전치유를 보였고 21명(48.8%)에서는 부분치유를 보인 반면 고용량 치료군 15명 중 12명(80%)에서 완전치유를 보였고 3명(20%)에서만 부분치유를 보여 고용량 치료군에서 유의하게 높은 완전치유를 얻을 수 있었다(p=0.05). 한편 부작용 발생빈도는 저용량 치료군 43명 중 13(30.2%), 고용량 치료군 15명 중 6명(40%)로 양군간에 유의한 차이가 없었다(p=0.46). 임상적인 병기, 연령 및 성별에 따라서는 치유의 차이가 없었다(p>0.05). 결론 : 혈중소실곡선으로부터 MPD를 결정하고 이를 토대로 환자 개개인별로 적절한 선량을 선택하여 치료하는 방법은 부작용을 최소화하면서도 치료효과를 높일 수 있는 매우 유용한 치료법이며, 고위험군 분화갑상선 암 환자에게 가장 적절한 치료법이라고 사료되었다. Purpose: Radioiodine (1-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up 1-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-does group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose 1-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.
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백혈병 세포에서 Multidrug Resistance Gene-1 (mdr1)의 과발현이 ^99m Tc-sestaMIBI 섭취에 미치는 영향
천경아,이재태,이상우,강도영,손상균,이종기,정준기,전수한,이규보 경북대학교 의학연구소 2000 경북대학교병원의학연구소논문집 Vol.4 No.1
Purpose: To determine whether 99mTc-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively 99mTc-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular 99mTc-MIBI uptake were also investigated in the presence of multidrug resistance gene-1(mdr1 gene) overexpression. Materisls and Methods: We measured percentage uptake of 99mTc-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of 99mTc-MIBI were also evaluated with or withouts overexpression of mdr1 gene in Cultured murine leukemia L1210 cells. Results: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of 99mTc-MIBI was higher in mdr1 negative L 1210 cells than those of mdr1 positive cells, and higher when incubated in 37℃ than 4℃. In the presence of verapamil, cyclosporin or dipyridamole, 99mTc-MIBI uptake was increased upto 604% in mdr1 positive cells. Conclusion: Cellular uptake of 99mTc-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest that 99mTc-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro. (Korean J Nucl Med 1999;33: 152-62)
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Development of the Korean Developmental Screening Test for Infants and Children (K-DST)
Chung, Hee Jung,Yang, Donghwa,Kim, Gun-Ha,Kim, Sung Koo,Kim, Seoung Woo,Kim, Young Key,Kim, Young Ah,Kim, Joon Sik,Kim, Jin Kyung,Kim, Cheongtag,Sung, In-Kyung,Shin, Son Moon,Oh, Kyung Ja,Yoo, Hee-Jeo The Korean Pediatric Society 2020 Clinical and Experimental Pediatrics (CEP) Vol.63 No.11
Background: Most developmental screening tools in Korea are adopted from foreign tests. To ensure efficient screening of infants and children in Korea, a nationwide screening tool with high reliability and validity is needed. Purpose: This study aimed to independently develop, standardize, and validate the Korean Developmental Screening Test for Infants and Children (K-DST) for screening infants and children for neurodevelopmental disorders in Korea. Methods: The standardization and validation conducted in 2012-2014 of 3,284 subjects (4-71 months of age) resulted in the first edition of the K-DST. The restandardization and revalidation performed in 2015-2016 of 3.06 million attendees of the National Health Screening Program for Infants and Children resulted in the revised K-DST. We analyzed inter-item consistency and test-retest reliability for the reliability analysis. Regarding the validation of K-DST, we examined the construct validity, sensitivity and specificity, receiver operating characteristic curve analysis, and a criterion-related validity analysis. Results: We ultimately selected 8 questions in 6 developmental domains. For most age groups and each domain, internal consistency was 0.73-0.93 and test-retest reliability was 0.77-0.88. The revised K-DST had high discriminatory ability with a sensitivity of 0.833 and specificity of 0.979. The test supported construct validity by distinguishing between normal and neurodevelopmentally delayed groups. The language and cognition domain of the revised K-DST was highly correlated with the K-Bayley Scales of Infant Development-II's Mental Age Quotient (r=0.766, 0.739), while the gross and fine motor domains were highly correlated with Motor Age Quotient (r=0.695, 0.668), respectively. The Verbal Intelligence Quotient of Korean Wechsler Preschool and Primary Scales of Intelligence was highly correlated with the K-DST cognition and language domains (r=0.701, 0.770), as was the performance intelligence quotient with the fine motor domain (r=0.700). Conclusion: The K-DST is reliable and valid, suggesting its good potential as an effective screening tool for infants and children with neurodevelopmental disorders in Korea.
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위 십이지장질환 환자들의 위액내 Fungus 에 관한 연구
정정명(Jung Myung Chung),박주열(Joo Youl Park),문기석(Key Seack Moon),김병제(Byoung Je Kim),김동민(Dong Min Kim),최하진(Ha Jin Choi) 대한내과학회 1986 대한내과학회지 Vol.31 No.1
N/A It is widely known that with recent environmental changes and improved methods of diagnosis, infection of fungi in a number of human organ is steadily increasing. Despite a few reports made by scientists on the relationship between candida infection and gastroenteric diseases, the infection and growth of fungi in a stomach and gastric juices has been seldom reported. In cases of gastric and duodenal disease, however, enviornmental changes within a stomach such as changes of gastric juices, disturbances of gastric motility and impairment of gastric mucosa are likely to come about, it can, therefore, be assumed that the growth of various fungi in a stomach and gastric juices is possible. Recently we have investigated the fungal infection in gastric juices aspirated from various gastroduodenal disease patients and obtained following results. 1) 40 patients have vague epigastric pain complaints for a long duration, although no definite pathological findings are endoscopically recognizable in stomach and duodenum, 16 duodenal ulcer patients, 30 gastric ulcer patients and 30 stomach cancer patients were studied on fungal growth in their salivas and gastric juices aspirated from their mouth and stomach. 2) pH of gastric juices from 21 patients in whom fungus was grown in their stomach aspirates was 4.85±1.45, whereas pH of gastric juices from another 21 patients in whom no fungus was grown was 1.91±0.61. A rather striking difference in their acidity between those 2 groups is recognizable, as already reported previously, 3) The frequency of fungal growth in gastric juices was found in following order. 32.5% of cases of non-ulcer, non-cancer patients, 18.8% of cases of duodenal ulcer patients, 73.3% of cases of gastric ulcer patients, and 83.3% of cases of stomach cancer patients. Among those patients who have fungal growth in their gastric juice, candida was found. 25.0% of cases of non-ulcer, non-cancer patients 6.3% of cases of duodenal ulcer patients, 60.0% of cases of gastric ulcer patients, and 70.0% of cases of stomach cancer patients. It was revealed that the frequency was rather higher in gastric ulcer and stomach cancer patients than in duodenal ulcer and non-ulcer, non-cancer patients. 4) Ten non-ulcer, non-cancer patients who had fungal growth in their gastric aspirates were, 6 cases of acute gastroenteritis, 2 cases of cirrhosis, 1 case of Parkinson's disease, and 1 case of renal stone.
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한기준(Key Joon Han),강진경(Jin Kyung Kang),송시영(Si Young Song),정재복(Jae Bock Chung),박인서(In Suh Park),이우정(Woo Jung Lee),김병로(Byong Ro Kim) 대한소화기학회 1995 대한소화기학회지 Vol.27 No.6
N/A Background/Aims: The early gastric cancer has been defined as that in which the depth of invasion is limited to the submucosa regardless of the lymph node(LN) metastasis. However, in the carcinoma of extrahepatic bile duct, the definition of early cancer may be different, because of the differences of histologic features such as lacking of muscularis mucosa and submucosal layer. Recently, Mizumoto et al. Proposed the definition of extrahepatic bile duct cancer, in which invasion limited to mucosa and fibromuscular layer, however there have been no data in Korea. The purpose of this study is to clarify the concept of early carcinoma of extrahepatic bile duct in Korea. Methods: We evaluated the 60 cases underwent radical operation due to extrahepatic bile duct carcinoma at Severance Hospital, Yonsei University from January l980 to December 1993. Results: The invasion limited to the mucosa(Tla) was noted in 2 cases(3.3%), fibromuscular layer(Tlb) in 11 cases(18.4%), adventitia of fibromuscular layer and serosa(T2) in 22 cases(36.77c) and invasion of adjacent organ(T3) in 25 cases(41.6%). The LN metastasis was found in 16 cases(26.7%). No LN metastasis was noted in Tl, however in T2 the LN metastasis was found in 27.3%(all Nl) and 40.0%(N1: 4 cases, N2: 6 cases) in T3. All cases of Tl but one who recurred at 16 months after surgery survived without recurrence. Disease-free survival according to the T stages were: in Tl, 100%, 90.9%, 90.9% at l, 3, and 5 year, respectively; in T2, 80%, 56% and 37%, respectively; in T3, 83%, 58%, 58%, respectively. The survival rate of Tl was significantly higher than that of T2 and T3(p=0.03). The mean survival in patients of T2 without LN metastasis was 50.5 months, which was longer than that of 38.7 months in cases of T2 with LN metastasis. Multivariate analysis revealed that the depth of invasion was the only significant prognostic factor. The polypoid type and papillary adenocarcinoma were frequently encountered in early cancer comparing advanced cancer. Conclusions: Early cancer of the extrahepatic bile duct could be defined as the tumor invaion restricted to the mucosa and fibromuscular layer. (Korean J Gastroenterol 1995;27:690 - 699)
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