Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

백서의 복강내에 투여한 Mitomycin-C-Polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

송규상,강대영,최정목,노승무,정경수,오정연,김진향,양준목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

To evaluate the in-vivo effects of mitomycin-C-polyglycolic acid composite(MMC-PGA) the disk: shaped composite were implanted into the peritoneal cavity of the Sprague-Dawley rats. The pathologic changes were examined at various time points up to 12 weeks. Initially the soft tissue around the inserted disks showed capillary congestion at 3 days. Inflammatory infiltrates with foreign body giant cells appeared from the 2nd week and reached peak response at 6-8 weeks. These reaction diminished prominently at 12 weeks. No specific pathologic change was found in the liver, the kidneys, and the heart. The above results suggest that the MMC-PGA composite can serve as a new device for intraperitoneal chemotherapy of various types of cancers.

삼출성 늑막액에서 양악성 감별지표로서 CEA, TPA, SCC Ag 측정의 의의

김경찬,김민수,김미정,권두영,한승범,전영준 啓明大學校 醫科大學 1998 계명의대학술지 Vol.17 No.4

상피 세포에서 기원한 대표적인 종양표지자인 carcinoembryonic antigen (이하 CEA로 약함)은 삼출성 늑막액 환자의 양악성 감별에 보고적으로 사용되고 있다. CEA 이외에 혈청에서 양악성감별의 보조적 지표로 알려진 tissue polypeptide antigen (이하 TPA로 약함)과 squamous cell carcinoma antigen (이하 SCC Ag으로 약함)을 혈청과 늑막에서 동시 측정하여 늑막삼출액의 악성 감별에 어느 정도의 임상적인 유용성이 있는지를 알아보기 위하여 이 연구를 시행하였다. 1997년 1월 1일부터 동년 8월 31일까지 계명대학교 동산의료원에 입원한 환자들 중 삼출성늑막액을 가진 61명을 대상으로 하여 혈청과 늑막액에서 CEA, TPA, SCC Ag의 수치를 방사면역법으로 측정하였다. 각각의 조양표지자들은 악성과 양성군으로 구분한 뒤 분석하였으며 악성군이 28례, 양성군이 33례이었다. 그리고 진단양성기준치를 설정한 뒤 종양표지자들의 특이도, 민감도를 산출하였고 상기 지표들을 종양표지자와 늑막액 세포검사르 조합한 경우에도 산출하여 비교 분석하였다. 혈청 CEA 와 TPA는 각각 7.0 ng/ml, 80.0 ng/ml, 늑막액 CEA와 TPA는 각각 50. ng/ml, 4700.0 ng/ml로 진단양성기준치를 설정하였을 때 특이도를 낮추지 않으면서 가장 높은 민감도를 보였다. 늑막액 세포검사와 동시에 혈청 TPA 도는 늑막액 CEA를 측정하였을 때 특이도는 떨어뜨리지 않으면서 민감도를 높이는 좋은 조합인 것으로 나타났으며 혈청 CEA 및 TPA수치를 늑막액 세포검사와 도시에 시행하였을 때 특이도를 떨어뜨리지 않으면서 가장 높은 민감도를 얻었다. 늑막액 세포검사가 음성인 경우에도 혈청 CEA와 TPA를 동시에 측정하여 높은 민감도와 특이도를 얻을 수 있었다. 따라서 CEA와 TPA는 늑막삼출액의 양악성 감별 진단 유용한 보조적 지표로서 사용할 수 있을 것으로 판단된다. Carcinoembryonic antigen(CEA), the most widely used tumor marker was measured in pleural fluid of patients with exudative pleural effusions in order to differentiate malignant from benign effusions. This study was performed to find out if there is any clinical utility in differential diagnosis of malignancy by measuring simultaneously CEA, tissue polypeptide antigen(TPA) and squamous cell carcinoma antigen(SCC Ag) in serum and pleural fluid. The study population was 61 patients with exudative pleural effusions who were admitted to Keimyung University Hospital from January 1 to August 31, 1997. Each CEA, TPA and SCC Ag level in serum and pleural fluid were measured using radioimmunoassay method. These patients were divided to malignant and benign group. Malignant group consists of 28 cases and benign group consists of 33 cases. And the sensitivity and specificity of each tumor marker was obtained using cut-off value and that combining tumor markers and pleural fluid cytology were also obtained and analyzed. When the cut-off value was applied to CEA and TPA in serum using 7.0 ng/ml and 80.0 ng/ml respectively, the highest sensitivity was obtained without specificity being lowered. The same result was obtained when the cut-off value was applied to CEA and TPA in pleural fluid using 5.0 ng/ml and 4700.0 ng/ml respectively. When CEA in pleural fluid or TPA in serum were measured in combining with pleural fluid cytology sensitivity was increased without decreasing specificity than measured in pleural fluid cytology alone. When CEA in serum and TPA in serum were measured in combining with pleural fluid cytology simultaneously, the highest sensitivity was produced without decreasing specificity than measured in any other combinations. In addition, when serum CEA and TPA in serum were measured in the negative group of pleural fluid cytology, high sensitivity and specificity were obtained. These data suggest that CEA and TPA can be used as useful tumor markers for the differential diagnosis of malignancy and benign condition in patients with exudative pleural effusions.

간세포암과 감별이 어려웠던 악성중피종 치험 1예

김선문,허원석,채경훈,강윤세,정재훈,김연수,박기오,문희석,이엄석,김석현,성재규,이병석,이헌영,신경숙,조준식,송인상,강대영 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Malignant peritoneal mesothelioma is a rare neoplasm that arises from the mesothelium of a serosal cavity and is a rapidly fatal disease with a median survival of 4 to 12 months for untreated cases. Recently, we experienced a case with malignant peritoneal mesothelioma who was suspected hepatocelluar carcioma by abdominal CT scan and was confirmed by biopsy including immunohistochemical stain(calretinin) after surgery. We performed tumor excisions and wedge resection of the liver(segment Ⅷ)and inserted Tencoff catheter in abdominal cavity at 25th day of post-operation. We treated with intraperitoneal paclitaxel(25mg/m^(2)/day for 5 days) six courses monthly. She was well tolerable and is still living without any evidence of recurrence for 14th month of post-operation.

방사선 조사에 의한 흰주 난포의 퇴축과 난포세포의 방사선 감수성

김수일,한승로,조근자,허대영,이영호,조문준,김무강,김원식 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.1

The aim of this study were to investigate radiation-induced atresia and radiation susceptibility in the rat ovary morphologically. Female rats (Sprague Dawley strain) of 4 weeks old were irradiated with dose of 4 Gy and 8 Gy, and sacrificed at hour 6, 12, and 24 after radiation. The H & E stain, the TUNEL method (ApopTag kit) and transmission electron microscopy (TEM) were used. In light microscopic observation, the number of atresia of ovarian follicles were increased significantly at 6h after irradiation (p<0.01). There was no significant difference between 4 Gy and 8 Gy irradiated groups. In TEM observation, granulosa cells in radio-sensitive follicles were characterized by several structural features including condensation of nuclear chromatin granules, nuclear fragmentation and apoptotic body formation. An apoptotic cell is observed to have been phagocytosed by a normal granulosa cell. Granulosa cells in radio-resistant follicles were characterized by several structural features including nuclear indentation, partial condensation of chromatin granules, mitochondrial swelling, dilatation of RER cisterns, accumulation of dense irregular masses, accumulation of lipid droplets, and increased lysosomal bodies. Number of gap junctions between granulosa cells were decreased, and intercellular space were widen than that of control animals. These findings were prominent at 6h after irradiation and were diminished at 12h and 24h after irradiation. With these results, it was concluded that radiation-induced follicular cell apoptosis and ovarian follicular atresia in rat ovary increased considerably at 6h after irradiation. Further studies are needed to reveal the more extensive differences between radiosensitive and radioresistant follicular granulosa cells.

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.

생체분해성 망막압정을 이용한 망막고정에 대한 실험적 연구

김용백,민병무,김창식,박근성,김승영,길숙종,조항진,이성복,노승무,송규상,강대영,조준식,양준묵,정경수,최선웅,이진호,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Biodegradable retinal fixation devices obtain mechnical fixation of the retina with desirable chorioretinal scarring and with the potential for local, sustained release of antimetabolites and steroids to inhibit proliferative vitreoretinopathy. We manufactured a biodegradable retinal tack with barb that was designed in order to prevent intrusion from implantation of retinal tacks. This study was carried to evaluate the efficacy for retinal fixation and the capability for sustained release of drugs with a newly designed biodegradable retinal tack Biodegradable retinal tacks were made of polymers of glycolic acids and were designed with barbs in a shape to prevent the disinsertion. Biodegradale retinal tacks are divided into 3 parts, a conical portion that is inserted into the sclera, a cylinder portion that remains in the vitreous, and a neck portion between the pin and the cylinder. The tapered conical end was manufactured to allow easy insertion through the retina and choroid into the sclera. A cylinder portion was manufactured with a tapered angle that fixes firmly into the orifice of 19 gauge spinal needle. A neck portion, 0.4 mm in diameter, was designed to prevent disinsertion from following implantation of retinal tack. The applicator was a 19 gauge spinal needle and its orifice was prepared to 15°angle to accept the tapered cylinder portion of the retinal tack. The retinal tacks, secured in the needles, were passed through the formed vitreous and inserted into the retina, choroid, and sclera and were released by pushing the internal needle, usually within 2-3mm of the medullary ray of the posterior rabbit retina A retinal tack was placed in each of 8 pigmented rabbit eyes. Slit-lamp biomicroscopy, indirect ophthalmoscopy and fundus photography were performed periodically from 1 day to 8 weeks after surgery. Eight eyes were enucleated and studied by light microscopy at 8 weeks. Biomicroscopic evaluation of the animals revealed edemas adjacent to the retinal surfaces immediately after insertion of the biodegradable retinal tacks in all the animals. These edemas disappeared after 1 week. The first noticeable change in the size of retinal tacks was shown after 2weeks. The size of the retinal tacks gradually got smaller, decreasing to about one-half at 4 weeks and about one-third at 8 weeks. All retinal tacks remained in inserted places without any movement for an 8 week period. On light microscopy, epiretinal proliferations were seen to extend into the vitreous cavity. Cellular capsules that lined the inner aspect of the scleral defect caused by tack insertion were found. However the adjacent retina had a normal cytologic appearance and architecture in all specimens. We manufactured a biodegradable retinal tack that is designed to prevent intrusion from implantation of retinal tacks. All biodegradable retinal tacks reduce in size with time, but no retinal tacks extruded from the inserted place. The newly designed biodegradable retinal tack can be used for retinal fixation and may be used as a vehicle for the introduction of pharmacologic agents to prevent the cellular events that promote proliferative vitreoretinopathy.

청소년의 인터넷 중독 정도에 따른 정신과적 공존질환 및 행동 양상에 관한 연구

이준영(June-Young Lee),박이진(E-Jin Park),조근호(Keun-Ho Joe),채숙희(Suk-Hi Chai),김성벽(Sung-Byuk Kim),이창욱(Chang-Uk Lee),김대진(Dai-Jin Kim) 한국중독정신의학회 2010 중독정신의학 Vol.14 No.1

Objectives:This study aimed to clarify the differences in psychiatric comorbidities and, behavioral patterns correlating with the severity of Internet addiction in adolescents. Methods:We assessed 321 adolescents recruited from an Internet rescue school, psychiatric outpatients, and 4 schools in Seoul and Gyeonggido. We divided them into a non-addicted group, a potential-risk group, and a high-risk group according to Young’s Internet Addiction Test (IAT). We evaluated their psychiatric comorbidities and behavioral patterns via psychiatric clinical interview, the Children’s Depression Inventory (CDI), the State-Trait Anxiety Inventory (STAI), and a self-report questionnaire about behavioral pat-terns. Results:There were significant differences in CDI and STAI scores among the 3 groups. The IAT, CDI, and STAI scores correlated positively with each other. There were differences in psychiatric comorbidity distributions between the potential-risk and high-risk groups, but only “other mood disorder” showed a significant difference. There were also significant differences in behavioral patterns among the 3 groups. Conclusion:This study suggests that there are psychiatric comorbidity and behavioral pat-tern differences according to Internet addiction severity in adolescents. We expect further studies will reveal more profound understandings of these relationships.

곰팡이에서 분리한 Helicobacter pylori 항균물질의 분리 및 구조규명

남궁준,연승우,백남수,김태한,김영호,김창진,김기원 충남대학교 약학대학 의약품개발연구소 1998 藥學論文集 Vol.14 No.-

Helicobacter pylori is a Gram-negative bacterium which causes chronic gastritis and is associated with gastric ulcer, duodenal ulcer and gastric carcinoma. In the process of screening of antibacterial activities against H. pylori from soil microorgani는, fungus No. 60686 was isolated. After fementaion of No. 60686, the antibacterial compound was isolated, purified and followed by extraction of mycelium with orgainic solvents, acetone and ethyl acetate, through silica gel chromatography, LH-20 gel chromatography and HPLC. As a result of the structural analyses of the compound by IR, ^1H- and ^13C-NMR, FAB/Mass spectrophotomer, the compound having the antimicrobial activity was idenfitied as chaetoglobosin A (C_32H_36N_2O_5), a cytochalasan derivative. The antimicrobial activity of chaetoglobosin A was tested against Gram-positive and negative bacteria by paper disk method. Among the test strains of 9 Gram-positive bacteria and 18 Gram-negative bacteria containing 4 H. pylori strains, the growth of 4 H. pylori strains and 3 S. aureus strains (SG 511, 285 and 503) was only inhibited by chaetoglobosin A. Also it was shown that its growth inhibition against H. pylori strains was stronger than that against S. aureus strains at the treatment of the same concentration. Therefore it was concluded that chaetoglobosin A has a specific growth inhibition against H. pylori of the tested bacteria.

급성 췌장염의 합병이 추정되는 한국형 출혈열 1예

박영수,김창오,김영근,홍성관,장경희,허애정,염준섭,송영구,김준명 대한감염학회 2001 감염 Vol.33 No.5

The Korean hemorrhagic fever (KHF) is an acute febrile disease with characteristic of fever, bleeding tendency, and renal failure. There are many complications of Korean hemorrhagic fever such as infection, anemia, internal bleeding, hypopituitarism, respiratory, and neurologic complication. A few cases were reported on acute pancreatitis with hemorrhagic fever abroad, but there was no case about Korean hemorrhagic fever with acute pancreatitis in this country. We experienced a case of Korean hemorrhagic fever associated with suspected acute pancreatits. With review of articles, we report a case of 51 year-old woman with KHF, where acute pancreatitis developed during management, (Korean J Infect Dis 33:376∼379, 2001)