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.

Rat의 복강에 삽입한 Filorouracil-Polyglycolic acid제형의 Fluorouracil용출에 관한 연구

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

A common form of relapse in adenocarcinoma of the stomach is intraperitioneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adenocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.

위암환자의 복강내에 투여한 Mitomycin C-Carbon Particle의 Mitomycin 용출에 관한 연구

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

Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherpy seems a logical choice for cancer chemotherapy. The Mitomycin C(MMC) adsorbed by the activated charcoal particles(CH) is relatively released when the drug concentration surrounding the carbon particles becomes low in the peritoneum of the peritoneal cavity. For the intraperitoneal chemotherapy on the advanced gastric adenocarcnoma, mitomycin C adsorbed on activated carbon particles was administered in the peritoneal cavity just before abdominal wall closure. The closed drainage tubes were inserted in the peritoneal cavity and clamped for tuo hours after completion of operation. MMC concentrations were serially measured in peritoneal fluid, plasma and urine at 2hour, 48 hour, 72 hour and 168 hour following its administration in order to study the efficacy of the MMC-CH as a drug delivery system. There were minimal toxicities in born marrow, liver, and gastrointestinal system after intraperitoneal MMC-CH administration. The data of this study suggested that MMC-CH may have a somewhat more beneficial effect than surgery alone when administered in optimal dose and schedules, but the MMC concentration of the peritoneal fluid was not sufficient to eradicate remnant cancer cells, and effective duration of maintenance was only below 24 hours in the peritoneal fluid and plasma.

Rat의 복강에 삽입한 Fluorouracil-Polyglycolic acid 제형의 Fluorouracil 용출에 관한 연구

노승무,정경수,오정연,김진향,양준묵,강대영,송규상,최정목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 忠南大學校 癌共同硏究所 1998 癌共同硏究所 硏究誌 Vol.2 No.1

A common form of relapse in adenocarcinoma of the stomach is intraperitoneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adcnocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.

위전절제시 단순공장간치술의 임상적 의의

노승무,배진선,정현용,이병석,조준식,신경숙,송규상,이태용 충남대학교 암연구소 2003 암연구소 업적집 Vol.3 No.-

Purpose: The aim of this study was to evaluate the short-term outcome of a jejunal interposition, by comparing it with a conventional Roux-en-Y gastrojejunostomy, after a total gastrectomy. Materials and Methods: For 28 patients (20 men and 8 women) with a gastric adenocarcinoma, who underwent an isoperistaltic simple jejunal interposition, weight, hemoglobin, hematocrit, serum protein and albumin, and cholesterol levels were checked before the operation and at 1 year and 2 years after the surgery. Also, endoscopy was performed to confirm reflux esophagitis. In this study, the data were collected between January 1993 and July 1999 at Chungnam National University Hospital, and the results were compared with those of the Roux-en-Y procedure. Results: The body weights at 1 year and 2 years after the surgery had returned to 86.0% and 87.6% of the recent original body weight in the jejunal interposition (Jl) group and to 90.8%, 87.0%, respectively in the Roux-en-Y (RY) group. The levels of hemoglobin (g/dl) were 13.3, 12.5, and 11.9 in the Jl group, and 13.8, 12.6, and 12.1 in the RY group at the time of the operation and at 1 year, and 2 years after the surgery, respectively. The total serum protein (g/dl) levels were 7.1, 7.2, and 7.5 in the Jl group and 7.1, 7.0, and 7.2 in the RY gropu at the time of the operation and at 1 year and 2 years after the surgery, respectively. The serum albumin (g/dl) levels were 4.2, 4.1, and 4.2 in the Jl group and 4.2, 4.2, and 4.2 in the RY group at the time of the operation and at 1 year, and 2 years after the surgery, respectively. The total serum cholesterol (mg/dl) levels were 186.5, 174, and 164 in the Jl group and 213.7, 171.1, and 141.0 in the RY group at the time of the operation and at 1 year and 2 years after the surgery, respectively. The endoscopic finding showed that reflux esophagitis occurred in 7.1% of the patients in the Jl group and in 3.5% in the RY group. Conclusion: We think that from the view point of quality of life, a jejunal interposition, as well as a Roux-en-Y procedure, is a useful reconstruction methods for a total gastrectomy. (J Korean Gastric Cancer Assoc 2001;1:210-214)

위전절제시 단순공장간치술의 임상적 의의

노승무,배진선,정현용,이병석,조준식,신경숙,송규상,이태용 충남대학교 암공동연구소 2003 암공동연구소 업적집 Vol.3 No.

Purpose: The aim of this study was to evaluate the short-term outcome of a jejunal interposition, by comparing it with a conventional Roux-en-Y gastrojejunostomy, after a total gastrectomy. Materials and Methods: For 28 patients (20 men and 8 women) with a gastric adenocarcinoma, who underwent an isoperistaltic simple jejunal interposition, weight, hemoglobin, hematocrit, serum protein and albumin, and cholesterol levels were checked before the operation and at 1 year and 2 years after the surgery. Also, endoscopy was performed to confirm reflux esophagitis. In this study, the data were collected between January 1993 and July 1999 at Chungnam National University Hospital, and the results were compared with those of the Roux-en-Y procedure. Results: The body weights at 1 year and 2 years after the surgery had returned to 86.0% and 87.6% of the recent original body weight in the jejunal interposition (Jl) group and to 90.8%, 87.0%, respectively in the Roux-en-Y (RY) group. The levels of hemoglobin (g/dl) were 13.3, 12.5, and 11.9 in the Jl group, and 13.8, 12.6, and 12.1 in the RY group at the time of the operation and at 1 year, and 2 years after the surgery, respectively. The total serum protein (g/dl) levels were 7.1, 7.2, and 7.5 in the Jl group and 7.1, 7.0, and 7.2 in the RY gropu at the time of the operation and at 1 year and 2 years after the surgery, respectively. The serum albumin (g/dl) levels were 4.2, 4.1, and 4.2 in the Jl group and 4.2, 4.2, and 4.2 in the RY group at the time of the operation and at 1 year, and 2 years after the surgery, respectively. The total serum cholesterol (mg/dl) levels were 186.5, 174, and 164 in the Jl group and 213.7, 171.1, and 141.0 in the RY group at the time of the operation and at 1 year and 2 years after the surgery, respectively. The endoscopic finding showed that reflux esophagitis occurred in 7.1% of the patients in the Jl group and in 3.5% in the RY group. Conclusion: We think that from the view point of quality of life, a jejunal interposition, as well as a Roux-en-Y procedure, is a useful reconstruction methods for a total gastrectomy. (J Korean Gastric Cancer Assoc 2001;1:210-214)

복막유착의 원인 규명과 예방을 위한 실험적 연구

강대영,송규상,노승무,조준식,이태용 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Postoperative peritoneal adhesion is the most common cause of intestinal obstruction, and intestinal obstruction is one of the most difficult problems in abdominal surgery. In this experimental study for developing peritoneal adhesion model and its prevention, we divided rats into 5 groups; the talc powder treated group, the cotton-fluff treated group, the talc+fluff treated group, the ischemia group and the control group. There were 16 rats in each group. We made incisions on the midabdomen of the rats and administered talc powder, cotton fluff and talc powder+fluff into the peritoneal cavity respectively. In the ischemia group, we clamped the root of superior mesenteric artery for two minutes to induce ischemia on the small bowel of the rat. We counted the number of the peritoneal adhesive sites in peritoneal cavity on the 7th, 14th , 21st and 42nd postoperative day after peritoneal adhesion induced operation, and observed the characters of the adhesion state. The average number of the peritoneal adhesions were 1.25 per one rat in the talc powder group, 1.44 in the fluff group, 1.31 in the talc+fluff group and 1.31 in the ischemia group compared with 0.94 per one rat in the control group performed sham operation. 91.6% of the all adhesions were observed on the peritoneum of the previous incision sites and only 8.4% of the adhesions were adhered to the peritoneal surface of non-incision sites. The data of this study suggest that peritoneal injury and inflammatory reaction is the major cause of peritoneal adhesion. Also this study indicates that foreign bodies can develop peritoneal adhesion, but the effect is much lower than that of peritoneal injury with inflammatoty reaction.

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.

오존 발생기용 전원장치 개발 및 특성에 관한 연구

김동희,이달해,성현직,오승훈,이봉섭,배상준 嶺南大學校 工業技術硏究所 1997 工業技術硏究所論文集 Vol.25 No.1

The power semiconductor switching devices(PSSD) continuously developed, Power Electronic Technology using PSSD is gradually extended. The high frequency inverter to generate the large power high frequency subject to power electronic technology pursuit various application. Also, in emboss with environmental destruction problem cause the atmosphere and the water pollution to growth of the commercial society, the research in favor of cleansing environmental a pollutant actively proceed. Cause of having a strong oxygenization in the physical world, the ozone has sterillization effect predominantly against virus, bacteria, etc and has application in decolorization, deodorization, food storage and air cleansing and has a merit that does not cause the secondary pollution by being restored to oxygen lastly. Therefore, This project describe study on the ozone generation power supply using the high frequency electric field method and the lamp type ozone generator using photochemistry, one of method of generate ozone.

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.