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.

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.

생체분해성 고분자를 이용한 사시수술용 제형개발 및 효용성에 대한 연구

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

A new device, muscle clamping system was developed to facilitate exact quatifying technique A strabismus surgery, and reduce the risk of complications. The device is composed of a lower fixing body with three jaws and an upper supporting body. They are used to clip an extraocular muscle and fix it to the sclera with a single bite. Superior rectus recession on 16 rabbit eyes were performed with this new device. Conjunctival injection, muscle adhesion strength, and light microscopic findings were examined at 1, 2, 4 and 8 weeks postoperatively. The Conjunctival injection were minimal, adhesion power ranged from 420 to 600 gram gravity, which is sufficient in withstand the normal pull of human extraocular muscle. In microscopic exam, some Inflammatory cells and fibrosis were found. The new device was technically easy, fast, and accurate, so it may be useful in stabismus surgery.

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.

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.

견관절 재발성 탈구에서 관절경적 견관절 전방 고정술의 결과 : 2년에서 6년간의 추시 관찰 Two to Six-Year Follow-up

김승호,하권익,노규철,류병담,오일빈 대한스포츠의학회 2003 대한스포츠의학회지 Vol.21 No.1

The purposes of this study were to prospectively evaluate the surgical otucome of the arthroscopic repair of the capsulolabral lesion using suture anchors in al large series of patients who were followed-up for mid-term periods. We evaluated 167 patients with traumatic recurrent anterior shoulder instability after an arthroscopic Bankart repair using suture anchors and nonabsorbable sutures. The mean age at the time of the operation was 25 years (15~46 years). There were 149 male and 18 female patients. Preoperatively and at the time of follow-up(mean, 44 months; range, 24~75 months), three objective outcome measurement tools(Rowe Score, University of California at Los Angeles Shoulder rating scale, and American Shoulder and Elbow Surgeons score) and two subjective measurements(pain and function visual analogue scale) sere assessed. The recurrence rate, range-of-motion, and risk factor for postoperative recurrence were evaluated. All shoulder scores improved after surgery(t-test, p<0.05). According to the Rowe scale, One hundred and thirty patients(78%) showed excellent, 29(17%) good, 6(4%) fair, and 2(2%) poor scored. Overall, postoperative recurrence of the instability was 4%(1 dislocation, 2 subluxation, and 4 positive anterior apprehensions). Postoperative recurrence was related with the glenoid defect of greater than 30%(Gehan's test, p<0.0001). In patients with postoperative instability, the recurrent episode was less frequent and shoulder function was related with the activity were increased after the surgery(t-test, p<0.001). One hundred and fifty-two patients(91%) returned to more than 90%of previous activities. The mean loss of external rotation was 2.0±4.0℃. In contrast to the previous reports on the results of the arthroscopic repair, arthroscopic capsulolabral repair using suture anchors provided satisfactory outcomes in terms of the recurrence, activity, and range of motion.

단계적 온도 하강법을 이용한 췌도세포 냉동보존법

정인경,오승훈,김병준,양태영,이병완,하창영,노정현,정재훈,민용기,이명식,이문규,김광원 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.26 No.1

연구배경:최근 당뇨병의 새로운 치료법으로 시도되고 있는 췌도이식은 충분한 췌도수의 확보와 췌도생존율을 높이기 위한 면역억제제 사용이 제한점이 되고 있다. 본 연구의 목적은 이식 전 충분한 췌도 수의 확보를 위해 분리한 췌도를 냉동보존하는 방법을 확립하고 냉동보존한 백서 췌도세포의 시험관내 그리고 생체내 기능을 조사하였다. 방법:분리한 백서의 췌장소도를 48시간 배양한 후 한 시험관당 췌도세포 1000개씩 나누었다. 냉동보존은 6개의 시험관에 DMSO를 첨가한 후 초 냉각(supercooling), 핵화(nucleation)단계를 거친 후 99% isopropanol과 액체질소가 들어있는 dewer를 이용하여-0.25℃/분의 냉각속도로 -40℃까지 단계적으로 얼린후-70℃ 액체질소 탱크에 보관했다. 해동은 냉동시킨 vial들을 액체 질소 태으에서 꺼내 37℃ 항온조에 담가 급격히 해동시킨 후, 원심분리하여 상층액을 제거하고 각 vial에 0.75M sucrose 용액을 가한 후, 10% fetal calf serum이 함유된 RPMI 1640 media에서 배양하였다 각각 6개의 시험관에서 해동한 췌도들을 광학현미경 및 형광현미경하에서 췌도의 모양과 생존율에 대해 조사하고 인슐린 정적반응을 알아보았다. 또한 분리한 췌도를 냉동보존하지 않고 이식한 경우를 대조군(6마리)과 생체내 기능을 비교하였다. 결과:① 냉동보존후 획득한 췌도의 수와 생존율 해동후 획득한 췌도의 수는 해동시킨 당일날이 902±21, 24시간 배양 후에는 857±16, 72시간 후에는 817±18개로 점차 감소되었다. AO/PI 염색상 각 췌도의 생존율은 냉동 전을 100으로 하였을 때 해동당일, 24시간 후, 72시간 후가 각각 60±5, 80±5, 90±5%로 해동후 3일간 배양하였을 때 냉동전의 수준으로 회복하였다. ② 냉동보존후 췌도의 포도당에 대한 정적 인슐린 분비능:냉동직후 감소된 경향을 보였으나 해동후 3일간 배양한 췌도의 인슐린 분비는 냉동전과 통계적으로 의미있는 차이가 없이 냉동보존 전의 수준으로 회복되었다. ③ 냉동보존후 췌도의 포도당에 대한 동적 인슐린 분비능:냉동보존한 췌도를 해동후 3일째의 인슐린 동적 분비능은 냉동 전과 마찬가지로 자극 인슐린의 반응의 제1기와 2기가 잘 관찰되었다. ④ 냉동보존한 췌도세포 이식 후 혈당 변화:스트렙토조토신으로 유도된 당뇨병 쥐에 췌도이식 후 혈당은 냉동보존한 췌도이식군에서 대조군에 비해 혈당의 조절효과가 더 오래 지속되었다. 결론:소동물에서 단계적 온도 하강법을 이용한 췌도세포 냉동보존법을 확립하였으며 이는 기능, 구조 및 생존율에 큰 이상을 보이지 않았으므로 장차 사람의 췌도세포 동종이식시 부족한 췌도세포수를 극복하고 면역반응을 줄일 수 있는 매우 유용한 방법이 될 것으로 판단된다. Background : Although islet transplantation has been attempted to reverse the state of diabetes, achieving a critical number of islets and modulating the immune response limit the success of islet transplantation. Cryo-preservation of islets offers many important benefits for islet transplantation by collecting islets with a wide variety of HLA phenotypes and islet MHC expression. The aims of this study was to determine the optimal conditions for cryo-preservation by using a controlled cooling method and to evaluate in vitro and in vivo functional properties of the cryo-preserved islets. Methods : Collagenase-isolated, Ficoll-purified islets were cultured for 48 hours. They were aliquoted into freezing tubes (1000 islets per tube), equilibrated with 2M dimethyl sulfoxide (DMSO) in three steps, supercooled, nucleated, and controll-cooled at rate of 0.25℃/min to - 40℃ prior to storage at - 196℃. Rapid thawing and removal of DMSO with 0.75 M sucrose preceded 48 hour of culture and the morphology, viability, glucose-induced insulin secretion, and in vivo function of rats transplanted with cryopreserved islets was reexamined. Results : ① Recovery was 90.2±0.2%, 85.7±0.1% and 81.7±0.1% immendiately after, 24 hours and 72 hours after thawing respectively. The viability was 60±5%, 80±5%, 90±5% immediately after, 24 hours and 72 hours after thawing respectively. ② The glucose-stimulated-insulin secretion (GSIS) tended to decrease immediately after thawing, but GSIS increase to the level of pre-cryopreservation 72 hours after thawing. ③ The in dynamic GSIS, the first and the second phase of insulin secretion were well preserved in islets cultured for 72 hours after thawing. ④ The cryopreserved islets were cultured for 3 days and transplanted into renal sub-capsular space of streptozotocin (STZ) induced diabetic rats. The duration of normoglycemia in the STZ-induced diabetic rats transplanted with cryopreserved islets was significantly longer than of the fresh islets. Conclusion : The optimal condition of cryopreservation using the controlled cooling method was established in rat pancreatic islets. This cryopreservation method can be a feasible approach for human islet transplantation (J Kor Diabetes Asso 26:64~74, 2002).

위암 환자의 복강내 투여를 위한 Activated Charcoal-Alginate Bead 제형으로부터 Mitomycin C의 용출 거동

이진호,최선웅,서중기,김동민,정경수,오정연,김진향,노승무,민병무,김용백,김창식,박근성,강대영,송규상,양준묵,조준식,정현용,김학용,인현빈 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 chemotherapy seems a logical choice for cancer chemotherapy. In this study, Mitomycin C (MMC)-activated charcoal (CH)-alginate (ALG) beads were prepared by the mixtures of CH particles adsorbed with MMC as an anti-cancer drug and aqueous alginate solution. The alginate is recognized as biodegradable, nontoxic, and biocompatible. The release of MMC from the beads in 0.1 M Tris buffer was stable and continuous until about 1 week. The MMC-CH-ALG beads can be applied in the peritoneal cavity for intraperitoneal chemotherapy since they provide a good adhesiveness on the tissue and controlled release pattern of the drugs.