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.

Negative Regulation of Hypoxic Responses via Induced Reptin Methylation

Jason S. Lee,김윤호,김익수,김보규,최희준,이지민,신희재,김정화,김지영,서상범,이호,Olivier Binda,Or Gozani,Gregg L. Semenza,김민형,김근일,황대희,백성희 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

불응성 자가면역질환에서의 자가조혈모세포이식

민도준,양동원,민창기,김완욱,이상헌,박성환,김동욱,이종욱,조철수,민우성,김범생,김호연,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 기존의 치료에 불응하고 예후가 불량한 자가면역질환 환자들에게 최근 고용량 면역억제 및 조혈모 세포이식이 새로운 치료방법으로 대두되고 있다. 저자들은 다발성 경화증(multiple sclerosis, MS) 및 류마티스 관절염(rheumatoid arthritis, RA) 등 2명의 자가면역질환 환자들에서 자가조혈모세포 이식을 시행하였다. 방법: 말초혈액 조혈모세포 가동화를 위하여 cyclophosphamide (4 g/㎡) 및 granulocyte colony stimulating factor (10 g/kg/day)를 투여하였고, CD34+ 세포를 분리·채집 하였다, 이식 전처치로 MS 환자에서 BEAM 및 antihymocyte globulin (ATG) (3.75 mg/kg), RA 환자에서 fludarabine (180 mg/㎡), ATG (10 mg/kg)와 busulfan (8 mg/kg)을 투여하였다. 결과: 호중구 수가 500/㎕ 이상으로 회복되는 기간은 MS 환자에서 9일, RA 환자에서 15일이었다. 혈소판이 20.000/㎕ 이상으로 회복되는 가간은 RA 환자에서 9일 이었고, MS 환자에서는 혈소판 감소증이 발생하지 않았다. 비혈액학적 독성으로 MS 환자에서 WHO 1도의 오심 및 점막염이 관찰되었다. MS 환자는 이식 6개월 후까지 시력감소가 남아있었으나, 이식전에 관찰되던 감각이상 및 운동장애 등의 신경학적 이상 소견은 더 이상 관찰되지 않았다. RA 환자는 이식 1개월 후 관절 증상 및 검사소견의 호전을 보였다. 결론: 불응성 자가면역질환 환자에서 고용량 면역억제 및 조혈모세포이식은 적은 독성으로 높은 치료효과를 기대할수 있으며, 향후 이 시술의 임상적 의의를 규명하기 위하여 전향적이고 장기적인 연구가 필요할 것으로 사료된다. Background: High-dose immunosuppressive therapy followed by autologous hemathpoietic stem cell transplantation (HSCT) has been proposed as a new approach to treat severe, refractory autoimmune diseases. We describe two patients with refractory autoimmune diseases (one multiple sclerosis 〔MS〕and one rheumatoid arthritis〔RA〕) who underwent T-cell-depleted autologous peripheral bleed stem cell transplantation for the first time in Korea. Methods: We mobilized autologous stem cells with cyclophisphamide (4 g/㎡) and granulocyte colony-stimulating factor (10 ㎍/kg/day). Stem cells were enriched ex vivo using CD34-positive immunoselection and reinfused after high-dose chemotherapy with BEAM and antithymocyte globulin (ATG) (3.75 mg/kg) in MS, or fludarabine (180 mg/㎡), ATG (10 mg/kg) and busulfan (8 mg/kg) in RA. Results: The engraftment with an absolute nerutrophil count greater than 500㎕ occurred on day 9 in MS and 15 in RA, respectively. The time to nontransfused platelet count greater than 2.000/㎕ was 9 day in RA. MS patient did not show ant episode of thrombocytopenia. Regimen-related non-hematopoietic toxicity was minimal. For 6 months since HSCT, them patient with MS had been free from previously existed sensory and motor abnormalities except decreased visual acuity. Then patient with RA and only one tender joint and two mildly swollen joints with improvement in laboratory parameters at one month after HSCT. Conclusion: These results underscore the feasibility and potential efficacy of intensive immunosuppression followed by autologous HSCT for treatment of intractable autoimmune diseases. The durability of remission, however, remains to be clarified.

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.

Negative Regulation of Hypoxic Responses via Induced Reptin Methylation

Jason S. Lee,김윤호,김익수,김보규,최희준,이지민,신희재,김정화,김지영,서상범,이호,Olivier Binda,Or Gozani,Gregg L. Semenza,김민형,김근일,황대희,백성희 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

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)

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.

T1b 병기의 신세포암에서 수술 후 예후를 예측할 수 있는 임상 및 병리학적 인자에 대한 연구

오승용, 김영원, 윤형윤, 서성필, 이상근, 김원태, 윤석중, 이상철, 김원재, 김용준 충북대학교 의과대학 충북대학교 의학연구소 2014 忠北醫大學術誌 Vol.24 No.1

연구목적: T1병기의 국소신세포암(localized clear-cell renal cell carcinoma)은 근치적신적출술이 나 부분신절제술이 표준치료이며 수술 후 타 병기에 비해 양호한 예후를 보인다. 하지만, 많은 수의 환 자에서 추적관찰 중 재발 및 사망이 발생하는데, 이는 T1b 병기에서 더 높게 보고되고 있다. 본 연구 에서는 국소신세포암 중 T1b 병기의 신세포암에서 표준적 치료 후 환자의 예후에 영향을 주는 임상 및 병리학적 인자에 대하여 알아보고자 하였다. 대상 및 방법: 1999년부터 2011년 까지 5개 기관에서 근치적신적출술이나 부분신제술을 시행 받은 3567명의 국소신세포암 환자들 중 병리학적 병기가 T1b로 확진 된 702명을 대상으로 하였다. 이들 환자가 가지는 임상 및 병리학적 특성 [연령, 성별, 고혈압, 당뇨, 비만도, European Cooperative Oncology Group(ECOG) 수행도, 증상유무, 수술방법, 종양크기, 분화도, 조직학적 형태 등]을 이용 하여 환자의 예후 [무재발생존율(relapse-free survival), 암특이생존율(cancer-specific survival) 및 전체생존율(overall survival)]에 영향을 미치는 인자에 대하여 다양한 방법으로 비교분석 하였다. 결과: 추적 관찰 기간은 34.0개월 (중앙값, 0-152개월)이었으며, 이 기간 중 재발, 사망 및 암특이사 망은 각각 72례 (10.3%), 57례 (8.1%) 및 24례 (3.4%)에서 발생하였다. 단변량 및 다변량 Cox 비례위험회귀분석에서 다양한 인자들이 무재발생존율(당뇨 유무, 종양크기 및 Fuhrman등급), 암특이 생존율(나이, 체질량지수, 당뇨 유무, 종양크기) 및 전체생존율(나이, 체질량지수, ECOG 수행도, 종 양크기)에 영향을 줄 수 있는 독립적 예후인자였다. 결론: 본 연구결과 국소신세포암의 예후를 예측할 수 있는 다양한 임상 및 병리학적 인자를 확인 할 수 있었다. 이러한 위험인자를 가지고 있는 환자는 보다 적극적인 추적관찰을 통하여 재발을 조기에 발 견한다면 이들의 생존율 향상에 많은 기여를 할 수 있을 것으로 생각한다.

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.