각종 난치성 혈액 질환에서의 비혈연간 골수이식

김동욱,한훈,김정아,김희제,민창기,엄현석,최정현,이종욱,한치화,홍영선,최일봉,신완식,민우성,김학기,김춘추,김원일,김동집 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

목적: 비혈연간 골수이식은 혈연내에 적절한 골수공여자가 없는 만성골수성백혈병, 고위험군의 급성별혁병, 면역억제치료에 실패한 재생불량성빈혈 및 각종 난치성 조혈모세포질환의 완치를 위한 표준적인 치료방법으로 정착되고 있다. 혈연간 표준적인 동종 이식에 비하여 비혈연간 이식시에는 생착부전, 이식편대숙주반응과 감염이 더 빈번하게 발생하며, 국내에서는 아직까지 체계적인 임상연구결과가 보고된 바 없었다. 이에 본 센터에서는 1995년 10월 이후로 약 20개월간 26예의 비혈연간 골수이식을 시행하였으며 3개월 이상의 추적관찰이 가능하여 이식초기 합병증의 관찰 및 분석이 가능하였던 20예의 환자를 대상으로 이식성적 및 문제점을 보고함으로써 새롭게 확대되고 있는 이 분야의 임상연구 및 진료의 활성화를 꾀하고자 한다. 방법: 각종 혈액 종양질환으로 비혈연간 이식을 시행한 총 26예의 환자중 3개월이상의 추적관찰이 가능하였던 20예를 대상으로 후향적으로 임상경과를 분석한 후 생존 분석을 시행하였고, 환자의 연령, 성별, 질병의 상태, 조식 적합 항원의 일치정도, 이식편대 숙주 반응의 유무와 생존기간과의 상관관계를 살펴보았다. 또한 표준위험군과 고위험군으로 나누어 생존율을 비교하였고 이식과 관계된 생착 부전, 이식편대숙주반응, 감염의 발생과 양상 그리고 그 합병증을 관찰하였다. 결과: 1. 환자와 공여자간에 HLA 불일치가 20예 중 4예에서 있었으며, 생착여부의 확인이 가능했던 17예 중 16예에서 생착이 확인되어 94.1%의 생착율을 보였다. 2. 급성이식편대숙주반응은 62.5%(10/16예)에서 발생하였으며 111도 이상의 급성의 이식편대숙주 반응은 25%(4/16예)에서 발생하였다. 만성이식편대숙주반응은 40%(2/5예)의 환자에서 발생하였으며 이들 모두 국소형으로 중증의 진행형 만성이식편대숙주반응이 관찰된 환자는 없었다. 3. 호흡기 합병증은 10예(50%)에서 발생하였으며 감염성 폐렴을 포함한 호흡기 합병증이 가장 흔한 일차적인 사망 원인이었다. 호흡기 합병증이 발생했던 10예중 6예가 감염에 의한 폐렴이 의심되었고 나머지 4예는 특발성 간질성 폐렴이었다. 4. 8.5개월의 중앙추적기간 중 35%의 생존율을 관찰할 수 있었고, 생존기간은0.5개월에서 15개월 (중앙치:4개월)이었다. 한편 고위험군은 25%(3/12예), 표준위험군은 50%(4/8)의 생존율을 관찰할 수 있었다. 5. 가장 흔한 사망 원인은 감염성 폐렴을 포함한 호흡기 합병증(6예)이었고, 이외의 사망 원인으로는 급성 이식편대숙주반응과 다장기부전이 각각 2예, 생착 부전, 간정맥 폐쇄, 그리고 재발이 각각 1예였다. Unrelated bone marrow transplantation(UBMT) has been increasingly recognized as the standard treatment for cure of chronic myelogenous leukemia, high risk acute leukemia, aplastic failed on immunotherapy, and the variety of refractory hematologic diseases in patients lacking a related donor. However, as compared to HLA identical sibing transplantation, UBMT carries higher incidence of graft failure, graft versus host disease(GVHD), and infection. In our center, 26 patients underwent UMBT between October 1995 and June 1997. The minimum follow-up of 3 months was possible in 20 patients, for whom early complications and clinical outcomes were assessed. The median age of the 20 patients was 24 years. 8 patients had standard risk disease and 12 patients had high risk disease. All patients received various preparative regimens including total body irradiation according to disease and disease status. 19 patients received CsA + short course MTX for GVHD prophylaxis. One patient received marrow that was depleted of T cells ex vivo using avidinbiotin column. The class I loci were typed by serological methods and HLA-A, HLA-B and HLA-DRB1. 3 additional pairs were one minor mismatched at the HLA-B locus. Another one patients was one major mismatched at the DRBI alleles. 17 patients were evaluable for engraftment. Successful enfraftment was confirmed in 16 patients(94.1%). Only one patient who was performed one major DRBI mismatched transplants experienced graft rejection. 16 patients were evaluable for acute GVHD. The overall incidence of acute GVHD developed in 4 patients(25%). Five patients were evaluable for the development of Ⅳ acute GVHD developed in 4 patients (25%). Five patients were evaluanle for the development of chronic GVHD. 2 patients(40%) developed limited chronic GVHD. Respiratory complications including pulmonary infection developed in 10 patients(50%) and these complications were the most common primary cause of death. Of these 10patients, 6 had pneumonia due to fungus(4 patients), pacterial (1 patient), and CMV infection (1 patient) and 4(20%) had idiopathic interstitial pneumonitis and/or adult respiratory distress syndrome. The duration of median follow- up was 8.5 months and 7 of 20 patients(35%) are alive at the time of this analysis with survival duration of 0.5 to 15 months(median survival duration: 4 months). The overall survival was 25% (3/12 patients) in high risk group and 50%(4/8 patients) in standard group. From these results, we can predict that the incidence and severity of GVHD in Korea are lesser than multiracial countries and the long-term survival of patients with standard risk disease can approach that of HLA matched sibling transplants. For the past two years, the performance of UBMT has been rapidly increasing and it will be possible to analyze much larger number of patients soon in Korea. In the future the problems of graft failure, GVHD, and infection due to long lasting immunocompromised status will need to be overcome by continued medical research. In addition, the volunteer donor pool will have to be expanded by the promotion of the national awareness of its need.

기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험

최영민(Youngmin Choi),이형식(Hyung-Sik Lee),권혁찬(Hyuk-Chan Kwon),한상영(Sang-Young Han),최종철(Jong-Cheol Choi),정주섭(Ju-Seop Chung),김창원(Chang-Won Kim),김동원(Dong-Won Kim),강치덕(Chi-Duk Kang) 대한방사선종양학회 2008 Radiation Oncology Journal Vol.26 No.2

목 적: 기존치료에 반응하지 않는 다발성 간전이를 동반한 대장암 환자에서 방사선치료와 병합한 수지상세포 면역 치료의 독성과 반응도를 조사하였다. 대상 및 방법: 2004년 5월부터 2006년 11월까지 다발성 간전이가 동반된 대장암 환자들 중에서 항암화학 요법에 반응하지 않은 환자 중 지원자를 대상으로 연구를 시행하였다. 본 임상 시험에 대하여 동아대학교병원과 부산대학교병원의 임상윤리심의위원회의 허가를 획득하였고, 동의서에 서명한 환자들을 임상 시험의 대상으로 등록하였다. 환자의 말초 혈액으로부터 수지상세포를 추출하여 배양하였다. 임상시험 일자에 맞추어서 6×106개의 수지상세포를 바이알(0.5 ml)에 넣어서 디씨백/아이알 주사를 만들었다. 수지상세포 면역치료는 2주 간격으로 간전이암조직에 3회 주사하고, 5주에 내약성 평가를 하였다. 내약성 평가를 통과한 환자에게는 8주에 4번째 수지상세포 면 역치료를 하였다. 병의 악화가 없거나 임상시험에 대한 환자의 동의 철회가 없는 경우에는 5, 6번째 수지상세포면역치료를 각각 12, 16주에 시행하였다. 방사선치료는 수지상세포 면역치료를 주사할 간전이암 부위에 주사하기 전일 및 당일에 4 Gy씩을 조사하였다. 내약성 평가는 3×106개의 수지상세포로부터 시작하여, 12×106개의 수지상세포까지 시행하였다. 내약성 평가의 최대 내성 용량으로 추가 임상시험을 하였다. 수지상세포 면역치료 주사를 맞은 모든 환자들에서 안전성 평가를 하였다. 4회 이상 주사를 맞은 환자들을 대상으로 10주에 치료 반응을 평가하여 유효성을 조사하였다. 결 과: 임상시험에 등록한 24명 중 22명에서 수지상세포 면역치료를 시행하였다. 내성약 평가에는 14명이 등록하여 11명에서 평가를 완료하였다. 시험약과의 관련성이 있을 것으로 생각되는 grade 3 이상의 약물반응으로 인한 이상반응은 없었다. 12×106개의 수지상세포를 내성용량으로 확인하였고, 내성용량인 12×106개 수지상세포 면역치료를 이용하여 8명에서 추가로 시험을 하였다. 치료에 대한 환자들의 내성은 양호하였고, grade 3을 초과하는 치명적인 부작용은 발생되지 않았다. 4회 이상의 수지상세포 면역치료 주사를 받은 환자가 17명이었고, 이 중의15명에서는 종양의 반응도 평가가 이루어졌다. 본 연구의 목적은 안전성 평가이지만, 면역치료의 유효성 평가를 위해, 방사선치료와 수지상세포 면역치료 주사가 시행된 부위 외의 간전이암에서 반응도를 조사 하였다. 면역치료의 반응은 평가가 이루어진 환자들에서 정지성 병변이 4명, 진행성 병변이 11명 이었다. 결 론: 수지상세포 면역치료와 병행한 방사선치료는 이론적으로 국소 및 전신 제어에 상승효과가 있을 것으로 기대할 수 있다. 하지만 기존 치료에 반응하지 않는 매우 진행된 직장암 환자들을 대상으로 한 본 연구에서는 방사선 치료와 병합한 수지상세포 면역치료로 인한 심각한 부작용의 발생은 없었다는 결과와 4예에서의 정지성 병변의 관찰을 보고한다. 수지상세포의 최대 투여 용량, 적절한 투여 방법, 적절한 방사선의 양, 방사선과 수지상 세포의적절한 투여 간격 등에 관한 추가 연구를 통하여, 향후 제 2상, 3상 시험으로서의 진행 여부에 긍정적인 결과를얻을 수 있다고 판단한다. Purpose: To assess the toxicity and tumor response induced by DCVac/IRⓇ dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6×106 DCs were packed into a vial (DCVac/IRⓇ, 0.5 ml) at the convenience of each patient’s schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3×106 to 12×106 DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The 12×106 DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The DCVac/IRⓇ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials

열공형과 비열공형 피질하 혈관성 치매에서 위험인자의 차이에 관한 비교 연구

배희준,정지향,유경호,나덕렬,김상윤,최경규,양동원,손의주,이상도,김재우,박경원,김응규,이재홍,박미영,한일우,함동석,최문성,하충건,최성혜,이애영,이병철,한설희 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.2

Backgrounds and Objectives: Vascular dementia is a group of dementing disoders arising from various stroke syndrome. Among these. subcortical ischemic vascular dementia (SIVD) is regarded as a relatively distinct clinical entity. However, MRI patterns of SIVD are not homogenous. In some patients, lacunes are dominant, and in others, subcortical white matter changes are. This study was designed to compare risk factor profiles between SIVD with and without multiple lacunes. Methods: We divided 47 subjects (22 males, mean age. 68 years) recruited from VADAPET (Multicenter Trial For Evaluation Of The Changes In the PET Images Of Subcortical Vascular Dementia Patient) study into two groups one with more than 5 lacunes in deep gray matter (lacune group) and the other with 5 or less(non-lacune group) Clinical characteristics and laboratory findings of two groups were compared. Results: Nineteen of 47 patients (40%) belonged to the lacune group. The lacune and non-lacune groups d d not differ in the following variables: age, hypertension, diabetes mellitus, hyperlipidemia heart disease, history of stroke or TIA, history of trauma or major surgery, family history of hypertension stroke, or dementia, age at diagnosis of dementia, body mass index, white blood cell count, ESR, CRP, fibrinogen, hemoglobin A1C, total cholesterol. LDL cholesterol creatinine, proteinuria, glucosuria, and microhematuria. However, male sex, smoking alcohol. hemoglobin, and HDL cholesterol were possibly associated more with lacune group SIVD than with non-lacune group (p<0 1) Multivariate analyses revealed that smoking, hemoglobin, and HDL cholesterol were independent predictors of SIVD with multiple lacunes Conclusion: Our study suggests that SIVD with multiple lacunes may be significantly different in smoking habits hemoglobin, and HDL cholesterol from SIVD without multiple lacunes.

壓挫시킨 家兎 軟骨의 生存

최동원,송중원,한기환,강진성,정재홍 大韓成形外科學會 1990 Archives of Plastic Surgery Vol.17 No.2

The deviated nose regardless whether it is due to traumatic or congenital origin results in troublesome symptoms coming from airway obstruction. Numerous methods for straightening the severely deviated septum have been described by many authors but none is wholly satisfactory. A new method that the crooked septal cartilage is being flattened by crushing and reimplanting into the septal pocket is introduced. The authors are desirous of knowing about the fate of the crushed cartilage graft. Forty rabbits weighing 2 to 3 kg were divided into 2 groups, septal group and conchal group. The cartilages were obtained from the nasal septum and ear; these cartilages were placed under the paraspinal subcutaneous tissue. Prior to paraspinal iplantation the obtained cartilage was halved; one piece of cartilage being crushed by Cottle's cartilage crusher before its placement into the recipient site and the other was placed without crushing. The cartilage specimens were removed at 6 and 12 weeks postoperatively and these were examined by the naked eyes and light microscope. The results were as follows: 1. The fissures and cleavages of cartilage developed during crushing process are restored to normal by 6 weeks postoperatively. 2. All of the ujncrushed cartilages remained viable in the subcutaneous pockets. The crushed cartilages not only appeared viable but also induced a new cartilage formation beneath the perihondrium at 12 weeks postoperatively and the thickness being increased compaired to the cartilage before crushing. 3. Crushed cartilage remained flat at 12 weeks postoperatively. 4. The degree of strength of the crushed cartilage is increased due to new cartilage formation and fibrosis of perichondrium at 12 weeks postoperatively. These findings support the clinical impression that the crushed autogenous cartilage is viable and can be reshaped according to the contour of the recipient site.

콘크리트 구조물용 GFRP리바의 기계적 특성에 관한 연구

한길영,이동기,김성용,전상기,최종대,박준식 조선대학교 에너지.자원신기술연구소 2000 에너지·자원신기술연구소 논문지 Vol.22 No.2

In this paper was studied on the mechanical characteristics of Glass Fiber Reinforced Plastics(GFRP) of the steel bar it is to replace The advantage of FRP such as high strength low weight and chemical inertness or noncorrosiveness can be fully exploited. GFRP bar were successfully fabricated at 10mm nominal diameters and hollow types using a pultrusion method Tensile and bending specimens from this bar were tested and compared with behavior of GFRP rebar and steel bar.

근치적 위절제술을 시행한 위암 환자에서 보조요법으로서 5-Fluorouracil, Epirubicin과 5-Epirubicil,Cisplatin의 복합화학요법의 효과 비교

최정혜,안명주,한동수,손주현,전용철,박훤겸,백홍규,이홍기,남영수 한양대학교 의과대학 2000 한양의대 학술지 Vol.20 No.2

To compare 5-fluorouracil plus epirubicin (FE) to 5-fluorouracil plus cisplatin (FP) chemotherapy as adjuvant therapy for patients with resected gastric cancer. Between August 1995 and March 2000, 46 patients with completely resected gastric cancer received six courses of FE (5-fluorouracil 1000mg/m2/day, D2-D5, epirubicin 70mg/m2, D1) or FP (5-fluorouracil 1000mg/m2/day, D2-D5, cisplatin 70mg/m2, D1) chemotherapy. The 23 patients were assigned to each treatment group. A total of 127 courses of treatment were given both FE and FP group. The FP group tended to show more risk of overall death rate. But there were no differences between FE and FP groups in terms of overall survival or disease-free survival. Both treatment arms were generally well tolerated to chemotherapy. We concluded to be no significant differences between FE and FP groups in terms of overall survival or disease-free survival. To define the efficacy of adjuvant chemotherapy for gastric adenocarcinoma, further prospective randomized trials with large number of patients should be warranted.

자궁경부 종양에서 Nested PCR을 이용한 인유두종 바이러스 16형 및 18형의 검출과 임상적 의의

최규연,이종국,최승도,배동한,김휘준,김민관 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.2

The aim of this study is to estimate the prevalence of HPV types(16, 18) in cervix of gynecologic patients and to elucidate the relationship of HPV types(16, 18) and clinical characteristics. Human papilloma virus(HPV) has attracted attention as one of the viruses linked to human cancers. Numerous clinical, epidemiological, and molecular studies indicate that certain genital HPV types are associated with cervical carcinoma. Of 100 types of HPV identified today, at least 40 have been found in the anogenital mucosa. A classification of these types into three groups with differing pathogenicity has been proposed: HPV type 6, 11, 42, 43, and 44 are detected more frequently in benign lesions such as condylomata; HPV type 31, 33, 35, 51, 52, and 58 are found more often in low grade squamous intraepithelial lesions than invasive lesions; and HPV 16, 18, 45, and 56 are predominant in high grade squamous intraepithelial lesions and invasive carcinoma. To detect HPV types prevalent in carcinoma of the uterine cervix, a type-specific, sensitive polymerase chain reaction(PCR)-based assay for HPV types 16, 18 was applied to 18 cervical carcinomas(15 squamous cell carcinomas and 3 adenocarcinomas), 21 cases of cervical intraepithelial neoplasia(CIN), and 42 samples of cervicitis and histologically normal. DNA extraction from cervical swab was done using DNAzol™(MBI, USA) and Nested PCR was done using HPV detection kit(Bioneer, Korea). The amplified product was analyzed directly on the basis of the site of ethidium bromide-stained band visible after agarose gel electrophoresis. The results were as follows 1. The positivity rates of HPV type 16 and HPV type 18 were 12.5%(90/718), 2,5%(18/718). so, HPV 16 positive cases(12.5%) was five folds as HPV 18 positive cases(2.5%) 2. Forty eight percents(39/81) of HPV 16 or HPV 18 positive cases were CIN, microinvasive cancer. 3. Age, Gestation number, Clinical stage, Histologic cell type in relation to HPV types were not statistically significant.

한국에서 분리한 사람 Caliviviruses의 RnA-dependent RNA Polymerase 유전자의 다양성

최종환,한동표,이현우,손준,김현원 연세대학교 원주의과대학 1997 원주의대논문집 Vol.10 No.1

개인식별 감정례

최종훈,이한영,이원태,이동주,김종열 大韓法醫學會 1999 대한법의학회지 Vol.23 No.2

It is noteworthy that most unidentified dead are unnatural and violent deaths. The accurate identification of a decedent permits certification of death and notification of next of kin. Only then may they proceed with the probate of wills, apply for disbursement of benefits and insurance, and begin to work through the grieving process. Law enforcement agencies need positive identification to pick up the leads of investigation to develop suspects, establish the corpus delicti of homicide and reconstruct the sequence of events of a crime. Agencies and a variety of consultants are involved in recognizing and developing the unique features of a decedent that lead to identification. Cooperative working relations with newspaper and other media will help in publicizing the need for persons with information to come forward diagrammatically. In this paper, 5 individual identification cases in unexpected or homicidal deaths are described. The comparison between the postmortem and antemortem records show that the victims are correctly identified.

장애인 엘리트체육의 실태 분석

최승권,이인경,문준혁,임찬규,한동기,김권일 한국특수체육학회 2005 한국특수체육학회지 Vol.13 No.1

The purposes of this study are to analyze actual status of elite sports for athletes with disabilities through investigating factors such as athletes constitutions, levels of game performance, and administrative and supporting organizations, which are critical bases for establishing the policy of elite sports for athletes with disabilities. The contents and scopes are as followings. First, analyzing composition of elite athletes with disabilities and current status of sports associations/federations. Second, analyzing the levels of game performance of elite sports for athletes with disabilities(Far East and South Pacific Games for the disabled, and Paralympics). Third, analyzing the support system such as administrative organization and support for athletes, leadership training, and financial support. Forth, analyzing survey on attitude and needs for elite sports of athletes with disabilities. Literature reviews, site visits, and survey were used to analyze the current status of elite sports for athletes with disabilities in Korea. The following outcomes were driven. First, this study revealed fewer numbers of sports federations, unbalanced composition of athletes in events, sex, and ages, and aging compared to international events and games. Second, this study revealed low performance level in team sports overall, and international competitive abilities but shooting, weight lifting, and archery were shown to be low. Third, this study revealed the weak establishment of administrative and financial supporting system.