제1형 당뇨병 환자에서 췌도세포 동종이식의 반복시행

양태영,정인경,서인아,오은영,조건영,오승훈,김성주,정재훈,민용기,이명식,이문규,김광원,도영수,주성욱 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.4

연구배경:췌도세포 이식은 시술이 간편하고 안전하기 때문에 반복이식이 가능하여 그 동안 여러 센터에서 반복이식의 성공을 보고한 바 있다. 국내에서도 본 병원을 비롯하여 몇몇 센터에서 췌도세포 이식이 활발히 시도되고 있으나 사람에서의 동종이식 및 동종 이식의 반복시행은 보고된 바 없는 실정이다. 저자 등은 국내 최초로 췌도세포 동종이식을 시행하여, 혈청 C­펩타이드가 증가하고 인슐린 요구량이 감소하였으며, 혈당농도와 당화혈색소의 안정을 보였다. 그러나 이식 70일 후 다시 인슐린 요구량이 증가하고 C­펩타이드가 감소하여 췌도세포 이식을 다시 시행한 바 있다. 2차 이식 후 70여일이 지난 현재 다시 혈청 C­펩타이드가 증가하고, 인슐린 요구량이 더 감소되어 췌도세포 이식에서 반복 시행의 유용성을 보고하는 바이다. 방법:환자는 32세 남자로 17년전 당뇨병 진단 후 인슐린 치료 중이었으며, 3년전 부터는 만성신부전증으로 혈액툭석을 하고있었다. 1999년 12월 25일 신장이식을 하였고 3일 후 췌도이식을 하였으며, 두번째 이식은 70일 후 시행하였다. 췌도분리는 변형된 Recordi방법과 비연속성 자당 농도차(discontinuous density gradient)를 이용하였으며 분리한 췌도는 배양 후 환자의 신장기능이 정상화되고 미생물학 검사에서 음성을 확인한 후 경피경간으로 간문맥을 접근하여 16G 폴리 에틸렌 카테터를 이용하여 간실질에 이식하였다. 결과:1차 췌도이식시 순수분리전 췌도수는 210,000개, 순수분리후 획득한 췌도수는 90,000개, 순도 95%, 세포양 1.0mL 이었고, 2차 췌도이식시 순수분리전 췌도수는 420,000개, 순수분리후 획득한 췌도수는 370,000개, 순도 95%, 세포양 1.5mL 이었다. 1,2차 모두 간문맥을 통해 약 20분에 걸쳐 간실질에 주입하였다. 췌도이식전 인슐린요구량은 75∼75U/일, HbA1e 8∼10%, C­펩타이드 0.6ng/mL 였으며, 1차 췌도이식수 7일째 인슐린 요구량은 40U/일, C­펩타이드 1.5ng/mL, FPS 109mg/mL 였고, 40일 추적관찰 후 인슐린 요구량이 36U/일, C­펩타이드 1.8ng/mL, HbA1e 6.5∼7.0%로 안정되었다. 그러나 이식 50일째부터 인슐린 요구량이 50∼56U/일, C­펩타이드 0.6ng/mL, FPS 130∼200mg/dL로 혈당 조절이 불안정하여 다시 췌도이식을 시행하였다. 2차 이식후 50일이 경과한 현재, 인슐린 요구량은 26U/일, C­펩타이드 1.8ng/mL, FPS 90∼120mg/dL로 다시 안정되었다. 결론:췌도이식은 반복이식이 가능하며, 본 환자의 경우 인슐린요구량 감소, 혈당의 안정화 및 C­펩타이드가 상승하여 이식한 췌도의 기능을 확인할 수 있었고, 향후 스테로이드 등 면역억제가 유지 용량으로 감량되면 인슐린 요구량은 더 감소될 것으로 기대된다. Over the past 20 years, significant advances have been made in human islet transplantation. However, cases of prolonged insulin independence after islet allotransplantation have rarely been reported and over time, a slight, gradual decrease in insulin secretion appears to occur, as suggested by the lower C-peptide. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more "traumatizing" whole-pancreas transplantation. Also, using islet, re-transplantation is possible. But it is not known whether re-transplantation of islet could be suitable for those patients who lost grafted islet function. The aim of the present study was to investigate the benefits of re-transplantation of islet in previously simultaneous islets-kidney transplant (SIK) patient who have lost graft function. Methods : The recipient was a 32 year old male. First islet transplantation was underwent at December 25, 1999. However, the grafted islets lost function after 70 days. So we performed re-transplantation of islets. The isolation of islet was conducted sterilely on a laminarflow hood and isolated by a modified Recordimethod. The islet was injected slowly into the liver via a cannular placed in the potalvein for 20 minutes. Results : Transplanted islets were 90,000 IEq at first islet transplantation, 370,000 IEq at second islet transplantation. The insulin requirement was reduced from 75-85 to 35-40 U/day, the basal C-peptide level was 1.5 ng/mL at 7 days posttransplant Unfortunately, the grafted islets lost function after 70 days. After second transplantation, the insulin requirement was reduced to 26 U/day. Conclusions : Despite the continuous need for exogenous insulin therapy, islet transplantation can prevent wide glucose fluctuations, thus resulting in normalization of glycemic control and improvement in HbAlc, and also, show that islets can be successfully and safely re-transplanted intraportally in patients who have lost previously grafted islet function (J Kor Diabetes Asso 457~466, 2000).

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).

남성화를 보이는 여성에서 발견된 난소의 Steroid Cell Tumor 1예

조인호,정대훈,박영미,서영진,손영실,정철회,강영미,정수전,김영남,이경복,성문수,김기태 인제대학교 2006 仁濟醫學 Vol.27 No.-

Steroid cell tumor is a rare ovarian sex cord-stromal tumor which accounts for 0.1% of all ovarian tumors. Until now, only 4 cases have been reported in domestic literatures. Steroid cell tumor often secrets testosterone and presents virilization in adult women or precocious puberty in children. Treatment is often performed by surgical removal, adjuvant chemotherapy and radiation, but completely accepted treatment was not existed. We experienced a case of steroid cell tumor, which was manifested by typical virilization in a 43-year old patient, who was previously performed hysterectomy and unilateral oophorectomy. So, we present with a brief review of the literatures.

Lyapunov 직접법에 의한 전력계통 전압 안정도 해석

文永鉉,盧台勳,朴能洙 연세대학교 산업기술연구소 1992 논문집 Vol.24 No.1

This paper presents an approach to voltage stability analysis in power systems by using the Lyapunov direct method. Recently it has been attempted to apply the direct method to voltage stability analysis by introducing an energy function. However, the energy function approach seems to be alienated since it could not produce even the voltage collapse conditions which agrees with the results from conventional linearization approaches or sensitivity analysis approaches. In this paper, a new approach of the direct method is proposed with a Lyapunov function, which is established by including the kinetic energy and the voltage dependency of real power loads. The proposed Lyapunov function is not suitable to calculate stability region or stability to calculate stability region or stability margin. However, it is very useful to calculate the voltage collapse conditions. This paper gives rigorous derivations of voltage collapse conditions by using the Lyapunov function, which yields the exactly same results as the conventional linearization approach and sensitivity analysis. On the other hand, the voltage collapse phenomenon is interpreted in the physical sense, and the causes of voltage collapse are analyzed with the use of the proposed Lyapunov function. It is also noted that a new method is developed to calculate the power capacity limit of transmission lines in the view point of voltage stability.

電解 Boronizing에서 Al-B合金 添加의 影響과 耐高溫酸化性에 對하여

양훈영,유병돈,김문철 연세대학교 산업기술연구소 1980 논문집 Vol.12 No.1

To investigate the effect of Al-B alloy addition on the boride thickness, hardness, wear and heat-resistance of the boride layer, an electrolytic boronizing with various amount of Al-B alloy in the electrolyte has been carried out at the current density of 0.5A/ ㎠ and in the temperature range of 800~1,000℃. Also aluminizing was conducted to the boronized specimen in order to find out whether aluminium would penetrate into the boride layer and improve the heat resisting property. From the experimental work, following results were obtained. 1) Increased thickness of boride layer and hardness were resulted with increased addition of Al-B alloy. Excess addition of the alloy, however, inhibited the boronizing because of the increasing viscosity of electrolyte. 2) Thickness of the boride layer increased rapidly with increasing temperature which improves the fluidity of electrolyte and diffusion rate. 3) Wear resistance improved markedly by boronizing and better result obtained by Al-B alloy addition. 4) Aluminium diffused into the boride layer by aluminizing of the boronized specimen, showing excellent heat resistivity even at 1,000℃.In this case,however, decreasing wear resistance was inevitable.

심근의 단독 비경화증(Isolated Noncompaction of Ventricular Myocardium)의 임상 양상

문은경,이훈영,장미영,길홍량,정용헌 대한소아과학회 2002 小兒科 Vol.45 No.12

관동맥우회술 후 발생한 급성 장간막경색 1예

문용화,김지현,강웅철,박병은,고영국,최동훈,유경종 대한내과학회 2004 대한내과학회지 Vol.66 No.3

관동맥우회술을 포함한 심장수술 후에 생기는 급성 장간막경색은 매우 드물지만 치명적인 합병증으로 발생률은 비교적 낮으나 사망률은 매우 높게 보고 되고 있다. 본 증례에서는 55세 여자 환자가 관동맥우회술을 시행받고 수술 후 1일째에 발생한 복부통증에 대해서 장간막경색증을 의심하지 못하고 수술과 연관된 비특이적 증상으로 판단하였으나 그 후 환자의 증상이 악화되면서 상장간막동맥 혈전 색전증에 의한 광범위한 급성 장괴사로 판명되었다. 관독맥우회술 후 상장간막 동맥에 생긴 혈전색전증에 의해 발생한 급성 장간막경색의 증례는 국내에 보고된 바 없고 본 증례를 통해 교육적인 경험을 하였기에 저자들은 문헌고찰과 함께 보고하는 바이다. 심폐우회술을 요하는 심장수술을 받은 환자 중 특히 급성 장간막허혈의 위험인자를 가지고 있는 환자에 대해서는 급성 장간막허혈이 생길 수 있다는 세심한 관찰이 진단이 늦어지지 않게 하는 방법이며 장간막허혈이 의심되면 즉시 적극적인 진단 및 치료적인 접근을 시도해야 하겠다. Acute mesenteric ischemia leading to massive bowel infarction following cardiac surgery particularly coronary artery bypass graft (CABG), is reported to be a very rare but serious life-threatening complication. In this case, a 55-year-old female underwent CABG and complained of abdominal pain on the first postoperative day, which was thought to be nonspecifically related to the operation wound, In the further hospital course, the patient was found to have extensive acute mesenteric infarction due to thromboembolism of superior mesenteric artery. This is a valuable educational case, since only high index of suspicion does not delay making a diagnosis especially in the patients with risk factors of acute mesenteric ischemia after cardiac surgery requiring cardiopulmonary bypass. On suspicion of acute mesenteric ischemia, an aggressive diagnostic and therapeutic approach should be performed immediately.(Korean J Med 66:317-320, 2004)

상아질 표면처리방법이 compomer의 전단결합 강도에 미치는 영향에 관한 연구

문주훈,조영곤,김수미 大韓齒科保存學會 1998 Restorative Dentistry & Endodontics Vol.23 No.2

입원 기간 중 발생한 첫 경련발작

이훈복,김종흥,김제,이애영,김재문 대한신경과학회 1997 대한신경과학회지 Vol.15 No.2

일부 수영장 욕수 및 이용객 urine내 Trihalomethane 농도

문경환,손종렬,김영환,변상훈,배은상 高麗大學校 倂設 保健大學 保健科學硏究所 1998 保健科學論集 Vol.24 No.1

Chlorination of swimming pool water leads to many chlorinated products. The most frequent derivative is trihalomethane(THMs). This study was performed to investigate the distribution of THMs in swimming pool water and ambient air, and to determine whether THMs concentrations in swimmers' urine Were influenced significantly after swimming. Water samples were collected from 22 indoor and outdoor swimming pools. Concentrations of THMs in swimmers' urine determined before and after their stay in swimming pools. Results of the study as follows. 1. The concentrations of THMs in the indoor swimming pools water(41.85±73.22㎍/L) were significantly increased(p<0.05) in comparison with that of outdoor swimming pools (10.15±15.45㎍/L). The average concentration of THMs in indoor ambient was 51.2㎍/㎥, which was significantly higher than that of air quality. 2. As a results of regression analysis between THMs and water quality factors, the concentration of pH, residual chlorine and KMnO₄ consumption were highly correlated in indoor swimming pools. 3. In almost all cases, only CHCl₃ was quantifiable. The proportions of THMs in urine correlated roughly with those in water and the secretion of THMs increased significantly after swimming in the pools.