중증 재생불량성빈혈에서 타인 혹은 HLA 불일치 혈연간 골수이식을 위한 cyclophosphamide와 antithymocyte globulin전처치 요법

이정희,이제환,김신,설미이,이정신,김우건,김상희,지현숙,박찬정,이규형 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: Cyclophosphamide와 ATG의 전처치 요법은 HLA가 일치하는 형제간 골수이식에서는 매우 효과적인 것으로 알려져 있으나, 타인 혹은 HLA 불일치 혈연간 골수이식에서는 전처치 요법으로서 불충분한 것으로 보고되었는데, 주요 문제는 착상 부전이었다. 우리나라를 포함하는 극동아시아 지역의 국가들에서 발표되는 보고에 의하면 타인이식을 포함하여 골수이식 후 착상 부전과 이식편대숙주질환의 발생이 서구 국가들로부터의 보고에서보다 적은 것으로 알려져 있다. 저자 등은 6예의 중증 재생불량성빈혈 환자들에서 질병 초기에 Cyclophosphamide와 ATG만을 이용하여 전처치를 한 후에 타인 혹은 HLA 불일치 혈연간 골수이식을 시행하였다. 방법: 1999년 5월부터 2000년 4월까지 서울중앙병원에서 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받은 성인 중증 재생불량성빈혈 환자들을 대상으로 하였다. 골수이식을 위한 전처치 요법으로 cyclophosphamide (50 mg/kg/d x 4)와 ATG (30 mg/kg/d x 3)를 투여하였는데, 골수이식 전에 ATG에 대하여 과민 반응을 보였던 한 예 (UPN 120)에서는 ATG 대신에 fludarabine (30 mg/m2/d x 3)을 투여하였다. 이식편대숙주질환의 예방을 위하여 cyclosporine과 methotrexate를 투여하였다. 결과: 연구 기간 중에 모두 6예가 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받았는데, 5예는 타인으로부터 골수를 공여 받았으며, 1예는 HLA의 표현형이 하나의 유전자좌에서 일치하지 않는 형제로부터 골수를 공여 받았다. 타인 골수이식을 받은 5예 중에서 3예의 공여자는 HLA의 표현형이 일치하였으며, 1예는 하나의 유전자좌가 major mismatch였고, 1예는 하나의 유전자좌가 minor mismatch였다. 추적기간의 중앙값은 406일 (범위, 328-643일)인데, 6예 모두에서 착상된 상태를 유지하면서 생존해있다. 2예에서 3도의 급성 이식편대숙주질환과 전신성 만성 이식편대숙주질환이 발생하였다. 결론: Cyclophosphamide와 ATG의 전처치 요법은 재생불량성빈혈의 초기에 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받은 한국인 환자들에서 충분히 착상을 가져올 수 있는 요법으로 생각된다. 비록 본 연구의 대상 환자 수가 적지만 결과는 매우 고무적이다. HLA가 일치하는 형제가 없는 중증 재생불량성빈혈 환자의 경우에 타인 골수 공여자에 대한 검색을 조기에 시행해야 하며, 타인 혹은 HLA 불일치 혈연간 골수이식을 질병 초기에 적극적으로 고려해야 할 것으로 생각된다. Background: Cyclophosphamide (CY) and ATG regimen was reported to be insufficient for alternative donor BMT in SAA patients due to high incidence of graft rejection. The rates of graft rejection and GVHD after allogeneic BMT including unrelated donor transplants seemed to be lower in reports from Asian countries of Far East. We applied CY/ATG regimen to six patients with early stage of SAA transplanted with marrow from alternative donors other than HLA-identical siblings. Methods: Three patients were transplanted from HLA-phenotypically identical unrelated donors, two from one-locus mismatched unrelated donors, and one from an one-locus mismatched sibling donor. Four patients received no previous therapy for SAA, and two received one course of immunosuppressive therapy with ATG. Preparative regimen was CY (200 mg/kg) plus ATG (90 mg/kg) in all patients except one who had had an anaphylactic reaction to ATG prior to BMT and received fludarabine (90 mg/m2) in place of ATG. Cyclosporine plus methotrexate were given for GVHD prophylaxis. Results: All six patients engrafted and all are alive with durable engraftment at a median follow-up of 406 days (range, 328 to 643). Two patients developed grade III acute GVHD and extensive chronic GVHD. Conclusions: CY/ATG regimen may be sufficient in Korean patients with early stage of SAA transplanted with marrow from alternative donors. Although the number of patients in present study is small, results are encouraging. Stem cell transplantation using alternative donors may be considered at early stage of aplastic anemia.

수입각증후군에 의한 급성 복증 1례

정은욱,지삼룡,이영태,박지훈,김동기,제인수,채두근,박성재,박은택,이연재,이상혁,설상영,정정명 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Afferent loop syndrome is an uncommon complication of a gastrectomy and Billroth Ⅱ reconstruction. It may cause symtoms at any time from the first postoperative day to many years after the gastrectomy. Afferent loop syndrome is characterized by abdominal pain, vomiting and elevation of serum amylase. Thus, it is difficult to differentiate afferent loop syndrome from other cause of acute pancreatitis. However, the history of gastrectomy can be an important clue for diagnosing afferent loop syndrome. We experienced one case of chronic afferent loop syndrome with acute pancreatitis. After appropriate management, the abdominal pain disappeared and serum amylase level decreased. We report this case with a review of relevant literatures.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.

PEG 분해균주의 분리와 PEG film의 상용성에 관한 연구

이제혁,정성제,이준열,전억한 경희대학교 부설 식량자원개발연구소 1993 硏究論文集 Vol.14 No.-

PEG를 sole carbon과 energy source로서 이용하는 미생물을 자연계에서 분리하였고, PEG의 분자량이 높아질수록 그 분해 미생물의 수가 감소하는 것을 확인하였다. 또한, liquid culture로서 PEG농도를 감소시키는 미생물을 선별하였고, 분해율은 PEG 8000이 약 18.8%였으며 PEG 10000은 약 25.4%인 것으로 조사되었다. PEG film의 제조를 위해 EMAA 및 EAA와의 상용성을 적외선 분광(IR) 스펙트럼을 사용하여 조사한 결과, EMAA와 EAA의 카르보닐기와 PEG의 에테르기와의 강한 수소결합이 형성으로 blend film제조시 상용성이 있는 것으로 확인되었다. Several strains capable of degrading PEGs(Polyethylene Glycols)were isolated and investigated for their biodgradation ability of PEGs. Microorganisms screened for the biodegradation studies were those grown on the PEG used as a sole carbon and energy source. It was known that the number of microorganisms decreased when grown on the high molecular weight of PEG(e.g. 20,000). A liquid culture was carried out with such microorgaisms and resulted in the decrease in PEG concentration meaning that PEG was degraded in the reactor. The biodegradability was found to be about 18.8% for PEG-8000 and 25.4% for PEG-10000, respectively. For the manufacture of biodegradable PEG film, EMAA/PEG and EAA/PEG blending ability was investigated with IR spectrum and showed that it was possible to produce blending film.

계승영구치가 선천적 결손된 유치의 치근 흡수

이정은,이제호,최형준,김성오,송제선,손흥규,최병재 대한소아치과학회 2009 大韓小兒齒科學會誌 Vol.36 No.4

유치의 정상적인 치근 흡수는 계승 영구치의 맹출 압력으로 단핵구 세포가 방출되어 파골세포로의 분화가 촉진되어 일어나며, 계승 영구치의 맹출 경로를 따라 유치의 치근이 흡수되어서 유치가 탈락하게 된다. 계승 영구치가 선천적으로 결손되었을 때에도 유치의 치근은 흡수될 수 있는데, 유치의 비정상적 치근흡수는 외상이나 염증, 교합압의 증가, 지지조직의 약화 등으로 발생할 수 있다. 치아의 선천적 결손은 인간에서 가장 흔한 발육이상이며, 영구치가 결손되었을 때 유치는 만기 잔존할 수 있다. 영구치의 선천적 결손은 전신질환이 있는 경우뿐만 아니라 국소적 원인이나 인류 진화에 따른 영향 등에 의해서도 발생한다. 이 증례들은 계승 영구치가 선천적으로 결손된 어린이에서 유치의 치근이 비정상적으로 흡수된 경우로 계승 영구치가 결손 된 유전치와 유견치, 유구치의 치근이 1/2 ~ 3/4정도까지 흡수 되었으며 흡수 부위는 불규칙적인 형태를 보였다. 원인으로는 흡수에 감수성이 높은 유치의 치주인대, 그리고 성장에 따라 증가되는 저작근육과 저작력, 혼합치열기에 유발되는 비정상적 교합 등을 생각할 수 있다. 계승 영구치가 결손된 유치가 비정상적인 치근 흡수를 보이는 경우에 유치는 유지될 수도 있지만, 여러 요인에 의하여 탈락될 경우에는 공간을 유지 할 것인지 판단해야 하며, 향후 보철치료나 교정치료를 요하므로 장기적인 치료계획을 수립해야 한다. Root resorption of primary teeth usually occurs as the succeeding permanent teeth erupt, which induces differentiation of the hemopoietic cells into osteoclasts. Their root resorption pattern reflects the eruption path of the succeeding permanent teeth, and eventually the primary teeth shed as their succeeding permanent teeth erupt. Even when a permanent tooth germ is congenitally missing, root resorption of the corresponding primary tooth may still occur due to various factors, such as inflammation, traumatic occlusal force, and weakness of periodontium etc. Such congenital missing of permanent teeth is a commonly observed phenomenon in human be ing, and it often accompanies delayed retention of primary teeth. The etiologic factors for congenital missing in elude not only systemic diseases, but also local factors and human evolution process. In the radiographs of the cases in this report, the primary teeth without succeeding permanent teeth show pathologic root resorption. Root resorption progressed about 1/2~3/4 of the roots, and the surfaces of the resorption area were irregular. Considering high susceptibility of the periodontal ligament of primary teeth to root resorption, pathologic root resorption of primary teeth with delayed retention can be explained by the increased masticatory muscle force and abnormal occlusion developed during the mixed dentition. When the primary teeth without succeeding permanent teeth are lost, decision for space maintenance is required and long-term treatment plan for further prosthetic or orthodontic treatment should be establsihed.

수모세포종과 대뇌 원시 신경외배엽 종양의 면역조직화학적 연구

이정일,왕규창,지제근,조병규 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.8

Although it is becoming widely accepted that medulloblastoma and cerebral primitive neuroectodermal tumor(PNET) are identical tumors occuring at different locations, there are some controversies in their origin and pathological classification. As a method of investigating whether the tumors are identical in pathological aspects, immunohistochemical characteristics of medulloblastomas and cerebral PNETs were compared in this study. Also the prognostic significance of the immunohistochemical findings in modulloblastoma patients was analyzed. Clinical features of twenty-seven patients with modulloblastoma and eleven patients with cerebral PNET were reviewed, excluding tumors with significant cellular differentiation such as ependymoblastoma, pineoblastoma and neuroblastoma. The presence of glial fibrillary acidic protein(GFAP), neurofilament(NF), S-100 protein, vimentin synaptophysin, and epithelial membrane antigen (EMA) was examined with immunohistochemical method and the differences of the results between the two tumors were statistically analyzed. The positive rates of NF and synaptophysin were significantly higher in medulloblastomas(p = 0.006 and 0.003, respectively) and so was the positive rate of vimentin in cerebral PNETs(p=0.004). S-100 protein showed a higher positive rate in cerebral PNETs although it was not statistically significant Univariate and multivariate analyses did not show any significant correlation between the duration of survival and the presence of cellular antigens.

熟地黃의 抱製에 따른 5-hydroxymethyl-2-furaldehyde 함량 연구

이제현,고정아,황은영,홍선표 대한본초학회 2002 大韓本草學會誌 Vol.17 No.2

Objectives : Rehmanniae Radix Preparata has been used to enrich blood and supply yin for a several thousand years. We have studied on the quantity of 5-hydroxymethyl-2-furaldehyde (5-HMF) from Rehmanniae Radix Preparata at various processings and tried to develop the making method. Methods : The Rehmanniae Radix Preparata was prepared from the steaming process with rice wine, sterilized rice wine, diluted ethanol and water each other. And the change of 5-HMF was determinated. The analysis of 5-HMF was conducted by HPLC with reversed-phase C18 column and a UV detector at 280 nm. Elution was carried out at 1.0 ml/min with 5% acetonitrile. Results and Conclusions : From this analysis, we found out that the content of 5-HMF was increased with the number of processing times and the content of 5-HMF from Rehmanniae Radix Preparata steamed for 4 times was the same as that of Korea pharmacopoeia.

거대 청신경초종의 수술치료성적 : 수술전 안면신경전위의 예견 Preoperative Prediction of Facial Nerve Displacement by MRI

정신,김태선,김재휴,김수한,강삼석,이제혁 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.12

A total of 22 patients(13 males and 9 females : mean age 49 years) with large acoustic neurinoma who underwent the retrosigmoid transmeatal approach from May 1993 to May )995 at the Chonnam university Hospital was reviewed retrospectively. The authors investigated the surgical results and accuracy in predicting the direction of displaced facial nerve which was determined by preoperative magnetic resonance(MRI) findings. In all cases the preferred method was the suboccipital transmeatal approach. The direction of displacement of the facial nerve could be predicted by preoperative axial and coronal MRI scans and verified intraoperatively. Gross total removal was performed in 82%, the accuracy rate for facial nerve displacement was 77% and anatomical preservation was accomplished in 82.3% of the totally removed cases. During follow-up good functional outcomes were achieved in 91% and fair in 45%. The authors conclude that such good surgical results can be attributed to advances in microsurgical technique and intraoperative facial monitoring. In addition preoperative prediction of the direction of displaced facial nerves has significantly reduced the incidence of severe facial nerve weakness.

중증 재생불량성 빈혈 환자의 동종골수이식 후에 병발한 간정맥폐색질환(Hepatic Veno-Occlusive Disease)의 임상 경과 및 혈액응고 인자들의 변화

이제환,이규형,최성준,민영주,김신,이정신,김상희,박찬정,지현숙,김우건 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 재생불량성 빈혈 경우에는 조혈모세포 이식 후 VOD의 발생에 관한 보고가 거의 없는 실정이다. 저자 등은 cyclophosphamide와 antithymocyte globulin으로 전처치 후에 동종골수이식을 시행한 재생불량성 빈혈 환자들을 대상으로 하여 VOD의 발생과 임상 양상, 혈액응고 인자들의 변화에 관하여 분석하여 보았다. 방법: 재생불량성 빈혈로 동종골수이식을 시행 받은 13예 환자를 대상으로 하였다. 임상적 기준에 따라 VOD를 진단하였으며 임상 경과에 따라서 경중을 분류하였다. Protein C, protein S, antithrombin Ⅲ, tPA, PAI-1 등의 혈액응고 인자들을 전처치 투여전, 골수 주입당일, 이식 후 제7, 14, 21일에 측정하였다. 결과: 7예(53.8%)에서 VOD가 발생하였으며, 경증 5예, 중등도 2예였다. VOD군에서 혈소판치가 20.000/㎕ 이상을 유지하는 데까지 걸리는 시간이 더 길었다(p=0.026). 또한 VOD군에서 적혈구 및 혈소판의 수혈 요구량이 각각 유의하게 많았다(p=0.025, 0.015). 혈액응고 인자들의 변화를 보면, 제 0일에 VOD군에서 PAI-1의 혈중 농도가 유의하게 더 높았다.(p=0.034). 결론: 재생불량성 빈혈환자에서도 조혈모세포 이식 후에 VOD의 높은 발생률을 관찰하였으며, 대부분이 경증이었다. VOD 환자에서의 혈액응고 인자들의 변화는 PAL-1이 VOD의 감별 진단을 위하여 이용될 수 있음을 시사하고 있다. Background: There are few reports about the occurrence of hepatic veno-occlusive disease(VOD) after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). We analyzed the incidence and clinical outcomes of VOD and changes of coagulation factors in patients with SAA who were conditioned with cyclophosphamide plus ATG and underwent allogeneic BMT. Methods: Thirteen patients with SAA who underwent allogeneic BMT were included. A diagnosis of VOD was made according to clinical criteria, and severity of VOD was classified according to clinical course. Plasma levels of protein C, protein S, antithrombin Ⅲ, t-PA, and PAI-1 were determined before preparative chemotherapy, in the day of marrow infusion, and days 7, 14, and 21. Results: VOD occurred in 7/13(53.8%). Five were mild VOD and two were moderate VOD. Time to platelet ≥20,000/L was slower (p=0.026) and red cell and platelet transfusion requirements were higher (p=0.025,0.015) in patients with VOD . The mean plasma level of PAI-1 at 0 were higher in patients with VOD (p=0.034). Conclusion: We observed the high incidence of VOD after allogeneic BMT in patients with SAA. A majority of cases of VOD were mild. The changes of PAI-1 after BMT may be useful marker of hepatic VOD

동종 골수이식을 시행받은 환자에서 폐색성 세기관지염에 의하여 발생한 자발성 기종격동과 피하 기종

이병환,이제중,이연경,안재숙,김여경,황호인,박무림,조상희,정익주,김형준 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2

저자들은 만성골수성백혈병으로 동종 골수이식과 이식편 부전으로 인하여 추가적인 말초혈액 조혈모세포이식을 시행 받은 환자에서 만성 이식편대숙주질환과 그 폐 합병증인 폐색성 세기관지염에 동반된 자발성 기종격동과 피하 기종이 병발한 1예를 경험하였기에 이를 보고하는 바이다. Obstructive lung disorders following after allogeneic bone marrow transplantation (BMT) in association with graft- versus-host disease (GVHD) contribute significant morbidity and mortality. We report a case of a 28-year-old man who developed spontaneous pneumomediatinum and subcutaneous emphysema complicating bronchiolitis obliterans after allogeneic BMT. He received an allogeneic BMT for chronic phase of chronic myeloid leukemia. Five months after BMT, he was boostered by allogeneic peripheral blood stem cells from the same donor due to graft failure. One month after the boostering, chronic GVHD developed and were treated with cyclosporine and steroid. The patients developed spontaneous pneumomediatinum and subcutaneous emphysema secondary to severe bronchiolitis obliterans 4 months after boostering donor cells. The air-leak syndromes were recovered by conservative management, including high-flow oxygen.