조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

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.

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.

Hydroxy Propyl Methyl Cellulose의 자연발화에 관한 연구

최재욱,목연수,하동명 한국화재소방학회 2001 한국화재소방학회논문지 Vol.15 No.4

HPM의 자연발화는 일정한 주위온도에서 자연발화의 연구와 Godbret-Greenwald가 고안한 전기로에서 운상상태의 최소발화온도를 구하였으며, 시료를 용기에 충전했을 경우 용기의 크기가 클수록 발화한계온도는 낮아졌으며, 겉보기활성화에너지는 Frank-Kamenetskii의 열발화이론으로부터 계산하였고, 운상상태의 발화온도는 21%의 산소농도하에서 최소발화온도를 구하였으며, 산소농도 변화의 실험결과 산소농도 10%에서 발화되지 않았으며 한계산소농도를 구할 수 있었다. The spontaneous ignition of hydroxypropyl methyl cellulose(HPMC) was investigated at constant ambient temperature in the oven and minimum ignition temperature of dust clouds with Godbret-Creenwald Furnace respectively, In the experiments of the vessel filled with sample, the larger the vessel was the lower the spontaneous ignition temperature and ambient temperature was calculated from the Frank-Kamenetskii thermal ignition theory, The minimum ignition temperature for the dust cloud state was found under 21% oxygen concentration. At the experiment with the change of oxygen concentration, HPMC was not ignite at 10% O2 and so the limiting oxygen concentration was obtained at 10%. Keywords : Spontaneous ignition, Ambient temperature, Minimum ignition temperature Frank-Kamenetskii thermal ignition theory

가연성물질의 인화점에 관한 연구 : Ⅰ. 순수성분 및 2성분계 혼합물 Ⅰ. Pure Substances and A Mixture of Binary System

최재욱,목연수,하동명 韓國火災 ·消防學會 1999 한국화재소방학회논문지 Vol.13 No.1

생물막 공정에서 질소제거효율 향상을 위한 유기성담체의 효용성 검토

최동욱,최영균,김대영,김윤중,정태학 대한상하수도학회 2003 상하수도학회지 Vol.17 No.3

Availability of organic media for improving nitrogen removal efficiency in a biofilter process was studied. Although, aerobic and anoxic phase could be clearly divided during the operation of single-stage biofilter process and nitrification efficiency was about 80%, denitrification efficiency was very low due to depletion of organic substrate in anoxic phase. However, the deficiency could be improved by addition of organic media in anoxic phase from the simulated result. Nitrogen removal efficiency in a biofilter process packed with organic media in anoxic phase was predicted to be 29% higher than that packed with inorganic media. In addition, about 79% of nitrogen removal efficiency could be obtained from a column test using organic media innoculated by activated sludge. Improvement in nitrogen removal efficiency was responsible for organic leaching from the organic media and the leaching rate was 0.21㎎COD/g-org.media/day.

국내 조혈모세포이식 환자에서 Human Cytomegalovirus gB 유전형의 분포와 질환과의 연관성 : 예비 보고

최수미,김진희,이동건,박선희,최정현,유진홍,박철민,이종욱,민우성,황응수,신완식,김춘추 대한감염학회 2007 감염과 화학요법 Vol.39 No.2

목적 : 사람 거대세포바이러스(Human cytomegalovirus, 이하 HCMV) glycoprotein B (gB)는 UL55 유전자에 의해 부호화되는 당단백으로, UL55 유전자의 염기서열변화에 따라 4가지 유전형으로 나뉜다. 본 연구에서는 국내 조혈모세포이식 환자들에서 HCMV gB 유전형의 분포와 그 특성을 알아보고, gB 유전형에 따라 특정 HCMV 질환 발생과 연관이 있는지 그 임상적 의미를 분석해 보고자 하였다. 재료 및 방법 : 동종 조혈모세포이식 환자 52명의 혈액검체 94개에 대해, Chou 등이 제시한 방법에 따라, 먼저 UL55 유전자 부위를 nested PCR로 증폭한 후, RsaI과HinfI으로 Restriction fragment length polymorphism(RFLP) 분석을 시행하였다. 결과 : gB type 1은 73.1% (38/52), gB type 2는 13.5%(7/52), gB type 3는 1.9% (1/52), gB type 1과 type 2에 의한 혼합감염은 9.6% (5/52)로 나타났다. gB type 4는 관찰되지 않았다. 1명(1.9%)에서 gB 유전형을 결정할 수 없었는데, RFLP 패턴으로 보아 Trincado 등이 제시한 gB type 7에 해당하는 것으로 생각되었고, 이 새로운 아형에 대해서는 현재 염기서열 분석 중이다. 52명 중 5명(9.6%)에서 HCMV 질환이 발생하였고, 3명에서 HCMV 폐렴, 1명에서 망막염과 위장관염, 나머지 1명에서 망막염이 발생하였다. 5명 중 HCMV 질환과 관련하여 사망한 예는 없었고, 감염된 HCMV는 모두 gB type 1이었다. HCMV gB유전형과 HCMV 질환 발생 사이에 유의한 연관성은 없었고, 단일 주에 의한 감염과 혼합감염에 따른 HCMV 질환발생 사이에도 유의한 연관성은 관찰되지 않았다. 자료 분석 중 gB type 2에 감염되어 있던 환자에서 gB type 1에 재감염 되면서 발열, 간효소 수치 상승 및 pp65 HCMV 항원혈증이 나타난 예가 있었다. 결론 : 연구결과 gB type 1이 아주 우세하고, gB type 4는 검출되지 않았으며, 혼합감염의 빈도가 비교적 낮은 분포를 보였다. 이는 외국의 보고와는 다른 국내 조혈모세포이식 환자에서의 독톡한 감염 양상으로 추정된다. 본 연구에서 HCMV gB 유전형과 질환 발생과의 연관성을 밝힐 수는 없었으나, HCMV 유전형에 대한 연구는 바이러스 감염의 발병기전이나 전파 경로 및 양식과 같은 역학적 연구에 중요한 자료가 될 것이다. 현재 더 많은 수의 조혈모세포이식 환자를 대상으로 연구가 진행 중에 있으며, 앞으로 다른 질환군의 환자나 건강한 잠복 감염자에서의 추가 연구가 필요할 것으로 생각된다. Background : Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. Materials and Methods : DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. Results : The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days’ follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. Conclusion : HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.

유방암의 뇌하수체 전이에 의한 양안 시력소실 1 예

최낙원,안명주,김재민,박동우,박용욱 한양대학교 의과대학 2000 한양의대 학술지 Vol.20 No.1

Pituitary gland metastasis is a rare clinical diagnosis, usually made in the setting of known primary systemic cancer with widespread metastasis to other organs. But visual loss as a presenting symptom of metastasis to the pituitary gland is unusal. We report here a case of 45-year-old woman who had been diagnosed as having metastatic breast cancer involving bone and liver 2 years ago, and received high dose chemotherapy with peripheral blood stem cell transplantation, developed sudden bilateral complete visual loss. At initial presentation, the patient had no light perception and no pupillary response to light in both eyes, but without evidence of panhypopituitarism, or diabetes insipidus. Brain MRI showed a large enhanced mass invasion to the cavernous sinus and extension to the suprasella portion without dura or base-of-skull metastasis. Pathologic examination showed metastatic breast cancer. Despite the transsphenoidal decompression surgery of metastatic tumor, the visual loss was not improved.

분진의 개수농도 및 질량농도에 입각한 서울시 지하철 역사내 오염원의 기여도 결정

최형욱,황인조,김신도,김동술 한국대기환경학회 2004 한국대기환경학회지 Vol.20 No.1

The subway play an important part in serious traffic problems. However, because subway system is a closed environment, many serious air pollution problems occurred in subway stations and injured passenger's health. Therefore, it is a necessary to identify sources and to estimate pollutant sources in order to protect passenger's health and to keep clean subway environment. The purpose of this study was to analyze a air quality in the subway stations and to apply a new receptor methodology for quantitatively estimate of PM 10 sources. In this study, the size distributions of particulate matters has been measured by using Aerosizer LD (U.S.A., API, Inc.). It's realtime measurement capability of time-of-flight technique offers a significant advantage of user convenience and air pollution management. Also, the mass concentrations of PM 10 has been measured by using mini-vol portable sampler (U.S.A., Airmetrics Co.). The sampling performed in Seoul subway stations during the period of February 2000 and April 2000. The number distribution data used in this study consisted of 26 raw data sets in the Jongno-sam-ga station. Correlation Analysis can be used in subway stations for source separation and identification. Then, number contribution from each source is determined by the particle number balance (PNB). The mass concentration data used in this study consisted of 31 raw data in the 8 different stations. The mass contributions of PM 10 sources in the concourse by using PMF/CMB model.