사람골수 세포에서 B 혈액형 항원의 출현에 대한 면역 전자현미경적 연구

유남진,김주성 大韓法醫學會 1985 대한법의학회지 Vol.9 No.1-2

Membrane antigens are extensively studied on different mammalian cell lines. Antigens of the erythrocyte series are often chemically well defined heterosaccharide determinants. since Yunis and Yunis (1963) gave strong evidence of the presence of A,B and H alloantigens on human normoblasts by indirect agglutination methods, several workers have detected A antigens by immunoelectron microscopy using peroxidase labelled antibodies (Reyes et al.,1974), staphylococcal protein A technique (Karhi et al., 1981) and fluorescence activated cell sorter (Sieff et al., 1981, 1982). Here we report immunoelectron microscopy observation of blood group B antigen on human normoblasts using peroxidase-labelled antibodies which allow detection of surface antigens on separated cells. The bone marrow specimens were selected from the ones which had been depleted of erythrocytes by a Ficoll-Hypaque technique and stored in liquid nitrogen(-196℃) as described (Seung & Kim, 1985). The selected specimens were from eight blood type B individuals with no disturbances in erythropoiesis. These experiments were carried out with cytocentrifuge smears and cell suspensions for light microscopic and electron microscopic observations respectively. The cell suspensions were fixed prior to incubation with reagents. Fixation was achieved by resuspending the cell pellet in phospate-buffered saline solution of 1.25% glutaraldehyde for 30min: followed by washes with a large quantity of the same buffer. They were resuspended in methanol containing 0.3% H₂O₂ for 30min. to block endogenous peroxidase and washed. And they were labelled by an indirect method using human Anti-B(IgM) and rabbit antihuman IgM antibodies labelled with horseradish peroxidase. The cytochemical detection of horseradish peroxidase was carried out by resuspending the cells for 30 min. in the dark in the usual medium containing diamino-benzidine and H₂O₂. Subsequently specimens were washed, postfixed with 1% OsO₄ for 30 min. and processed for dehydration in alcohol and acetone. For transmission electron microscopy they were embedded in Epon, sectioned and stained and stained with uranyl acetate and lead citrate. The results were as follows: 1. Under a light microscope the smears showed that brown positive cells were mixed with negative cells, but the precise identification of the cell types was difficult. 2. Under anelectron microscope a continuous or incontinuous labelling of blood group B antigens was seen in contact with the membrane of all normoblasts. 3. The myeloid precursor cells are not labelled, but occasionally limited labelling of the membrane of granulocytic and monocytic cells could be seen.

혈액질환 환자에서 조혈모세포 이식과 화학요법 후의 침습성 진균감염의 분석

유진홍,최정현,이동건,최수미,신완식,김춘추 대한감염학회 2004 감염과 화학요법 Vol.36 No.1

목적 : 조혈모세포 이식이나 화학요법을 받은 혈액질환 환자에서 침습성 진균감염의 양상을 분석하고 예후 인자를 정하기 위하여 이 연구를 실시하였다. 방법 : 2000년 3월부터 2001년 2월까지 가톨릭 조혈모세포이식센터에 입원한 318명의 환자들 중 진균 감염으로 의심되어 항진균제를 투여받은 122명의 환자를 대상으로 후향적 분석을 실시하였다. 결과 : 74명의 환자가 EORTC/MSG 기준에 의해 침습성 진균증으로 판정되었다. 이들 중 6명이 확진이었고, 46명이 추정, 22명이 가능 증례이었다. 가장 많이 침습된 장기는 하부 호흡기이었다(72/74). 사망률은 32.4%이었다. 단변량 분석으로 예후 인자를 도출한 결과 입원 기간, 진단까지 걸린 시일, 그리고 amphotericin B의 총 투여량이 유의한 인자로 나왔다. 그러나 다변량 분석을 시행한 결과 입원 기간만이 독립적으로 유의하게 영향을 미치는 예후 인자로 산출되었다. 결론 : 침습성 진균 감염은 현재도 조혈모세포 이식이나 화학요법 후의 중요한 합병증으로 작용하고 있음을 알 수 있었다. 진균 감염 합병증의 예후에 영향을 미치는 요소로 입원 기간이외에 진단의 신속성과 항진균제의 투여도 유의한지에 대해서는 후속 연구를 통해 재치 규명해야 할 것으로 생각된다. Background : Invasive fungal infections (IFI) are one type of representing total infections in compromised patients. To analyze the characteristics and to determine the prognostic factors of IFI in patients with hematologic diseases undergoing hematopoietic stem cell transplantation (HSCT) and/or chemotherapy. Methods : We retrospectively reviewed consecutive patients (n=122) who received antifungal treatment with the impression of fungal infection complicating post-HSCT or chemotherapy from March-2000 to February-2001. Results : Seventy-four out of 122 registered patients belonged to the IFI on the basis of EORTC/MSG criteria. Six patients were proven IFI, 46 were probable, and 22 were in the category of possible one. The most commonly involved organ was lower respiratory tract (72/74). The mortality was 32.4%. Univariate analysis revealed duration of hospitalization, days to diagnosis of IFI, and total amount of amphotericin B as significant prognostic factors. But multivariate analysis determined only duration of hospitalization from these variables as an independently influencing factor on the prognosis. Conclusion : Invasive fungal infection is still the major threatening complication of HSCT and chemotherapy. Further follow-up and extension of this study is necessary to elucidate more prognostic factors.

혈청 감마지티(gamma glutamyl transferase)치와 대사증후군의 연관성

장미,유병욱,조용진,오정은,홍성호,조주연 순천향의학연구소 2008 Journal of Soonchunhyang Medical Science Vol.14 No.1

Background: Serum gamma glutamyl transferase(GGT) level has been widely used as an index of liver dysfunction and a marker of alcohol intake. But, recently it is identified that the elevated GGT level was associated with insulin resistance. This study aimed to examine the association between metabolic syndrome and elevated GGT level in the women who had less alcoholic influence generally. Methods: From 585 women who received their annual health check-up, 577 women were selected for analysis except for 28 women who had hepatitis B surface antigen positive or antibody to hepatitis C virus positive, Categories of serum GGT were classified into four groups by quartile and then evaluated. Results: A abnormal GGT level(≥52U/L) was seen in 29(5.2%) of the 557 women. As GGT level increased, the prevalence rate of factors(body mass index≥25kg/m2, hypertension, hemoglobin≥14g/dL, total cholesterol≥220mg/dL, triglyceride≥150mg/dL, fasting plasma glucose≥110mg/dL, HDL-choles tero1<50mg/dL) except for hyperuhcemia was increased. The GGT level was correlated with age, body mass index, thglyceride and uric acid in women with fatty liver, but not in women without fatty liver. Factors independently contributing to elevated GGT level was diabetes, hyperthglycehdemia and obesity. Conclusion: The elevated, albeit normal, GGT level was strongly associated with the factors of metabolic syndrome in Korean women. Because measurement of serum GGT level is easy, reliable, and not expensive, it might have more important implication as predictive factor of metabolic syndrome.

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.

혈청 감마지티(gamma glutamyl transferase)치와 대사증후군 연관성

장미,유병욱,조용진,오정은,홍성호,조주연 순천향대학교 의학연구소 2008 Journal of Soonchunhyang Medical Science Vol.14 No.1

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최근 5년간 급성 A형 간염으로 입원한 환자들에 대한 입원 내용 분석

장재영,유병욱,조용진,오정은,홍성호,조주연 순천향대학교 의학연구소 2009 Journal of Soonchunhyang Medical Science Vol.15 No.1

Abstract Background : Due to improvements in Korea's sanitary conditions, antibody rates to the hepatitis A virus is decreasing rapidly and admission due to the disease is increasing, Patients who were admitted for hepatitis A during the last 5 years were selected and yearly differences in admission, clinical picture, medical fees, and differences according to age and gender were analyzed. Methods : Patients who were admitted to the Seoul Soonchunhyang University Hospital during the 5 year period between May of 2003 and April of 2008 and tested positive for IgM anti-HAV were selected and their medical records retrospectively analyzed. Results : 156 subjects [91 male (58%), 65 female (42%) were selected. The average age was 29.2 years (range; 21.4-37), average admission period 12.6 days (range; 12.5-1 7.7) days, and average medical fees 2,295,151 (range; 932,097-3,658,205) KRW(Korean Won), Yearly incidence rates were as follows : 10 for May, 2003 to April, 2004, 14 for May, 2004 to April, 2005, 23 for May, 2005 to April, 2006, 69 for May, 2006 to April, 2007, and 41 for May, 2007 to April, 2008, The maximum value median of AST, ALT, and bilirubin during admission was 989 IU/L, 1999 IU/L, and 5.6 mg/dL each, Each factors were all positively correlated with the patient's age. Conclusions : Recent decrease in antibody positivity of the hepatitis A virus and subsequent surge of acute hepatitis A is a cause of rising socioeconomic costs. A large scale epidemiologic research on whether HAV vaccination should be made mandatory and health insurance applied seems to be needed. Key words : Hepatitis A, Age, Medical fees, Vaccination

성인 급성 림프구성백혈병 고위험군에서 일차관해시 동종 및 자가 조혈모세포이식의 성적 비교 : 단일기관 치료경험 A Single Center Experience

이석,민우성,민창기,김동욱,이종욱,김유진,박은정,박윤희,김춘추 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.2

배경:성인 ALL에서 동종 조혈모세포이식은 전처치요법 및 이식편대백혈병 효과에 의한 효과적인 백혈병세포의 제거가 가능하다는 측면에서 활발히 시행되고 있으나 자가 조혈모세포이식과 화학요법과의 비교 연구에서는 대상환자의 다양성 등으로 인하여 상이한 결과가 보고되었다. 그러나 최근 진단당시 환자의 임상적·세포생물학적 특성 및 관해유도요법 후의 백혈병세포의 제거 속도 등을 기준으로 한 위험인자가 정의되면서 이를 근간으로 위험도에 따른 관해 후 치료방침의 결정이 타당성 있는 접근방법으로 제시되고 있고, 특히 고위험군에서의 동종 조혈모세포이식의 역할이 강조되고 있다. 방법: 성인 ALL 고위험군에서 일차 완전관해시 동종 조혈모세포이식의 역할을 규명하기 위해 최근 5년간 가톨릭의대 조혈모세포이식센터에서 ALL로 진단 후 일차 완전관해 상태에서 동종 및 자가 조혈모세포이식을 시행받고 임상적 특성과 세포면역학적 특성 및 세포유전학적 검사결과가 모두 확인 가능하였던 환자 중 고위험군에 해당된 50례를 대상으로 후향적 분석을 시행하였다. 고위험군은 진단시 연령이 30세 이상인 경우, 백혈구수가 30,000/μL 이상인 경우, 관해유도기간이 30일 이상 소요된 경우, Ph 혹은 t(4;11)이 동반된 경우 중 하나 이상의 인자를 갖고 있는 경우로 정의하였다. 결과: 대상환자의 중앙연령은 30세(15~43세)이었고, 남녀 비는 27:23이었다. FAB 분류상 L1 29례(58.0%), L2 21례(42.0%)였으며, precursor B-lineage 항원이 양성인 경우는 36례(72.0%), T-세포 항원이 양성인 경우는 9례(18.0%), 골수구계 항원이 동시에 발현된 경우는 5례(10.0%)였다. 세포유전학적 검사상 23례(46.0%)에서 불량한 염색체유형 [Ph 19례, t(4;11) 4례]이 동반되었다. 전체 환자 중 31례에서 동종 조혈모세포이식을 시행하였으며, 19례에서는 자가 조혈모세포이식이 시행되었다. 동종 및 자가 조혈모세포이식 환자군간의 임상적 특성은 양군간의 유의한 차이가 없었다. 대상환자의 중앙 추적관찰기간은 27개월(7~72개월)이었고, 전체 환자의 2년 무병생존율 및 전체생존율은 각각 59.0±7.6%, 68.2±7.1%이었다. 조혈모세포이식에 따른 치료성적을 비교한 결과 전체생존율은 동종 조혈모세포이식군 71.4±8.6%, 자가 조혈모세포이식군 62.7±12.4%로 양군간의 유의한 차이가 없었던 반면, 재발율은 동종 조혈모세포이식군에서 유의하게 낮은 빈도를 보였으며(25.8% vs 52.6%, P=0.05), 무병생존율에 있어서도 각각 70.6±9.0%, 42.1±12.2%로 동종 조혈모세포이식군에서 보다 높은 경향을 보였다(P=0.07). 이식 후 생존율에 영향을 주는 위험인자를 분석한 결과, 진단시 연령, 백혈구수, 관해유도기간에 따른 차이는 관찰되지 않았다. 다만 Ph 혹은 t(4;11)이 동반된 경우에서 무병생존율이 동종(28.5±16.0% vs 94.4±5.4%, P=0.0002) 및 자가 조혈모세포이식군(18.1±11.6% vs 80.0±17.8%, P=0.0046) 모두에서 유의하게 감소되었다. 결론: 본 연구를 통하여 일차관해시 조혈모세포이식을 시행받은 고위험군 성인 ALL에서는 관해 후 치료법으로써 동종 조혈모세포이식이 우선적으로 고려될 수 있는 치료법임을 확인할 수 있었다. 이는 추후 국내에서도 보다 장기간의 추적관찰을 통한 전향적 임상연구를 시행하여 보다 정립된 관해 후 치료방침의 결정 필요성을 제시하였다는 측면에서 임상적 의의가 있을 것으로 사료된다. Background:Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In this study, we compared allogeneic bone marrow transplantation (alloBMT) with autologous peripheral blood stem cell transplantation (autoPBSCT) using the result of the human leukocyte antigen typing (HLA). Methods:Patients were eligible if they were in first remission (CR1) and had either: adverse cytogenetics [Philadelphia chromosome (Ph), t(4;11)], age >30 years, required more than 1 induction course to achieve remission (time-to-CR1 >30 days) or presenting WBC >30,000/μL. From July 1994 to June 1999, 50 consecutive adult patients with high-risk ALL underwent HLA-matched alloBMT (n=31) or autoPBSCT (n=19) at the Catholic Hemopoietic Stem Cell Transplantation Center. Results:There were 27 males and 23 females with median age 30 (range, 15~43) years. The distribution of phenotype was as follows: L1 (n=29), L2 (n=21), precursor B (n=36), T (n=9), myeloid marker coexpression (n=5). Adverse cytogenetic abnormalities at diagnosis were shown in 23 (46.0%) cases. All pretransplant characteristics were well balanced between these two groups. Most patients were treated with total body irradiation containing regimen as part of the conditioning. With a median follow-up of 27 months in both groups, disease-free survival (DFS) and overall survival probabilities at 2 years were 59.0±7.6% and 68.2±7.1%, respectively. The relapse rates were significantly different between alloBMT and autoPBSCT groups (25.8% vs 52.6%, P=0.05). There was no significant difference in overall survival between the two groups. However, alloBMT had a trend toward better DFS (70.6±9.0% vs 42.1±12.2%, P=0.07). None of the pretransplant characteristics significantly affected outcome after transplantation, except adverse cytogenetics. Prognosis of ALL with Ph or t(4;11) was significantly poorer than that of the remaining high-risk ALL patients (P<0.01). Conclusion: We conclude that alloBMT appears to be more effective than autoPBSCT in prolonging initial CR for high-risk ALL patients. Prospective studies addressing additional clinical variables are needed to guide clinical decision making about transplant choices for adult patients with ALL. New therapeutic strategies for the management of ALL with adverse cytogenetics will be also required.

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.

국내 혈액질환 환자에서 침습성 진균 감염의 구제치료로서 Caspofungin의 효과와 안전성

최수미,박선희,이동건,최정현,유진홍,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.5

목적 : 본 연구에서는 국내 혈액질환 환자들에서 일차 항진균제를 부작용으로 인해 투여할 수 없거나, 일차 항진균제에 반응이 없는 침습성 진균 감염증의 구제치료로서 caspofungin의 효과와 이상반응에 대한 임상 경험을 소개하고, 예후인자를 분석해 보았다. 재료 및 방법 : Caspofungin은 첫날 70 mg, 이틀째 부터 50 mg을 하루 일회 투여하였고, caspofungin 종료시 그리고 종료 4주 후 반응을 평가하였다. 결과 : 총 55명의 환자가 분석에 포함되었고, 남자 32명, 여자 23명, 평균 나이는 38.2세(16-65세)였다. 기저 질환은 급성 백혈병 33명, 골수이형성 증후군 12명, 만성 백혈병 3명, 기타 7명이었다. 진균 감염은 확진 1명, 가능 5명, 추정 47명, 불확실 2명이었고, 감염 장소는 폐를 침범한 경우가 49명, 파종감염 6명이었다. 전체적으로 41.8% 환자에서 양호한 반응을 보였으며, 치료군, 치료후 기저질환의 상태, 침습성 진균 감염 진단시 호중구 감소증 여부, 스테로이드 등 면역억제제 사용 여부가 유의한 예후인자였다. 약제관련 이상반응은 14.5%에서 관찰되었고, 발열, 피부 발진, 간기능 저하 등으로 나타났다. 이중 4명에서 이상반응과 관련하여 투약을 중지하였고, 약제 중단 후 증상은 모두 호전되었다. Caspofungin 관련 신독성은 관찰되지 않았다. 결론 : Caspofungin은 국내 혈액질환 환자에서 침습성 진균 감염증의 구제치료에 효과적으로 안전하게 사용될 수 있겠다. 최근 여러 항진균제들이 개발되어 임상에 도입되고 있는 바, 항진균 작용 범위, 독성, 약역동학적 특성, 비용-효과면 등을 고려하여 환자별로 직절한 항진균제를 선택하도록 해야 할 것이다. Background : Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy. Patients with IFI who fail to standard therapy have poor prognoses. We investigated the efficacy and safety of caspofungin (CAS) in Korean adults with hematologic diseases and IFI who did not respond to the conventional antifungal therapy. Materials and Methods : Patients with IFI refractory or intolerant to standard antifungal therapy received CAS 50 mg IV daily after 70 mg loading dose on day 1. Efficacy and safety of CAS were assessed in patients who received more than one dose. Favorable response [complete (CR) or partial (PR)] was defined as significant improvement of all clinical symptoms, signs, and radiologic abnormalities. Results : From Feb. 2004 to Feb. 2005, 55 patients who met the inclusion criteria were enrolled. There were 32 male and 23 female patients with mean age of 38.2 years (range, 16-65). Underlying diseases were acute leukemia (33 cases), myelodysplastic syndrome (12 cases), chronic myelogenous leukemia (3 cases), and other hematologic diseases (7 cases). Thirty-six patients were receiving chemotherapy and 13 patients were under hematopoietic stem cell transplantation (HSCT). The number of proven, probable, possible, and indeterminate IFI cases was 1, 5, 47, and 2, respectively. Conventional amphotericin B, intravenous itraconazole, and liposomal amphotericin B were administered for average of 14.9 days prior to administering CAS. Mean duration of CAS therapy was 12.8 days (range, 1-45). Twenty-three patients (41.8%) showed favorable responses (CR : PR=8 : 15) at the end of CAS therapy. Chemotherapy group, neutropenic state, remitted state of underlying disease, and no steroid therapy were significant prognostic factors for favorable response. Eight (14.5%) patients developed drug-related adverse events such as fever, skin eruption, and hepatic dysfunction which were reversible after discontinuation of CAS. Drug-related nephrotoxicity was not observed. Conclusion : On the basis of our investigation, CAS was effective and safe as a salvage therapy of refractory IFI or as an alternative for patients intolerant to standard antifungal agents.

호중구 감소성 발열환자에게 경험적으로 투여한 Teicoplanin의 효과

이동건,임동석,최수미,박선희,유진홍,최정현,민우성,신완식,김춘추 대한감염학회 2004 감염과 화학요법 Vol.36 No.2

목적 : 호중구감소성 발열 환자에게 경험적으로 teicoplanin을 투여할 때의 효과를 알아보고자 전향적 연구를 시행하였다. 방법 : 2003년 7월부터 12월까지 가톨릭조혈모세포이식센터에 입원하여 항암치료 혹은 조혈모세포이식을 시행하고 호중구감소성 발열이 있는 환자 중 초기 항균요법에 반응이 없어 경험적 teicoplanin 투여가 필요한 49명을 대상으로 A, B 제조회사에서 제공한 teicoplanin을 무작위로 어느 한 쪽 치료군에 배정하여 투여하였다. 용량은 첫날 400㎎ 부하용량을 정맥내 bolus로 투여하고 매 24시간마다 200㎎ 유지용량을 투여하였다. 결과 : A군 27명, B군 22명이 연구에 참여하였고 대부분의 환자가 신독성이 있는 약제를 병용하고 있었다. A군 8명, B군 7명에서 그람양성균이 동정되었고, teicoplanin에 대한 내성률은 A군 22.2%, B군 28.6%로 유의한 차이는 없었다(P=1.00; 0.61<95%CI<1.95). 미생물학적 확인 감염이 있었던 환자 중 평균 53.3%에서 완치 혹은 개선의 반응이 있었고 양 군간 유의한 차이는 없었다(A군 4명 [50.0%], B군 4명 [57.1%], P=1.00; 0.29<95%CI<2.60). 미생물학적 제거율은 평균 62.5% (A군 55.6%, B군 71.4%)이었고 그 외 미생물학적 효과는 A군에서 제거 후 재발 2명(22.2%), 내성 2명(22.2%)이었고 B군에서 각각 0명(0.0%), 2명(28.6%)이었으며 양 군간 유의한 차이는 없었다(P=0.28). 발열기간(P=0.89), teicoplanin 사용기간(P=0.47) 및 전체적인 사망률(P=1.00; 0.78<95%CI<1.24)도 양 군간 유의한 차이는 없었다. 이상반응 중 신독성은 16.3% (A군 18.5%, B군 13.6%)에서 나타났고 양 군에 차이는 없었으며(P=0.72; 0.39<95%CI<3.51), 신기능 이상과 관련있는 약제를 적어도 2개 이상 병용하고 있었다. 피부발진은 A군에서 1명, B군에서 3명 발생하였다(P=0.31; 0.93<95%CI<1.34). 결론 : 호중구감소성 발열환자에게 teicoplanin을 투여하였을 때 임상적 반응률은 평균 53.3%(A군 50.5%, B군 57.1%), 미생물학적 제거율은 평균 62.5%(A군 55.6%, B군 71.4%)이었고 두 제조회사간 차이가 없었고 이상반응도 양 군간 차이가 없었다. 앞으로 국내 호중구감소증 환자에서의 teicoplanin의 적정 용량, 용법 등을 알기 위한 집단 약동학 등의 연구를 시행할 예정이다. Background : This study was done to elucidate the efficacy of teicoplanin as the empirical treatment for febrile neutropenia. Methods : Patients were randomized to two groups according to pharmaceutical company (company A or B). Total of 49 patients (A, 27; B, 22) with neutropenic fever were studied prospectively for 6 months (Jul. 2003-Dec. 2003). Patients received 400 mg i.v. once, then 200 mg i.v. once daily. Results : Groups were matched for all demographic variables. Most of the patients were concurrently receiving nephrotoxic drugs. Gram positive microorganisms were isolated in 8 patients for A and 7 patients for B. Resistance rate against teicoplanin was 22.2% in A and 28.6% in B (P=1.0; 0.61 < 95% confidence interval [Cl] < 1.95). Among the patients with microbiologically documented infection, clinical cure or improvement was seen in 4 (50%) of 8 patients for A and 4 (57.1%) of 7 patients for B (P=1.00; 0.29 <95%CI <2.60). Bacteriologic efficacy was assessed as follows; elimination in 5 (55.6%), elimination with relapse in 2 (22.2%), resistance in 2 (22.2%) out of 9 gram-positive bacteria for A and 5 (51.4%), 0 (0.0%), 2 (28.6%) out of 7 bacteria for B, respectively (P=Q.28). There were no significant differences in duration of fever, duration of use of teicoplanin, and overall mortality. The incidence of nephrotoxicity and ototoxicity was not significant. Conclusion : For using teicoplanin as the empirical therapy for febrile neutropenia, the rate of clinical, microbiological response, and nephrotoxicity was 53.3%, 62.5%, and 16.3% respectively with no significant differences between the 2 preparations of teicoplanin. Supplementary evaluation on the adequate dose and duration of teicoplanin may be required.