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.

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.

소아 신경심장성 실신환자에서 비정상적 심박수 프랙탈 상관에 대한 연구

김경용,주은영,염명걸,오재원,김창렬,김남수,이철범,노정일 대한소아과학회 2002 小兒科 Vol.45 No.9

中部 急傾斜 森林小流域內의 地中水變化

金載水 충북대학교 농업과학기술연구소 1993 農業科學硏究 Vol.11 No.1

A small forested catchment with rather steep topography is selected to study the hydrological process and its inner relationship to its topographic factors in the middle part of Korea. The main objective of this study is to investigate the effects of topographical factors and the extent to which the subsurface flow is influenced in a whole catchment. To evaluate the effects of vegetations and topography, it is necessary to make clear the compo-nents of hillside hydrological process, especially variations of subsurface flow in a catchment due to rainfall inflow. Measurement of runoff rates are carried out in the wolak experimental forest of Chungbuk National University near Chungju lake. Mathematical modeling is simultaneously conducted. The catchment area is 3.5 ha of which 0.5 ha is covered with rock surface, 0.7 ha with more than 50cm in soil depth, 2.3 ha with shallow soil depth. Its mean slope gradient is 28 degrees. The hillslope subsurface flow shows significant contribution to recession hydrograph of Wolak catchment discharges based on the mathematical model. Even the steep catchment needs a proper management to produce a good water yield.

과학자에 대한 초등학교 일반 학생과 과학 영재반 학생의 인식 비교 분석

김소형,박재일,정진수,이혜정,권용주,박국태 한국초등과학교육학회 2005 초등과학교육 Vol.24 No.1

This study was designed to compare the understanding of ordinary elementary school students and scientifically gifted students about scientists. 473 fourth, fifth, and sixth graders in ordinary elementary schools and 40 students attending scientific educational institutions for the gifted were studied with the help of questionnaires and interviews. The survey showed that there were no significant differences between the two subject groups in relation to the external images of scientists. The subjects turned out to have four fixed external images. The scientifically gifted students had a better understanding of the internal images of scientists than ordinary elementary school students. Both the subject groups turned out to be influenced by the press media and off-campus education, thinking that scientists served as inventors producing something useful in daily life rather than as researchers studying natural phenomena or laws. It was found out that both groups admired Edison. The ordinary students respected Einstein and Jang Yeong-Sil whereas the scientifically gifted students respected Curie, Jang Yeong-Sil, and Nobel. The subjects admired them because of their achievements instead of their backgrounds or individual characteristics.

林內사면에서의 根系흡수모델

金載水 충북대학교 농업과학기술연구소 1991 農業科學硏究 Vol.9 No.1

Root water uptake is a main source of transpiration in a densely forested slope as subsurface flow mostly occurs in a unsaturated condition. Considering soil-plant-atmosphere continuum concept, a sink term was introduced, defined by soil depth, root distribution and soil moisture content, to combine with a physically based model in a unsaturated soil mass. And it was used to explain the root uptake using a finite differential method and tested with a sequential field data. The sink term represented root and vertical soil water distribution and as the soil moisture decreased, the unsaturated conductivity also decreased and it meant the available root density did not reflect a real root density, but the root uptake was designed to reflect the effective distribution of root density. Calculated soil water tension was well fitted to the observed data through the physically based model. However, a dried zone could not be explained around the 100 cm soil depth after a dry season. In spite of the relatively small number of roots found deep in the soil under forest stands the soil was often dried to the extremly dry condition.

순수 에탄올 경화요법을 통한 경부 및 견부 임파관종 치험 1 예

김동익,허승,이병붕,도영수,이순정,박제훈 대한혈관외과학회 1998 Vascular Specialist International Vol.14 No.2

Cystic lymphangioma is congenital anomaly originated from the lymphatic system. It occurs at head and neck area mainly. But its unusual location is possible. Treatment of cystic lymphangioma was surgical removal, but recently nonsurgical approach were studied, including sclerotherapy. Bleomycin, OK-432, and absolute ethanol were used as sclerotherapeutic agents. A 31 year-old female patient was treated by sclerotherapy with absolute ethanol for a cystic lymphangioma in neck and shoulder region. She had detected a mass in neck and shoulder region 8 years ago and had been done excisional surgery twice, 7 years and 4 years ago respectively. She had a 5 ×4×12 cm sized mass, that was recurred, in her neck and shoulder region. She had sclerotherapy twice in a 3-month interval. Its size decreased 2 cm in diameter from 12 cm.

보조 리간드가 결합한 Cr(Ⅲ)-네자리 거대고리 착물들의 합성 및 특성

김구철,한충훈,윤정수,변종철 濟州大學校 基礎科學硏究所 2003 基礎科學硏究 Vol.16 No.1

cis-(5.5.7.12.12.14-hexamethyl-1.4.8.11-tetraazacyclotetradecane)dichloro chromium(Ⅲ) chloride{cis-[Cr([14]-decane)(Cl)₂]Cl}를 출발 물질로 하여 보조 리간드{L_(a)=malonate (mal^(2-). acetylacetonate (acac^(-). benzoate (bz^(-). p-chlorobenzoate(cbz^(-). chloroacetate(ca^(-))}를 결합시킨 착물들을 합성하였다. 이들 Cr(Ⅲ) 착물들은 6배위 착물을 형성한다. cis-[Cr([14]-decane)(acac)](ClO₄)₂ 결정은 a=20.021(1)Å. b=30.112(1)Å. c=12.708Å. α=90˚. β=127.112(1)˚. γ=90˚. V=6101.1(4)ų 및 Z=8의 cell constant를 갖고 있는 C_(2/c) 공간군이며, 단사결정체이다. Cr^(3+) 이온 주위에 4개의 amine 질소 원자와 bidentate로 결합한 acetyacetonate의 2개 산소 원자가 capped square pyramid 구조를 형성하면서 6배위 기하구조를 갖는다. cis-[Cr(tetb)(cbz)₂]ClO₄ 결정은 a=12.093(1)Å. b=20.358(1)Å. c=28.852Å. α=90˚. β=90˚. γ=90˚. V=7103.1(7)ų 및 Z=8의 cell constant를 갖고 있는 P_(bca) 공간군이며, 사방정계 결정체이다. Cr^(3+) 이온 주위에 4개의 amine 질소원자와 2개의 p-chlorobenzoate에서 각각 1개 산소원자가 capped square pyramid 구조를 형성하면서 6배위 기하구조를 갖는다. New chromium(Ⅲ) complexes are synthesized from the starting material of cis-(5.5.7.12.12.14-hexamethyl-1.4.8.11-tetraazacyclotetradecane)dichloro chromium(Ⅲ) chloride{cis-[Cr([14]-decane)(Cl)₂]Cl} with auxiliary ligands {L_(a)=malonate (mal^(2-). acetylacetonate (acac^(-). benzoate (bz^(-). p-chlorobenzoate(cbz^(-). chloroacetate(ca^(-))}. The compounds are a six-coordinated chromium(Ⅲ) complexes. The crystal of cis-[Cr([14]-decane)(acac)](ClO₄)₂ is monoclinic. space group C_(2/c). with cell constant a=20.021(1)Å. b=30.112(1)Å. c=12.708Å. α=90˚. β=127.112(1)˚. γ=90˚. V=6101.1(4)ų. and Z=8. The hexacoordination geometry around Cr^(3+) ion is a capped square pyramid made up of four amine nitrogens and bidentate acetyacetonate two oxygens. The crystal of cis-[Cr(tetb)(cbz)₂]ClO₄ is orthorhombic. space group P_(bca) with cell constant a=12.093(1)Å. b=20.358(1)Å. c=28.852Å. α=90˚. β=90˚. γ=90˚. V=7103.1(7)ų. and Z=8. The hexacoordination geometry around Cr^(3+) ion is a capped square pyramid made up of four amine nitrogens and two oxygens of two p-chlorobenzoate.

産褥期 感染 誘發 細菌의 生育을 억제하는 韓藥材 探索에 關한 硏究

임재연,성연수,김희진,이태균 동국대학교 한의학연구소 1997 東國韓醫學硏究所論文集 Vol.6 No.1

産褥期 感染이란 分娩後 生殖器의 細菌에 의한 感染을 意味하며, 産後 體溫上昇의 大部分은 骨盤感染에 의한 것으로 産褥期 感染의 重要한 指漂가 된다. 한의학에서 産後發熱의 病因病耭는 주로 邪毒感染, 血瘀, 外感, 血虛 등으로 보았으며, 치료는 一般的으로 産後疾患에는 處證이 많아 發表攻裏를 過度하게 하지 않고, 氣血과 營衛의 調和에 위주로 하나, 外感과 裏實證을 疏怒히 하면 안된다. 따라서 産後發熱을 惹起하는 各種 原因菌에 對한 客觀的인 抑制效果의 檢證은 産後發熱의 治療率을 높이는데 중요하다. 그 결과 산욕기감염을 유발하는 各種 細菌에 對해 黃連, 烏梅, 五味子 등의 水溶性 抽出物이 杭菌活性이 相對的으로 좋은 效果를 보였다. 따라서 産褥期 感染의 治療에 이들 韓藥材를 이용하면 보다 效果的일 것으로 생각된다. Deparment of Oriental Medicine, Graduate School of Dongguk University, Major in Oriental Ob & Gy. Various kinds of medicinal herbs and prescribed herb medicines which have usually been used for treatment of reducing fever, purging intense heat, and detoxication were secreened for antibacterial activity against Proteus vulgaris, S. aureus, and E. faecalis which causing puerperal infection. Minimal inhibitory concentrations of water- and ethanol-soluble extracts of Hwangyon(C. japonica), Omae(P. mume), and Omiza(S. chinensis) were determined and using thin-layer chromatography the extracts of Hwangyon and Omiza were separated. The results obtained were as follows: 1. The water-soluble extracts of Keumeunhwa(L. japonica), Chiza(G. jasminoides), Hwangyon(C. japonica), Dansam(S. miltiorrhiza), Omae(P. mume) and Omiza(S. chinensis) showed antibacterial activities against P. vulgaris ; among them, the extracts of Hwangyon, Omae, and Omiza showed high antibacterial activities. The water-soluble extracts of Keumeunhwa(L. japonica), Hwangyon(C. japonica), Hwangkeum(S. baicalensis), Hwangbaek(P. amurense), Dansam(S. miltiorrhiza), Daehwang(R. coreanum), Omae(P. mume), Omiza(S, chinensis), Gingseng(P. ginseng), and Gamcho(G. uralensis) showed antibacterial activities against S. aureus ; among them, the extracts of Hwangyon and Omiza showed high antibacterial activities. The water-soluble extracts of Banggi(C. trilobus), Daehwang(R. coreanum), Omae(P. mume), Omiza(S. chinensis), and Gamcho(G. uralensis) inhibited the cell growth of E. faecalis ; among them, Omae and 0miza showed high antibacterial activities. The extract of Hwangyon(C. japonica) and Omae(P. mume) showed no inhibition against E. coli. However, the extract of Omiza(S. chinensis) inhibited cell growth of both E. coli and B. subtilis. 2. The water- and ethanol-soluble extract of Hwangyon(C. japonica) showed antibacterial activities against P. vulgaries and S. aureus, those of Omae(P. mume) against P. vulgaris and E. faecalis, and those of Omize(S. chinensis) against all species tested, P. vulgaris, S. aureus, and E. faecalis. With the exception that ethanol-soluble extract of Hwangyon(C. japonica) showed much higher antibacterial activity against S. aureus than water-soluble one, antibacterial activities of both water- and ethanol-soluble ones were similar to each of other two medicinal herbs. 3.When the prescribed herb medicines were tested, Sambohwan showed antibacterial activities against P. vulgaris and S. aureus. No prescribed herb medicine inhibited the cell growth of E. faecalis. 4. Minimal inhibitory concentrations(MICs) of both water- and ethanol-soluble extracts of Hwangyon (C. japonica), Omae(P. mume), and Omiza (S. chinensis) against P. vulgaris were 2.5㎎/㎖, 10㎎/㎖, and 20㎎/㎖, respectively. Those of both Hwangyon (C. japonica) and Omiza(S. chinensis) against S. aureus were 1.25㎎/㎖ and 10㎎/㎖, respectively. MICs of water-soluble extracts of Omae(P. mume) and Omiza(S. chinensis) aganist E. faecalis were 2.5㎎/㎖ and 5㎎/㎖, and those of ethanol-soluble extracts were 5㎎/㎖ and 10㎎/㎖, respectively. Except for those of E. faecalis, the cell growth of P. vulgaris and S. aureus were inhibited by much lower concentration of ethanol-soluble extracts used. As a result, the antibacterial compounds against P. vulgaris, S. aureus, and E. aecalis are contained in the extracts of Hwangyon(C, japonica), 0mae(P. mume), 0miza(S. chinensis), the prescribed herb medicine, Sambohwan, and might be used for treatment of puerperal infection. Further study should be carried out to identify which compounds affect the cell growth inhibition of P. vulgaris, S. aureus, and E. faecalis.