Purge & Trap-GC를 이용한 의약품 필름코팅 정제 중 잔류용제에 관한 연구

장준식,이명자,소유섭,문춘선,이주헌,박희라,김진숙,강경모,이선옥,방성연,유미자,유문균,금오성,이병욱 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

의약품은 약물을 생체에 적풋하기 위하여 유효성분의 효과가 언제나 일정하게 확보되고 사응에 편리하도록 만들어지는 것이므로 유효썽분 이외에 약효에 영향을 주지 않는 성분이 첨가되는 경운가 많다. 이 때 사용되는 용매들은 제피의 광택 및 건쪼시간의 단축 등을 위하여 휘발점이 낮을 용매들이 주로 사용되어진다. 본 연구는 의약품 필름코팅정제 중 잔류용매 4종(chlorofonr benzen, trichloro ethylen, 1,4-dioxane)에 대한 변형된 pirge & trap-GC 장치를 이용한 동시분석방법을 개발하였으며, 각 표준품의 RSD 값은 chloroform 3.03%, benzen 3.17%, trichloroethylen 3.69% and 1,4-dioxane 3.41%였다. 또한 시중 유통중인 의약품 50종에 대하여 잔류웅매 양을 측정하였으며, 검출되는 잔류용매는 한 건도 없었다. This study nras carried out to develope the analytical method for the mixture of chlorefonn, benzen, trichloroethylen and 1,4-dioxane simultaneously and determine the remainingorgauic solvents in coating tablets by Purge & Trap-GC. The results were as follouFs ; 1. Chloroform, benzen, trio:tloroethylen and 1,4-dioxane separated by tenax #5 trap by HP-624GC column by terrlperature programming. The peaks were separated completely at retentiontime of 6.88min for chloroform, 8.21min for benzen, 10.38miu for trichloroethylen and 11.95minfor 1,4-dioxane. 2. Standard RSD were individually chloroform 3.03%, benzen 3.17%, trichloroethylen 3.69%and 1,4-diorane 3.41%. 3. 60 samples were not detrcted chloroform, benzen, trichloroethylen and 1,4-dioxane.

동종 조혈모세포이식 후 발생한 치명적 홍역 폐렴 1예

백창렬,이동건,최정현,정현화,조유경,박훈준,이승훈,박윤희,이교영,민우성,김춘추,신완식 대한감염학회 2001 감염 Vol.33 No.4

As a result of the enlarging pool of unvaccinated children and young adults, there has been an increase in measles in our countries. In these situation, it has been reported that measles associated pneumoinia is easily complicated with fatal respiratory failure, espycially in immunocompromised patients. Herein we report the case of lethal measles pneumonia after allogenic hematopoietic stem cell transplantation in adults proven by autopsy. Recently, one case of measles was encountered in 39-year-old female patients after allogenic bone marrow transplanted case (chronic myelogenous leukemia), who progressed into interstitial pneumonia pattern, despite treatment including antibiotics, immunoglobulin. The patient died of giant cell pneumonia compatible with that of measles which was comfirmed in the section of necropsy lung specimen. (Korean J Infect Dis 33:301∼309, 2001)

동종 조혈모세포이식 후 폐합병증 : 미만성 폐침윤에서 기관지경의 유용성

민창기,엄기성,이동건,김동욱,이종욱,민우성,김춘추,정정임,김태연,송정섭 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.1

배경:동종 조혈모세포이식을 받고 백혈구수가 회복한 이후의 폐합병증은 대부분 국소적 폐렴이 아닌 미만성의 폐침윤(diffuse pulmonary infiltrate) 소견을 보이고 이식 후 불완전한 면역 재구성 또는 이식편대 숙주질환(graft-versus-host disease; GVHD) 등과 관련된다고 알려져 있다. 원인은 세균보다는 바이러스(주로 cytomegalovirus; CMV), Pneumocytis carinii (PC) 등이며 원인을 규명할 수 없는 특발성의 경우도 상당수를 차지하고 있으나 아직 국내에서는 자세히 보고된바 없다. 저자들은 본 센터에서 동종 조혈모세포이식 후 발생한 폐합병증의 진단 및 치료성적을 보고하고자한다. 방법:1997년 1월부터 1999년 8월까지 본 센터에서 동종 조혈모세포이식을 받은 321예의 환자 중에 방사선학적으로 미만성 폐침윤을 보여 기관지경 검사를 받은 환자 35예를 대상으로 하였으며 5예의 환자는 임상적인 경과의 변화로 기관지경 검사를 2회 실시 받았다. 환자들의 임상적 특성, 영상학적 검사 그리고 기관지경 검사로 기관지 폐포세척술을 실시하여 얻은 가검물에서 원인 미생물을 배양하거나 폐조직 생검을 통하여 진단하였다. 각 환자에서 진단에 따른 치료 및 반응을 관찰하였다. 결과:1) 환자연령의 중앙치는 31 (16~40)세, 이식 후 미만성 폐침윤이 발생하기까지 기간의 중앙치는 162 (55~965)일 이었다. 이식 당시 질환은 CML 16예, AML 10예, ALL 5예, NHL 2예, MDS 1예 그리고 CLL 1예 이었으며 35예 중 11예에서 2차 관해 이상의 진행된 질환을 갖고 있었다. 35예 중 비혈연간 또는 혈연간 HLA 부분일치 동종 조혈모세포이식 환자는 12예였고, 전처치에 전신 방사선조사를 받은 환자가 27예 항암제만 받은 환자는 8예 이었다. 2) GVHD 예방 약제로는 cyclosporin+methotrexate (n=26) 또는 tacrolimus+methotrexate (n=9) 조합을 사용하였다. 감염 예방으로 경구로 trimethoprim-sulfamethoxazole, acyclovir을 투여를 받은 환자는 9예(25.7%) 이었다. II도 이상의 급성 GVHD를 가진 환자가 12예(34.3%) 이었고, 27예(77.1%)에서 만성 GVHD를 갖고 있었다. 3) 기관지 폐포세척술의 가검물 배양 결과 미만성 폐침윤의 원인 미생물로는 CMV 8예, PC 6예, 두 미생물의 혼합감염 10예, 폐렴구균 1예, 그리고 Mycobacterium tuberculosis 1예 이었고, 나머지 14예(35%)에서는 원인균이 동정되지 않았다. 경기관지 폐조직생검은 19예 중 3예(15.8%)에서 진단적 가치가 있었다. 4) 기관지경을 시행한 40예 중 8예(20%)에서 폐포세척술 검체의 배양 및 경기관지 폐생검의 결과에 따라 치료를 하였음에도 불구하고 호전되지 않았다. 5) 35예 중 9예의 환자가 사망하였으며 이중 5예는 폐합병증으로 사망하였고 나머지 4예는 재발 또는 이식편대숙주질환에 의해 사망하였다. 폐합병증으로 사망한 환자의 원인으로는 CMV 1예, PC 1예, 혼합감염 1예, 그리고 원인 불명의 폐합병증이 2예 있었다. 결론:동종 조혈모세포이식 후 발생한 미만성의 폐침윤의 주된 원인은 CMV, PC 등이며 단독 감염보다는 혼합 감염의 형태를 보였다. 기관지경 검사 및 폐포세척술은 미만성 폐침윤의 진단에 유용하며 안전한 시술로 사료된다. 폐합병증은 주로 만성 GVHD 환자에서 출현하였으며 원인이 밝혀지지 않은 경우에 면역억제 치료가 효과적이었다. Background:Diffuse pulmonary infiltrates (DPI) after a neutropenic phase following allogeneic stem cell transplantation (allo-SCT) are common and include various causes. Multiple factors are thought to contribute to these pulmonary complications, including the graft-versus-host disease (GVHD), incomplete immune reconstruction and infections. This study was undertaken to determine the results of fiberoptic bronchoscopy (FOB) in patients with DPI after allo-SCT. Methods:Three hundreds twenty one patients underwent allo-SCT from January 1997 through August 1999 at Catholic Hemopoietic Stem Cell Transplantation Center. Out of 321 patients, 40 FOBs were performed in 35 patients who were aged 16 to 40 years (median age 31 years). In all cases, bronchoalveolar lavage (BAL) was achieved. Transbronchial forceps biopsy (TBFB) was also carried out in 47.5% (19/40). Clinical, radiologic, pulmonary function, microbiological and pathologic tests were reviewed. Results: 1)The underlying diseases were predominantly chronic myeloid leukemia and acute leukemia (31/35, 88.5%). Median time to FOB following SCT was 162 days (range, 55-965). The patients with acute GVHD more than grade II were 34.3% (12/35) and those with chronic GVHD were 77.1% (27/35). 3) An etiological diagnosis could be obtained in 26/40 (65%) of cases; mixed infection of cytomegalovirus (CMV) and Pneumocystis carinii (PC) was the most common finding (10/40, 25%), CMV and PC were isolated in BAL in 8/40 and 6/40 respectively, Pneumococci in one and Mycobacterium tuberculosis in one. In 14 procedures (35%), the results were negative. TBFB were valuable for diagnosis for only 3 out of 19 patients. There was one minor bleeding following FOB and TBFB. 4) Thirty two cases (80%) of FOB improved after treatment according to etiology. The patients with unknown etiology showed a good response to steroid (11/14, 78.6%). 5) Overall mortality in patients with DPI was 9/35 (25.7%). Five episodes of DPI were to refractory to treatment and were causes of death. Five causes consisted of 1 CMV, 1 PC, 1 mixed infection, and 2 unknown etiologies. Conclusion:FOB is a safe and valuable procedure for the evaluation of DPI after allo-SCT, which were commonly associated with GVHD, CMV and PC. The mixed infections were more predominant than those due to single isolated organism. Steroid was effective for patients with DPI in whom causative organisms were not able to be identified.

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.

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.

동종 조혈모세포이식 후 발생한 크립토콕쿠스 척추염 1예

고윤호,임동준,이성수,조유경,이동건,최정현,김유진,민창기,김동욱,박정미,김춘추,신완식 대한감염학회 2001 감염 Vol.33 No.4

Skeletal cryptococcosis is an uncommon infection. Cryptococcus is a common cause of meningitis and infects 7∼10% of patients with AIDS. As well as AIDS, the infection may be seen in association with leukemia, lymphoma, Hodgkin's disease, sarcoidosis, tuberculosis and diabetes, also in patients on steroid medication. But there is no case report of skeletal cryptococcosis following allogeneic hematopoietic stem cell transplantation. A 40-year-old woman was admitted to the hospital because of low back pain. She had chronic myelogenous leukemia for 2 years and underwent allogeneic hematopoietic stem cell transplantation 8 months ago. She have been treated with steroid and cyclosporine orally because of chronic graft versus host disease. On examination she was afebrile and had posterior lower lumbar tenderness. But, she had no reduced strength of low extremities. Open biopsy was underwent. Histology demonstrated budding, round-to-oval, refractile yeast-like organisms within debris. The results of a lumbar puncture were unremarkable and cerebrospinal fluid culture failed to grow bacteria and yeast. The patient was treated with amphotericin B (1 gram) and AmBisome□ (2.8 gram) over 6 weeks. Three months after cessation of therapy, the patient was doing well.(Korean J Infect Dis 33:298∼301, 2001)

단위 역률로 동작하는 3상 PWM AC-DC BOOST콘버어터에 관한 연구

천창근(Chang-Gun Chun),박성준(Sung-Jun Park),권순재(Soon-Jae Kwon),김철우(Chul-U Kim) 대한전기학회 1994 대한전기학회 학술대회 논문집 Vol.1994 No.7

Neutron 빔조사 담배 및 벼식물체의 특성

배창휴(Chang-Hyu Bae),채종서(Jong-Seo Chai),김재홍(Jae-Hong Kim),양태건(Tae-Gun Yang),류재일(Jae-Il Ryu),이효연(Hyo-Yeon Lee),양덕춘(Deok-Chun Yang) 한국자원식물학회 2005 한국자원식물학회지 Vol.18 No.3

재배종담배(Nicotiana tabacum L. cv.), 야생종담배 (N. plumbaginifolia)와 벼종자(Orya sativa L, cv.)에 neutron빔을 각각 조사(irradiation)하여 발아, 식물체의 생장과 DNA의 변이에 미치는 영향을 검토하였다. 담배종자와 벼종자에 90, 180, 270, 360, 450, 540 Gy까지 조사로 발아율은 크게 감소하지 않았고, 생장에 있어 유의적인 차이는 없었다. 그러나 담배식물체에서 총 200개체 중 71개체(약 36%)가 잎에서 형태 이상을 나타내었다. 또한 줄기색 변이체, 엽색변이체, 화형변이체를 유도하였다. 이 결과는 neutron빔이 유용한 돌연변이원으로서 가능성이 있음을 시사해 준다. Neutron빔을 조사한 후 생장한 담배식물체의 잎에 대하여 총 34개의 primer를 이용하여 RAPD 분석한 결과 20개의 primer에서 총 104개의 DNA 단편이 증폭되었고, 중성자 빔조사처리구에서만 출현하는 DNA 단편은 나타나지 않았다. Effects of neutron beam irradiation on seed germination, growth and RAPD pattern of tobacco (Nicotiana tabacum L. cv.; N. plumbaginifolia) and rice (Orya sativa L. cv.) plants were estimated. Seed germination rate was not significantly changed by the neutron beam treatment in both tobacco and rice seeds. And there was no significant differance in growth of the plants by the neutron beam treatment. Interestingly, however, some of morphological changes, including leaf shape (about 36%), stem color and leaf color were observed in neutron beam treated tobacco plants. In addition, abnormal flower in petal was observed in the neutron beam treated plant. This results indicate that neutron beam is able to use as an effective mutagen in plant mutations. Scorable products from 20 primers were obtained by RAPD analysis in the leaves of the beam irradiated tobacco plants and most of the plants showed the similar band patterns.

골수이식 후 발생한 종격동 결핵성 농양 및 림프절염 1예

김창욱,임동준,장데레사,손태서,이동건,김미영,최정현,신완식,김춘추 대한감염학회 1999 감염 Vol.31 No.3

Analysis of Colonoscopy Quality in Clinical Practices of Korea: Cohort Study of Patients Referred to Tertiary Hospital after Colonoscopy Examinations

( Chang Gyun Chun ),( Hyun Gun Kim ),( Seong Ran Jeon ),( Bong Min Ko ),( Byung Hoo Lee ),( Jin Oh Kim ) 대한장연구학회 2013 Intestinal Research Vol.11 No.3

Background/Aims: Although the quality of colonoscopy is considered important to improve screening efficacy, there is little evidence and few statistical reports which properly reflects the colonoscopy quality of clinical practices in Korea. We aimed to investigate the quality indicators of colonoscopy performing in clinical practice. Methods: We analyzed the computerized photo-documentation files of patients who were transferred to tertiary academic hospital from private clinics or primary and secondary hospitals from January 2012 to October 2012. Quality indicators including cecal intubation rate, withdrawal time, bowel preparation status, colonoscopy report form were analyzed. Bowel preparation was assessed by 4 steps on the preparation scale (excellent, good, fair, poor). Results: A total of 198 patients (134 male, 64 female) were enrolled and analyzed. Cecal intubation rate was 91.4% (181/198) and photo-documentation of appendiceal orifice and ileocecal valve was achieved as 84.3% (167/198) and 71.7% (142/198), relatively. Overall, 83.3% of cases were adequate bowel preparation state (excellent 52%, good 31.3%). Withdrawal time could be estimated at 94.4% (187/198) of cases and mean withdrawal time of diagonostic colonoscopy (n=165) was 8.6 minutes. However, the rate of cases which withdrawal time was more than 6 minutes was 69.7% (115/165). Total of 30 institution`s colonoscopy report forms were analyzed and among nearly half enrolled institutions (46.6%, 14/30) were just recording patient`s information and colonoscopic diagnosis. Conclusions: Considerable portion of colonoscopy examination in the primary clinical practice has been performed with low procedure quality. We thus need careful attention to maintain the quality of colonoscopy in daily practice routines. (Intest Res 2013;11:198-203)