Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

치과 기공사들에게서 나타나는 호흡기 증상과 이의 관련 요인

김웅철,오세윤,김지환,김진완,이준석,이가영,이세훈,유진호,김태석 高麗大學校 倂設 保健大學 保健科學硏究所 2001 保健科學論集 Vol.27 No.1

This study was carried out to investigate subjective respiratory symptoms and their attributable factors in Korean dental laboratory technicians. A questionnaire was mailed to randomly selected 1,900 dental laboratory technicians. Among them, 1,344 dental technicians completed the questionnaires and returmned them. Validity and reliability tests on the questionnaires were carried out before the main survey. To investigate risk factors on respiratory subjective symptoms, we performed analysis on distribution of characteristics, and then investigated univariate analysis and multiple logistic regression analysis. The prevalence rate of wheezing, cough and phlegm, and dyspnea was 4.8%, 33.9%, 54.9%, respectively. Statistically significant factors inducing subjective respiratory symptoms by multiple logistic regression analysis were sex, smoking, exercise, health examination, work hours a day, investment gas, investment dust, metal fume, resin vapor, and asbestos dust. Considering the results above, it seems that most subjective respiratory symptoms are related with health habits and occupational environmental-related factors. The result, consideration in mind, suggest that health promotion programs for smoking cessation, regular health examination, and physical exercise in health habit, and improvement on casting and resin work in dental technological environment be necessary.

성인 지역사회 폐렴의 원인 미생물에 대한 전향적 다기관 연구 : Legionella, Leptospira, Hantaan virus and Orientia tsutsugamushi

김민자,정희진,손장욱,심희선,박대원,박승철,우준희,강재명,김유겸,신완식,김양리,이환종,김지희 대한감염학회 2001 감염 Vol.33 No.1

Background : Despite rigorous investigations, the etiology of community-acquired pneumonia remains unknown in about 50% of hospitalized patients. The diagnosis of the etiological agent is becoming more challenging and more critical as number of newer pathogens have been recognized in recent years. In the 3-year period prospective study we investigated adult patients with community-acquired pneumonia for Legionella, Leptospira, Hantaan virus and Orientia tsutsugamushi as potential etiologic agents. Methods : A prospective multicenter study was performed from May 1997 to April 2000. A total of 431 patients with community-acquired pneumonia under the inclusion criteria were examined for specific microbial diagnosis; sputum culture and PCR, and serologic teats including indirect immunofluorescence antibody (IFA) test for Legionella, and hemagglutination tests for Leptosoira, Hantaan virus and O. tsutsugamushi. Etiologic diagnosis was determined on the basis of the review of case record forms and specific laboratory diagnostic criteria. Results : During the study period a total of 385 sputum and 283 serum samples were examined. Legionella pneumonia was diagnosed in 2.3% (10/431) of the cases examined : 1.4% cases with PCR-positive (5/367) and 2.1% with positive IFA test (6/283). Leptospirosis and scrub typhus were diagnosed in 0.4% (1/252) and 2.0% (5/252), respectively. All 5 cases with scrub typhus occurred in late fall, and rash or eschar was not found. None of cases was Hantaan virus infection. Conclusion : The results suggest that Legionella, Leptospira, and O. tsutsugamushi should be considered in the etiologic diagnosis and empirical antibiotic therapy of community-acquired pneumonia. (Korean J Infect Dis 32:24∼31, 2001)

조혈모세포이식 후 발생한 주폐포자층 폐렴에 대한 고찰

주지현,최정현,이동건,백지연,고윤호,이혜정,김세희,신호진,박윤희,박지영,김유진,신완식,김춘추 대한감염학회 2001 감염 Vol.33 No.4

Background : Pneumocytitis cainii pneumonia (PCP) can occur in immunocompromised hosts especially such as AIDS or cancer patients. Although recent research had focused on PCP in AIDS patients, few studies have described the clinical presentations of PCP in recipients of stem cell transplantation (SCT). We evaluated the clinical manifestations of PCP in SCT patients admitted at St. Mary's hospital, Seoul, Korea. Methods : The medical records of 17 PCP patients undergoing SCT between Feb. 1998 and Feb. 2000 were reviewed. The diagnosis of PCP was confirmed through the demonstration of Pneumocytitis cainii via either cytology of brochoalveolar lavage (BAL) or histological technique of lung biopsy. CMV disease and CMV infection were confirmed by BAL culture and antigenemia respectively . Results : Seventeen patients were all recipients of allogeneic SCT and 7 of 17 patients were performed non-sibling SCT. Patients presented with symptoms including brief period (4 ∼23 days) of fever (76%), dyspnea (70%), cough (64%), and signs such as rare(58.8%), Sixteen patients (94%) had been receiving immunosuppressive agent such as cyclosporine A (64%) or Fk506 (35%) without PCP prophylaxis. Eleven patients (64%) were treated with corticosteroid with mean dose of 16 mg/day prednisolone and mean duration of 4.6 months after post-SCT period. Twelve patients were co-infected with CMV. Another co-infected miCroorganisms were Pseudomonas aeruginosa, Mycobacterium tuberculosis, herpes simplex virus, parainfluenza virus, Average duration of treatment with trimethoprim-sulfamethoxazole (TMP/SMX) was 21 ±9 days. Four patients died, and three of them were related with PCP. Conclusion : PCP developed frequently in patients who were taking immunosuppressive drug due to graft versus host disease or were not taking TMP/SMX prophylaxis. High risk patients showing fever, cough, or dyspnea should be considered to take early bronchoscopic intervention for detection of PCP. When treat for PCP, it also be considered to the possibility of coinfection such as CMV. (Korean J Infect Dis 33:273∼279, 2001)

악안면 골격 형태에 따른 교합평면각의 변화에 관한 두부 방사선학적 연구

오세윤,김웅철,김지환,이준석,김진완,유진호,김태석 高麗大學校 倂設 保健大學 保健科學硏究所 1999 保健科學論集 Vol.25 No.1

A correlation analysis was made to understand the interaction between the growth patterns of some craniofacial skeletal components and occlusal plane inclination. 5 angular measurements(S.a. Ar.a, Go.a, UGo.a, LGo.a), 6 linear measurements(ACBL, PCBL, RH. MBL. AFH. PFH) and OP/SN. obtained from 83 cephalometric tracing records, were selected and the relationship between the occlusal plane angle and those measurements were analyzed statistically. Ramus Height(r=-0.55), Posterior Facial Height(r=-0.41), were found to be negatively related with Occlusal Plane angle, while Lower Gonial angle(r= 0.35), Saddle angle(r= 0.24) were found to be positively related with Occlusal Plane angle(p(0.05). The results obtained from the above analysis were further assessed with stepwise regression analysis, using Occlusal Plane angle as a dependant variable, and RH, LGo.a and S.a as explanatory variables. Stepwise regression analysis revealed that all the explanatory variables were found to be significant.(p<0.05) [OP/SN] = -8.74-0.33(RH)+0.23(S.a)+0.20(LGo.a). (R²=0.44). This stepwise regression analysis explains, to some extent, the relationship between the growth patterns of some craniofacial skeletal components and the occlusal plane inclination. 1. The inclination of Occlusal Plane angle is noticeably related with the growth patterns of some craniofacial skeletal components, i.e. RH, PFH, Saddle angle and Lower Gonial angle 2. In high Occlusal Plane angle, the Ram us Height tends to be shorter, and the Saddle angle and Lower Gonial angle tend to be obtuse.

대량의 각혈로 사망한 장티푸스 1예

한상우,유진홍,권순석,김성훈,박지찬,홍은정,최경성,박용완,장준희,안지원,박유경,강지영,박상미,신완식 대한감염학회 2004 감염과 화학요법 Vol.36 No.5

We experienced a 25 year-old male patient with typhoid fever complicated with massive hemoptysis. Pulmonary complication in typhoid fever is very rare and to our knowledge, there has been no report of hemoptysis as a main cause of death with this disease. We herein report a rare case of typhoid fever.

우리나라 사람면역결핍바이러스(Human Immunodeficiency Virus) 감염환자에서 발병한 악성종양

최평균,송진수,조재현,김성한,박경화,방지환,박완범,김홍빈,김동완,김태유,허대석,오명돈,김남중,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

Background : Since highly active antiretroviral therapy has lengthened the life span of individuals infected with human immunodeficiency virus (HIV), the importance of malignancy associated with HIV has been increased. The relative frequencies of malignancies in HIV infected patients may vary in different race and region. The aim of this study is to determine the prevalence and characteristics of malignancies in patients with HIV infection in South Korea. Materials and Methods : To identify HIV patients with malignancy, we reviewed the electronic database of pathological reports for all HIV-infected patients seen from January 1986 to December 2005 at the Seoul National University Hospital. We retrospectively reviewed the medical records of them. Results : Among 850 patients infected with HIV, 33 episodes of malignant diseases were diagnosed in 32 patients (3.76%). Thirty were males, and median age was 46 years (range 29-70). At the time of the diagnosis of malignancy, median CD4^(+) lymphocytes count was 100/uL (range 5-620) and in 27 (82%) patients, CD4^(+) lymphocytes count were less than 200/uL. For 13 patients (40%), malignancy was initial presentation of HIV infection. Excluding patients initially diagnosed as malignancy, median follow-up duration from the first visit to diagnosis of malignancy was 36 months (range 3-96). Non-Hodgkin's lymphoma was the most frequent malignancy (13 patients), followed by Kaposi's sarcoma (7), Hodgkin‘s disease (3), acute myeloid leukemia (1), and other solid cancer (9) including one case of anal cancer associated with human papillomavirus. Among 13 patients with non- Hodgkin's lymphoma, 4(31%) achieved the complete remission after chemotherapy and/or radiation therapy, and had been followed without evidence of recurrence. Conclusion : Malignancy was diagnosed in 3.76% of patients infected with HIV. Non-Hodgkin‘s lymphoma is the most prevalent malignancy in HIV patients in South Korea. 목적 : 효과적인 항레트로바이러스 다제요법이 도입됨에 따라, HIV 감염환자들의 수명이 증가되었고, 이에 따라 HIV 감염환자에서 악성종양의 중요성 또한 증가하고 있다. 본 연구의 목적은 우리나라 HIV 감염환자에서 악성종양의 유병률과 호발하는 악성종양의 특성을 밝히는 것이다. 재료 및 방법 : 1986년부터 2005년까지 서울대학교병원에서 치료를 받은 HIV 감염환자의 의무기록을 후향적으로 분석하였고, 병리학적 검사 결과를 검토하여 악성종양이 진단된 환자들을 대상으로 연구를 시행하였다. 결과 : 총 850명의 환자 중, 32명(3.76%)에서 33예의 악성종양이 진단되어, 악성종양의 발병률은 1,000인년 당13.0명(95% 신뢰구간: 8.6∼17.4명)이었다. 그 중 남자는 30명이었고, 악성종양 진단 당시 연령의 중간값은 46 (29-70)세이었다. 악성종양 진단받을 당시, CD4 림프구 수의 중간값은 lOO/uL (5-620 uL) 이었고, CD4 림프구수가 200/ uL 미만인 환자가 27명(82%)이었다. 악성종양에 대한 검사 도중에 HIV 감염사실이 밝혀진 환자가 13명(40%)이었다. HIV를 진단 받은 후 악성종양이 발병한 환자들에서, HIV 진단 후 악성종양의 발병까지는 평균 36개월(3-96개월)이 걸렸다. 13명의 HIV 감염 환자에서 진단된 비호지킨림프종이 가장 흔한 악성종양이었고, 이외에 카포시육종이 7명, 호지킨병이 3명, HPV와 연관된 항문암이 1명의 HIV 환자에서 진단되었다. 그 밖에 급성백혈병, 방광암, 췌장장, 폐암, 진행성위암, 갑상선암, 간세포암, 후두암이 각각 1예씩 진단되었다. 비호지킨림프종이 진단된13명 환자 중, 4명(31%)은 항암치료 및 방사선치료를 받아 완전관해가 되었고, 현재 재발의 증거 없이 외래에서 경과 관찰 중이다. 결론 : 우리나라 HIV 감염환자에서 악성종양의 유병률은 3.76%이었고, 비호지킨림프종이 가장 흔한 악성종양이었다.

국내 다기관에서 조사한 지역사회획득 메티실린내성 황색포도알균의 빈도와 임상적 특성

송진수,최평균,송경호,조재현,김성한,방지환,이창섭,박경화,박경운,신수,최희정,김의석,김동민,이미숙,박완범,김남중,오명돈,김의종,김홍빈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

목적 : 최근 전세계적으로 지역사회획득 메티실린내성 황색포도알균(community-associated methicillin-resistant Staphylococcus aureus, CA-MRSA)의 보고가 증가하고 있다. 하지만, 우리나라에서는 CA-MRSA 감염증에 대한 증례보고만 있을 뿐 아직까지 체계적인 연구결과가 없는 실정이다. 저자들은 국내에서 CA-MRSA의 빈도, 감염증의 임상적 양상, 분리된 균주의 항균제내성 양상을 조사하였다. 재료 및 방법 : 2005년 1월부터 2005년 6월까지 7개 병원에서 MRSA가 분리된 환자의 명단을 파악한 후 의무기록지와 건강보험심사평가원의 자료를 검토하였다. 외래나 응급실에서 혹은 입원 후 72시간 이내에 균주가 분리되고 MRSA 획득과 관련된 위험인자가 없는 경우 CA-MRSA로 정의하였으며, 분리된 균주의 임상적 의미에 따라 원인병원체(pathogen), 집락화(colonizer), 미결정(undetermined)으로 분류하였다. Penicillin과 oxacillin을 제외하고 3개 이상의 다른 계열 항균제에 내성이면 다제내성으로 정의하였다. 결과 : 연구기간동안 총 3,251주의 황색포도알균이 분리되었으며, 이 중 MRSA는 1,900주(58.4%)였다. MRSA 가운데 CA-MRSA는 114주(6.0%) 였으며, 이들이 분리된 부위는 귀(62주), 비뇨기계(14주), 피부 및 연부조직(11주), 호흡기계(10주), 혈액(3주) 등이었다. CA-MRSA 균주 가운데 집락균은 22주, 원인병원체는 22주였으며, 나머지 균주에 대해서는 그 임상적 의미를 결정할 수 없었다. 항균제 감수성 검사를 시행한 73균주 중 47주(64.4%)는 다제내성이었다. CA-MRSA 감염증 22예 중 피부 및 연부조직 감염(9예)과 중이염/외이도염(9예)이 가장 흔하였다. 침습적 감염증(invasive infection)은 4명(원발성 균혈증 3예, 감염성 관절염 1예)에서 확인되었지만, CA-MRSA 감염증으로 사망한 환자는 없었다. 결론 : 병원내 감염증에서는 MRSA가 심각한 문제이지만, 아직까지 지역사회 감염증에서 CA-MRSA는 흔하지 않았다. Background : Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. In Korea, little is known about the epidemiology and clinical features of community-associated MRSA (CA-MRSA). Material and Methods : Clinical microbiology laboratory databases of 7 hospitals were reviewed to identify the patients from whom MRSA was isolated during the period of January to July 2005. Only one isolate per patient was enrolled. In order to identify the risk factors of MRSA acquisition, the medical records and the Health Insurance Review Agency databases were reviewed. CA-MRSA was defined as MRSA isolated from patient without established risk factors. We analyzed patient demographics, underlying medical conditions, characteristics of infection, and antimicrobial susceptibility profiles. Results : Of total 3,251 S. aureus isolates, 1900 (58.4%) were MRSAs. Of the MRSA isolates, 114 (6.0%) were CA-MRSA. Of 114 CA-MRSA isolates, 22 (19.3%) were colonizers, 22 (19.3%) were pathogens, and the clinical significance of remaining 70 (61.4%) could not be determined. Median age of the 22 patients with CA-MRSA disease was 47 years. Nine patients had skin and soft tissue infections, 9 ear infections, 3 bacteremia, 1 septic arthritis. Seven patients had underlying medical disease. None died of the CA-MRSA infections. Of the 73 isolates of CA-MRSA, 47 (64.4%) were resistant to more than 3 classes of antibiotics besides β-lactams. Conclusion : Although MRSA is highly prevalent among hospital-associated S. aureus infection, CA-MRSA infections are not common.

급냉응고된 Mg-9Al-xCa 합금의 시효특성에 관한 연구

金完哲,朴祉河 홍익대학교 산업기술연구소 1999 産業技術 Vol.9 No.-

Mg-Al-Si-Ca alloys were fabricated into the ribbons by rapid solidification using a single-roll melt spinner. The time and temperature effect on age-hardening was investigated for the ribbons with varying Ca contents of 1, 3, 6 and 10 wt%. The behavior of precipitates, phase transitions, and mechanical properties were examined by measurements of micro-hardness, XRD analysis, and transmission electron microscopy. For the case of 1 hour's isochronal heat treatment, the temperature of 200℃ gave the most significant age hardening effect and the increase in Ca content caused enhanced hardening. In the aging treatment at 200℃, the hardness decreased with the increase in aging time from 1 up to 81 hour. The microstructural analysis for Ca-added sample showed uniformly distributed compounds of Al_4Ca and Al_2Ca, forming coherent precipitates with matrix. When the alloy contains more Ca than the solubility limit, the excess Ca precipitates as Mg_2Ca and an increased hardness is observed.

코자 정(로자탄 칼륨 50mg)에 대한 로자르탄 정의 생물학적 동등성

김용원,박완수,김성수,서지형,조성희,이헌우,류재환,이경태 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.2