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.

ECVAM 등의 국제 독성시험법 국내 확립 및 적용

이진영 ( Jin Young Lee ),강미선 ( Mi Sun Kang ),김지명 ( Ji Myoung Kim ),곽승준 ( Seung Jun Kwack ),한의식 ( Eui Sik Han ),한범석 ( Beom Seok Han ),박순희 ( Sue Nie Park ),강태석 ( Tae Seok Kang ),한순영 ( Soon Young Han ) 한국동물실험대체법학회 2010 동물실험대체법학회지 Vol.4 No.1

Repeated dose toxicity testing in rodents is used to have information on potential target organs in terms of toxicity, and the NOAEL (no-observed-adverse-effect-level). ECVAM and ICCVAM have not validated any non-animal methods for assessing chronic toxicity endpoints or repreated exposure target organ toxicity because in vivo systems often poorly resemble in vitro cell culture systems. However, recently ECVAM recommended a proposed approach for the assessment of repeated dose toxicity in vitro. We applied ECVAM`s proposal to assess target organ toxicity using liver and kidney cell lines. In order to predict liver and kidney target organ toxicities, we used three kinds of kidney toxicants(HgCl2, CH3HgCl, CdCl2) and two kinds of liver toxicants(acetaminophen, CuCl2) in human hepatoma(HepG2) cells, human renal tubular epithelial(HK-2) cells and human embryonic kidney(HEK293) cells. We performed cytotoxicity assays, mitochondria damage and calcium influx tests to predict target organ toxicity. Cell viability and cell proliferation were assessed by NRU assay and MTT assays, respectively. Mitochondria potential and cell calcium concentration([Ca2+]i) were estimated by a fluorescence microscopy using JC-1 dye and a fluorometer using Fluo-4/AM dye, respectively. The cytotoxicity of nephrotoxicants(HgCl2, CH3HgCl, CdCl2) from the result of NRU and MTT assay was higher in the kidney cells than in the liver cells. Also, the cytotoxicity of hepatotoxicants(acetaminophen, CuCl2) was higher in the liver cells than in the kidney cells. Mitochondria potential and [Ca2+]i show compatability with cytotoxicity results in the kidney cells but not in the liver cells. The results demonstrated that nephrotoxicants can predict target organ toxicity by in vitro tests like NRU, MTT assay, mitochondria potential and [Ca2+]i. However, hepatotoxicants can predict target organ toxicity by cytotoxicity assays like NRU and MTT assays but not by mitochondria potential and [Ca2+]i.

연구논문 : ECVAM 등의 국제 독성시험법 국내 확립 및 적용

이진영 ( Jin Young Lee ),강미선 ( Mi Sun Kang ),김지명 ( Ji Myoung Kim ),곽승준 ( Seung Jun Kwack ),한의식 ( Eui Sik Han ),한범석 ( Beom Seok Han ),박순희 ( Sue Nie Park ),강태석 ( Tae Seok Kang ),한순영 ( Soon Young Han ) 한국동물실험대체법학회 2010 동물실험대체법학회지 Vol.4 No.1

Repeated dose toxicity testing in rodents is used to have information on potential target organs in terms of toxicity, and the NOAEL (no-observed-adverse-effect-level). ECVAM and ICCVAM have not validated any non-animal methods for assessing chronic toxicity endpoints or repreated exposure target organ toxicity because in vivo systems often poorly resemble in vitro cell culture systems. However, recently ECVAM recommended a proposed approach for the assessment of repeated dose toxicity in vitro. We applied ECVAM`s proposal to assess target organ toxicity using liver and kidney cell lines. In order to predict liver and kidney target organ toxicities, we used three kinds of kidney toxicants(HgCl2, CH3HgCl, CdCl2) and two kinds of liver toxicants(acetaminophen, CuCl2) in human hepatoma(HepG2) cells, human renal tubular epithelial(HK-2) cells and human embryonic kidney(HEK293) cells. We performed cytotoxicity assays, mitochondria damage and calcium influx tests to predict target organ toxicity. Cell viability and cell proliferation were assessed by NRU assay and MTT assays, respectively. Mitochondria potential and cell calcium concentration([Ca2+]i) were estimated by a fluorescence microscopy using JC-1 dye and a fluorometer using Fluo-4/AM dye, respectively. The cytotoxicity of nephrotoxicants(HgCl2, CH3HgCl, CdCl2) from the result of NRU and MTT assay was higher in the kidney cells than in the liver cells. Also, the cytotoxicity of hepatotoxicants(acetaminophen, CuCl2) was higher in the liver cells than in the kidney cells. Mitochondria potential and [Ca2+]i show compatability with cytotoxicity results in the kidney cells but not in the liver cells. The results demonstrated that nephrotoxicants can predict target organ toxicity by in vitro tests like NRU, MTT assay, mitochondria potential and [Ca2+]i. However, hepatotoxicants can predict target organ toxicity by cytotoxicity assays like NRU and MTT assays but not by mitochondria potential and [Ca2+]i.

Pulmonary graft-versus-host disease after autologous hematopoietic stem cell transplantation

( Sue In Choi ),( Eun Joo Lee ),( Dong Oh Kang ),( Sang Yeub Lee ),( Kwang Ho In ),( Han-kyeom Kim ),( Sanghoon Park ) 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.6

The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study.

Kang, Eunyoung,Seong, Moon-Woo,Park, Sue K,Lee, Jong Won,Lee, Jihyoun,Kim, Lee Su,Lee, Jeong Eon,Kim, Sung Yong,Jeong, Joon,Han, Sang Ah,Kim, Sung-Won M. Nijhoff ; Kluwer Academic Publishers 2015 Breast cancer research and treatment Vol.151 No.1

<P>The Korean Hereditary Breast Cancer (KOHBRA) study was established to evaluate the prevalence and spectrum of BRCA1/2 mutations in Korean breast cancer patients at risk for hereditary breast and ovarian cancer. A total of 2953 subjects (2403 index patients and 550 family members of affected carriers) from 36 centers participated in this study between May 2007 and December 2013. All participants received genetic counseling and BRCA genetic testing. In total, 378 mutation carriers among 2403 index patients were identified. The prevalence of BRCA mutations in specific subgroups was as follows: 22.3?% (274/1228) for breast cancer patients with a family history of breast/ovarian cancers, 8.8?% (39/441) for patients with early-onset (<35?years) breast cancer without a family history, 16.3?% (34/209) for patients with bilateral breast cancer, 4.8?% (1/21) for male patients with breast cancer, and 37.5?% (3/8) for patients with both breast and ovarian cancer. From an analysis of the mutation spectrum, 63 BRCA1 and 90 BRCA2 different mutations, including 44 novel mutations, were identified. The c.7480 (p.Arg2494Ter) mutation in BRCA2 (10.1?%) was the most commonly identified in this cohort. The KOHBRA study is the largest cohort to identify BRCA mutation carriers in Asia. The results suggest that the prevalence of BRCA mutations in familial breast cancer patients is similar to that among Western cohorts. However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population.</P>

음경에 발생한 해면상혈관종 1례

성수용,권병산,한창희,강성학,이은정 大韓泌尿器科學會 1998 Korean Journal of Urology Vol.39 No.4

Baseline General Characteristics of the Korean Chronic Kidney Disease: Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Kang, Eunjeong,Han, Miyeun,Kim, Hyunsuk,Park, Sue Kyung,Lee, Joongyub,Hyun, Young Youl,Kim, Yong-Soo,Chung, Wookyung,Kim, Hyo Jin,Oh, Yun Kyu,Ahn, Curie,Oh, Kook-Hwan The Korean Academy of Medical Sciences 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.2

<P>The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was developed to investigate various clinical courses and risk factors for progression of Korean chronic kidney disease (CKD). The KNOW-CKD study consists of nine clinical centers in Korea, and patients aged between 20 and 75 years with CKD from stage 1 to 5 (predialysis) were recruited. At baseline, blood and urine samples were obtained and demographic data including comorbidities, drugs, quality of life, and health behaviors were collected. Estimated glomerular filtration rate (eGFR) was calculated by 4-variable Modification of Diet in Renal Disease (MDRD) equation using isotope dilution mass spectrometry (IDMS)-calibrated serum creatinine measured at a central laboratory.</P><P>As a dynamic cohort, a total of 2,341 patients were enrolled during the enrollment period from 2011 until 2015, among whom 2,238 subjects were finally analyzed for baseline profiles. The mean age of the cohort was 53.7 ± 12.2 year and 61.2% were men. Mean eGFR was 50.5 ± 30.3 mL/min/1.73 m<SUP>2</SUP>. The participants with lower eGFR had a tendency to be older, with more comorbidities, to have higher systolic blood pressure (BP) and pulse pressure, with lower income level and education attainment. The patients categorized as glomerulonephritis (GN) were 36.2% followed by diabetic nephropathy (DN, 23.2%), hypertensive nephropathy (HTN, 18.3%), polycystic kidney disease (PKD, 16.3%), and other unclassified disease (6.1%). The KNOW-CKD participants will be longitudinally followed for 10 years. The study will provide better understanding for physicians regarding clinical outcomes, especially renal and cardiovascular outcomes in CKD patients.</P>

Multiplex genotyping of 1107 SNPs from 232 candidate genes identified an association between IL1A polymorphism and breast cancer risk.

Han, Wonshik,Kang, So Young,Kang, Daehee,Park, Sue K,Lee, Ji-Young,Kim, Ho,Park, Ae Kyung,Noh, Dong-Young National Hellenic Research Foundation 2010 ONCOLOGY REPORTS Vol.23 No.3

<P>We sought to identify genes and polymorphisms associated with breast cancer risk among Korean women using multiplex genotyping. The SNPs (n=1536) of 264 candidate genes were genotyped using the Illumina Golden Gate assay. These genes are involved in the pathways controlling apoptosis/anti-apoptosis, the immune and inflammatory responses, cytokines, DNA repair, cell adhesion, and cell cycle/proliferation. Breast cancer cases (n=209) were recruited from Seoul National University Hospital. Age-matched control subjects (n=209) were selected from a health examinees cohort. Gene-based and SNP-based tests were performed. The final analysis includes 117 cases and 164 controls with 1107 SNPs in 232 genes. Gene-based analyses showed that IL1A, TNFRSF10B, TNFRSF1B, ICAM, and TNFSF9 were significantly associated with breast cancer risk (p<0.01). IL1A was the most significant gene associated with breast cancer risk [p for likelihood ratio test, 1 degree of freedom (df)=6x10(-7); FDR-adjusted p-value, 1df=4x10(-4), 2df=0.0071, respectively]. Individual SNP-based analyses revealed that the rare allele of the IL1A SNP rs2856836, Ex7-592Tright curved arrow C, was strongly associated with breast cancer risk (FDR-adjusted p-value, 1df=0.0027, 2df=0.0162). This SNP was found to increase risk for breast cancer [odds ratio (OR)=2.88, 95% confidence interval (CI)=1.58-5.27 for heterozygote and OR=8.17, 95% CI=2.23-29.99 for rare homozygote]. In summary, we identified a common genetic variant in IL1A strongly associated with breast cancer risk.</P>

The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study.

Han, Sang-Ah,Kim, Sung-Won,Kang, Eunyoung,Park, Sue K,Ahn, Sei-Hyun,Lee, Min Hyuk,Nam, Seok-Jin,Han, Wonshik,Bae, Young Tae,Kim, Hyun-Ah,Cho, Young Up,Chang, Myung Chul,Paik, Nam Sun,Hwang, Ki-Tae,Kim Kluwer Academic Publishers 2013 Familial cancer Vol.12 No.1

<P>The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.</P>

Trough Concentration Over 12.1 mg/L is a Major Risk Factor of Vancomycin-Related Nephrotoxicity in Patients With Therapeutic Drug Monitoring

Han, Hye Kyung,An, Hyungmi,Shin, Kwang-Hee,Shin, Donghoon,Lee, Sue Hyun,Kim, Ju Han,Cho, Sang-Heon,Kang, Hye-Ryun,Jang, In-Jin,Yu, Kyung-Sang,Lim, Kyoung Soo by Lippincott Williams Wilkins 2014 Therapeutic drug monitoring Vol.36 No.5

BACKGROUND:: High doses of vancomycin increase the risk of nephrotoxicity, but the quantitative relationship between vancomycin exposure and nephrotoxicity is still controversial. This study evaluated the relationship between vancomycin trough concentration and nephrotoxicity, and risk factors for nephrotoxicity in patients undergoing therapeutic drug monitoring. METHODS:: A total of 1269 cases from patients who underwent therapeutic drug monitoring were collected from 2006 to 2010. Receiver operating characteristic curve analysis was used to evaluate the relationship between trough concentration and the incidence of nephrotoxicity. Logistic regression using the generalized Least Absolute Shrinkage and Selection Operator (lasso) method was used to evaluate possible risk factors for nephrotoxicity. The data were divided into high/low-concentration groups by the cutoff value obtained from the receiver operating characteristic curve, and additional logistic regression using the generalized lasso method was performed for each group. RESULTS:: The cutoff value of the vancomycin trough concentration was 12.1 mg/L. Patients with high concentrations (>12.1 mg/L) were more likely to develop nephrotoxicity (odds ratio = 16.0, 95% confidence interval, 8.2–31.1). The vancomycin trough concentration was the only significant risk factor for nephrotoxicity identified using the generalized lasso (P < 0.001). In contrast, no factor was associated with nephrotoxicity in the low-concentration group. CONCLUSIONS:: Vancomycin trough concentrations over 12.1 mg/L were associated with an increased risk of nephrotoxicity. This is lower than the known threshold. Trough vancomycin concentration over the threshold was the only risk factor of nephrotoxicity among demographic factors, dosing regimen, and other clinical conditions in this study. It is suggested that vancomycin trough concentrations greater than 12.1 mg/L require close monitoring for nephrotoxicity.